record_id,pubmedID,title,authors,abstract,year,label_included,label_abstract_screening
1,10051933,The effectiveness of clonidine as an analgesic in paediatric adenotonsillectomy.,E J Reimer; G S Dunn; C J Montgomery; P M Sanderson; L D Scheepers; P M Merrick,"To compare the analgesic effects of preoperative oral clonidine with intraoperative intravenous fentanyl in children undergoing tonsillectomy or adenotonsillectomy. This randomized, controlled, double-blind study of 36 ASA I-II children, age 7-12 yr undergoing adenotonsillectomy was conducted at a tertiary care paediatric teaching hospital. Either 4 micrograms.kg-1 clonidine po was given 60-90 min preoperatively or 3 micrograms.kg-1 fentanyl i.v. was given intraoperatively. Postoperatively visual analog pain scores (VAS) were recorded at rest and on swallowing every 10 min for the first 30 min and then every 15 min for two hours. Morphine 0.05 mg.kg-1 i.v. was given for VAS > or = 5. If > 3 doses were required, 1.5 mg.kg-1 codeine po and 20 mg.kg-1 acetaminophen po were given. Sedation and anxiety scores were recorded preoperatively. Haemodynamic changes, blood loss, recovery scores, and the incidence of vomiting, hypotension, and airway obstruction were recorded. Children who received clonidine had a higher incidence of preoperative sedation (63%) than those receiving fentanyl (6%). Preinduction mean arterial pressure was lower in the clonidine group but required no intervention. VAS scores were similar throughout the observation period. There was no difference either in the number of morphine or codeine rescue doses administered or in the incidence of side effects. Oral clonidine is an effective analgesic and sedative for children undergoing tonsillectomy or adenotonsillectomy.",1999.0,0,0
2,10053177,"A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation.",D E Jorenby; S J Leischow; M A Nides; S I Rennard; J A Johnston; A R Hughes; S S Smith; M L Muramoto; D M Daughton; K Doan; M C Fiore; T B Baker,"Use of nicotine-replacement therapies and the antidepressant bupropion helps people stop smoking. We conducted a double-blind, placebo-controlled comparison of sustained-release bupropion (244 subjects), a nicotine patch (244 subjects), bupropion and a nicotine patch (245 subjects), and placebo (160 subjects) for smoking cessation. Smokers with clinical depression were excluded. Treatment consisted of nine weeks of bupropion (150 mg a day for the first three days, and then 150 mg twice daily) or placebo, as well as eight weeks of nicotine-patch therapy (21 mg per day during weeks 2 through 7, 14 mg per day during week 8, and 7 mg per day during week 9) or placebo. The target day for quitting smoking was usually day 8. The abstinence rates at 12 months were 15.6 percent in the placebo group, as compared with 16.4 percent in the nicotine-patch group, 30.3 percent in the bupropion group (P<0.001), and 35.5 percent in the group given bupropion and the nicotine patch (P<0.001). By week 7, subjects in the placebo group had gained an average of 2.1 kg, as compared with a gain of 1.6 kg in the nicotine-patch group, a gain of 1.7 kg in the bupropion group, and a gain of 1.1 kg in the combined-treatment group (P<0.05). Weight gain at seven weeks was significantly less in the combined-treatment group than in the bupropion group and the placebo group (P<0.05 for both comparisons). A total of 311 subjects (34.8 percent) discontinued one or both medications. Seventy-nine subjects stopped treatment because of adverse events: 6 in the placebo group (3.8 percent), 16 in the nicotine-patch group (6.6 percent), 29 in the bupropion group (11.9 percent), and 28 in the combined-treatment group (11.4 percent). The most common adverse events were insomnia and headache. Treatment with sustained-release bupropion alone or in combination with a nicotine patch resulted in significantly higher long-term rates of smoking cessation than use of either the nicotine patch alone or placebo. Abstinence rates were higher with combination therapy than with bupropion alone, but the difference was not statistically significant.",2000.0,0,0
3,10066996,Effects of methylphenidate on complex cognitive processing in attention-deficit hyperactivity disorder.,Tamara Berman; Virginia I Douglas; Ronald G Barr,"Three experiments were conducted to explore the effects of methylphenidate (MPH), attention-deficit hyperactivity disorder (ADHD) diagnosis, and age on performance on a complex visual-memory search task. Results showed that the effects of MPH varied with information load. On low-processing loads, all doses of MPH helped children with ADHD to improve accuracy with no cost to reaction time (RT), whereas on high loads, higher MPH doses improved error rates while slowing RT. Without medication, children with ADHD showed high error rates and slow RTs across both low and high loads, as did younger, normal control children. Because MPH slowed performance on only the most difficult, high-load conditions, it is argued that the drug improves self-regulatory ability, enabling children with ADHD to adapt differentially to high and low loads.",1999.0,0,1
4,10072008,Spinal clonidine prolongs labor analgesia from spinal sufentanil and bupivacaine.,R D'Angelo; E Evans; L A Dean; R Gaver; J C Eisenach,"We sought to determine whether spinal clonidine 50 microg prolongs the analgesia from the spinal administration of sufentanil 7.5 microg and bupivacaine 2.5 mg early in the first stage of labor. Thirty patients were randomized to receive a 2-mL spinal injection of sufentanil 7.5 microg + bupivacaine 2.5 mg with or without clonidine 50 microg using a combined spinal-epidural (CSE) technique. Pain, nausea, pruritus, sedation, motor block, blood pressure, and heart rate were assessed until the patient requested additional analgesia. Analgesia was significantly prolonged in patients who received spinal sufentanil + bupivacaine + clonidine (197 +/- 70 vs 132 +/- 39 min; P = 0.004). Pain scores and side effects, including motor block, sedation, and hypotension, were similar between groups. Spinal clonidine significantly prolongs labor analgesia from spinal sufentanil and bupivacaine without producing serious adverse side effects. We studied the effects of spinal clonidine administered with spinal sufentanil and bupivacaine on labor analgesia using a combined spinal-epidural technique and conclude that spinal clonidine significantly prolongs labor analgesia from spinal sufentanil and bupivacaine without producing serious adverse effects.",1999.0,0,0
5,10072410,Low-dose clozapine for the treatment of drug-induced psychosis in Parkinson's disease.,Parkinson Study Group,"Drug-induced psychosis is a difficult problem to manage in patients with Parkinson's disease. Multiple open-label studies have reported that treatment with clozapine at low doses ameliorates psychosis without worsening parkinsonism. We conducted a randomized, double-blind, placebo-controlled trial of low doses of clozapine (6.25 to 50 mg per day) in 60 patients at six sites over a period of 14 months. The patients (mean age, 72 years) had idiopathic Parkinson's disease and drug-induced psychosis of at least four weeks' duration. All the patients continued to receive fixed doses of antiparkinsonian drugs during the four weeks of the trial. Blood counts were monitored weekly in all the patients. The mean dose of clozapine was 24.7 mg per day. The patients in the clozapine group had significantly more improvement than those in the placebo group in all three of the measures used to determine the severity of psychosis. The mean (+/-SE) scores on the Clinical Global Impression Scale improved by 1.6+/-0.3 points for the patients receiving clozapine, as compared with 0.5+/-0.2 point for those receiving placebo (P<0.001). The score on the Brief Psychiatric Rating Scale improved by 9.3+/-1.5 points for the patients receiving clozapine, as compared with 2.6+/-1.3 points for those receiving placebo (P=0.002). The score on the Scale for the Assessment of Positive Symptoms improved by 11.8+/-2.0 points for the patients receiving clozapine, as compared with 3.8+/-1.9 points for those receiving placebo (P=0.01). Seven patients treated with clozapine had an improvement of at least three on the seven-point Clinical Global Impression Scale, as compared with only one patient given placebo. Clozapine treatment improved tremor and had no deleterious effect on the severity of parkinsonism. In one patient, clozapine was discontinued because of leukopenia. Clozapine, at daily doses of 50 mg or less, is safe and significantly improves drug-induced psychosis without worsening parkinsonism.",1999.0,0,0
6,10078501,Predictors of relapse following response from a first episode of schizophrenia or schizoaffective disorder.,D Robinson; M G Woerner; J M Alvir; R Bilder; R Goldman; S Geisler; A Koreen; B Sheitman; M Chakos; D Mayerhoff; J A Lieberman,"We examined relapse after response to a first episode of schizophrenia or schizoaffective disorder. Patients with first-episode schizophrenia were assessed on measures of psychopathologic variables, cognition, social functioning, and biological variables and treated according to a standardized algorithm. The sample for the relapse analyses consisted of 104 patients who responded to treatment of their index episode and were at risk for relapse. Five years after initial recovery, the cumulative first relapse rate was 81.9% (95% confidence interval [CI], 70.6%-93.2%); the second relapse rate was 78.0% (95% CI, 46.5%-100.0%). By 4 years after recovery from a second relapse, the cumulative third relapse rate was 86.2% (95% CI, 61.5%-100.0%). Discontinuing antipsychotic drug therapy increased the risk of relapse by almost 5 times (hazard ratio for an initial relapse, 4.89 [99% CI, 2.49-9.60]; hazard ratio for a second relapse, 4.57 [99% CI, 1.49-14.02]). Subsequent analyses controlling for antipsychotic drug use showed that patients with poor premorbid adaptation to school and premorbid social withdrawal relapsed earlier. Sex, diagnosis, obstetric complications, duration of psychotic illness before treatment, baseline symptoms, neuroendocrine measures, methylphenidate hydrochloride challenge response, neuropsychologic and magnetic resonance imaging measures, time to response of the initial episode, adverse effects during treatment, and presence of residual symptoms after the initial episode were not significantly related to time to relapse. There is a high rate of relapse within 5 years of recovery from a first episode of schizophrenia and schizoaffective disorder. This risk is diminished by maintenance antipsychotic drug treatment.",1999.0,0,0
7,10084637,"Comparison of risperidone and placebo for psychosis and behavioral disturbances associated with dementia: a randomized, double-blind trial. Risperidone Study Group.",I R Katz; D V Jeste; J E Mintzer; C Clyde; J Napolitano; M Brecher,"We report the findings from the first large, double-blind, placebo-controlled study conducted to evaluate the efficacy and safety of risperidone in the treatment of psychotic and behavioral symptoms in institutionalized elderly patients with dementia. 625 patients (67.8% women; mean age = 82.7 years) with DSM-IV diagnoses of Alzheimer's disease (73%), vascular dementia (15%), or mixed dementia (12%) and significant psychotic and behavioral symptoms were included. Each patient was randomly assigned to receive placebo or 0.5 mg/day, 1 mg/day, or 2 mg/day of risperidone for 12 weeks. The primary outcome measure was the Behavioral Pathology in Alzheimer's Disease rating scale (BEHAVE-AD). The study was completed by 70% of the patients. Baseline Functional Assessment Staging scores were 6 or 7 in more than 95% of the patients, indicating severe dementia. At endpoint, significantly greater reductions in BEHAVE-AD total scores and psychosis and aggressiveness subscale scores were seen in patients receiving 1 and 2 mg/day of risperidone than in placebo patients (p = .005 and p < .001, respectively). At week 12, 0.5 mg/day of risperidone was superior to placebo in reducing BEHAVE-AD aggression scores (p = .02). More adverse events were reported by patients receiving 2 mg/day of risperidone than 1 mg/day. The most common dose-related adverse events were extrapyramidal symptoms, somnolence, and mild peripheral edema. The frequency of extrapyramidal symptoms in patients receiving 1 mg/day of risperidone was not significantly greater than in placebo patients. Risperidone significantly improved symptoms of psychosis and aggressive behavior in patients with severe dementia. Results show that 1 mg/day of risperidone is an appropriate dose for most elderly patients with dementia.",1999.0,0,0
8,10088136,THA improves word priming and clonidine enhances fluency and working memory in Alzheimer's disease.,P Riekkinen; M Riekkinen,"We investigated the effects of a single administration of a cholinesterase inhibitor, tetrahydroaminoacridine (THA, 25 and 50 mg, orally), and an alpha 2-agonist, clonidine (0.5 and 2 micrograms/kg, orally), on neuropsychologic performance in two groups of patients with Alzheimer's disease (AD). Clonidine enhanced a spatial working memory and verbal fluency, but had no effect on spatial span or word priming. THA enhanced word priming, but had no effect on other performance measures. Our data suggests that degeneration of the LC noradrenergic system and the cholinergic cells of the basal forebrain have different functional consequences during the progression of AD. Finally, a combined treatment with noradrenergic and cholinergic drugs might produce a qualitatively broader effect on cognitive functions than either of the treatments alone, and more effectively attenuate clinical dementia.",2001.0,0,0
9,10090111,Diuretics and beta-blockers do not have adverse effects at 1 year on plasma lipid and lipoprotein profiles in men with hypertension. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.,M R Lakshman; D J Reda; B J Materson; W C Cushman; E D Freis,"Concern based on the reported short-term adverse effects of antihypertensive agents on plasma lipid and lipoprotein profiles (PLPPs) has complicated the therapy for hypertension. To compare the long-term (1-year) effects of 6 different antihypertensive drugs and placebo on PLPPs in a multicenter, randomized, double-blind, parallel-group clinical trial in 15 US Veterans Affairs medical centers. A total of 1292 ambulatory men, 21 years or older, with diastolic blood pressures (DBPs) ranging from 95 to 109 mm Hg taking placebo were randomized to receive placebo or 1 of 6 antihypertensive drugs: hydrochlorothiazide, atenolol, captopril, clonidine, diltiazem, or prazosin. After drug titration, patients with a DBP of less than 90 mm Hg were followed up for 1 year. Plasma lipids and lipoprotein profiles were determined at baseline, after initial titration, and at 1 year. After 8 weeks on a regimen of hydrochlorothiazide, increases of 3.3 mg/dL (0.09 mmol/L) in total cholesterol and 2.7 mg/dL in apolipoprotein B were significantly different (P< or =.05) from decreases of 9.3 mg/dL in total cholesterol and 5.4 mg/dL in ApoB levels while receiving prazosin but not from placebo. Patients achieving positive DBP control using hydrochlorothiazide (responders) showed no adverse changes in PLPPs, whereas nonresponders exhibited increases in triglycerides, total cholesterol, and low-density lipoprotein cholesterol levels. Plasma lipids and lipoprotein profiles did not change significantly among treatment groups after 1 year except for minor decreases in high-density lipoprotein 2 levels using hydrochlorothiazide, clonidine, and atenolol. None of these 6 antihypertensive drugs has any long-term adverse effects on PLPPs and, therefore, may be safely prescribed. Previously reported short-term adverse effects from using hydrochlorothiazide are limited to nonresponders.",1999.0,0,0
10,10091617,Selegiline-induced postural hypotension in Parkinson's disease: a longitudinal study on the effects of drug withdrawal.,A Churchyard; C J Mathias; A J Lees,"The United Kingdom Parkinson's Disease Research Group (UKPDRG) trial found an increased mortality in patients with Parkinson's disease (PD) randomized to receive 10 mg selegiline per day and L-dopa compared with those taking L-dopa alone. Recently, we found that therapy with selegiline and L-dopa was associated with selective systolic orthostatic hypotension which was abolished by withdrawal of selegiline. This unwanted effect on postural blood pressure was not the result of underlying autonomic failure. The aims of this study were to confirm our previous findings in a separate cohort of patients and to determine the time course of the cardiovascular consequences of stopping selegiline in the expectation that this might shed light on the mechanisms by which the drug causes orthostatic hypotension. The cardiovascular responses to standing and head-up tilt were studied repeatedly in PD patients receiving selegiline and as the drug was withdrawn. Head-up tilt caused systolic orthostatic hypotension which was marked in six of 20 PD patients on selegiline, one of whom lost consciousness with unrecordable blood pressures. A lesser degree of orthostatic hypotension occurred with standing. Orthostatic hypotension was ameliorated 4 days after withdrawal of selegiline and totally abolished 7 days after discontinuation of the drug. Stopping selegiline also significantly reduced the supine systolic and diastolic blood pressures consistent with a previously undescribed supine pressor action. This study confirms our previous finding that selegiline in combination with L-dopa is associated with selective orthostatic hypotension. The possibilities that these cardiovascular findings might be the result of non-selective inhibition of monoamine oxidase or of amphetamine and metamphetamine are discussed.",1999.0,0,0
11,10093649,[Gamma-hydroxybutyrate for treatment of alcohol withdrawal syndrome in intensive care patients. A comparison between with two symptom-oriented therapeutic concepts].,E Lenzenhuber; C Müller; H Rommelspacher; C Spies,"Seeing as gamma-hydroxybutyrate (GHB) and benzodiazepines interact with the GABA-transmitter system, we investigated whether GHB can replace the conventional therapy, which uses benzodiazepines in the treatment of alcohol withdrawal syndrome in ICU settings. 42 chronic alcoholics were included in this prospective and randomized study. Following the development of alcohol withdrawal syndrome, the patients were randomly allocated to the GHB or to the flunitrazepam group. In addition to this, clonidine was administered in order to treat autonomic signs of withdrawal. In cases were hallucinations occurred, haloperidol was administered. There was no significant difference in the efficacy of treatment used in the duration of mechanical ventilation and intensive care unit stay between groups. The patients in the GHB-group required significantly higher dosages of haloperidol and significantly lower dosages of clonidine. 14 out of 21 patients from the GHB-group developed hypernatriaemia and 15 out of 21 developed a metabolic alkalosis. Symptoms of the autonomic nervous system were more effectively prevented by GHB as evident in the lower dosage requirement of clonidine. However, GHB may not sufficiently block the hyperactivity of the dopaminergic system or may have an hallucinogenic effect itself. This may be evident from the higher dosages of haloperidol which were necessary. Due to the latter fact, the administration of GHB cannot be recommended in all patients suffering from AWS in ICU settings.",1999.0,0,0
12,10103294,Stimulant medication withdrawal during long-term therapy in children with comorbid attention-deficit hyperactivity disorder and chronic multiple tic disorder.,E E Nolan; K D Gadow; J Sprafkin,"In this study we examined changes in attention-deficit hyperactivity disorder behaviors and motor and vocal tics during withdrawal from long-term maintenance therapy with stimulant medication. Subjects were 19 children with attention-deficit hyperactivity disorder and chronic tic disorder who had received methylphenidate (n = 17) or dextroamphetamine (n = 2) for a minimum of 1 year. Children were switched to placebo under double-blind conditions. Treatment effects were assessed by using direct observations of child behavior in a simulated (clinic-based) classroom and behavior rating scales completed by parents and clinician. There was no change (group data) in the frequency or severity of motor tics or vocal tics during the placebo condition compared with maintenance dose of stimulant medication (ie, no evidence of tic exacerbation while receiving medication or of a withdrawal reaction). There was no evidence of tic exacerbation in the evening as a rebound effect. Treatment with the maintenance dose was also associated with behavioral improvement in attention-deficit hyperactivity disorder behaviors, indicating continued efficacy. Abrupt withdrawal of stimulant medication in children receiving long-term maintenance therapy does not appear to result in worsening of tic frequency or severity. Nevertheless, these findings do not preclude the possibility of drug withdrawal reactions in susceptible individuals.",1999.0,0,1
13,10150160,"Translating safety, efficacy and compliance into economic value for controlled release dosage forms.",M P Cramer; S R Saks,"Advanced controlled release (CR) dosage forms are relative newcomers to pharmaceutical markets, and few studies relate their efficacy, safety or compliance benefits to economic value. This literature review was undertaken to assess the cost effectiveness of CR dosage forms using such measures as purchase costs, total treatment costs, and economic value of improved therapeutic outcomes compared with those with non-CR dosage forms.  Three therapeutic areas were examined: cardiovascular therapy, pain management and estrogen replacement therapy.  In cardiovascular therapy, prescription costs of sustained release (SR) verapamil were significantly higher than for conventional release verapamil.  However, these were more than offset by lower physician, hospital and laboratory expenditures for the SR group, in whom compliance was superior.  Similarly, patients receiving SR diltiazem had better prescription refill compliance than those using a conventional formulation of the drug, as well as significantly lower aggregate healthcare costs during a 1-year study period.  These lower costs with both SR verapamil and diltiazem may relate to better compliance.  CR nifedipine has lower daily acquisition costs than the conventional form, simplifies the dosage regimen to once daily, extends the indications of the drug to hypertension as well as angina, and reduces vasodilatory adverse effects by reducing peak plasma drug concentrations and the postdose rate of increase in concentration. Compared with oral clonidine given twice daily, transdermal clonidine, given once weekly, had higher purchase costs, but was associated with improved compliance, reduced adverse effects (due to control of plasma concentrations), and lower nondrug health costs, such as physician, hospital and laboratory costs.  Lower costs were also found for once daily oral formulations of various antihypertensives, suggesting that the economics of both types of CR dosage forms related to compliance. CR metoprolol 50 or 100mg and conventional release atenolol 50mg, each given once daily, provided effective beta1-adrenoceptor blockade. The conventional formulation caused deterioration in the sense of well-being that was temporally associated with sharp peaking of its plasma concentrations.  Such peaking did not occur with either dose of CR metoprolol, nor did any deterioration in the sense of well-being. Transdermal nitroglycerin (glyceryl trinitrate), compared with long-acting oral nitrates, improved quality of life (QOL) {despite a higher incidence of some adverse effects, such as headache, dizziness and skin irritation}.  Furthermore, in some studies, this formulation reduced angina attacks, sublingual nitroglycerin use, and hospitalisation or emergency room use.  Cost comparisons between transdermal products favoured those that have superior adhesion.(ABSTRACT TRUNCATED AT 400 WORDS)",1994.0,0,0
14,10192826,"Guanfacine, but not clonidine, improves planning and working memory performance in humans.",P Jäkälä; M Riekkinen; J Sirviö; E Koivisto; K Kejonen; M Vanhanen; P Riekkinen,"The present study compares, using a double-blind, placebo controlled design the effects of two alpha 2-agonists, clonidine (0.5, 2, and 5 micrograms/kg) and guanfacine (7 and 29 micrograms/kg) on spatial working memory, planning and attentional set-shifting, functions thought to be dependent on the ""central executive"" of the prefrontal cortex. Blood pressure and the subjective feeling of sedation were affected equally by clonidine and guanfacine. The 0.5 microgram/kg and 5 micrograms/kg doses of clonidine disrupted spatial working memory, but the medium dose had no effect. The 0.5 and 2 micrograms/kg doses of clonidine increased impulsive responding in the planning test. The 5 micrograms/kg dose of clonidine slowed responding at effortful levels of planning and attentional set-shifting tests. The 29 micrograms/kg dose of guanfacine improved spatial working memory and planning. Guanfacine had no effect on attentional set-shifting. These data indicate that guanfacine improved planning and spatial working memory, but clonidine dose-dependently disrupted performance. It is possible that the greater selectivity of guanfacine for alpha 2A-adrenoceptor subtype may underlie its differences from clonidine.",2001.0,0,0
15,10192829,Ziprasidone 80 mg/day and 160 mg/day in the acute exacerbation of schizophrenia and schizoaffective disorder: a 6-week placebo-controlled trial. Ziprasidone Study Group.,D G Daniel; D L Zimbroff; S G Potkin; K R Reeves; E P Harrigan; M Lakshminarayanan,"In this double-blind study, patients with an acute exacerbation of schizophrenia or schizoaffective disorder were randomized to receive either ziprasidone 80 mg/day (n = 106) or 160 mg/day (n = 104) or placebo (n = 92), for 6 weeks. Both doses of ziprasidone were statistically significantly more effective than placebo in improving the PANSS total, BPRS total, BPRS core items, CGI-S, and PANSS negative subscale scores (p < .05). Ziprasidone 160 mg/day significantly improved depressive symptoms in patients with clinically significant depression at baseline (MADRS > or = 14, over-all mean 23.5) (p < .05) as compared with placebo. The percentage of patients experiencing adverse events was similar in each treatment group, and resultant discontinuation was rare. The most frequent adverse events associated with ziprasidone were generally mild dyspepsia, nausea, dizziness, and transient somnolence. Ziprasidone was shown to have a very low liability for inducing movement disorders and weight gain. The results indicate that ziprasidone is effective and well tolerated in the treatment of the positive, negative, and depressive symptoms of an acute exacerbation of schizophrenia or schizoaffective disorder.",1999.0,0,0
16,10195528,The neurotoxicity of drugs given intrathecally (spinal),P S Hodgson; J M Neal; J E Pollock; S S Liu,"Overall, most spinal drugs in clinical use have been poorly studied for spinal cord and nerve root toxicity. Laboratory studies indicate that all local anesthetics are neurotoxic in high concentrations and that lidocaine and tetracaine have neurotoxic potential in clinically used concentrations. However, spinal anesthesia (including lidocaine and tetracaine) has a long and enviable history of safety. Spinal analgesics such as morphine, fentanyl, sufentanil, clonidine, and neostigmine seem to have a low potential for neurotoxicity based on laboratory and extensive clinical use. Most antioxidants, preservatives, and excipients used in commercial formulations seem to have a low potential for neurotoxicity. In addition to summarizing current information, we hope that this review stimulates future research on spinal drugs to follow a systematic approach to determining potential neurotoxicity. Such an approach would examine histologic, physiologic, and behavioral testing in several species, followed by cautious histologic, physiologic, and clinical testing in human volunteers and patients with terminal cancer refractory to conventional therapy.",1999.0,0,0
17,10197827,Long-term methylphenidate therapy in children with comorbid attention-deficit hyperactivity disorder and chronic multiple tic disorder.,K D Gadow; J Sverd; J Sprafkin; E E Nolan; S Grossman,"This study examined changes in attention-deficit hyperactivity (ADHD) behaviors and motor and vocal tics during long-term treatment with methylphenidate. Thirty-four prepubertal children with ADHD and chronic multiple tic disorder (who had participated in an 8-week, double-blind, placebo-controlled methylphenidate evaluation) were evaluated at 6-month intervals for 2 years as part of a prospective, nonblind, follow-up study. Treatment effects were assessed using direct observations of child behavior in a simulated (clinic-based) classroom and behavior rating scales completed by parents and physician. Videotapes of the simulated classroom were scored by coders who were blind to treatment status. There was no evidence (group data) that motor tics or vocal tics changed in frequency or severity during maintenance therapy compared with diagnostic or initial double-blind placebo evaluations. Behavioral improvements demonstrated during the acute drug trial were maintained during follow-up. There was no evidence (group data) of clinically significant adverse drug effects on cardiovascular function or growth at the end of 2 years of treatment. Long-term treatment with methylphenidate seems to be safe and effective for the management of ADHD behaviors in many (but not necessarily all) children with mild to moderate tic disorder. Nevertheless, careful clinical monitoring is mandatory to rule out the possibility of drug-induced tic exacerbation in individual patients.",1999.0,1,1
18,10201102,Further analysis of the separate and interactive effects of methylphenidate and common classroom contingencies.,J Northup; I Fusilier; V Swanson; J Huete; T Bruce; J Freeland; V Gulley; S Edwards,"We evaluated separate and interactive effects between common classroom contingencies and methylphenidate (MPH) on disruptive and off-task behaviors for 4 children with a diagnosis of attention deficit hyperactivity disorder. Analogue conditions consisting of contingent teacher reprimands, brief time-out, no interaction, and alone were conducted in a multielement design. Medication status (MPH or placebo) was alternated across days in a superordinate multielement design. Results indicate that (a) the behavioral effects of MPH were influenced by one or more of the analogue conditions for each participant, and (b) time-out was associated with zero or near-zero levels of both disruptive and off-task behavior for 3 of the 4 participants during MPH and placebo conditions. Implications for the clinical effectiveness of MPH and possible behavioral mechanisms of action of MPH in applied settings are discussed.",1999.0,0,0
19,10211146,Olanzapine versus haloperidol in the treatment of schizoaffective disorder. Acute and long-term therapy.,P V Tran; G D Tollefson; T M Sanger; Y Lu; P H Berg; C M Beasley,"The effectiveness of antipsychotic monotherapy in schizoaffective disorder is limited, and further constrained by safety concerns. We aimed to compare the efficacy, tolerability and safety profile of the new pharmaceutical, olanzapine, with haloperidol. Data were assessed from 300 DSM-III-R schizoaffective subjects from a larger double-blind prospective international study. Subjects were randomly allocated to six weeks of olanzapine (5-20 mg) or haloperidol (5-20 mg) treatment; responders were followed for up to one year of double-blind, long-term maintenance therapy. Olanzapine-treated patients achieved a statistically significant greater improvement than haloperidol treated patients on overall measures of efficacy, including clinical response. Significantly fewer olanzapine patients left the study early, and fewer adverse events were observed among those receiving olanzapine. During maintenance, olanzapine-treated patients continued to experience additional improvement, with fewer EPS but more weight gain than those on haloperidol. Olanzapine demonstrated substantial advantages over the conventional antipsychotic haloperidol in the management of schizoaffective disorder.",2001.0,0,0
20,10211147,Randomised double-blind comparison of the incidence of tardive dyskinesia in patients with schizophrenia during long-term treatment with olanzapine or haloperidol.,C M Beasley; M A Dellva; R N Tamura; H Morgenstern; W M Glazer; K Ferguson; G D Tollefson,"Tardive dyskinesia is important in the side-effect profile of antipsychotic medication. The development of tardive dyskinesia was evaluated in patients treated with double-blind, randomly assigned olanzapine or haloperidol for up to 2.6 years. Tardive dyskinesia was assessed by the Abnormal Involuntary Movement Scale (AIMS) and Research Diagnostic Criteria for Tardive Dyskinesia (RD-TD), it was defined as meeting RD-TD criteria at two consecutive assessments. The risk of tardive dyskinesia, the relative risk, incidence rate, and incidence rate ratio were estimated. The relative risk of tardive dyskinesia for the overall follow up period for haloperidol (n = 522) v. olanzapine (n = 1192) was 2.66 (95% CI = 1.50-4.70). Based on data following the initial six weeks of observation (during which patients underwent medication change and AIMS assessments as frequently as every three days), the one-year risk was 0.52% with olanzapine (n = 513) and 7.45% with haloperidol (n = 114). The relative risk throughout this follow-up period was 11.37 (95% CI = 2.21-58.60). Our results indicated a significantly lower risk of tardive dyskinesia with olanzapine than with haloperidol.",1999.0,0,0
21,10227114,Pre-AIDS mortality and morbidity among injection drug users in Amsterdam and Baltimore: an ecological comparison.,E J van Ameijden; A Krol; D Vlahov; C Flynn; H J van Haastrecht; R A Coutinho,"Mortality and morbidity between injecting drug users in Amsterdam (n = 624) and Baltimore (n = 2,185) are compared to generate a hypothesis about the role of different health care systems and drug user policies (universal care and harm reduction versus episodic care and criminalization, respectively). Overdose/suicide mortality was twofold higher in Amsterdam; no sufficient explanation was found. Other independent ""risk factors"" for overdose/suicide mortality were recent injecting, polydrug use, and HIV-seropositivity (especially with CD4 count < 200/mm3). High dose methadone maintenance was associated with lower mortality. Incidence of hospitalizations and emergency room visits was substantially lower in Amsterdam, suggesting that higher accessibility to primary care in Amsterdam lowers (inpatient) hospital visits and presumably societal costs.",1999.0,0,0
22,10229041,Response to methylphenidate in boys with attention-deficit hyperactivity disorder.,P Zeiner; G Bryhn; C Bjercke; K Truyen; G Strand,"The response to methylphenidate was examined in 36 boys, aged 7-11 y, with attention-deficit hyperactivity disorder (ADHD) in a double-blind, placebo-controlled, crossover design. Hyperactivity and conduct problems were significantly reduced during methylphenidate treatment. Stimulant medication was associated with improvements on tests of sustained attention, working memory and motor steadiness. When individual changes were studied, it was found that 83% showed a significant improvement in their hyperactivity at home or at school, and for 60% their levels of hyperactive behaviour were within the normal range. High levels of hyperactivity at school and relatively low age were significant predictors of normalization of hyperactivity in at least one setting. However, these predictors could only classify correctly 71% of the children. In clinical practice a trial with stimulants is indicated in ADHD children who show symptoms that are sufficiently severe to cause impairment at home and at school.",1999.0,0,1
23,10230181,Stimulant medications.,L L Greenhill; J M Halperin; H Abikoff,"To review the short- and long-term safety and efficacy of stimulants for the treatment of children with attention-deficit/hyperactivity disorder (ADHD). A Medline search was conducted for both randomized controlled trials and reviews to determine the efficacy and safety of stimulant drugs for treating children with ADHD. Information was obtained on adverse events associated with their use, including their impact on height and weight gain during childhood. Animal data were reviewed for information on tolerance, sensitization, and the impact of high-dose stimulant effects on neurons and on the development of hepatic tumors. Human data on dopamine transporter occupancy by stimulants were also included. Stimulant treatment studies show robust short-term efficacy and a good safety profile. Longer-term studies are few in number but have produced no conclusive evidence that careful therapeutic use of these medications is harmful. Current evidence indicates that stimulants show efficacy and safety in studies lasting up to 24 months.",1999.0,0,1
24,10230185,Antipsychotics in children and adolescents.,M Campbell; J L Rapoport; G M Simpson,"To present a critical overview of the available evidence for the efficacy and safety of antipsychotic agents in children and adolescents and to identify knowledge gaps and needs for further research. Data from adults that are relevant to children are discussed. Mainly reports of double-blind, placebo-controlled studies were reviewed. In children and adolescents, antipsychotics are used to treat psychotic and a variety of nonpsychotic conditions. The amount of data based on well-designed, double-blind, placebo-controlled studies with satisfactory sample sizes in diagnostically homogeneous subjects is modest. Currently available standard antipsychotics have a definite role in the treatment of children and adolescents. The use of these agents is limited mainly by tardive and withdrawal dyskinesias and, in some patients, by excessive sedation. The atypical antipsychotics should be critically assessed and compared with psychosocial interventions; if effective, the combination of both types of treatments should be evaluated.",1999.0,0,0
25,10319784,Epidural clonidine or bupivacaine as the sole analgesic agent during and after abdominal surgery: a comparative study.,M De Kock; P Gautier; A Pavlopoulou; M Jonniaux; P Lavand'homme,"The rationale of this study was to compare high-dose epidural clonidine with a more commonly used agent, such as bupivacaine. This was performed to give a more objective idea of the relative analgesic potency of epidural clonidine. Sixty patients undergoing intestinal surgery during propofol anesthesia were studied. At induction, the patients received epidurally a dose of 10 micrograms/kg [corrected] clonidine in 7 ml saline followed by an infusion of 6 micrograms [corrected] x kg(-1) x h(-1) (7 ml/h) (group 1, n = 20), a dose of 7 ml bupivacaine, 0.5%, followed by 7 ml/h bupivacaine, 0.25% (group 2, n = 20), or a dose of 7 ml bupivacaine, 0.25%, followed by 7 ml/h bupivacaine, 0.125% (group 3, n = 20). Intraoperatively, increases in arterial blood pressure or heart rate not responding to propofol (0.5 mg/kg) were treated with intravenous alfentanil (0.05 mg/kg). Additional doses of propofol were given to maintain an adequate bispectral index. The epidural infusions were maintained for 12 h. In cases of subjective visual analogue pain scores up to 5 cm at rest or up to 8 cm during coughing, the patients were given access to a patient-controlled analgesia device. During anesthesia, patients in group 1 required less propofol than those in groups 2 and 3 (78 [36-142] mg vs. 229 [184-252] mg and 362 [295-458] mg; P < 0.05) and less alfentanil than patients in group 3 (0 [0-0] mg vs. 11 [6-20] mg; P < 0.05). Analgesia lasted 380 min (range, 180-645 min) in group 1 versus 30 min (range, 25-40 min) in group 2 and 22 min (range, 12.5-42 min) in group 3 (P < 0.05). There was no suggestion of a hemodynamic difference among the three groups except for heart rates that were significantly reduced in patients in group 1. Sedation scores were significantly higher in this group during the first 2 h postoperatively. Our results show that high doses of epidural clonidine potentiate general anesthetics and provide more efficient postoperative analgesia than the two bupivacaine dosage regimens investigated.",1999.0,0,0
26,10321415,Safety profile of sustained-release bupropion in depression: results of three clinical trials.,E C Settle; S M Stahl; S R Batey; J A Johnston; J A Ascher,"This series of studies was undertaken to assess the safety profile of sustained-release (SR) bupropion in the treatment of depressed outpatients. Adults with a diagnosis of major depression were evaluated in 1 of 3 multicenter, randomized, double-masked, parallel-group, placebo-controlled trials conducted in private-practice psychiatric outpatient clinics. Following a 1-week, single-masked, placebo lead-in period, patients received bupropion SR for 8 weeks (study 1: 150 or 300 mg/d; study 2: 100, 200, 300, or 400 mg/d; study 3: 50 to 150 or 100 to 300 mg/d). Safety assessments included monitoring adverse events, patient discontinuation rates, changes in weight, vital signs, and clinical laboratory test results. Across studies, the most frequently reported adverse events were headache, dry mouth, and nausea. The incidence of adverse events was similar (< or =5% difference) between the bupropion SR and placebo groups, with the exception of dry mouth (bupropion SR, 16%; placebo, 7%). Dry mouth, nausea, and insomnia occurred significantly more often in bupropion SR-treated patients than in patients who received placebo (P<0.05). Nearly all (94% to 99%) adverse events reported in these studies were mild or moderate. Less than 10% of patients in either group discontinued treatment prematurely because of adverse events, and no deaths or serious drug-related adverse events were reported. Sexual dysfunction was reported as an adverse event by <1% of patients in either group. Bupropion SR was associated with dose-related weight loss in all 3 studies. No consistent patterns of change were observed in vital signs or in the results of clinical laboratory tests. Data from these 3 clinical trials demonstrate the favorable safety profile of bupropion SR in the treatment of depressed outpatients.",1999.0,0,0
27,10327902,Olanzapine versus placebo in the treatment of acute mania. Olanzapine HGEH Study Group.,M Tohen; T M Sanger; S L McElroy; G D Tollefson; K N Chengappa; D G Daniel; F Petty; F Centorrino; R Wang; S L Grundy; M G Greaney; T G Jacobs; S R David; V Toma,"The primary intent of this study was to compare the efficacy and safety of olanzapine and placebo in the treatment of acute mania. The design involved a random-assignment, double-blind, placebo-controlled parallel group study of 3 weeks' duration. After a 2- to 4-day screening period, qualified patients were assigned to either olanzapine (N = 70) or placebo (N = 69). Patients began double-blind therapy with either olanzapine, 10 mg, or placebo given once per day. After the first day of treatment, the daily dose could be adjusted upward or downward, as clinically indicated, by one capsule (olanzapine, 5 mg/day) within the allowed range of one to four capsules. The primary efficacy measure in the protocol was defined as a change from baseline to endpoint in total score on the Young Mania Rating Scale. Clinical response was defined a priori as a decrease of 50% or more from baseline in Young Mania Rating Scale total score. The olanzapine group experienced significantly greater mean improvement in Young Mania Rating Scale total score than the placebo group. On the basis of the clinical response criteria, significantly more olanzapine-treated patients (48.6%) responded than those assigned to placebo (24.2%). Somnolence, dizziness, dry mouth, and weight gain occurred significantly more often with olanzapine. There were no statistically significant differences between the olanzapine-treated and placebo-treated patients with respect to measures of parkinsonism, akathisia, and dyskinesias. No discontinuations of treatment due to adverse events occurred in the olanzapine treatment group. The results from this study suggest that compared with placebo, olanzapine has superior efficacy for the symptoms of acute mania.",1999.0,0,0
28,10350032,Controlled trial of high doses of pemoline for adults with attention-deficit/hyperactivity disorder.,T E Wilens; J Biederman; T J Spencer; J Frazier; J Prince; J Bostic; M Rater; J Soriano; M Hatch; M Sienna; R B Millstein; A Abrantes,"Despite the increasing awareness of attention-deficit/hyperactivity disorder (ADHD) in adults, there are a limited number of controlled pharmacologic studies of this disorder. Because the stimulant medication magnesium pemoline (Cylert, Abbott Laboratories, Abbott Park, IL) has been found effective in treating ADHD in pediatric groups, we tested its efficacy in adults with ADHD using higher daily doses than those previously studied. We conducted a 10-week, double-blind, placebo-controlled, crossover design study of pemoline at a target daily dose of 3 mg/kg per day in 35 adult patients with DSM-III-R and -IV ADHD. We used standardized structured psychiatric instruments for diagnosis. To measure improvement, we used separate assessments of ADHD, depressive, and anxiety symptoms at baseline and at each biweekly visit. ADHD outcome was determined using the ADHD symptom checklist and Clinical Global Impression scales of Severity and Improvement. Of the 35 adults with ADHD who were randomized in the trial, 27 (77%) completed the protocol. Treatment with pemoline in the final week of the 4-week active phase was best tolerated at doses substantially lower than the target dose of 3 mg/kg per day (mean dose, 2.2 mg/kg per day; mean+/-SD, 148+/-95 mg). Pemoline was significantly better at reducing ADHD symptoms compared with placebo (z = 2.4,p < 0.02). Using a predefined 30% reduction in symptoms as an indication of improvement, 50% of pemoline-treated subjects and 17% of subjects in the placebo group were considered positive responders (chi2 = 7.1, p = 0.008). These results indicate that pemoline is moderately effective in the treatment of ADHD in adults. Although robust doses were targeted, most adults preferred more moderate dosing (120-160 mg/day). Given the limited efficacy, tolerability, and concerns of hepatic dysfunction, pemoline should be considered as second-line medication for treating ADHD in adults.",1999.0,1,1
29,10350037,Schizophrenia and schizoaffective disorder treated with high doses of olanzapine.,A Fanous; J P Lindenmayer,,1999.0,0,0
30,10356632,Event-related potential indices of auditory selective attention in dependent amphetamine users.,R McKetin; N Solowij,"The aim of the present study was to further investigate a previously reported attention-related impairment in dependent amphetamine users using event-related potential (ERP) indices of selective attention. ERPs were recorded during an auditory selective attention task (SAT) that involved detecting infrequent long-duration target tones presented among short-duration tones that varied in location (left vs. right ear) and pitch (low vs. high). Amphetamine users (n = 19) were divided into two groups, high dependence (n = 10) and low dependence (n = 10), based on amphetamine Severity of Dependence Scale scores, and compared to an age-matched control group (n = 9). The high-dependence group showed slowed reaction time and reduced early processing negativity and peak N1 amplitude to location-relevant nontarget stimuli. Poor performance on the SAT was highly correlated with deficits in early processing, which were also related to poor performance on the Wechsler Memory Scale Attention/Concentration index. It is suggested that severely dependent users suffer an inability to selectively enhance the sensory processing of relevant auditory information. This may produce poor automatic preferential processing of relevant information and increase load on limited attentional resources.",1999.0,0,0
31,10357339,Adding clonidine to lidocaine for intravenous regional anesthesia prevents tourniquet pain.,M Gentili; J M Bernard; F Bonnet,"Tourniquet pain often complicates the use of the pneumatic tourniquet during surgical procedures performed under IV regional anesthesia. Clonidine-containing local anesthetic solutions have better analgesic properties than plain solutions when used for spinal, epidural, or peripheral blocks. We tested the hypothesis that the addition of clonidine may improve the quality of IV regional anesthesia, especially tourniquet tolerance. Forty patients were allocated randomly in a double-blinded, randomized study to receive 40 mL of 0.5% lidocaine and either 1 mL of isotonic saline or clonidine (150 microg). A double-cuffed tourniquet was kept inflated until patients complained of pain, leading to release of the distal cuff. Pain at the tourniquet site, at the surgical site, and in the distal part of the arm was rated on a visual analog scale (VAS) and a verbal rating scale (VRS) every 15 min during tourniquet placement and every 15 min for 1 h after tourniquet deflation. Motor blockade, sedation, arterial pressure, and heart rate were also recorded. VAS and VRS scores were significantly lower in the clonidine group 30 and 45 min after tourniquet inflation. The tolerance for the distal tourniquet was also significantly longer in the clonidine group (median [range]: 22 [10-40] vs 10 [5-20] min; P < 0.05); motor blockade was comparable between the two groups. Pain was not different in the two groups after tourniquet release. The clonidine group experienced a higher degree of sedation. We conclude that clonidine improves tourniquet tolerance when added to a local anesthetic solution. A 150-microg dose of clonidine added to lidocaine improved tourniquet tolerance during IV regional anesthesia.",1999.0,0,0
32,10363731,A placebo-controlled comparison of the antidepressant efficacy and effects on sexual functioning of sustained-release bupropion and sertraline.,H Croft; E Settle; T Houser; S R Batey; R M Donahue; J A Ascher,"Sexual dysfunction, a frequently reported side effect of many antidepressants, may result in patient dissatisfaction and noncompliance with treatment regimens. This paper describes the results of the first placebo-controlled comparison of the efficacy, safety, and effects on sexual functioning of sustained-release bupropion (bupropion SR) and the selective serotonin reuptake inhibitor sertraline. This randomized, double-masked, double-dummy, parallel-group, multicenter trial enrolled 360 patients with moderate-to-severe recurrent major depression. Patients were treated with bupropion SR 150 to 400 mg/d, sertraline 50 to 200 mg/d, or placebo for up to 8 weeks. Patients' depression and sexual functioning were assessed at weekly or biweekly clinic visits; safety was assessed by regular monitoring of adverse events, vital signs, and body weight. Treatment groups were similar at baseline in terms of age, sex, and race, and most patients had a diagnosis of moderate uncomplicated depression. Patients treated with bupropion SR or sertraline showed similar improvements on all efficacy measures; both active treatments were superior to placebo in improving scores on all rating scales for depression at various time points. Significantly more patients treated with sertraline experienced orgasmic dysfunction throughout the study than did patients treated with bupropion SR or placebo (P < 0.001). Headache was the most frequently reported adverse event in all 3 treatment groups and occurred with similar frequency in each group (30% to 40%). Nausea (31%), diarrhea (26%), insomnia (18%), and somnolence (17%) occurred in significantly more patients in the sertraline group than in the bupropion SR group (18%, 7%, 13%, and 3%, respectively) and the placebo group (10%, 11%, 4%, and 6%, respectively). Dry mouth occurred more frequently with bupropion SR (19%) than with sertraline (14%) or placebo (12%), although the differences were not significant. Changes in vital signs were similar in all groups. Similar (small, but not statistically significant) decreases in mean body weight were seen in both the bupropion SR (-1.06 kg) and sertraline (-0.79 kg) groups, whereas the placebo group experienced a minor increase (0.21 kg). Although bupropion SR and sertraline were similarly well tolerated and effective in the treatment of depression, sertraline treatment was more often associated with sexual dysfunction and certain other adverse events compared with bupropion SR and placebo. Therefore, bupropion SR may be an appropriate choice as an antidepressant for the treatment of sexually active patients.",2001.0,0,0
33,10365192,Pergolide mesylate for cocaine abuse: a controlled preliminary trial.,F R Levin; D McDowell; S M Evans; D Brooks; C Spano; E V Nunes,"A small, controlled study was conducted to assess whether pergolide mesylate has clinical promise as a treatment for cocaine abuse prior to embarking on a larger, randomized, double-blind, controlled trial. Fourteen individuals were placed on placebo for 2 weeks, followed by a 24-week single-blind study in which they were placed on pergolide for 12 weeks, followed by placebo for 12 weeks. Another 14 patients received single-blind placebo for two weeks and then were randomized into a 24-week double-blind, placebo-controlled, multiple baseline design. Initially, patients enrolled in the study were placed on risperidone (n = 9) or placebo (n = 5). During the first 12 weeks, retention was worse for those receiving pergolide compared to risperidone or placebo. Neither risperidone nor pergolide were more efficacious in reducing cocaine use than placebo. Although earlier open studies found pergolide to show promise as a treatment for cocaine abuse, this study did not support these earlier findings. Comparing an agent to both an active control and placebo group may better predict whether a promising new agent will have clinical utility compared to the standard open trial.",1999.0,0,0
34,10366082,Efficacy of apraclonidine 1% versus pilocarpine 4% for prophylaxis of intraocular pressure spike after argon laser trabeculoplasty.,J Ren; D H Shin; H S Chung; C M Birt; B K Glover; M S Juzych; B A Hughes; C Kim,"The authors compared the efficacy of apraclonidine 1% versus pilocarpine 4% prophylaxis of post-argon laser trabeculoplasty (ALT) intraocular pressure (IOP) spike. Prospective randomized clinical trial. Two hundred twenty-eight eyes of 228 patients with primary open-angle glaucoma undergoing ALT were studied. Patients were given 1 drop of either apraclonidine 1% (n = 114) or pilocarpine 4% (n = 114) 15 minutes before ALT. Peri-ALT IOPs and incidences of post-ALT IOP spikes at 5 minutes, 1 hour, and 24 hours were compared between the two groups. The two groups were similar in age, race, and medical dependency. Post-ALT mean IOPs at 5 minutes, 1 hour, and 24 hours were significantly lower than pre-ALT mean IOPs in both apraclonidine (P < 0.001) and pilocarpine (P < 0.001) groups. Incidences of IOP spikes greater than 1, 3, and 5 mmHg at 1 hour post-ALT were 21.1%, 14.9%, and 8.8% for the apraclonidine group and 12.3%, 5.3%, and 4.4% for the pilocarpine group (P = 0.076, 0.015, and 0.18 chi-square test). In the apraclonidine prophylaxis group, patients on long-term apraclonidine showed significantly higher incidence of post-ALT IOP spike than the patients without such long-term apraclonidine use (35.7%, 15 of 42 eyes, vs. 12.5%, 9 of 72 eyes; P = 0.003). In addition, peri-ALT pilocarpine prophylaxis tended to be less effective in patients undergoing long-term pilocarpine therapy but without statistical significance (17.4%, 8 of 46 eyes, vs. 9.4%, 6 of 64 eyes; P = 0.17). Peri-ALT pilocarpine 4% was at least as effective as, if not more effective than, apraclonidine 1% in post-ALT IOP spike prophylaxis. Peri-ALT apraclonidine prophylaxis was not effective in patients on long-term apraclonidine, and peri-ALT pilocarpine prophylaxis tended to be less effective in patients undergoing long-term pilocarpine therapy. Pilocarpine 4% can be considered as a first-choice drug for post-ALT IOP spike prophylaxis, especially in patients under treatment with apraclonidine.",1999.0,0,0
35,10376125,Choreoathetoid movements in cocaine dependence.,G Bartzokis; M Beckson; D A Wirshing; P H Lu; J A Foster; J Mintz,"To evaluate the severity of choreoathetoid movements in cocaine dependent (CD) subjects and age-matched normal control subjects. Choreoathetoid movements were evaluated using the Abnormal Involuntary Movement Scale (AIMS) in samples of 71 CD, 56 normal control, and 9 amphetamine-dependent male subjects. The CD subjects had a significantly increased nonfacial (limbs plus body) AIMS subscore. When the nonfacial AIMS scores of the two groups were compared in relation to age, a significant age by diagnosis interaction was observed, indicating that the differences between groups were most marked in the younger age groups. The facial AIMS scores were also increased but only in the youngest CD cohort (under 32 years of age). The comparison group of 9 younger amphetamine-dependent subjects also showed increased AIMS scores. Increases in choreoathetoid movements in younger cocaine and amphetamine-dependent subjects may be related to their psychostimulant use. The absence of differences in choreoathetoid movements between the older CD subjects and normal control subjects may represent an age-related self-selection effect.",1999.0,0,0
36,10376129,EEG correlates of methylphenidate response among children with ADHD: a preliminary report.,S K Loo; P D Teale; M L Reite,"Recent electrophysiologic studies have found fairly consistent differences between children with attention-deficit/hyperactivity disorder (ADHD) and age-matched control subjects. The present study examined electroencephalogram (EEG) changes associated with a double blind, placebo-controlled administration of methylphenidate among children with ADHD. Subjects were 10 children, ages 8 to 13, with a primary diagnosis of ADHD. Brain electrical activity was recorded with 7 electrodes in the frontal, central, and midline areas during baseline and cognitive activation conditions. Repeated-measures ANOVAs indicate that children exhibiting a positive medication response had reductions of theta and alpha as well as increased beta in the frontal regions, while nonresponders showed the opposite pattern (p < .05). Significant correlations between improvement on a vigilance task and changes in beta activity in the frontal electrodes emerged as well. These preliminary findings indicate that there are different electrophysiologic correlates to methylphenidate among ADHD children who are medication responders and nonresponders.",1999.0,0,0
37,10385840,Behavioral and electrophysiologic predictors of treatment response to stimulants in children with attention disorders.,R J Chabot; A A Orgill; G Crawford; M J Harris; G Serfontein,"Behavioral and quantitative electroencephalography (EEG) techniques were used to evaluate treatment response to stimulant therapy in children with attention disorders. A sample of 130 children with attention disorders were evaluated with Conners and Diagnostic and Statistical Manual of Mental Disorders--III rating scales, and with neurometric quantitative EEG before and 6 to 14 months after treatment with stimulants. Significant quantitative EEG differences were found between the normal control population (N = 31) and the children with attention problems. Quantitative EEG abnormalities involved increased theta or alpha power, greatest in frontal regions, frontal theta/alpha hypercoherence, and posterior interhemispheric power asymmetry. Behavioral improvement after stimulant treatment was seen in 81.5% of the children with attention-deficit hyperactivity disorder and 44.7% of the children with attention-deficit disorder, with the degree of correspondence between behavioral and quantitative EEG changes at 78.5%. Pretreatment clinical and quantitative EEG features could predict treatment response with a sensitivity of 83.1% and a specificity of 88.2%. A combined behavioral and quantitative EEG approach can be useful for following and predicting treatment response to stimulants in children with attention disorders.",1999.0,0,0
38,10401913,Clozapine and obsessions in patients with recent-onset schizophrenia and other psychotic disorders.,L de Haan; D H Linszen; R Gorsira,"The increase or emergence of obsessions was compared in young patients with recent-onset schizophrenia or other psychotic disorders taking clozapine and other antipsychotic drugs. We conducted a retrospective cohort study. Subjects were 121 consecutively admitted patients diagnosed with DSM-III-R schizophrenia, schizoaffective disorder, schizophreniform disorder, or psychotic disorder not otherwise specified. Obsessions were diagnosed according to DSM-IV criteria. More clozapine-treated subjects (20.6%) than subjects treated with other antipsychotic drugs (1.3%) experienced an emergence or increase of obsessions (p<.01). Use of clozapine is associated with the emergence or increase of obsessions in early-phase schizophrenia.",1999.0,0,0
39,10416728,Risperidone versus haloperidol on secondary memory: can newer medications aid learning?,R S Kern; M F Green; B D Marshall; W C Wirshing; D Wirshing; S R McGurk; S R Marder; J Mintz,"The introduction of the new generation of antipsychotic medications for the treatment of schizophrenia has been accompanied by a growing interest in the neurocognitive effects of these drugs. The present study compared the effects of risperidone and haloperidol on secondary memory in a group of treatment-resistant schizophrenia patients. The study design included a baseline phase and two double-blind phases in which patients were randomly assigned to medication under two different dose conditions (fixed dose and flexible dose). Secondary memory was assessed at baseline, fixed-dose, and flexible-dose phases, using the California Verbal Learning Test (CVLT). Six measures were selected, which formed three factors (general verbal learning ability, retention, and learning strategy). Risperidone-treated patients showed greater improvement than haloperidol-treated patients in general verbal learning ability, a finding characterized by significant treatment effects on CVLT measures of learning acquisition, recall consistency, and recognition memory. After controlling for benztropine status, differences on the measures of learning acquisition and recall consistency remained significant, and differences in recognition memory weakened slightly (p = 0.07). No significant treatment effects were noted on retention or learning strategy. These findings suggest that risperidone may exert a facilitating effect on the acquisition of new verbal information, an effect that does not appear to be due to the activation of semantic encoding strategies.",2001.0,0,0
40,10417466,Nefopam and clonidine in the prevention of postanaesthetic shivering.,S N Piper; S W Suttner; C C Schmidt; W H Maleck; B Kumle; J Boldt,"Postanaesthetic shivering affects up to 70% of patients after general anaesthesia, and may be very distressing. Various drugs have been used to treat or prevent postanaesthetic shivering, but the ideal one has not yet been found. Sixty patients undergoing elective abdominal or orthopaedic surgery under general anaesthesia were included in a randomised, double-blind study. Patients received clonidine (3 microgram.kg-1), nefopam (0.15 mg.kg-1) or saline 0.9% as a placebo at the end of surgery, prior to extubation. Nefopam and clonidine significantly reduced the incidence and severity of shivering in comparison with the placebo. The recovery time, between the end of anaesthesia and extubation, was significantly longer in the clonidine-treated patients [13.6 (5.2) min] than in either the nefopam [9.6 (2.8) min] or the placebo [10.0 (5.4) min] groups. Mean arterial blood pressure and heart rate were significantly lower in the clonidine group compared with both other groups. Our results suggest that nefopam and clonidine are effective in the prevention of postanaesthetic shivering. However, following clonidine administration the recovery time was prolonged and hypotension was significantly greater than after nefopam.",2000.0,0,0
41,10423584,Alpha 2-agonist versus alpha 1-antagonist in mild-to-moderate hypertension: comparison of transdermal clonidine and terazosin monotherapies.,S I Harris; C Alvarez,"A double-blind, double-dummy, parallel-group trial that used a predominantly Hispanic patient population with mild-to-moderate hypertension was designed to compare the efficacy, safety, and acceptability of monotherapy with either transdermal clonidine applied once a week or terazosin tablets taken once a day. Of 44 patients admitted, 20 of 22 in the transdermal clonidine group and 15 of 21 in the terazosin group (one patient was lost to follow-up) met the response criteria. These criteria included the completion of 1 full week of therapy with the smallest dose that resulted in a seated diastolic blood pressure of <90 mm Hg and the subsequent entrance into an 8-week maintenance therapy phase. At the end of the 8-week maintenance phase the mean seated diastolic blood pressure remained <90 mm Hg in the clonidine cohort but not in the terazosin cohort, yet the difference was not statistically significant. There was a significantly better response to clonidine when all patients who received treatment were considered. No adverse first-dose effects were experienced with terazosin. One patient who received transdermal clonidine developed contact dermatitis and withdrew from the study prematurely. The most common side effects associated with clonidine were dry mouth and fatigue while those associated with terazosin were headache and fatigue. Compliance was excellent in both groups. Seventy-nine percent of patients found transdermal clonidine preferable to the oral regimen.",2000.0,0,0
42,10432470,Effect of methylphenidate on attention in children with attention deficit hyperactivity disorder (ADHD): ERP evidence.,G A Sunohara; M A Malone; J Rovet; T Humphries; W Roberts; M J Taylor,"Methylphenidate is the most common treatment for attention deficit hyperactivity disorder (ADHD) and has been shown to improve attention and behaviour. However, the precise nature of methylphenidate on specific aspects of attention at different dose levels remains unclear. We studied methylphenidate effects in ADHD from a neurophysiological perspective, recording event-related potentials (ERPs) during attention task performance in normal controls and children with ADHD under different dose conditions. Twenty children with ADHD and 20 age matched controls were assessed with a continuous performance task requiring subjects to identify repeating alphabetic characters. ERPs and behavioural measures were recorded and analyzed for trials where a correct response was made. The ADHD group was assessed off drug (baseline) and on placebo, low (0.28 mg/kg) and high (0.56 mg/kg) dose levels of methylphenidate. The results showed that the ADHD group at baseline was more impulsive and inattentive than controls and had shorter P2 and N2 latencies and longer P3 latencies. Low dose methylphenidate was associated with reduced impulsivity (fewer false alarms) and decreased P3 latencies, whereas the higher dose level was associated with reduced impulsivity and less inattention (more hits), as well as increased P2 and N2 latencies and decreased P3 latencies. Amplitudes were unaffected and there were no adverse effects of the higher dose for any of the children. These results suggest differential dosage effects and a dissociation between dose levels and aspects of processing.",1999.0,0,0
43,10432791,"Perceptual and response interference in children with attention-deficit hyperactivity disorder, and the effects of methylphenidate.",L M Jonkman; C Kemner; M N Verbaten; H Van Engeland; J L Kenemans; G Camfferman; J K Buitelaar; H S Koelega,"Fourteen children with attention-deficit hyperactivity disorder (ADHD) and 14 normal control children were compared with respect to stimulus- and response-related processes. Subjects with ADHD took part in two additional sessions under methylphenidate or placebo. In both experiments, performance and electrophysiological measures such as the P2, N2, and P3 components of event-related potential and electromyogram (EMG) activity were measured during an Eriksen flanker task. In both groups of children, reaction times (RTs) to arrow stimuli incongruent with the target were longer than those to neutral stimuli (response interference), which were again slower than RTs to target-alone stimuli (perceptual interference). Children with ADHD made more errors to incongruent stimuli and showed more response interference. For correct responses, no differences between the groups in response interference effects on reaction time, P2, N2, and P3 latency, or EMG onset were found. Methylphenidate had a general enhancing effect on accuracy but did not specifically reduce interference from the flanking stimuli. Methylphenidate had no effects on RT, N2 and P2 latency, P3 amplitude or latency, or EMG activity. The conclusion that methylphenidate did not influence response processes contrasts sharply with findings reported by authors using the Sternberg memory search task.",1999.0,0,1
44,10434228,Population pharmacokinetics of methylphenidate in children with attention-deficit hyperactivity disorder.,R I Shader; J S Harmatz; J R Oesterheld; D X Parmelee; F R Sallee; D J Greenblatt,"Sources of individual variation in plasma methylphenidate (MP) concentrations during usual clinical use are not established. This was evaluated in a series of patients receiving clinical treatment with MP. A single plasma MP concentration was determined in each of 273 children and adolescents ages 5 to 18 years (mean: 11.1 years) who were clinically good responders to MP for the treatment of attention-deficit hyperactivity disorder. MP was given on a twice-daily schedule (mean dose: 25 mg/day) in 40% of patients and three times daily (mean dose: 39.3 mg/day) in 60%. A nonlinear regression model was applied to estimate overall population values of MP clearance and elimination half-life (t1/2), assuming a one-component model with first-order absorption and elimination, and further assuming that clearance is linearly related to body weight. The model incorporated each patient's dosage size and schedule, body weight, and time of the plasma sample. Iterated solutions of best fit were: t1/2, 4.5 hours (95% confidence interval [CI]: 3.1-8.1 hours), and apparent clearance, 90.7 ml/min/kg (95% CI: 74.6-106.7 ml/min/kg). The model explained 43% of the overall variance in MP concentrations (r2 = 0.43, p < .001). In a small subsample (N = 16), a second plasma sample was drawn at the same time of day and at the same dose; the correlation between the two concentration values was 0.83. The relatively noninvasive approach used in this study allows the assessment of pharmacokinetic properties of medications under conditions of appropriate clinical use in special populations such as children, adolescents, and the elderly.",1999.0,0,0
45,10434822,,,,,0,0
46,10435394,Pharmacokinetic-pharmacodynamic modeling of risperidone effects on electroencephalography in healthy volunteers.,D Y Lee; K U Lee; J S Kwon; I J Jang; M J Cho; S G Shin; J I Woo,"CNS-active drugs produce specific electroencephalographic changes and the concentration-effect relationship of antipsychotics may be elucidated by adopting electroencephalography (EEG) as an effect measurement tool. The purpose of the present study was to determine the concentration-effect relationship of risperidone by assessing the EEG effect after oral administrations of single dose risperidone in healthy young males. Nine healthy male volunteers received a 1 mg single oral dose of risperidone according to a placebo controlled crossover design. Plasma levels of risperidone and its active metabolite 9-hydroxyrisperidone were measured by radioimmunoassay. Quantitative EEG parameters were obtained for each of four frequency bands through spectral EEG analysis. The difference in the absolute power in the delta frequency band for the F3 lead between risperidone and placebo was used as a drug effect parameter. For pharmacokinetic-pharmacodynamic modeling, the hypothetical effect compartment kinetically linked to plasma by a first-order process was postulated. All curve fittings were done with the non-linear curve-fitting program NONLIN. Our results showed that absolute powers in delta and theta frequency bands were higher for risperidone administration than for placebo at all EEG leads, and the maximum effects were detected at about 3 h after administration of the drug. The hysteresis loop was observed in the plot of plasma concentration of risperidone or sum of risperidone and 9-hydroxyrisperidone (Cp) versus EEG effect for each subject. A linear model adequately described the relationship between the effect compartment concentrations (Ce) and EEG effects, and the two limbs of hysteresis in the Cp-effect plot were collapsed in the Ce-effect plot for risperidone or risperidone plus 9-hydroxyrisperidone. The increases of absolute power for delta and theta frequency bands of EEG were induced by single oral administration of risperidone. The linear PK-PD model fit well with the relationship between effect compartment concentrations (Ce) and EEG effects of risperidone.",1999.0,0,0
47,10435771,A comparison of olanzapine with haloperidol in cannabis-induced psychotic disorder: a double-blind randomized controlled trial.,M Berk; S Brook; A I Trandafir,"Little controlled data exist on the treatment of substance induced psychotic disorders. In this study, 30 patients meeting DSM-IV criteria for cannabis induced psychotic disorder were randomly allocated to receive either olanzapine or haloperidol in a 4-week double-blind clinical trial. There were no significant outcome differences between the two groups on any of the primary outcome measures, the Brief Psychiatric Rating Scale (haloperidol 25.7; olanzapine 27.1; P = 0.70); Clinical Global Impression (CGI) severity scale (haloperidol 1.8, olanzapine 2.3; P = 0.21) or the CGI improvement scale (haloperidol 1.3, olanzapine 1.7; P = 0.16). The haloperidol group however, developed significantly more extrapyramidal side-effects as measured by the Simpson Angus Scale (haloperidol 11.4, olanzapine 2.5; P = 0.014). Significantly (P = 0.027) more biperidin was used for extrapyramidal side-effects in the haloperidol (7.143 mg) than in the olanzapine (0.357 mg) group. Olanzapine appears to be as effective as haloperidol in the treatment of cannabis induced psychotic disorder, but is associated with a lower rate of extrapyramidal side-effects.",1999.0,0,0
48,10440593,"Double-blind, randomized, placebo-controlled clinical trials with non-prescription medications for the treatment of obesity.",F Greenway; D Herber; W Raum; D Herber; S Morales,"Phenylpropanolamine (PPA) and benzocaine are non-prescription medications approved for treating obesity. The dose of PPA for weight loss is 75 mg/day. PPA has the same chemical similarity to pseudoephedrine that amphetamine has to methamphetamine. Because benzocaine causes weight loss by altering taste and PPA by central appetite suppression, they may induce additional weight loss when combined. These studies explore the safety and efficacy of low-dose PPA, pseudoephedrine, and PPA with benzocaine in causing weight loss. Study 1 compared PPA 12.5 mg tid with 25 mg tid and placebo in a 6-week trial in 108 obese subjects. Study 2 compared pseudoephedrine 120 mg/day and a placebo in a 12-week trial with 72 obese subjects. Study 3 compared 4 groups of 20 obese subjects using PPA 75 mg/day, benzocaine gum 96 mg/day, PPA with benzocaine gum, and a placebo over 12 weeks. Both doses of PPA gave twice the weight loss of placebo, but the difference did not reach statistical significance. Pseudoephedrine was no different than placebo in inducing weight loss. The PPA with benzocaine group had more adverse events than the benzocaine group (p = 0.03), the placebo group (p = 0.03), or the PPA group (p = 0.09) without additional weight loss. We conclude that further studies with low-dose PPA for weight loss are indicated, that pseudoephedrine is not effective for weight loss, and that adding benzocaine to phenylpropanolamine increases adverse effects without increasing weight loss.",1999.0,0,0
49,10453796,Development of depression during placebo-controlled trials of bupropion for smoking cessation: case reports.,C A Patten; T A Rummans; I T Croghan; R D Hurt; J T Hays,"Recent attention has focused on the relationship between depression and smoking cessation. This article describes 5 cases of severe depression that occurred during 2 multicenter trials using bupropion for smoking cessation. Subjects were participants in 2 randomized, double-blind, placebo-controlled studies investigating the efficacy of bupropion for smoking cessation. Data from both trials were restricted to subjects at the Rochester, Minn., site in order to have access to the medical records for information on depression diagnosis, treatment, and follow-up. The first trial involved 205 smokers who received active bupropion or placebo for 7 weeks. In the second trial, 252 smokers received open-label bupropion therapy for 7 weeks. Those abstinent from smoking at the end of week 7 (N = 148) were randomly assigned to a 45-week, double-blind, relapse-prevention phase. In the first trial, 1 of the 205 participants (0.49%) experienced major depression during the 7-week treatment phase. In the second trial, none of the 252 subjects developed major depression during the 7-week, open-label phase. When results of both trials across the 7-week treatment phase (study 1, N = 205; study 2, N = 252) are combined, the rate of developing major depression was 0.22% (1 of 457). Of the 457 subjects, none of the 51 who received placebo and 1 (0.25%) of the 406 who received active bupropion developed major depression. In the second trial, 4 (2.7%) of the 148 subjects randomly assigned to the 45-week, relapse-prevention phase developed depression. Overall, 4 of the 5 cases from the 2 trials had a past history of major depression prior to study entry, but none had current major depression. Major depression may occur in some individuals during smoking cessation treatment with bupropion.",1999.0,0,0
50,10468313,Safety of amisulpride (Solian): a review of 11 clinical studies.,C Coulouvrat; L Dondey-Nouvel,"We assessed the overall safety profile of amisulpride based on the results from 11 clinical studies performed in patients suffering from schizophrenia with predominance of positive or negative symptoms. A total of 1933 patients were randomly assigned to treatment with amisulpride (n = 1247) or haloperidol (n = 309), risperidone (n = 113), flupentixol (n = 62) and placebo (n = 202). Safety data collection was performed using open reporting, UKU scales or specific extrapyramidal side-effect scales; electrocardiogram recording and vital signs examination; laboratory data collection. Amisulpride demonstrated a satisfactory global safety profile in the range of doses usually prescribed. The number of patients having at least one extrapyramidal side-effect was higher in haloperidol patients compared with both amisulpride and risperidone patients (50% versus 30% in the two latter groups). For endocrine events, a similar rate was observed between amisulpride and risperidone groups (4% versus 6%, respectively) versus 1% in the haloperidol group. Electrocardiogram results were satisfactory, confirmed by the absence of cardiovascular events. The overall laboratory safety profile of amisulpride did not show clinically relevant abnormalities in liver function tests nor haematological abnormalities. Our extensive clinical data confirm the satisfactory safety profile of amisulpride which is superior to standard reference compounds.",1999.0,0,0
51,10472699,[Preoperative clonidine comedication within the scope of balanced inhalation anesthesia with sevoflurane in oral surgery procedures].,T Frank; V Thieme; D Olthoff,"Both clonidine and sevoflurane are interesting drugs for anaesthesia in maxillo-facial surgery. The present study was performed to discover how far it is possible to combine the benefits of sevoflurane (fast modulation of depth of anaesthesia, rapid emergence and recovery) and clonidine (reduction of perioperative stress response, prophylaxis of postoperative shivering, analgetic, antiemetic and anaesthetic-saving effect) without compromising the pharmacokinetic of sevoflurane. Twenty-eight patients were included in the present double-blinded prospective study. These patients were randomly treated with an infusion of 4 micrograms kg-1 clonidine (group 1) or a placebo (group 2) preoperatively. For anaesthesia a standardized procedure with fentanyl, propofol, rocuronium, N2O/O2/sevoflurane and an antiemetic prophylaxis with DHB was performed. The depth of anaesthesia was controlled by using spectral edge frequency (target--SEF90 = 10 Hz). Perioperative stress response was assessed by noting the effects on haemodynamic parameters (MAP, heart rate), and emergence and recovery were assessed by using established standardized tests. We confirmed the anaesthetic-saving property of clonidine only for fentanyl (-20%). On the other hand, there was no difference in MAC-sevoflurane values between the groups in keeping a steady target--SEF90 (1.62 +/- 0.26 versus 1.65 +/- 0.24 vol.%). The time until emergence and recovery was not significantly different. Even the occurrence of PONV, the VAS level or the postoperative analgesic requirement did not differ in the two groups. However, the incidence of postoperative shivering was significantly higher in the placebo group. The stress response to intubation or extubation was lower in the clonidine group. The haemodynamic parameters in the clonidine group were intraoperatively always below the baseline, in some cases by more than 20%, making therapy for hypotension or bradycardia frequently necessary. Postoperatively, the majority of the patients showed similar changes in these parameters, but did not reach the 20% mark. Preoperative clonidine comedication seems to complicate the management of anaesthesia. On the other hand, it is beneficial during the early postoperative period (e.g. stability in haemodynamics, prophylaxis of shivering) without compromising emergence and recovery. Our results show that therapy with clonidine should be better placed at the end of anaesthesia.",1999.0,0,0
52,10478300,[Drug therapy of hyperkinetic diseases in adults].,C Adam; M Döpfner; G Lehmkuhl,"Attention deficit hyperactivity disorder (ADHD) is often diagnosed in children. Some major studies proved that symptoms can persist until the patients are grown up and that the prevalence of adult ADHD is underestimated. The classification systems ICD-10 and DSM-IV allow a diagnosis for adults, they differ, however, from childhood regarding symptoms. The diagnostic procedure requires extensive exploration and information from parents and school. Diagnostic interview procedures and questionnaires for self and expert rating are available to date only for English speaking countries. Apart from counselling and psychotherapeutic intervention pharmacotherapy is a third option. Especially stimulants proved to be an efficient treatment. Alternatively tricyclic antidepressants can be considered, other agents play only a minor role. Clinical trials trying to evaluate the efficacy of different pharmacotherapeutic agents are lacking.",1999.0,0,0
53,10480663,The treatment of tardive dyskinesia--a systematic review and meta-analysis.,K V Soares; J J McGrath,"This systematic review aimed to collate randomized controlled trials (RCTs) of various interventions used to treat tardive dyskinesia (TD) and, where appropriate, to combine the data for meta-analysis. Clinical trials were identified by electronic searches, handsearches and contact with principal investigators. Data were extracted independently by two reviewers, for outcomes related to improvement, deterioration, side-effects and drop out rates. Data were pooled using the Mantel-Haenzel Odds Ratio (fixed effect model). For treatments that had significant effects, the number needed to treat (NNT) was calculated. From 296 controlled clinical trials, data were extracted from 47 trials. For most interventions, we could identify no RCT-derived evidence of efficacy. A meta-analysis showed that baclofen, deanol and diazepam were no more effective than a placebo. Single RCTs demonstrated a lack of evidence of any effect for bromocriptine, ceruletide, clonidine, estrogen, gamma linolenic acid, hydergine, lecithin, lithium, progabide, seligiline and tetrahydroisoxazolopyridinol. The meta-analysis found that five interventions were effective: L-dopa, oxypertine, sodium valproate, tiapride and vitamin E; neuroleptic reduction was marginally significant. Data from single RCTs revealed that insulin, alpha methyl dopa and reserpine were more effective than a placebo. There was a significantly increased risk of adverse events associated with baclofen, deanol, L-dopa, oxypertine and reserpine. Meta-analysis of the impact of placebo (n=485) showed that 37.3% of participants showed an improvement. Interpretation of this systematic review requires caution as the individual trials identified tended to have small sample sizes. For many compounds, data from only one trial were available, and where meta-analyses were possible, these were based on a small number of trials. Despite these concerns, the review facilitated the interpretation of the large and diverse range of treatments used for TD. Clinical recommendations for the treatment of TD are made, based on the availability of RCT-derived evidence, the strength of that evidence and the presence of adverse effects.",1999.0,0,0
54,10484947,Risperidone in treatment-refractory schizophrenia.,D A Wirshing; B D Marshall; M F Green; J Mintz; S R Marder; W C Wirshing,"The purpose of this study was to evaluate the clinical safety and efficacy of risperidone compared to haloperidol in patients with treatment-refractory schizophrenia. Sixty-seven medication-unresponsive subjects were randomly assigned to treatment with risperidone (N = 34) or haloperidol (N = 33). After a 3-7 day-placebo washout period, there was a 4-week, double-blind, fixed-dose comparison trial that was followed by a 4-week, flexible-dose phase. Measures of clinical change were quantified by standard psychopathologic and neuromotor instruments. Risperidone demonstrated clinical efficacy superior to that of haloperidol on the total Brief Psychiatric Rating Scale (BPRS) after the first 4 weeks of treatment. Risperidone did not show any advantage over haloperidol after an additional 4 weeks. Overall improvement on the BPRS at 4 weeks was significantly better for the risperidone group (24%) than for the haloperidol group (11%). Risperidone-treated subjects were significantly less likely than haloperidol-treated subjects to require concomitant anticholinergic medication after 4 weeks (20% versus 63%); they also had significantly les observable akathisia (24% versus 53%) and significantly less severe tardive dyskinesia. Baseline characteristics that correlated significantly with risperidone response were positive symptoms, conceptual disorganization, akathisia, and tardive dyskinesia. Risperidone was better tolerated and more effective in a subset of patients with treatment-refractory schizophrenia. Positive psychotic symptoms and extrapyramidal side effects at baseline appear to be powerful predictors of subsequent response to risperidone.",2001.0,0,0
55,10485774,Intravenous regional anesthesia using lidocaine and clonidine.,S S Reuben; R B Steinberg; J L Klatt; M L Klatt,"Clonidine has been added to local anesthetic regimens for various peripheral nerve blocks, resulting in prolonged anesthesia and analgesia. The authors postulated that using clonidine as a component of intravenous regional anesthesia (IVRA) would enhance postoperative analgesia. Forty-five patients undergoing ambulatory hand surgery received IVRA with lidocaine, 0.5%, and were assigned randomly and blindly to three groups. The control group received intravenous saline, the intravenous clonidine group received 1 microg/kg clonidine intravenously, and the IVRA clonidine group received 1 microg/kg clonidine as part of the IVRA solution. After their operations, the patients' pain and sedation scores and analgesic use were recorded. Patients in the IVRA clonidine group had a significantly longer period of subjective comfort when they required no analgesics (median [range]) for 460 min (215-1,440 min), compared with 115 min (14-390 min) for the control group and 125 min (17-295 min) for the intravenous clonidine group (P<0.0001). The patients who received IVRA with clonidine reported significantly lower pain scores 1 and 2 h after tourniquet deflation compared with the other groups, and they required no fentanyl in the postanesthesia care unit. They also required fewer analgesic tablets (325 mg acetaminophen with 30 mg codeine) in the first 24 h (2+/-1, mean +/- SD) compared with the other two groups, 5+/-1 tablets (control) and 4+/-2 tablets (intravenous clonidine) (P<0.0001). No significant postoperative sedation, hypotension, or bradycardia developed in any of the patients. The addition of 1 microg/kg clonidine to lidocaine, 0.5%, for IVRA in patients undergoing ambulatory hand surgery improves postoperative analgesia without causing significant side effects during the first postoperative day.",1999.0,0,0
56,10505583,Precision and comparability of adverse event rates of newer antidepressants.,S Vida; K Looper,"Due to the scarcity of clinical trials (CTs) directly comparing newer antidepressants, clinicians and reviewers often compare drugs on the basis of active drug and placebo-subtracted adverse event rates (AERs) published in references such as the Physician's Desk Reference in the United States, the Compendium of Pharmaceutical Specialities in Canada, and product monographs. This study examined the suitability of the above data and methods for comparing AERs of nine newer antidepressants: bupropion, citalopram, fluoxetine, fluvoxamine, moclobemide, nefazodone, paroxetine, sertraline, and venlafaxine. First, the authors examined data precision and comparability across drugs by analyzing placebo-arm AERs and their 95% confidence limits for each drug and by testing the homogeneity of placebo-arm AERs across drugs. The rationale was that placebo AER heterogeneity is likely a reflection of heterogeneity of nonpharmacologic factors among CTs. For all 16 adverse events examined, placebo AERs were found to be significantly heterogenous, suggesting significant nonpharmacologic heterogeneity across drugs. Second, using placebo AER heterogeneity as a measure of nonpharmacologic heterogeneity, the authors estimated the degree to which active drug and placebo-subtracted AERs were related to nonpharmacologic heterogeneity by estimating the degree of association between active drug and placebo AERs and between placebo-subtracted and placebo AERs. Also, 95% confidence limits for placebo-subtracted AERs were calculated. It was found that most active drug AERs and some placebo-subtracted AERs were significantly correlated with placebo AERs, suggesting a relationship with nonpharmacologic heterogeneity. Placebo-subtracted AERs were less strongly related than were active drug AERs. Finally, the authors discuss factors that may be associated with the observed heterogeneity and offer suggestions that may improve the methodology and reporting of CTs.",1999.0,0,0
57,10505585,"Controlled, double-blind investigation of the clozapine discontinuation symptoms with conversion to either olanzapine or placebo. The Collaborative Crossover Study Group.",G D Tollefson; M A Dellva; C A Mattler; J M Kane; D A Wirshing; B J Kinon,"The abrupt appearance of clozapine discontinuation symptoms represents a particularly unique situation that has not been characterized in a double-blind, placebo-controlled trial. A randomized, double-blind comparison of placebo (N = 53) and olanzapine 10 mg (N = 53) for 3 to 5 days following the abrupt discontinuation of clozapine (< 300 mg/day) was carried out. Subjects were assessed with the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression Scale of Severity, the Montgomery-Asberg Depression Rating Scale (MADRS), and the Mini-Mental State Evaluation. Subsequently both groups received open-label olanzapine (10-25 mg/day) for an additional 9 weeks. Statistically significantly more placebo-treated (24.5%) than olanzapine-treated (7.5%) patients experienced clozapine discontinuation symptoms (p = 0.017). Core symptoms included delusions, hallucinations, hostility, and paranoid reaction and translated into a significantly higher worsening from baseline on the PANSS total, PANSS General Psychopathology subscale, and MADRS among subjects randomly assigned to receive placebo. After open-label treatment with olanzapine for 9 weeks, both groups were clinically stable, suggesting that the discontinuation symptoms were transient. However, subjects who had been randomly assigned to the 3- to 5-day placebo discontinuation segment achieved somewhat less global clinical improvement. Although a pharmacologic interpretation is speculative, evidence of a clozapine discontinuation syndrome was apparent. In most cases, the direct substitution of a pharmacologically similar agent (olanzapine) prevented the syndrome. Clozapine discontinuation or noncompliance should be considered in the differential assessment of an acutely emergent psychosis. The possibility that subjects who experience a clozapine discontinuation syndrome may take longer or are less likely to clinically restabilize warrants further investigation.",1999.0,0,0
58,10513460,Evaluation of individual subjects in the analog classroom setting: II. Effects of dose of amphetamine (Adderall).,S B Wigal; J M Swanson; L Greenhill; B Waslick; D Cantwell; W Clevenger; M Davies; M Lerner; R Regino; E Fineberg; M Baren; R Browne,"Multiple dependent variables were graphed for 29 subjects who participated in a double-blind evaluation of 4 doses of Adderall, plus positive (methylphenidate) and placebo control conditions. Five judges ranked the conditions for each subject, and analyses of individual subjects indicated that these rankings were concordant (reliable) across judges. Consensus rankings were assigned to each subject, and an analysis of these ranks showed that the conditions differed significantly. The choice of best conditions were judged to be across 3 doses of Adderall (10, 15, and 20 mg). This confirms the clinical impression of individual differences in optimal dose of stimulant medication. The methodological, graphical, and statistical methods presented in this article provide a systematic, reliable procedure for evaluating relative response of individuals to different doses of stimulant medication.",1999.0,0,0
59,10513857,Treatment of depression in patients with heart disease.,S P Roose; E Spatz,"Patients with depression are more likely than patients without depression to develop ischemic heart disease and suffer cardiac-related death. Recent evidence suggests that the association between depression and increased cardiac mortality may in part be due to an increase in platelet activity and an imbalance in sympathetic and parasympathetic activity that makes the patient more susceptible to ventricular fibrillation. Available data suggest that the tricyclic antidepressants (TCAs) may increase the risk of mortality in patients with ischemic heart disease. Three studies with the selective serotonin reuptake inhibitors (SSRIs), including a double-blind, randomized comparison of paroxetine with nortriptyline, support the conclusion that the SSRIs have a relatively benign cardiovascular profile. Therefore, they are preferable to the TCAs for treatment of depression in patients at risk for cardiac events. Additional studies are needed to definitively establish the cardiovascular safety of the SSRIs.",1999.0,0,0
60,10520611,Diagnosis of attention-deficit/hyperactivity disorder and use of psychotropic medication in very young children.,M D Rappley; P B Mullan; F J Alvarez; I U Eneli; J Wang; J C Gardiner,"Increases in diagnosis and treatment of attention-deficit/hyperactivity disorder (ADHD) have elicited public and professional concern. Research suggests that this trend warrants the inclusion of previously underdiagnosed children and adults. It is not clear whether this trend includes young children. To identify patterns of diagnosis and treatment of ADHD in very young children over time. Descriptive study of Michigan Medicaid claims data. Inclusion criteria included recorded ADHD diagnosis, continuous Medicaid eligibility during a 15-month period, and age 3 years or younger at the first date of service. Diagnoses of ADHD, conditions commonly comorbid with ADHD, other chronic health conditions, and injuries; treatments such as psychological services and psychotropic medication; and the number of ambulatory visits. We identified 223 children aged 3 years or younger diagnosed with ADHD. Many had conditions commonly comorbid with ADHD (44%), other chronic health conditions (41%), and injuries (40%). More than half received psychotropic medication (57%); fewer received psychological services (27%). Twenty-two different psychotropic medications were used. Patterns included more than 1 psychotropic medication (46%) in 30 combinations of simultaneous use and 44 combinations of sequential use. The mean number of ambulatory visits was 18. Children aged 3 years or younger had ADHD diagnosed and received markedly variable psychotropic medication regimens. Little information is available to guide these practices. The presence of comorbid conditions and injuries attests to these children's vulnerability. Resources must be identified that will enable physicians to better respond to the compelling needs of these children and their families.",1999.0,0,0
61,10553730,Antipsychotic-induced weight gain: a comprehensive research synthesis.,D B Allison; J L Mentore; M Heo; L P Chandler; J C Cappelleri; M C Infante; P J Weiden,"The purpose of this study was to estimate and compare the effects of antipsychotics-both the newer ones and the conventional ones-on body weight. A comprehensive literature search identified 81 English- and non-English-language articles that included data on weight change in antipsychotic-treated patients. For each agent, a meta-analysis and random effects metaregression estimated the weight change after 10 weeks of treatment at a standard dose. A comprehensive narrative review was also conducted on all articles that did not yield quantitative information but did yield important qualitative information. Placebo was associated with a mean weight reduction of 0.74 kg. Among conventional agents, mean weight change ranged from a reduction of 0.39 kg with molindone to an increase of 3.19 kg with thioridazine. Among newer antipsychotic agents, mean increases were as follows: clozapine, 4.45 kg; olanzapine, 4.15 kg; sertindole, 2.92 kg; risperidone, 2.10 kg; and ziprasidone, 0.04 kg. Insufficient data were available to evaluate quetiapine at 10 weeks. Both conventional and newer antipsychotics are associated with weight gain. Among the newer agents, clozapine appears to have the greatest potential to induce weight gain, and ziprasidone the least. The differences among newer agents may affect compliance with medication and health risk.",1999.0,0,0
62,10553837,Interscalene brachial plexus analgesia after open shoulder surgery: continuous versus patient-controlled infusion.,F J Singelyn; S Seguy; J M Gouverneur,"In this prospective, randomized, double-blinded study, we assessed the efficacy of patient-controlled analgesia (PCA) for continuous interscalene analgesia after open shoulder surgery. Sixty patients were divided into three groups of 20. During a 48-h period, they received, via an interscalene catheter, a continuous infusion of 0.125% bupivacaine with sufentanil 0.1 microg/mL and clonidine 1 microg/mL at 10 mL /h in Group 1; a continuous infusion of the same solution at 5 mL/h plus PCA boluses (2.5 mL/30 min) in Group 2; and only PCA boluses (5 mL/30 min) of the same solution in Group 3. Pain scores, sensory block, supplemental analgesia, bupivacaine consumption, side effects, and satisfaction scores were recorded. At 24 and 48 h, sensory block was more frequent and pain control was significantly better in Groups 1 and 2 than in Group 3 (P < 0.001). In Group 3, larger doses of paracetamol were required. Bupivacaine consumption was significantly less in Groups 2 and 3 than in Group 1 (P < 0.001). Satisfaction was significantly higher in Groups 1 and 2 than in Group 3 (P < 0.01). Side effects were comparable in the three groups. We conclude that continuous interscalene analgesia requires a background infusion after open shoulder surgery. Because it reduces the local anesthetic consumption and allows the patients to rapidly reinforce the block shortly before physiotherapy, a basal infusion rate of 5 mL/h combined with PCA boluses (2.5 mL/ 30 min) is the recommended technique. In this study, we demonstrated that continuous interscalene analgesia requires a background infusion to provide efficient pain relief after open shoulder surgery. A basal infusion of 5 mL/h combined with patient-controlled analgesia boluses (2.5 mL/30 min) seems to be the most appropriate technique.",1999.0,0,0
63,10565800,Olanzapine compared to lithium in mania: a double-blind randomized controlled trial.,M Berk; L Ichim; S Brook,"Neuroleptics are of established efficacy in mania. Controlled data on the use of olanzapine in mania is however, absent. In this study, 30 patients meeting DSM-IV criteria for mania were randomly allocated to receive either olanzapine or lithium in a 4 week double-blind randomized controlled design. There were no significant outcome differences between the two groups on any of the primary outcome measures, the Brief Psychiatric Rating Scale (lithium 28.2; olanzapine 28.0; P = 0.44); Clinical Global Impression (CGI) improvement scale (lithium 2.75, olanzapine 2.36; P = 0.163) or the Mania Scale (lithium 13.2, olanzapine 10.2; P = 0.315). Olanzapine was however, significantly superior to lithium on the CGI-severity scale at week 4 (lithium 2.83, olanzapine 2.29; P = 0.025). Olanzapine did not differ from lithium in terms of treatment emergent extrapyramidal side-effects as measured by the Simpson-Angus Scale. Olanzapine appears to be at least as effective as lithium in the treatment of mania.",1999.0,0,0
64,10587774,Pharmacological treatment of depression. Consulting with Dr Oscar.,M J Berber,"To review the pharmacological treatment of depression and to evaluate current strategies for treatment to maximize the benefits of antidepressant medications. MEDLINE was searched to January 1999, using the headings depression, combination, augmentation, lithium, triiodothyronine, pindolol, buspirone, methylphenidate, and electroconvulsive therapy, for randomized controlled trials, systematic overviews, and consensus reports. Recent high-quality reviews were often found. References from papers retrieved were scrutinized for other relevant reports. Preference was given to more recent articles and well-designed studies. Recommendations from academic groups were analyzed. Optimization of antidepressant therapy is the cornerstone of pharmacological treatment of depression. When symptoms persist despite optimization, further strategies include substitution, combination, augmentation, and reviewing and sometimes referring. Decisions are based on the evidence supporting the various strategies. Antidepressants will work only if prescribed correctly. Awareness of the strategies for using antidepressants and evaluating their effectiveness improves primary care physicians' ability to treat this common disorder.",1999.0,0,0
65,10589634,Oral clonidine premedication enhances postoperative analgesia by epidural morphine.,T Goyagi; M Tanaka; T Nishikawa,"This study was designed to evaluate the effects of oral clonidine premedication on postoperative analgesia by epidural morphine in a prospective, randomized, double-blinded design. Sixty consenting patients, scheduled for total abdominal hysterectomy, were randomly assigned to one of three groups (n = 20 each); the clonidine-morphine group received oral clonidine 5 microg/kg 90 min before arriving in the operating room and epidural morphine 2 mg before induction of general anesthesia, the clonidine-placebo group received oral clonidine 5 microg/kg and no epidural morphine, and the placebo-morphine group received no clonidine and epidural morphine 2 mg. An epidural catheter was placed at the L1-2 or L2-3 interspace, and 1.5% lidocaine was used for surgical anesthesia in all patients. General anesthesia was then induced with propofol, and maintained with a continuous infusion of propofol and 67% nitrous oxide in oxygen during surgery. Four patients were subsequently withdrawn from the study. After surgery, patient-controlled analgesia using IV morphine was used to assess analgesic requirement. Morphine consumptions determined every 6 h after surgery in the clonidine-morphine and placebo-morphine groups were significantly less than the clonidine-placebo group until 12 h after surgery, whereas those of the clonidine-morphine group were significantly less than the placebo-morphine group from 13 to 42 h after surgery. Visual analog (pain) scale (VAS) scores in the clonidine-morphine group were significantly lower than the placebo-morphine group at 48 h at rest, and at 1, 24, 36, and 48 h with movement. Similarly, VAS scores in the clonidine-morphine group were significantly lower than the clonidine-placebo group at 1 and 6 h both at rest and with movement, whereas VAS scores in the clonidine-placebo group were significantly lower than the placebo-morphine group at 24, 36, and 48 h at rest and with movement. The incidence of nausea and pruritus was similar between groups. We conclude that the combination of oral clonidine and epidural morphine produces more potent and longer lasting postoperative analgesia than either drug alone without increasing the incidence of adverse effects after major gynecologic surgeries. A small dose of epidural morphine is often used for postoperative analgesia. We found that oral clonidine premedication 5 microg/kg improves the analgesic efficacy of epidural morphine without increasing the incidence of adverse side effects.",1999.0,0,0
66,10591283,A 14-month randomized clinical trial of treatment strategies for attention-deficit/hyperactivity disorder. The MTA Cooperative Group. Multimodal Treatment Study of Children with ADHD.,,"Previous studies have demonstrated the short-term efficacy of pharmacotherapy and behavior therapy for attention-deficit/hyperactivity disorder (ADHD), but no longer-term (i.e., >4 months) investigations have compared these 2 treatments or their combination. A group of 579 children with ADHD Combined Type, aged 7 to 9.9 years, were assigned to 14 months of medication management (titration followed by monthly visits); intensive behavioral treatment (parent, school, and child components, with therapist involvement gradually reduced over time); the two combined; or standard community care (treatments by community providers). Outcomes were assessed in multiple domains before and during treatment and at treatment end point (with the combined treatment and medication management groups continuing medication at all assessment points). Data were analyzed through intent-to-treat random-effects regression procedures. All 4 groups showed sizable reductions in symptoms over time, with significant differences among them in degrees of change. For most ADHD symptoms, children in the combined treatment and medication management groups showed significantly greater improvement than those given intensive behavioral treatment and community care. Combined and medication management treatments did not differ significantly on any direct comparisons, but in several instances (oppositional/aggressive symptoms, internalizing symptoms, teacher-rated social skills, parent-child relations, and reading achievement) combined treatment proved superior to intensive behavioral treatment and/or community care while medication management did not. Study medication strategies were superior to community care treatments, despite the fact that two thirds of community-treated subjects received medication during the study period. For ADHD symptoms, our carefully crafted medication management was superior to behavioral treatment and to routine community care that included medication. Our combined treatment did not yield significantly greater benefits than medication management for core ADHD symptoms, but may have provided modest advantages for non-ADHD symptom and positive functioning outcomes.",1999.0,0,1
67,10591284,Moderators and mediators of treatment response for children with attention-deficit/hyperactivity disorder: the Multimodal Treatment Study of children with Attention-deficit/hyperactivity disorder.,,"Intent-to-treat analyses of the study revealed that medication management, alone or combined with intensive behavioral treatment, was superior to behavioral treatment and community care in reducing attention-deficit/hyperactivity disorder (ADHD) symptoms; but only combined treatment showed consistently greater benefit than community care across other outcome domains (disruptive and internalizing symptoms, achievement, parent-child relations, and social skills). We examine response patterns in subgroups defined by baseline variables (moderators) or variables related to treatment implementation (mediators). We reconducted random-effects regression (RR) analyses, adding factors defined by moderators (sex, prior medication use, comorbid disruptive or anxiety disorder, and public assistance) and a mediator (treatment acceptance/attendance). Study outcomes (N = 579) were upheld in most moderator subgroups (boys and girls, children with and without prior medication, children with and without comorbid disruptive disorders). Comorbid anxiety disorder did moderate outcome; in participants without anxiety, results paralleled intent-to-treat findings. For those with anxiety disorders, however, behavioral treatment yielded significantly better outcomes than community care (and was no longer statistically different from medication management and combined treatment) regarding ADHD-related and internalizing symptoms. In families receiving public assistance, medication management yielded decreased closeness in parent-child interactions, and combined treatment yielded relatively greater benefits for teacher-reported social skills. In families with high treatment acceptance/attendance, intent-to-treat results were upheld. Acceptance/attendance was particularly important for medication treatments. Finally, two thirds of children given community care received stimulants. Behavioral treatment did not significantly differ from, but medication management was superior to, this subgroup. Exploratory analyses revealed that our study (the Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder [MTA]) results were confirmed across most baseline variables and treatment acceptance/attendance. In children with ADHD plus anxiety, behavioral treatment surpassed community care and approached medication-based treatments regarding parent-reported ADHD symptoms.",1999.0,0,0
68,10591285,Development of clinical services for attention-deficit/hyperactivity disorder.,E Taylor,,1999.0,0,0
69,10591309,"Double-blind methylphenidate trials: practical, useful, and highly endorsed by families.",M A Kent; C S Camfield; P R Camfield,"To evaluate a 3-week, randomized, double-blind, methylphenidate placebo-controlled trial (MPT) in routine practice for children with attention-deficit disorder. School-aged children with attention-deficit/hyperactivity disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) who enrolled an ""N of 1"" trial at a pediatric tertiary care center were eligible. Families (n = 50) with a child eligible for the MPT were given 3 bottles of identical capsules. The capsules contained, in random order: placebo of the prescribed dose of methylphenidate (Ritalin) hydrochloride (0.3 mg/kg or 0.6 mg/kg). Families gave the child 1 capsule at 8 AM and 1 capsule at noon. The family, teacher, and physician were blinded for the order of medication. Conners questionnaires (Conners Parent Questionnaire and Conners Teacher Questionnaire) and written comments were completed by parents and teachers at baseline and at the end of each week. Once MPT results were known and following discussion with the physician, families decided whether to continue methylphenidate therapy. Families were interviewed by telephone 14 to 21 months after the MPT. Forty-three (86%) of the 50 eligible children (mean age, 129 months) were contacted. No family found the MPT difficult, but 6 trials were incomplete, usually because of side effects. All families used the MPT to decide if methylphenidate was the correct treatment choice for their child and 68% (34 of 50 families) used the results exclusively. The remaining 16 families believed the MPT was helpful. Overall, 31 (72%) of the 43 children had a good response to methylphenidate treatment--20 (47%) continued to use it for longer than 12 months and 8 (26%) for 2 to 12 months; 3 responders chose not to use it after the MPT. Nine of the 43 families chose not to use methylphenidate treatment; however, all indicated that participating in the MPT helped them to make that decision. In follow-up interviews, the same proportion of methylphenidate users and nonusers reported improvement in many areas of function including significantly less time spent doing homework. Users reported reduced aggression (P<.001) and fewer discipline problems (P<.01) compared with nonusers. An ""N of 1"" MPT was easily performed and permitted families to decide whether to use methylphenidate for long-term treatment of attention-deficit disorder or attention-deficit/hyperactivity disorder. Regardless of methylphenidate use or lack of use, the condition of all of these children was improved at follow-up.",1999.0,0,1
70,10596559,[Adverse hemodynamic changes during laparoscopic cholecystectomy and their possible suppression with clonidine premedication. Comparison with intravenous and intramuscular premedication].,J Málek; J Knor; A Kurzová; M Lopourová,"Laparoscopic cholecystectomies have adverse haemodynamic effects which limit their use in risk patients with heart disease. This applies in particular to significant hypertension. The etiology is analysed in detail in a review of the literature. The authors confirmed in their work involving 21 patients the incidence of these effects and tried to suppress them by premedication with clonidine (CATAPRESAN, Boehringer). 21 patients were given 0.15 mg clonidine in an infusion 15 minutes before operation and 21 patients 0.15 mg clonidine by the i.m. route 60-90 min. before operation. Standard anaesthesia was administered. A highly significant drop in the incidence of hypertension was recorded during operation for systolic pressure (p < 0.001) after both ways of administration, as well as of diastolic pressure (p < 0.01 for intravenous and p < 0.05 for intramuscular premedication). Premedication with intravenous clonidine can be recommended as a routine procedure before laparoscopic cholecystectomies.",1999.0,0,0
71,10596735,Sexual dysfunction associated with the treatment of depression: a placebo-controlled comparison of bupropion sustained release and sertraline treatment.,C C Coleman; L A Cunningham; V J Foster; S R Batey; R M Donahue; T L Houser; J A Ascher,"This study compared the sexual functioning effects as well as the safety and efficacy of bupropion sustained release (bupropion SR) and sertraline. Three hundred sixty-four patients with normal sexual functioning and recurrent major depression were treated with bupropion SR (150-400 mg/day), sertraline (50-200 mg/day), or placebo for 8 weeks in this randomized, double-blind, multicenter study. Patients' depression, sexual functioning, and overall safety were assessed at regular clinic visits. Significantly (P < 0.05) more patients treated with sertraline experienced orgasm dysfunction compared with patients treated with bupropion SR or placebo. Bupropion SR, but not sertraline, was statistically significantly superior to placebo in improving scores on all depression scales by the end of the study. Headache occurred with similar frequency in all groups. Gastrointestinal disturbances occurred more frequently with sertraline; insomnia and agitation occurred more frequently with bupropion SR. Small decreases in mean weight were seen with both active treatments; the placebo group experienced a minor increase in mean weight. Both bupropion SR and sertraline were generally well tolerated, although sertraline was more often associated with sexual dysfunction. Bupropion SR, but not sertraline, was statistically superior to placebo in relieving depression by the end of the study. Bupropion SR may offer advantages over sertraline in treating depressed patients concerned with sexual functioning.",1999.0,0,0
72,10598217,Lofexidine for opiate detoxification: review of recent randomised and open controlled trials.,J Strang; J Bearn; M Gossop,"The objective of this article was to review the data from recently published trials of lofexidine in the treatment of opiate withdrawal, with particular attention to evidence on efficacy, side-effects (particularly hypotension), and the acceptability of this new treatment to the patient population. The authors reviewed data contained within peer-reviewed published reports of clinical trials of lofexidine compared with detoxification using reducing doses of the opiate agonist methadone or the alpha-adrenergic agonist clonidine. Five published reports of clinical trials of lofexidine have been identified from peer-reviewed journals in the eight years between 1990 and 1998--all published within the last three years. Three of the reports compare lofexidine with clonidine, while the remaining two compare it with methadone detoxification. The three comparisons with clonidine find lofexidine to be similar in its moderating effect on the withdrawal syndrome, but without the same extent of problems with hypotension. Comparisons with methadone show a more rapid resolution of withdrawal symptoms with lofexidine--particularly with the accelerated 5-day lofexidine protocol. Such problems of hypotension as were encountered with lofexidine were adequately managed with dose reduction. Acceptability of the treatment to the patient (as measured by retention in treatment) appears to be greater with lofexidine than clonidine, although possibly less than with methadone. Lofexidine is an alpha-2 adrenergic agonist that is increasingly used in the management of opiate withdrawal--notably in the UK. The available data indicate that it is a useful new addition to the armamentarium of the clinician. Future studies should explore its application with improved protocols and in new treatment settings. This article reviews the recent advances in the study of lofexidine as a new treatment for opiate detoxification. It examines the background of the development and introduction of lofexidine into the U.K., with data on the extent to which it is now used in the U.K. in the treatment of opiate addiction. A review is then provided of the published evidence on the use of lofexidine in the management of opiate detoxification, mainly concentrating on the data from recent double-blind randomised trials. Finally, the possible future role of lofexidine in this field is considered.",1999.0,0,0
73,10601673,Relative potency of epidural to intrathecal clonidine differs between acute thermal pain and capsaicin-induced allodynia.,J C Eisenach; D D Hood; R Curry,"Clonidine is approved in the US for epidural administration in the treatment of intractable neuropathic cancer pain, but is also administered intrathecally for this indication and both epidurally and intrathecally in the treatment of acute, postoperative pain. The purpose of the current study was to estimate the relative potency of clonidine by epidural and intrathecal routes in the treatment of capsaicin-induced hyperalgesia and allodynia as a model of central hypersensitivity and of noxious heat as a model of acute pain. Twenty-four healthy volunteers were randomized to receive either intrathecal clonidine (75, 150, or 300 micrograms) or epidural clonidine (150, 300, or 600 micrograms) and rated pain from a Peltier-controlled thermode at a lumbar, thoracic, and cervical dermatomal site before and after drug administration. In addition, they rated pain from intradermal capsaicin injections at a lumbar dermatome before and 60 min after clonidine injection and described areas of hyperalgesia and allodynia to mechanical stimuli. Clonidine's effect differed with route of administration and modality of sensory testing. For acute thermal pain, intrathecal clonidine produced a dose-dependent analgesia with a lumbar>thoracic>cervical gradient, whereas only one dose of epidural clonidine reduced thermal pain and this was at the thoracic testing site. In contrast, the potency of clonidine to reduce capsaicin-induced allodynia was similar between the two routes of injection, and for hyperalgesia, clonidine was only slightly more potent after intrathecal than epidural injection. These data support clinical studies from non-comparative trials and suggest there is a >6-fold potency ratio of intrathecal:epidural administration of clonidine for acute pain, but a <2-fold potency ratio for these routes for mechanical hypersensitivity.",2000.0,0,0
74,10606837,Pharmacokinetic analysis of felodipine-grapefruit juice interaction based on an irreversible enzyme inhibition model.,H Takanaga; A Ohnishi; H Matsuo; H Murakami; H Sata; K Kuroda; A Urae; S Higuchi; Y Sawada,"Aims Ingestion of grapefruit juice (GFJ) alters the pharmacokinetics of various orally administered drugs. Quantitative evaluation of this GFJ-drug interaction is required for the proper clinical management of patients. Methods Using felodipine as a model drug, we constructed a pharmacokinetic model based on irreversible inhibition of intestinal cytochrome P450 3A4 (CYP3A4) by GFJ. We fitted previously published data [5, 6] for felodipine ER (extended release formulation) to the ratio of CLGI,int before and after grapefruit juice ingestion by nonlinear least-squares regression analysis to estimate the reaction rate constant between GFJ and CYP3A4 (K) and the elimination rate constant of CYP3A4 (k ). The model gave a turnover rate of CYP3A4 of 0.0849 h-1, corresponding to a half-life of 8.16 h, in agreement with reported values. The AUC-time profiles of felodipine ER in the case of different amounts and schedules of GFJ ingestion were simulated using the parameter values estimated from the model. The modelling leads to the important conclusion that GFJ-felodipine interaction increases with increasing frequency and amount of GFJ ingestion, and that an interval of 2-3 days between GFJ intake and felodipine administration is necessary if GFJ-felodipine interaction is to be avoided.",2000.0,0,0
75,10606838,Effect of caffeine on clozapine pharmacokinetics in healthy volunteers.,S Hägg; O Spigset; T Mjörndal; R Dahlqvist,"To assess the effects of caffeine on the pharmacokinetics of clozapine in healthy volunteers. This was an open label randomized crossover study in 12 nonsmoking healthy male volunteers. The subjects received a single oral dose of 12.5 mg clozapine in each phase with or without concomitant intake of caffeine (mean dose: 550 mg day-1, range: 400-1000 mg day-1 ). Serum concentrations of clozapine and its metabolites desmethyl-clozapine and clozapine-N-oxide were measured during a 48 h period in each phase. In addition, serum concentrations of caffeine and the metabolite paraxanthine were monitored. A 19% increase in mean clozapine AUC(0,infinity) (P=0.05) and a 14% decrease of mean oral clearance of clozapine were observed during concomitant intake of caffeine (P=0.05) compared with intake of only clozapine. Statistically significant decreases of mean ratios between AUC(0, 12h) for desmethyl-clozapine and AUC(0,12h) for clozapine (-18%), and between AUC(0,12h) for clozapine-N-oxide and AUC(0,12h) for clozapine (-23%) were observed during the caffeine phase (P=0.03 and 0.02, respectively). Oral clearance of clozapine and the ratio AUC(0, 12h) for desmethyl-clozapine/AUC(0,12h) for clozapine were correlated with the paraxanthine/caffeine ratio in serum after intake of caffeine (rs=0.62; P=0.03 and rs=0.77; P=0.003, respectively). These results suggest that caffeine in daily doses of 400-1000 mg inhibits the metabolism of clozapine to an extent that might be clinically significant in certain individuals.",2000.0,0,0
76,10616134,Validation of a Bengali adaptation of the Conners' Parent Rating Scale (CPRS-48).,D K Pal; G Chaudhury; T Das; S Sengupta,"The Conners' Parent Rating Scales (CPRS) have been used to measure behavioural problems in drug trials in children for many years. This study in rural India aimed to validate a translated version of the CPRS-48 for use in a study of anti-epileptic drug side-effects. The Scale was translated into local dialect, back-translated, and piloted among healthy families. The revised version was then administered to mothers of 60 healthy children and 63 children with epilepsy. Tests of internal reliability, test-retest reliability and factor analysis were performed. Cronbach's alpha ranged from 0.60 to 0.75 for the subscales, and correlation coefficients after retesting from 0.84 to 0.99. The overall factor structure was very similar to that reported in the original USA sample. The Bengali version of the CPRS-48 and its Hyperactivity Index have validity for rural Bengali children, and the process demonstrates that such instruments can be usefully adapted for local purposes.",2000.0,0,0
77,10625080,Randomized double-blind controlled trial comparing the effects of ibuprofen with indomethacin on cerebral hemodynamics in preterm infants with patent ductus arteriosus.,J Patel; I Roberts; D Azzopardi; P Hamilton; A D Edwards,"A prospective randomized controlled trial was performed to compare the effects of ibuprofen with indomethacin on cerebral hemodynamics measured using near infrared spectroscopy in preterm infants during treatment for patent ductus arteriosus. Infants were randomly assigned to three intravenous doses of either indomethacin (0.20-0.25 mg/kg, 12 hourly) or ibuprofen (5-10 mg/kg, 24 hourly) and also received a dose of saline. The primary end points of the study were the effects of the first dose on cerebral blood flow (CBF) and cerebral blood volume. Fifteen infants received indomethacin and 18 received ibuprofen. The group mean (SD) values for CBF (mL x 100 g(-1) x min(-1)) before and after the first dose of indomethacin were 13.6 (4.1) and 8.3 (3.1), respectively, the change being significant (p<0.001). In contrast, no significant changes in CBF were observed with the first dose of ibuprofen, the respective before and after values being 13.3 (3.2) and 14.9 (4.7) mL x 100 g(-1) x min(-1). The median (interquartile range) value for change in cerebral blood volume (mL/100 g) after the first dose in the indomethacin group was -0.4 (-0.3 to -0.6) and in the ibuprofen group was 0.0 (0.1 to -0.1), the difference between the two groups being significant (p<0.001). Cerebral oxygen delivery changed significantly after the first dose in the indomethacin group but not in the ibuprofen group. Significant reductions in CBF, cerebral blood volume, and cerebral oxygen delivery also occurred after the 24-h dose of indomethacin, but there were no significant changes after the 48-h dose of saline in the indomethacin group or after the 24- and 48-h doses of ibuprofen. The patent ductus arteriosus closure rates after indomethacin and ibuprofen were 93 and 78%, respectively. We conclude that ibuprofen, unlike indomethacin, has no adverse effects on cerebral hemodynamics and appears to mediate patent ductus arteriosus closure.",2000.0,0,1
78,10632912,Pretreatment with oral clonidine attenuates cardiovascular responses to tracheal extubation in children.,Y Fujii; Y Saitoh; H Tanaka; H Toyooka,"This study was designed to evaluate the effects of diazepam and clonidine orally given preoperatively on cardiovascular responses to tracheal extubation in children. Fifty children, ASA physical status I, aged 4-10 years, undergoing minor elective surgery (inguinal hernia, phimosis) received orally, in a randomized, double-blind manner, diazepam 0.4 mg.kg-1 or clonidine 4 microgram.kg-1 (n=25 of each). These drugs were administered 105 min before an inhalational induction of anaesthesia. The same standard general anaesthetic technique was employed throughout. The maximum changes in heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were less in patients who had received clonidine than in those who had received diazepam (HR, 12 vs 24; SBP, 14 vs 26; DBP, 9 vs 16; mean, P < 0.05). In conclusion, compared to diazepam given orally, pretreatment with oral clonidine attenuates haemodynamic changes associated with tracheal extubation in children.",2000.0,0,0
79,10637400,Dementia in developing countries. A consensus statement from the 10/66 Dementia Research Group.,M Prince,"Less than one-tenth of all population-based research into dementia is directed towards the two-thirds or more of cases living in developing parts of the world. The 10/66 Dementia Research Group has been formed to redress this imbalance, encouraging active research collaboration between centres in different developing countries and between developed and developing countries. The 10/66 group consisted initially of researchers attending a symposium on dementia research in developing countries, held at the 1998 Alzheimer's Disease International conference. They noted a growing interest in this area, with many active researchers and others wishing to start new studies. There was felt to be an urgent need for more research: quantifying prevalence and incidence, exploring regional variations in international collaborations using harmonized methodologies, describing care arrangements for people with dementia, quantifying the impact on caregivers and evaluating the effectiveness of any newly implemented services. Methodological problems need to be addressed, particularly development of culture- and education-fair dementia diagnostic procedures. Good-quality research can generate awareness, pioneer service development and influence policy.",2000.0,0,0
80,10637676,Fact versus fancy concerning the multimodal treatment study for attention-deficit hyperactivity disorder.,P S Jensen,"Findings from the Multimodal Treatment Study of Children With Attention-Deficit Hyperactivity Disorder (ADHD), the MTA, have been much discussed but frequently misinterpreted or mischaracterized. Misinterpretations regarding the specific nature of and rationale for the study design, the effectiveness of the behavioural treatment arm, the possible advantages of combined treatments over single-component (medication management or behavioural therapy) interventions, and the feasibility and applicability of MTA treatments for ""real-world"" practitioners are addressed. Careful interpretation of the MTA findings suggests that for ADHD symptoms, carefully crafted medication-management approaches are superior to behavioural treatment and to routine community care that includes medication. For non-ADHD areas of functioning (for example, social skills, academic performance), combined treatments may offer modest advantages over single-component approaches. Longer-term outcomes past 14 months of intensive MTA treatments (as well as their relative effectiveness with respect to each other) remain unknown, pending further MTA analyses. The MTA treatments by and large consisted of evidence-based ""best practices."" Thus, rather than characterizing these treatments as infeasible, the substantially superior outcomes of these treatments (versus routine clinical care) across diverse settings should help set the standard for future treatment practices in real-world settings. Despite important study limitations, the MTA study, by virtue of its size, scope, and length; parallel-groups design; explicit use of manualized, evidence-based treatments; and comprehensive range of outcome assessments sets an important benchmark for future trials testing new treatments for childhood ADHD and defines a new standard for optimal outcomes that can be achieved with the best of clinical care.",2000.0,0,0
81,10637677,The NIMH multimodal treatment study for attention-deficit hyperactivity disorder: just say yes to drugs alone?,W E Pelham,"The outcome, merits, and limitations of the Multimodal Treatment Study for Children With Attention-Deficit Hyperactivity Disorder (ADHD), the MTA study, are described and discussed. Consideration is given to design issues that make the MTA a landmark study for clinicians and researchers working with ADHD children. These include the large, heterogeneous sample, the state-of-the-art treatment, the lengthy treatment period, the extensive documentation of treatment manuals, and the attention paid to treatment fidelity and adherence. Also highlighted are facets of the design that predisposed the study in favour of a differentially positive outcome for pharmacological relative to behavioural treatment. Primary among these is the fact that outcome was measured 4-6 months after the intensive phase of behaviour treatment and after therapeutic contact with the behaviour therapist had ended but while medication treatment was active and in its most intensive phase. Finally, the outcome for the combined treatment condition in the MTA is discussed in the context of the extant literature and directions for future research.",2000.0,0,0
82,10637678,Lessons from large trials: the MTA study as a model for evaluating the treatment of childhood psychiatric disorder.,M H Boyle; A R Jadad,"To review the methodology of the Multimodal Treatment Study of Children With Attention-Deficit Hyperactivity Disorder (ADHD), the MTA study, and its implications for the design of future child mental health treatment studies. The characteristics of large-scale studies envisioned by trialists engaged in cardiovascular and cancer research provide the framework for reviewing key elements of the MTA study--objectives, research questions, measurement, sampling, and exposure to treatment--and discussing important methodological decisions the MTA investigators had to make. The MTA study is a complex, standardized, carefully implemented, randomized control trial. Review of the MTA study indicated that future studies should be aligned clearly with either effectiveness or efficacy objectives but not both. Questions selected for study should be simple, clear, and important. Measurement, sampling, and data collection must adhere to the principle of simplicity to ensure maximum participation. All methodological decisions should be geared to attaining the research objectives: in effectiveness trials, this means evaluating treatments that have a high potential for dissemination if proven successful and recruiting only new referrals from child mental health settings. The MTA study has raised the standard for technical excellence in child treatment research and will draw attention to some fundamental issues in large-scale child treatment studies, including articulating objectives and questions, setting priorities for measurement and sampling, and identifying treatments for evaluation that have a high probability of dissemination if found effective.",2000.0,0,0
83,10637679,,,,,0,0
84,10637684,Parental knowledge of attention-deficit hyperactivity disorder and opinions of treatment options: impact on enrollment and adherence to a 12-month treatment trial.,P Corkum; P Rimer; R Schachar,"This study examines the relationship between parents' knowledge of attention-deficit hyperactivity disorder (ADHD) and opinions of treatment and their impact on enrolment in and adherence to both pharmacological and nonpharmacological interventions for children with ADHD. Participants in the study were the parents of 81 children who reached diagnostic criteria for ADHD and who were referred to a treatment study of ADHD involving stimulant medication and parent groups. The mothers completed a modified version of the ADHD Knowledge and Opinion Scale (AKOS) prior to receiving diagnostic feedback and prior to the families' decisions to participate in a 12-month randomized trial (medication [methylphenidate or placebo] and parent groups [training or support]). Treatment enrolment and adherence were monitored over the 12-month trial, and families who remained in the study at 12 months completed another modified AKOS. A higher level of knowledge of ADHD was found to be related to more favourable opinions of parent groups but not of medication. Moreover, parents who were more knowledgeable about ADHD were more likely to enroll in both pharmacological and nonpharmacological treatments. Adherence to pharmacological and nonpharmacological treatments was not predicted by parental knowledge of ADHD or opinions of the treatment. Parents' knowledge of ADHD and opinions of treatments play a significant role in enrollment in treatments for their children with ADHD. Providing information to parents regarding ADHD prior to offering treatment modalities could have a favourable impact on treatment enrollment and hence treatment adherence.",2000.0,0,0
85,10647097,Lack of drug interactions between mirtazapine and risperidone in psychiatric patients: a pilot study.,A J Loonen; C H Doorschot; M C Oostelbos; J M Sitsen,"An open-label, non-randomized, pilot study has been performed in inpatients in need of treatment with an antipsychotic (risperidone) and an antidepressant (mirtazapine) with the objective to preliminarily assess a possible pharmacokinetic interaction and the tolerability of this combination. A 1-4-week single drug treatment phase (risperidone 1-3 mg bid or mirtazapine 30 mg nocte) was followed by a 2-4-week combined drug treatment phase at unchanged doses. Twelve patients were enrolled, nine of whom were treated with risperidone in the single drug phase. Results of plasma level measurements are available for six patients and indicate that adding mirtazapine to risperidone does not alter steady-state plasma concentrations of risperidone and its 9-hydroxy metabolite. Data from one patient suggest that adding risperidone to mirtazapine does not result in clinically relevant changes in plasma concentrations of either compound. The combination was well tolerated and no major or relevant adverse events were observed. Adding risperidone to mirtazapine probably does not necessitate a change of the dosage of either drug, but more extensive investigations are needed.",2000.0,0,0
86,10653210,Laboratory measures of methylphenidate effects in cocaine-dependent patients receiving treatment.,J D Roache; J Grabowski; J M Schmitz; D L Creson; H M Rhoades,"Two experiments examined the effects of methylphenidate in male and female patients enrolled in an outpatient treatment program for primary cocaine dependence. The first study was a component of a double-blind efficacy trial wherein 57 patients were first tested in a human laboratory for their initial responsiveness to medication. Patients were randomly assigned to receive either placebo or methylphenidate treatment and received their first dose in the human laboratory environment before continuing in outpatient treatment. Methylphenidate was given as a 20-mg sustained-release dose (twice daily) plus an additional 5-mg immediate-release dose combined with the morning dose. Methylphenidate increased heart rate and subjective ratings; however, the subjective effects were primarily of a ""dysphoric"" nature, and significant effects were limited to increases in anxiety, depression, and anger on the Profile of Mood States; shaky/jittery ratings on a visual analog scale; and dysphoria on the lysergic acid diethylamide (LSD) scale of the Addiction Research Center Inventory. Methylphenidate did not increase cocaine craving nor ratings suggesting abuse potential (i.e., Morphine-Benzedrine Group or drug-liking scores, etc.). None of the drug effects observed in the human laboratory was of clinical concern, and no subject was precluded from continuing in the outpatient study. After outpatient treatment completion, 12 patients were brought back into a second double-blind human laboratory study in which three doses (15, 30, and 60 mg) of immediate-release methylphenidate were administered in an ascending series preceded and followed by placebo. Methylphenidate produced dose-related increases in heart rate, subjective ratings of shaky/jittery, and LSD/dysphoria without significantly altering cocaine craving or stimulant euphoria ratings. These results suggest that stimulant substitution-type approaches to the treatment of cocaine dependence are not necessarily contraindicated because of cardiovascular toxicity or medication abuse potential. However, they also suggest that the subjective effects of methylphenidate may not be positive enough for an adequate replacement approach.",2000.0,0,0
87,10660814,"A pilot study of methylphenidate, clonidine, or the combination in ADHD comorbid with aggressive oppositional defiant or conduct disorder.",D F Connor; R A Barkley; H T Davis,"A pilot comparison of the safety and efficacy of methylphenidate (MPH) combined with clonidine, clonidine monotherapy, or MPH monotherapy in 6- to 16-year-old children diagnosed with attention deficit hyperactivity disorder (ADHD) and comorbid aggressive oppositional defiant disorder or conduct disorder was completed. Study design was a 3-month, randomized, blinded, group comparison with eight subjects per group. No placebo comparison was used. All three treatment groups showed significant improvements in attention deficits, impulsivity, oppositional, and conduct disordered symptoms as assessed by parent and teacher rating scales and laboratory measures. Significant differences among treatment groups were found only on a few measures. Only the clonidine monotherapy group showed significantly decreased fine motor speed. These results suggest the safety and efficacy of clonidine alone or in combination with MPH for the treatment of ADHD and aggressive oppositional and conduct disorders.",2000.0,0,1
88,10663415,The effect of bupropion on nicotine craving and withdrawal.,S Shiffman; J A Johnston; M Khayrallah; C A Elash; C J Gwaltney; J A Paty; M Gnys; G Evoniuk; J DeVeaugh-Geiss,"Bupropion has demonstrated efficacy for smoking cessation. Given the importance of nicotine craving and withdrawal in the smoking cessation process, the current study examined the effects of bupropion on these parameters during smoking abstinence. During a 2-day Baseline phase with ad lib smoking, 91 non-depressed smokers (who were not trying to quit permanently) were administered measures of nicotine craving, withdrawal symptoms, and timed measures of cognitive performance five times daily. Participants were then assigned randomly to a 14-day treatment regimen with bupropion 300 mg/day, bupropion 150 mg/day, or placebo. Thereafter, the above measures were re-administered during 3 days of abstinence on a closed research ward. Relative to placebo, 300 mg bupropion significantly reduced abstinence-associated increases in rated depression, difficulty concentrating, and irritability, and attenuated a decrease in positive affect. The results also suggested that bupropion might have a positive effect on performance measures during the withdrawal period. No effects were observed on craving, anxiety, restlessness, or hunger. The lack of findings on craving measures may be explained by a floor effect; except on the first day of abstinence, neither drug nor placebo groups showed much craving elevation during abstinence. Study results indicate that bupropion ameliorates some nicotine withdrawal symptoms.",2000.0,0,0
89,10671847,Effect of clonidine premedication on haemodynamic responses to fibreoptic bronchoscopy.,I Matot; Y Kuras; M R Kramer,"The usual haemodynamic response to fibreoptic bronchoscopy is an increase in heart rate and blood pressure. We therefore compared, in a prospective, randomised, double-blind study, the effect of two doses of oral clonidine premedication (150 microg or 300 microg) with placebo (control group) on the haemodynamic alterations in 62 patients who underwent elective fibreoptic bronchoscopy. Significant increases in blood pressure and heart rate were observed during fibreoptic bronchoscopy only in the control group. Clonidine 150 microg blunted the haemodynamic response to fibreoptic bronchoscopy (p < 0.05). Significant decreases in systolic blood pressure (< 90 mmHg) were observed in all patients premedicated with 300 microg clonidine. Throughout the study nine patients (75%) in the 300 microg clonidine group were treated at least once for hypotension. Compared with the control group, time to awakening was significantly longer only in patients premedicated with 300 microg clonidine. In conclusion, premedication with 150 microg oral clonidine attenuates haemodynamic responses to fibreoptic bronchoscopy, without causing excessive haemodynamic depression and sedation. These data encourage the administration of clonidine as premedication in patients undergoing fibreoptic bronchoscopy, particularly in those with, or at risk for, coronary artery disease.",2000.0,0,0
90,10671903,Non-linear pharmacokinetics of MDMA ('ecstasy') in humans.,R de la Torre; M Farré; J Ortuño; M Mas; R Brenneisen; P N Roset; J Segura; J Camí,"3,4-Methylenedioxymethamphetamine (MDMA, commonly called ecstasy) is a synthetic compound increasingly popular as a recreational drug. Little is known about its pharmacology, including its metabolism and pharmacokinetics, in humans in controlled settings. A clinical trial was designed for the evaluation of MDMA pharmacological effects and pharmacokinetics in healthy volunteers. A total of 14 subjects were included. In the pilot phase six received MDMA at 50 (n=2), 100 (n=2), and 150 mg (n=2). In the second phase eight received MDMA at both 75 and 125 mg (n=8). Subjects were phenotyped for CYP2D6 activity and were classified as extensive metabolizers for substrates, such as MDMA, whose hepatic metabolism is regulated by this enzyme. Plasma and urine samples were collected throughout the study for the evaluation of MDMA pharmacokinetics. Body fluids were analysed for the determination of MDMA and its main metabolites 3,4-methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxy-methamphetamine (HMMA) and 4-hydroxy-3-methoxy-amphetamine (HMA). As the dose of MDMA administered was increased, volunteers showed rises in MDMA concentrations that did not follow the same proportionality which could be indicative of nonlinearity. In the full range of doses tested the constant recovery of HMMA in the urine combined with the increasing MDMA recovery seems to point towards a saturation or an inhibition of MDMA metabolism (the demethylenation step). These observations are further supported by the fact that urinary clearance was rather constant while nonrenal clearance was dose dependent. It has previously been postulated that individuals genetically deficient for the hepatic enzyme CYP2D6 (about 10% of the Caucasian people) were at risk of developing acute toxicity at moderate doses of MDMA because the drug would accumulate in the body instead of being metabolized and inactivated. The lack of linearity of MDMA pharmacokinetics (in a window of doses compatible with its recreational use) is a more general phenomenon as it concerns the whole population independent of their CYP2D6 genotype. It implies that relatively small increases in the dose of MDMA ingested are translated to disproportionate rises in MDMA plasma concentrations and hence subjects are more prone to develop acute toxicity.",2000.0,0,0
91,10688158,Dopamine D2 receptor occupancy by olanzapine or risperidone in young patients with schizophrenia.,J Lavalaye; D H Linszen; J Booij; L Reneman; B P Gersons; E A van Royen,"A crucial characteristic of antipsychotic medication is the occupancy of the dopamine (DA) D2 receptor. We assessed striatal DA D2 receptor occupancy by olanzapine and risperidone in 36 young patients [31 males, 5 females; mean age 21.1 years (16-28)] with first episode schizophrenia, using [123I]iodobenzamide (IBZM) SPECT. The occupancy of DA D2 receptors was not significantly different between olanzapine and risperidone. However, in subgroups of most prescribed doses, DA D2 occupancy was higher in the risperidone 4-mg group (79%) compared to the olanzapine 15-mg group (62%). [123I]IBZM binding ratios decreased with olanzapine dose (r = -0.551; P < 0.01), indicating higher DA D2 receptor occupancy with higher olanzapine dose. Akathisia and positive symptoms were correlated with [123I]IBZM binding ratio (r = -0.442; P < 0.01; and r = -0.360; P < 0.05, respectively). Prolactin (PRL) levels were elevated in the risperidone, but not in the olanzapine group, at comparable D2 receptor occupancy levels. In the olanzapine group, PRL levels were correlated with [123I]IBZM binding ratio (r = -0.551; P < 0.01). In conclusion, both olanzapine and risperidone induce a high striatal D2 receptor occupancy, dependent on dose and group formation. The lower incidence of prolactin elevation with olanzapine, compared to risperidone, may not be attributed to a lower D2 receptor occupancy.",2000.0,0,0
92,10691221,Low-dose clonidine and neostigmine prolong the duration of intrathecal bupivacaine-fentanyl for labor analgesia.,M D Owen; O Ozsaraç; S Sahin; N Uçkunkaya; N Kaplan; I Magunaci,"Intrathecal (IT) opioid and local anesthetic combinations are popular for labor analgesia because of rapid, effective pain relief, but the duration of analgesia is limited. This study was undertaken to determine whether the addition of clonidine and neostigmine to IT bupivacaine-fentanyl would increase the duration of analgesia without increasing side effects for patients in labor. Forty-five healthy parturients in active labor were randomized to receive a 2-ml IT dose of one of the following dextrose-containing solutions using the combined spinal-epidural technique: (1) bupivacaine 2.5 mg and fentanyl 25 microg (BF); (2) BF plus clonidine 30 microg (BFC); or (3) BFC plus neostigmine 10 microg (BFCN). Pain, sensory levels, motor block, side effects, maternal vital signs, and fetal heart rate were systematically assessed. Patients administered BFCN had significantly longer analgesia (165+/-32 min) than those who received BF (90+/-21 min; P<0.001) or BFC (123+/-21 min; P<0.001). Pain scores, block characteristics, maternal vital signs, Apgar scores, maternal satisfaction, and side effects were similar among groups except for nausea, which was significantly greater in the BFCN group (P<0.05 as compared with BFC). The addition of clonidine and neostigmine significantly increased the duration of analgesia from IT bupivacaine-fentanyl during labor, but neostigmine caused more nausea. Although serious side effects were not observed in this study, safety must be further addressed before the routine use of multiple IT drugs is advocated.",2000.0,0,0
93,10704958,Olanzapine increases slow-wave sleep: evidence for blockade of central 5-HT(2C) receptors in vivo.,A L Sharpley; C M Vassallo; P J Cowen,"The study aimed to determine the effects of the atypical antipsychotic agent, olanzapine, on the polysomnogram in healthy subjects. We predicted that olanzapine, via serotonin(2C) (5-HT(2C)) receptor blockade, would increase slow-wave sleep (SWS). We studied the effects of single evening doses of olanzapine (5 mg and 10 mg orally) on the polysomnogram of 9 healthy male volunteers, using a placebo-controlled, double-blind, cross-over design. Compared to placebo, the 5-mg and 10-mg doses of olanzapine significantly increased SWS, sleep continuity measures, and subjective sleep quality. In addition, 10 mg of olanzapine suppressed rapid eye movement (REM) sleep and increased REM sleep latency. Olanzapine (5 mg and 10 mg) produced substantial (59.1% and 83.3%) and highly significant dose-related increases in SWS in humans probably via blockade of brain 5-HT(2C) receptors. 5-HT(2C) receptor antagonism may account for some of the therapeutic and adverse effects of olanzapine therapy.",2000.0,0,0
94,10711900,The use of topical aqueous suppressants in the prevention of postoperative intraocular pressure elevation after pars plana vitrectomy with long-acting gas tamponade.,R A Mittra; J S Pollack; S Dev; D P Han; W F Mieler; J S Pulido; T B Connor,"To determine whether topical aqueous suppressant therapy applied after pars plana vitrectomy with gas tamponade prevents postoperative intraocular pressure (IOP) elevation. Prospective, nonrandomized comparative study. Forty-one patients who met inclusion criteria and underwent pars plana vitrectomy with gas tamponade (SF6 18%-20% or C3F8 12%-16%) over a 1-year period. Treatment eyes received topical aqueous suppressants at the end of surgery. Postoperative IOP at 4 to 6 hours, 1 day, and 1 week. Twenty-one control and 20 treatment eyes met the inclusion criteria. The IOP (in mmHg) measured at 4 to 6 hours (23.05 [control, 14.73 [treatment]) and 1 day (23.24 [control], 17.28 [treatment]) postoperatively showed a statistically significant difference between the groups (P = 0.0038) at 4 to 6 hours and a trend toward significance (P = 0.057) at 1 day. Eleven control and three treatment eyes had an IOP spike above 25 mmHg at 4 to 6 hours or 1 day postoperatively (P = 0.02), and six control eyes and one treatment eye had postoperative IOP greater than 30 mmHg. A pressure rise greater than 40 mmHg was seen in two control eyes and no treatment eyes. Use of topical aqueous suppressants after pars plana vitrectomy with long-acting gas tamponade is effective in preventing significant postoperative IOP elevation in most cases.",2000.0,0,0
95,10716102,Rapid opiate detoxication in outpatient treatment: relationship with naltrexone compliance.,G Gerra; A Zaimovic; P Rustichelli; B Fontanesi; U Zambelli; M Timpano; C Bocchi; R Delsignore,"A variety of detoxification methods have been utilized for the treatment of heroin withdrawal before individuals begin long-term opiate-free and naltrexone programs. While methadone in decreasing doses is still widely used for detoxication procedures, rapid and ultrarapid protocols including clonidine and opiate receptors antagonists have been proposed. This study compares the efficacy of different detoxification methods and investigates possible changes in naltrexone compliance. Ninety-eight heroin-addicted individuals were studied to evaluate withdrawal symptoms, craving, mood, urine toxicologic screens, and drop-out rate during therapy with: Group A: clonidine only (5 days); Group B: clonidine, oxazepam, baclofen, and ketoprofene with naloxone and naltrexone (2 days); and Group C: methadone in decreasing doses (10 days). Naltrexone compliance and relapse rates were evaluated during a 6-month follow-up period. Rapid detoxification with opiate antagonists (Group B) induced slight and transient withdrawal symptoms, and resulted in a significantly lower percentage of heroin catabolites in urine controls during the detoxification procedure, lower negative and positive craving, less mood problems, and higher compliance in extended naltrexone treatment. In comparison with clonidine only (Group A) and methadone (Group C), the early use of naltrexone during detoxification in combination with benzodiazepines and clonidine facilitated extended naltrexone acceptance and improved the recovery outcome in outpatients.",2000.0,0,0
96,10720292,Randomized trial of modafinil as a treatment for the excessive daytime somnolence of narcolepsy: US Modafinil in Narcolepsy Multicenter Study Group.,,"This is one of two separate clinical trials to evaluate the efficacy and safety of modafinil, a novel wake-promoting agent, in patients with excessive daytime sleepiness (EDS) associated with narcolepsy. In this 9-week, randomized, placebo-controlled, double-blind, 21-center clinical trial, patients were randomized to receive fixed daily doses of modafinil 200 mg, modafinil 400 mg, or placebo. A placebo-controlled, 2-week treatment discontinuation phase was included to evaluate the effects of withdrawal on patients who had been receiving modafinil. A total of 271 patients who were naive to modafinil received study medication in the 9-week trial and 240 patients received study medication in the discontinuation phase. Treatment with modafinil resulted in significant improvement in two objective measures of EDS: the Multiple Sleep Latency Test and the Maintenance of Wakefulness Test. Additionally, patient self-assessment of sleepiness was significantly improved, as measured by the Epworth Sleepiness Scale, and level of illness was significantly reduced on the independent clinician assessment, the Clinical Global Impression of Change. Nighttime sleep, monitored by nocturnal polysomnography, was not adversely effected with modafinil treatment compared with placebo treatment. The most frequent adverse experience was headache, which was not significantly greater for modafinil than placebo. During treatment discontinuation, individuals who had been receiving modafinil experienced a return of their EDS to baseline levels. During treatment discontinuation, patients did not experience symptoms associated with amphetamine withdrawal syndrome. For up to 9 weeks of daily use there was no evidence for the development of dependence at the dose levels studied. The data indicate that modafinil has an excellent safety profile and is very well tolerated. Modafinil is an effective treatment for excessive daytime sleepiness in narcolepsy and shows continued efficacy with up to 9 weeks of daily use.",2000.0,0,0
97,10722180,"A multicentre, double-blind, randomized comparison of quetiapine (ICI 204,636, 'Seroquel') and haloperidol in schizophrenia.",D L Copolov; C G Link; B Kowalcyk,"Quetiapine (ICI 204,636, 'Seroquel') is a new atypical antipsychotic agent with a similar binding profile to the original atypical antipsychotic, clozapine. Its clinical efficacy has already been demonstrated at multiple fixed doses (150-750 mg/day) and has been suggested to be comparable with haloperidol (12 mg/day). This international, 6-week, multicentre, double-blind, randomized, parallel-group trial compared quetiapine with haloperidol (455 mg and 8 mg mean total daily doses, respectively) in 448 hospitalized patients with acute exacerbation of chronic or subchronic schizophrenia (DSM-III-R), in order to establish their equivalence in terms of efficacy, and the nature of their tolerability profiles, especially in terms of extrapyramidal symptoms (EPS) and serum prolactin levels. Both quetiapine and haloperidol produced a clear reduction in the Positive and Negative Syndrome Scale (PANSS) scores and Clinical Global Impression (CGI) Severity of Illness and Global Improvement scores. At day 42, the PANSS total score was reduced by -18.7+/-1.63 in the quetiapine group, and -22.1+/-1.63 in the haloperidol group (P = 0.13, between-treatment). Quetiapine was better tolerated than haloperidol in terms of EPS as demonstrated by the significant differences in the Simpson Scale and Abnormal Involuntary Movement Scale scores (P < 0.05). Although patients in both groups had elevated serum prolactin concentrations at baseline, mean serum prolactin concentration decreased (by 16.5 microg/l) in quetiapine-treated patients, yet increased (by 5.9 microg/l) in patients treated with haloperidol. Quetiapine is an effective and well tolerated antipsychotic of comparable efficacy to haloperidol and lacks the latter compound's effect on prolactin and EPS.",2000.0,0,0
98,10731625,"Effects of isradipine, a dihydropyridine-class calcium channel antagonist, on D-methamphetamine-induced cognitive and physiological changes in humans.",B A Johnson; N Ait-Daoud; L T Wells,"D-methamphetamine is abused for its euphoric effects and stimulatory action on cognitive function. Its abuse can, however, be associated with massive hypertension resulting in strokes, ruptured aneurysms, or myocardial infarction. We examined the utility of isradipine, a dihydropyridine-class calcium channel antagonist, in treating d-methamphetamine induced hypertension and evaluated its effects on cognitive function, both of which are mediated by dopaminergic mechanisms. D-methamphetamine dose-dependently increased all vital signs (systolic, diastolic, and mean arterial pressure, and pulse rate) parameters. Isradipine significantly reduced d-methamphetamine-induced increases in diastolic and mean arterial pressure; however, this potentially beneficial therapeutic effect was offset by a significant reflex rise in pulse rate. D-methamphetamine also improved attention, accuracy of reasoning ability, and performance on computerized cognitive function tasks. D-methamphetamine's cognitive improving effects were not altered significantly by isradipine. Isradipine increased the false responding rate but was without significant effect on any other attentional task, or on reasoning ability, or performance. Isradipine does not appear to enhance cognitive function in healthy humans.",2000.0,0,0
99,10731626,"Acute psychological effects of 3,4-methylenedioxymethamphetamine (MDMA, ""Ecstasy"") are attenuated by the serotonin uptake inhibitor citalopram.",M E Liechti; C Baumann; A Gamma; F X Vollenweider,"3,4-Methylenedioxymethamphetamine (MDMA, ""Ecstasy"") is a recreational drug that has been shown to release serotonin (5-HT) and dopamine (DA) in animals. The effect of MDMA on 5-HT release can be blocked by 5-HT uptake inhibitors such as citalopram, suggesting that MDMA interacts with the 5-HT uptake site. It is unknown whether this mechanism is also responsible for the psychological effects of MDMA in humans. We investigated the effect of citalopram pretreatment (40 mg iv) on the psychological effects of MDMA (1.5 mg/kg po) in a double-blind placebo-controlled psychometric study in 16 healthy human volunteers. MDMA produced an emotional state with heightened mood, increased self-confidence and extroversion, moderate derealization, and an intensification of sensory perception. Most of these effects were markedly reduced by citalopram. This finding suggests that the psychological effects of MDMA are mediated via action at the 5-HT uptake site to increase 5-HT release through the carrier, as expected from animal studies.",2000.0,0,0
100,10735784,The hemodynamic and adrenergic effects of perioperative dexmedetomidine infusion after vascular surgery.,P Talke; R Chen; B Thomas; A Aggarwall; A Gottlieb; P Thorborg; S Heard; A Cheung; S L Son; A Kallio,"We tested dexmedetomidine, an alpha(2) agonist that decreases heart rate, blood pressure, and plasma norepinephrine concentration, for its ability to attenuate stress responses during emergence from anesthesia after major vascular operations. Patients scheduled for vascular surgery received either dexmedetomidine (n = 22) or placebo (n = 19) IV beginning 20 min before the induction of anesthesia and continuing until 48 h after the end of surgery. All patients received standardized anesthesia. Heart rate and arterial blood pressure were kept within predetermined limits by varying anesthetic level and using vasoactive medications. Heart rate, arterial blood pressure, and inhaled anesthetic concentration were monitored continuously; additional measurements included plasma and urine catecholamines. During emergence from anesthesia, heart rate was slower with dexmedetomidine (73 +/- 11 bpm) than placebo (83 +/- 20 bpm) (P = 0.006), and the percentage of time the heart rate was within the predetermined hemodynamic limits was more frequent with dexmedetomidine (P < 0.05). Plasma norepinephrine levels increased only in the placebo group and were significantly lower for the dexmedetomidine group during the immediate postoperative period (P = 0.0002). We conclude that dexmedetomidine attenuates increases in heart rate and plasma norepinephrine concentrations during emergence from anesthesia. The alpha(2) agonist, dexmedetomidine, attenuates increases in heart rate and plasma norepinephrine concentrations during emergence from anesthesia in vascular surgery patients.",2000.0,0,0
101,10735806,"A comparison of urapidil, clonidine, meperidine and placebo in preventing postanesthetic shivering.",S N Piper; W H Maleck; J Boldt; S W Suttner; C C Schmidt; D G Reich,"This placebo-controlled study was performed to evaluate the efficacy of urapidil compared with clonidine and meperidine in preventing postanesthetic shivering, which is common after anesthesia administration and may be very distressing. We studied 120 patients undergoing elective abdominal or orthopedic surgery under standardized general anesthesia. After surgery, patients were randomly assigned to one of four groups (each group n = 30) using a double-blinded protocol: Group A received 0.2 mg/kg urapidil; Group B, 3 microg/kg clonidine; Group C, 0.4 mg/kg meperidine; and Group D, saline 0.9% as placebo. Postanesthetic shivering was scored by using a five-point scale. Clonidine and meperidine significantly reduced the incidence and the severity of shivering in comparison with placebo, whereas there were no significant differences between the urapidil and placebo groups. Both clonidine and meperidine caused a significantly prolonged emergence time (13.4 +/- 5.8 and 13. 3 +/- 5.0 min, respectively) compared with placebo (10.4 +/- 5.3 min) and urapidil (11.4 +/- 2.9 min). We confirmed that both clonidine and meperidine are effective in preventing postanesthetic shivering, whereas urapidil, in our setting and dosage, was not effective. Patients who received clonidine or meperidine had a prolonged emergence time. In the dosage used, urapidil seems to be unable to prevent postanesthetic shivering. Shivering (irregular muscle activity) is common after surgery and anesthesia. This study compared urapidil (an antihypertensive drug) as a prophylaxis with two established antishivering drugs (meperidine and clonidine) and placebo. In the dosage used, we were unable to show a significant benefit of urapidil.",2000.0,0,0
102,10742158,Functional deficits in basal ganglia of children with attention-deficit/hyperactivity disorder shown with functional magnetic resonance imaging relaxometry.,M H Teicher; C M Anderson; A Polcari; C A Glod; L C Maas; P F Renshaw,"Attention-deficit/hyperactivity disorder is a highly heritable and prevalent neuropsychiatric disorder estimated to affect 6% of school-age children. Its clinical hallmarks are inattention, hyperactivity and impulsivity, which often respond substantially to treatment with methylphenidate or dextroamphetamine. Etiological theories suggest a deficit in corticostriatal circuits, particularly those components modulated by dopamine. We developed a new functional magnetic resonance imaging procedure (T2 relaxometry) to indirectly assess blood volume in the striatum (caudate and putamen) of boys 6-12 years of age in steady-state conditions. Boys with attention-deficit/hyperactivity disorder had higher T2 relaxation time measures in the putamen bilaterally than healthy control subjects. Relaxation times strongly correlated with the child's capacity to sit still and his accuracy in accomplishing a computerized attention task. Daily treatment with methylphenidate significantly changed the T2 relaxation times in the putamen of children with attention-deficit/hyperactivity disorder, although the magnitude and direction of the effect was strongly dependent on the child's unmedicated activity state. There was a similar but nonsignificant trend in the right caudate. T2 relaxation time measures in thalamus did not differ significantly between groups, and were not affected by methylphenidate. Attention-deficit/hyperactivity disorder symptoms may be closely tied to functional abnormalities in the putamen, which is mainly involved in the regulation of motor behavior.",2000.0,0,0
103,10761165,Single- and multiple-dose pharmacokinetics of an oral once-a-day osmotic controlled-release OROS (methylphenidate HCl) formulation.,N B Modi; B Lindemulder; S K Gupta,"Methylphenidate is used for the treatment of attention deficit hyperactivity disorder (ADHD). OROS (methylphenidate HCl) is an osmotic controlled-release delivery system designed for once-daily oral dosing. The pharmacokinetics of OROS (methylphenidate HCl) 18 mg qd, sustained-release (SR) methylphenidate 20 mg qd, and the immediate-release (IR) formulation given as three 5 mg doses every 4 hours (tid) were compared in adults. In addition, the single- and multiple-dose pharmacokinetics of the OROS formulation were studied. Following OROS (methylphenidate HCl), there was a gradual increase in the mean methylphenidate plasma concentrations with peak concentrations noted at 6 to 8 hours. With the SR formulation, peak plasma concentrations were noted at approximately 4 hours. Following the IR regimen, methylphenidate plasma concentrations fluctuated in tandem with oral dosing; peak concentrations were noted at 6.5 hours. The terminal half-life of methylphenidate was similar for the three formulations. The dose-normalized methylphenidate Cmax for OROS (methylphenidate HCl) was significantly lower than for IR and SR methylphenidate. The bioavailability of methylphenidate and PPA from OROS (methylphenidate HCl) relative to the IR and SR formulations was complete. Mean methylphenidate AUC and terminal half-life were similar after single (32.9 ng.h/mL and 3.9 hours) and multiple doses (35.2 ng.h/mL and 3.9 hours) of OROS (methylphenidate HCl).",2000.0,0,0
104,10770448,Evaluation of sexual functioning in depressed outpatients: a double-blind comparison of sustained-release bupropion and sertraline treatment.,R T Segraves; R Kavoussi; A R Hughes; S R Batey; J A Johnston; R Donahue; J A Ascher,"Sexual dysfunction is a frequently reported side effect of many antidepressants, including serotonin reuptake inhibitors. Bupropion, an antidepressant of the aminoketone class, is relatively free of adverse sexual effects. In a randomized, double-blind, multicenter trial, sustained-release bupropion (bupropion SR) and sertraline, a selective serotonin reuptake inhibitor, were found to be similarly efficacious in the treatment of outpatients with moderate to severe depression. This report describes the results of a double-blind comparison of the sexual side effect profiles of bupropion SR and sertraline. Two hundred forty-eight patients who had received a diagnosis of moderate to severe major depression were randomly assigned to receive treatment with bupropion SR (100-300 mg/day) or sertraline (50-200 mg/day) for 16 weeks. Eligible patients were required to be in a stable relationship and to have normal sexual functioning. Sexual functioning was assessed by the investigator at each clinic visit using investigator-rated structured interviews. A significantly greater percentage of sertraline-treated patients (63% and 41% of men and women, respectively) developed sexual dysfunction compared with bupropion SR-treated patients (15% and 7%, respectively). Sexual dysfunction was noted as early as day 7 in sertraline-treated patients at a dose of 50 mg/day and persisted until the end of the 16-week treatment phase. Four patients, all of whom were treated with sertraline, discontinued from the study prematurely because of sexual dysfunction. Given the similar efficacy of the two drugs in treating depression, bupropion SR may be a more appropriate antidepressant choice than sertraline in patients for whom sexual dysfunction is a concern.",2000.0,0,0
105,10773503,"Effects of oral clonidine premedication on side effects of intravenous ketamine anesthesia: a randomized, double-blind, placebo-controlled study.",F Handa; M Tanaka; T Nishikawa; H Toyooka,"To determine the effects of oral clonidine premedication on hemodynamic changes during the entire course of ketamine anesthesia and incidence of postoperative adverse reactions. Randomized, prospective, double-blind, placebo-controlled study. Department of Anesthesiology, University of Tsukuba Hospital, Ibaraki, Japan. 39 ASA physical status I and II patients undergoing superficial surgeries. Placebo, clonidine 2.5 micrograms/kg, and clonidine 5 micrograms/kg groups received respective doses of oral clonidine 90 minutes prior to surgery. Anesthesia was induced with ketamine 2 mg/kg intravenously (i.v.), trachea was intubated, and anesthesia was maintained with 67% nitrous oxide, oxygen, and supplemental ketamine (1 mg/kg) when systolic blood pressure and heart rate (HR) exceeded 180 mmHg and 100 bpm, respectively. In the clonidine 2.5 micrograms/kg group, HR response to tracheal intubation was significantly less, while in the clonidine 5 micrograms/kg group both mean arterial pressure and HR responses were significantly suppressed, compared with the placebo group. Intraoperative coefficients of variations of HR were significantly less in both clonidine groups than the placebo group. Incidence of nightmare and degree of salivation were significantly less in the clonidine 5 micrograms/kg group than in the placebo group. Oral clonidine 2.5 micrograms/kg and clonidine 5 micrograms/kg attenuates cardiostimulatory effects, while clonidine 5 micrograms/kg was associated with reduced incidence and severity of nightmare and salivation attributable to i.v. ketamine.",2000.0,0,0
106,10776835,Levobupivacaine: a review of its pharmacology and use as a local anaesthetic.,R H Foster; A Markham,"Based on findings that the cardiotoxicity infrequently observed with racemic bupivacaine shows enantioselectivity, i.e. it is more pronounced with the R(+)-enantiomer, the S(-)-enantiomer (levobupivacaine) has been developed for clinical use as a long acting local anaesthetic. The majority of in vitro, in vivo and human pharmacodynamic studies of nerve block indicate that levobupivacaine has similar potency to bupivacaine. However, levobupivacaine had a lower risk of cardiovascular and CNS toxicity than bupivacaine in animal studies. In human volunteers, levobupivacaine had less of a negative inotropic effect and, at intravenous doses >75 mg, produced less prolongation of the QTc interval than bupivacaine. Fewer changes indicative of CNS depression on EEG were evident with levobupivacaine. Levobupivacaine is long acting with a dose-dependent duration of anaesthesia. The onset of action is < or = 15 minutes with various anaesthetic techniques. In studies of surgical anaesthesia in adults, levobupivacaine provided sensory block for up to 9 hours after epidural administration of < or = 202.5 mg, 6.5 hours after intrathecal 15 mg, and 17 hours after brachial plexus block with 2 mg/kg. Randomised, double-blind clinical studies established that the anaesthetic and/or analgesic effects of levobupivacaine were largely similar to those of bupivacaine at the same dose. Sensory block tended to be longer with levobupivacaine than bupivacaine, amounting to a difference of 23 to 45 minutes with epidural administration and approximately 2 hours with peripheral nerve block. With epidural administration, levobupivacaine produced less prolonged motor block than sensory block. This differential was not seen with peripheral nerve block. Conditions satisfactory for surgery and good pain management were achieved by use of local infiltration or peribulbar administration of levobupivacaine. Levobupivacaine was generally as effective as bupivacaine for pain management during labour, and was effective for the management of postoperative pain, especially when combined with clonidine, morphine or fentanyl. The tolerability profiles of levobupivacaine and bupivacaine were very similar in clinical trials. No clinically significant ECG abnormalities or serious CNS events occurred with the doses used. The most common adverse event associated with levobupivacaine treatment was hypotension (31%). Levobupivacaine is a long acting local anaesthetic with a clinical profile closely resembling that of bupivacaine. However, current preclinical safety and toxicity data show an advantage for levobupivacaine over bupivacaine. Clinical data comparing levobupivacaine with ropivacaine are needed before the role of the drug can be fully established. Excluding pharmacoeconomic considerations, levobupivacaine is an appropriate choice for use in place of bupivacaine.",2000.0,0,0
107,10781465,Novel analgesic adjuncts for brachial plexus block: a systematic review.,D B Murphy; C J McCartney; V W Chan,"This article reviews current evidence for the efficacy of adding novel analgesic adjuncts to brachial plexus block, the goal of which is to prolong analgesic effect without the disadvantage of systemic side effects or prolonged motor block. It may also allow for a reduction in the total dose of local anesthetic used. Novel adjuncts studied to date include opioids, clonidine, neostigmine, and tramadol. Twenty-four studies were reviewed and assessed by using specific inclusion criteria, and only those studies satisfying these criteria were included in the final assessment. Satisfactory studies were then assessed for inclusion of a systemic control group to determine peripheral effect, as opposed to possible systemic effect, of an adjunct administered peripherally. Evidence regarding the analgesic benefit of opioid adjuncts remains equivocal and more evidence is required before their routine use can be recommended. Clonidine appears to have significant analgesic benefit and to cause minimal adverse effects when used in doses up to 150 microg. Data regarding other drugs, such as tramadol and neostigmine, are not sufficient to allow for any recommendations, and further studies are required.",2000.0,0,0
108,10817105,Bupropion sustained release versus paroxetine for the treatment of depression in the elderly.,K L Weihs; E C Settle; S R Batey; T L Houser; R M Donahue; J A Ascher,"Depression is a serious and widespread emotional disorder among the elderly. This study compared the efficacy and safety of bupropion sustained release (SR) with the selective serotonin reuptake inhibitor paroxetine in the treatment of major depression in elderly outpatients. Elderly (> or = 60 years) outpatients with major depressive disorder (DSM-IV criteria) were evaluated in this 6-week multicenter, randomized, double-blind study comparing bupropion SR, 100-300 mg/day, and paroxetine, 10-40 mg/day. Efficacy was assessed by changes in scores on the Hamilton Rating Scales for Depression (HAM-D) and Anxiety (HAM-A) and the Clinical Global Impressions-Severity of Illness and -Improvement scales. Safety was assessed by monitoring adverse events, vital signs, and body weight. A total of 100 patients ranging in age from 60 to 88 years were randomly assigned to treatment with bupropion SR (N = 48) or paroxetine (N = 52). Measurements of efficacy were similar between the 2 treatment groups, with both groups showing improved scores on all depression rating scales. Headache, insomnia, dry mouth, agitation, dizziness, and nausea occurred in > 10% of patients in both groups; somnolence, diarrhea, constipation, and anorexia occurred in > 10% of patients in the paroxetine group. No statistically significant differences between groups in vital signs or weight were found. Both bupropion SR and paroxetine were safe and effective for the treatment of depression in the elderly. Because of its favorable side effect profile, bupropion SR may provide a safe and effective nonserotonergic treatment alternative that is well suited as an antidepressant for the elderly.",2000.0,0,0
109,10819701,Oral clonidine in postmenopausal patients with breast cancer experiencing tamoxifen-induced hot flashes: a University of Rochester Cancer Center Community Clinical Oncology Program study.,K J Pandya; R F Raubertas; P J Flynn; H E Hynes; R J Rosenbluth; J J Kirshner; H I Pierce; V Dragalin; G R Morrow,"Hot flashes are the most frequently reported side effect of tamoxifen treatment. Although hormones are an effective treatment, their safety is questionable in women with breast cancer. It is therefore important to evaluate nonhormonal treatments for hot flashes. To evaluate the effectiveness of oral clonidine for control of hot flashes associated with tamoxifen therapy in postmenopausal women with breast cancer. Randomized, double-blind, placebo-controlled clinical trial. University of Rochester Cancer Center Community Clinical Oncology Program. 194 postmenopausal women with breast cancer who were receiving adjuvant tamoxifen therapy. Oral clonidine hydrochloride, 0.1 mg/d, or placebo for 8 weeks. In a daily diary, patients recorded number, duration, and severity of hot flashes and overall quality-of-life score (on a 10-point scale) during a 1-week baseline period and during the 4th, 8th, and 12th weeks of the study. Patients in the placebo and treatment groups were similar in age, duration of tamoxifen use, reported frequency and duration of hot flashes at baseline, and dropout rates. One hundred forty-nine patients completed 12 weeks of follow-up. The mean decrease in hot flash frequency was greater in the clonidine group than in the placebo group after 4 weeks of treatment (37% compared with 20% [95% CI for difference, 7% to 27%]) and 8 weeks of treatment (38% compared with 24% [CI for difference, 3% to 27%]). Patients receiving clonidine were more likely than patients receiving placebo to report difficulty sleeping (41% compared with 21%; P = 0.02). A significant difference was seen in the mean change in quality-of-life scores (0.3 points in the clonidine group compared with -0.2 points in the placebo group; P = 0.02) at 8 weeks, although the median difference was 0 in both groups. Oral clonidine, 0.1 mg/d, is effective against tamoxifen-induced hot flashes in postmenopausal women with breast cancer.",2000.0,0,0
110,10825334,Ondansetron given before induction of anesthesia reduces shivering after general anesthesia.,R M Powell; D J Buggy,"The neurotransmitter pathways involved in the mechanism of postanesthetic shivering (PAS) are poorly understood. Meperidine, clonidine, and physostigmine are all effective treatments, indicating that opioid, alpha(2)-adrenergic, and anticholinergic systems are probably involved. We investigated the effect of ondansetron, a 5-HT(3) antagonist used to treat postoperative nausea and vomiting, on intraoperative core and peripheral temperatures and PAS. Eighty-two patients (age, 18-60 yr) undergoing orthopedic, general, or urological surgery were randomized into three groups in this double-blinded, placebo-controlled, study: Group O4 (n = 27) received ondansetron 4 mg IV, Group O8 (n = 27) received ondansetron 8 mg IV, and Group C (n = 28) received saline IV immediately before the anesthetic induction. Core (tympanic) and fingertip temperature (dorsum of middle finger) were recorded. Anesthesia was induced with IV fentanyl 1 microg/kg and propofol 2.0-2.5 mg/kg and maintained with 1 minimum alveolar anesthetic concentration isoflurane in 70% nitrous oxide/oxygen. The occurrence of shivering was documented clinically during recovery by nursing staff, who were unaware of the group assignment. PAS occurred in 16 of 28 (57%) patients in Group C, compared with 9 of 27 (33%) in Group O4 (P = 0.13) and 4 of 27 (15%) patients in Group O8 (P = 0.003). Within each group, core temperature decreased and peripheral temperature increased significantly, but there were no significant differences among the groups at any time interval. We conclude that ondansetron 8 mg IV given during the induction of anesthesia prevents PAS without affecting the core-to-peripheral redistribution of heat during general anesthesia. This suggests that serotonergic pathways have a role in the regulation of PAS. In a randomized, double-blinded, placebo-controlled, clinical study, ondansetron 8 mg IV, given just before the induction, reduced the incidence of postanesthetic shivering compared with saline. The anticipated core-to-peripheral redistribution of body temperature during general anesthesia was not affected. This implies that ondansetron probably acts by a central inhibitory mechanism, and that 5-hydroxytryptaminergic pathways have a role in regulating postanesthetic shivering.",2000.0,0,0
111,10831015,Longitudinal comparative study of risperidone and conventional neuroleptics for treating patients with schizophrenia. The Quebec Schizophrenia Study Group.,R H Bouchard; C Mérette; E Pourcher; M F Demers; J Villeneuve; M H Roy-Gagnon; Y Gauthier; D Cliche; A Labelle; M J Filteau; M A Roy; M Maziade,"This study compared the long-term (12 months) effectiveness of risperidone (RP) with that of conventional neuroleptics (CNs) in a population with chronic schizophrenia who had shown suboptimal response to CNs. A randomized, open, parallel, multicenter design was used. One hundred eighty-four subjects meeting DSM-IV criteria for schizophrenia were randomly assigned to receive either RP or a CN, and 165 of them completed the follow-up. Outcome measures were taken at 3, 6, and 12 months and included the Positive and Negative Syndrome Scale (PANSS) and the Extrapyramidal Symptom Rating Scale. Within this 12-month follow-up, RP was found to be superior to CNs in terms of both the average change in score from baseline on the PANSS (p = 0.006) and the proportion of good responders (as defined by a 20% decrease in total PANSS scores;p = 0.03). For positive symptoms, the effectiveness of the RP treatment tended to increase over time. At 12 months, the percentage of good responders in the RP group was twice as large as that in the CN group (30% vs. 15%;p = 0.03). The superiority of RP over CNs was constant over the three dose categories. In both the RP and the CN groups, the maximum decrease in psychopathology was achieved with the lowest dose range. A worsening of akathisia was less frequent in subjects receiving RP than in those receiving CNs (p = 0.02). In conclusion, this study showed that, compared with CNs, RP is beneficial in the treatment of patients with chronic schizophrenia and that some of these benefits may appear only after longer-term treatment.",2000.0,0,0
112,10831016,"Risperidone for the treatment of cocaine dependence: randomized, double-blind trial.",J Grabowski; H Rhoades; P Silverman; J M Schmitz; A Stotts; D Creson; R Bailey,"A partial blockade of the multiple actions of cocaine is one strategy by which cocaine dependence may be treated. Risperidone, a 5-hydroxytryptamine and dopamine D2 antagonist, is an atypical antipsychotic and was a candidate medication for the treatment of cocaine dependence. One hundred ninety-three cocaine-dependent subjects were enrolled in a 12-week, randomized, double-blind, placebo-controlled trial. Subjects initially received either placebo or 4 or 8 mg of risperidone, with a subsequent change to active doses of 2 mg and 4 mg. Subjects attended the clinic twice each week, provided urine samples, obtained medication, and underwent one behavioral therapy session per week. The study was terminated at the interim analysis. Retention was worse for the 4- and 8-mg active medication groups. Side effects were primarily associated with the 8-mg dose, although neither 2 mg nor 4 mg was well accepted by subjects. There was no reduction in cocaine use associated with risperidone. The results suggest that although antagonists might be a useful treatment approach, such as in the treatment of opiate dependence, risperidone is unlikely to find broad acceptance with the treatment-seeking population.",2000.0,0,0
113,10839333,A positron emission tomography study of quetiapine in schizophrenia: a preliminary finding of an antipsychotic effect with only transiently high dopamine D2 receptor occupancy.,S Kapur; R Zipursky; C Jones; C S Shammi; G Remington; P Seeman,"Quetiapine is a new atypical antipsychotic medication. As such, relatively little has been published regarding its in vivo effects at the dopamine type 2 (D2) and serotonin type 2a (5-HT2a) receptor systems. The following study was undertaken to explore these effects across the clinical dose range and relate this information to its clinical profile. Twelve patients with schizophrenia were randomly assigned to doses of 150 to 600 mg/d (n=3, at 150, 300, 450, and 600 mg/d) of quetiapine. After 3 weeks of treatment, D2 and 5-HT2a occupancy were measured using positron emission tomography (PET) imaging, 12 to 14 hours after the last dose. Clinical efficacy and adverse effect ratings were obtained at baseline, at the time of PET scanning, and at 12 weeks. Two additional patients were included to examine the effects of the drug 2 to 3 hours after last dose. Quetiapine was an effective antipsychotic and improved the extrapyramidal symptoms and prolactin level elevation noted at baseline. It achieved these results with minimal (0%-27%) D2 occupancy 12 hours after the last dose. Study of the additional subjects revealed that quetiapine does give rise to transiently high (58%-64%) D2 occupancy 2 to 3 hours after a single dose that then decreases to minimal levels in 12 hours. Quetiapine shows a transiently high D2 occupancy, which decreases to very low levels by the end of the dosing interval. Quetiapine's low D2 occupancy can explain its freedom from extrapyramidal symptoms and prolactin level elevation. The data suggest that transient D2 occupancy may be sufficient for its antipsychotic effect. Future studies controlling for nonpharmacological effects as well as activities on other receptors will be necessary to confirm this suggestion.",2000.0,0,0
114,10847307,The safety of olanzapine compared with other antipsychotic drugs: results of an observational prospective study in patients with schizophrenia (EFESO Study). Pharmacoepidemiologic Study of Olanzapine in Schizophrenia.,J C Gómez; J A Sacristán; J Hernández; A Breier; P Ruiz Carrasco; C Antón Saiz; E Fontova Carbonell,"Results of controlled clinical trials should be confirmed through safety and effectiveness studies in nonselected patient cohorts treated according to routine clinical practice. Outpatients with schizophrenia (ICD-10 criteria) entered this prospective, naturalistic study when they received a new prescription for an antipsychotic drug. Treatment assignment was based on purely clinical criteria, as the study did not include any experimental intervention. Safety was evaluated through the collection of spontaneous adverse events and a specific questionnaire for extrapyramidal symptoms. Global clinical status was measured through the Clinical Global Impressions-Severity (CGI-S) and the Global Assessment of Functioning (GAF) scales. From the 2967 patients included, 2128 patients were treated with olanzapine as monotherapy or combined with other drugs (olanzapine group), and 821 were treated with other antipsychotic drugs as monotherapy or combined with other drugs (control group). There were no statistical differences between treatment groups at baseline regarding age, gender, disease duration, or severity of symptoms. Olanzapine was well tolerated and effective in this study. Overall incidence of adverse events was significantly lower in the olanzapine group compared with the control group (p < .001). Somnolence and weight gain were significantly more frequent in the olanzapine group, and akathisia, dystonia, extrapyramidal syndrome, hypertonia, hypokinesia, and tremor were significantly higher in the control group. Clinical improvement at endpoint, measured through the mean change in the CGI-S and the GAF, was significantly higher in the olanzapine group compared with the control group (p = .004). These results show that olanzapine is safe and effective in nonselected schizophrenic outpatients and are consistent with the efficacy and safety profile that olanzapine has shown in previous controlled clinical trials.",2000.0,0,0
115,10847315,Medication continuation and compliance: a comparison of patients treated with clozapine and haloperidol.,R Rosenheck; S Chang; Y Choe; J Cramer; W Xu; J Thomas; W Henderson; D Charney,"This study compares medication continuation and regimen compliance with the atypical antipsychotic medication clozapine versus the conventional antipsychotic haloperidol. Data from a 15-site double-blind, randomized clinical trial (N = 423) were used to compare patients with DSM-III-R schizophrenia assigned to clozapine or haloperidol in terms of duration of participation while taking the randomly assigned study drug (continuation) and the proportion of prescribed pills that were taken (compliance). Multiple regression analysis was used to determine the relationship of baseline characteristics and measures of clinical change to continuation for the entire sample and for patients assigned to each medication. Patients assigned to clozapine continued taking the study drug for a mean of 35.5 weeks as compared with only 27.2 among patients assigned to haloperidol (F = 4.45, df = 1,422; p = .0001). No differences were found between the groups in the proportion of prescribed pills that were returned at any timepoint. Among patients assigned to haloperidol, poorer continuation was associated with being older and greater continuation with receiving public support. Among patients on clozapine treatment, continuation was poorer among African American patients and greater among patients who showed reduced clinical symptoms and akathisia. Continuation with clozapine was greater even after adjusting for these factors. Continuation with medication is greater with clozapine than haloperidol and is partly explained by greater symptom improvement and reduced side effects. No differences were found in regimen compliance.",2000.0,0,0
116,10868465,Atypical antipsychotics and weight gain--a systematic review.,D M Taylor; R McAskill,"To review systematically data relating to weight changes with atypical antipsychotics. We conducted a Medline search on October 29 1999 and covered the period 1980-99. All recovered papers were examined for further relevant reports. In addition, we wrote to pharmaceutical manufacturers and 10 practising clinicians to ask them to provide other relevant reports known to them. Eighty reports mentioning change in body weight were retrieved. Data relating to weight changes were of variable quality. Weight changes were indicated by a variety of measures. The majority of reports related to short-term changes. All atypical drugs, with the exception of ziprasidone, have been associated with weight increases. Clozapine seems to have the highest risk of weight gain, followed by olanzapine and quetiapine. There is probably a lower risk with risperidone, sertindole and zotepine and a still lower risk with amisulpride. Ziprasidone appears not to be associated with weight gain. In the absence of more compelling data, these rankings must be considered approximate and preliminary. Longer, more robust trials are needed.",2000.0,0,0
117,10873925,Low incidence of persistent tardive dyskinesia in elderly patients with dementia treated with risperidone.,D V Jeste; A Okamoto; J Napolitano; J M Kane; R A Martinez,"The authors studied the incidence of tardive dyskinesia in elderly institutionalized patients with dementia being treated with risperidone. After participating in a 12-week multicenter double-blind study during which they received placebo or one of three doses of risperidone, 330 patients (mean age=82.5 years) with Alzheimer's, vascular, or mixed dementia were enrolled in a 1-year open-label study during which they received flexible doses of risperidone. Persistent emergent tardive dyskinesia was defined according to scores on the dyskinesia subscale of the Extrapyramidal Symptom Rating Scale. The mean modal risperidone dose was 0.96 mg/day (SD=0.53), and the median length of risperidone use was 273 days. The 1-year cumulative incidence of persistent emergent tardive dyskinesia among the 255 patients without dyskinesia at baseline was 2.6%. Patients with dyskinetic symptoms at baseline experienced significant reductions in the severity of dyskinesia. Patients who received 0.75-1.5 mg/day of risperidone showed a significant improvement in psychopathologic symptoms over the 1-year period. Although there was no control group, the observed incidence of persistent tardive dyskinesia with risperidone seemed to be much lower than that seen in elderly patients treated with conventional neuroleptics. The average optimal dose of risperidone in elderly dementia patients was found to be 0.75-1.5 mg/day.",2000.0,0,0
118,10882838,Profiles of cognitive dysfunction in chronic amphetamine and heroin abusers.,T J Ornstein; J L Iddon; A M Baldacchino; B J Sahakian; M London; B J Everitt; T W Robbins,"Groups of subjects whose primary drug of abuse was amphetamine or heroin were compared, together with age- and IQ-matched control subjects. The study consisted of a neuropsychological test battery which included both conventional tests and also computerised tests of recognition memory, spatial working memory, planning, sequence generation, visual discrimination learning, and attentional set-shifting. Many of these tests have previously been shown to be sensitive to cortical damage (including selective lesions of the temporal or frontal lobes) and to cognitive deficits in dementia, basal ganglia disease, and neuropsychiatric disorder. Qualitative differences, as well as some commonalities, were found in the profile of cognitive impairment between the two groups. The chronic amphetamine abusers were significantly impaired in performance on the extra-dimensional shift task (a core component of the Wisconsin Card Sort Test) whereas in contrast, the heroin abusers were impaired in learning the normally easier intra-dimensional shift component. Both groups were impaired in some of tests of spatial working memory. However, the amphetamine group, unlike the heroin group, were not deficient in an index of strategic performance on this test. The heroin group failed to show significant improvement between two blocks of a sequence generation task after training and additionally exhibited more perseverative behavior on this task. The two groups were profoundly, but equivalently impaired on a test of pattern recognition memory sensitive to temporal lobe dysfunction. These results indicate that chronic drug use may lead to distinct patterns of cognitive impairment that may be associated with dysfunction of different components of cortico-striatal circuitry.",2000.0,0,0
119,10884491,No side effects after low-dose amphetamine administration in stroke rehabilitation.,H Unwin; D Walker-Batson,,2000.0,0,0
120,10885641,Clozapine augmentation: safety and efficacy.,S A Chong; G Remington,"While clozapine has been demonstrated to be efficacious in refractory schizophrenia and possibly schizoaffective as well as bipolar disorders, a substantial number of patients still remain unresponsive. One strategy in treating these refractory patients is to augment clozapine with other somatic treatments. This article reviews the efficacy and safety of the combination of clozapine with other somatic treatments. A total of 70 articles were obtained from a manual, as well as computerized (Medline), search of the English language literature from 1978 to March 1998. Few controlled studies exist; most were case reports/series. From these data, the greatest risk of adverse effects seems to be associated with clozapine combined with benzodiazepines, valproate, or lithium, but no currently evaluated combination is absolutely unsafe. In terms of efficacy, the data suggest a number of potential augmentation strategies, although controlled data are few. Combination therapies with clozapine are common in clinical practice, despite a lack of empirical data, and the benefits and risks of these combinations need to be systematically reviewed.",2001.0,0,0
121,10885682,"Naming speed performance and stimulant effects indicate effortful, semantic processing deficits in attention-deficit/hyperactivity disorder.",R Tannock; R Martinussen; J Frijters,"This study investigated rapid automatized naming and effects of stimulant medication in school-age children with attention-deficit/hyperactivity disorder (ADHD) with and without concurrent reading disorder (RD). Two ADHD groups (67 ADHD only; 21 ADHD + RD) and a control group of 27 healthy age-matched peers were compared on four variables: color naming speed, letter naming speed, phonologic decoding, and arithmetic computation. Discriminant function analysis (DFA) was conducted to predict group membership. The four variables loaded onto two discriminant functions with good specificity: phonologic decoding, letter naming speed, and arithmetic defined the first function; color naming speed defined the second function. Both ADHD groups were significantly slower in color naming than controls, but did not differ from one another. DFA correctly classified 96% of the control group, 91% of ADHD + RD, and 82% of ADHD only. A subset of children in the ADHD groups participated subsequently in an acute, randomized, placebo-controlled, crossover trial with three single doses (10, 25, 20 mg) of methylphenidate. Methylphenidate selectively improved color-naming speed but had no effect on the speed of naming letters or digits. These findings challenge the tenet that naming speed deficits are specific to RD and implicate naming speed deficits associated with effortful semantic processing in ADHD, which are improved but not normalized by stimulant medication.",2001.0,0,1
122,10899363,,,,,0,0
123,10901338,Low-dose amphetamine salts and adult attention-deficit/hyperactivity disorder.,J P Horrigan; L J Barnhill,"Effective treatments for attention-deficit/hyperactivity disorder (ADHD) in adults are still being defined. Pediatric studies have suggested that a mixed amphetamine salt product (Adderall) is safe and effective in the treatment of childhood forms of ADHD. Presently, there are no reports in the scientific literature concerning the safety and efficacy of Adderall in adults with ADHD, which is the focus of this study. Twenty-four outpatients (mean age = 33.3 years) with DSM-IV ADHD were administered Adderall in an open-label fashion, starting at 5 mg p.o. b.i.d., with titration according to clinical response, across a 16-week period. Relatives or spouses of each patient completed serial checklists (including the Copeland Symptom Checklist and the Brown Attention-Deficit Disorder Scales). Prospectively collected data were analyzed retrospectively. Thirteen patients (54%) responded in a positive manner to Adderall, based on Clinical Global Impressions-Improvement scale scores. The mean end dose for responders was 10.77 mg/day (0.14 mg/kg/day). An intent-to-treat analysis revealed a decrease in the mean Copeland score from 99.05 to 63.3 (p < .001), while the mean Brown score dropped from 76.75 to 50.85 (p < .0001). Nine patients (38%) were poor responders or nonresponders to Adderall. Acute anxiety symptoms occurred in 4 of 7 patients with a comorbid anxiety diagnosis. Adderall may be an effective agent for the treatment of adult forms of ADHD, with positive responses occurring at relatively low doses, at least for some individuals. However, Adderall may precipitate anxiety in vulnerable individuals. Further study is required.",2000.0,0,0
124,10901343,Electrocardiographic abnormalities in patients treated with clozapine.,U G Kang; J S Kwon; Y M Ahn; S J Chung; J H Ha; Y J Koo; Y S Kim,"Cardiovascular side effects of clozapine are not uncommon, but few systematic studies of these effects have been performed. In this study, we reviewed data on the electrocardiographic (ECG) abnormalities in patients treated with clozapine. Sixty-one patients treated with clozapine were selected from the Seoul National University Hospital Treatment-Resistant Schizophrenia Clinic. A retrospective chart review was conducted to identify ECG abnormalities and cardiovascular side effects. The prevalence of ECG abnormalities in patients who had been using antipsychotics other than clozapine was 13.6% at baseline, which increased significantly to 31.1% after commencement of clozapine treatment. Among the 53 patients without baseline ECG abnormalities, 13 showed new-onset ECG abnormalities after using clozapine. Normal ECG under previous antipsychotic medication reduced the risk of new-onset ECG abnormalities, whereas increased age was found to increase the risk. The occurrence of orthostatic hypotension or tachycardia was not related to the development of ECG abnormalities. Most of the newly developed abnormalities had little clinical significance, and they tended to occur during the initial phase of treatment. In 10 patients, ECGs normalized despite the continued use of clozapine. Clozapine increased corrected QT interval (QTc) in a dose-dependent fashion; however, the clinical significance of this observation is uncertain. Pathologic prolongation of QTc was found to be rare. Although a substantial portion of patients treated with clozapine developed ECG abnormalities, most of the abnormalities were benign and did not hinder further treatment.",2000.0,0,0
125,10910854,Small-dose clonidine prolongs postoperative analgesia after sciatic-femoral nerve block with 0.75% ropivacaine for foot surgery.,A Casati; L Magistris; G Fanelli; P Beccaria; G Cappelleri; G Aldegheri; G Torri,"To evaluate the effects of adding small-dose clonidine to 0.75% ropivacaine during peripheral nerve blocks, 30 ASA physical status I and II patients undergoing hallux valgus repair under combined sciatic-femoral nerve block were randomly allocated in a double-blinded fashion to receive block placement with 30 mL of either 0.75% ropivacaine alone (group Ropivacaine, n = 15) or 0.75% ropivacaine plus 1 microg/kg clonidine (group Ropivacaine-Clonidine, n = 15). Hemodynamic variables, oxygen saturation, and levels of sedation, as well as the time required to achieve surgical block and time to first analgesic request, were recorded by a blinded observer. Time to surgical blockade required 10 min in both groups. Patients in the Ropivacaine-Clonidine group were more sedated than patients in the Ropivacaine group only 10 min after block placement. No differences in oxygen saturation and hemodynamic variables, degree of pain measured at first analgesic request, and consumption of postoperative analgesics were observed between the two groups. The mean time from block placement to first request for pain medication was shorter in group Ropivacaine (13.7 h; 25th-75th percentiles: 11. 8-14.5 h) than in group Ropivacaine-Clonidine (16.8 h; 25th-75th percentiles: 13.5-17.8 h) (P = 0.038). We conclude that adding 1 microg/kg clonidine to 0.75% ropivacaine provided a 3-h delay in first request for pain medication after hallux valgus repair, with no clinically relevant side effects. This prospective, randomized, double-blinded study demonstrated that, when providing combined sciatic-femoral nerve block for hallux valgus repair, the addition of 1 microg/kg clonidine to 0.75% ropivacaine prolongs the duration of postoperative analgesia by 3 h, with only a slight and short-lived increase in the degree of sedation and no hemodynamic adverse effects.",2000.0,0,0
126,10917410,Risperidone for the treatment of stuttering.,G A Maguire; G D Riley; D L Franklin; L A Gottschalk,"A randomized, double-blind, placebo-controlled study was conducted to assess the efficacy of risperidone in the treatment of developmental stuttering in 16 adults. Eight subjects received placebo and eight received risperidone at 0.5 mg once daily at night, increased to a maximum of 2 mg/day. After 6 weeks of treatment, decreases in all measures of stuttering severity were greater in the risperidone group than in the placebo group; the between-treatment difference was significant (p < 0.05) on the most important measure, the percentage of syllables stuttered. In the risperidone group, reductions from baseline in scores for the percentage of syllables stuttered, time stuttering as a percentage of total time speaking, and overall stuttering severity were significant (p < 0.01); changes in scores on the fourth measure of stuttering, duration, were not significant. No significant decreases occurred in the placebo group. Among the eight patients in the risperidone group, five responded best to 0.5 mg/day, with stuttering recurring at higher doses. The remaining three patients responded better with increasing doses of risperidone. Risperidone was generally well tolerated. The results of this small study indicate that risperidone may be effective in the treatment of developmental stuttering. This finding needs to be confirmed in a larger trial.",2001.0,0,0
127,10920469,"A double-blind, placebo-controlled study of risperidone addition in serotonin reuptake inhibitor-refractory obsessive-compulsive disorder.",C J McDougle; C N Epperson; G H Pelton; S Wasylink; L H Price,"To date, only 1 controlled study has found a drug (haloperidol) to be efficacious in augmenting response in patients with obsessive-compulsive disorder (OCD) refractory to serotonin reuptake inhibitor (SRI) monotherapy; patients with comorbid chronic tic disorders showed a preferential response. This report describes the first controlled study of risperidone addition in patients with OCD refractory to treatment with SRI alone. Seventy adult patients with a primary DSM-IV diagnosis of OCD received 12 weeks of treatment with an SRI. Thirty-six patients were refractory to the SRI and were randomized in a double-blind manner to 6 weeks of risperidone (n = 20) or placebo (n = 16) addition. Behavioral ratings, including the Yale-Brown Obsessive Compulsive Scale, were obtained at baseline and throughout the trial. Placebo-treated patients subsequently received an identical open-label trial of risperidone addition. For study completers, 9 (50%) of 18 risperidone-treated patients were responders (mean daily dose, 2.2 +/-0.7 mg/d) compared with 0 of 15 in the placebo addition group (P<. 005). Seven (50%) of 14 patients who received open-label risperidone addition responded. Risperidone addition was superior to placebo in reducing OCD (P<.001), depressive (P<.001), and anxiety (P =.003) symptoms. There was no difference in response between OCD patients with and without comorbid diagnoses of chronic tic disorder or schizotypal personalty disorder. Other than mild, transient sedation, risperidone was well tolerated. These results suggest that OCD patients with and without comorbid chronic tic disorders or schizotypal personality disorder may respond to the addition of low-dose risperidone to ongoing SRI therapy.",2000.0,0,0
128,10929273,Olanzapine in severe Gilles de la Tourette syndrome: a 52-week double-blind cross-over study vs. low-dose pimozide.,M Onofrj; C Paci; G D'Andreamatteo; L Toma,"We selected four patients with severe Gilles de la Tourette syndrome, high frequency of tics (two to ten per minute), vocalizations, and lack of comorbidity. These patients (aged 19-40 years) underwent a 52-week double-blind cross-over study with olanzapine (5 and 10 mg daily) vs. low-dose pimozide (2 and 4 mg daily). The reduction in rating scale scores for the syndrome was highly significant with 10 mg olanzapine vs. basal and vs. 2 mg pimozide, and was significant for 5 mg olanzapine vs. 4 mg pimozide. Only moderate sedation was reported by one patient during olanzapine treatment while three complained of minor motor side effects and sedation during pimozide treatment. At the end of the study all patients opted for olanzapine treatment.",2001.0,0,0
129,10937603,Treatment of men with major depression: a comparison of sequential cohorts treated with either cognitive-behavioral therapy or newer generation antidepressants.,M E Thase; E S Friedman; A L Fasiczka; S R Berman; E Frank; E A Nofzinger; C F Reynolds,"This report compares response to cognitive-behavioral therapy (CBT) and pharmacotherapy in sequential cohorts of men with DSM-III-R major depression. Patients were enrolled in consecutive standardized 16-week treatment protocols conducted in the same research clinic. The first group (N = 52) was treated with Beck's model of CBT, whereas the second group (N = 23) received randomized but open-label treatment with either fluoxetine (N = 10) or bupropion (N = 13). Crossover to the alternate medication was permitted after 8 weeks of treatment for antidepressant nonresponders. The patient groups were well matched prior to treatment. Outcomes included remission and nonresponse rates, as well as both independent clinical evaluations and self-reported measures of depressive symptoms. Despite limited statistical power to detect differences between treatments, depressed men treated with pharmacotherapy had significantly greater improvements on 4 of 6 continuous dependent measures and a significantly lower rate of nonresponse (i.e., 13% vs. 46%). The difference favoring pharmacotherapy was late-emerging and partially explained by crossing over nonresponders to the alternate medication. The advantage of pharmacotherapy over CBT also tended to be larger among the subgroup of patients with chronic depression. Results of prior research comparing pharmacotherapy and CBT may have been influenced by the composition of study groups, particularly the gender composition, the choice of antidepressant comparators, or an interaction of these factors. Prospective studies utilizing flexible dosing of modern antidepressants and, if necessary, sequential trials of dissimilar medications are needed to confirm these findings.",2000.0,0,0
130,10937608,Comparative efficacy of risperidone and clozapine in the treatment of patients with refractory schizophrenia or schizoaffective disorder: a retrospective analysis.,Z A Sharif; A Raza; S S Ratakonda,"Clozapine is effective in up to 60% of patients with refractory schizophrenia, whereas the efficacy of risperidone remains unknown. This retrospective study examined the relative efficacy of these drugs in chronically institutionalized patients refractory to conventional antipsychotic agents. A total of 24 patients who at different time periods had received adequate trials of both clozapine and risperidone and met our inclusion criteria for minimum dose and duration of each trial were included; for clozapine, a minimum dose of 300 mg/day had to be maintained for at least 12 weeks, and for risperidone, a minimum dose of 6 mg/day for at least 6 weeks. Information obtained from systematic retrospective chart review was blindly rated by 2 psychiatrists using the 7-point Clinical Global Impressions-Improvement (CGI-I) scale on overall clinical state and along specific symptom domains of positive symptoms, negative symptoms, and aggressive behavior. The mean +/- SD dose was 520+/-94 mg/day for clozapine and 7.5+/-2.2 mg/day for risperidone. Fourteen patients (58%) were classified as responders to clozapine, while 6 (25%) responded to risperidone (CGI-I score of 1 or 2); on specific symptom domains, response rates to clozapine were 38% (9/24) on positive symptoms, 29% (7/24) on negative symptoms, and 71% (12/17) on aggressive behavior. For risperidone, response rates were 17% (4/24) on positive symptoms, 8% (2/24) on negative symptoms, and 41% (7/17) on aggressive behavior. The results of this study support the utility of first giving a risperidone trial in a treatment algorithm for refractory patients because of its better risk/benefit profile compared with clozapine. Clozapine, however, remains our gold standard in the management of these patients.",2000.0,0,0
131,10949680,[Premedication in maxillofacial surgery under total intravenous anesthesia . Effects of clonidine compared to midazolam on the perioperative course].,T Frank; V Thieme; L Radow,"The effects of the currently favoured preanaesthetic drugs (benzodiazepines, alpha 2-adrenoceptor agonists) on the perioperative course are inadequately investigated for new ways of performing anaesthesia with recently introduced drugs (e.g. remifentanil). Therefore clonidine and midazolam were used for premedication in maxillo-facial surgery under total intravenous anesthesia, and the perioperative courses were analyzed. Thirty patients (ASA 1-2) were included in the present doubleblinded, prospective study. 60-90 minutes preoperatively these patients got an oral premedication with 5 micrograms kg-1 clonidine or 100 micrograms kg-1 midazolam. For anaesthesia a standardized procedure with propofol, remifentanil and rocuronium was performed. After induction of anaesthesia the infusion of remifentanil was regulated by using spectral edge frequency (target-SEF90, 10-13 Hz). The efficiency of the premedication as well as the emergence and recovery were assessed by using established standardized tests. The perioperative stress response was assessed by recording the effects on haemodynamic parameters (NIBP. heart rate. Holter-ECG). Referring to the effects of premedication (sedation, anxiety) there were no differences between the groups. The clonidine group required a lower remifentanil rate in keeping a steady-target-SEF90 (-24%). The time until emergence and recovery was not significantly different. Even the occurrence of PONV, VAS or the postoperative analgetic requirement did not differ between the two groups. However, the incidence of postoperative shivering was significantly higher in the midazolam group. Intraoperatively the values of MAP were quite equal between the groups. However, heart rate was significantly lower in the clonidine group. Postoperatively both MAP as well as heart rate were lower in the clonidine group. Furthermore, in the midazolam group there was a significantly higher cumulative duration of tachycardia (heart rate > 100 min-1; following descripted as medium with 25% and 75%-percentage; clonidine: 29/0/563 sec.: midazolam: 1058/232/3171 sec.). After remifentanil supplemented anesthesia there is, especially in the postoperative period, a benefit in using clonidine compared to the premedication with midazolam.",2000.0,0,0
132,10954143,Amphetamine abuse during pregnancy: environmental factors and outcome after 14-15 years.,M Eriksson; B Jonsson; G Steneroth; R Zetterström,"The aim of this study was to assess the influence of social environmental factors on school performance and behavioural problems among 14-year-old children who had been exposed to amphetamine during foetal life. The study group comprised a cohort of 65 children who had suffered intrauterine exposure to amphetamine due to maternal drug abuse. This group has been followed since birth and examined at regular intervals. Information regarding the academic performance of the children was gathered from the school authorities. The psychosocial environment of the children was determined through interviews and through information obtained from the social authorities. Of the 64 children who attended a school within the state school system, 10 (15%) were a year behind for their age. The mean grades were significantly lower than those of their classmates. Behavioural problems were mentioned in the social authority documentation of one-third of the children, regardless of whether the child was placed in a foster home or was residing with the biological mother. A positive significant correlation was found between maternal age and the outcome of the children, as well as between therapy during pregnancy and outcome, whilst several environmental factors, particularly during the child's first four years, correlate negatively to outcome. Psychosocial factors early in life influence the outcome at 14 years. The positive effect of intervention during pregnancy illustrates the importance of early identification preferable during pregnancy.",2001.0,0,0
133,10980811,,,,,0,0
134,10981082,Centrally acting antihypertensive drugs: re-emergence of sympathetic inhibition in the treatment of hypertension.,C R Benedict,"Central regulation of the sympathetic nervous system plays an important role in the maintenance of blood pressure. In a subset of patients with essential hypertension, sympathetic activation may contribute to the development and maintenance of hypertension. Unlike the first generation of centrally active antihypertensive drugs, the second generation may be superior because of its selectivity to I1-imidazoline receptor and selective binding to the vasomotor center. Lack of a2 effects differentiates moxonidine from clonidine with respect to monoxidine""s superior side-effect profile (little or no sedation or dry mouth). Clinical trials show that moxonidine is as effective as angiotensin-converting enzyme inhibitors (eg, enalapril and captopril), b-blockers (e.g., atenolol), calcium-channel blockers (e.g., long-acting nifedipine), and diuretics (eg, hydrochlorothiazide) in lowering blood pressure and that it has superior tolerability. Thus, central modulation of the sympathetic nervous system has re-emerged as an exciting target for blood pressure reduction. Given the multiple adverse effects of sympathetic stimulation in various disease processes, including congestive heart failure, moxonidine may be the next therapeutic option for the management of hypertension and the prevention of target organ dysfunction.",2001.0,0,0
135,10986547,"Efficacy of olanzapine in acute bipolar mania: a double-blind, placebo-controlled study. The Olanzipine HGGW Study Group.",M Tohen; T G Jacobs; S L Grundy; S L McElroy; M C Banov; P G Janicak; T Sanger; R Risser; F Zhang; V Toma; J Francis; G D Tollefson; A Breier,"We compared the efficacy and safety of olanzapine vs placebo for the treatment of acute bipolar mania. Four-week, randomized, double-blind, parallel study. A total of 115 patients with a DSM-IV diagnosis of bipolar disorder, manic or mixed, were randomized to olanzapine, 5 to 20 mg/d (n = 55), or placebo (n = 60). The primary efficacy measure was the Young-Mania Rating Scale (Y-MRS) total score. Response and euthymia were defined, a priori, as at least a 50% improvement from baseline to end point and as a score of no less than 12 at end point in the Y-MRS total score, respectively. Safety was assessed using adverse events, Extrapyramidal Symptom (EPS) rating scales, laboratory values, electrocardiograms, vital signs, and weight change. Olanzapine-treated patients demonstrated a statistically significant greater mean (+/- SD) improvement in Y-MRS total score than placebo-treated patients (-14.8 +/- 12.5 and -8.1 +/- 12.7, respectively; P<.001), which was evident at the first postbaseline observation 1 week after randomization and was maintained throughout the study (last observation carried forward). Olanzapine-treated patients demonstrated a higher rate of response (65% vs 43%, respectively; P =.02) and euthymia (61% vs 36%, respectively; P =. 01) than placebo-treated patients. There were no statistically significant differences in EPSs between groups. However, olanzapine-treated patients had a statistically significant greater mean (+/- SD) weight gain than placebo-treated patients (2.1 +/- 2.8 vs 0.45 +/- 2.3 kg, respectively) and also experienced more treatment-emergent somnolence (21 patients [38.2%] vs 5 [8.3% ], respectively). Olanzapine demonstrated greater efficacy than placebo in the treatment of acute bipolar mania and was generally well tolerated.",2000.0,0,0
136,10989263,Mazindol treatment of negative symptoms.,W T Carpenter; A Breier; R W Buchanan; B Kirkpatrick; P Shepard; E Weiner,"Hypodopaminergic and hyponoradrenergic pathophysiology may be a basis for primary and/or secondary negative symptoms in schizophrenia. The hypothesis that enhanced neurotransmission in these systems would be therapeutic for negative symptoms was tested by comparing mazindol and placebo in a double-blind, cross-over design trial. Outcome following mazindol supplementation was comparable to placebo supplementation (F(1,30) = 0.9; p = .57). Results for deficit and non-deficit schizophrenia subjects were similar, and were not affected by whether concurrent the antipsychotic drug treatment was clozapine, fluphenazine, or haloperidol. The efficacy hypothesis was not supported for either primary or secondary negative symptoms.",2001.0,0,0
137,10989857,Optimal dose of intrathecal clonidine added to sufentanil plus bupivacaine for labour analgesia.,A T Sia,"The combination of intrathecal (IT) 5 microg sufentanil plus 1.25 mg bupivacaine is useful for inducing labour analgesia, albeit of short duration and slow onset. As a supplementation to this regimen, the effect of IT clonidine on the duration of analgesic action was investigated. Forty-eight healthy parturients were randomly assigned into three groups to receive 0 microg (group C0), 15 microg (C15) or 30 microg (C30) of clonidine IT in addition to 5 microg sufentanil plus 1.25 mg bupivacaine IT for labour analgesia. The quality of pain relief was assessed on 0-100 visual analogue scale by the author. The occurrence of side effects was also evaluated before the request for additional analgesia. Clonidine (C15 and C30), produced a longer duration of analgesia than C0 (mean 144 +/- sd 27.9, 165 +/- 31.8 vs 111 +/- 21.9 min, P < 0.01). Also, C15 and C30 produced a more rapid onset and a higher quality of analgesia than C0, (P < 0.01). The most cephalad level of sensory block was higher in C30 than C15 (median T3 vs T4, P < 0.05) but lowest in C0 (median T7 vs T3,T4, P < 0.01). Side effects, sedation and hypotension, occurred more frequently in C30 than in either C0 or C 15, (9 vs 2,5 and 9 vs 1,3, respectively, P < 0.05). The optimal dose of intrathecal clonidine to enhance labour analgesia with the current sufentanil-bupivacaine regimen is 15 microg. In view of the side effect profile, doses greater than 30 microg clonidine are unlikely to be useful.",2001.0,0,0
138,10993998,Low-dose olanzapine for levodopa induced dyskinesias.,A J Manson; A Schrag; A J Lees,"To assess the usefulness of low-dose olanzapine (2.5 to 7. 5 mg/day) for Levodopa-induced-dyskinesias (LID) in patients with PD. Ten patients with PD and LID took part in this randomized, placebo-controlled, double blind, crossover trial. Patients received a 2-week course of olanzapine or placebo in each treatment phase with 1-week washout in between. Dyskinesias were assessed at baseline and after each treatment period with an acute dopaminergic challenge and unified PD rating scale (UPDRS) questionnaires. Patients also kept on/off and dyskinesia diaries for the last 3 days prior to each assessment. There was a 41% difference in dyskinesia reduction on olanzapine compared to placebo, as measured by objective dyskinesia rating scales (mean percentage reduction abnormal involuntary movement score: 30% versus -11.2%, p < 0.02). Similar differences were demonstrated by patient diaries (mean reduction: 46% versus -2%, p < 0.02) and UPDRS items 32 and 33. Compared with placebo, treatment with olanzapine resulted in significant increases in 'off' time as measured by patient diaries (30% versus 2%) and reported adverse events (1.7 versus 0.1) including increased parkinsonism (1.1 versus 0.1) and a nonsignificant reported increase in drowsiness. Low-dose olanzapine is effective in reducing dyskinesias in PD, but even at very low doses can result in unacceptable increases in parkinsonism and 'off' time.",2001.0,0,0
139,11018228,,,,,0,0
140,11020745,Oral clonidine premedication does not change efficacy of simulated epidural test dose in sevoflurane-anesthetized children.,M Shiga; K Nishina; K Mikawa; T Uesugi; N Maekawa; H Obara,"Caudal epidural anesthesia is often used as an adjunct to general anesthesia and for postoperative pain relief in children. In anesthetized children, epinephrine and isoproterenol are reliable indicators to detect accidental intravascular injection of a test dose. Oral clonidine, a useful premedicant in pediatric anesthesia, modifies hemodynamic responses to sympathomimetics, including catecholamines. The aim of the current study was to determine whether oral clonidine premedication alters the efficacy of a simulated intravascular test dose containing epinephrine or isoproterenol in sevoflurane-anesthetized children. One hundred twenty children (aged 1-7 yr) were randomly divided into six groups; control-saline, control-epinephrine, control-isoproterenol, clonidine-saline, clonidine-epinephrine, and clonidine-isoproterenol. The three clonidine groups received oral clonidine 4 microg/kg [DOSAGE ERROR CORRECTED] as premedication, whereas the three control groups did not receive any premedication. Anesthesia was maintained with sevoflurane at a level of 1.2 minimum alveolar concentration. After hemodynamics were stable, 0.1 ml/kg of 1% lidocaine containing epinephrine 0.5 mg/kg or isoproterenol 75 ng/kg was intravenously given to the two epinephrine or isoproterenol groups, respectively, to simulate intravascular injection of a test dose. The saline groups received saline alone instead of the test dose. Heart rate, blood pressure, and T-wave amplitude of electrocardiogram were recorded before and after administration of study drugs for subsequent analysis. Test solution containing epinephrine increased heart rate, systolic blood pressure, and T-wave amplitude. Oral clonidine had no effect on elevation of these variables in response to epinephrine. The isoproterenol-containing test dose produced a prominent increase in heart rate and a less pronounced increase in systolic blood pressure and T-wave amplitude. Oral clonidine also failed to modify isoproterenol-induced hemodynamic and T-wave changes. Calculated sensitivity and specificity of epinephrine or isoproterenol were all 100% based on a new heart rate criterion (positive if >/= 10 beats/min) and were unaltered by oral clonidine premedication. Epinephrine or isoproterenol is a reliable marker to detect accidental intravascular injection of a test dose with 100% sensitivity and specificity based on a new heart rate criterion in sevoflurane-anesthetized children. These data suggest that oral clonidine premedication does not alter the efficacy of a simulated epidural test dose containing epinephrine or isoproterenol.",2001.0,0,0
141,11025232,Preoperative clonidine attenuates stress response during emergence from anesthesia.,M P Zalunardo; A Zollinger; D R Spahn; B Seifert; T Pasch,"To investigate whether a single preoperative IV dose of clonidine blunts the hemodynamic and hyperadrenergic responses not only to intubation, but also to extubation. Randomized, double-blind, placebo-controlled study. 29 ASA physical status I and II patients (ages 18-65) who were scheduled for noncardiac, elective surgery. Patients were randomly assigned to either receive clonidine 3 microg/kg IV immediately before anesthesia induction or placebo. Insertion of a 14 G cannula in a large cubital vein for the determination of plasma catecholamines using local anesthesia. Insertion of a radial artery catheter for measuring blood pressure (BP) using local anesthesia. Transthoracic echocardiography to determine cardiac output (CO). Heart rate (HR), mean arterial pressure (MAP), CO, and plasma catecholamine concentrations. Measurements were performed: before induction (baseline), during intubation, 10 min after intubation, after surgery, during extubation, and 10 min after extubation. During intubation MAP, HR, and CO were lower in the clonidine group. Compared with baseline measurements, MAP and CO increased less in the clonidine group during intubation. During extubation, MAP was lower in the clonidine group. CO and MAP increased less as compared with baseline measurements in the clonidine group. Compared with the measurements after surgery CO less in the clonidine group during extubation (p < 0.05 for all results). A single preoperative IV dose of clonidine (3 microg/kg) blunts the hemodynamic responses due to extubation in noncardiac surgery of intermediate duration.",2001.0,0,0
142,11025234,Low-dose intrathecal clonidine combined with sufentanil as analgesic drugs in abdominal gynecological surgery.,M C Julião; G R Lauretti,"To determine whether a low dose of spinal clonidine either alone or combined with sufentanil would provide effective analgesia following abdominal surgery, as a supplement to bupivacaine spinal anesthesia. Randomized double-blind study. Gynecological surgery, teaching hospital. 73 ASA physical status I and II patients undergoing gynecological abdominal surgery with spinal anesthesia. Patients were randomly assigned to one of four groups and prospectively studied to examine anesthesia, analgesia, and adverse effects. The control group received saline as the test drug; the sufentanil group received 10 microg of sufentanil; the clonidine group received 30 microg of clonidine; and the sufentanil/clonidine group received 5 microg of sufentanil plus 15 microg of clonidine. All groups received intrathecal 15 mg of bupivacaine (3 mL) plus the intrathecal test drug (2 mL). The concept of visual analog scale (VAS) was introduced. All patients were premedicated with intravenous midazolam. Rescue analgesics were available. The groups were demographically the same. Sensory block to pinprick at 10 min was higher for clonidine and sufentanil/clonidine groups compared to the control group (p < 0.02). Anesthetic time (Bromage score 2) was also longer for clonidine and sufentanil/clonidine groups compared to the control and sufentanil groups (p < 0.05). Time to first rescue analgesics was shorter in the control group compared to the other groups (p < 0.02). The number of IM diclofenac dose injections in 24 hours was higher in the control group compared to all other groups (p < 0.05). The incidence of adverse effects and ephedrine consumption were similar among groups. Intrathecal 15- and 30-microg clonidine doses expanded the anesthesia sensory block and duration of motor block, and provided analgesia.",2001.0,0,0
143,11028253,"Dose-proportional and stereospecific pharmacokinetics of methylphenidate delivered using an osmotic, controlled-release oral delivery system.",N B Modi; B Wang; R J Noveck; S K Gupta,"Methylphenidate hydrochloride (HCl) is frequently used for the treatment of attention deficit/hyperactivity disorder (ADHD). A study was conducted in healthy subjects to evaluate the dose-ranging pharmacokinetics of 18, 36, and 54 mg methylphenidate HCl delivered using an oral, osmotic, controlled-release formulation (OROS). Plasma concentrations of l-methylphenidate were 40-fold lower than those of d-methylphenidate, whereas plasma concentrations of d-alpha-phenyl-2-piperidine acetic acid (d-PPA) and l-PPA, the major metabolite of methylphenidate, were comparable. Mean AUCinf values for d-methylphenidate were 42.2, 80.9, and 120 ng.h/mL for the 18, 36, and 54 mg doses, respectively, increasing dose proportionally. AUCinf values for l-methylphenidate were only approximately 1% of d-methylphenidate (0.43, 0.96, and 1.82 ng.h/mL for the 18, 36, and 54 mg dose groups, respectively). In contrast, AUCinf values of d- and l-PPA were comparable. The dose-normalized d- and l-methylphenidate plasma concentration-time profiles for the three treatment groups were superimposable. Similarly, dose-normalized plasma concentrations of d- and l-PPA were superimposable. Methylphenidate metabolism, measured as the ratio of d-methylphenidate AUCinf to d-PPA AUCinf and as l-methylphenidate AUCinf to l-PPA AUCinf, was similar for the three dose groups, indicating that methylphenidate metabolism was not affected by increasing dose. OROS (methylphenidate HCl) exhibits dose-proportional and linear pharmacokinetics.",2001.0,0,0
144,11061283,,,,,0,0
145,11071034,Low-dose oral clonidine as premedication before intraocular surgery in retrobulbar anesthesia.,J Weindler; R T Kiefer; A Rippa; K Wiech; K W Ruprecht,"We investigated whether low-dosed oral clonidine premedication before elective intraocular surgery in retrobulbar anesthesia is effective in terms of anxiolysis, sedation, stable hemodynamics, lower intraocular pressure and perioperative endocrine stress response. In a prospective, randomised, double-blind study, 44 patients scheduled for elective intraocular surgery received either 0.15 mg clonidine (n=22) or a matched placebo (n=22) orally 60 minutes before retrobulbar anesthesia. The main study parameters were sedation, anxiolysis, hemodynamics and intraocular pressure. Additionally, mediators of endocrine stress responses were measured five times, in 13 patients after clonidine and 12 after placebo. After clonidine 86% of the patients showed sedation and after placebo 90.9% showed no sedation (p<0.01). Clonidine produced effective anxiolysis (Erlanger-Anxiety-Scale: 31.6 +/- 2.6 points vs. 38.1 +/- 8.5 points) before the operation (p<0.01). Systolic blood pressure was significantly lower after clonidine. Effects on mean and diastolic blood pressure were small but statistically significant. Norepinephrine and cortisol plasma concentrations were significantly lower after clonidine. Intraocular pressure was significantly lower too (p<0.05). No clinically relevant adverse effects were observed e.g. inappropriate sedation, hypotension (<100 mmHg), bradycardia (<50 bpm) or hypoxemia (SpO2<90%). Oral low-dose clonidine produces light sedation, significant anxiolysis and stable hemodynamics, and attenuates the endocrine response to perioperative stress. Thus, clonidine seems sufficient to increase patient comfort for intraocular surgery and might even offer clinically worthwhile benefits such as stable hemodynamics and a reduced response to perioperative stress.",2001.0,0,0
146,11098812,Augmentation with sulpiride for a schizophrenic patient partially responsive to clozapine.,J H Stubbs; C M Haw; C J Staley; C Q Mountjoy,Schizophrenic patients who are only partially responsive to clozapine pose a therapeutic challenge. In these circumstances some clinicians would consider adding in a second antipsychotic. We present a case report and review evidence for the efficacy of such augmentation strategies. Single case report and literature review. The total number of patients in studies and case reports of combining clozapine with other antipsychotics is small. There has been only one randomized controlled trial. This found the addition of sulpiride to clozapine resulted in clinical improvement in some patients. Further randomized controlled studies of augmentation of clozapine therapy are needed to provide scientific justification for this clinical practice.,2001.0,0,0
147,11116699,Randomised fellow eye comparison of the effectiveness of dorzolamide and apraclonidine on intraocular pressure following phacoemulsification cataract surgery.,G Rainer; R Menapace; O Findl; M Georgopoulos; B Kiss; G Heinze,"To compare the effectiveness of 2% dorzolamide and 0.5% apraclonidine on intraocular pressure (IOP) following phacoemulsification cataract surgery. This prospective, randomised study comprised 54 eyes of 27 consecutive patients with age-related cataract scheduled for cataract surgery in both eyes. In each patient the eye with the higher degree of cataract was randomly assigned to receive one drop of either dorzolamide or apraclonidine immediately after surgery. The fellow eye was operated on later and received the other treatment. Cataract surgery was performed with a superior 6.0 mm sutureless frown incision, phacoemulsification and implantation of a three-piece PMMA intraocular lens. The IOP was measured pre-operatively as well as 6 h and 20-24 h and 1 week post-operatively. The mean pre-operative IOP was not significantly different between the groups (dorzolamide group, 14.9 +/- 2.3 mmHg; apraclonidine group, 14.6 +/- 2.5 mmHg; p = 0.450). At 6 h post-operatively, the mean IOP was significantly lower in the dorzolamide than in the apraclonidine group (15.6 +/- 3.9 mmHg vs 18.0 +/- 4.0 mmHg; p < 0.001). An IOP increase of more than 5 mmHg at 6 h post-operatively occurred in 3 (12%) eyes in the dorzolamide group and in 9 (36%) eyes in the apraclonidine group (p = 0.034). At 20-24 h post-operatively and at 1 week post-operatively no difference was found between the groups. 2% Dorzolamide is more effective than 0.5% apraclonidine in preventing the early post-operative IOP increase following phacoemulsification cataract surgery.",2001.0,0,0
148,11120421,"Risperidone versus haloperidol in psychotic patients with disturbing neuroleptic-induced extrapyramidal symptoms: a double-blind, multi-center trial.",A H Heck; P M Haffmans; I W de Groot; E Hoencamp,"A randomized, double-blind, multi-center trial was started to compare the severity of extrapyramidal symptoms (EPS) during risperidone and haloperidol treatment in schizophrenic patients who had disturbing EPS during their previous neuroleptic treatment. Additional objectives of this trial were comparing the antipsychotic effectiveness of the two treatments and the use of antiparkinsonian medication. Effects of flexible doses of risperidone and haloperidol were compared in 77 psychotic patients (83% with chronic schizophrenia) with disturbing neuroleptic-induced EPS (risperidone 40 patients, haloperidol 37). The trial was completed by 47 patients: 25 in the risperidone group (12 women, 13 men), and 22 in the haloperidol group (10 women, 12 men). An adequate antipsychotic effect was obtained in most patients by both treatments. The primary aim of this trial was comparing parkinsonism measured with the extrapyramidal syndrome rating scale (ESRS) during treatment with risperidone and haloperidol. Two primary parameters were selected: the change from baseline to the worst score during treatment of ESRS II (parkinsonism) and ESRS VI (clinical global impression of severity of parkinsonism). The CGI of severity of parkinsonism was better with risperidone (P=0.025), while the parkinsonism total score tended to be better with risperidone (P<0. 10). Before the double-blind treatment, 34 (of the 77) had used antiparkinson medication (risperidone 18, haloperidol 16). During the double-blind treatment phase, 21 patients had used antiparkinson medication (risperidone 11, haloperidol 10). The larger reduction of parkinsonism in the risperidone group was not due to a difference in the use of anti-parkinsonian medication. In this group of schizophrenic patients with disturbing EPS during previous neuroleptic treatment, a stronger reduction of parkinsonism was observed with risperidone than with haloperidol.",2001.0,0,0
149,11126856,Depression in children and adolescents.,S E Son; J T Kirchner,"Depression among children and adolescents is common but frequently unrecognized. It affects 2 percent of prepubertal children and 5 to 8 percent of adolescents. The clinical spectrum of the disease can range from simple sadness to a major depressive or bipolar disorder. Risk factors include a family history of depression and poor school performance. Evaluation should include a complete medical assessment to rule out underlying medical causes. A structured clinical interview and various rating scales such as the Pediatric Symptom Checklist are helpful in determining whether a child or adolescent is depressed. Evidence-based treatment guidelines from the literature are limited. Psychotherapy appears to be useful in most children and adolescents with mild to moderate depression. Tricyclic antidepressants and selective serotonin reuptake inhibitors are medical therapies that have been studied on a limited basis. The latter agents are better tolerated but not necessarily more efficacious. Because the risk of school failure and suicide is quite high in depressed children and adolescents, prompt referral or close collaboration with a mental health professional is often necessary.",2001.0,0,0
150,11130217,Effects of steady-state bupropion on the pharmacokinetics of lamotrigine in healthy subjects.,J Odishaw; C Chen,"To evaluate the effect of steady-state bupropion SR sustained-release (BUP) on the pharmacokinetics of a single 100-mg dose of lamotrigine (LTG). Randomized, open-label, two-way crossover study Clinical Studies Ltd., Fort Lauderdale, Florida. Twelve healthy subjects. Treatment A: LTG 100 mg with steady-state BUP 150 mg twice/day; treatment B: LTG 100 mg. The pharmacokinetics of LTG were determined by noncompartmental methods using plasma and urine concentrations. Geometric least squares mean ratios and 90% confidence intervals were calculated for treatment comparison. Safety assessments included clinical laboratory tests, vital signs, and adverse events monitoring. Pharmacokinetic parameters of LTG were not significantly different between treatments. Five subjects experienced seven mild, potentially drug-related adverse events (insomnia [2]; nausea, headache, facial pain, fatigue, and depression [1 each]) that resolved spontaneously. Steady-state BUP caused no clinically relevant changes in the pharmacokinetics of a single dose of LTG.",2001.0,0,0
151,11133600,A comparison of oral clonidine and oral midazolam as preanesthetic medications in the pediatric tonsillectomy patient.,L Fazi; E C Jantzen; J B Rose; C D Kurth; M F Watcha,"We compared the effects of oral clonidine (4 microg/kg) and midazolam (0.5 mg/kg) on the preanesthetic sedation and postoperative recovery profile in children during tonsillectomy with or without adenoidectomy. In a double-blinded, double-dummy study design, 134 ASA physical status I-II children aged 4-12 yr were randomized to receive a combination of either clonidine and placebo (Group A), or placebo and midazolam (Group B) at 60-90 min and 30 min, respectively, before the induction of anesthesia. Children in the clonidine group exhibited more intense anxiety on separation and during induction of anesthesia via a mask as measured by the modified Yale Preoperative Anxiety Scores. They also had significantly lower mean intraoperative arterial blood pressures, shorter surgery, anesthesia, and emergence times, and a decreased need for supplemental oxygen during recovery compared with the midazolam group. However, the clonidine group had larger postoperative opioid requirements, maximum excitement and pain scores based on the Children's Hospital of Eastern Ontario scale in the Phase 1 postanesthetic care unit. There were no differences between the two groups in the times to discharge readiness, postoperative emesis, unanticipated hospital admission rates, postdischarge maximum pain scores, and 24 h analgesic requirements. The percentage of parents who were completely satisfied with the child's preoperative experience was significantly higher in the midazolam group. There were no differences in parental satisfaction with the recovery period. We conclude that under the conditions of this study, oral midazolam is superior to oral clonidine as a preanesthetic medication in this patient population. We compared preanesthetic sedation and postoperative recovery after oral clonidine (4 microg/kg) and midazolam (0.5 mg/kg) in children during tonsillectomy. The clonidine group had greater preoperative anxiety and shorter surgery and anesthesia times, but required more postoperative analgesia. Delayed recovery and discharge times did not differ. Midazolam was superior to clonidine as oral preanesthetic medication for these patients.",2001.0,0,0
152,11133627,Clonidine combined with a long acting local anesthetic does not prolong postoperative analgesia after brachial plexus block but does induce hemodynamic changes.,X Culebras; E Van Gessel; P Hoffmeyer; Z Gamulin,"Clonidine in brachial plexus block prolongs analgesia of local anesthetics of short and intermediate duration. We performed a prospective randomized double-blinded study to determine the efficacy and adverse effects of clonidine mixed with a long-acting local anesthetic on postoperative analgesia. Sixty adult patients underwent elective rotator cuff repair using interscalene brachial plexus block combined with general anesthesia and were randomly divided into one of the following three groups. Placebo (n = 20): interscalene block with 40 mL of 0.5% bupivacaine with epinephrine (1/200000) and 1 mL of 0.9% saline, completed by 1 mL of 0.9% saline IM in the controlateral shoulder; Control (n = 20): interscalene block with 40 mL of 0.5% bupivacaine with epinephrine and 1 mL of 0. 9% saline, completed by 150 microg (=1 mL) of clonidine IM; Clonidine (n = 20): interscalene block with 40 mL of 0.5% bupivacaine with epinephrine and 150 microg (=1 mL) of clonidine, completed by 1 mL of 0.9% saline IM. During anesthesia hemodynamic variables and fractional expired isoflurane concentration (FeISO) were recorded. The following postoperative variables were assessed: duration of interscalene block, quality of pain relief on a visual analog scale, side effects, and consumption of morphine with a patient-controlled analgesia device over 48 h. Patient characteristics were comparable. During anesthesia mean arterial pressure, heart rate, and FeISO were significantly decreased in Clonidine and Control groups compared with Placebo group. Duration of analgesia, defined as the time elapsed from interscalene injection to the first morphine request, was 983 +/- 489 min in the Placebo, 909 +/- 160 min in the Control, and 829 +/- 159 min in the Clonidine groups. Pain scores and consumption of morphine at 24 h and 48 h showed no differences among the three groups. We conclude that adding 150 microg of clonidine in interscalene block does not prolong analgesia induced by 40 mL of bupivacaine 0.5% with epinephrine, but decreases mean arterial blood pressure and heart rate. Clonidine in brachial plexus block does not improve postoperative analgesia when mixed with a long-lasting anesthetic. Nevertheless, with or without clonidine, bupivacaine in interscalene block provides a long-lasting analgesia of approximately 15 h.",2001.0,0,0
153,11133640,"A comparison between meperidine, clonidine and urapidil in the treatment of postanesthetic shivering.",K R Schwarzkopf; H Hoff; M Hartmann; H G Fritz,"Postanesthetic shivering can be treated with many types of drugs. We compared the effects of meperidine, clonidine, and urapidil on postanesthetic shivering. Sixty patients shivering during recovery from general anesthesia were treated in a randomized, double-blinded fashion with 25 mg meperidine IV, 0.15 mg clonidine IV, or 25 mg urapidil IV in three separate groups of 20 patients each. If shivering did not stop within 5 min, the treatment was repeated once; clonidine was replaced with saline for the second dose. Rectal temperature, arterial blood pressure, heart rate, SaO(2) and vigilance were monitored. Clonidine stopped shivering in all 20 patients. A single dose of meperidine stopped the shivering in 18 of 20 patients, with the other 2 patients needing a second dose. Urapidil was less effective: the first dose stopped the shivering in only six patients; the second dose was effective in another six; the drug was ineffective in 8 of 20 patients. Meperidine and clonidine were both nearly 100% effective in treating postanesthetic shivering without negative side effects. By comparison, urapidil was only effective in 60% of patients treated (P <0.01). Patients shivering during recovery from general anesthesia were treated in a randomized double-blinded fashion with meperidine, clonidine, or urapidil. Meperidine and clonidine were both very effective, whereas urapidil was only effective in 60% of patients treated.",2001.0,0,0
154,11136647,A novel augmentation strategy for treating resistant major depression.,R C Shelton; G D Tollefson; M Tohen; S Stahl; K S Gannon; T G Jacobs; W R Buras; F P Bymaster; W Zhang; K A Spencer; P D Feldman; H Y Meltzer,"Treatment-resistant depression is a significant public health concern; drug switching or augmentation often produce limited results. The authors hypothesized that fluoxetine could be augmented with olanzapine to successfully treat resistant depression. An 8-week double-blind study was conducted with 28 patients who were diagnosed with recurrent, nonbipolar, treatment-resistant depression without psychotic features. Subjects were randomly assigned to one of three groups: olanzapine plus placebo, fluoxetine plus placebo, or olanzapine plus fluoxetine. Fluoxetine monotherapy produced minimal improvement on various scales that rate severity of depression. The benefits of olanzapine monotherapy were modest. Olanzapine plus fluoxetine produced significantly greater improvement than either monotherapy on one measure and significantly greater improvement than olanzapine monotherapy on the other measures after 1 week. There were no significant differences between treatment groups on extrapyramidal measures nor significant adverse drug interactions. Olanzapine plus fluoxetine demonstrated superior efficacy for treating resistant depression compared to either agent alone.",2001.0,0,0
155,11140235,Managing ADHD in general practice. N of 1 trials can help!,C M Duggan; G Mitchell; C J Nikles; P P Glasziou; C B Del Mar; A Clavarino,"To pilot single patient trials designed to improve decision making about stimulant use for attention deficit hyperactivity disorder (ADHD) in general practice. Patients previously stabilised on dexamphetamine were enrolled from a general practice. Each undertook a six week same patient randomised, double blind, placebo controlled crossover comparison of dexamphetamine with placebo for ADHD. Rating scales were completed weekly by self, parent and teacher. Three of the four patients were clear responders to dexamphetamine (including a noncompleter, as his results still demonstrated a clear response). The results were clinically useful in each case. Management was confirmed for three patients and changed for one (who ceased dexamphetamine). Prescribing stimulant medications only to children with diagnosed ADHD and who are found to respond, limits use of these worrisome drugs to those who will respond, and minimises their use in those who will not benefit.",2001.0,0,1
156,11143833,Impact of risperidone on seclusion and restraint at a state psychiatric hospital.,K N Chengappa; J Levine; R Ulrich; H Parepally; J S Brar; R Atzert; R Brienzo; A Gopalani,"To evaluate the impact of risperidone on seclusion and restraint in patients at a state psychiatric facility, shortly after risperidone's release. Patients who were in the hospital for at least 3 months prior to receiving risperidone and subsequently received risperidone for at least 3 months formed the cohort. A mirror-image design was used with duration to a maximum of 1 year before and 1 year after initiation of risperidone. The hospital population that did not receive either risperidone or clozapine during the same time period was used for comparison of trends of seclusion and restraint. Seventy-four patients (most with schizophrenia) met the inclusion criteria of the risperidone group. There were statistically significant decreases in the number of seclusion hours (2.2 [SD 5.5] to 0.26 [SD 0.06]) and of events (0.23 [SD 0.59] to 0.05 [SD 0.14]) per person per month during risperidone treatment, compared with the prerisperidone treatment period (P = 0.01). The comparison group also evidenced decreases on these measures during the same time period, but the risperidone-treated cohort achieved a proportionally greater reduction. There were similar trends toward reduction in the restraint measures during risperidone treatment compared with prerisperidone, but these did not achieve statistical significance. The comparison group also showed slightly decreased use of restraints over the study period. Risperidone appears to have had a positive impact on seclusion in this state-hospital psychiatric population. These data support the positive impact of risperidone on violence found in other studies. Violence and aggression are major factors that affect morale among psychiatric patients and staff. So, any benefit in this regard as a result of antipsychotic drug treatment is salutary for patients, families, and health care providers.",2001.0,0,0
157,11147929,Clozapine-induced agranulocytosis and hereditary polymorphisms of clozapine metabolizing enzymes: no association with myeloperoxidase and cytochrome P4502D6.,M Dettling; C Sachse; B Müller-Oerlinghausen; I Roots; J Brockmöller; A Rolfs; I Cascorbi,"The pathomechanisms of most drug-induced agranulocytoses are unclear; however, there are some studies pointing to genetic determinants. Some drug-induced agranulocytoses such as clozapine-induced agranulocytosis (CA) may be regarded as an idiosyncratic drug reaction because of its preclinical and clinical characteristics. To study some aspects of the genetic background of CA further, polymorphisms of specific metabolizing enzyme systems of clozapine were examined. Thirty-one schizophrenic patients with CA and 77 schizophrenic comparison subjects without this adverse effect underwent genotyping of a recently discovered G(-463)A polymorphism of myeloperoxidase (MPO) gene and cytochrome P4502D6. Neither the MPO mutation nor specific genotypes of cytochrome P4502D6 were associated with CA. Both were equally distributed among CA patients and controls. Thus, our data suggest lack of evidence of an association of CA and genetically variable activity of these specific drug metabolizing enzymes; however, this may be due to statistical reasons only. Thus, further studies with greater CA samples are necessary to draw final conclusions about these genetically based hypotheses.",2001.0,0,0
158,11156812,A controlled clinical trial of bupropion for attention deficit hyperactivity disorder in adults.,T E Wilens; T J Spencer; J Biederman; K Girard; R Doyle; J Prince; D Polisner; R Solhkhah; S Comeau; M C Monuteaux; A Parekh,"Despite the increasing recognition of attention deficit hyperactivity disorder (ADHD) in adults, there is a paucity of controlled pharmacological trials demonstrating the effectiveness of compounds used in treatment, particularly nonstimulants. The authors report results from a controlled investigation to determine the anti-ADHD efficacy of bupropion in adult patients with DSM-IV ADHD. This was a double-blind, placebo-controlled, randomized, parallel, 6-week trial comparing patients receiving sustained-release bupropion (up to 200 mg b.i.d.) (N=21) to patients receiving placebo (N=19). The authors used standardized structured psychiatric instruments for diagnosis of ADHD. To measure improvement, they used separate assessments of ADHD, depression, and anxiety symptoms at baseline and each weekly visit. Of the 40 subjects (55% male) enrolled in the study, 38 completed the study. Bupropion treatment was associated with a significant change in ADHD symptoms at the week-6 endpoint (42% reduction), which exceeded the effects of placebo (24% reduction). In analyses using a cutoff of 30% or better reduction to denote response, 76% of the subjects receiving bupropion improved, compared to 37% of the subjects receiving placebo. Similarly, in analyses using Clinical Global Impression scale scores, 52% of the subjects receiving bupropion reported being ""much improved"" to ""very improved,"" compared to 11% of the subjects receiving placebo. These results indicate a clinically and statistically significant effect of bupropion in improving ADHD in adults. The results suggest a therapeutic role for bupropion in the armamentarium of agents for ADHD in adults, while further validating the continuity of pharmacological responsivity of ADHD across the lifespan.",2001.0,1,1
159,11163780,Double-blind comparison of olanzapine versus clozapine in schizophrenic patients clinically eligible for treatment with clozapine.,G D Tollefson; M A Birkett; G M Kiesler; A J Wood; Lilly Resistant Schizophrenia Study Group,"The treatment of schizophrenic patients who fail to respond to adequate trials of neuroleptic drugs is a major challenge. Clozapine has been one treatment option; however, it is not universally effective and is limited in its use by safety concerns. With the introduction of newer agents, their performance relative to clozapine is of great clinical interest. The primary objective of this study was to evaluate the efficacy and safety of olanzapine versus clozapine among treatment resistant DSM-IV schizophrenic patients. The study was primarily designed to demonstrate the ""noninferiority"" of olanzapine compared to clozapine after 18 weeks of double-blind treatment. Conclusions were based on the one-sided lower 95% confidence limit about the treatment effect observed from the primary efficacy variable (Positive and Negative Syndrome Scale [PANSS] Total). Mean changes from baseline to end point in PANSS Total score, using a last observation carried forward technique, showed that both agents were comparably effective in neuroleptic resistant patients, i.e., demonstrated the ""noninferiority"" of olanzapine when compared to clozapine. Overall, significantly fewer olanzapine-treated patients (4%) discontinued for an adverse event than their clozapine-treated (14%) counterparts (p =.022). Among spontaneously reported adverse events, increased salivation, constipation, dizziness, and nausea were reported significantly more often among clozapine-treated patients, whereas only dry mouth was reported more often among olanzapine-treated patients. Olanzapine was demonstrated to be noninferior to clozapine and better tolerated among resistant schizophrenic patients clinically eligible for treatment with clozapine.",2001.0,0,0
160,11185396,Clinical trials. Planned Ritalin trial for tots heads into uncharted waters.,E Marshall,"U.S. scientists are gearing up for a major clinical trial intended to measure the effects of a popular but controversial drug used to treat attention deficit hyperactivity disorder, methylphenidate (Ritalin), on a previously untested population--children aged 3 to 6. But in doing so, they are running up against ethical concerns about using young subjects in clinical trials. The scientists involved in the study admit that they are concerned about the drug's effect on the children's still-developing personalities and brains, as well as their inability to give informed consent. But they believe that such trials are the only way to answer concerns about rising use of the drug among this population.",2001.0,0,0
161,11198061,Refractory schizophrenia and atypical antipsychotics.,D M Taylor; D Duncan-McConnell,"Treatment resistant or refractory schizophrenia is a difficult to define condition of largely unknown prevalence. For 10 years, clozapine has been the standard treatment in this condition and is recognized unequivocally as being effective. However, clozapine is sometimes poorly tolerated and has the potential for severe toxicity. Partly as a result of this, other atypicals have recently been evaluated as treatments for refractory schizophrenia. In order to evaluate the evidence base relating to the drug treatment of refractory schizophrenia, we developed a refractoriness rating based on previous work. Using this rating, we assessed all trials of atypicals in schizophrenia unresponsive to at least one drug. Overall, clozapine was consistently shown to be effective in refractory schizophrenia, even when stringently defined. Data relating to olanzapine and risperidone are equivocal at best, and there is some evidence to suggest that they are less effective than clozapine. There is essentially no cogent evidence to support the use of any other atypical in refractory schizophrenia. Clozapine remains the drug of choice in this condition.",2001.0,0,0
162,11199944,"Ziprasidone in the short-term treatment of patients with schizoaffective disorder: results from two double- blind, placebo-controlled, multicenter studies.",P E Keck; K R Reeves; E P Harrigan; Ziprasidone Study Group,"This study assessed the efficacy of ziprasidone for the treatment of schizoaffective disorder. Data were taken from subsets of patients with schizoaffective disorder, derived from two separate double-blind, placebo-controlled, parallel-group, multicenter studies. A total of 115 hospitalized patients with an acute episode of schizoaffective disorder were randomly assigned to receive either fixed oral doses of ziprasidone 40 mg/day (N = 16), 80 mg/day (N = 18), 120 mg/day (N = 22), 160 mg/day (N = 25), or placebo (N = 34) for 4 to 6 weeks. Mean baseline-to-endpoint changes in Brief Psychiatric Rating Scale (BPRS) total, BPRS Core, Clinical Global Impressions Severity scale (CGI-S), BPRS Depressive, BPRS Manic, and Montgomery-Asberg Depression Rating Scale total scores were compared between the placebo and ziprasidone groups. Neurological (Simpson-Angus, Barnes Akathisia, Abnormal Involuntary Movement Scale [AIMS]) and other side effects were also assessed. Significant dose-related improvements on all primary efficacy variables (BPRS total, BPRS Core, CGI-S) and for BPRS Manic items were observed with ziprasidone treatment in a combined analysis of data from both studies (p < or = 0.01). Ziprasidone 160 mg/day was significantly more effective than placebo in improving mean BPRS total, BPRS Core, BPRS Manic, and CGI-S scores (p < 0.05). At 120 mg/day, ziprasidone was significantly more effective than placebo in improving mean CGI-S scores (p < 0.05). The incidence of individual adverse events was generally low in all treatment groups and was not dose-related. In addition, no significant differences were observed between baseline-to-endpoint mean changes in Simpson-Angus and AIMS scores with placebo or ziprasidone 40 to 160 mg/day. These results suggest that ziprasidone may have efficacy in the treatment of affective as well as psychotic symptoms of schizoaffective disorder, with a low side-effect burden.",2001.0,0,0
163,11199955,The effects of concomitant phenytoin administration on the steady-state pharmacokinetics of quetiapine.,Y W Wong; C Yeh; P T Thyrum,"Quetiapine fumarate ('Seroquel') is a newly introduced atypical antipsychotic with demonstrated efficacy in the treatment of positive and negative symptoms of schizophrenia. It is extensively metabolized, predominantly by cytochrome P450 3A4. Therefore, concurrent administration of drugs that induce or inhibit this enzyme may affect quetiapine pharmacokinetics. This study demonstrated that the potent cytochrome P450 enzyme-inducer phenytoin did indeed have a marked effect on the metabolism of quetiapine, resulting in a 5-fold increase in clearance when administered concomitantly to patients with DSM-IV-diagnosed schizophrenia, schizoaffective disorder, or bipolar disorder. These results indicate that dosage adjustment of quetiapine may be necessary when the two drugs are given concurrently and that caution may be required when administering other drugs that inhibit or induce cytochromes, particularly P450 3A4.",2001.0,0,0
164,11199956,A preliminary study of bupropion sustained-release for smoking cessation in patients with chronic posttraumatic stress disorder.,M A Hertzberg; S D Moore; M E Feldman; J C Beckham,"This study was conducted to evaluate the effect of bupropion sustained-release (SR) on smoking cessation in patients with chronic posttraumatic stress disorder (PTSD). Fifteen veterans with chronic PTSD who desired to stop smoking enrolled in a 12-week double-blind evaluation of bupropion SR and placebo. Patients were randomly assigned in a 2:1 ratio to receive either bupropion SR or placebo. Bupropion SR was initiated at 150 mg daily for 3 or 4 days and increased to a final dose of 150 mg twice daily (300 mg daily total). Ten patients received bupropion SR and five received placebo. Nine of the patients who received bupropion SR were already being treated with at least one other psychotropic medication. One of the ten patients did not complete the study because of medication side effects. Eighty percent of patients receiving bupropion SR successfully stopped smoking by the end of week 2, and 6 (60%) of these 10 maintained smoking cessation at the study endpoint (week 12). At the 6-month follow-up, 40% of the patients (4 of 10) who received bupropion SR maintained smoking cessation. One (20%) of the five patients who received placebo stopped smoking and maintained smoking cessation at the 6-month follow-up. Bupropion SR was generally well-tolerated in combination with other psychotropic medications. Bupropion SR may be effective in helping patients who desire to quit smoking and who also have a concomitant anxiety disorder, such as PTSD.",2001.0,0,0
165,11199957,Effects of bupropion sustained-release on sexual functioning and nocturnal erections in healthy men.,L A Labbate; P S Brodrick; R P Nelson; R B Lydiard; G W Arana,"Many antidepressants are known to cause adverse sexual effects. Bupropion is an antidepressant with fewer reported adverse sexual effects. Studies of sexual side effects are often confounded by psychiatric and medical conditions affecting sexual function. In this study, the effects of bupropion on subjective and objective sexual functioning were measured in healthy men. Thirteen men without psychiatric or medical illness completed a 2-week, placebo-controlled, double-blind, crossover trial of bupropion sustained-release 300 mg/day. Subjects had a 1-week washout period between trials. Sexual function was measured using a validated, self-administered questionnaire and the RigiScan, an instrument measuring nocturnal penile tumescence and rigidity. No differences were found in self-reported sexual function, number of erections, total erection time, or penile rigidity in subjects taking bupropion compared with those taking placebo or baseline. These findings support that bupropion does not have subjective adverse sexual side effects and does not affect nocturnal erections in healthy men.",2001.0,0,0
166,11206599,Intramuscular ziprasidone compared with intramuscular haloperidol in the treatment of acute psychosis. Ziprasidone I.M. Study Group.,S Brook; J V Lucey; K P Gunn,"This 7-day, randomized, open-label, multicenter, international study compared the efficacy and tolerability of intramuscular (i.m.) ziprasidone with haloperidol i.m. and the transition from i.m. to oral treatment in hospitalized patients with acute psychotic agitation (related to DSM-III-R diagnoses). Patients received up to 3 days of flexible-dose ziprasidone i.m. (N = 90) or haloperidol i.m. (N = 42) followed by oral treatment to day 7. After an initial ziprasidone i.m. dose of 10 mg, subsequent i.m. doses of 5 to 20 mg could be given every 4 to 6 hours (maximum daily dose = 80 mg) if needed, followed by oral ziprasidone, 80-200 mg/day. Haloperidol i.m. doses of 2.5 to 10 mg were given on entry, followed by 2.5 to 10 mg i.m. every 4 to 6 hours (maximum daily dose = 40 mg) if needed, then by oral haloperidol, 10-80 mg/day. The mean reductions in Brief Psychiatric Rating Scale (BPRS) total, BPRS agitation items, and Clinical Global Impressions-Severity scale scores were statistically significantly greater (p < .05, p < .01, and p < .01, respectively) after ziprasidone i.m. treatment compared with haloperidol i.m. treatment. Further reductions in these scores also occurred in both groups following transition to oral treatment. Ziprasidone was associated with a lower incidence of movement disorders and a reduced requirement for anticholinergic medication during both i.m. and oral treatment compared with haloperidol. Movement disorder scale scores improved with ziprasidone i.m. and oral treatment, but deteriorated with haloperidol. Other adverse events were rare with both treatments. Ziprasidone i.m. was significantly more effective in reducing the symptoms of acute psychosis and was better tolerated than haloperidol i.m., particularly in movement disorders. The transition from ziprasidone i.m. to oral ziprasidone was effective and well tolerated.",2001.0,0,0
167,11214032,Effects of methylphenidate on sensitivity to reinforcement in children diagnosed with attention deficit hyperactivity disorder: an application of the matching law.,L K Murray; S H Kollins,"The behavior of children diagnosed with attention deficit hyperactivity disorder (ADHD) has been hypothesized to be the result of decreased sensitivity to consequences compared to typical children. The present study examined sensitivity to reinforcement in 2 boys diagnosed with ADHD using the matching law to provide more precise and quantitative measurement of this construct. This experiment also evaluated the effects of methylphenidate (MPH) on sensitivity to reinforcement of children with ADHD. Subjects completed math problems to earn tokens under four different variable-interval (VI) schedules of reinforcement presented in random order under both medicated and nonmedicated conditions. Results showed that, in the medicated condition, the matching functions for both subjects resulted in higher asymptotic values, indicating an overall elevation of behavior rate under these conditions. The variance accounted for by the matching law was also higher under the medicated conditions, suggesting that their behavior more closely tracked the changing rates of reinforcement while taking MPH compared to placebo. Under medicated conditions, the reinforcing efficacy of response-contingent tokens decreased. Results are discussed with respect to quantifying behavioral changes and the extent to which the drug interacts with prevailing contingencies (i.e., schedule values) to influence behavioral variability.",2001.0,0,1
168,11214033,Testing the ability of children with attention deficit hyperactivity disorder to accurately report the effects of medication on their behavior.,S P Ardoin; B K Martens,"Children with attention deficit hyperactivity disorder (ADHD) are often treated with central nervous system stimulants, making the evaluation of medication effects an important topic for applied behavior analysts. Because assessment protocols emphasize informant reports and direct observations of child behavior, little is known about the extent to which children themselves can accurately report medication effects. Double-blind placebo-controlled procedures were used to examine whether 6 children with ADHD could recognize the effects of their medication. The children were given math worksheets to complete for 15 min during each of 14 sessions while on medication and placebo. Children completed a self-evaluation form at the end of each session, and ratings were compared to observed behavior and academic performance. Results indicated that 3 children were able to accurately report their medication status at levels greater than chance, whereas the accuracy of reports by all children was related to dosage level, differences in behavior, and the presence of adverse effects. The implications of these results for placebo-controlled research, self-monitoring of dosage levels, and accuracy training are discussed.",2001.0,0,0
169,11215574,Clozapine for the treatment of drug-induced psychosis in Parkinson's disease: results of the 12 week open label extension in the PSYCLOPS trial.,S A Factor; J H Friedman; M C Lannon; D Oakes; K Bourgeois; Parkinson Study Group,"To report the results of the 12-week, prospective, open label extension of the 4-week, multicenter, placebo-controlled, double-blind PSYCLOPS (PSYchosis and CLOzapine in the treatment of Parkinsonism) trial. This extension examined the chronic safety and efficacy of clozapine in the treatment of drug-induced psychosis in Parkinson's disease (PD). Psychosis is a serious late complication of PD and may be a harbinger to increased mortality. Clozapine, the first atypical antipsychotic, was shown in several small open label studies to improve psychosis without worsening of motor symptoms. This was recently confirmed in the double-blind PSYCLOPS trial. The 53 patients who completed the double-blind portion of PSYCLOPS were evaluated on their original randomized treatment (clozapine or placebo), then had study medication stopped. All were started on clozapine. The patients from both treatment groups were evaluated every 4 weeks over a 12-week period using standardized measures for psychosis and PD. The mean dose of clozapine was 28.78 mg/day. Those originally treated with placebo improved significantly in Brief Psychiatric Rating Scale and clinical global scores for psychosis to the same degree as the group originally randomized to clozapine in the double-blind study. Both groups maintained their response to week 16 (end of the combined double-blind and open label portions). There was no worsening of motor features as measured by the Unified Parkinson's disease rating scale. Eighteen patients were either hospitalized or died during the trial. The most common reasons were pulmonary. Low-dose clozapine is effective in treating drug-induced psychosis without worsening motor features of PD, and the response is maintained for at least 4 months. Patients with psychosis and PD were previously described as a group with high risk for morbidity and mortality. The high risk continues despite antipsychotic therapy.",2001.0,0,0
170,11217867,Olanzapine: an updated review of its use in the management of schizophrenia.,N Bhana; R H Foster; R Olney; G L Plosker,"Olanzapine, a thienobenzodiazepine derivative, is a second generation (atypical) antipsychotic agent which has proven efficacy against the positive and negative symptoms of schizophrenia. Compared with conventional antipsychotics, it has greater affinity for serotonin 5-HT2A than for dopamine D2 receptors. In large, well controlled trials in patients with schizophrenia or related psychoses, olanzapine 5 to 20 mg/day was significantly superior to haloperidol 5 to 20 mg/day in overall improvements in psychopathology rating scales and in the treatment of depressive and negative symptoms, and was comparable in effects on positive psychotic symptoms. The 1-year risk of relapse (rehospitalisation) was significantly lower with olanzapine than with haloperidol treatment. In the first double-blind comparative study (28-week) of olanzapine and risperidone, olanzapine 10 to 20 mg/day proved to be significantly more effective than risperidone 4 to 12 mg/day in the treatment of negative and depressive symptoms but not on overall psychopathology symptoms. In contrast, preliminary results from an 8-week controlled study suggested risperidone 2 to 6 mg/day was superior to olanzapine 5 to 20 mg/day against positive and anxiety/depressive symptoms (p < 0.05), although consistent with the first study, both agents demonstrated similar efficacy on measures of overall psychopathology. Improvements in general cognitive function seen with olanzapine treatment in a 1-year controlled study of patients with early-phase schizophrenia, were significantly greater than changes seen with either risperidone or haloperidol. However, preliminary results from an 8-week trial showed comparable cognitive enhancing effects of olanzapine and risperidone treatment in patients with schizophrenia or schizoaffective disorder. Several studies indicate that olanzapine has benefits against symptoms of aggression and agitation, while other studies strongly support the effectiveness of olanzapine in the treatment of depressive symptomatology. Olanzapine is associated with significantly fewer extrapyramidal symptoms than haloperidol and risperidone. In addition, olanzapine is not associated with a risk of agranulocytosis as seen with clozapine or clinically significant hyperprolactinaemia as seen with risperidone or prolongation of the QT interval. The most common adverse effects reported with olanzapine are bodyweight gain, somnolence, dizziness, anticholinergic effects (constipation and dry mouth) and transient asymptomatic liver enzyme elevations. In comparison with haloperidol, the adverse events reported significantly more frequently with olanzapine in > or = 3.5% of patients were dry mouth, bodyweight gain and increased appetite and compared with risperidone, only bodyweight gain occurred significantly more frequently with olanzapine. The high acquisition cost of olanzapine is offset by reductions in other treatment costs (inpatient and/or outpatient services) of schizophrenia. Pharmacoeconomic analyses indicate that olanzapine does not significantly increase, and may even decrease, the overall direct treatment costs of schizophrenia, compared with haloperidol. Compared with risperidone, olanzapine has also been reported to decrease overall treatment costs, despite the several-fold higher daily acquisition cost of the drug. Olanzapine treatment improves quality of life in patients with schizophrenia and related psychoses to a greater extent than haloperidol, and to broadly the same extent as risperidone. Olanzapine demonstrated superior antipsychotic efficacy compared with haloperidol in the treatment of acute phase schizophrenia, and in the treatment of some patients with first-episode or treatment-resistant schizophrenia. The reduced risk of adverse events and therapeutic superiority compared with haloperidol and risperidone in the treatment of negative and depressive symptoms support the choice of olanzapine as a first-line option in the management of schizophrenia in the acute phase and for the maintenance of treatment response.",2001.0,0,0
171,11247108,Long-term olanzapine treatment: weight change and weight-related health factors in schizophrenia.,B J Kinon; B R Basson; J A Gilmore; G D Tollefson,"Weight change and the weight-related health factors of nonfasting serum glucose, serum cholesterol, and diastolic blood pressure levels were analyzed in patients with DSM-III-R schizophrenia and related disorders who received treatment with olanzapine for up to 3 years, and comparisons were made to patients treated with haloperidol. Baseline body mass index (BBMI; kg/m2) and dose (mg/day) were investigated as predictors of long-term weight change experienced during olanzapine treatment. This analysis retrospectively examined 573 patients receiving olanzapine and 103 patients receiving haloperidol for 39 weeks or more from a study of 1,996 patients randomly assigned 2:1 to either olanzapine, 5 to 20 mg/day, or haloperidol, 5 to 20 mg/day. After 6 weeks of acute therapy, patients continued for 1 year or more with either double-blind or open-label olanzapine therapy or double-blind haloperidol therapy. Mean weight gain for olanzapine-treated patients observed for a median of 2.54 years trended toward a plateau after the first 39 weeks of treatment with a last-observation-carried-forward mean weight change of 6.26 kg (13.8 lb) and a median of 5.90 kg (13.0 lb). This was significantly higher than that for haloperidol-treated patients, whose mean weight gain was 0.69 kg (1.5 lb) after 1.15 years (p < .001). Patients with higher BBMI (> 27.6) gained significantly less weight during treatment with olanzapine than their lighter counterparts (BBMI < 27.6) (p < .001). The effect of olanzapine dose on weight was not significant (p > or = . 183). Median serum glucose at endpoint was not significantly associated (p = .096) with weight change for olanzapine. Median serum cholesterol and diastolic blood pressure for olanzapine-treated patients at endpoint showed a relationship with weight change that was statistically (p < or = .001) but not clinically significant. The difference in incidence of elevated serum glucose, cholesterol, or diastolic blood pressure between olanzapine and haloperidol therapy groups was not different (p > .05). Mean weight gain during olanzapine treatment trended toward a plateau after the initial 39 weeks of treatment with no further significant gain out to 3 years. Higher BBMI was predictive of a lower long-term weight gain, while dose was not a significant predictor of greater longer term weight change. The relationship between weight change and glucose was not statistically significant. The association between weight change and changes in cholesterol as well as changes in diastolic blood pressure was statistically significant but not considered clinically relevant based on the ranges observed.",2001.0,0,0
172,11270920,Comparing guanfacine and dextroamphetamine for the treatment of adult attention-deficit/hyperactivity disorder.,F B Taylor; J Russo,"The objective of this study was to compare the efficacy of the alpha-2a agonist guanfacine with that of dextroamphetamine for the treatment of adult attention-deficit/hyperactivity disorder (ADHD). Seventeen adult outpatients who met DSM-IV criteria for ADHD participated in a double-blind, placebo-controlled, crossover study comparing drug effects on ADHD symptoms. Measures of change included the DSM-IV ADHD Behavior Checklist for Adults and the Copeland Symptom Checklist for Adult Attention Deficit Disorders. Cognitive measures of attention included the Stroop and Controlled Oral Word Association Test using the letters ""C,"" ""F,"" and ""L"" (COWAT, CFL version). For each trial, the drug was administered daily and titered up to optimal doses of maximum efficacy but with a minimum of side effects, and then data were collected. Both drugs significantly reduced ADHD symptoms on the DSM-IV Adult Behavior Checklist for Adults over placebo (p < 0.05). The Stroop Color subscale showed significant improvement for both drugs (p < 0.05), but the Color-Word measures showed significant improvement for guanfacine only (p < 0.01). The average dose of guanfacine was 1.10 (SD = 0.60), and the most common side effect of guanfacine was fatigue. No subjects discontinued drug trials. This preliminary study indicates that guanfacine may be a well-tolerated treatment option for adult ADHD.",2001.0,1,1
173,11282684,Effectiveness of second-generation antipsychotics in patients with treatment-resistant schizophrenia: a review and meta-analysis of randomized trials.,M Chakos; J Lieberman; E Hoffman; D Bradford; B Sheitman,"The authors conducted a review and meta-analysis of studies that compared the efficacy and tolerability of typical and second-generation antipsychotics for patients with treatment-resistant schizophrenia. A systematic search revealed 12 controlled studies (involving 1,916 independent patients), which were included in the review. For the seven studies that compared clozapine to a typical antipsychotic, a meta-analysis was performed to examine clozapine's effects on overall psychopathology, response rate, extrapyramidal symptoms, and tardive dyskinesia. The meta-analysis confirmed that treatment-resistant schizophrenic patients have more favorable outcomes when treated with clozapine rather than a typical antipsychotic, as reflected by Brief Psychiatric Rating Scale total score, categorical response rate, Scale for the Assessment of Negative Symptoms score, Simpson-Angus Rating Scale score, and compliance rate. Clozapine also conferred benefits on the sickest treatment-resistant schizophrenic patients. Patients treated with olanzapine also had more favorable outcomes with regard to categorical response and compliance rates. In the aggregate, the results of a meta-analysis indicated that clozapine exhibits superiority over typical antipsychotics in terms of both efficacy (as measured by improvement in overall psychopathology) and safety (in terms of reduced extrapyramidal side effects). However, the magnitude of the clozapine treatment effect was not consistently robust. Efficacy data for other second-generation antipsychotics in the treatment of patients with refractory schizophrenia were inconclusive. There is, therefore, a growing need to consider new and different treatment strategies, whether they be adjunctive or monotherapeutic, for schizophrenia that continues to be resistant or only partially responsive to treatment.",2001.0,0,0
174,11282699,An MRI study of basal ganglia volumes in first-episode schizophrenia patients treated with risperidone.,D J Lang; L C Kopala; R A Vandorpe; Q Rui; G N Smith; V M Goghari; W G Honer,"The basal ganglia may contribute to extrapyramidal movement disorders, affective disturbances, and cognitive deficits in schizophrenia. Basal ganglia volumes are putatively affected by antipsychotic medications. The purpose of this study was to determine the long-term effects of risperidone treatment in a cohort of first-episode patients with schizophrenia. The subjects were 30 patients with first-episode schizophrenia, 12 patients chronically treated with typical antipsychotics, and 23 healthy comparison subjects. They were scanned by magnetic resonance imaging at baseline. The first-episode patients received 1 year of continuous risperidone treatment, after which they and the comparison subjects were rescanned. Caudate, putamen, and globus pallidus volumes were determined from coronal images. The baseline caudate, putamen, and globus pallidus volumes were significantly larger in the chronically treated patients than in the untreated first-episode subjects and comparison subjects. These volumes did not differ between the first-episode patients and healthy comparison subjects. Basal ganglia volumes were unchanged after 1 year of exposure to risperidone in the first-episode subjects. Extrapyramidal movement disorders were present in the majority of chronically treated patients and more than one-third of the never-medicated first-episode patients at baseline. This group of first-episode patients did not exhibit abnormalities of basal ganglia volumes, nor were basal ganglia volumes affected by exposure to risperidone. Movement disorders were observed in both first-episode and chronically treated patients, suggesting effects of both illness and medications.",2001.0,0,0
175,11305704,A comparison of long-term outcome in first-episode schizophrenia following treatment with risperidone or a typical antipsychotic.,A K Malla; R M Norman; D J Scholten; S Zirul; V Kotteda,"Most reports assessing the efficacy and tolerability of risperidone have involved patients previously treated with typical antipsychotics. Such patients are more likely to have a greater resistance or intolerance to treatment, thus restricting our interpretation of the impact a new treatment might have on the course of schizophrenia and possibly biasing the results. The present study examines the relative effectiveness of risperidone and typical antipsychotics in patients being treated for their first episode of schizophrenia. From a cohort of 126 patients, 2 groups of 19 first-episode DSM-III-R/DSM-IV schizophrenia patients matched for age, gender, length of illness, and length of treatment and treated with either a typical antipsychotic or risperidone for a minimum of 1 year were compared on a number of outcome dimensions during their course of treatment and at follow-up. Treatment allocation was not random, and patients were judged to be compliant with medication. Patients treated with typical antipsychotics were followed up for a statistically nonsignificantly longer time (mean = 2.7 vs. 1.9 years). Six patients (31.6%) from the typical antipsychotic group were admitted to the hospital within the first year following the index admission compared with 1 patient (5.3%) in the risperidone group (admitted at month 14). Patients in the risperidone group showed a statistically significantly lower length of first hospitalization (p < .01), utilization of inpatient beds during the course of treatment (p < .001), and use of anticholinergic medication (p < .05). There were no statistically significant differences in symptom levels, either during the course of treatment or at follow-up; in the use of antidepressant, antianxiety, or mood-stabilizing drugs; or in changes in living circumstances or employment. These findings confirm at least equal long-term efficacy of typical antipsychotics and risperidone, but a possible advantage for risperidone in decreased service utilization and decreased use of anticholinergic drugs.",2001.0,0,0
176,11305706,Analysis of the QTc interval during olanzapine treatment of patients with schizophrenia and related psychosis.,J Czekalla; C M Beasley; M A Dellva; P H Berg; S Grundy,"There may be a temporal association between some antipsychotics and prolongation of the heart-rate-corrected QT interval (QTc) representing a delay in ventricular repolarization. QTc prolongation significantly exceeding normal intra-individual and interindividual variation may increase the risk of ventricular tachydysrhythmias, especially torsade de pointes, and therefore, sudden cardiac death. Electrocardiogram recordings obtained as part of the safety assessment of olanzapine in 4 controlled, randomized clinical trials (N = 2,700) were analyzed. These analyses were conducted to characterize any change in QTc temporally associated with olanzapine, compared with placebo, haloperidol, and risperidone, in acutely psychotic patients (DSM-III-R and DSM-IV) and to characterize variability and temporal course of the QTc in this patient population. Changes from baseline to minimum and maximum QTc were tested for significance, and baseline to acute-phase endpoint change in mean QTc was tested for significance within treatments and for differences between olanzapine and comparators. The possibility of a linear relationship between dose of olanzapine and mean change in QTc, as well as incidence of treatment-emergent prolongation of QTc (change from < 430 msec at baseline to > or =430 msec at endpoint), was tested. The incidence of maximum QTc > or = 450 msec during treatment was approximately equal to the incidence of QTc > or =450 msec at baseline. Results of these analyses suggest that olanzapine, as therapeutically administered to patients with schizophrenia and related psychoses, does not contribute to QTc prolongation resulting in potentially fatal ventricular arrhythmias.",2001.0,0,0
177,11313165,Effect of amantadine on weight gain during olanzapine treatment.,M Floris; J Lejeune; W Deberdt,"Patients treated with olanzapine may gain weight, especially in the first months of therapy. Amantadine (100-300 mg/day) was started in 12 patients having a mean weight gain of 7.3 kg during olanzapine treatment. The patients' weight stabilised and over 3-6 months they lost an average of 3.5 kg. No clinical deterioration occurred and no adverse effects were reported. These observations merit confirmation in randomised, controlled trials.",2001.0,0,0
178,11317065,Diagnosis and management of attention-deficit/ hyperactivity disorder in children.,K Kirby; V Floriani; H Bernstein,,2001.0,0,0
179,11320158,A double-blind placebo-controlled case study of the use of donepezil to improve cognition in a schizoaffective disorder patient: functional MRI correlates.,S C Risch; S McGurk; M D Horner; Z Nahas; S D Owens; M Molloy; C Gilliard; S Christie; J S Markowitz; C L DeVane; J Mintzer; M S George,"Cognitive impairment in multiple domains is common in patients with schizophrenia and may be a powerful determinant of poor functional ability and quality of life. We report a double-blind, placebo-controlled, cross-over study of donepezil augmentation in a schizoaffective disorder patient stabilized on olanzapine pharmacotherapy. The patient showed significant improvements in several cognitive measures and increased activation of prefrontal cortex and basal ganglia on functional MRI during the donepezil augmentation. In addition, the donepezil augmentation resulted in a reduction of depressive symptoms and in significant improvements in functional abilities and quality of life. Further studies of donepezil augmentation of neuroleptics in schizophrenia are warranted.",2001.0,0,0
180,11322056,"[Reduction of ocular pulse amplitude by apraclonidine--prospective double-blind, randomized clinical trial with 10 subjects].",G B Kuba; P Austermann,"The alpha-agonist Apraclonidin lowers effective intraocular pressure.  Ischemia gains increasing importance in the pathogenesis of glaucoma.  Therefore, an antiglaucomatous drug should also be investigated in regard of its influence on ocular hemodynamics. In a double masked, randomized, clinical trial 0.5% Apraclonidin eye drops were applied in 10 health subjects twice daily for 8 days.  The control group (10 healty volunteers) received a placebo medication (0.9% NaCI) according to the same protocol. IOP, heart rate, blood pressure and ocular pulse amplitudes (OBF Labs, UK) were measured at baseline (1T0), 90 minutes after instillation of one eye drop (1T90), after 7 days of therapy (8T0) and again 90 minutes after an acute instillation (8T90).  For statistical analysis the wilcoxon test for paried samples was used. In Apraclonindin treated subjects IOP dropped significantly (P<0.01) from 15.6 mm Hg to 11.4/12.4/10.3 mm Hg (1T0/1T90/8T0/8T90. The control group showed a significant reduction at 1T90 (p + 0.01)and at 8T90 (p = 0.005) from 3.22 mm Hg to 2.48/31/2.35 mm Hg (1T0/1T90/8T0/8T90), in the control group the pulse amplitude remained constant. After one week of therapy with 0.5% Apralonidin, intraocular pressure dropped as expected in health volunteers.  The observed reduction in pulse amplitudes in pulse amplitudes however could have a negative effect on long-term therapy in patients with chronic open-angle glaucoma .",2001.0,0,0
181,11329400,A randomized double-blind study of risperidone and olanzapine in the treatment of schizophrenia or schizoaffective disorder.,R R Conley; R Mahmoud,"The safety and efficacy of risperidone and olanzapine were compared in a double-blind trial that used doses widely accepted in clinical practice. Subjects (N=377) who met DSM-IV criteria for schizophrenia or schizoaffective disorder were randomly assigned to receive 2-6 mg/day of risperidone (mean modal dose=4.8 mg/day) or 5-20 mg/day of olanzapine (mean modal dose=12.4 mg/day) for 8 weeks. The two study groups were similar at baseline except that the olanzapine group was slightly younger than the risperidone group. Seventy-five percent of the participants completed the trial, with no between-treatment differences in the proportion of dropouts. Similar proportions of the risperidone and olanzapine groups reported extrapyramidal symptoms (24% and 20%, respectively). Severity of extrapyramidal symptoms was low in both groups, with no between-group differences. Total Positive and Negative Syndrome Scale scores and scores on the five Positive and Negative Syndrome Scale factors were improved in both groups at week 8 (subjects who completed the study) and endpoint (all subjects, including dropouts). There were overall between-treatment differences in efficacy. Comparison of individual factors found no significant differences at endpoint; at week 8, however, improvements on Positive and Negative Syndrome Scale factors for positive symptoms and anxiety/depression were greater with risperidone than olanzapine. An increase in body weight of > or =7% was seen in 27% of olanzapine participants and 12% of risperidone participants. Both treatments were well tolerated and efficacious. The frequency and severity of extrapyramidal symptoms were similar in the two treatment groups. Greater reductions in severity of positive and affective symptoms were seen with risperidone than with olanzapine treatment among study completers. There was no measure on which olanzapine was superior. Greater weight gain was associated with olanzapine than with risperidone treatment.",2001.0,0,0
182,11329407,"Sustained-release bupropion for selective serotonin reuptake inhibitor-induced sexual dysfunction: a randomized, double-blind, placebo-controlled, parallel-group study.",P S Masand; A K Ashton; S Gupta; B Frank,"The authors compared low-dose sustained-release bupropion with placebo for sexual dysfunction induced by selective serotonin reuptake inhibitors (SSRIs). Thirty adults who had received SSRIs for at least 6 weeks, who were euthymic, and who had sexual dysfunction as determined by a total score greater than 19 out of a possible 30 on the Arizona Sexual Experience Scale were randomly assigned to receive either 150 mg/day of sustained-release bupropion or placebo at 6:00 p.m. for 3 weeks. There were no significant differences between the sustained-release bupropion and placebo groups as measured by change in Arizona Sexual Experiences Scale or Hamilton Depression Rating Scale scores or side effects. Future studies should compare higher doses of bupropion for treating sexual dysfunction and should include a greater number of subjects.",2001.0,0,0
183,11332061,[Addition of clonidine to 0.5% lidocaine for intravenous locoregional anesthesia].,M A Samkaoui; A Bouaggad; R al Harrar; M A Bouderka; O Abbassi,"Evaluate the effect of the addition of clonidine to lidocaine on postoperative pain after intravenous regional anaesthesia. Double blind prospective study. Forty-five patients were randomly allocated to two groups: group 1 (n = 25) receiving 3 mg.kg-1 of lidocaine 0.5% added to saline and group 2 (n = 20) receiving 3 mg.kg-1 of lidocaine 0.5% added to clonidine (150 micrograms). Postoperative analgesia was assessed using a visual analogue pain score (VAPS) and the time to first analgesic request. The incidence of side effects after tourniquet release was noted. Analysis of variance, Kruskall Wallis and chi 2 tests were used for statistical analysis. A p-value of < 0.05 was considered significant. Age, ASA class, duration and type of surgery, tourniquet time and sensory block duration were comparable for the two groups. The time to first antalgic request after deflation of tourniquet was similar in the two groups (38 +/- 15 min versus 44 +/- 19 min), while VAPS score was lower (p < 0.05) in the clonidine group (5.2 versus 6.8). The incidence of side effects was comparable in the two groups. The addition of clonidine (150 micrograms) to lidocaine for intravenous regional anaesthesia improved postoperative analgesia but in a limited and short-lasting manner.",2001.0,0,0
184,11333516,"[Incidence of extrapyramidal symptoms during treatment with olanzapine, haloperidol and risperidone: results of an observational study].",J A Sacristán; J C Gómez; F Ferre; J Gascón; A Pérez Bravo; J M Olivares,"To analyze the incidence of extrapyramidal symptoms (EPS) and the concomitant use of anticholinergic drugs in outpatients diagnosed of schizophrenia treated with olanzapine (OLZ) in comparison with haloperidol (HAL) and risperidone (RIS) under routine clinical practice conditions. The analysis was carried out on the basis of the information obtained in the EFESO study, an observational, prospective study carried out in outpatients diagnosed of schizophrenia and treated with olanzapine compared to other antipsychotic agents used in the clinical practice. The incidence of EPS in the OLZ treated group compared to the haloperidol and risperidone treatment groups in which over 100 patients were included is analyzed in the present work. The study duration was 6 months and the data were collected by 293 psychiatrists from mental health care areas. The percentage of patients who presented at least one adverse event (AE) (p 3/4 0.001) was less in the OLZ groups (47.8%) compared to those of the HAL (79.8%) and RIS (57.2%) subgroups. A lower percentage of patients treated with OLZ (36.9%) presented EPS in comparison to the RIS (49.6%) and HAL (76%) subgroups (p 3/4 0.001). A lower rate of patients from the OLZ group (10.2%) received anticholinergic treatments compared to the RIS (19.9%) and HAL (44%) subgroups (p< 0.001 in both cases). OLZ-treated patients presented a lower incidence of EPS and required less anticholinergic treatment than the HAL and RIS treated patients. These results, obtained in naturalistic conditions, coincide with the conclusions reached in randomized clinical trials carried out prior to the marketing of OLZ.",2001.0,0,0
185,11336590,Moxonidine: some controversy.,S A Doggrell,"Initially it was considered that moxonidine, like clonidine, acted at central (2)-adrenoceptors to reduce blood pressure. With the characterisation of imidazoline binding sites distinct from (2)-adrenoceptors, the consensus became that moxonidine was acting predominantly at imidazoline I(1) receptors in the rostral ventrolateral medulla to lower blood pressure. Moxonidine acts at prejunctional (2)-adrenoceptors on sympathetic nerve endings to decrease noradrenaline release and this may contribute to its ability to lower blood pressure. The predominant site of action of moxonidine may also depend on route of administration, with imidazoline I(1) receptors being predominant after central, and (2)-adrenoceptors predominant after systemic administration. The controversy over the mechanism and site of action with moxonidine is ongoing. In animal models, moxonidine lowers blood pressure, reduces cardiac hypertrophy and remodelling, reduces cardiac arrhythmias and increases blood flow in cerebral ischaemia. Moxonidine also has beneficial effects in animal models of diabetes and kidney disease. Moxonidine increases sodium and water excretion in rats, but not humans. Animal studies indicate that moxonidine may be useful in the treatment of glaucoma by reducing intra-ocular pressure. Animal studies show that moxonidine may also be effective in pain and in ethanol withdrawal. In humans, the pharmacokinetics of moxonidine are of the one-compartment model with first-order absorption. Renal elimination is the major route of elimination and individual titration of moxonidine is needed in patients with renal impairment. There is overwhelming evidence that moxonidine is a safe and effective antihypertensive. A large clinical trial of moxonidine in heart failure, MOXCON, was stopped because of excessive deaths in the moxonidine group. Moxonidine should not be used in patients with heart failure, but there are no obvious reasons to stop its use as an antihypertensive, or its development for other clinical uses.",2002.0,0,0
186,11347795,"Toward individualized evidence-based medicine: five ""N of 1"" trials of methylphenidate in geriatric patients.",I H Jansen; M G Olde Rikkert; H A Hulsbos; W H Hoefnagels,"To investigate the efficacy of methylphenidate in depressed or apathetic geriatric patients. Five ""N of 1"" trials (individual cross-over, double-blinded, randomized trials). Department of Geriatrics, University Medical Center, Nijmegen, and two nursing homes in Nijmegen, the Netherlands. Patients suffered from depression due to a general medical condition (n = 2); depression resistant to antidepressive drugs (n = 1), chronic apathy due to mild and moderate severe dementia (n = 2). Methylphenidate (5 mg bid) and placebo (both for two subsequent days) in 5 weeks of randomized treatment blocks. Montgomery Asberg Depression Rating Scale (MADRS), Apathy Evaluation Scale (AES)-clinician, the AES-informant, Barthel index and a semiquantitative checklist of adverse effects. Among the three depressed patients, two showed significant improvement on the MADRS (P = .089 and P = .001; alpha = 0.10), one patient's apathy showed significant improvement on AES-clinician and -informant (P = .077 and P = .086). One apathetic patient's trial was stopped because AES could not be completed. None of the patients showed significant changes in the Barthel index. No side effects developed. ""N of 1"" trials are useful in evaluating efficacy of methylphenidate in depressed or apathetic geriatric patients. Single-patient trials can be a useful tool in pharmacotherapeutic decision-making in frail older subjects.",2001.0,0,0
187,11354590,Detecting improvement in quality of life and symptomatology in schizophrenia.,J Cramer; R Rosenheck; W Xu; W Henderson; J Thomas; D Charney; Department of Veterans Affairs Cooperative Study Group on Clozapine in Refractory Schizophrenia,"Instrument-based scores are often used as outcome measures. However, little is known about what changes in scores mean in terms of a clinical assessment of improvement or deterioration. The purpose of this report was to determine how much change in standard instrument scores represents a clinically detectable improvement or deterioration. The Veterans Affairs (VA) Cooperative Study of Clozapine in Refractory Schizophrenia evaluated 423 patients on clozapine or haloperidol. Symptoms and quality of life scales were completed at baseline; 6 weeks; and 3, 6, and 12 months. Among patients judged as ""improved"" by clinicians, the average percentage changes were a 21 percent decrease in Positive and Negative Syndrome Scale (PANSS) scores and a 26 percent increase in Quality of Life Scale (QLS) scores across all followup periods. The change in mean seven-point item scores were -0.46 (PANSS) and 0.23 (QLS). A major gain in clinically assessed improvement to ""much better"" was associated with a 45 percent decline in PANSS scores and 50 percent increase in QLS scores (change in mean seven-point item scores -0.88 and 0.92, respectively). Thus, modest changes in psychometric scales assessing symptoms and quality of life reflect clinically detectable improvement.",2001.0,0,0
188,11356587,,,,,0,0
189,11377926,Response in relation to baseline anxiety levels in major depressive disorder treated with bupropion sustained release or sertraline.,A J Rush; M H Trivedi; T J Carmody; R M Donahue; T L Houser; C Bolden-Watson; S R Batey; J A Ascher; A Metz,"Our objective was to determine if pretreatment anxiety levels were associated with preferential response to bupropion sustained release (n = 122) or sertraline (n = 126) during a 16-week randomized acute phase treatment study. Both agents had comparable antidepressant activity, and comparable anxiolytic effects using the intent-to-treat sample. Baseline anxiety levels were not related to antidepressant efficacy, and they did not differentiate responders to each agent. Time to clinically significant anxiolysis did not differentiate between treatment groups or between responders to each agent. These results contradict the commonly held, but unsubstantiated, belief that in clinically depressed anxious patients, serotonergic antidepressants are especially anxiolytic and that such patients preferentially benefit from the antidepressant or anxiolytic effects of selective serotonin reuptake inhibitors. Thus, the clinical decision to select between these two agents when treating depressed outpatients cannot rest on either levels of pretreatment anxiety or on anticipation of more rapid or more complete anxiolysis.",2001.0,0,0
190,11379837,A randomized controlled trial of risperidone in the treatment of aggression in hospitalized adolescents with subaverage cognitive abilities.,J K Buitelaar; R J van der Gaag; P Cohen-Kettenis; C T Melman,"Risperidone is an atypical antipsychotic drug that blocks dopamine as well as serotonin receptor systems. The present study was designed to examine the efficacy and safety of risperidone in a 6-week double-blind, randomized, parallel-group design in the treatment of aggression in adolescents with a primary diagnosis of DSM-IV disruptive behavior disorders and with subaverage intelligence. We randomly assigned 38 adolescents (33 boys; 10 subjects with slightly subaverage IQ, 14 with borderline IQ, and 14 with mild mental retardation), who were hospitalized for treatment of psychiatric disorders associated with severe aggression, to receive risperidone or placebo. The main efficacy measures were the Clinical Global Impressions-Severity of Illness scale (CGI-S), the modified Overt Aggression Scale (OAS-M), and the Aberrant Behavior Checklist (ABC). Side effects were measured using the Extrapyramidal Symptom Rating Scale (ESRS). The mean daily dose of risperidone at the end of treatment was 2.9 mg (range, 1.5-4 mg). Risperidone, compared with placebo, was associated with significant improvements on the CGI-S (p < .001) and the at-school ABC overall and hyperactivity scales (p < .05). During a 2-week washout following the 6-week trial, a statistically significant worsening was found in the risperidone group on the CGI-S scale, the OAS-M. and the ABC. Extrapyramidal symptoms were absent or very mild during risperidone treatment. Transient tiredness was present in 11 (58%) of 19 drug-treated subjects. Other untoward effects included sialorrhea, nausea, and slight weight gain (mean = 3.5% of body weight in the risperidone group). No clinically relevant changes were found in laboratory parameters, electrocardiogram, heart rate, or blood pressure. These results suggest that risperidone may be effective for severe aggression in adolescents with disruptive behavior disorders and subaverage intelligence, and these results are consistent with reports suggesting its effectiveness for treating severe aggression in adolescents in general.",2001.0,0,0
191,11379842,Long-term olanzapine therapy in the treatment of bipolar I disorder: an open-label continuation phase study.,T M Sanger; S L Grundy; P J Gibson; M A Namjoshi; M G Greaney; M F Tohen,"Olanzapine has demonstrated efficacy in the treatment of acute mania in 2 double-blind, placebo-controlled trials. We describe the results of the open-label extension from one of these trials. In a 3-week, double-blind study of patients with DSM-IV bipolar I disorder, olanzapine was superior to placebo for the treatment of acute manic symptoms. Of the 139 patients who entered the double-blind phase of the 3-week study, 113 patients continued into the 49-week open-label extension. Efficacy measurements including the Young Mania Rating Scale (YMRS), the 21-item Hamilton Rating Scale for Depression (HAM-D-21), the Clinical Global Impressions scale-Bipolar Version, and the Positive and Negative Syndrome Scale and safety measurements including the Simpson-Angus scale, the Barnes Akathisia Scale, and the Abnormal Involuntary Movement Scale were completed throughout. The analysis considered all treatment results, starting with the first olanzapine dose. Adjunctive lithium and fluoxetine were allowed during the open-label extension. The mean length of olanzapine treatment was 6.6 months, with a mean modal dose of 13.9 mg/day. A significant mean improvement in the YMRS total score, baseline to endpoint (-18.01, p < .001), was observed. During treatment, 88.3% of patients experienced a remission of manic symptoms (YMRS total score < or =12), and only 25.5% subsequently relapsed (YMRS total score > or = 15). Significant improvement in HAM-D-21 scores was observed (p < .001). Forty-one percent of patients were maintained on olanzapine monotherapy. The most common treatment-emergent adverse events reported were somnolence (46.0%), depression (38.9%), and weight gain (36.3%). During up to 1 year of olanzapine therapy, either as monotherapy or in combination with lithium and/or fluoxetine, patients with bipolar disorder demonstrated significant improvement in mania and depression symptoms with a favorable safety profile. Further double-blind, controlled studies are needed to confirm these results.",2001.0,0,0
192,11394732,"Late-term smoking cessation despite initial failure: an evaluation of bupropion sustained release, nicotine patch, combination therapy, and placebo.",B D Jamerson; M Nides; D E Jorenby; R Donahue; P Garrett; J A Johnston; M C Fiore; S I Rennard; S J Leischow,"The purpose of this study was to evaluate the efficacy of long-term use of bupropion sustained release (SR), the nicotine patch, and the combination of these 2 treatments in patients who initially failed treatment. This was a post hoc analysis of a multicenter, double-blind, randomized, placebo-controlled clinical trial in 893 smokers. Patients were randomly assigned to 9 weeks of treatment with placebo (n = 160), bupropion SR (n = 244), nicotine patch (n = 244), or a combination of nicotine patch and bupropion SR (n = 245). The study was originally designed with a follow-up period of 52 weeks. In this analysis, short-term success was defined as smoking cessation after 14 or 21 days of therapy and long-term success was defined as smoking cessation after >21 days of therapy. Patients who did not achieve short-term success were evaluated for long-term success at week 9 (end of treatment), 6 months, and 1 year after the start of the study. The mean age of the smokers was 44 years. The majority (93%) of patients were white, and 52% were female. The study subjects smoked an average of 27 cigarettes per day. Among the 467 patients who initially failed treatment in the first 3 weeks, treatment with bupropion SR alone and in combination with the nicotine patch produced significant increases in successful smoking cessation rates from weeks 4 to 9 (19% bupropion SR or combination, 7% nicotine patch, 7% placebo), at month 6 (11% bupropion SR, 13% combination, 2% nicotine patch, 3% placebo), and at month 12 (10% bupropion SR, 7% combination, 2% nicotine patch, 1% placebo) (P < 0.05 for bupropion SR and combination vs nicotine patch or placebo). Among patients who initially failed treatment, continued therapy with bupropion SR, either alone or in combination with the nicotine patch, resulted in significantly higher short- and long-term smoking cessation rates than treatment with the nicotine patch alone or placebo.",2001.0,0,0
193,11401000,"Intramuscular (IM) ziprasidone 20 mg is effective in reducing acute agitation associated with psychosis: a double-blind, randomized trial.",D G Daniel; S G Potkin; K R Reeves; R H Swift; E P Harrigan,"Intramuscular (IM) conventional antipsychotics and/or benzodiazepines are effective in the short-term treatment of acutely agitated psychotic patients but may be associated with adverse effects. A short-acting IM formulation of the novel antipsychotic, ziprasidone, which may offer advantages over conventional agents, has been developed. To compare ziprasidone IM 2 mg (n=38) and 20 mg (n=41) in the acute control and short-term management of agitated psychotic patients. A prospective, randomized, double-blind, 24-h study assessed efficacy using the Behavioral Activity Rating Scale (BARS) and the PANSS. The BARS is a validated rating scale for the assessment of treatment response in acute agitation associated with psychosis. Following the initial dose, three more doses could be given 4 h apart if needed during the 24-h period. The mean BARS score had decreased 15 min after the first 20 mg IM dose and was statistically significantly lower than the 2 mg group at 30 min post-dose. The improvement with the 20 mg dose increased until 2 h, and was maintained until at least 4 h post-dose (P<0.001). Two hours after the first injection, almost all of the patients receiving ziprasidone 20 mg were BARS responders compared with just one-third of those receiving 2 mg ziprasidone (P<0.001). The calming effect of ziprasidone was also evident by the significant reduction in PANSS agitation items (P<0.05) and CGI-severity at 4 h (P=0.008). Both ziprasidone doses were very well tolerated. Ziprasidone IM 20 mg was not associated with EPS, dystonia, akathisia, respiratory depression or with excessive sedation. Ziprasidone IM 20 mg substantially and significantly reduced the symptoms of acute agitation in patients with psychotic disorders. Ziprasidone 20 mg IM was very well tolerated and produced no dystonia or akathisia.",2001.0,0,0
194,11401006,Bupropion SR worsens mood during marijuana withdrawal in humans.,M Haney; A S Ward; S D Comer; C L Hart; R W Foltin; M W Fischman,"Symptoms of withdrawal after daily marijuana smoking include increased ratings of irritability and depression. Similar mood symptoms are reported by cigarette smokers during nicotine abstinence. Given the successful use of sustained-release bupropion in treating nicotine dependence, this study investigated how maintenance on bupropion influenced symptoms of marijuana withdrawal compared to maintenance on placebo. Marijuana smokers (n=10) were maintained outpatient on active (300 mg/day) or placebo (0 mg/day) bupropion for 11 days, and were then maintained inpatient on the same bupropion dose for 17 days. For the first 4 inpatient days, participants smoked active marijuana [2.8% delta9-tetrahydrocannabinol (THC)] 5 times/day. For the remaining inpatient days, participants smoked placebo marijuana (0.0% THC) 5 times/day. Participants were then maintained outpatient on the alternate dose of bupropion for 11 days, followed by a second inpatient residential stay, paralleling the first. Medication administration was double-blind. Mood, psychomotor task performance, food intake, and sleep were measured daily during each inpatient phase. The order of active and placebo bupropion maintenance was counterbalanced between groups. Bupropion had few behavioral effects when participants smoked active marijuana. During placebo marijuana smoking, i.e., active marijuana withdrawal, ratings of irritability, restlessness, depression, and trouble sleeping were increased by bupropion compared to placebo maintenance. These data suggest that bupropion does not show promise as a potential treatment medication for marijuana dependence.",2001.0,0,0
195,11403983,Effects of olanzapine and haloperidol on serum prolactin levels in male schizophrenic patients.,E Esel; M Basturk; A Saffet Gonul; M Kula; M Tayfun Turan; I Yabanoglu; S Sofuoglu,"It has been proposed that new atypical antipsychotics cause minimal prolactin (PRL) elevation compared to traditional antipsychotic agents because they spare dopamine blockade within the brain's tuberoinfundibular tract. The aim of this study was to compare the effects of olanzapine and haloperidol on PRL secretion in male schizophrenic patients. Twenty-nine male schizophrenic inpatients were included in the study. Fifteen of them were given olanzapine in a fixed dose of 10 mg/day PO and 14 of them were given haloperidol in a fixed dose of 10 mg/day PO for 6 weeks after a 2-week drug washout period. Fifteen age-matched healthy control subjects were used as control group. PRL levels were measured both before and after the 6-week treatment period in the patients. At the end of the 6th week, the PRL values observed with olanzapine treatment were significantly less than those observed with haloperidol, but not different from those of the controls. There was a significant positive correlation between the PRL values and the severity of extrapyramidal side effects in only the haloperidol group after the six week's treatment period. Our data indicate that short-term olanzapine treatment at doses of 10 mg/day PO causes minimal elevations in PRL secretion in male schizophrenic patients in contrast to haloperidol. This finding is consistent with the previous reports and may be attributed to olanzapine's differential effects on dopamine neurotransmission.",2001.0,0,0
196,11412287,Pharmacological control of opioid-induced pruritus: a quantitative systematic review of randomized trials.,F Kjellberg; M R Tramèr,"Numerous drugs have been used to prevent or to treat opioid-induced pruritus in the surgical setting. Their relative efficacy is not well understood. The methods employed involved the systematic search (MEDLINE, EMBASE, Cochrane library, bibliographies, without language restriction, up to June 2000) for full reports of randomized comparisons of any intervention which is thought to be anti-pruritic (active) compared with placebo or no treatment (control) in surgical (including labour) patients receiving opioids. The number of patients who had no pruritus were analysed using relative risk and number-needed-to-treat with 95% confidence interval. Twenty-two trials (1477 patients) were analysed. Two trials (66 patients), both with low-dose propofol, were on treatment of established pruritus; propofol had no anti-pruritic effect compared with Intralipid. In prophylaxis trials, the average incidence of pruritus with control was 59% (range, 10% to 100%). Most mu-receptor antagonists were efficacious: intravenous naloxone 0.25-2.4 microg kg-1 h-1, relative risk 2.31 (95% confidence interval, 1.5 to 3.54), number-needed-to-treat to prevent pruritus compared with control 3.5; oral naltrexone 9 mg, relative risk 2.80 (1.35-5.80), number-needed-to-treat 1.7; naltrexone 6 mg was less effective and 3 mg did not work; different intravenous and epidural nalbuphine regimens, relative risk 1.71 (1.12-2.62), number-needed-to-treat 4.2. Intravenous nalmefene 0.5 or 1 mg was not anti-pruritic. Intravenous (but not epidural) droperidol 2.5 mg was efficacious, relative risk, 1.71 (1.28-2.29), number-needed-to-treat 4.9. There was a lack of evidence for any anti-pruritic efficacy with prophylactic propofol, epidural or intrathecal epinephrine, epidural clonidine, epidural prednisone, intravenous ondansetron, or intramuscular hydroxyzine. Naloxone, naltrexone, nalbuphine and droperidol are efficacious in the prevention of opioid-induced pruritus; minimal effective doses remain unknown. There is a lack of valid data on the efficacy of interventions for the treatment of established pruritus.",2001.0,0,0
197,11416103,Cancer fatigue: one drug fails but more are in the pipeline.,C McNeil,,2001.0,0,0
198,11429342,The dose-response relationship for clonidine added to a postoperative continuous epidural infusion of ropivacaine in children.,P De Negri; G Ivani; C Visconti; P De Vivo; P A Lonnqvist,"Epidurally administered clonidine enhances the quality and duration of postoperative analgesia when it is used as an adjunct to local anesthetics in children. We investigated the dose-response relationship for epidural clonidine when added to a continuous postoperative epidural infusion of ropivacaine. By use of an observer-blinded design, 55 pediatric patients (1-4 yr old) were randomly given a postoperative epidural infusion of plain ropivacaine 0.1% 0.2 mg. kg(-1). h(-1) (Group R), ropivacaine 0.08% 0.16 mg. kg(-1). h(-1) plus clonidine 0.04 microg. kg(-1). h(-1) (Group RC1), ropivacaine 0.08% 0.16 mg. kg(-1). h(-1) plus clonidine 0.08 microg. kg(-1). h(-1) (Group RC2), or ropivacaine 0.08% 0.16 mg. kg(-1). h(-1) plus clonidine 0.12 microg. kg(-1). h(-1) (Group RC3). A clear dose-response relationship could be identified for a continuous infusion of epidural clonidine, with clonidine dosages in the 0.08-0.12 microg. kg(-1). h(-1) range providing improved postoperative analgesia (reduced Children's Hospital of Eastern Ontario pain score, increased time to first supplemental analgesic demand, and a reduced total number of doses of supplemental analgesics during the first 48 h after surgery). Analgesia was improved without any signs of increased sedation or other side effects. The adjunct use of epidural clonidine in the dosage range of 0.08-0.12 microg. kg(-1). h(-1) appears effective and safe for use in children. The addition of clonidine (0.08-0.12 microg.kg(-1).h(-1))to a continuous epidural infusion of ropivacaine was found to improve postoperative pain relief in children. No clinically significant signs of sedation or other side effects were observed.",2001.0,0,0
199,11431228,A placebo-controlled study of guanfacine in the treatment of children with tic disorders and attention deficit hyperactivity disorder.,L Scahill; P B Chappell; Y S Kim; R T Schultz; L Katsovich; E Shepherd; A F Arnsten; D J Cohen; J F Leckman,"This study evaluated the efficacy and safety of guanfacine in treating children with tic disorders and attention deficit hyperactivity disorder (ADHD). Subjects from a specialty tic disorders clinic were randomly assigned to receive 8 weeks of treatment with guanfacine or placebo under double-blind conditions. Follow-up visits occurred every 2 weeks for safety monitoring and dose adjustment. Thirty-four medication-free subjects (31 boys and three girls with a mean age of 10.4 years) with ADHD, combined type, and a tic disorder participated. After 8 weeks of treatment, guanfacine was associated with a mean improvement of 37% in the total score on the teacher-rated ADHD Rating Scale, compared to 8% improvement for placebo. Nine of 17 subjects who received guanfacine were blindly rated on the Clinical Global Improvement scale as either much improved or very much improved, compared with none of 17 subjects who received placebo. The mean score on the parent-rated hyperactivity index improved by 27% in the guanfacine group and 21% in the placebo group, not a significant difference. On the Continuous Performance Test, commission errors decreased by 22% and omission errors by 17% in the guanfacine group, compared with increases of 29% in commission errors and of 31% in omission errors in the placebo group. Tic severity decreased by 31% in the guanfacine group, compared to 0% in the placebo group. One guanfacine subject with sedation withdrew at week 4. Guanfacine was associated with insignificant decreases in blood pressure and pulse. Guanfacine appears to be a safe and effective treatment for children with tic disorders and ADHD.",2001.0,1,1
200,11432684,Dropout rates in randomised antipsychotic drug trials.,K Wahlbeck; A Tuunainen; A Ahokas; S Leucht,"It has been assumed that new atypical drugs improve treatment compliance due to fewer adverse effects. Data supporting this assumption are scarce. The aim of this study was to study attrition rates in randomised controlled trials of oral administration of conventional antipsychotic drugs, atypical antipsychotic drugs and placebo. The database of the Schizophrenia Module of the Cochrane Library was utilised for the present study. The data in the Cochrane Module are collected by identifying relevant randomised controlled trials from several electronic databases and other sources. Number of dropouts was defined as patients leaving the study preterm due to any reason. Data from 328 treatment groups, consisting of 18,585 randomised subjects from 163 drug trials, were entered in the analysis. One-third of the subjects had dropped out of the trials. The dropout rates significantly increased for each calendar year. Year of trial publication, type of drug and trial length remained statistically significant contributors to dropout rates. In a model incorporating year of publication and trial length, placebo groups and groups treated with conventional antipsychotics had significantly higher attrition rates than groups treated with atypical drugs. When clozapine-treated groups were excluded from the analysis, no statistically significant advantage for atypical drugs over conventional drugs remained. Trial data implicate that a better compliance can be achieved by favouring atypical drugs rather than conventional alternatives in the treatment of schizophrenia. However, this effect is found only when groups treated with the atypical antipsychotic clozapine are included in the analysis. Our study did not find evidence for a statistically significant superiority in acceptability of novel atypical drugs when compared to conventional antipsychotics.",2002.0,0,0
201,11434401,A qualitative assessment of the neurological safety of antipsychotic drugs; an analysis of a risperidone database.,W W Fleischhacker; P Lemmens; B van Baelen,"Neurological side effects of antipsychotic agents limit the use of these drugs, and development of newer antipsychotic agents has been focused on a reduced risk of extrapyramidal symptoms (EPS) as well as effective symptom control. A qualitative analysis of EPS was performed using Extrapyramidal Symptom Rating Scale (ESRS) data from 11 double-blind risperidone trials. An ESRS factor analysis and maximum changes in ESRS scores were compared for the risperidone, haloperidol, and placebo groups. The factor analysis revealed five factors. Between-group comparisons showed no differences between placebo and 1 to 2 mg/day-risperidone groups. Parkinsonism, tremor, akathisia, and sialorrhea were more likely to occur with haloperidol than with placebo or risperidone at 1 to 6 mg/day. Similar results were noted by maximum changes in ESRS scores. At risperidone doses of more than 8 mg/day, acute EPS severity lay between that of the placebo and haloperidol groups. The severity of tardive dyskinesia was greater in patients receiving placebo than in those receiving either active treatment. As the results described above were derived from a post hoc analysis of an existing database, conclusions must remain tentative. To provide more definitive answers, EPS assessments in future studies should be refined to more accurately predict the type of EPS expected with a given agent in clinical practice.",2002.0,0,0
202,11435270,Effects of long-term treatment with antipsychotics on serum leptin levels.,A Herrán; M T García-Unzueta; J A Amado; M T de La Maza; C Alvarez; J L Vázquez-Barquero,"Abnormal regulation of the adipocyte-derived hormone leptin could play a role in body weight gain induced by antipsychotics. To study the effects of long-term antipsychotic treatment on leptin levels in patients with schizophrenia. Serum leptin levels were determined in 59 out-patients with chronic schizophrenia and in the same number of healthy subjects controlled by gender, age and body mass index. Leptin levels did not differ between patients and controls. Leptin levels in patients with schizophrenia correlated with weight gain, even after controlling for current weight, but did not show any association with clinical variables. Antipsychotic class tended to exert different effects over leptin levels (among atypicals, olanzapine induced a greater increase). Elevation of leptin levels induced by chronic antipsychotic treatment can be attributed to weight gain, but other mechanisms could be involved.",2001.0,0,0
203,11440294,Meta-analysis comparing newer antipsychotic drugs for the treatment of schizophrenia: evaluating the indirect approach.,L Sauriol; M Laporta; M D Edwardes; M Deslandes; N Ricard; S Suissa,"Meta-analysis is a useful method to assess the efficacy of newer antipsychotic drugs compared with older drugs or placebo. However, few trials directly compare novel drugs to each other. The purpose of this study was to evaluate the method of indirect meta-analysis by applying it to data on olanzapine versus haloperidol and risperidone versus haloperidol to enable a comparison between olanzapine and risperidone. Published randomized controlled trials (RCTs) of risperidone, olanzapine, and/or haloperidol were identified through literature searches (1983 to 1999) of the MEDLINE, Current Contents, and HealthSTAR databases and reviewed. Data for the Brief Psychiatric Rating Scale (BPRS) total score, the Positive and Negative Syndrome Scale (PANSS) negative subscale, the percentage of patients using anticholinergic drugs, and the percentage of patients dropping out due to lack of efficacy, side effects, or any cause were extracted and combined using the indirect method. These findings were compared with those from a direct comparative study of olanzapine and risperidone. The literature search yielded 8 RCTs comparing risperidone to haloperidol and 3 comparing olanzapine to haloperidol. Only 1 trial directly comparing olanzapine and risperidone was found. In this trial, the change in BPRS total and PANSS negative subscale scores tended to be higher with olanzapine by 1.80 and 1.10, respectively, but these differences were not statistically significant. Indirect meta-analysis yielded similar results. Changes in both BPRS total scores and PANSS negative subscale scores tended to be higher with olanzapine by 0.37 and 0.54, respectively, and again, the differences were not statistically significant. In the indirect meta-analysis, the rate of anticholinergic drug use was 19.5% greater among patients treated with risperidone than among patients treated with olanzapine (P < 0.05). In the direct comparative RCT, the rate was 13.1% higher among patients treated with risperidone (P < 0.05). The dropout rates were similar for patients treated with risperidone and those treated with olanzapine in both analyses. An indirect meta-analysis of studies comparing olanzapine with haloperidol and risperidone with haloperidol yielded conclusions similar to those found in a direct comparative RCT of olanzapine and risperidone.",2002.0,0,0
204,11448085,"Comparative study of mortality rates and cardiac dysrhythmias in post-marketing surveillance studies of sertindole and two other atypical antipsychotic drugs, risperidone and olanzapine.",L V Wilton; E L Heeley; R M Pickering; S A Shakir,"Sertindole (Serdolect), an atypical antipsychotic, was voluntarily suspended in the European Union in 1998 following regulatory concerns over reports of serious cardiac dysrhythmias and sudden unexpected deaths. The reported causes of death, their frequency, prolongation of the rate corrected QT interval (QTc) and cardiac dysrhythmias in patients prescribed sertindole were compared with those for patients treated with two other atypical antipsychotics. All patients in England, prescribed atypical antipsychotics by general practitioners during each drug's immediate post-marketing period, were identified using an observational cohort technique, prescription-event monitoring. Mortality rates in the sertindole cohort were compared with those in a comparator cohort using standardized mortality ratios and incidence rate ratios. Cardiovascular events were reviewed and followed up to identify cases of prolongation of QTc interval. There was no statistically significant difference in mortality rates between sertindole and the comparator cohort, although confidence intervals (CI) were wide due to small numbers in the sertindole cohort. A much smaller number of patients were prescribed sertindole than the other antipsychotics. Six cases of prolongation of QTc interval were identified in 462 patients (1.3%, 95% CI 0.5-2.8) treated with sertindole and one with unspecified electrocardiogram changes in the comparator cohort of 16,542 patients. This study contributes to the understanding of the occurrence of prolongation of QTc interval during clinical use of sertindole, the incidence of which was similar to that in clinical trials. Although no statistically significant difference was shown in mortality rates between sertindole and comparator cohort, the sertindole cohort was too small to rule out an association between the use of this drug and cardiovascular deaths.",2002.0,0,0
205,11448249,"Double-blind, placebo-controlled trial of clonidine in hyperactive children with mental retardation.",V Agarwal; P Sitholey; S Kumar; M Prasad,"A 12-week, double-blind, randomized, placebo-controlled trial of oral clonidine in three fixed doses (4, 6, and 8 mcg/kg/day) using a crossover design was conducted with 10 children who had hyperkinetic disorder (mean age 7.6 years +/-.54). All had comorbid mental retardation. Both parents' ratings on the Parent Symptom Questionnaire and clinicians' ratings on the Hillside Behaviour Rating Scale showed a marked dose-related response to clonidine in hyperactivity, impulsivity, and inattention. Drowsiness was a common side effect of clonidine. It wore off by the 2nd to 4th week in most cases. Thus, clonidine is a safe and effective medication in young hyperkinetic children with comorbid mental retardation.",2001.0,0,1
206,11459333,Olanzapine in the treatment of post-traumatic stress disorder: a pilot study.,M I Butterfield; M E Becker; K M Connor; S Sutherland; L E Churchill; J R Davidson,"Because the atypical antipsychotic olanzapine may be efficacious in treating post-traumatic stress disorder (PTSD) symptoms, we conducted a 10-week, double-blind, placebo-controlled evaluation in which 15 patients were randomized 2:1 to either olanzapine or placebo. The initial dosage was 5 mg/day and was titrated to a maximum of 20 mg/day. Eleven patients completed the study. Patients in both groups showed improvement in PTSD symptoms, but no between-group differences in treatment response were observed and a high placebo response rate was found. Both treatments were tolerated well, although the olanzapine treatment group had more weight gain. Olanzapine fared no better than placebo in this preliminary study in the treatment of PTSD. The lack of difference between olanzapine and placebo may in part be due to olanzapine's not being effective in PTSD or, alternatively, a small sample size, a high placebo response in certain forms of PTSD and the chronicity of PTSD symptoms in some patients.",2002.0,0,0
207,11462747,Adult ADHD. Controlled medication assessment.,M Kinsbourne; G B De Quiros; D Tocci Rufo,"Many adults with ADHD respond to stimulant therapy, but controlled medication assessments have not been reported. We administered an effortful working memory task in four half-day sessions, double blind, at methylphenidate levels of 0, 5, 10 and 20 mg. Dose-response curves were established individually. Fifteen of 17 patients displayed a favorable response to one or more levels of medication; that is, they achieved more correct responses and less variability than on placebo. Each dose level elicited optimal performance from some of the patients. Unlike monitoring by self-report, the objective medication assessment offers an expeditious approximation to the ultimate optimal dose, potentially saving the patient weeks on an ineffective and/or excessive dosage regime.",2001.0,1,1
208,11473855,Clonidine prevents sevoflurane-induced agitation in children.,P J Kulka; M Bressem; M Tryba,"In a double-blinded trial, 40 male children (age 2-7 yr) undergoing circumcision were randomly assigned to receive clonidine 2 microg/kg IV or placebo after anesthetic induction. For induction and maintenance of anesthesia, we used sevoflurane as the sole anesthetic. For pain treatment, a penile block was performed before surgery. After surgery the incidence and severity of agitation was measured during an observation period of 2 h. Severe agitation was treated with midazolam. In 16 placebo and 2 clonidine-treated patients agitation was observed (P < 0.001). In 6 patients of the Placebo group, agitation was graded as severe, whereas none of the patients in the Clonidine group developed severe agitation (P = 0.02). During the postoperative period heart rate and blood pressure were significantly decreased in clonidine treated patients (P < 0.05). We conclude that clonidine effectively prevents agitation after sevoflurane anesthesia. The recovery from sevoflurane anesthesia may be complicated by the presence of agitation in pediatric patients. Clonidine 2 microg/kg IV after anesthetic induction effectively reduces the incidence of agitation without resulting in clinically relevant bradycardia and hypotension.",2001.0,0,0
209,11473971,Randomized placebo controlled trial of lofexidine hydrochloride for chronic pelvic pain in women.,R W Stones; L Bradbury; D Anderson,"We hypothesised that the orally-active alpha(2)-adrenoceptor agonist lofexidine hydrochloride would ameliorate chronic pelvic pain in women. A randomized placebo-controlled parallel group trial was undertaken in the University Hospital Gynaecology Clinic. Women with pelvic pain of at least 6 months duration were eligible, and were randomized using a sealed envelope system to receive up to 600 mg lofexidine hydrochloride twice daily over 8 weeks or placebo. Outcome measures were summary and daily diary visual analog scales for pain (VAS) and a 5 point self rating scale. 9/19 women randomized to lofexidine completed the study compared to 14/20 of those randomized to placebo. Intention-to-treat analysis showed that 4/19 in the lofexidine group achieved 50% or greater reduction in VAS compared with 8/20 in the placebo group (OR 2.5, 95% CI 0.6--10.3). Summary and diary VAS were closely correlated. Within the limits of a small study with power to detect only a substantial effect, we conclude that lofexidine hydrochloride is not effective for the treatment of chronic pelvic pain.",2001.0,0,0
210,11476119,"A double-blind, randomized, prospective evaluation of the efficacy and safety of risperidone versus haloperidol in the treatment of schizoaffective disorder.",P G Janicak; P E Keck; J M Davis; J W Kasckow; K Tugrul; S M Dowd; J Strong; R P Sharma; S M Strakowski,"The relative efficacy and safety of risperidone versus haloperidol in the treatment of schizoaffective disorder was studied. Sixty-two patients (29 depressed type; 33 bipolar type) entered a three-site, randomized, double-blind, 6-week trial of risperidone (up to 10 mg/day) or haloperidol (up to 20 mg/day). Trained raters assessed baseline, weekly, and end-of-study levels of psychopathology with the Positive and Negative Syndrome Scale (PANSS), the 24-item Hamilton Rating Scale for Depression (HAM-D-24) and the Clinician-Administered Rating Scale for Mania (CARS-M). The authors were unable to statistically distinguish between risperidone and haloperidol in the amelioration of psychotic and manic symptoms. In addition, there was no difference in worsening of mania between the two agents in either subgroup (i.e., depressed or bipolar subgroups). For the total PANSS, risperidone produced a mean decrease of 16 points from baseline compared with a 14-point decrease with haloperidol. For the total CARS-M scale, risperidone and haloperidol produced mean change scores of 5 and 8 points, respectively, and for the CARS-M Mania subscale, 3 and 7 points, respectively. Additionally, risperidone produced a mean decrease of 13 points from the baseline 24-item HAM-D, compared with an 8-point decrease with haloperidol. In those patients who had more severe depressive symptoms (i.e., HAM-D baseline score >20), risperidone produced at least a 50% mean improvement in 12 (75%) of 16 patients in comparison to 8 (38%) of 21 patients receiving haloperidol. Haloperidol produced significantly more extrapyramidal side effects and resulted in more dropouts caused by any side effect. There was no difference between risperidone and haloperidol in reducing both psychotic and manic symptoms in this group of patients with schizoaffective disorder. Risperidone did not demonstrate a propensity to precipitate mania and was better tolerated than haloperidol. In those subjects with higher baseline HAM-D scores (i.e., >20), risperidone produced a greater improvement in depressive symptoms than haloperidol.",2002.0,0,0
211,11476123,"A double-blind, randomized comparison of the efficacy and safety of intramuscular injections of olanzapine, lorazepam, or placebo in treating acutely agitated patients diagnosed with bipolar mania.",K Meehan; F Zhang; S David; M Tohen; P Janicak; J Small; M Koch; R Rizk; D Walker; P Tran; A Breier,"There are no rapid-acting intramuscular formulations of atypical antipsychotics available for quickly calming an agitated patient with bipolar disorder. In this study, 201 agitated patients with bipolar mania were randomly assigned to receive one to three injections of the atypical antipsychotic olanzapine (10 mg, first two injections; 5 mg, third injection), the benzodiazepine lorazepam (2 mg, first two injections; 1 mg, third injection), or placebo (placebo, first two injections; olanzapine, 10 mg, third injection) within a 24-hour period. Agitation was measured at baseline, every 30 minutes for the first 2 hours, and at 24 hours after the first injection using the Positive and Negative Syndrome Scale-Excited Component subscale and two additional agitation scales. At 2 hours after the first injection, patients treated with olanzapine showed a significantly greater reduction in scores on all agitation scales compared with patients treated with either placebo or lorazepam. At 24 hours after the first injection, olanzapine remained statistically superior to placebo in reducing agitation in patients with acute mania, whereas patients treated with lorazepam were not significantly different from those treated with placebo or olanzapine. Furthermore, no significant differences among the three treatment groups were observed in safety measures, including treatment-emergent extrapyramidal symptoms, the incidence of acute dystonia, or QTc interval changes. These findings suggest that intramuscular olanzapine is a safe and effective treatment for reducing acute agitation in patients with bipolar mania.",2002.0,0,0
212,11476125,An evaluation of risperidone drug interactions.,C L DeVane; C B Nemeroff,"Risperidone, an atypical antipsychotic drug, is widely used in the treatment of psychoses associated with schizophrenia, Alzheimer's disease, and other psychiatric disorders. Polypharmacology is a necessary condition for the optimal treatment of many patients with comorbid psychiatric and medical illness. One concern raised by the widespread use of multiple concurrent pharmacotherapies is the potential for drug-drug interactions to adversely affect patient outcome. Accordingly, the biomedical literature was reviewed for reports of drug interactions involving risperidone, and the clinical significance of each report was evaluated. Additionally, the potential for risperidone to participate in drug interactions was evaluated by considering the drug's pharmacokinetic properties. Controlled studies and case reports indicate that risperidone has a low potential for metabolic drug interactions. Drugs that inhibit cytochrome P450 (CYP) 2D6 or induce or inhibit CYP3A4 may alter risperidone plasma concentrations, but the clinical significance of such interactions seems to be minimal. Adherence to a few guidelines for the design of dosage regimens should limit the effect of drug-drug interactions on patient status and contribute to optimal pharmacotherapy with risperidone.",2002.0,0,0
213,11481167,A double-blind comparative study of clozapine and risperidone in the management of severe chronic schizophrenia.,J M Azorin; R Spiegel; G Remington; J M Vanelle; J J Péré; M Giguere; I Bourdeix,"This prospective, double-blind, multicenter, parallel-group study compared the efficacy and safety of therapeutic doses of clozapine and risperidone in patients with severe chronic schizophrenia and poor previous treatment response. Male or female patients aged 18-65 years who met DSM-IV criteria for schizophrenia and study requirements for poor previous treatment response (N=273) were randomly assigned to double-blind treatment with either clozapine or risperidone administered over 12 weeks in increasing increments. The primary efficacy measures were the magnitude of improvement in Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression (CGI) scores. Adverse events were recorded throughout the study. The magnitude of improvement in mean BPRS and CGI scores from baseline to end of the study was significantly greater in the clozapine group than in the risperidone group. Statistically significant differences in favor of clozapine were also seen for most of the secondary efficacy measures (Positive and Negative Syndrome Scale, Calgary Depression Scale, Psychotic Depression Scale, and Psychotic Anxiety Scale). The adverse event profile was similar for both treatment groups, with a lower risk of extrapyramidal symptoms in the clozapine group. Clozapine showed superior efficacy over risperidone in this patient population. Both treatments were equally well tolerated as demonstrated through their adverse event profiles, although as expected clozapine was associated with a lower risk of extrapyramidal symptoms than risperidone.",2001.0,0,0
214,11483144,,,,,1,1
215,11483145,Attention-deficit/hyperactivity disorder in adults: beyond controversy.,K D Gadow; M Weiss,,2001.0,0,0
216,11487742,"A randomized, double-blind, placebo-controlled trial of docosahexaenoic acid supplementation in children with attention-deficit/hyperactivity disorder.",R G Voigt; A M Llorente; C L Jensen; J K Fraley; M C Berretta; W C Heird,"To determine whether docosahexaenoic acid (DHA) supplementation for 4 months decreases the symptoms of attention-deficit/hyperactivity disorder (ADHD). Sixty-three 6- to-12-year-old children with ADHD, all receiving effective maintenance therapy with stimulant medication, were assigned randomly, in a double-blind fashion, to receive DHA supplementation (345 mg/d) or placebo for 4 months. Outcome variables included plasma phospholipid fatty acid patterns, scores on laboratory measures of inattention and impulsivity (Test of Variables of Attention, Children's Color Trails test) while not taking stimulant medication, and scores on parental behavioral rating scales (Child Behavior Checklist, Conners' Rating Scale). Differences between groups after 4 months of DHA supplementation or placebo administration were determined by analysis of variance, controlling for age, baseline value of each outcome variable, ethnicity, and ADHD subtype. Plasma phospholipid DHA content of the DHA-supplemented group was 2.6-fold higher at the end of the study than that of the placebo group (4.85 +/- 1.35 vs 1.86 +/- 0.87 mol % of total fatty acids; P <.001). Despite this, there was no statistically significant improvement in any objective or subjective measure of ADHD symptoms. A 4-month period of DHA supplementation (345 mg/d) does not decrease symptoms of ADHD.",2001.0,0,0
217,11504278,Steady-state pharmacokinetics and tolerability of modafinil given alone or in combination with methylphenidate in healthy volunteers.,E T Hellriegel; S Arora; M Nelson; P Robertson,"The potential for a pharmacokinetic (PK) drug-drug interaction between modafinil and methylphenidate, each at steady state, was investigated in an open-label, randomized, single-period study in 32 healthy male and female volunteers. All subjects received modafinil once daily orally for 28 days (200 mg on Days 1-7 and 400 mg on Days 8-28). On Days 22 to 28, half of the subjects also received 20 mg of methylphenidate orally 8 hours after their modafinil dose. PK profiles of modafinil were obtained on Days 21 and 28 and compared between the two groups. There were no statistically significant differences between the treatment groups in the mean changes in PK parameters for modafinil. Parameters for its metabolites were also similar between the groups, and all treatments were well tolerated. The results indicate that administration of low-dose methylphenidate 8 hours after treatment with modafinil does not appear to alter the steady-state pharmacokinetics of modafinil in healthy volunteers.",2002.0,0,0
218,11512420,"[Therapies for smoking cessation (antidepressants, nicotine-replacement and counseling) and implications for the treatment of patients with chronic obstructive pulmonary disease].",E J Wagena; M J Huibers; C P van Schayck,"Only a small percentage of smokers who state they want to stop smoking in the next half year, succeed in doing so. This is not only due to the addictive nature of smoking cigarettes, but also because of psychological and social factors. Approximately 80% of the people who have used nicotine-replacement therapy return to smoking after some time. Therefore, the interest in non-nicotine pharmacotherapy has increased considerably in recent years. The antidepressants bupropion and nortriptyline are, compared to a placebo, particularly effective smoking cessation aids (relative risk (RR)nortriptyline: 2.7; 95% CI: 1.3-5.3; RRbupropion: 1.5; 95% CI: 1.1-2.6). A combined strategy of nicotine-replacement therapy with counselling or antidepressants (bupropion or nortriptyline) with counselling, in which the physiological as well as the psychological aspects of smoking cessation are treated, seems to be the most effective. Although smoking cessation is seen as the single most important way of preventing a further deterioration of the lung function at all stages of chronic obstructive pulmonary disease (COPD), little research has been conducted amongst COPD patients. Especially the use of the antidepressants bupropion or nortriptyline seems particularly interesting for the treatment of patients with COPD. This is not only because smoking cigarettes is the major risk factor for the development of the disease, but also because COPD patients have a higher than normal prevalence of depression. Furthermore, an association has been found between smoking cigarettes and depression, and the presence of depression or depressive symptoms appears to be an important cause of relapse.",2001.0,0,0
219,11519769,A placebo-controlled comparison of the effects on sexual functioning of bupropion sustained release and fluoxetine.,C C Coleman; B R King; C Bolden-Watson; M J Book; R T Segraves; N Richard; J Ascher; S Batey; B Jamerson; A Metz,"Many antidepressants are associated with sexual dysfunction, a side effect that may lead to patients' dissatisfaction and noncompliance with treatment. This study compared the efficacy, tolerability, and effects on sexual functioning of bupropion sustained release (bupropion SR) and the selective serotonin reuptake inhibitor fluoxetine. In this multicenter, randomized, double-blind, double-dummy, parallel-group study, patients with recurrent major depression were treated with bupropion SR 150 to 400 mg/d, fluoxetine 20 to 60 mg/d, or placebo for up to 8 weeks. Depression and sexual-functioning status were assessed by site-specific trained investigators at weekly clinic visits; tolerability was assessed primarily by monitoring adverse events. Four hundred fifty-six patients participated in the study, 150 receiving bupropion SR, 154 fluoxetine, and 152 placebo. The majority of patients in each group completed the study (63% each, bupropion SR [n = 94] and fluoxetine [n = 97]; 67%, placebo [n = 102]). Bupropion SR and fluoxetine were similarly effective in the treatment of depressive symptoms. Beginning at week 2 and continuing throughout the study, significantly more fluoxetine-treated patients experienced orgasm dysfunction than did patients receiving bupropion SR or placebo (P < 0.001); similar results were seen in patients defined as clinical responders (> or =50% decrease from baseline in 21-item Hamilton Rating Scale for Depression [HAM-D] total score) (P < 0.001) and in those experiencing remission of depression (HAM-D total score <8) (P < 0.05). At various time points, worsened sexual functioning, sexual desire disorder, sexual arousal disorder, and dissatisfaction with sexual functioning in those satistied at baseline were more frequently associated with fluoxetine treatment than with bupropion SR or placebo. Both active treatments were well tolerated. Bupropion SR and fluoxetine were similarly effective and well tolerated in the treatment of depression. Fluoxetine, however, was more frequently associated with sexual dysfunction compared with bupropion SR. Bupropion SR may be an appropriate initial choice for the treatment of depression in patients concerned about sexual functioning.",2002.0,0,0
220,11524026,Methylphenidate (OROS formulation).,G M Keating; K McClellan; B Jarvis,"Methylphenidate is a CNS stimulant that is thought to block the reuptake of dopamine and noradrenaline (norepinephrine) into the presynaptic neuron. A sustained release (OROS formulation of the drug has been developed for use in children with attention deficit/hyperactivity disorder (ADHD). In children aged 6 to 12 years with ADHD, the maximum plasma concentration of OROS methylphenidate 18 to 54 mg was reached after approximately 7 to 8 hours. In adults, the plasma concentration-time profile of OROS methylphenidate differed markedly from that of the sustained release and immediate release (IR) methylphenidate formulations. In a clinical trial involving 282 children with ADHD, once daily OROS methylphenidate 18 to 54 mg was significantly more effective than placebo and demonstrated an effect similar to IR methylphenidate 5 to 15 mg 3 times daily in reducing the symptoms of ADHD. OROS methylphenidate demonstrated sustained efficacy in a 1-year noncomparative study involving children with ADHD. In clinical trials, the OROS formulation of methylphenidate had a tolerability profile similar to that of IR methylphenidate.",2001.0,0,0
221,11541691,Relative efficacy of the proposed Space Shuttle antimotion sickness medications.,J R Hordinsky; E Schwartz; J Beier; J Martin; G Aust,"Space motion sickness has been estimated as affecting between 1/3 and 1/2 of all space flight participants. NASA has at the moment proposed a combination of promethazine and ephedrine (P/E) and one of scopolamine and dextroamphetamine (S/D), both given orally, as well as a transdermally applied scopolamine (TAS), as preventive and ameliorative measures. The reported double-blind study, tests the early phase actions and efficacy of the transdermal scopolamine (Transderm (TM)-V of ALZA Corporation) and compares these in detail to the oral medications. Motion sickness resistance was tested by standardized head movements while accelerating at 0.2 degree/sec2 to a maximum rotation of 240 degrees/sec, with an intermediate plateau of 10 min at 180 degrees/sec. To permit weighting motion sickness protection against other system influences, cardiovascular, psychological (subjective and objective), and visual parameter changes were documented for the three therapeutic modes. The relative impact of the various modalities on operational and experimental components of space missions is discussed. A comparison to intramuscularly administered promethazine (a backup therapeutic mode suggested for Space Shuttle use) is also included.",2001.0,0,0
222,11546713,Urapidil does not prevent postanesthetic shivering: a dose-ranging study.,S N Piper; M T Fent; K D Röhm; W H Maleck; S W Suttner; J Boldt,"To investigate the effect of 0.2 mg x kg(-1), 0.3 mg x kg(-1) and 0.4 mg x kg(-1) urapidil on the incidence and severity of postanesthetic shivering. One hundred and fifty patients (ASA I-III) scheduled for elective abdominal, urologic or orthopedic surgery under standardized general anesthesia were randomly allocated to one of five groups (each group n=30) using a double-blind protocol: group A received 0.2 mg x kg(-1) urapidil, group B: 0.3 mg x kg(-1) urapidil, group C: 0.4 mg x kg(-1) urapidil, group D: 3 microg x kg(-1) clonidine (positive control group), and group E: saline 0.9% as placebo (negative control group). Postanesthetic shivering was scored using a five-point scale. Twelve patients of group A, 11 of group B, nine of group C, three of group D and 14 of group E showed signs of postanesthetic shivering. Postanesthetic shivering was significantly decreased in the clonidine group compared to the three urapidil groups and the placebo group. Significantly less patients treated with clonidine needed anti-shivering therapy. There were no significant differences between the urapidil and placebo groups. Therapeutic interventions for hemodynamic effects were not required in any group. Time to extubation, but not time to discharge, was prolonged in the clonidine group. Urapidil showed no beneficial effect on shivering in any of the doses evaluated, whereas prophylactic administration of clonidine was effective in preventing postanesthetic shivering.",2001.0,0,0
223,11549212,Antipsychotic-induced extrapyramidal syndromes. Risperidone compared with low- and high-potency conventional antipsychotic drugs.,I Schillevoort; A de Boer; R M Herings; R A Roos; P A Jansen; H G Leufkens,"To compare the risk of extrapyramidal syndromes (EPS) between patients using risperidone and those using low-potency conventional antipsychotic drugs (APDs) in outpatient clinical practice, as measured by the use of anticholinergic medication. We tried to replicate results from previous clinical trials that compared risperidone with high-potency APDs. Data was obtained from the PHARMO database containing filled prescriptions of 450,000 community-dwelling people in The Netherlands from 1986 to 1998. From the patients aged 15-54 years who had been newly treated with APDs, we defined mutually exclusive cohorts according to the APD first prescribed to a patient. APD exposure was followed until the first prescription of anticholinergic medication and was censored when APD prescribing was interrupted or switched. We estimated relative risks between risperidone and commonly used low-potency and high-potency APDs using Cox proportional hazards models, adjusting for age, gender, dose and other potential confounders. In 4094 patients who had been newly prescribed antipsychotic drugs, the overall incidence rate of anticholinergic drug therapy was 556 per 1000 person-years, which was dose dependent. Prescribed doses of all antipsychotics were low. While, in accordance with previous trials, risperidone showed a lower risk of EPS than the high potency APDs such as haloperidol (RR 0.26; 95% CI 0.10-0.64), we did not observe a lower EPS rate than low-potency APDs (risperidone vs thioridazine RR 1.73, 95% CI 0.49-6.13; risperidone vs pipamperone RR 2.50, 95% CI 0.78-8.04). The reduced EPS rates observed when comparing risperidone with high-potency antipsychotics such as haloperidol may not apply to comparisons with low-potency drugs.",2002.0,0,0
224,11552769,Treatment of the symptoms of schizophrenia: a combined analysis of double-blind studies comparing risperidone with haloperidol and other antipsychotic agents.,I D Glick; P Lemmens; E Vester-Blokland,"Combined data on efficacy were available from 12 double-blind short-term (maximum 8 weeks) trials comparing risperidone and other antipsychotics in patients with chronic schizophrenia. Patients received risperidone (n = 1056) or other antipsychotics (n = 703). Haloperidol (n = 473) was the most frequently prescribed other antipsychotic. Efficacy assessments include the Positive and Negative Syndrome Scale (PANSS) total, subscale (positive symptoms, negative symptoms and general psychopathology), cluster (cognitive and affective symptoms) and item (anxiety and hostility) scores. At endpoint, the mean decrease from baseline in PANSS total scores was significantly greater for patients receiving risperidone (-20.9) than other antipsychotics (-16.2; P < 0.001), or the subset receiving haloperidol (-14.3; P < 0.001). Risperidone-treated patients showed a significantly greater decrease in the positive (P < 0.01), negative (P < 0.05) and general psychopathology (P < 0.001) scores than patients receiving other antipsychotics or haloperidol. Scores for cognition, affective symptoms, anxiety and hostility each improved significantly (P < 0.05) more for patients receiving risperidone than those receiving other antipsychotics or haloperidol. Efficacy data on patients with an acute exacerbation were available from seven trials (risperidone n = 372, other antipsychotics n = 285, including haloperidol n = 120). At endpoint, the mean decrease from baseline in PANSS total scores was significantly greater for patients receiving risperidone (-24.7) than other antipsychotics (-19.8, P < 0.01) including haloperidol (-19.8, P < 0.05). Risperidone-treated patients also showed a greater decrease in positive symptom scores (-7.8) than those receiving other antipsychotics (-6.3; P < 0.01) or haloperidol (-7.1). A > or = 20% reduction in PANSS total score with risperidone, haloperidol and other antipsychotics was achieved by 65.9%, 54.3% and 54.9%, respectively; a > or = 30% PANSS reduction by 54.0%, 46.6% and 46.5% of patients, respectively; and a > or = 40% reduction by 43.8%, 33.7% and 34.4% of patients, respectively. These findings are consistent with earlier findings that show risperidone is more efficacious than haloperidol for reducing the symptoms of schizophrenia.",2002.0,0,0
225,11557835,Bupropion for weight loss: an investigation of efficacy and tolerability in overweight and obese women.,K M Gadde; C B Parker; L G Maner; H R Wagner; E J Logue; M K Drezner; K R Krishnan,"On the basis of the clinical observations that bupropion facilitated weight loss, we investigated the efficacy and tolerability of this drug in overweight and obese adult women. A total of 50 overweight and obese (body mass index: 28.0 to 52.6 kg/m(2)) women were included. The core component of the study was a randomized, double-blind, placebo-controlled comparison for 8 weeks. Bupropion or placebo was started at 100 mg/d with gradual dose increase to a maximum of 200 mg twice daily. All subjects were prescribed a 1600 kcal/d balanced diet and compliance was monitored with food diaries. Responders continued the same treatment in a double-blind manner for an additional 16 weeks to a total of 24 weeks. There was additional single-blind follow-up treatment for a total of 2 years. Subjects receiving bupropion achieved greater mean weight loss (last-observation-carried-forward analysis) over the first 8 weeks of the study (p = 0.0001): 4.9% +/- 3.4% (n = 25) for bupropion treatment compared with 1.3% +/- 2.4% (n = 25) for placebo treatment. For those who completed the 8 weeks, the comparison was 6.2% +/- 3.1% (n = 18) vs. 1.6% +/- 2.9% (n = 13), respectively(p = 0.0002), with 12 of 18 of the bupropion subjects (67%) losing over 5% of baseline body weight compared with 2 of 13 in the placebo group (15%; p = 0.0094). In the continuation phase, 14 bupropion responders who completed 24 weeks achieved weight loss of 12.9% +/- 5.6% with fat accounting for 73.5% +/- 3.7% of the weight lost and no change in bone mineral density as assessed by DXA. Bupropion was generally well-tolerated in this sample. Bupropion was more effective than placebo in achieving weight loss at 8 weeks in overweight and obese adult women in this preliminary study. Initial responders to bupropion benefited further in the continuation phase.",2001.0,0,0
226,11560455,"Sustained-release bupropion for pharmacologic relapse prevention after smoking cessation. a randomized, controlled trial.",J T Hays; R D Hurt; N A Rigotti; R Niaura; D Gonzales; M J Durcan; D P Sachs; T D Wolter; A S Buist; J A Johnston; J D White,"Smoking relapse is common after successful pharmacologic treatment for smoking cessation. No previous studies have examined long-term drug therapy used expressly for prevention of smoking relapse. To evaluate the efficacy of bupropion to prevent smoking relapse. Randomized, placebo-controlled trial. 784 healthy community volunteers who were motivated to quit smoking and who smoked at least 15 cigarettes per day. The participants received open-label, sustained-release bupropion, 300 mg/d, for 7 weeks. Participants who were abstinent throughout week 7 of open-label treatment were randomly assigned to receive bupropion, 300 mg/d, or placebo for 45 weeks and were subsequently followed for an additional year after the conclusion of the medication phase. Participants were briefly counseled at all follow-up visits. At the end of open-label bupropion treatment, 461 of 784 participants (58.8%) were abstinent from smoking. Self-reported abstinence was confirmed by an expired air carbon monoxide concentration of 10 parts per million or less. The point prevalence of smoking abstinence was significantly higher in the bupropion group than in the placebo group at the end (week 52) of drug therapy (55.1% vs. 42.3%, respectively; P = 0.008) and at week 78 (47.7% vs. 37.7%; P = 0.034) but did not differ at the final (week 104) follow-up visit (41.6% vs. 40.0%). The median time to relapse was significantly greater for bupropion recipients than for placebo recipients (156 days vs. 65 days; P = 0.021). The continuous abstinence rate was higher in the bupropion group than in the placebo group at study week 24 (17 weeks after randomization) (52.3% vs. 42.3%; P = 0.037) but did not differ between groups after week 24. Weight gain was significantly less in the bupropion group than in the placebo group at study weeks 52 (3.8 kg vs. 5.6 kg; P = 0.002) and 104 (4.1 kg vs. 5.4 kg; P = 0.016). In persons who stopped smoking with 7 weeks of bupropion treatment, sustained-release bupropion for 12 months delayed smoking relapse and resulted in less weight gain.",2001.0,0,0
227,11564483,"Effect of levodopa in combination with physiotherapy on functional motor recovery after stroke: a prospective, randomised, double-blind study.",K Scheidtmann; W Fries; F Müller; E Koenig,"Functional disability is generally caused by hemiplegia after stroke. Physiotherapy used to be the only way of improving motor function in such patients. However, administration of amphetamines in addition to exercise improves motor recovery in animals, probably by increasing the concentration of norepinephrine in the central nervous system. Our aim was to ascertain whether levodopa could enhance the efficacy of physiotherapy after hemiplegia. We did a prospective, randomised, placebo-controlled, double-blind study in which we enrolled 53 primary stroke patients. For the first 3 weeks patients received single doses of levodopa 100 mg or placebo daily in combination with physiotherapy. For the second 3 weeks patients had only physiotherapy. We quantitatively assessed motor function every week with Rivermead motor assessment (RMA). Six patients were excluded from analyses because of non-neurological complications. Motor recovery was significantly improved after 3 weeks of drug intervention in those on levodopa (RMA improved by 6.4 points) compared with placebo (4.1), and the result was independent of initial degree of impairment (p<0.004). The advantage of the levodopa group was maintained at study endpoint 3 weeks after levodopa was stopped. At the end of the study the total RMA score gain for the levodopa group was 8.2 points compared with 5.7 in the placebo group (p=0.020). A single dose of levodopa is well tolerated and, when given in combination with physiotherapy, enhances motor recovery in patients with hemiplegia. In view of its minimal side-effects, levodopa will be a possible add- on during stroke rehabilitation.",2001.0,0,0
228,11571765,Bupropion SR in the naturalistic treatment of elderly patients with major depression.,D C Steffens; P M Doraiswamy; D R McQuoid,"Bupropion immediate release (IR) and bupropion sustained release (SR) are frequently used to treat geriatric depression, as they have few cardiovascular, gastrointestinal and sexual adverse effects. We sought to examine the efficacy and dosing patterns of bupropion in a naturalistic cohort of elderly subjects with major depression (MD). 31 elderly ( > 60 years) patients with unipolar MD (DSM-IV) who were enrolled in Duke's Mental Health Clinical Research Center for the Study of Depression in Later Life were prescribed bupropion SR or IR, alone or in combination with other antidepressant agents, for 12 weeks. Montgomery-Asberg depression rating scale (MADRS) scores and clinical global impression (CGI) severity scores were used to define response. 74% (23/31) of the sample were responders (MADRS < 15) and 53% (16/30) achieved a partial (CGI = 2) or complete (CGI = 1) remission of MD at week 12. Among patients treated with bupropion SR monotherapy, the mean (range) maximal daily dose achieved was 240 mg (150-400 mg). Among those treated with bupropion IR, the mean (range) maximum daily dose achieved was 258 mg (150-450 mg). In subjects on monotherapy, 67% (10/15) of MD subjects were responders (MADRS < 15) and 50% (7/14) achieved full or partial remission. Response rates did not differ statistically among those with high and low medical comorbidity. In this naturalistic 12-week study, geriatric MD patients with high and low medical comorbidity responded well to bupropion and bupropion SR. In elderly patients, four to eight week acute treatment periods may be insufficient. Our findings suggest that nearly 50% of elderly depressed subjects at a tertiary center may need combination therapy over the course of their illness. Controlled randomized studies to establish the long-term efficacy and optimal dose of the newer antidepressants in geriatric depression are urgently needed.",2001.0,0,0
229,11576036,Clozapine and haloperidol in moderately refractory schizophrenia: a 6-month randomized and double-blind comparison.,J M Kane; S R Marder; N R Schooler; W C Wirshing; D Umbricht; R W Baker; D A Wirshing; A Safferman; R Ganguli; M McMeniman; M Borenstein,"Despite the demonstrated efficacy of clozapine in severely refractory schizophrenia, questions remain regarding its efficacy for primary negative symptoms, comparison with a moderate dose of a first-generation antipsychotic, and adverse effects during a longer-term trial. This study examined its efficacy in partially responsive, community-based patients, compared clozapine with moderate-dose haloperidol, and extended treatment to 6 months. Randomized, double-blind, 29-week trial comparing clozapine (n = 37) with haloperidol (n = 34). Subjects with schizophrenia who were being treated in community settings at 3 collaborating clinical facilities were enrolled. Subjects treated with haloperidol were significantly more likely to discontinue treatment for lack of efficacy (51%) than were those treated with clozapine (12%). A higher proportion of clozapine-treated subjects met an a priori criterion of improvement (57%) compared with haloperidol-treated subjects (25%). Significantly greater improvement was seen in symptoms of psychosis, hostile-suspiciousness, anxiety-depression, thought disturbance, and total score measured on the Brief Psychiatric Rating Scale. No differences were detected in negative symptoms using the Brief Psychiatric Rating Scale or the Schedule for Assessment of Negative Symptoms. Subjects treated with clozapine experienced more excess salivation, dizziness, and sweating and less dry mouth and decreased appetite than those treated with haloperidol. Compared with a first-generation antipsychotic given in a moderate dose, clozapine offers substantial clinical benefits to treatment-refractory subjects who can be treated in the community. Advantages are seen in a broad range of symptoms but do not extend to negative symptoms.",2001.0,0,0
230,11579009,Association of olanzapine-induced weight gain with an increase in body fat.,U Eder; B Mangweth; C Ebenbichler; E Weiss; A Hofer; M Hummer; G Kemmler; M Lechleitner; W W Fleischhacker,"The goal of this study was to explore the pathophysiology of weight gain during treatment with olanzapine for schizophrenia. The authors used a prospective, controlled, open study comparing body weight, body mass index, and related biological measures in mentally and physically healthy volunteers and olanzapine-treated patients with schizophrenia. Weight, eating behavior, leptin serum levels, body mass index, and body composition were assessed over an 8-week observation period. A significant increase in body weight, leptin serum levels, and percentage of body fat was seen in patients treated with olanzapine, but the drug-free comparison group did not show any significant changes. The weight gain during antipsychotic treatment with olanzapine was mainly attributable to an increase in body fat; patients' lean body mass did not change. In addition to the original finding that an increase in body fat is mainly responsible for olanzapine-induced weight gain, these findings confirm results obtained in other studies showing increases in body weight and serum leptin levels during treatment with second-generation antipsychotics.",2001.0,0,0
231,11581440,"Randomized, controlled trial of oros methylphenidate once a day in children with attention-deficit/hyperactivity disorder.",M L Wolraich; L L Greenhill; W Pelham; J Swanson; T Wilens; D Palumbo; M Atkins; K McBurnett; O Bukstein; G August,"A new once-a-day methylphenidate (MPH) formulation, Concerta (methylphenidate HCl) extended-release tablets (OROS MPH), has been developed. This study was conducted to determine the safety and efficacy of OROS MPH in a multicenter, randomized, clinical trial. Children with attention-deficit/hyperactivity disorder (ADHD; n = 282), all subtypes, ages 6 to 12 years, were randomized to placebo (n = 90), immediate-release methylphenidate (IR MPH) 3 times a day (tid; dosed every 4 hours; n = 97), or OROS MPH once a day (qd; n = 95) in a double-blind, 28-day trial. Outcomes in multiple domains were assessed, and data were analyzed using analysis of variance and Kaplan Meier product limit estimates for time to study cessation. The primary time point for analysis was the last available patient visit using last observation carried forward. Children in the OROS and IR MPH groups showed significantly greater reductions in core ADHD symptoms than did children on placebo. This was true both at the end of week 1 and at the end of treatment on the basis of mean teacher and parent IOWA Conners ratings. IR MPH tid and OROS MPH qd did not differ significantly on any direct comparisons. Forty-eight percent of the placebo group discontinued early compared with 14% and 16% in the IR MPH and OROS MPH groups, respectively. For the treatment of core ADHD symptoms, OROS MPH dosed qd and IR MPH dosed tid were superior to placebo and were not significantly different from each other.attention-deficit/hyperactivity disorder, methylphenidate, OROS, Concerta.",2002.0,0,0
232,11584516,The Conners' Parent Rating Scales: a critical review of the literature.,W J Gianarris; C J Golden; L Greene,"The Conners' Parent Rating Scales (CPRS) have undergone a considerable amount of scrutiny--and subsequent refining, reshaping, and revising--since their development in 1970. While such longitudinal scrutiny has ultimately led to a more reliable, valid assessment tool, it has left behind a wake of literature filled with misinformation and ambiguity. Multiple versions of the Conners' Rating Scales (CRS), their misuse, and inaccurate reporting by researchers have created a body of literature that is difficult to interpret and misleading to both researchers and clinicians. This review is aimed at clarifying issues regarding the proper use of the CPRS as both a diagnostic instrument and a research tool.",2002.0,0,0
233,11586978,Safety profile of bupropion for chronic obstructive pulmonary disease.,F García-Río; S Serrano; O Mediano; A Alonso; J Villamor,,2001.0,0,0
234,11590972,Use of the Medication Event Monitoring System to estimate medication compliance in patients with schizophrenia.,E Diaz; H B Levine; M C Sullivan; M J Sernyak; K A Hawkins; J A Cramer; S W Woods,"To determine the feasibility of using the Medication Event Monitoring System (MEMS) to estimate medication compliance in patients with schizophrenia or schizoaffective disorder. Fourteen of 35 consecutive patients admitted to a psychiatric inpatient hospital with schizophrenia or schizoaffective disorder who met eligibility requirements and gave informed consent. After random assignment to either risperidone or typical antipsychotic treatment, medication upon discharge from hospital was dispensed in a bottle with a MEMS cap which recorded the number of bottle openings and the date and time of each opening. The first 6 patients were asked to return monthly for data downloading. The next 8 were asked to return weekly during the first month and every 2 weeks thereafter; they were also paid $5 for returning each bottle. MEMS data collected over a 6-month period and hospital readmission data. Patient medication compliance data were collected from 10 (71%) of 14 patients during the first month, from 7 (58%) of 12 (2 patients dropped out) during the second and from 5 (45%) of 11 (a third patient dropped out) during months 3-6. Mean compliance rates were 63% for the first month and ranged from 56% to 45% over the next 5. First-month compliance rates were significantly lower for those who were subsequently readmitted to hospital (n = 7) than for those who were not (p < 0.01). Electronic monitoring devices can be used to estimate compliance with medication regimens in patients with severe schizophrenic disorders, but there are methodological improvements that can be made to increase data recovery and compliance, and these are discussed.",2002.0,0,0
235,11592671,"The influence of stimulants, sedatives, and fatigue on tunnel vision: risk factors for driving and piloting.",K C Mills; S E Spruill; R W Kanne; K M Parkman; Y Zhang,"A computerized task was used in two studies to examine the influence of stimulants, sedatives, and fatigue on single-target and divided-attention responses in different parts of the visual field. The drug effects were evaluated over time with repeated behavioral and subjective measures against ascending and descending drug levels. In the first study, 18 fully rested participants received placebo, alprazolam (0.5 mg), and dextroamphetamine (10 mg). Alprazolam impairs performance, whereas dextroamphetamine induces enhancement and tunnel vision. Study 2 exposed 32 participants to fatigue and no fatigue with a repeated-measures crossover design. Four independent groups subsequently received placebo, dextroamphetamine (10 mg), caffeine (250 mg), or alcohol (.07%). Under fatigue, stimulants have no performance-enhancing effects, whereas impairment from alcohol is severe. Under no fatigue, alcohol has a modest effect, caffeine has no effect, and dextroamphetamine significantly enhances divided-attention performance coincident with tunnel vision. Participants rate all drug effects more stimulating and less sedating while fatigued. Implications for transportation safety are discussed. Actual or potential applications of this research include driver and pilot training.",2001.0,0,0
236,11669086,The effects of olanzapine on neurocognitive functioning in medication-refractory schizophrenia.,R C Smith; M Infante; A Singh; A Khandat,"Neurocognitive deficits are an enduring characteristic of schizophrenia, and remain prominent in patients whose positive symptoms have decreased after treatment with typical neuroleptics. Recent research has reported that olanzapine improves cognitive functioning in relapsing schizophrenia followed in an outpatient setting. Whether olanzapine will have an effect on improving cognitive function in chronic schizophrenics who have been hospitalized for long periods of time, and have shown a poor response to other conventional and atypical neuroleptics, has not been established. This study investigated cognitive function in chronic medication refractory schizophrenics who were treated with olanzapine or haloperidol in a double-blind study for 8 wk, and followed in an open olanzapine study for several additional months. Patients were evaluated with psychopathology rating scales and a battery of neuropsychological tests at baseline, end of double-blind and end of open-label phases of the study. At the end of the double-blind phase there were no significant differences between olanzapine and haloperidol, except for a trend for improvement on the Wisconsin Card Sort Test on olanzapine, which was significant at traditional but not corrected significance levels. After an additional 3 months of treatment with olanzapine doses of 20-40 mg/d, our statistical analysis showed significant improvement on overall neuropsychological test performance and specific cognitive tasks assessing verbal memory. However, these open-label results are difficult to interpret definitively because of the lack of a comparison drug group and the olanzapine dose escalation over time. Neurocognitive changes were not correlated with changes in psychopathology as assessed by PANSS or SANS scores.",2002.0,0,0
237,11682384,Plasma lidocaine concentrations during continuous thoracic epidural anesthesia after clonidine premedication in children.,S Inomata; E Tanaka; M Miyabe; Y Kakiuchi; A Nagashima; Y Yamasaki; S Nakayama; Y Baba; H Toyooka; K Okuyama; Y Kohda,"There is no report concerning oral clonidine's effects on epidural lidocaine in children. Therefore, we performed a study to assess the concentrations of plasma lidocaine and its major metabolite (monoethylglycinexylidide [MEGX]) in children receiving continuous thoracic epidural anesthesia after oral clonidine premedication. Ten pediatric patients, aged 1-9 yr, were randomly allocated to the Control or Clonidine 4 microg/kg group (n = 5 each). Anesthesia was induced and maintained with sevoflurane in oxygen and air (FIO2 40%). Epidural puncture and tubing were carefully performed at the Th11-12 intervertebral space. An initial dose of 1% lidocaine (5 mg/kg) was injected through a catheter into the epidural space, followed by 2.5 mg x kg(-1) x h(-1). Plasma concentrations of lidocaine and MEGX were measured at 15 min, 30 min, and every 60 min for 4 h after the initiation of continuous epidural injection. The concentrations of lidocaine and MEGX were measured using high-pressure liquid chromatography with ultraviolet detection. Hemodynamic variables were similar between members of the Control and Clonidine groups during anesthesia. The Clonidine group showed significantly smaller lidocaine concentrations (p < 0.05) and the concentration of MEGX tended to be smaller in the plasma of the Clonidine group for the initial 4 h after the initiation of epidural infusion. In conclusion, oral clonidine preanesthetic medication at a dose of 4 microg/kg decreases plasma lidocaine concentration in children. Oral clonidine decreases the plasma lidocaine concentration in children. Our finding may have clinical implications in patients receiving continuous epidural anesthesia. Additionally, perhaps an additional margin of safety regarding lidocaine toxicity is gained through the use of oral clonidine in children who will receive epidural lidocaine.",2002.0,0,0
238,11696143,How to prolong postoperative analgesia after caudal anaesthesia with ropivacaine in children: S-ketamine versus clonidine.,P De Negri; G Ivani; C Visconti; P De Vivo,"The aim of the study was to determine whether caudal S-ketamine or clonidine prolonged analgesia together with ropivacaine. Sixty-three boys, aged 1-5 years, who were undergoing minor surgery, were allocated in order to receive one of three solutions for caudal anaesthesia. Group R received 2 mg x kg(-1) 0.2% ropivacaine; group C, 2 mg x kg(-1) 0.2% ropivacaine + clonidine 2 microg x kg(-1); and group K, 2 mg x kg(-1) 0.2% ropivacaine + S-ketamine 0.5 mg x kg(-1). Postoperative analgesia assessed by CHEOPS lasted 701 min in group K (P < 0.05) compared with 492 min in group C and 291 min in group R. There were no significant differences between the groups for incidence of haemodynamic and respiratory alterations, motor block or sedation. This study demonstrates that S-ketamine 0.5 mg x kg(-1) when added to 0.2% caudal ropivacaine provides better postoperative analgesia than clonidine without any clinically significant side-effect.",2002.0,0,0
239,11696146,Analgesia for circumcision in a paediatric population: comparison of caudal bupivacaine alone with bupivacaine plus two doses of clonidine.,P Sharpe; J R Klein; J P Thompson; S C Rushman; J Sherwin; J G Wandless; D Fell,"Clonidine is often used to improve the duration and quality of analgesia produced by caudal epidural blockade, although the optimum dose of clonidine with bupivacaine remains uncertain. We compared the effect of clonidine, 1 and 2 microg x kg(-1), added to bupivacaine (1.25 mg x kg(-1)) with that of bupivacaine alone in 75 male children undergoing elective circumcision. There was a trend towards increasing duration of analgesia with increasing dose of clonidine [group B (bupivacaine) 280.7 (171.6) min, C1 (bupivacaine + clonidine 1 microg x kg(-1)) 327.8 (188.3) min and C2 (bupivacaine + clonidine 2 microg x kg(-1)) 382.0 (200.6) min], although this difference was not statistically significant. Mean time to arousal from anaesthesia was significantly prolonged with clonidine 2 microg kg(-1) (group C2 21.3 (13-36) min, group C1 14.0 (6-25) min and group B 14.4 (2-32) min. Supplementary analgesic requirements and incidence of adverse effects were low, with no differences between the groups. For paediatric circumcision, under general anaesthesia, the addition of clonidine 2 microg x kg(-1) to low volume (0.5 ml x kg(-1)) caudal anaesthetics has a limited clinical benefit for children undergoing circumcision.",2002.0,0,0
240,11700151,Olanzapine: a review of its use in the treatment of bipolar I disorder.,N Bhana; C M Perry,"Olanzapine, a thienobenzodiazepine derivative, is a psychotropic agent that has shown efficacy in the treatment of patients with bipolar I disorder. Olanzapine has a multireceptorial binding profile including a greater affinity for serotonin 5-HT(2A) than for dopamine D(2) receptors. Olanzapine 5 to 20 mg/day demonstrated significantly greater antimanic efficacy than placebo in two double-blind, randomised 3- or 4-week trials of patients with bipolar I disorder of either manic or mixed episodes, with or without psychotic features. Additionally, in one of these trials, improvements in cognitive function and hostility were superior with olanzapine. In cohorts of severely depressed and rapid cycling patients, improvements in manic and depressive symptoms and in manic symptoms only, were superior with olanzapine compared with placebo. Significant improvements from baseline in symptoms of mania, depression, cognitive functioning and hostility were seen with olanzapine in a 49-week extension phase study. In double-blind trials, olanzapine 10 mg/day appeared to have similar antimanic efficacy to oral lithium 400mg twice daily in the treatment of patients with pure mania (4-week small study). In patients with acute manic or mixed episodes olanzapine 5 to 20 mg/day appeared to be more effective than oral valproate semisodium (divalproex sodium) 500 to 2500 mg/day (3-week study) and at least as effective as oral haloperidol 3 to 15 mg/day (12-week study). Preliminary results from a large 6-week placebo-controlled study suggest that olanzapine 5 to 20 mg/day in combination with mood stabilisers (lithium or valproate semisodium) provides effective augmentation of antimanic treatment of patients with bipolar I disorder, with benefits seen in the first week. Adverse events reported significantly more often with olanzapine than with placebo were somnolence, dry mouth, dizziness and bodyweight gain, and in comparison with valproate semisodium were somnolence, dry mouth, increased appetite and bodyweight gain. Olanzapine was generally well tolerated with no clinically relevant abnormalities in laboratory tests, vital signs or electrocardiogram results. Olanzapine demonstrated superior efficacy compared with placebo in the short-term treatment of patients with bipolar I disorder with manic or mixed episodes, with or without psychotic features, and was generally well tolerated. According to preliminary data the antimanic efficacy of olanzapine appears similar to that of haloperidol and better than that of valproate semisodium in patients with bipolar I disorder experiencing a manic or mixed episode; among nonpsychotic patients with manic or mixed episodes olanzapine appears to be superior to haloperidol. Available data support the choice of olanzapine as an option in the short-term management of mania in patients with bipolar I disorder with manic or mixed episodes, with or without psychotic features.",2002.0,0,0
241,11706096,"Double-blind, randomized trial of bupropion SR for the treatment of neuropathic pain.",M R Semenchuk; S Sherman; B Davis,"To evaluate the effectiveness and safety of bupropion sustained-release (SR) for the treatment of neuropathic pain. This single-center, outpatient, randomized, double-blind, placebo-controlled, crossover study consisted of two phases. Forty-one nondepressed patients with neuropathic pain spent 6 weeks in each phase in random order and received identical tablets of 150 mg bupropion SR or placebo. Patients were instructed to take one tablet once daily for 1 week followed by one tablet twice daily for 5 weeks. While the patients took bupropion SR, neuropathic pain relief was improved or much improved in 30 (73%) patients, and one of these patients became pain-free. The mean average pain score at baseline was 5.7, which remained unchanged at the end of week 6 with placebo, but decreased by 1.7 points to 4.0 (p < 0.001) during therapy with bupropion SR. Pain relief with bupropion SR was significant at week 2 (p < 0.05) and continued throughout weeks 3 through 6 (p < 0.001). A significant decrease in interference of pain on quality of life was observed while patients were receiving bupropion SR compared with placebo. Side effects experienced with bupropion SR were not dose-limiting and consisted primarily of dry mouth, insomnia, headache, gastrointestinal upset, tremor, constipation, and dizziness. This placebo-controlled crossover trial showed that bupropion SR (150-300 mg daily) was effective and well tolerated for the treatment of neuropathic pain.",2002.0,0,0
242,11708938,Effects of risperidone on aberrant behavior of persons with developmental disabilities: I. A double-blind crossover study using multiple measures.,J R Zarcone; J A Hellings; K Crandall; R M Reese; J Marquis; K Fleming; R Shores; D Williams; S R Schroeder,"The efficacy of the atypical antipsychotic risperidone was evaluated in the treatment of aberrant behavior (e.g., aggression, self-injury) in 20 individuals with developmental disabilities. A double-blind, crossover design was used to compare risperidone with placebo in a 22-week trial with a 6-month follow-up phase. Based on a 50% reduction in mean Aberrant Behavior Checklist--Community total scores, 50% of the participants were identified as responders. Naturalistic observations of a subset of five individuals showed that for 4 out of 5 participants, risperidone was effective in reducing aberrant behavior. Side effects included weight gain (84% of participants) and sedation (40% of participants). The advantages of conducting a comprehensive analysis of the effects of medication on aberrant behavior are discussed.",2002.0,0,0
243,11712620,Risperidone versus haloperidol in the treatment of acute exacerbations of chronic inpatients with schizophrenia: a randomized double-blind study.,X Y Zhang; D F Zhou; L Y Cao; P Y Zhang; G Y Wu; Y C Shen,"The purpose of this study was to compare the efficacy and safety of risperidone and haloperidol in treatment-resistant chronic schizophrenic patients. Subjects (n = 78) who met DSM-III criteria for schizophrenia were randomly assigned to receive 6 mg/day of risperidone or 20 mg/day of haloperidol for 12 weeks. Clinical efficacy was determined using the Positive and Negative Syndrome Scale (PANSS), and side-effects with the Treatment Emergent Symptom Scale (TESS). Risperidone produced a mean 39.8 +/- 24.1% reduction in total PANSS score compared to a mean 28.3 + 19.4% reduction in the haloperidol group (P < 0.05). Analysis of changes for the three subscores of the PANSS revealed that the general psychopathology and negative subscores were significantly improved in the risperidone group compared to the haloperidol group. As for the side-effects, the risperidone group showed a significantly lower TESS total score, as well as nervous system symptoms subscore and cardiovascular symptoms subscore, compared to the haloperidol group. Risperidone appears to be a more effective and better tolerated antipsychotic drug in treatment-refractory Chinese schizophrenia than haloperidol.",2002.0,0,0
244,11717374,Loss of dopamine transporters in methamphetamine abusers recovers with protracted abstinence.,N D Volkow; L Chang; G J Wang; J S Fowler; D Franceschi; M Sedler; S J Gatley; E Miller; R Hitzemann; Y S Ding; J Logan,"Methamphetamine is a popular drug of abuse that is neurotoxic to dopamine (DA) terminals when administered to laboratory animals. Studies in methamphetamine abusers have also documented significant loss of DA transporters (used as markers of the DA terminal) that are associated with slower motor function and decreased memory. The extent to which the loss of DA transporters predisposes methamphetamine abusers to neurodegenerative disorders such as Parkinsonism is unclear and may depend in part on the degree of recovery. Here we assessed the effects of protracted abstinence on the loss of DA transporters in striatum, in methamphetamine abusers using positron emission tomography and [(11)C]d-threo-methylphenidate (DA transporter radioligand). Brain DA transporters in five methamphetamine abusers evaluated during short abstinence (<6 months) and then retested during protracted abstinence (12-17 months) showed significant increases with protracted abstinence (caudate, +19%; putamen, +16%). Although performance in some of the tests for which we observed an association with DA transporters showed some improvement, this effect was not significant. The DA transporter increases with abstinence could indicate that methamphetamine-induced DA transporter loss reflects temporary adaptive changes (i.e., downregulation), that the loss reflects DA terminal damage but that terminals can recover, or that remaining viable terminals increase synaptic arborization. Because neuropsychological tests did not improve to the same extent, this suggests that the increase of the DA transporters was not sufficient for complete function recovery. These findings have treatment implications because they suggest that protracted abstinence may reverse some of methamphetamine-induced alterations in brain DA terminals.",2002.0,0,0
245,11724088,Euglycemic clamp study in clozapine-induced diabetic ketoacidosis.,A M Avram; V Patel; H C Taylor; J P Kirwan; S Kalhan,"To describe the fifth case of clozapine-induced diabetic ketoacidosis (DKA) with complete resolution of abnormal glucose metabolism after discontinuation of clozapine as assessed by oral glucose tolerance testing (OGTT) and the first to be serially studied with markers of pancreatic autoimmunity; to demonstrate insulin resistance using the euglycemic clamp study and reduced pancreatic insulin reserve using intravenous glucose tolerance testing (IVGTT) in clozapine-induced diabetes mellitus and DKA, when the OGTT was normal; and to systematically review the previously described cases of clozapine-induced diabetes mellitus and DKA. A 33-year-old white man without past or family history of diabetes mellitus presented with DKA after eight months of clozapine therapy (50 mg twice daily). After treatment of DKA and discontinuation of clozapine, glucose tolerance and concurrent serum insulin concentrations reverted to normal as measured by two OGTT performed 60 and 320 days after resolution of DKA. Antiislet-cell antibodies, antiglutamic acid decarboxylase antibodies, and human insulin antibody were negative on two separate occasions. Euglycemic clamp study demonstrated insulin resistance manifested by a glucose disposal rate of approximately 55% of mean normal values. IVGTT demonstrated a low rate of glucose disappearance (KG = 0.95) and diminished first-phase insulin response when OGTT was normal, indicating impairment in insulin sensitivity and reduction in beta cell function 323 days after discontinuance of clozapine. This adverse reaction is considered probable according to the Naranjo probability scale. The occurrence of cases of DKA and new or worsening diabetes mellitus in patients using clozapine suggests a causal relationship. We hypothesize that the mechanism by which clozapine may produce glucose intolerance may require a preexisting latent defect in insulin secretion and insulin action. With the administration of clozapine, some of these patients may develop worsening insulin resistance and may fail to mount an appropriate compensatory beta cell insulin secretion for the degree of insulin resistance. As a consequence, hyperglycemia develops and its persistence results in glucose toxicity, further suppressing beta cell insulin secretion. Such combined defects in insulin secretion and sensitivity are known to be synergistic, leading to the development of abnormal glucose tolerance, which can be clinically manifested as a spectrum ranging from impaired glucose tolerance through severe hyperglycemia to DKA. Patients being started on clozapine should be carefully followed for the development or worsening of diabetes mellitus, regardless of the dose of the drug.",2002.0,0,0
246,11726444,"Neostigmine combined with bupivacaine, clonidine, and sufentanil for spinal labor analgesia.",R D'Angelo; L S Dean; G C Meister; K E Nelson,"We previously found that spinal clonidine prolongs labor analgesia when combined with spinal bupivacaine and sufentanil. We sought to determine whether the addition of spinal neostigmine to these drugs would further enhance labor analgesia. By use of a combined spinal/epidural technique, 36 patients were randomized to receive a hyperbaric spinal injection of bupivacaine 2.5 mg plus clonidine 50 microg and sufentanil 10 microg with or without neostigmine 10 microg. Pain, maternal hemodynamics, fetal heart rate, nausea, pruritus, sedation, motor block, sensory levels to pinprick, and maternal oxygen saturation were assessed at regularly specified intervals after spinal injection until additional analgesia was requested. The duration of spinal analgesia was similar between groups (215 +/- 60 min in the Control group versus 205 +/- 62 min in the Neostigmine group). Likewise, pain scores, the duration of labor, Apgar scores, and side effects were similar between groups except that patients administered neostigmine experienced significantly more nausea and vomiting (53% vs 7%, P = 0.01). We conclude that spinal neostigmine 10 microg produces severe nausea and does not potentiate the duration of spinal analgesia in laboring women from spinal bupivacaine, clonidine, and sufentanil. Spinal neostigmine 10 microg as an adjunct to spinal bupivacaine, clonidine, and sufentanil produces severe nausea and fails to potentiate analgesia in laboring women.",2002.0,0,0
247,11726451,A dose response study of clonidine with local anesthetic mixture for peribulbar block: a comparison of three doses.,R Madan; N Bharti; D Shende; S K Khokhar; H L Kaul,"Clonidine prolongs anesthesia and analgesia of local anesthetics in various neural blocks as well as the duration of retrobulbar block. We assessed the dose-response relationship of clonidine added to lidocaine in peribulbar block. Sixty patients undergoing cataract surgery were given peribulbar block with 7 mL of 2% lidocaine and hyaluronidase with either saline (Control) or clonidine in 0.5-microg/kg (0.5 Clon), 1.0-microg/kg (1.0 Clon), or 1.5-microg/kg (1.5 Clon) doses. The onset and duration of lid and globe akinesia, globe anesthesia and analgesia, postoperative analgesic requirement, and adverse effects (hypotension, bradycardia, hypoxia, sedation, and dizziness) were recorded. The success rate and onset of block were comparable in all groups. The duration of lid and globe akinesia, globe anesthesia and analgesia was significantly (P < 0.01) prolonged in patients receiving 1.0 and 1.5 microg/kg clonidine as compared with the Control group. Perioperative pain scores and analgesic requirement were significantly less in these groups. 0.5 microg/kg clonidine did not increase the duration of anesthesia and analgesia significantly. Hypotension and dizziness were observed more in patients receiving 1.5 microg/kg clonidine as compared with other groups. We conclude that 1.0 microg/kg clonidine with a mixture of lidocaine (2%) significantly prolonged the duration of anesthesia and analgesia after peribulbar block with limited side effects. We studied the effect of the addition of 0.5, 1.0 and 1.5 microg/kg clonidine to a lidocaine-hyaluronidase mixture on the onset and duration of peribulbar block and perioperative analgesia. A dose of 1.0 microg/kg produced a significant increase in duration of anesthesia and analgesia with minimal side effects.",2002.0,0,0
248,11727145,,,,,0,0
249,11735643,Amisulpride: a review of its use in the management of schizophrenia.,M P Curran; C M Perry,"Amisulpride, a substituted benzamide derivative, is a second-generation (atypical) antipsychotic. At low doses, it enhances dopaminergic neurotransmission by preferentially blocking presynaptic dopamine D2/D3 autoreceptors. At higher doses, amisupride antagonises postsynaptic dopamine D2 and D3 receptors, preferentially in the limbic system rather than the striatum, thereby reducing dopaminergic transmission. In patients with acute exacerbations of schizophrenia, the recommended dosage of amisulpride is 400 to 800 mg/day, although dosages < or =1200 mg/day may be administered. In comparative trials, amisulpride administered within this range (400 to 1200 mg/day) was as effective as haloperidol 5 to 40 mg/day, flupenthixol 25 mg/day and risperidone 8 mg/day in patients with acute exacerbations of schizophrenia with predominantly positive symptoms. Amisulpride was more effective than haloperidol but equally effective as risperidone in controlling negative symptoms. Amisulpride 400 to 800 mg/day was more effective than haloperidol, risperidone and flupenthixol in controlling affective symptoms in these patients. In randomised, double-blind trials involving patients with predominantly negative symptoms of schizophrenia, amisulpride 50 to 300 mg/day was more effective than placebo. Amisulpride is effective as maintenance therapy in patients with chronic schizophrenia. Long-term treatment with amisulpride was associated with improvements in quality of life and social functioning. Amisulpride is generally well tolerated. In well-controlled trials, the neurological tolerability profile (including ratings on extrapyramidal symptom scales) of amisulpride 400 to 1200 mg/day was superior to that of the conventional antipsychotics (haloperidol or flupenthixol), but was similar to that of the atypical antipsychotic risperidone. At low dosages of amisulpride (< or =300 mg/day), the incidence of adverse events (including extrapyramidal symptoms) reported with amisulpride was similar to that with placebo. In comparative trials, amisulpride 400 to 1200 mg/day showed efficacy in reducing overall symptomatology and positive symptoms similar to that of conventional antipsychotics and newer atypical antipsychotics in patients with acute exacerbations of schizophrenia. Moreover, its effective alleviation of negative and affective symptoms, its lower association with extrapyramidal symptoms and loss of cognitive function than conventional antipsychotics and its long-term efficacy justifies consideration of the use of higher dosages of amisulpride in this group of patients. Consequently, the dosage of amisulpride that is recommended in patients with acute exacerbations of schizophrenia is 400 to 800 mg/day, although dosages < or =1200 mg/day may be administered. Lower dosages of amisulpride (50 to 300 mg/day) should be considered for the management of patients with negative symptoms of schizophrenia. Amisulpride is a first-line treatment option in the management of schizophrenia in the acute phase and for the maintenance of treatment response.",2002.0,0,0
250,11735845,Antipsychotics and the risk of sudden cardiac death.,W A Ray; S Meredith; P B Thapa; K G Meador; K Hall; K T Murray,"Case reports link antipsychotic drugs with sudden cardiac deaths, which is consistent with dose-related electrophysiologic effects. Because this association has not been confirmed in controlled studies, we conducted a retrospective cohort study in Tennessee Medicaid enrollees, which included many antipsychotic users; there were also computer files describing medication use and comorbidity. The study was conducted before the introduction of risperidone and, thus, did not include the newer atypical agents. The cohort included 481,744 persons with 1,282,996 person-years of follow-up. This included 26,749 person-years for current moderate-dose antipsychotic use (>100-mg thioridazine equivalents), 31,864 person-years for current low-dose antipsychotic use, 37,881 person-years for use in the past year only, and 1 186,501 person-years for no use. The cohort had 1487 confirmed sudden cardiac deaths; from these, we calculated multivariate rate ratios adjusted for potential confounding factors. When current moderate-dose antipsychotic use was compared with nonuse, the multivariate rate ratio was 2.39 (95% confidence interval, 1.77-3.22; P<.001). This was greater than that for current low-dose (rate ratio, 1.30; 95% confidence interval, 0.98-1.72; P=.003) and former (rate ratio, 1.20; 95% confidence interval, 0.91-1.58; P<.001) use. Among cohort members with severe cardiovascular disease, current moderate-dose users had a 3.53-fold (95% confidence interval, 1.66-7.51) increased rate relative to comparable nonusers ( P<.001), resulting in 367 additional deaths per 10,000 person-years of follow-up. Patients prescribed moderate doses of antipsychotics had large relative and absolute increases in the risk of sudden cardiac death. Although the study data cannot demonstrate causality, they suggest that the potential adverse cardiac effects of antipsychotics should be considered in clinical practice, particularly for patients with cardiovascular disease.",2002.0,0,0
251,11735847,"Clozapine use in patients with schizophrenia and the risk of diabetes, hyperlipidemia, and hypertension: a claims-based approach.",B C Lund; P J Perry; J M Brooks; S Arndt,"Numerous case reports have linked clozapine to the development of diabetes mellitus and hyperlipidemia in patients with schizophrenia. However, investigators have been unable to clearly demonstrate this association when compared with a control group receiving conventional antipsychotics. Medical and pharmacy claims from the Iowa Medicaid program were used to compare incidence rates for diabetes, hyperlipidemia, and hypertension in 552 patients receiving clozapine and 2461 patients receiving conventional antipsychotics (eg, haloperidol, chlorpromazine hydrochloride), with the use of a retrospective cohort design. Logistic regression was used to compare incidence rates adjusting for age, sex, and duration of available follow-up. No significant differences in overall incidence rates for diabetes, hyperlipidemia, or hypertension were observed in patients receiving clozapine vs conventional antipsychotics. However, among younger patients (aged 20-34 years), clozapine administration was associated with a significantly increased relative risk of diabetes (2.5 [95% confidence interval, 1.2-5.4]) and hyperlipidemia (2.4 [95% confidence interval, 1.1-5.2]), but not hypertension (0.9 [95% confidence interval, 0.4-2.0]). These data suggest that clozapine may not be an independent cause of diabetes or hyperlipidemia, but instead acts as an effect modifier in susceptible populations by increasing weight or affecting insulin secretion and resistance. This finding requires confirmation in other settings and patient populations and with the other atypical antipsychotics (risperidone, olanzapine, and quetiapine fumarate). The potential long-term medical and economic implications of the early induction of diabetes and hyperlipidemia in patients with schizophrenia warrant further study.",2002.0,0,0
252,11748775,A double-blind randomised comparison of risperidone and haloperidol in the treatment of behavioural and psychological symptoms in Chinese dementia patients.,W C Chan; L C Lam; C N Choy; V P Leung; S W Li; H F Chiu,"Behavioural and psychological symptoms (BPSD) are common during the course of dementia and present severe problems to patients and their caregivers. To assess the therapeutic efficacy and safety of haloperidol and risperidone in treating BPSD in Chinese dementia patients. A 12-week double-blind randomised comparison of haloperidol and risperidone treatments was conducted in 58 patients with DSM-IV diagnosis of dementia of Alzheimer's type or vascular dementia. They were randomly assigned to receive flexible doses (0.5 to 2 mg/day) of haloperidol or risperidone. Clinical response was evaluated using the Cohen-Mansfield Agitation Inventory (CMAI), the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD), Simpson-Angus Scale, Functional Assessment Staging and Cantonese version of the Mini-Mental State Examination. The mean doses at the last week were 0.90 mg/day of haloperidol and 0.85 mg/day of risperidone. Both haloperidol and risperidone significantly reduced the severity of BPSD (scores on CMAI and BEHAVE-AD), with no significant between-group differences. Haloperidol-treated patients showed a worsening on Simpson-Angus scale while there was no significant change in this measure in risperidone-treated patients. Low-dose haloperidol and risperidone were well tolerated and associated with reductions in the severity and frequency of behavioural symptoms in subjects with dementia. Risperidone may have a more favourable risk-benefit profile in view of its lower propensity to induce extrapyramidal symptoms.",2002.0,0,0
253,11755456,A dose-ranging exploratory study of the effects of ethyl-eicosapentaenoate in patients with persistent schizophrenic symptoms.,Malcolm Peet; David F Horrobin; E-E Multicentre Study Group,"The objective was to test effects of ethyl eicosapentaenoate (E-E) on persistent ongoing symptoms in patients receiving different types of anti-schizophrenic drugs, typical antipsychotics, new atypical antipsychotics, and clozapine. 115 patients with DSM-IV-defined schizophrenia were studied, 31 on clozapine, 48 on new atypical drugs and 36 on typical antipsychotics. Placebo or 1, 2 or 4 g/day of E-E was given for 12 weeks in addition to the background medication. The main assessment was change from baseline to 12 weeks on the PANSS and its sub-scales. There were no treatment-related side effects or adverse biochemical or haematological effects. Patients on 2 and 4 g/day E-E showed significant reductions in triglyceride levels which had been elevated by clozapine. In patients given 2 g/day E-E there were improvements on the PANSS and its sub-scales, but there was also a large placebo effect in patients on typical and new atypical antipsychotics and no difference between active treatment and placebo. In patients on clozapine, in contrast, there was little placebo response, but a clinically important and statistically significant effect of E-E on all rating scales. This effect was greatest at 2 g/day. There was a positive relationship between improvement on rating scales and rise in red blood cell arachidonic acid concentration.",2002.0,0,0
254,11763010,"Therapeutic effect of pirenzepine for clozapine-induced hypersalivation: a randomized, double-blind, placebo-controlled, cross-over study.",Y M Bai; C C Lin; J Y Chen; W C Liu,"The objective of this study was to investigate the efficacy of pirenzepine in the treatment of clozapine-induced hypersalivation. Pirenzepine is reported to counteract hypersalivation by its selective antagonistic activity on the M4-muscarinic receptor, which is stimulated by clozapine. Twenty patients with clozapine-induced hypersalivation underwent a random-order, double-blind, placebo-controlled, cross-over trial which lasted 8 weeks each for the pirenzepine and placebo investigations, with a 4-week washout period in between. The severity of hypersalivation was assessed using an objective measure: saliva production monitored through the diameter of wetted surface on tissue paper placed over the patient's pillow. Our study showed that pirenzepine had no significant therapeutic effect on hypersalivation compared with placebo, suggesting that hypersalivation induced by clozapine might have a neurobiological basis other than the M4-muscarinic receptor.",2002.0,0,0
255,11768836,"A comparison of the relative safety, efficacy, and tolerability of quetiapine and risperidone in outpatients with schizophrenia and other psychotic disorders: the quetiapine experience with safety and tolerability (QUEST) study.",J Mullen; M D Jibson; D Sweitzer,"The few published direct comparative studies of the tolerability and efficacy of atypical antipsychotic agents were performed in relatively homogeneous populations that may not be typical of patients seen in clinical practice. The Quetiapine Experience with Safety and Tolerability (QUEST) study compared the relative safety, tolerability, and efficacy of quetiapine and risperidone in outpatients with a broad range of psychotic symptoms. This was a multicenter, 4-month, open-label, randomized clinical trial. Patients were randomized in a 3:1 ratio to receive quetiapine or risperidone. Doses were adjusted to maximize efficacy and to minimize adverse events. Extrapyramidal symptoms (EPS) were assessed with an EPS checklist; adverse events were recorded. Efficacy was assessed using the Clinical Global Impression (CGI) scale, Positive and Negative Symptom Scale (PANSS), and Hamilton Rating Scale for Depression (HAM-D). A total of 728 patients were randomized, 553 to quetiapine and 175 to risperidone. Mean prescribed doses over the study period were 253.9 mg/d quetiapine and 4.4 mg/d risperidone. At the end of 4 months, EPS declined in both treatment groups, but quetiapine-treated patients were significantly less likely to require dose adjustment or concurrent anti-EPS medication (P < 0.001). The most common adverse events in the quetiapine and risperidone groups were somnolence (31.3% and 15.4%, respectively), dry mouth (14.5% and 6.9%), and dizziness (12.7% and 6.9%). Overall, tolerance to side effects with the 2 drugs, measured by dropout rates, was comparable. At each visit, a higher percentage of quetiapine-treated patients showed improvement on the CGI scale, but there were no significant between-group differences on the PANSS. At end point, quetiapine-treated patients had significantly lower HAM-D scores (P = 0.028). The results of this study suggest that quetiapine is as effective as risperidone for the treatment of psychotic symptoms, is more effective for depressive symptoms, may have a more favorable EPS profile, and has comparable overall tolerability.",2002.0,0,0
256,11768842,Pharmacotherapies for attention-deficit/hyperactivity disorder: expected-cost analysis.,A Marchetti; R Magar; H Lau; E L Murphy; P S Jensen; C K Conners; R Findling; E Wineburg; I Carotenuto; T R Einarson; M Iskedjian,"Attention-deficit/hyperactivity disorder (ADHD) is a common childhood neurobehavioral disorder characterized by inattention, hyperactivity, and impulsivity. Prevalence estimates in elementary school children generally range from 3% to 8%. ADHD is frequently treated with psychostimulant medications, which have been shown to improve both cognitive and behavioral outcomes for most children. The goal of this study was to estimate the total expected costs for the treatment and management of school-age children with ADHD using 6 commonly prescribed pharmacotherapies: methylphenidate immediate-release/extended-release (MPH IR/ER), methylphenidate immediate-release (MPH IR), Metadate CD (branded MPH IR/ER), Concerta (branded MPH ER), Ritalin (branded MPH IR), and Adderall (a combination of dextroamphetamine and amphetamine salts). A literature review and clinical assessment using a 27-question survey instrument were used to capture information on the clinical characteristics of ADHD, including common treatment regimens, clinical management of patients, pathways of care, and components of care. A meta-analysis provided response rates for 3 commonly used pharmacotherapies: Metadate CD, MPH IR, and Adderall. Information from the clinical assessment and the meta-analysis were used to populate a decision-analytic model to compute total expected cost for each comparator. The average total annual expected cost per patient was $1,487 for Metadate CD, $1,631 for Concerta. $1,792 for MPH IR/ER, $1,845 for MPH IR, $2,080 for Ritalin, and $2,232 for Adderall. Metadate CD had the lowest total expected cost and Adderall had the highest total expected cost among the ADHD pharmacotherapies evaluated. The differences were attributable to differences in drug-acquisition costs and the need for in-school dosing of twice-daily and thrice-daily medications.",2002.0,0,0
257,11769820,The pharmacovigilance of olanzapine: results of a post-marketing surveillance study on 8858 patients in England.,P N Biswasl; L V Wilton; G L Pearcel; S Freemantle; S A Shakir,"Olanzapine is an 'atypical' antipsychotic indicated for the treatment of schizophrenia. We analysed adverse events (AEs) reported in primary practice in England. Dispensed prescriptions issued between December 1996 and May 1998 provided exposure data. Questionnaires sent to general practitioners provided outcomes. Frequently reported AEs were: drowsiness/sedation (n = 19), extrapyramidal disorder (n = 13) and unspecified side-effects (n = 33). Events with highest incidence density in first month and reason for stopping were: drowsiness/sedation [n = 153, incidence density (ID)1 18.9], weight gain (n = 117, ID1 8.9) and malaise/lassitude (n = 65, ID1 5.2). Extrapyramidal disorders were more common in elderly population (> 70 years, ID1 3.6, risk 26.0 per 1,000 patients) compared to < 70 years (ID1 1.1, risk 8.4 per 1,000 patients). Serious suspected adverse reactions were neuroleptic malignant syndrome (n = 1) and angioneurotic ooedema (n = 2). There were eight reports of diabetes mellitus assessed as possibly due to olanzapine. Diabetes mellitus was an unlabelled AE and possible signal generated by prescription-event monitoring.",2002.0,0,0
258,11772722,Fluoxetine and olanzapine for resistant depression.,Franco Benazzi,,2002.0,0,0
259,11772810,Dolasetron for preventing postanesthetic shivering.,Swen N Piper; Kerstin D Röhm; Wolfgang H Maleck; Moritz T Fent; Stefan W Suttner; Joachim Boldt,"We designed this study to assess the efficacy of dolasetron compared with clonidine and placebo in prophylaxis of postanesthetic shivering. We included 90 patients undergoing elective abdominal or urologic surgery. The patients were randomly assigned to one three groups (each group n = 30) using a double-blinded study protocol: Group A received 12.5 mg dolasetron, Group B 3 microg/kg clonidine, and Group C saline 0.9% as placebo. The medication was given after the induction of anesthesia. Postanesthetic shivering was judged by using a five-point scale. In the Clonidine group, 86.6% showed no shivering, whereas in the Dolasetron and Placebo groups, only 63.3% and 66.6%, respectively, were symptom free. Only clonidine, but not dolasetron, significantly reduced the incidence and the severity of shivering. We conclude that clonidine is effective in preventing shivering when given before surgery, whereas dolasetron, at the dose used, is not effective. Shivering, an irregular muscular fasciculation lasting longer than 15 s, is a common complication secondary to general anesthesia. We compared dolasetron with clonidine (an established antishivering drug) in the prevention of postanesthetic shivering. Dolasetron 12.5 mg was not effective.",2002.0,0,0
260,11773815,,,,,0,0
261,11777998,A comparison of risperidone and haloperidol for the prevention of relapse in patients with schizophrenia.,John G Csernansky; Ramy Mahmoud; Ronald Brenner; Risperidone-USA-79 Study Group,"Prevention of relapse is a major goal of maintenance treatment in patients with psychotic disorders. We performed a long-term comparison of a newer, atypical antipsychotic drug, risperidone, and an older, conventional neuroleptic drug, haloperidol, in terms of the rate of relapse in patients with schizophrenia and schizoaffective disorder. In a double-blind, prospective study at 40 sites, we randomly assigned adult outpatients in stable condition with chronic schizophrenia or schizoaffective disorder to receive treatment with flexible doses of either risperidone or haloperidol for a minimum of one year. Of the 397 patients who underwent randomization, data from 2 were excluded because they did not receive study medication; data from all 30 patients from one site were excluded by the sponsor, the Janssen Research Foundation, because of concern about the integrity of the data. The median duration of treatment was 364 days in the risperidone group and 238 days in the haloperidol group (P=0.02). Of the 177 patients assigned to risperidone and the 188 assigned to haloperidol who remained in the analysis, 44.1 percent and 52.7 percent, respectively, discontinued treatment for reasons other than relapse. The Kaplan-Meier estimate of the risk of relapse at the end of the study was 34 percent for the risperidone group and 60 percent for the haloperidol group (P<0.001); the risk ratio for relapse with haloperidol, from the Cox model, was 1.93 (95 percent confidence interval, 1.33 to 2.80; P<0.001). Early discontinuation of treatment for any reason was more frequent among haloperidol-treated patients (risk ratio, 1.52; 95 percent confidence interval, 1.18 to 1.96). Patients in the risperidone group had greater reductions in the mean severity of both psychotic symptoms and extrapyramidal side effects than those in the haloperidol group. Adult outpatients with clinically stable schizophrenia or schizoaffective disorder have a lower risk of relapse if they are treated with risperidone than if they are treated with haloperidol.",2002.0,0,0
262,11779284,Efficacy of olanzapine in combination with valproate or lithium in the treatment of mania in patients partially nonresponsive to valproate or lithium monotherapy.,Mauricio Tohen; K N Roy Chengappa; Trisha Suppes; Carlos A Zarate; Joseph R Calabrese; Charles L Bowden; Gary S Sachs; David J Kupfer; Robert W Baker; Richard C Risser; Elisabeth L Keeter; Peter D Feldman; Gary D Tollefson; Alan Breier,"A 6-week double-blind, randomized, placebo-controlled trial was conducted to determine the efficacy of combined therapy with olanzapine and either valproate or lithium compared with valproate or lithium alone in treating acute manic or mixed bipolar episodes. The primary objective was to evaluate the efficacy of olanzapine (5-20 mg/d) vs placebo when added to ongoing mood-stabilizer therapy as measured by reductions in Young Mania Rating Scale (YMRS) scores. Patients with bipolar disorder (n = 344), manic or mixed episode, who were inadequately responsive to more than 2 weeks of lithium or valproate therapy, were randomized to receive cotherapy (olanzapine + mood-stabilizer) or monotherapy (placebo + mood-stabilizer). Olanzapine cotherapy improved patients' YMRS total scores significantly more than monotherapy (-13.11 vs -9.10; P = .003). Clinical response rates (> or = 50% improvement on YMRS) were significantly higher with cotherapy (67.7% vs 44.7%; P< .001). Olanzapine cotherapy improved 21-item Hamilton Depression Rating Scale (HAMD-21) total scores significantly more than monotherapy (4.98 vs 0.89 points; P< .001). In patients with mixed-episodes with moderate to severe depressive symptoms (DSM-IV mixed episode; HAMD-21 score of > or = 20 at baseline), olanzapine cotherapy improved HAMD-21 scores by 10.31 points compared with 1.57 for monotherapy (P< .001). Extrapyramidal symptoms (Simpson-Angus Scale, Barnes Akathisia Scale, Abnormal Involuntary Movement Scale) were not significantly changed from baseline to end point in either treatment group. Treatment-emergent symptoms that were significantly higher for the olanzapine cotherapy group included somnolence, dry mouth, weight gain, increased appetite, tremor, and slurred speech. Compared with the use of valproate or lithium alone, the addition of olanzapine provided superior efficacy in the treatment of manic and mixed bipolar episodes.",2002.0,0,0
263,11780884,"A pilot double-blind, dose-comparison study of risperidone in drug-naive, first-episode schizophrenia.",H Y Lane; W H Chang; C C Chiu; M C Huang; S H Lee; J Y Chen,,2002.0,0,0
264,11782326,A systematic review of adjuncts for intravenous regional anesthesia for surgical procedures.,Andrew Choyce; Philip Peng,"To review the use of adjuncts to intravenous regional anesthesia (IVRA) for surgical procedures in terms of their intraoperative effects (efficacy of block and tourniquet pain) and postoperative analgesia. A systematic search (Medline, Embase, reference lists) for randomized, controlled and double-blinded studies using adjuncts to IVRA for surgical procedures was conducted. Data were collected on intraoperative effects (onset/offset and quality of block and tourniquet pain), postoperative effects (pain intensity and analgesic consumption) and side effects recorded. Statistical significance as indicated in the original report and likely clinical relevance were taken into account to arrive at a judgment of overall benefit. Twenty-nine studies met all inclusion criteria. Data on 1,217 study subjects are included. Adjuncts used were opioids (fentanyl, meperidine, morphine, sufentanil), tramadol, non-steroidal anti-inflammatory drugs (NSAIDs; ketorolac, tenoxicam, acetyl-salicylate), clonidine, muscle relaxants (atracurium, pancuronium, mivacurium), alkalinization with sodium bicarbonate, potassium and temperature. There is good evidence to recommend NSAIDs in general and ketorolac in particular, for improving postoperative analgesia. Clonidine 1 microg/kg also appears to improve postoperative analgesia and prolong tourniquet tolerance. Opioids are poor by this route; only meperidine 30 mg or more has substantial postoperative benefit but at the expense of postdeflation nausea, vomiting and dizziness. Muscle relaxants improve intraoperative motor block and aid fracture reduction. Using NSAIDs or clonidine as adjuncts to IVRA improves postoperative analgesia and muscle relaxant improves motor block.",2002.0,0,0
265,11791949,Bupropion SR vs. methylphenidate vs. placebo for attention deficit hyperactivity disorder in adults.,S Kuperman; P J Perry; G R Gaffney; B C Lund; K A Bever-Stille; S Arndt; T L Holman; D J Moser; J S Paulsen,"Despite the increasing recognition of attention-deficit hyperactivity disorder (ADHD) in adults, there are few controlled trials demonstrating the effectiveness of pharmacological treatments, particularly with nonstimulants. One controlled trial found bupropion SR more effective than placebo in the treatment of ADHD adults. We conducted a controlled study to contrast the effectiveness of bupropion SR and methylphenidate to placebo in ADHD adults. A randomized, double-blind, parallel design was used in this study. Following a 7-day placebo lead-in, 30 ADHD (DSM-IV) subjects (18-60 years old) were randomized to bupropion, methylphenidate, or placebo for 7 weeks. Methylphenidate was titrated over 1 week to a maximum dose of 0.9 mg/kg/d divided into 3 doses while bupropion was titrated over 2 weeks to a maximum dose of 200 mg A.M. and 100 mg P.M. Response rates based on Clinical Global Impression improvement ratings in patients receiving bupropion, methylphenidate, and placebo were 64, 50, and 27%, respectively. The difference in response rates between active treatment and placebo was not statistically significant (p = 0.14). Neuropsychological testing demonstrated trends favoring drug treatment on measures of immediate recall and verbal fluency. While bupropion SR may be a viable clinical alternative for adults with ADHD, further investigation is needed.",2002.0,1,1
266,11793611,"Risk of extrapyramidal syndromes with haloperidol, risperidone, or olanzapine.",I Schillevoort; A de Boer; R M Herings; R A Roos; P A Jansen; H G Leufkens,"To compare the risk of extrapyramidal syndrome (EPS) between risperidone, olanzapine, and haloperidol, taking into account patients' past antipsychotic drug use and past EPS. Data were obtained from the PHARMO-database, containing filled prescriptions of 450,000 community-dwelling people in the Netherlands from 1986 through 1999. We defined cohorts of first-time users of haloperidol, risperidone, or olanzapine aged 15 to 54 years. In the first 90 days of treatment, we assessed the occurrence of EPS, defined as first use of any antiparkinsonian agent. We estimated relative risks of EPS for risperidone and olanzapine versus haloperidol using a Cox proportional hazards model. Patients were subdivided according to prior use of antipsychotic and antiparkinsonian drugs. We identified 424 patients starting treatment with haloperidol, 243 with risperidone, and 181 with olanzapine. Prior use of antipsychotic plus antiparkinsonian medication was significantly more frequent among users of risperidone and olanzapine than in those using haloperidol (36.2%, 40.3%, and 4.5%, respectively; p < 0.001). Within most subgroups of comparable treatment history, patients using risperidone and olanzapine showed reduced risks of EPS compared with haloperidol, although some of these findings did not reach statistical significance (RR 0.03-0.22). However, this was not observed for patients using risperidone who had experienced EPS in the past (RR 1.30; 95% CI 0.24 to 7.18). In general, we observed reduced risks of EPS for risperidone and olanzapine compared with haloperidol within subgroups of patients with a similar treatment history. However, the added value of risperidone in patients who have experienced EPS in the past needs further study.",2002.0,0,0
267,11793630,Bupropion versus selective serotonin-reuptake inhibitors for treatment of depression.,C E Nieuwstraten; L R Dolovich,"To compare the benefits and risks of bupropion and selective serotonin-reuptake inhibitors (SSRIs) in adults with depression. MEDLINE (1966-September 1999), Embase (1980-August 1999), PsyclNFO (1887-August 1999), International Pharmaceutical Abstracts (1970-August 1999), and CIANHL databases were searched. References from the selected citations, review articles, and the manufacturer were also screened. Included studies were randomized, double-blind, controlled trials evaluating bupropion versus SSRIs for depression in adults. Studies were assessed independently in duplicate. Discrepancies were resolved by consensus. Data are reported as absolute weighted mean differences or relative risks and 95% confidence intervals comparing bupropion relative to SSRIs. Data not combined are presented qualitatively. Six full-length studies were included of 257 citations identified. SSRI comparators were fluoxetine, sertraline, and paroxetine. No differences in Hamilton Rating Scale for Depression (HAM-D) and Clinical Global Impressions Scale for Improvement of illness (CGI-I) were found, but data were not able to be quantitatively combined. The absolute weighted mean differences were 0.10 (95% CI -0.2 to 0.4) for the CGI for Severity of Illness and 0.37 (95% CI -0.85 to 1.6) for the Hamilton Rating Scale for Anxiety measurements. Relative risks of bupropion compared with SSRIs were 0.6 (95% CI 0.41 to 0.89), 0.31 (95% CI 0.16 to 0.57), and 0.27 (95% CI 0.15 to 0.48) for nausea, diarrhea, and somnolence, respectively. Sexual arousal disorder, orgasmic dysfunction, and sexual desire disorder occurred less with bupropion than with SSRIs, with relative risks of 0.46 (95% CI 0.26 to 0.83), 0.22 (95% CI 0.12 to 0.40), and 0.65 (95% CI 0.51 to 0.84), respectively. Bupropion and SSRIs have similar effectiveness; however, bupropion was associated with less nausea, diarrhea, somnolence, and sexual dysfunction.",2002.0,0,0
268,11799340,"Risperidone in the treatment of tourette syndrome: a double-blind, placebo-controlled trial.",Yves Dion; Lawrence Annable; Paul Sandor; Guy Chouinard,"A double-blind, placebo-controlled trial was performed to determine the efficacy and tolerability of 8 weeks of treatment with risperidone in the management of 48 adolescent and adult patients with Tourette syndrome. Twenty-four patients were randomly assigned to treatment with risperidone in doses of 0.5 to 6.0 mg/day, and 24 were assigned to placebo. The dosage of medication was increased in fixed increments during the first week of double-blind treatment and thereafter in a flexible dose regimen according to clinical response. Risperidone, at a median dose of 2.5 mg/day (range, 1 to 6 mg/day), was found to be significantly ( p < 0.05) superior to placebo on the Global Severity Rating of the Tourette Syndrome Severity Scale. The proportion of patients who improved by at least one point on this seven-point scale was 60.8% in the risperidone group and 26.1% in the placebo group. Treatment with risperidone was accompanied by an improvement in global functioning in patients with average to above-average impairment at baseline as measured by the Global Assessment of Functioning scale. With respect to extrapyramidal symptom scores measured on the Extrapyramidal Symptom Rating Scale, hypokinesia and tremor increased in the risperidone group, but the effect on tremor was largely confined to subjects with higher baseline tremor scores. There were no significant differences in dystonic reactions, dyskinetic movements, subjective parkinsonism, or akathisia. Risperidone did not increase obsessive-compulsive symptoms. Fatigue and somnolence were the most common adverse events associated with risperidone.",2002.0,0,0
269,11803729,,,,,0,0
270,11806864,Adjunctive high-dose glycine in the treatment of schizophrenia.,D C Javitt; G Silipo; A Cienfuegos; A M Shelley; N Bark; M Park; J P Lindenmayer; R Suckow; S R Zukin,"Glycine is an agonist at brain N-methyl-D-aspartate receptors and crosses the blood-brain barrier following high-dose oral administration. In a previous study, significant improvements in negative and cognitive symptoms were observed in a group of 21 schizophrenic patients receiving high-dose glycine in addition to antipsychotic treatment. This study evaluated the degree to which symptom improvements might be related to alterations in antipsychotic drug levels in an additional group of 12 subjects. Glycine treatment was associated with an 8-fold increase in serum glycine levels, similar to that observed previously. A significant 34% reduction in negative symptoms was observed during glycine treatment. Serum antipsychotic levels were not significantly altered. Significant clinical effects were observed despite the fact that the majority of subjects were receiving atypical antipsychotics (clozapine or olanzapine). As in earlier studies, improvement persisted following glycine discontinuation.",2002.0,0,0
271,11812718,Pharmacological treatment of postoperative shivering: a quantitative systematic review of randomized controlled trials.,Peter Kranke; Leopold H Eberhart; Norbert Roewer; Martin R Tramèr,"Shivering is a frequent complication in the postoperative period. The relative efficacy of interventions that are used for the treatment of postoperative shivering is not well understood. We performed a systematic search (MEDLINE, EMBASE, Cochrane Library, hand searching, all languages, to August, 2000) for full reports of randomized comparisons of any pharmacological antishivering intervention (active) with placebo (control) in the postoperative period. Dichotomous data on absence of further shivering after treatment and adverse effects were extracted from original reports. Relative risk (RR) and number-needed-to-treat (NNT) were calculated with 95% confidence interval (CI) using a fixed effect model. Data from 20 trials (944 adults received an active intervention, 413 were controls) were analyzed. Antishivering efficacy depended on the active regimen and the length of follow-up. Efficacy with meperidine 25 mg, clonidine 150 microg, ketanserin 10 mg, and doxapram 100 mg was reported in at least three trials; all were significantly more effective than control. After 1 min, the NNT of meperidine 25 mg for no further shivering compared with placebo was 2.7 (RR, 6.8; 95% CI, 2.5-18.5). After 5 min, the NNT of meperidine 25 mg was 1.3 (RR, 9.6; 95% CI, 5.7-16), the NNT of clonidine 150 microg was 1.3 (RR, 6.8; 95% CI, 3.3-14.2), the NNT of doxapram 100 mg was 1.7 (RR 4.0; 95% CI, 2.4-6.5), and the NNT of ketanserin 10 mg was 2.3 (RR 3.1; 95% CI, 1.9-5.1). After 10 min, the NNT of meperidine 25 mg was 1.5 (RR 4.0; 95% CI, 2.5-6.2). After 15 min, the NNT of ketanserin 10 mg was 3.3 (RR 1.5; 95% CI, 1.2-1.9). Long-term outcome data were lacking. There were not enough data for alfentanil, fentanyl, morphine, nalbuphine, lidocaine, magnesium, metamizol, methylphenidate, nefopam, pentazocine, and tramadol to draw meaningful conclusions. Reporting of adverse drug reactions was sparse. Fewer than two shivering patients need to be treated with meperidine 25 mg, clonidine 150 microg, or doxapram 100 mg for one to stop shivering within 5 min who would have continued to shiver had they all received a placebo. Less than two shivering patients need to be treated with meperidine 25 mg, clonidine 150 microg, or doxapram 100 mg for one to stop shivering within 5 min who would have continued to shiver had they all received a placebo.",2002.0,0,0
272,11816864,The effects of olanzapine on the 5 dimensions of schizophrenia derived by factor analysis: combined results of the North American and international trials.,J M Davis; N Chen,"The choice of drug to treat a patient with schizophrenia is one of the most critical clinical decisions. Controversy exists on the differential efficacy of olanzapine. Raw data from all 4 registrational double-blind, random-assignment studies of olanzapine compared with placebo or haloperidol were obtained from Eli Lilly and Company for this meta-analysis. Analysis of covariance of the intent-to-treat last-observation-carried-forward endpoint scores was used to assess efficacy on Brief Psychiatric Rating Scale (BPRS) and Positive and Negative Syndrome Scale (PANSS) total scores and the 5 factors derived by factor analysis (negative symptoms, positive symptoms, disorganized thoughts, impulsivity/hostility, and anxiety/depression). Olanzapine produced a statistically significantly greater reduction in schizophrenic symptoms than haloperidol (p < .05) on total scores on the BPRS and PANSS on each of the 5 factors as well as on almost all items. Olanzapine induced a response at a rate equal to that induced by haloperidol in the first few weeks, but by the end of the study produced a greater percentage of responders. Compared with haloperidol, olanzapine produced a somewhat greater response on symptoms responsive to haloperidol, but a markedly better response on symptoms unresponsive to haloperidol. This difference favoring olanzapine occurred to an equal degree in all subgroups examined. The incidence of parkinsonism or akathisia following olanzapine treatment was extremely low and not statistically distinguishable from placebo. Olanzapine produced a greater improvement than haloperidol particularly by benefiting a much larger number of items or factors. Extrapyramidal side effects and akathisia during olanzapine treatment were statistically indistinguishable from effects seen with placebo.",2002.0,0,0
273,11816866,Do bupropion SR and sertraline differ in their effects on anxiety in depressed patients?,M H Trivedi; A J Rush; T J Carmody; R M Donahue; C Bolden-Watson; T L Houser; A Metz,"To examine the effects of bupropion sustained release (SR) and sertraline on anxiety in outpatients with recurrent DSM-IV-defined major depressive disorder. This retrospective analysis was conducted using pooled data from 2 identical, 8-week, acute-phase, double-blind, placebo-controlled, parallel-group studies of bupropion SR (N = 234), sertraline (N = 225), and placebo (N = 233). Symptoms of anxiety and depression were measured using the 14-item Hamilton Rating Scale for Anxiety (HAM-A) and the 21-item Hamilton Rating Scale for Depression (HAM-D-21), respectively. Percentage reduction in baseline HAM-A total score for each treatment week was calculated to determine whether the time to onset of anxiolytic activity differed among antidepressant responders to each agent. Central nervous system (CNS) adverse events were tabulated. Bupropion SR and sertraline were comparably effective, both were superior to placebo in reducing depressive symptoms. and they did not differ in their effect on anxiety symptoms. Antidepressant responders (> 50% reduction in baseline HAM-D-21 score) in both groups showed marked and comparable reductions in HAM-A scores (baseline to exit). There were no differences between bupropion SR and sertraline in the median time (4 weeks) to reach a clinically significant anxiolytic effect (> or = 50% reduction in baseline HAM-A score). CNS adverse events were comparable for bupropion SR and sertraline, except for somnolence, which was more common in sertraline-treated patients. Bupropion SR and sertraline had comparable antidepressant and anxiolytic effects and an equally rapid onset of clinically significant anxiolytic activity. There was no difference in the activating effects between the 2 antidepressants. Selection between these 2 agents cannot be based on either anticipation of differential anxiolytic activity or differential CNS side effect profiles.",2002.0,0,0
274,11817518,Effects of clonidine in schizophrenic patients with primary polydipsia: three single case studies.,Nicholas J Delva; Anna Chang; Emily R Hawken; J Stuart Lawson; James A Owen,"A pilot study was conducted in schizophrenic patients with primary polydipsia to determine the tolerability of adding clonidine to an existing antipsychotic drug regimen and to seek evidence of an antidipsic effect. Three patients with chronic schizophrenia and primary polydipsia underwent open controlled prospective trials of treatment with clonidine in doses of up to 800 microg/day. The trials lasted from 2 to 5 months each, and analysis of variance was used to test for changes in dependent variables on a case-by-case basis. Blood pressure and pulse declined significantly in a dose-dependent manner, but fluid intake, as assessed by measurements of weight and 24-h urine volume, was not affected. Hypotension and bradycardia limited the extent to which the dose of clonidine could be increased. The lack of evident effect of clonidine on polydipsia in this small sample and the inconsistent results of two other recent studies of clonidine in patients with schizophrenia and primary polydipsia provide little overall support for the effectiveness of clonidine treatment in primary polydipsia associated with schizophrenia.",2002.0,0,0
275,11818763,Efficacy of clonidine for prevention of perioperative myocardial ischemia: a critical appraisal and meta-analysis of the literature.,Kahoru Nishina; Katsuya Mikawa; Takanobu Uesugi; Hidefumi Obara; Munetaka Maekawa; Isao Kamae; Nobuo Nishi,"There is a belief that clonidine may be effective in reducing perioperative myocardial ischemic events, although the results of several trials are conflicting. The aim of the current study was to provide a systematic review of randomized controlled trials that tested the efficacy of clonidine in this regard. Data was collected from a MEDLINE search of English-language studies published from 1980 to 1999 and a manual search of bibliographies from retrieved articles. A total of 28 studies were assessed. According to the selection criteria (study design, population, intervention, and outcome) and a quality scoring system, seven studies were finally included in the meta-analysis. After homogeneity was established by Q value, the data were then combined using the fixed-effects model. The pooled odds ratio was calculated. A subgroup analysis based on the types of surgery and administration route was also performed to qualify the results. The results were expressed as odds ratio and 95% confidence interval. Heterogeneity of outcome data was negative in the trials. The pooled odds ratio was 0.49 (95% confidence interval 0.34-0.71). In the subgroup analysis, clonidine reduced the incidence of myocardial ischemia in patients undergoing cardiac and noncardiac surgery. Rates of bradycardia were similar in clonidine and placebo groups. The meta-analysis suggests that perioperative clonidine reduces cardiac ischemic episodes in patients with known, or at risk of, coronary arterial disease without increasing the incidence of bradycardia. Therefore, these findings strongly justify planning and execution of a definitive study seeking the benefits of clonidine.",2002.0,0,0
276,11823257,"Amisulpride, an unusual ""atypical"" antipsychotic: a meta-analysis of randomized controlled trials.",Stefan Leucht; Gabi Pitschel-Walz; Rolf R Engel; Werner Kissling,"The ""atypical"" profile of the new antipsychotics clozapine, olanzapine, quetiapine, and risperidone has been linked to combined antagonism of serotonin 2 (5-HT(2)) and dopamine 2 (D(2)) receptors. Although amisulpride is a highly selective D(3)/D(2) receptor antagonist, it is assumed to have atypical properties as well. The purpose of this article was to compare the atypical profile of amisulpride with that of the 5-HT(2)/D(2) antagonists. Randomized controlled trials that compared amisulpride with conventional antipsychotics or placebo for patients with schizophrenia were identified and included in a meta-analysis. The mean effect sizes found for amisulpride were compared with those of an updated meta-analysis of the 5-HT(2)/D(2) antagonists. Eighteen randomized controlled trials of amisulpride (N=2,214) were found. In 11 studies of acutely ill patients it proved to be consistently more effective than conventional antipsychotics for global schizophrenic symptoms (measured with the Brief Psychiatric Rating Scale) and negative symptoms. Amisulpride is to date the only atypical antipsychotic for which several studies of patients suffering predominantly from negative symptoms have been published. In four such studies amisulpride was significantly more effective than placebo. Three small studies with conventional antipsychotics as comparators showed only a trend in favor of amisulpride in this regard. Amisulpride was associated with clearly lower use of antiparkinsonian medication and with fewer dropouts due to adverse events than conventional antipsychotics. These results cast some doubt on the notion that combined 5-HT(2)/D(2) antagonism is the reason that the newer antipsychotic medications are effective for negative symptoms and have fewer extrapyramidal side effects.",2002.0,0,0
277,11823268,"Clozapine, olanzapine, risperidone, and haloperidol in the treatment of patients with chronic schizophrenia and schizoaffective disorder.",Jan Volavka; Pal Czobor; Brian Sheitman; Jean-Pierre Lindenmayer; Leslie Citrome; Joseph P McEvoy; Thomas B Cooper; Miranda Chakos; Jeffrey A Lieberman,"The authors compared the efficacy and safety of three atypical antipsychotics (clozapine, olanzapine, and risperidone) with one another and with haloperidol in the treatment of patients with chronic schizophrenia or schizoaffective disorder. In a double-blind trial, 157 inpatients with a history of suboptimal treatment response were randomly assigned to treatment with clozapine, olanzapine, risperidone, or haloperidol for 14 weeks (an 8-week escalation and fixed-dose period followed by a 6-week variable-dose period). Clozapine, risperidone, and olanzapine (but not haloperidol) resulted in statistically significant improvements in total score on the Positive and Negative Syndrome Scale. Improvements seen in total and negative symptom scores with clozapine and olanzapine were superior to haloperidol. The atypical drugs, particularly olanzapine and clozapine, were associated with weight gain. The effects of atypical antipsychotics in this population were statistically significant but clinically modest. The overall pattern of results suggests that clozapine and olanzapine have similar general antipsychotic efficacy and that risperidone may be somewhat less effective. Clozapine was the most effective treatment for negative symptoms. However, the differences among treatments were small.",2002.0,0,0
278,11831499,Use ecology and drug use motivations of methamphetamine users admitted to substance abuse treatment facilities in Los Angeles: an emerging profile.,Mayrhauser Christina von; Mary-Lynn Brecht; M Douglas Anglin,"Who are methamphetamine (MA) users and what are the circumstances that surround their drug use? This article provides a foundation for future ethnographic studies and collaborative clinician-researcher assessments of MA use by describing use ecology and drug use motivation for 260 MA users admitted to treatment at public Los Angeles County facilities in 1996. Use ecology data include MA varieties and street names, first introductions to use, drug use histories, access, selling and manufacturing, routes of administration, unwanted results of use, and participants' use behavior in the year before the 1996 treatment. Use motivation data describe clients using MA as a substitute for other stimulants; to cope with mental distress; to stay awake; to enhance sexual experience; and to lose weight. Qualitative case studies illustrate the findings and demonstrate the complex inter-relations of society, culture, psyche and soma shaping MA use over time.",2002.0,0,0
279,11831544,Effect of modafinil at steady state on the single-dose pharmacokinetic profile of warfarin in healthy volunteers.,Philmore Robertson; Edward T Hellriegel; Sanjay Arora; Michael Nelson,"Modafinil has been reported to produce a concentration-related suppression of CYP2C9 activity in vitro in primary cultures of human hepatocytes. To determine whether this effect occurs in vivo, the pharmacokinetics of (S)-warfarin was investigated after single oral doses of racemic warfarin (5 mg; COUMADIN) in a placebo-controlled, single-blind, single-period study in 28 volunteers. Subjects received an oral dose of warfarin prior to administration of modafinil (200 mg for 7 days, followed by 400 mg for 21 days) or placebo and they received another after 4 weeks of treatment. Treatment with modafinil did not significantly alter the pharmacokinetics of (S)- or (R)-warfarin relative to placebo. Since (S)-warfarin is predominantly metabolized via CYP2C9, the results indicate that the marked suppression of CYP2C9 activity in vitro does not translate into a similar effect clinically. However, limitations arising from investigation of single doses of warfarin preclude global conclusions about the potential for more subtle interactions after chronic warfarin administration.",2002.0,0,0
280,11834192,[Usefulness of olanzapine in the levodopa-induced psychosis in patients with Parkinson's disease].,J R Chacón; E Durán; J A Durán; M Alvarez,"To evaluate the antipsychotic efficacy of olanzapine (OLZ) in patients with Parkinson's disease (PD) and drug-induced psychosis (DIP) and its repercussion on the motor function. Ten patients (5 women and 5 men) diagnosed of PD and DIP, aged 67 years (range: 50-81), with PD duration of 11.1 years (range: 6-23), treated chronically with levodopa per day, received a dose of 2.5 or 5.0 mg OLZ daily. Data concerning improvement of psychosis and worsening of motor function was based on Positive And Negative Symptoms Scale (PANSS) and Unified Parkinsons Disease Rating Scale (UPDRS) motor. Psychotic symptoms were improved in all patients. In most of them the improvement was almost total. Seven patients increased levodopa dose on OLZ, but significant worsening of motor function was reported just in one patient. None of the patients had agranulocytosis in the blood monitoring. Two patients presented weight gain. Seven patients improved their cognitive status. We conclude that OLZ at the doses studied may have efficacy for DIP which appears in PD and does not induce worsening of motor function in most of the patients.",2002.0,0,0
281,11862632,Methylphenidate isomer approved by FDA.,,,2002.0,0,0
282,11865128,Treatment of ADHD in children with tics: a randomized controlled trial.,Tourette's Syndrome Study Group,"The treatment of children with attention deficit hyperactivity disorder (ADHD) and Tourette syndrome (TS) has been problematic because methylphenidate (MPH)--the most commonly used drug to treat ADHD--has been reported to worsen tics and because clonidine (CLON)--the most commonly prescribed alternative--has unproven efficacy. The authors conducted a multicenter, randomized, double-blind clinical trial in which 136 children with ADHD and a chronic tic disorder were randomly administered CLON alone, MPH alone, combined CLON + MPH, or placebo (2 x 2 factorial design). Each subject participated for 16 weeks (weeks 1-4 CLON/placebo dose titration, weeks 5-8 added MPH/placebo dose titration, weeks 9-16 maintenance therapy). Thirty-seven children were administered MPH alone, 34 were administered CLON alone, 33 were administered CLON + MPH, and 32 were administered placebo. For our primary outcome measure of ADHD (Conners Abbreviated Symptom Questionnaire--Teacher), significant improvement occurred for subjects assigned to CLON (p < 0.002) and those assigned to MPH (p < 0.003). Compared with placebo, the greatest benefit occurred with combined CLON + MPH (p < 0.0001). CLON appeared to be most helpful for impulsivity and hyperactivity; MPH appeared to be most helpful for inattention. The proportion of individual subjects reporting a worsening of tics as an adverse effect was no higher in those treated with MPH (20%) than those being administered CLON alone (26%) or placebo (22%). Compared with placebo, measured tic severity lessened in all active treatment groups in the following order: CLON + MPH, CLON alone, MPH alone. Sedation was common with CLON treatment (28% reported moderate or severe sedation), but otherwise the drugs were tolerated well, including absence of any evident cardiac toxicity. Methylphenidate and clonidine (particularly in combination) are effective for ADHD in children with comorbid tics. Prior recommendations to avoid methylphenidate in these children because of concerns of worsening tics are unsupported by this trial.",2002.0,1,1
283,11874209,Obsessive-compulsive symptoms during treatment with olanzapine and risperidone: a prospective study of 113 patients with recent-onset schizophrenia or related disorders.,Lieuwe de Haan; Nico Beuk; Britt Hoogenboom; Peter Dingemans; Don Linszen,"To determine whether severity of obsessive-compulsive symptoms (OCS) differs during treatment with olanzapine or risperidone and to establish whether duration of antipsychotic treatment is related to severity of OCS. We conducted a prospective study of consecutively hospitalized young patients (mean age = 22.4 years) with DSM-IV schizophrenia or related disorders (N = 113) who were treated with olanzapine or risperidone. Olanzapine or risperidone was randomly prescribed for patients who were drug-naive or were treated with typical antipsychotics before admission (N = 36). Patients who had started olanzapine (N = 39) or risperidone treatment (N = 23) prior to admission continued with that medication if they showed initial clinical response. Patients who prior to admission started olanzapine (N = 6) or risperidone (N = 9) but showed no response or suffered from adverse effects switched at admission to risperidone or olanzapine, respectively. Medical records, parents, and patients revealed information on duration of treatment and compliance with olanzapine or risperidone prior to admission. The Yale-Brown Obsessive Compulsive Scale (YBOCS) was administered at admission and 6 weeks thereafter. At baseline and 6-week assessments, OCS were found in about 30% of 106 evaluable cases and 15% met DSM-IV criteria for obsessive-compulsive disorder. No differences in OCS were found in the patients randomly assigned to olanzapine or risperidone. The 35 subjects treated with olanzapine at both assessments had significantly (p = .01) more severe OCS at week 6 than the 20 subjects treated with risperidone at both assessments. Duration of treatment with olanzapine was significantly (p < .01) related to severity of OCS. There are no differences in the short-term propensity of olanzapine or risperidone to induce or exacerbate OCS. However, severity of OCS was associated with duration of treatment with olanzapine.",2002.0,0,0
284,11879174,Acute tryptophan depletion in schizophrenic patients treated with clozapine.,Tony P George; Marc N Potenza; Kathleen Degen; Michael J Sernyak; Scott Woods; Christopher J McDougle,,2002.0,0,0
285,11886019,Psychopharmacology and aggression. I: A meta-analysis of stimulant effects on overt/covert aggression-related behaviors in ADHD.,Daniel F Connor; Stephen J Glatt; Ivan D Lopez; Denise Jackson; Richard H Melloni,"To determine by meta-analysis the effect size for stimulants on overt and covert aggression-related behaviors in children with attention-deficit/hyperactivity disorder (ADHD), separately from stimulant effects on the core symptoms of ADHD. A review of the literature from 1970 to 2001 revealed 28 studies meeting inclusion/exclusion criteria for meta-analysis. These studies yielded 28 independent effects of overt aggression and 7 independent effects of covert aggression. The overall weighted mean effect size was 0.84 for overt and 0.69 for covert aggression related behaviors in ADHD. Comorbid conduct disorder is associated with diminishing stimulant effect size for overt aggression. Stimulant effects for aggression-related behaviors in ADHD have effect sizes similar to those for the core symptoms of ADHD.",2002.0,0,1
286,11886692,"Mirtazapine, yohimbine or olanzapine augmentation therapy for serotonin reuptake-associated female sexual dysfunction: a randomized, placebo controlled trial.",David Michelson; Kristen Kociban; Roy Tamura; Mary F Morrison,"Many agents have been proposed as potential treatments for SSRI-associated sexual dysfunction, but few placebo-controlled trials have been reported. After a 1-month baseline evaluation, pre-menopausal women with moderate to severe sexual dysfunction associated with the institution of fluoxetine therapy were randomized to augmentation therapy with placebo (N=39), mirtazapine (N=36), yohimbine (N=35) or olanzapine (N=38) for a 6-week period. Outcomes were measured using a daily diary, a biweekly self-report assessment, and a computer assisted structured interview. At baseline, orgasm was most severely impaired. After 6 weeks, there was statistically significant improvement on most measures for the overall group of patients, however there were few differences between treatment groups. Isolated treatment differences were observed for the patient self-report of overall sexual function (olanzapine superior to placebo) and the structured interview sexual satisfaction item (mirtazapine inferior to placebo). No drug assessed was consistently associated with differences from placebo. The results of the study do not support uncontrolled reports of efficacy for these agents in premenopausal women.",2002.0,0,0
287,11890188,"Time to study discontinuation, relapse, and compliance with atypical or conventional antipsychotics in schizophrenia and related disorders.",I D Glick; P H Berg,"To more clearly clarify the efficacy of the atypical antipsychotics compared to conventional antipsychotics, we add data on the outcome of patients diagnosed with schizophrenia from two large, international clinical trials comparing olanzapine with haloperidol (n = 1996) and olanzapine with risperidone (n = 339). Both studies comprised double-blinded, placebo controlled, random assignment trials. Health outcomes reported include: (i) time to discontinuation in the trial; (ii) clinical relapse; and (iii) time to drug non-compliance. When outcome was measured as time to discontinuation due to adverse events or lack of efficacy, olanzapine showed superiority over haloperidol and no difference compared to risperidone. Of those patients who had an initial response, there was no significant difference between olanzapine and haloperidol when outcome was measured using either: (i) 52-week relapse rates or (ii) time to first non-compliance. Using the measures of study discontinuation, relapse and non-compliance, in one trial the atypical antipsychotic olanzapine was superior to haloperidol, while in a second trial there were no differences between olanzapine and risperidone.",2002.0,0,0
288,11895270,Alpha2-adrenergic agonists in opioid withdrawal.,Linda R Gowing; Michael Farrell; Robert L Ali; Jason M White,"This paper presents the main findings of a systematic (Cochrane) review of the effectiveness of alpha2-adrenergic agonists in managing opioid withdrawal. The original systematic review included controlled trials that compared alpha2-adrenergic agonists with another form of treatment (or placebo) in participants who were primarily opioid-dependent. Ten studies compared a treatment regime based on an alpha2-adrenergic agonist with one based on reducing doses of methadone. Withdrawal intensity is similar to, or marginally greater with alpha2-adrenergic agonists, but signs and symptoms of withdrawal occur and resolve earlier in treatment. Participants stay in treatment longer with methadone. The likelihood of completing withdrawal is similar, or slightly less, with clonidine or lofexidine. Clonidine is associated with more adverse effects than reducing doses of methadone. Three studies compared the alpha2-adrenergic agonists, clonidine and lofexidine. Lofexidine does not reduce blood pressure to the same extent as clonidine, but is otherwise similar to clonidine. Participants stay in treatment longer with methadone regimes, which may provide greater opportunity for psychosocial intervention. Methadone regimes may be preferable for withdrawal in outpatient settings where the risk of relapse to heroin use is high. The use of methadone may also facilitate transfer to maintenance treatment should completion of withdrawal become unlikely. For those who are well prepared for withdrawal and seeking earlier resolution of withdrawal symptoms, alpha2-adrenergic agonist treatment may be preferred. Clonidine and lofexidine appear equally effective for inpatient settings, but the lower incidence of hypotension makes lofexidine more suited to use in outpatient settings.",2002.0,0,0
289,11901288,A comparison of the short-term hypotensive effects and side effects of unilateral brimonidine and apraclonidine in patients with elevated intraocular pressure.,Nurşen Yüksel; Levent Karabaş; Ozgül Altintaş; Yusuf Yildirim; Yusuf Cağlar,"To compare the short-term ocular hypotensive efficacy and side effects of 0.2% brimonidine and 0.5% apraclonidine in patients with elevated intraocular pressure (IOP). We performed a double-masked, placebo-controlled study to compare the efficacy of the application of 0.2% brimonidine and 0.5% apraclonidine for the effect of IOP, systemic blood pressure and heart rate in 20 newly diagnosed ocular hypertensive patients. Effects on the untreated fellow eye and ocular side effects were also determined. All measurements were performed 1, 2, 4, 6 and 8 h after the instillation of one drop. Brimonidine and apraclonidine significantly reduced IOP from baseline at all observation times. No significant difference was observed between the treatment groups. IOP decreased significantly in the untreated fellow eye in the brimonidine group at 4-, 6- and 8-hour checks and at 6-hour checks in the apraclonidine group when compared with placebo. Blood pressure and heart rate decreased significantly in the brimonidine group compared with placebo. Apraclonidine did not affect blood pressure or heart rate any differently than placebo. The pupil diameter and the interpalpebral fissure width significantly increased in the apraclonidine group, but not in the brimonidine group. There were no significant differences in the overall incidence of foreign body sensation, burning and stinging and dry mouth in the treatment groups. In the short-term, brimonidine was effective in reducing IOP in patients with elevated IOP and was equivalent in efficacy to apraclonidine. On the other hand, a significant change in blood pressure and heart rate was observed with brimonidine; there was no change at all in the apraclonidine group.",2002.0,0,0
290,11904128,A double blind placebo controlled trial of donepezil adjunctive treatment to risperidone for the cognitive impairment of schizophrenia.,Joseph I Friedman; David N Adler; Evelyn Howanitz; Philip D Harvey; Grant Brenner; Humberto Temporini; Leonard White; Michael Parrella; Kenneth L Davis,"Despite the beneficial effects of atypical antipsychotics on cognition, these improvements will not return most schizophrenic patients to normative standards of cognitive functioning. Therefore, other treatments need to be considered. Subtle changes in cholinergic function in schizophrenic patients provide the rationale to test the effectiveness of cholinesterase inhibitors in treating cognitive impairment in schizophrenia. Given this, a 12-week, double-blind, placebo-controlled trial of donepezil (5 mg and 10 mg) as adjunctive treatment to risperidone was conducted in a total of 36 schizophrenic patients. Neither the 5-mg nor 10-mg dose of donepezil produced significant improvements in any cognitive measure compared with placebo. It is possible that nicotinic receptor desensitization produced by chronic tobacco use in these patients rendered their nicotinic receptors refractory to the effects of increased agonist activity produced by donepezil. An alternative treatment is the allosterically potentiating ligands, which enhance the activity of (sensitize) nicotinic receptors in the presence of acetylcholine.",2002.0,0,0
291,11910256,"The safety and pharmacokinetics of quetiapine when coadministered with haloperidol, risperidone, or thioridazine.",Steven G Potkin; Per T Thyrum; Gustavo Alva; Rimal Bera; Chiao Yeh; Lisa A Arvanitis,"The effects of haloperidol, risperidone, and thioridazine on the pharmacokinetics and side-effect profile of quetiapine were investigated in 36 patients with schizophrenia, schizoaffective disorder, or bipolar disorder in a single-center, two-period, multiple-dose, open-label, randomized trial. Over a one-to two-week period, quetiapine doses were escalated to 300 mg twice daily (bid). Patients were then treated for at least 7 days at the target quetiapine dose and subsequently entered into the combination therapy period, receiving haloperidol (7.5 mg, bid), risperidone (3 mg, bid), or thioridazine (200 mg, bid) for 8.5 days (after 3 days of dose escalation). Key assessments included the pharmacokinetics of quetiapine at steady state (area under the curve within a dosing interval [AUCtSS], maximum [CmaxSS], and minimum [CminSS] observed plasma concentrations, and oral clearance [Cl/f]), as well as the UKU Side Effect Rating Scale scores and safety evaluations. Neither risperidone nor haloperidol had significant effects on quetiapine pharmacokinetics. However, thioridazine produced statistically significant changes, decreasing the least squares means values of the AUCtSS, CmaxSS, and CminSS by 40%, 47%, and 31%, respectively, and increasing Cl/f by 68%. Increases in the following adverse events were noted during coadministration: somnolence (risperidone), insomnia and dry mouth (all three coadministered therapies), and dizziness (thioridazine). UKU side effect items that became worse in >or= 25% of patients during each coadministration period included sedation and increased sleep duration. Results of laboratory tests, electrocardiograms, and vital sign measurements revealed few clinically important changes. Clinical stability can be maintained with good tolerability during the transition from quetiapine monotherapy to periods of coadministration with haloperidol, risperidone, or thioridazine. Coadministration of either haloperidol or risperidone did not have any important effects on the steady-state pharmacokinetics of quetiapine. Thioridazine significantly increased the oral clearance of quetiapine. Increased doses of quetiapine may be necessary to control psychotic symptoms when thioridazine is coadministered with quetiapine.",2002.0,0,0
292,11910263,Effect of fluoxetine and imipramine on the pharmacokinetics and tolerability of the antipsychotic quetiapine.,Steven G Potkin; Per T Thyrum; Gustavo Alva; Danilo Carreon; Chiao Yeh; Amir Kalali; Lisa A Arvanitis; Pharmacokinetic Study Group,"The effects of fluoxetine and imipramine on the pharmacokinetics and nonpsychiatric side effect profile of quetiapine fumarate were investigated in 26 patients with schizophrenia, schizoaffective disorder, or bipolar disorder in a multicenter, two-period, multiple-dose, open-label, randomized trial. Over a 1- to 2-week period, patients were titrated to a 300-mg twice-daily dose of quetiapine. Patients treated for at least 7 days at the target dose entered a combination therapy period, receiving fluoxetine (60 mg daily) or imipramine (75 mg twice daily) for 8 days. Key assessments included pharmacokinetic analysis of quetiapine, the Udvalg for kliniske undersøgelser (UKU) Side Effect Rating Scale, and safety evaluations (e.g., adverse events, electrocardiograms, laboratory tests, and vital signs). Fluoxetine increased the quetiapine area under the plasma concentration time curve during a 12-hour interval (+12%), maximum plasma concentration during the dosing interval (C(ss)(max); +26%), and minimum plasma concentration at the end of the dosing interval (+8%), although it decreased oral clearance (-11%). The change in C(ss)(max) was statistically although not clinically significant. Imipramine did not affect the pharmacokinetics of quetiapine. Overall, scores on the UKU Side Effect Rating Scale improved during combination therapy with either agent, and no statistically significant deterioration was observed for any item. For safety assessments, the only clinically remarkable event was an imipramine-associated complete left bundle branch block in one patient. No unexpected side effects were reported. In conclusion, combination therapy with quetiapine and fluoxetine or imipramine had a minimal effect on quetiapine pharmacokinetics and was well tolerated.",2002.0,0,0
293,11910268,The anxiolytic effect of the novel antipsychotic ziprasidone compared with diazepam in subjects anxious before dental surgery.,Keith D Wilner; Richard J Anziano; Arlene C Johnson; Jeffrey J Miceli; James R Fricke; Cynthia K Titus,"The novel atypical antipsychotic ziprasidone has a pharmacologic profile notable for potent agonism of serotonin (5-HT)1A receptors, antagonism at 5-HT1D receptors, and reuptake inhibition of norepinephrine. 5-HT1A receptor agonism, in particular, suggests anxiolytic activity, and ziprasidone has shown preliminary efficacy in treating the symptoms of anxiety associated with psychotic disorders. In this study, the anxiolytic efficacy of ziprasidone was evaluated in nonpsychotic subjects who were anxious before undergoing minor dental surgery. We compared a single oral dose of 20 mg ziprasidone (N = 30) with that of 10 mg diazepam (N = 30) and placebo (N = 30) in a randomized, parallel-group, double-blind study. The peak anxiolytic effect of ziprasidone compared with that of placebo was similar to that of diazepam but had a later onset. At 3 hours postdose, the anxiolytic effect of ziprasidone was significantly greater than that of placebo (p < 0.05) and somewhat greater than that of diazepam. Diazepam showed a significantly greater anxiolytic effect than placebo at 1 hour (p < 0.05) but not at 3 hours. The sedative effect of ziprasidone was never greater than that of placebo, whereas that of diazepam was significantly greater than that of placebo 1 to 1.5 hours postdose. Ziprasidone was generally well tolerated. Only one patient reported treatment-related adverse events (nausea and vomiting) and, unlike diazepam, ziprasidone did not cause reductions in blood pressure. Dystonia, extrapyramidal syndrome, akathisia, and postural hypotension were not seen with ziprasidone. Thus, ziprasidone may possess anxiolytic effects in addition to its antipsychotic properties.",2002.0,0,0
294,11912568,The evolving role of topiramate among other mood stabilizers in the management of bipolar disorder.,K N Chengappa; S Gershon; J Levine,"Topiramate, a structurally novel anticonvulsant, is being evaluated for other neurological conditions such as migraine, neuropathic pain, and essential tremor, and also for psychiatric conditions such as bipolar disorder, bulimia, post-traumatic stress disorder, and schizoaffective disorder, in addition to obesity. This article will focus on the use of topiramate for bipolar disorder. The pharmacological profile of topiramate is compared to other established and putative mood stabilizers, and a rationale for its use in bipolar disorder is presented. Data from open clinical trials of topiramate for depression, mania, and rapid-cycling bipolar disorder are summarized. Preliminary data from one pilot dose-finding, double-blind, random-assignment, placebo-controlled, 3-week parallel group study of two doses of topiramate for acute bipolar I mania is reported. Safety data regarding topiramate was reviewed. Finally, the potential place of this agent in bipolar illness is considered. The pharmacological advantages for topiramate are low protein binding, minimal hepatic metabolism and mainly unchanged renal excretion, a 24-h half-life, and minimal drug interactions. Open clinical studies suggest a 50-65% response for refractory bipolar mania, and a 40-56% response for refractory bipolar depression in mainly add-on treatment. Open clinical studies of topiramate for rapid-cycling subjects and those for comorbid bulimia, substance abuse, post-traumatic stress, migraine, and obesity report effectiveness. The primary efficacy endpoint data (change from baseline Y-MRS total scores) of the placebo-controlled, random assignment parallel group phase II dose-finding study were not statistically significant. However, once the antidepressant-associated manias (28 of the sample, of 97 subjects) were excluded from the controlled study, the post-hoc analyses indicated the higher dose (512 mg/day) topiramate treatment group showed a statistically significant reduction in endpoint Y-MRS change scores as compared to placebo (p < 0.03). Adverse effects of topiramate in bipolar subjects include attention, concentration and memory problems, fatigue, sedation, transient paraesthesias, nausea, and anorexia. Some subjects experience word-finding difficulty. Weight loss may be seen in several topiramate-treated subjects with bipolar disorder. Topiramate appears to show promise as an addition to the agents available to treat bipolar disorder. More definitive controlled data on the efficacy of topiramate in the acute and continuation phases as well as for the prophylaxis either as monotherapy or as combination treatment of bipolar disorder are ongoing, and the results are awaited.",2002.0,0,0
295,11921147,"Reducing the burden of caring for Alzheimer's disease through the amelioration of ""delusions of theft"" by drug therapy.",Kazue Shigenobu; Manabu Ikeda; Ryuji Fukuhara; Naruhiko Maki; Kazuhiko Hokoishi; Akihiko Nebu; Kenjiro Komori; Hirotaka Tanabe,"Delusions of theft (delusions involving the theft of possessions) are one of the most frequent neuropsychiatric manifestations of Alzheimer's disease (AD). The current study investigated the presence and extent of such delusions before and after drug treatment in a group of AD patients, and the consequent effects on the burden of care on caregivers. The study was an open-label cohort design. The delusions studied consisted only of those involving theft of possessions. Sixteen AD patients served as subjects in order to assess the efficacy of Risperidone administration, in the reduction or elimination of these delusions. The caregiver burden was evaluated using the Zarit Caregiver Burden Interview (ZBI) before the administration of Risperidone and 12 weeks after administration, for cases where delusions of theft were eliminated or reduced. The burden of care on caregivers was significantly reduced (p < 0.001) through the elimination or reduction of delusions of theft. Delusions of theft are considered to be a major factor in increasing the burden of care, and the treatment of these, through appropriate drug therapy, is therefore of great importance in the continuation of satisfactory care in the home.",2002.0,0,0
296,11927174,"Comparison of rapidly acting intramuscular olanzapine, lorazepam, and placebo: a double-blind, randomized study in acutely agitated patients with dementia.",Karena M Meehan; Huei Wang; Stacy R David; Jennifer R Nisivoccia; Barry Jones; Charles M Beasley; Peter D Feldman; Jacobo E Mintzer; Louise M Beckett; Alan Breier,"This double-blind study investigated the efficacy and safety of rapid-acting intramuscular olanzapine in treating agitation associated with Alzheimer's disease and/or vascular dementia. At 2 h, olanzapine (5.0 mg, 2.5 mg) and lorazepam (1.0 mg) showed significant improvement over placebo on the PANSS Excited Component (PANSS-EC) and Agitation-Calmness Evaluation Scale (ACES), and both 5.0 mg olanzapine and lorazepam showed superiority to placebo on the Cohen-Mansfield Agitation Inventory. At 24 h, both olanzapine groups maintained superiority over placebo on the PANSS-EC; lorazepam did not. Olanzapine (5.0 mg) and lorazepam improved ACES scores more than placebo. Simpson-Angus and Mini-Mental State Examination scores did not change significantly from baseline. Sedation (ACES > or =8), adverse events, and laboratory analytes were not significantly different from placebo for any treatment. No significant differences among treatment groups were seen in extrapyramidal symptoms or in corrected QT interval at either 2 h or 24 h, and no significant differences among treatment groups were seen in vital signs, including orthostasis. Intramuscular injection of olanzapine may therefore provide substantial benefit in rapidly treating inpatients with acute dementia-related agitation.",2002.0,0,0
297,11936571,Steady-state pharmacokinetics and tolerability of modafinil administered alone or in combination with dextroamphetamine in healthy volunteers.,Edward T Hellriegel; Sanjay Arora; Michael Nelson; Philmore Robertson,"The potential for a drug-drug interaction between modafinil and dextroamphetamine, each at steady state, was investigated in an open-label, randomized, single-period studyin 32 healthy male and female volunteers. All subjects received modafinil orally once daily for 28 days (200 mg on Days 1-7; 400 mg on Days 8-28). On Days 22 to 28, half of the subjects also received dextroamphetamine (20 mg) orally 7 hours after modafinil. Samples for pharmacokinetic (PK) profiling were obtained on Days 21 and 28. The mean changes in PK parameters for modafinil and its two circulating metabolites between the two groups were not statistically significantly different, except Cmax for modafinil acid. Adverse events obtained in the two groups were similar and mild or moderate in nature. The results indicate that administration of low-dose dextroamphetamine in this dosing regimen does not alter the steady-state pharmacokinetics of modafinil. The combination has a similar tolerability profile as modafinil alone.",2002.0,0,0
298,11943529,,,,,0,0
299,11948436,[Augmentation of selective serotonin reuptake inhibitors (SSRI) with atypical antipsychotics in the treatment of depression].,E Weimer; D F Braus; I Cavus; J Thome,"The treatment of severe depression represents a difficult task in the daily psychiatric practice. In certain cases, augmentation therapies in order to improve the efficacy of SSRIs can be useful. Recently, it has become possible to use atypical antipsychotics for SSRI augmentation. This option adds to the existing strategies in the treatment of depression and primary systematic studies show encouraging results. In this review, the possibility of a SSRI augmentation by additionally administering risperidone or olanzapine is critically discussed.",2002.0,0,0
300,11949778,A systematic review of the use of atypical antipsychotics in autism.,L Barnard; A H Young; J Pearson; J Geddes; G O'Brien,"Conventional antipsychotic medication is commonly prescribed to patients with autistic spectrum disorder. However, a high incidence of severe adverse reactions highlights the need to find more favourable treatments. Atypical antipsychotics may combine efficacy in ameliorating some autistic symptoms with a lower incidence of some adverse reactions. This article reviews the use of atypical antipsychotics in autistic disorder, with particular focus on behaviour, cognition and physical well-being. Thirteen studies using risperidone, three using olanzapine, one using clozapine, one using amisulpride and one using quetiapine were identified. Few firm conclusions can be drawn due to the limitations of the studies; however, there is an indication that risperidone may be effective in reducing hyperactivity, aggression and repetitive behaviours, often without inducing severe adverse reactions. Olanzapine and clozapine may also be effective; however, there is little evidence for using amisulpride or quetiapine in this population. Randomized trials are required to clarify the effectiveness of these agents.",2002.0,0,0
301,11958362,Use of olanzapine for elderly patients with psychotic disorders: a review.,S Madhusoodanan; S Sinha; R Brenner; S Gupta; O Bogunovic,"The number of elderly persons with psychosis will increase with the increasing geriatric population. Olanzapine is one of the newer atypical antipsychotics with efficacy for positive and negative symptoms and safer side effect profile compared to conventional antipsychotics. The manuscript describes the pharmacology, efficacy and tolerability studies, adverse effects and dosing considerations in the elderly. Further studies are needed to fully assess the efficacy and safety of olanzapine in the elderly. Current research supports a role for olanzapine in treating elderly patients with schizophrenia, schizoaffective disorder and behavioral and psychological symptoms of dementia.",2002.0,0,0
302,11967475,A review of the pharmacotherapy of adults with attention-deficit/hyperactivity disorder.,Timothy E Wilens; Thomas J Spencer; Joseph Biederman,"Despite the increasing recognition of attention deficit hyperactivity disorder (ADHD) in adults, the use of pharmacotherapeutics remains less established. A systematic review of the literature identified 15 studies (N = 435 subjects) of stimulants, and 22 studies of non-stimulant medications (N = 421 subjects) including antidepressants, antihypertensives, amino acids, and wake-promoting agents for the treatment of ADHD in adults. Studies with stimulants and antidepressants demonstrated significant short-term improvement in ADHD symptoms compared to placebo in adults. Methylphenidate (MPH) and amphetamine had an immediate onset of action whereas the ADHD response to pemoline and antidepressants appeared delayed. The response to amphetamine and MPH appears to be dose-dependent. Controlled data on nicotonic and noradrenergic compounds appear promising. There was considerable variability in diagnostic criteria, dosing parameters, and response rates between the various studies. Under controlled conditions, the aggregate literature shows that the stimulants and noradrenergic antidepressants had a clinically and statistically significant beneficial effect on treating ADHD in adults.",2002.0,0,1
303,11978164,Ziprasidone: the fifth atypical antipsychotic.,Charles F Caley; Chandra K Cooper,"To review the pharmacology, pharmacokinetics, clinical efficacy, and adverse effects of ziprasidone as a treatment for schizophrenia. Information was selected from a MEDLINE search (July 2000-October 2001) of English-language medical literature using ziprasidone as the search term. Manual searches of pertinent journal article references, request for medical information from Pfizer, and access of the Web site of the Food and Drug Administration were also performed. All available published information regarding the pertinent characteristics of ziprasidone were considered for selection. Pharmacology and pharmacokinetic studies were selected to provide a comprehensive description of these characteristics. Clinical investigations were evaluated for design, sample size, diagnosis, duration, and outcome. Data from all investigations were selected by 1 author and reviewed by both authors. Ziprasidone is a benzisothiazolyl piperazine-type atypical antipsychotic that shares the serotonin(2A)/dopamine(2) (5-HT(2A)/D(2)) profile of the available atypical antipsychotics. Ziprasidone has demonstrated in vitro activity as a 5-HT(1A) receptor agonist and as a very weak inhibitor of serotonin and norepinephrine reuptake. These data do not support ziprasidone as being a clinically meaningful inhibitor of serotonin/norepinephrine reuptake. Oral bioavailability of ziprasidone taken with food is approximately 60%, half-life is approximately 6-7 hours, and protein binding is extensive at >99%. Twelve metabolites have been identified, yet only 4 of these are considered to be primary metabolites. Metabolism of ziprasidone by aldehyde oxidase produces its only metabolite with potential pharmacologic activity; CYP3A4 also contributes to the metabolism of ziprasidone. Clinical studies support ziprasidone as efficacious for the treatment of patients with acute exacerbations of schizophrenia or schizoaffective disorder. Daily doses permitted in these clinical trials ranged from 40 to 160 mg, but only doses between 120 and 160 mg/d have been superior to placebo. Future research efforts should be directed toward refractory schizophrenia, cognitive impairment in schizophrenia, affective and anxiety symptoms associated with schizoaffective disorder, and bipolar disorder. Adverse effect characteristics of ziprasidone commonly include headache, nausea, and somnolence; infrequent effects include extrapyramidal symptoms and weight gain. Ziprasidone has been reported to cause an average QTc prolongation of approximately 20 msec; there have only been 2 patients (0.06%) reported by the manufacturer to have a measured QTc interval >500 msec. Ziprasidone is a safe and efficacious atypical antipsychotic for the acute management of schizophrenia. Efficacy data and most safety data for ziprasidone support its use as a first-line treatment for schizophrenia; however, its potential effects on ventricular repolarization relegate it to second-line status in patients with comorbid cardiovascular risks.",2002.0,0,0
304,11982448,"A double-blind, placebo-controlled dose-response comparison of intramuscular olanzapine and haloperidol in the treatment of acute agitation in schizophrenia.",Alan Breier; Karena Meehan; Martin Birkett; Stacy David; Iris Ferchland; Virginia Sutton; Cindy C Taylor; Rebecca Palmer; Martin Dossenbach; Geri Kiesler; Shlomo Brook; Padraig Wright,"An intramuscular (IM) formulation of olanzapine has been developed because there are no rapid-acting IM atypical antipsychotic drugs currently available in the United States for treating acute agitation in patients with schizophrenia. Recently hospitalized acutely agitated patients with schizophrenia (N = 270) were randomized to receive 1 to 3 IM injections of olanzapine (2.5, 5.0, 7.5, or 10.0 mg), haloperidol (7.5 mg), or placebo within 24 hours. A dose-response relationship for IM olanzapine in the reduction of agitation was assessed by measuring the reduction in Positive and Negative Syndrome Scale Excited Component (PANSS-EC) scores 2 hours after the first injection. Safety was assessed by recording adverse events and with extrapyramidal symptom scales and electrocardiograms at 24 hours after the first injection. Olanzapine exhibited a dose-response relationship for reduction in agitation (F(1,179)= 14.4; P<.001). Mean PANSS-EC reductions 2 hours after the first injection of olanzapine (2.5 mg = -5.5; 5.0 mg = -8.1; 7.5 mg = -8.7; 10.0 mg = -9.4) were superior to those with placebo (-2.9; P =.01 vs olanzapine at 2.5 mg; P<.001 for each other olanzapine dose) but not with haloperidol (-7.5). A dose of 5.0, 7.5, or 10.0 mg of olanzapine caused a greater reduction in agitation than placebo 30 minutes after the first injection. There were no differences between treatment groups for hypotension, the most frequently reported adverse event, or for clinically relevant changes in the QTc interval. There was a greater incidence of treatment-emergent parkinsonism during treatment with IM haloperidol (16.7%) than with 2.5 (P =.03), 5.0 (P =.03), or 7.5 mg (P =.01) of IM olanzapine (0%) or with placebo (0%) (P =.01). Intramuscular olanzapine at a dose of 2.5 to 10.0 mg per injection exhibits a dose-response relationship in the rapid treatment of acute agitation in patients with schizophrenia and demonstrates a favorable safety profile.",2002.0,0,0
305,11983189,Continuation phase treatment with bupropion SR effectively decreases the risk for relapse of depression.,Karen L Weihs; Trisha L Houser; Sharyn R Batey; John A Ascher; Carolyn Bolden-Watson; Rafe M J Donahue; Alan Metz,"This was the first controlled continuation phase study (up to 1-year total treatment) to evaluate the safety and efficacy of bupropion SR for decreasing the risk for relapse of depression in patients who responded to bupropion SR. Patients with recurrent major depression were treated with bupropion SR 300 mg/day during an 8-week open-label phase. Responders (based on Clinical Global Impressions Scale for Improvement of Illness scores) entered a randomized, double-blind phase where they received bupropion SR 300 mg/day or placebo for up to 44 weeks. After randomization, relapse was defined as the point at which the investigator intervened by withdrawing the patient from the study to treat depression. Four hundred twenty-three patients were randomized. A statistically significant difference in favor of bupropion SR over placebo was seen in the time to treatment intervention for depression when survival curves were compared (log-rank test, p =.003). Statistically significant separation between bupropion SR and placebo began at double-blind week 12 (p <.05). Adverse events in bupropion SR-treated patients accounted for 9% and 4% of discontinuations from the open-label and double-blind phases, respectively. Bupropion SR was shown to be effective and well tolerated in decreasing the risk for relapse of depression for up to 44 weeks.",2002.0,0,0
306,11994888,"A pilot, randomized, open-label trial assessing safety and pharmakokinetic parameters of co-administration of rivastigmine with risperidone in dementia patients with behavioral disturbances.",Mark Weiser; Heschi H Rotmensch; Amos D Korczyn; Richard Hartman; Ana Cicin-Sain; Ravi Anand; Rivastigmine-Risperidone Study Group,"The majority of patients with Alzheimer's disease (AD) or vascular dementia display, in addition to cognitive impairment, various degrees of behavioral disturbances. As the use of cholinesterase inhibitors for the treatment of cognitive impairment in dementia becomes widespread, many of these patients will be treated concomitantly with cholinesterase inhibitors and with anti-psychotic drugs to ameliorate behavioral disturbances. Despite the widespread use of this combination in clinical practice, the safety and tolerability of such combination therapy has not been evaluated in controlled clinical trials. This pilot study examined the effects of addition of risperidone 0.5-2 mg/day to patients on rivastigmine 3-12 mg/day, and vice versa. 65 patients suffering from AD, 10 from vascular dementia, and 15 from both were randomized to open label rivastigmine and risperidone, alone or in combination, for 20 weeks. Adverse events caused by co-administration were assessed. No clinically relevant adverse interactions were observed. These preliminary results indicate that rivastigmine and risperidone can be safely co-administered. Confirmation of these results in large clinical trials studies is warranted.",2002.0,0,0
307,12000209,Phenylpropanolamine appears not to promote weight loss in patients with schizophrenia who have gained weight during clozapine treatment.,Mary C Borovicka; Matthew A Fuller; P Eric Konicki; John C White; Vickie M Steele; George E Jaskiw,"Weight gain is a common side effect of clozapine treatment and may expose patients to obesity-associated health risks. We proposed that concomitant treatment with an appetite suppressant such as phenylpropanolamine (PPA) would lead to a decrease in appetite and therefore loss of weight. This was a 12-week, double-blind, randomized, placebo-controlled trial of PPA, 75 mg/day, in outpatients with treatment-refractory schizophrenia (DSM-IV) who were stable on clozapine treatment for at least 4 months and had gained > 10% of their baseline body weight since starting clozapine. Patients were evaluated for adverse effects and weighed weekly. A Positive and Negative Syndrome Scale (PANSS) assessment, a short dietary quiz, and blood indices were completed monthly. Sixteen patients were equally randomly assigned to receive PPA or placebo. The groups did not differ in mean age, baseline weight, dose of clozapine, baseline PANSS scores, or the percent of weight gained since the start of clozapine. There was no significant effect of treatment on weight (t = 0.219, df = 10, p = .831). There was no significant change in either the total PANSS scores (t = -0.755, df = 10, p = .468), the positive or negative symptom cluster scores, or any of the remaining variables. Phenylpropanolamine 75 mg/day was well tolerated but was not effective in reversing established weight gain associated with clozapine treatment in stable outpatients with schizophrenia.",2002.0,0,0
308,12005317,Treatment of ADHD in neurofibromatosis type 1.,Victor-F Mautner; Lan Kluwe; Sarang D Thakker; Robert A Leark,"Forty-six of 93 children with neurofibromatosis type 1 (NF1) were found to satisfy the diagnostic criteria for attention-deficit-hyperactivity disorder (ADHD). Detailed comparisons were made among 20 children with NF1 and ADHD (12 males, 8 females; mean age 10.7 years, SD 2.2), 26 control children with NF1 (15 males, 11 females; mean age 11.3 years, SD 2.3), 14 control children with ADHD (7 males; mean age 9.9 years, SD 1.9), and 14 normally developing control children (7 males; mean age 11.2 years, SD 2.8). Children with NF1 and ADHD had the lowest IQ scores among the four groups. Test of Variables of Attention (TOVA) scores were poorer in the NF1-ADHD and ADHD control groups than in the two non-ADHD groups. Those with NF1 and ADHD were rated significantly poorer on the Child Behavior Checklist (CBCL) than were the NF1 control group. By administrating low doses (5 to 15 mg) of methylphenidate to the NF1-ADHD group, significantly improved TOVA scores were obtained. One-year follow-up yielded significantly improved CBCL scores. Our results show a high incidence of ADHD in NF1 and support an association between ADHD and learning and social problems in children with NF1. It was demonstrated that stimulant medication can lead to improvement in cognitive, academic, and social problems of children with NF1 and ADHD.",2002.0,0,0
309,12006893,Antipsychotic-induced weight gain and therapeutic response: a differential association.,Pál Czobor; Jan Volavka; Brian Sheitman; Jean-Pierre Lindenmayer; Leslie Citrome; Joseph McEvoy; Thomas B Cooper; Miranda Chakos; Jeffrey A Lieberman,"This study investigated the association between antipsychotic-induced weight gain and therapeutic response to haloperidol and three commonly used atypical neuroleptic medications in schizophrenia and schizoaffective disorder. The subjects were 151 patients enrolled in a double-blind experiment with a duration of 14 weeks comparing the therapeutic efficacy of haloperidol (n = 36), clozapine (n = 38), olanzapine (n = 38), and risperidone (n = 39). Absolute and relative (%) gain in body weight and body mass index (BMI) was determined for the entire duration of the double-blind treatment period; therapeutic response was assessed by the total score and the individual subscales of the Positive and Negative Symptom Scale. Compared with the pretreatment baseline, results indicated that for olanzapine and clozapine, therapeutic response was closely related to an absolute and relative gain in weight and to a gain in BMI. No association between weight gain and therapeutic response was found for risperidone and haloperidol. These findings suggest that patients who are likely to have the maximal benefits of olanzapine or clozapine treatment for symptom alleviation are at the highest risk of a clinically significant increase in weight gain.",2002.0,0,0
310,12006897,Anxiety and depression symptoms and response to methylphenidate in children with attention-deficit hyperactivity disorder and tic disorder.,Kenneth D Gadow; Edith E Nolan; Jeffrey Sverd; Joyce Sprafkin; Joseph Schwartz,"This study examined response to methylphenidate in children with attention-deficit/hyperactivity disorder (ADHD) and chronic multiple tic disorder. The primary goal was to determine if children with anxiety or depression symptoms showed a less favorable response to treatment. Subjects were 38 prepubertal children who participated in an 8-week, double-blind, placebo-controlled, methylphenidate crossover evaluation. Treatment effects were assessed with direct observations of child behavior in public school and clinic settings; rating scales completed by parents, teachers, and clinicians; and laboratory analogue tasks. There was little evidence (group data) that children with anxiety or depression symptoms responded in a clinically different manner to methylphenidate than youngsters who did not exhibit these symptoms, particularly in school observations of the core features of ADHD. Seeming differences between children with and without comorbid anxiety or depression symptoms and drug response are likely explained by differences in pretreatment levels of negativistic behaviors (i.e., symptoms of oppositional defiant disorder or conduct disorder). Methylphenidate appears to be effective for the management of ADHD behaviors in children with mild to moderate anxiety or depression symptoms; nevertheless, much research remains to be performed in this area.",2002.0,0,1
311,12007591,Sex differences in clinical response to olanzapine compared with haloperidol.,Jill M Goldstein; Lee S Cohen; Nicholas J Horton; Hang Lee; Scott Andersen; Mauricio Tohen; Ann- Marie K Crawford; Gary Tollefson,"There is current disagreement over whether men and women respond differently to typical or atypical antipsychotic medications. This study reanalyzed a large international clinical trial of olanzapine (Olz) compared with haloperidol (Hal) to test for sex differences in treatment response, controlling for illness chronicity and menopausal status. We hypothesized that women would show a greater response to either medication than men, particularly among first admission, premenopausal women. DSM-III-R schizophrenia inpatients (700 women and 1295 men) were randomly assigned to a 6-week trial of Olz vs. Hal. Longitudinal random effect models were used to test for interactions of sex with medication, chronicity and menopausal status on treatment response. Findings showed that women on olanzapine had a greater drop in overall symptomatology by week 4 than any other group, and their level of symptomatology remained lower throughout the 6-week trial. The sex differences in treatment response in olanzapine compared with haloperidol were, in part, dependent on chronicity and, in women, menopausal status. That is, first episode women on haloperidol exhibited an increase in symptomatology over the 6-week trial compared to their male counterparts, while multiply hospitalized women had a better treatment response on haloperidol than their male counterparts. Women on olanzapine had a significantly better treatment response than men, regardless of chronicity. Finally, premenopausal women had a significantly better treatment response than postmenopausal women, regardless of treatment and chronicity.",2002.0,0,0
312,12017410,Effect on body weight of bupropion sustained-release in patients with major depression treated for 52 weeks.,Harry Croft; Trisha L Houser; Brenda D Jamerson; Robert Leadbetter; Carolyn Bolden-Watson; Rafe Donahue; Alan Metz,"Short-term studies have demonstrated a modest weight-reducing to weight-neutral effect among patients receiving bupropion sustained-release (SR) for the treatment of depression. This study was conducted to evaluate the long-term effects of bupropion SR on body weight in patients with depression. This analysis was conducted within a long-term relapse-prevention study in patients with major depression. Those whose depression had responded to open-label treatment with bupropion SR were randomized to 44 weeks of double-blind treatment with bupropion SR 300 mg/d or placebo. Patients were categorized by body mass index (BMI) as follows: BMI < 22, BMI 22 to 26, BMI > or = 27, and BMI > or = 30. Four hundred twenty-three patients were enrolled in the double-blind phase of the study, 210 receiving bupropion SR and 213 receiving placebo. At the end of the open-label phase, the following mean weight losses were seen in the 4 BMI groups: BMI < 22, 0.5 kg; BMI 22 to 26, 1.1 kg; and BMI > or = 27 and BMI > or = 30, 1.8 kg each. At the end of double-blind treatment, mean change-from-baseline weights were as follows: BMI < 22, -0.1 kg; BMI 22 to 26, -0.6 kg; BMI > or = 27, -1.4 kg; and BMI > or = 30, -2.4 kg. The rate of change in body weight during the double-blind phase was statistically significant compared with baseline BMI (P < 0.001, analysis of covariance). Modest mean weight losses that increased with increasing baseline body weight were observed with long-term bupropion SR treatment. The findings of this analysis suggest that bupropion SR may be an appropriate therapeutic option in normal-weight or overweight patients with depression who are concerned about weight gain.",2002.0,0,0
313,12019665,Effects of olanzapine on prolactin levels of female patients with schizophrenia treated with risperidone.,Kwang-Soo Kim; Chi-Un Pae; Jeong-Ho Chae; Won-Myong Bahk; Tae-Youn Jun; Dai-Jin Kim; Ruth A Dickson,"This study was conducted to prospectively examine the effect of switching from risperidone to olanzapine on female schizophrenia patients who experienced menstrual disturbances, galactorrhea, and/or sexual dysfunction. Twenty female patients with DSM-IV schizophrenia who were taking risperidone and were suffering from menstrual disturbances, galactorrhea, and/or sexual dysfunction were enrolled. Patients were switched from risperidone to olanzapine over a 2-week period, then treated with olanzapine for 8 additional weeks. The serum prolactin concentrations were examined every 2 weeks. The Positive and Negative Syndrome Scale (PANSS), Abnormal Involuntary Movement Scale (AIMS), Simpson-Angus Scale for Extrapyramidal Symptoms (SAS), and questions from the Dickson-Glazer Sexual Functioning Scale were administered to evaluate efficacy, extrapyramidal side effects, and sexual and reproductive functioning at baseline and the endpoint of 10 weeks. Serum prolactin levels decreased significantly (p < .01) following the switch from risperidone to olanzapine. Scores of PANSS, AIMS, and SAS at the endpoint were also significantly decreased (p < .01) compared to those of baseline. Patients experienced improvements in menstrual functioning and perceptions of sexual side effects. Olanzapine reversed hyperprolactinemia in risperidone-treated female schizophrenic patients. This was associated with a decrease in amenorrhea, improved cycle regularity, and a decrease in sexual side effects that the women attributed to antipsychotic medication. This study suggests that switching to olanzapine is a safe and effective alternative method for patients with antipsychotic-induced hyperprolactinemia associated sexual and/or reproductive dysfunction. Long-term follow-up studies are warranted, with particular attention to the course of sexual and reproductive dysfunction.",2002.0,0,0
314,12019667,Clinical predictors of response to clozapine treatment in ambulatory patients with schizophrenia.,Daniel S Umbricht; William C Wirshing; Donna A Wirshing; Marjorie McMeniman; Nina R Schooler; Stephen R Marder; John M Kane,"Despite the advent of new atypical antipsychotics, clozapine remains an important option in the treatment of patients with poor response to conventional antipsychotics. Clinicians would be well served if clinical characteristics could be identified that predict a favorable response to clozapine. A few studies addressing this issue have reported inconsistent results. The association of clinical characteristics with a sustained response was investigated in 37 partially treatment-refractory outpatients with a DSM-III-R diagnosis of chronic schizophrenia who had been assigned to clozapine treatment in a double-blind, haloperidol-controlled, long-term (29-week) study of clozapine. Response was defined as a 20% decrease of the Brief Psychiatric Rating Scale (BPRS) psychosis factor score sustained over 2 consecutive ratings. Differences between responders and nonresponders with regard to selected baseline variables were analyzed with t tests and chi2 tests. In addition, Cox regression analyses were performed to identify variables that best predicted a response to clozapine treatment. Clozapine responders were rated as less severely ill, showed a lesser degree of negative symptoms, and demonstrated fewer extrapyramidal side effects at baseline as compared with nonresponders. In addition, higher BPRS total scores--after controlling for the effects of the other variables--were associated with a response. In a cohort of partially treatment-refractory outpatients, a favorable response to clozapine was associated with characteristics describing less severely ill patients. The history of patients did not affect their response to clozapine.",2002.0,0,0
315,12019668,"A retrospective comparison of weight, lipid, and glucose changes between risperidone- and olanzapine-treated inpatients: metabolic outcomes after 1 year.",Jonathan M Meyer,"Metabolic side effects have been increasingly noted during therapy with novel antipsychotics, but there is a dearth of comprehensive comparative data in this area. The goal of this retrospective study was to examine the changes in weight parameters, fasting glucose, and fasting lipids in long-term inpatients treated with either risperidone or olanzapine. A retrospective study was performed by reviewing charts of patients at Oregon State Hospital, Salem, who were treated during July and August 1999, comparing metabolic outcomes during the first year of therapy with either risperidone or olanzapine. Data were analyzed also by age, sex, and concurrent use of lithium or valproate. Included for analysis were patients at least 18 years old with baseline weights obtained within 3 weeks of drug initiation, and baseline fasting triglycerides, cholesterol, and glucose obtained within 3 months prior to drug initiation and at 1 year of treatment (+/- 4 weeks). The patients meeting these criteria in each drug cohort (risperidone, N = 47; olanzapine, N = 47) included 1 patient with diagnosed diabetes mellitus prior to onset of treatment. Among those patients under 60 years old, olanzapine patients (N = 37) experienced significantly greater increases at 1 year in all metabolic parameters than the risperidone group (N = 39), except for weight variables: triglycerides +104.8 mg/dL (olanzapine) versus +31.7 mg/dL (risperidone) (p = .037); cholesterol +30.7 mg/dL (olanzapine) versus +7.2 mg/dL (risperidone) (p = .004); glucose +10.8 mg/dL (olanzapine) versus +0.74 mg/dL (risperidone) (p = .030). Patients under 60 years of age with concurrent use of lithium or valproate were associated with greater weight gain in both drug groups, but this difference was statistically significant only for the olanzapine cohort. Neither weight change nor use of lithium or valproate was associated with increases in glucose or lipids among those under 60 years old for either drug. Olanzapine therapy is associated with significantly greater increases in fasting glucose and lipid levels for nongeriatric adult patients than risperidone, and the increases are not correlated with changes in weight parameters. Appropriate monitoring of fasting glucose and serum lipid levels should be considered during extended treatment with atypical antipsychotics.",2002.0,0,0
316,12020058,Nicotine dependence: the role for antidepressants and anxiolytics.,Maria A Sullivan; Lirio S Covey,"The addictive nature of cigarette smoking has been appreciated only in the past two decades. Prior to the publication of DSM-III in 1980, excessive tobacco use had not been considered as a psychiatric problem requiring treatment [1]. Smoking has been recognized as a serious medical problem since thefirst Surgeon General's Report on Smoking and Health in 1964. An important development during the 10 to 20 years following this report was the growth of knowledge regarding the physiological effects of regular tobacco use and the importance of nicotine as the main pharmacological ingredient in tobacco. This body of information culminated in the 1988 Surgeon General's Report, which recognized chronic tobacco use as a form of addictive behavior [2]. Nicotine, like other drugs of abuse, has reinforcing psychoactive effects that lead to its repeated self-administration. Nicotine stimulates the release of several neurotransmitters including dopamine, norepinephrine, acetylcholine, 5-hydroxytryptamine, gamma-aminobutyric acid (GABA) and endorphins [3]. Through its effects on the dopaminergic, or 'reward', system, nicotine exerts psychoactive effects such as an increased sense of enjoyment. The norepinephrinergic effects of nicotine may account for increased attentiveness and improved performance in repetitive tasks, while its anxiolytic effects are likely mediated through GABA and the endorphins.",2002.0,0,0
317,12026370,"Full-day ADHD symptom control that ""lasts from home to homework"".",,,2002.0,0,0
318,12032011,The hypnotic and analgesic effects of oral clonidine during sevoflurane anesthesia in children: a dose-response study.,Shinichi Inomata; Shin-Ichi Kihara; Masayuki Miyabe; Kenji Sumiya; Yasuyuki Baba; Yukinao Kohda; Hidenori Toyooka,"Although clonidine has both hypnotic and analgesic actions, the dose relationship for each actions is still unknown in a clinical setting when clonidine is used as a premedication in children. We studied 80 ASA physical status I children (age range, 3-8 yr). Subjects were randomly divided into two groups (minimum alveolar anesthetic concentration [MAC]-Awake group, n = 40; MAC-Tetanus group, n = 40). Each patient received one dose of clonidine from 1 to 5 microg/kg orally, 100 min before arrival at the operating room. Anesthesia was induced and maintained with sevoflurane in oxygen and air. Before tracheal intubation, end-tidal sevoflurane was decreased stepwise by 0.2% at the start of 1.2%, a verbal command was given to the patients, and MAC-awake was determined in each patient. We also investigated MAC-tetanus, determined with transcutaneous electric tetanic stimulations, after tracheal intubation in each patient by observing the motor response to a transcutaneous electric tetanic stimulus to the ulnar nerve at a sevoflurane concentration decreased stepwise by 0.25% at the start of 2.75%. The initial reduction in MAC-tetanus was not as steep as that in MAC-awake. Clonidine reduced MAC-tetanus by 40% at the maximal dose of 5 microg/kg, whereas MAC-awake was already reduced by 50% at 2 microg/kg. We conclude that separate dose-response relationships for oral clonidine are present regarding the hypnotic and analgesic effects in children undergoing sevoflurane anesthesia. Separate dose-response relationships for oral clonidine were found regarding the hypnotic and analgesic effects in children undergoing sevoflurane anesthesia.",2002.0,0,0
319,12038875,Insomnia in children: when are hypnotics indicated?,Mohammed Younus; Michael J Labellarte,"Insomnia in children is a nonspecific impairing symptom that may be the result of normal developmental changes, psychosocial duress, a sleep disorder, a psychiatric disorder, other medical disorders, substance misuse, or an adverse effect of medication. Careful clinical assessment of insomnia in children may include the use of symptom rating scales, laboratory testing, or other medical assessment. Short- and long-term treatment of insomnia in children involves management of etiological factors and associated syndromes. Controlled treatment studies of pediatric insomnia are limited to <10 published studies of psychosocial and/or psychopharmacological treatment in young children. Directive parent education and behavior modification techniques have been effective in short-term treatment of insomnia in young children, and may be the preferred treatment of extrinsic insomnia, as well as an important adjunctive treatment of any insomnia symptoms. Two benzodiazepines [flurazepam and delorazepam (chlordesmethyldiazepam)], one antihistamine (niaprazine) and one phenothiazine [alimemazine (trimeprazine)] have been shown to be effective in the short-term treatment of insomnia in young children, although none of these agents have US Food and Drug Administration approval for pediatric insomnia. Short-acting benzodiazepines may have a role in the brief treatment of pediatric insomnia associated with an anxiety or mood disorder, psychosis, aggression, medication- induced activation, or anticipatory anxiety associated with a medical procedure. However, tachyphylaxis and risk of misuse preclude the long-term use of benzodiazepines for the treatment of insomnia in children. Newer hypnotics, which appear better tolerated than the benzodiazepines in studies of adults, may have a role when combined with psychosocial treatments of pediatric insomnia. Treatment of intrinsic pediatric insomnia may additionally involve chronotherapy or medical management.",2002.0,0,0
320,12042193,Beneficial antipsychotic effects of celecoxib add-on therapy compared to risperidone alone in schizophrenia.,Norbert Müller; Michael Riedel; Constanze Scheppach; Bernd Brandstätter; Safet Sokullu; Karin Krampe; Markus Ulmschneider; Rolf R Engel; Hans-Jürgen Möller; Markus J Schwarz,"Abnormalities in the immune system in schizophrenia have been described. However, important findings such as high levels of activating cytokines in the CSF and signs of CNS inflammation have been controversial. The authors conducted a trial of the new selective cyclooxygenase-2 inhibitor celecoxib, an immunomodulatory drug, in schizophrenic patients to evaluate its therapeutic effects. In a prospective, double-blind evaluation, 50 patients with an acute exacerbation of schizophrenia were randomly assigned to either risperidone plus celecoxib or risperidone plus placebo. After a washout period, 25 patients received 2-6 mg/day of risperidone plus placebo and 25 received risperidone plus 400 mg/day of celecoxib for 5 weeks. The treatment effect was calculated by analysis of covariance. There were no significant differences between groups in age, sex, duration or severity of disease or psychopathology, or risperidone dose or plasma level. Over 5 weeks, both groups of patients showed significant improvement in scores on the Positive and Negative Syndrome Scale and on all subscales. However, the celecoxib group showed significantly greater improvement in the total score. Additional treatment with celecoxib has significant positive effects on the therapeutic action of risperidone with regard to total schizophrenia psychopathology. Moreover, the fact that treatment with an immunomodulatory drug showed beneficial effects on schizophrenia symptoms indicates that immune dysfunction in schizophrenia is not just an epiphenomenon but is related to the pathomechanism of the disorder. However, a nonimmunological therapeutic effect of celecoxib mediated by the N-methyl-D-aspartic acid receptor has to be taken into account.",2002.0,0,0
321,12042201,"Olanzapine-induced weight gain in patients with first-episode schizophrenia: a double-blind, placebo-controlled study of fluoxetine addition.",Michael Poyurovsky; Artashes Pashinian; Irit Gil-Ad; Rachel Maayan; Michael Schneidman; Camil Fuchs; Abraham Weizman,"Since olanzapine-induced weight gain may be attributable to the antagonistic activity of olanzapine at the serotonin-2C receptor, the authors hypothesized that it might be attenuated by addition of the selective serotonin reuptake inhibitor fluoxetine. First-episode hospitalized schizophrenia patients (N=30) were randomly assigned in an 8-week double-blind study of olanzapine, 10 mg/day, coadministered with either fluoxetine, 20 mg/day (N=15), or placebo (N=15). The group receiving olanzapine plus fluoxetine showed significantly less improvement in positive and disorganized symptom dimensions than the group receiving olanzapine plus placebo. The two groups demonstrated similar and substantial gradual weight gains. These results suggest that fluoxetine coadministration is clinically ineffective and cannot attenuate olanzapine-induced weight gain.",2002.0,0,0
322,12045315,Efficacy of olanzapine and risperidone for treatment-refractory schizophrenia among long-stay state hospital patients.,Hassan S Dinakar; Robert N Sobel; James H Bopp; Anita Daniels; Sondra Mauro,"The authors studied the efficacy of olanzapine and risperidone among patients with treatment-refractory schizophrenia who had been hospitalized for more than five years and who were not suitable candidates for a clozapine trial. The patients were systematically reassessed and were given olanzapine or risperidone as part of a ""second-chance program."" The patients in both groups showed significant improvement in scores on the 18-item Brief Psychiatric Rating Scale after three months. Forty-four percent of the patients in the olanzapine group and 43 percent of those in the risperidone group were discharged to supervised residences on the basis of their clinical improvement. There is value in reassessing long-stay patients who have treatment-refractory schizophrenia and giving them systematic trials with new medications that become available.",2002.0,0,0
323,12045757,Attention-Deficit/Hyperactivity Disorder and methylphenidate: a dose-response analysis and parent-child comparison of somatic complaints.,Mark D Rapport; Robert Randall; Catherine Moffitt,"The authors examined parent and child ratings of somatic complaints in 65 children with Attention-Deficit/Hyperactivity Disorder (ADHD) who received four doses (5 mg, 10 mg, 15 mg, 20 mg) of methylphenidate (MPH) in the context of a double-blind, placebo controlled, within-subject (crossover) experimental design. Results indicated that parent and child ratings of somatic complaints decreased in a linear fashion from baseline levels as a function of increasing MPH dose and showed minimal variation across MPH conditions. Statistical comparisons of specific somatic complaints indicated minimal agreement between parents and children in contrast to the nearly identical parent-child dose-response curves. The paradoxical findings of fewer somatic complaints associated with MPH, importance of obtaining children's perceptions of MPH treatment, and implications for measuring somatic complaints are discussed.",2002.0,0,1
324,12046640,Improving outcome in schizophrenia: the potential importance of EPS and neuroleptic dysphoria.,Jes Gerlach,"Despite half a century of antipsychotic drug treatment, the outcome of therapy in schizophrenia remains disappointing. Relapse, rehospitalization, limited fulfilment of social roles, and suicide remain frequent, and the economic costs are high. Current relapse rates may be two to three times higher than those that could be achieved with optimal use of therapy. Poor compliance with treatment is considered to be a significant preventable cause of poor outcome and is in turn likely to be influenced by the patient's experience of drug treatment. There is some evidence that extrapyramidal symptoms (EPS), particularly akathisia and neuroleptic dysphoria, are associated with poor compliance and poor treatment outcome. Atypical antipsychotics have a lower risk of EPS than do standard antipsychotics. Some (risperidone, olanzapine, and ziprasidone) show evidence of a dose-related increase in EPS, but clozapine and quetiapine have demonstrated a placebo-level incidence of EPS across the dose range. Quetiapine does not require the regular blood monitoring mandated for clozapine, and results from a patient survey indicate a high degree of patient satisfaction with treatment. While further research is needed, it is possible that wider use of medications with low EPS and high patient acceptability could promote better compliance and improve the outcome of schizophrenia treatment.",2002.0,0,0
325,12046641,Phenomenology of and risk factors for new-onset diabetes mellitus and diabetic ketoacidosis associated with atypical antipsychotics: an analysis of 45 published cases.,Hua Jin; Jonathan M Meyer; Dilip V Jeste,"Case reports and small retrospective studies suggest that atypical antipsychotic agents may be associated with new-onset Type II diabetes mellitus (DM) or diabetic ketoacidosis (DKA); however, these reports often provide limited or no information on demographic variables such as age, gender, ethnicity, relationship to weight gain, and time course. We analyzed 45 published cases of new-onset DM or DKA for which followed initiation of atypical antipsychotic treatment. Of the 45 patients, 20 had received clozapine, 19 olanzapine, 3 quetiapine, and 3 risperidone. Eighty-seven percent patients were male, and 47% African American. Forty-two percent of these patients presented as DKA, and 50% manifested no weight gain at time of presentation with DM or DKA, although 84% were overweight before antipsychotic therapy. Eighty-four percent presented within 6 months and 59% within 3 months of commencing atypical antipsychotics. The DKA cohort had significantly younger age, less overweight at baseline, and higher proportion of women than did those with DM alone, without significant differences in distribution of ethnicity, weight gain, family history of DM, or duration of exposure to atypical agents. Clinicians should be aware of the potential risks of new-onset DM and DKA in patients taking atypical antipsychotics, and utilize appropriate clinical and laboratory monitoring to prevent serious adverse events.",2002.0,0,0
326,12047021,Clinical profile of an atypical antipsychotic: risperidone.,John M Davis; Nancy Chen,"Stimulated by Dawkins and colleagues' (1999) and Remington and Kapur's (2000) calls to develop clinical profiles of the new atypical antipsychotic drugs and by Mattes's critiques (1997, 1998), we performed two sets of analyses for risperidone. First, we reanalyzed data from the North American risperidone trial: risperidone was superior to haloperidol to an equal degree in patients with and without the deficit syndrome, in patients with paranoid and nonparanoid schizophrenia, in treatment-resistant and treatment-responsive patients (patients hospitalized for longer and shorter periods), and in patients with or without weight gain. Moreover, risperidone was more effective than haloperidol on symptoms nonresponsive and responsive to haloperidol; its effects on negative symptoms were independent of its effects on extrapyramidal symptoms; and it was effective in treating depression in schizophrenia. Second, we performed a meta-analysis of 18 controlled risperidone trials: risperidone was consistently more effective than conventional antipsychotics in treating positive and negative symptoms.",2002.0,0,0
327,12079730,A placebo controlled trial of bupropion for smoking cessation in schizophrenia.,Tony P George; Jennifer C Vessicchio; Angelo Termine; Thomas A Bregartner; Alan Feingold; Bruce J Rounsaville; Thomas R Kosten,"Schizophrenic patients have high rates of cigarette smoking compared with the general population. We compared sustained-release (SR) bupropion with placebo for smoking cessation in patients with schizophrenic disorders. We also examined how antipsychotic class predicts smoking cessation outcomes with bupropion. Thirty-two subjects meeting DSM-IV criteria for schizophrenia or schizoaffective disorder and nicotine dependence were randomized to bupropion SR (BUP, 300 mg/day) or placebo (PLA). Outcomes included treatment retention, smoking abstinence rates, expired breath carbon monoxide (CO) levels, psychotic symptoms, and medication side effects. Bupropion significantly increased trial endpoint 7-day point prevalence smoking abstinence rates compared with placebo [BUP, 8/16 (50.0%), PLA, 2/16 (12.5%); chi(2) = 5.24, df = 1, p <.05], and reduced CO levels during the trial [Medication x Time interaction; Z = 3.09, p <.01]. Positive schizophrenia symptoms were not altered by BUP, but negative symptoms were significantly reduced. Atypical antipsychotic drug treatment enhanced smoking cessation responses to BUP. Major side effects were dry mouth, gastrointestinal symptoms, headache, and insomnia. Our results suggest that 1) BUP enhances smoking abstinence rates compared with PLA in nicotine-dependent schizophrenic smokers; 2) BUP is well-tolerated and safe for use in these patients; and 3) atypical antipsychotics may enhance smoking cessation outcomes with BUP.",2002.0,0,0
328,12084413,Newer atypical antipsychotic medication in comparison to clozapine: a systematic review of randomized trials.,Arja Tuunainen; Kristian Wahlbeck; Simon Gilbody,"The aim of this study was to evaluate the effectiveness of newer atypical antipsychotic drugs in comparison to clozapine for schizophrenia. Publications in all languages were searched from all relevant databases and all randomized controlled trials comparing clozapine with newer atypical drugs were included. The review and meta-analysis includes eight studies, most of them short in duration. Newer atypical drugs were broadly similar to clozapine when improvement was measured using a psychosis symptom rating scale or a global index. There was a trend for clozapine to be more effective than the others for positive symptoms, and less effective for the negative symptoms. The adverse effect profile of clozapine and newer atypical drugs was dissimilar: while clozapine produced more fatigue, hypersalivation, and orthostatic dizziness, new atypical drugs, with the exception of olanzapine, produced more extrapyramidal symptoms. As these results were obtained from few studies and a relatively small amount of patients, the equal effectiveness and tolerability of new atypical drugs in comparison with clozapine is not yet demonstrated. More trials of sufficient power, with longer duration, and measuring clinically important outcomes are urgently needed.",2002.0,0,0
329,12088164,A 28-week comparison of ziprasidone and haloperidol in outpatients with stable schizophrenia.,Steven R Hirsch; Werner Kissling; Josef Bäuml; Aidan Power; Rory O'Connor,"Ziprasidone is a novel antipsychotic with a unique pharmacologic profile. This study compared ziprasidone with the conventional antipsychotic haloperidol in outpatients with stable schizophrenia. Three hundred one outpatients with stable chronic or subchronic schizophrenia (DSM-III-R) were randomized and participated in this double-blind, multicenter, parallel-group clinical study comparing flexible-dose oral ziprasidone, 80-160 mg/day (N = 148), with haloperidol, 5-15 mg/day (N = 153), over 28 weeks. Patients were assessed using the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions-Severity of Illness scale, the Montgomery-Asberg Depression Rating Scale, the Simpson-Angus Scale, the Barnes Akathisia Scale, and the Abnormal Involuntary Movement Scale. Modal doses at endpoint were 80 mg/day for ziprasidone and 5 mg/day for haloperidol. Improvements in all mean efficacy variables with both ziprasidone and haloperidol were observed. Significantly more patients were categorized as negative symptom responders (> or = 20% reduction in PANSS negative subscale score) in the ziprasidone group (48%) compared with the haloperidol group (33%) (p < .05). Ziprasidone had clear advantages over haloperidol in all evaluations of movement disorders. Changes in body weight were negligible with both treatments. No pattern of laboratory or cardiovascular changes was observed. Ziprasidone and haloperidol were both effective in reducing overall psychopathology; ziprasidone demonstrated effective treatment of negative symptoms and was better tolerated than haloperidol. Ziprasidone appears to offer an effective alternative to haloperidol in the long-term treatment of stable outpatients with schizophrenia.",2002.0,0,0
330,12088306,Children with ADHD and motor dysfunction compared with children with ADHD only.,Raymond C Tervo; Scott Azuma; Bruce Fogas; Helen Fiechtner,"The purpose of this study was to identify group differences in children with attention-deficit-hyperactivity disorder and motor dysfunction (ADHD-MD) and ADHD only, and to evaluate the medication responsiveness of ADHD-MD. Sixty-three children (49 males and 14 females; mean age 9 years 10 months, SD 2 years 10 months) underwent a triple blind, placebo-controlled crossover study evaluating two dose levels of methylphenidate (0.3 mg/kg and 0.5 mg/kg [DOSAGE ERROR CORRECTED], twice daily) and placebo. Forty-nine trials were completed. Nineteen were children with ADHD-MD, 44 had ADHD only. Behavior and functioning were assessed at home and at school. Treatment effects were assessed using the Abbreviated Symptom Questionnaire for Parents and Teachers. Children with ADHD-MD were more likely to have severe ADHD-combined type and other neurodevelopmental and behavioral problems. Both groups of children had a linear dose response to medication (placebo, low, high) and there was no evidence of a group by dose interaction or an overall group effect at home or school. The lack of group effect suggests that these children responded to medication like the other subgroups.",2002.0,0,1
331,12090443,"Prevalence of obesity, lipid and glucose abnormalities in outpatients prescribed clozapine.",P Leonard; A Halley; S Browne,"Individuals with schizophrenia have standardised mortality rates which are double that of the general population. In addition to suicide, high rates of cardiovascular and respiratory disease contribute to this raised mortality rate. Although clozapine has been reported to improve psychotic symptoms and decrease suicide rates, attention has recently focussed on its potential to increase cardiovascular risk factors including obesity, dyslipidemia and diabetes mellitus. This study aimed to ascertain the prevalence of these risk factors in a cohort of Irish outpatients treated with clozapine.",2002.0,0,0
332,12091192,"Combination of a mood stabilizer with risperidone or haloperidol for treatment of acute mania: a double-blind, placebo-controlled comparison of efficacy and safety.",Gary S Sachs; Fred Grossman; S Nassir Ghaemi; Akiko Okamoto; Charles L Bowden,"The study assessed the efficacy and safety of risperidone as an adjunctive agent to mood stabilizers in the treatment of acute mania. This 3-week randomized, double-blind, placebo-controlled study included 156 bipolar disorder patients with a current manic or mixed episode who received a mood stabilizer (lithium or divalproex) and placebo, risperidone, or haloperidol. The primary efficacy measure was the Young Mania Rating Scale. Other assessments used the Brief Psychiatric Rating Scale, the Clinical Global Impression scale, and safety measures. The trial was discontinued by 25 (49%) of the 51 placebo group patients, 18 (35%) of the 52 risperidone group patients, and 28 (53%) of the 53 haloperidol group patients. Mean modal doses were 3.8 mg/day (SD=1.8) of risperidone and 6.2 mg/day (SD=2.9) of haloperidol. Significantly greater reductions in Young Mania Rating Scale scores at endpoint and over time were seen in the risperidone group and in the haloperidol group, compared with the placebo group. Young Mania Rating Scale total scores improved with risperidone and with haloperidol both in patients with psychotic features and in those without psychotic features at baseline. Extrapyramidal Symptom Rating Scale total scores at endpoint were significantly higher in the haloperidol patients than in the placebo patients. Antiparkinsonian medications were received by 8%, 17%, and 38% of patients in the placebo, risperidone, and haloperidol groups, respectively. Risperidone plus a mood stabilizer was more efficacious than a mood stabilizer alone, and as efficacious as haloperidol plus a mood stabilizer, for the rapid control of manic symptoms and was well tolerated.",2002.0,0,0
333,12105117,Cell-mediated immune response in MDMA users after repeated dose administration: studies in controlled versus noncontrolled settings.,R Pacifici; P Zuccaro; M Farré; S Pichini; S Di Carlo; P N Roset; I Palmi; J Ortuño; E Menoyo; J Segura; R de la Torre,"Acute administration of 3,4-methylenedioxymethamphetamine (MDMA, ""ecstasy"") produces time-dependent immune dysfunction in humans. Recreational use of MDMA generally includes repeated drug consumption, often in association with other drugs, such as alcohol and cannabis. In the laboratory setting, repeated MDMA administration to healthy MDMA consumers produced a time-dependent immune dysfunction similar to that observed with the ingestion of a single dose, and the first of the two administrations paralleled the time-course of MDMA-induced cortisol stimulation kinetics and MDMA plasma concentrations. A significant decrease in CD4 T-helper cells with simultaneous increase in natural killer (NK) cell and a decrease in functional responsiveness of lymphocytes to mitogenic stimulation was observed. Response to the second dose was either long-lasting compared with the first dose or disproportionate and did not show any parallelism with cortisol and MDMA plasma concentrations. This circumstance extended the critical period during which immunocompetence is highly impaired as a result of MDMA use. Accumulation of MDMA in the body of a poor metabolizer induced higher immunomodulatory effects with statistically significant differences in NK cell function compared with extensive metabolizers. When basal values of lymphocyte subsets were examined in a population of recreational MDMA users participating in different clinical trials, alterations in several immunological parameters were observed. The absolute number of lymphocytes, in particular T lymphocytes and CD4 T-helper cell subsets, showed a trend toward reduced values, although cell counts were within normal limits. By contrast, NK cells in MDMA consumers were reduced to one-third of those from healthy persons. A statistically significant decrease in affected immune parameters was recorded during a 2-year observation period in a subgroup of recreational MDMA users. These permanent alterations in immunologic homeostasis may result in impairment of general health and subsequent increased susceptibility to infection and immune-related disorders.",2002.0,0,0
334,12135536,Efficacy of Adderall and methylphenidate in attention deficit hyperactivity disorder: a drug-placebo and drug-drug response curve analysis of a naturalistic study.,Stephen V Faraone; Elizabeth J Short; Joseph Biederman; Robert L Findling; Christine Roe; Michael J Manos,"Stimulant medication has, for many years, been the pharmacological treatment of choice for children and adults with attention deficit hyperactivity disorder (ADHD). Recently, several studies have documented the efficacy of a new stimulant, Adderall. Although these initial studies provide useful information for clinicians treating ADHD children, their method of data presentation has provided limited information about the clinical significance of drug effects. Thus, to address the issue of clinical significance, we completed drug-placebo response curve analyses of a blinded, placebo-controlled study of Adderall and methylphenidate (MPH). Our results show that the efficacy of Adderall and MPH to improve functioning is seen throughout the full range of improvement scores. Both drugs prevent worsening and, for a majority of patients, lead to improvements that are well into the normal range. The analyses also highlight an important subgroup of placebo responders, which suggests that future research should focus on how to predict robust placebo response in ADHD patients.",2003.0,1,1
335,12139535,Postoperative pain relief following intrathecal bupivacaine combined with intrathecal or oral clonidine.,I Dobrydnjov; K Axelsson; J Samarütel; B Holmström,"The purpose of the present study was to evaluate the postoperative analgesic and adverse effects of equal doses of oral or intrathecal clonidine in spinal anaesthesia with bupivacaine plain. Forty-five ASA I-III orthopaedic patients scheduled for osteosynthesis of a traumatic femur fracture were randomised in a double-blind fashion to one of 3 groups. Patients received 15 mg of plain bupivacaine intrathecally (group B) or an intrathecal mixture of bupivacaine 15 mg and clonidine 150 mg (group CIT). In group CPO oral clonidine 150 mg was administered 60 min before intrathecal injection of bupivacaine 15 mg. Oral and intrathecal clonidine prolonged the time until the first request for analgesics, 313 +/- 29 and 337 +/- 29 min, respectively, vs. 236 +/- 27 min in group B (P < 0.01). The total 24- h PCA morphine dose was significantly lower in group CIT(19.3 +/- 1.3 mg) compared to groups B and CPO(33.4 +/- 2.0 and 31.2 +/- 3.1 mg). MAP was decreased significantly during the first hour after intrathecal clonidine(14%) and during the first 5 h after oral clonidine(14-19%). HR decreased in CIT during the 5th and 6th postoperative hours(7-9%) and during the first 2 h(9%) in CPO (P < 0.01). The degree of sedation was more pronounced in group CPO during the first 3 h. Four patients had pruritus in group B. Addition of intrathecal clonidine prolonged analgesia and decreased morphine consumption postoperatively more than oral clonidine. Hypotension was more pronounced after oral than after intrathecal clonidine. Intrathecal clonidine is therefore recommended.",2002.0,0,0
336,12142861,An experimental comparison of Pycnogenol and methylphenidate in adults with Attention-Deficit/Hyperactivity Disorder (ADHD).,S Tenenbaum; J C Paull; E P Sparrow; D K Dodd; L Green,"Twenty-four adults (24 to 53 years old) with Attention-Deficit/Hyperactivity Disorder (ADHD), Combined Type, were studied in a double-blind, placebo-controlled, crossover study of Pycnogenol  and methylphenidate. Pycnogenol is an antioxidant derived from the bark of the French maritime pine tree. Methylphenidate is a standard pharmaceutical intervention for ADHD. Anecdotal reports suggest that Pycnogenol improves concentration in adults with ADHD without adverse side effects. Participants received Pycnogenol, methylphenidate, and placebo, each for three weeks, in a randomized and counterbalanced order. Although ADHD symptoms improved during treatment, neither methylphenidate nor Pycnogenol outperformed the placebo control, as measured by self-report rating scales, rating scales completed by the individual's significant other, and a computerized continuous performance test. The conservative dosage levels and relatively brief length of treatment may have contributed to the absence of significant differences among treatment conditions. Implications for future research are noted.",2002.0,1,1
337,12142863,Efficacy of Adderall for Attention-Deficit/Hyperactivity Disorder: a meta-analysis.,S V Faraone; J Biederman,"Stimulant medication has, for many years, been the pharmacological treatment of choice for children and adults with Attention-Deficit/Hyperactivity Disorder (ADHD). Several studies have shown Adderall , to be efficacious for measures of inattention, hyperactivity-impulsivity, aggression, disruptive behavior, and academic productivity. Although these studies provide useful information for clinicians treating ADHD children and adults, the variability in efficacy among the different types of measures used within each study has not been comprehensively examined. Thus, to provide a clearer picture of what conclusions can be drawn from these studies, we performed a meta-analysis. Data from the six available studies of standard release Adderall  show it to be efficacious for symptoms of inattention, hyperactivity-impulsivity, and aggression, as well as global ratings. Its efficacy was significant for clinician, parent, and teacher ratings, and for both fixed- and best-dose designs.",2002.0,0,1
338,12143912,Switching to olanzapine from previous antipsychotics: a regional collaborative multicenter trial assessing 2 switching techniques in Asia Pacific.,Chien-Te Lee; Bernardo Jorge L Conde; Mahmud Mazlan; Taweesin Visanuyothin; Adrian Wang; Michael M C Wong; Daniel J Walker; Suraja M Roychowdhury; Huei Wang; Pierre V Tran,"This open-label, multicenter, randomized study compared the efficacy and safety of switching moderately ill Asian patients with schizophrenia from their current regimen of antipsychotic medication to the atypical antipsychotic olanzapine using either a direct switch method or a start-taper switch method. Asian inpatients and outpatients with DSM-IV schizophrenia (N = 108) currently treated with predominantly typical antipsychotics were switched to olanzapine (initial dose of 10 mg/day) for 6 weeks. Patients were randomly assigned to 1 of 2 groups: the direct switch group (N = 54) received only olanzapine, while the start-taper switch group (N = 54) received olanzapine and their usual antipsychotic in decreasing doses for the first 2 weeks. A successful switch was defined as completing 6 weeks of therapy without worsening of symptoms (Clinical Global Impressions-Severity of Illness scale [CGI-S]) or extrapyramidal side effects (Simpson-Angus Scale). Overall efficacy was assessed using the Positive and Negative Syndrome Scale (PANSS), and safety was assessed by recording adverse events and measuring vital signs. Statistically significant (p < .001) improvements from baseline to endpoint occurred in both switch groups in the CGI-S score and the PANSS total score and subscores. However, no significant differences were observed between the switch groups for any efficacy measure. Both techniques had comparable rates of successful switching (direct switch, 74.1% vs. start-taper switch, 67.9%). The frequency of treatment-emergent adverse events was similar between switch groups with no clinically significant differences in any laboratory value or vital sign. Weight gain occurred in both switch groups (p < .001), but the groups were not statistically different from each other. Both switch groups showed statistically significant (p < .01) improvements from baseline to endpoint on the Simpson-Angus Scale and Barnes Akathisia Scale. Moderately ill Asian patients with schizophrenia may experience a decrease in symptom severity and improvement in extrapyramidal symptoms when switched from their current medication to olanzapine therapy.",2002.0,0,0
339,12151468,Risperidone in children with autism and serious behavioral problems.,James T McCracken; James McGough; Bhavik Shah; Pegeen Cronin; Daniel Hong; Michael G Aman; L Eugene Arnold; Ronald Lindsay; Patricia Nash; Jill Hollway; Christopher J McDougle; David Posey; Naomi Swiezy; Arlene Kohn; Lawrence Scahill; Andres Martin; Kathleen Koenig; Fred Volkmar; Deirdre Carroll; Allison Lancor; Elaine Tierney; Jaswinder Ghuman; Nilda M Gonzalez; Marco Grados; Benedetto Vitiello; Louise Ritz; Mark Davies; James Robinson; Don McMahon; Research Units on Pediatric Psychopharmacology Autism Network,"Atypical antipsychotic agents, which block postsynaptic dopamine and serotonin receptors, have advantages over traditional antipsychotic medications in the treatment of adults with schizophrenia and may be beneficial in children with autistic disorder who have serious behavioral disturbances. However, data on the safety and efficacy of atypical antipsychotic agents in children are limited. We conducted a multisite, randomized, double-blind trial of risperidone as compared with placebo for the treatment of autistic disorder accompanied by severe tantrums, aggression, or self-injurious behavior in children 5 to 17 years old. The primary outcome measures were the score on the Irritability subscale of the Aberrant Behavior Checklist and the rating on the Clinical Global Impressions - Improvement (CGI-I) scale at eight weeks. A total of 101 children (82 boys and 19 girls; mean [+/-SD] age, 8.8+/-2.7 years) were randomly assigned to receive risperidone (49 children) or placebo (52). Treatment with risperidone for eight weeks (dose range, 0.5 to 3.5 mg per day) resulted in a 56.9 percent reduction in the Irritability score, as compared with a 14.1 percent decrease in the placebo group (P<0.001). The rate of a positive response, defined as at least a 25 percent decrease in the Irritability score and a rating of much improved or very much improved on the CGI-I scale, was 69 percent in the risperidone group (34 of 49 children had a positive response) and 12 percent in the placebo group (6 of 52, P<0.001). Risperidone therapy was associated with an average weight gain of 2.7+/-2.9 kg, as compared with 0.8+/-2.2 kg with placebo (P<0.001). Increased appetite, fatigue, drowsiness, dizziness, and drooling were more common in the risperidone group than in the placebo group (P<0.05 for each comparison). In two thirds of the children with a positive response to risperidone at eight weeks (23 of 34), the benefit was maintained at six months. Risperidone was effective and well tolerated for the treatment of tantrums, aggression, or self-injurious behavior in children with autistic disorder. The short period of this trial limits inferences about adverse effects such as tardive dyskinesia.",2002.0,0,0
340,12153335,Spotlight on ziprasidone in schizophrenia and schizoaffective disorder.,Nishan S Gunasekara; Caroline M Spencer; Gillian M Keating,"Ziprasidone is a novel antipsychotic agent with a pharmacological profile distinct from that of other currently available novel or classical antipsychotics. In preclinical studies, ziprasidone was predicted to have efficacy against positive, negative and affective symptoms of schizophrenia with a favourable tolerability profile, including a low propensity to induce extrapyramidal adverse effects. The drug has been administered orally to >300 patients with an acute exacerbation of schizophrenia or schizoaffective disorder in published 4- to 6-week randomised, double-blind trials. When given twice daily at dosages of between 80 and 160 mg/day, ziprasidone produced significantly greater improvements in overall symptomatology than placebo. In the largest study, ziprasidone 80 or 160 mg/day was also significantly more effective than placebo in reducing negative symptoms and, at 160 mg/day, was significantly more effective than placebo in improving depressive symptoms in patients with associated clinically significant depression. Data from a 4-week trial indicate that ziprasidone 160 mg/day has similar efficacy to haloperidol 15 mg/day. Ziprasidone 40 to 160 mg/day was more effective than placebo with respect to prevention of impending relapse and improvement of negative symptoms in 294 stable patients with chronic schizophrenia who were treated for up to 1 year. In addition, significantly more ziprasidone than haloperidol recipients achieved a negative symptom response in a 28-week study involving 301 stable patients with chronic or subchronic schizophrenia. In general, oral ziprasidone is well tolerated with an overall incidence of adverse events similar to placebo. Importantly, the drug has a low propensity to induce extrapyramidal effects and a negligible effect on bodyweight. Ziprasidone is associated with slight prolongation of the QTc interval; the clinical significance of this is not yet clear. The drug does not appear to be associated with sustained elevation of plasma prolactin levels. Preliminary data indicate that long-term oral ziprasidone treatment is well tolerated. Ziprasidone is the only novel antipsychotic currently available in a rapid-acting intramuscular formulation. Short-term treatment with intramuscular ziprasidone was effective and well tolerated in patients with acute agitation associated with psychosis. In addition, intramuscular ziprasidone reduced agitation scores by a significantly greater extent than haloperidol in a study involving patients with acute agitation associated with psychosis. Ziprasidone is a promising new antipsychotic that has shown significant efficacy in the oral treatment of patients with schizophrenia or schizoaffective disorder. The drug is well tolerated with a low propensity to induce extrapyramidal effects and a negligible effect on bodyweight. In addition, intramuscular ziprasidone shows efficacy and good tolerability in the treatment of acute agitation associated with psychotic disorders.",2002.0,0,0
341,12153824,Effects of methylphenidate on functional magnetic resonance relaxometry of the cerebellar vermis in boys with ADHD.,Carl M Anderson; Ann Polcari; Steven B Lowen; Perry F Renshaw; Martin H Teicher,"The authors used functional magnetic resonance imaging (fMRI) to test the effects of methylphenidate on steady-state blood volume in the midline vermis of the cerebellum in boys with attention deficit hyperactivity disorder (ADHD). This region was selected as it has been observed to be significantly smaller in children with ADHD. Also, in preclinical studies, the vermis has been shown to modulate forebrain dopamine systems, to influence locomotor activity, and to contain a significant density of dopamine transporters. T(2) relaxometry was used to indirectly assess blood volume in the cerebellum (hemispheres and midline vermis) of 10 boys with ADHD who were administered placebo or one of three different doses of methylphenidate continuously for 1 week. T(2) relaxation time values are inversely proportional to local cerebral blood volume. After each week of treatment, and within 1-3 hours of the boys' afternoon dose, testing for drug efficacy was performed by using objective measures of activity. Moderate and high doses of methylphenidate increased T(2) relaxation time in a rate-dependent manner-increasing T(2) relaxation time in the most active children with ADHD and reducing T(2) relaxation time in subjects with ADHD who were not objectively hyperactive. This preliminary study supports a role for the vermis in ADHD and suggests that further research is needed to clarify the relationship between vermal size, vermal blood flow, stimulant response, and the developmental pathophysiology of ADHD.",2002.0,0,0
342,12153826,"Double-blind, placebo-controlled study of risperidone for the treatment of disruptive behaviors in children with subaverage intelligence.",Michael G Aman; Goedele De Smedt; Albert Derivan; Ben Lyons; Robert L Findling; Risperidone Disruptive Behavior Study Group,"The short-term efficacy and safety of risperidone in the treatment of disruptive behaviors was examined in a well-characterized cohort of children with subaverage intelligence. In this 6-week, multicenter, double-blind, parallel-group study of 118 children (aged 5-12 years) with severely disruptive behaviors and subaverage intelligence (IQ between 36 and 84, inclusive), the subjects received 0.02-0.06 mg/kg per day of risperidone oral solution or placebo. The a priori primary efficacy measure was the change in score from baseline to endpoint on the conduct problem subscale of the Nisonger Child Behavior Rating Form. The risperidone group showed significantly greater improvement than did the placebo group on the conduct problem subscale of the Nisonger Child Behavior Rating Form from week 1 through endpoint (change in score of -15.2 and -6.2, respectively). Risperidone was also associated with significantly greater improvement than placebo on all other Nisonger Child Behavior Rating Form subscales at endpoint, as well as on the Aberrant Behavior Checklist subscales for irritability, lethargy/social withdrawal, and hyperactivity; the Behavior Problems Inventory aggressive/destructive behavior subscale; a visual analogue scale of the most troublesome symptom; and the Clinical Global Impression change score. The most common adverse effects reported during risperidone treatment were headache and somnolence. The extrapyramidal symptom profile of risperidone was comparable to that of placebo. Mean weight increases of 2.2 kg. and 0.9 kg occurred in the risperidone and placebo groups, respectively. Risperidone was effective and well tolerated for the treatment of severely disruptive behaviors in children with subaverage IQ.",2002.0,0,0
343,12153919,Assessment of independent effect of olanzapine and risperidone on risk of diabetes among patients with schizophrenia: population based nested case-control study.,Carol E Koro; Donald O Fedder; Gilbert J L'Italien; Sheila S Weiss; Laurence S Magder; Julie Kreyenbuhl; Dennis A Revicki; Robert W Buchanan,"To quantify the association between olanzapine and diabetes. Population based nested case-control study. United Kingdom based General Practice Research Database comprising 3.5 million patients followed between 1987 and 2000. 19 637 patients who had been diagnosed as having and treated for schizophrenia. 451 incident cases of diabetes were matched with 2696 controls. Diagnosis and treatment of diabetes. Patients taking olanzapine had a significantly increased risk of developing diabetes than non-users of antipsychotics (odds ratio 5.8, 95% confidence interval 2.0 to 16.7) and those taking conventional antipsychotics (4.2, 1.5 to 12.2). Patients taking risperidone had a non-significant increased risk of developing diabetes than non-users of antipsychotics (2.2, 0.9 to 5.2) and those taking conventional antipsychotics (1.6, 0.7 to 3.8). Olanzapine is associated with a clinically important and significant increased risk of diabetes.",2002.0,0,0
344,12165576,"A randomized, double-blind, placebo-controlled, parallel-group study of SLI381 (Adderall XR) in children with attention-deficit/hyperactivity disorder.",Joseph Biederman; Frank A Lopez; Samuel W Boellner; Mark C Chandler,"SLI381 (Adderall XR) is a 2-component extended-release capsule formulation of Adderall designed to produce a therapeutic effect that lasts throughout the day with 1 morning dose. The primary objective of this study was to assess the efficacy and safety of SLI381 compared with placebo in the treatment of attention-deficit/hyperactivity disorder (ADHD) in children in a naturalistic school and home setting. A secondary objective was to assess the diurnal variation in responses based on morning and afternoon assessments. A multicenter, randomized, double-blind, parallel-group, placebo-controlled trial was conducted at 47 sites. After a 1-week washout of any previous stimulant medication, patients were randomized to receive single-daily morning doses of placebo or SLI381 10 mg, 20 mg, or 30 mg for 3 weeks. Participants aged 6 to 12 years inclusive who satisfied Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria diagnosis of ADHD were included. The primary efficacy parameter was the Conners Global Index Scale for Teachers. Secondary efficacy parameters included the Conners Global Index Scale for Parents, the Clinical Global Impressions Scale for improvement, and the Parent Global Assessment for improvement. Safety was assessed by recording adverse events, laboratory tests, and vital signs at each visit during the study. Physical examinations and electrocardiograms were performed at the screening and the end of the study. Five hundred eighty-four children were randomized, 563 were included in the intent-to-treat population, and 509 completed the entire study. Intention-to-treat analysis of Conners Global Index Scale for Teachers and Conners Global Index Scale for Parents scores revealed significant improvement in morning, afternoon, and late afternoon behavior for all active treatment groups versus placebo. All active treatment groups showed significant dose-related improvement in behavior from baseline. Both the Clinical Global Impressions Scale for improvement and Parent Global Assessment for improvement showed all doses of SLI381 to be superior to placebo at treatment end and both confirmed the dose-response relationship between improvement and the SLI381 dose. The incidence of spontaneously reported adverse events was low and similar for active treatments and placebo. SLI381 produced consistent, dose-related improvements on all measures of efficacy. The extended-release nature of the SLI381 formulation was shown by continued, significant improvement in afternoon assessments by teachers and afternoon and late afternoon assessments by parents. The time course and therapeutic effects of SLI381 suggests that this medication is an efficacious once-daily treatment for children with ADHD.",2002.0,0,1
345,12167135,"Chronic daily headache prophylaxis with tizanidine: a double-blind, placebo-controlled, multicenter outcome study.",Joel R Saper; Alvin E Lake; Deborah T Cantrell; Paul K Winner; Jeffery R White,"To assess the efficacy of tizanidine hydrochloride versus placebo as adjunctive prophylactic therapy for chronic daily headache (chronic migraine, migrainous headache, or tension-type headache). Tizanidine is an alpha2-adrenergic agonist that inhibits the release of norepinephrine at both the spinal cord and brain, with antinociceptive effects that are independent of the endogenous opioid system. Previous open-label studies have suggested the drug may be effective for treatment of chronic daily headache. Two hundred patients completed a 4-week, single-blind, placebo baseline period, with 134 fulfilling selection criteria and then randomized to tizanidine or placebo. Ninety-two patients completed at least 8 weeks of treatment (tizanidine, n = 45; placebo, n = 47), and 85 patients completed 12 weeks of treatment (tizanidine, n = 44; placebo, n = 41). Most patients (77%) met the diagnostic criteria for migraine of the International Headache Society; 23% had either chronic migrainous headache or chronic tension-type headache. Tizanidine was slowly titrated over 4 weeks to 24 mg or the maximum dose tolerated (mean, 18 mg; SD, 6.4; median, 20.0; range, 2 to 24), divided equally over three dose intervals per day. Overall headache index ([headache days x average intensity x duration in hours]/28 days) was the primary end point. Tizanidine was shown to be superior to placebo in reducing the overall headache index (P =.0025), as well as mean headache days per week (P =.0193), severe headache days per week (P =.0211), average headache intensity (P =.0108), peak headache intensity (P =.0020), and mean headache duration (P =.0127). The mean percentage improvement during the last 4 weeks of treatment with tizanidine versus placebo was 54% versus 19% for the headache index (P =.0144), 55% versus 21% for severe headache days (P =.0331), 35% versus 19% for headache duration (P =.0142), 35% versus 20% for peak headache intensity (P =.0106), 33% versus 20% for average headache intensity (P =.0281), and 30% versus 22% for total headache days (P =.0593). Patients receiving tizanidine also scored higher ratings of overall headache improvement on a visual analog scale (P =.0069). There was no statistically significant difference in outcome for patients with chronic migraine versus those with only migrainous or tension-type headache. Adverse effects reported by more than 10% of the patients included somnolence (47%), dizziness (24%), dry mouth (23%), and asthenia (19%). Dropouts due to adverse events did not differ significantly between tizanidine and placebo. The results support tizanidine as an effective prophylactic adjunct for chronic daily headache, including migraine, migrainous headache, and tension-type headache. These results also suggest the possible importance of an alpha2-adrenergic mechanism underlying the pathophysiology of this spectrum of headache disorders.",2002.0,0,0
346,12173195,Comparison of caudal and intravenous clonidine in the prevention of agitation after sevoflurane in children.,M Bock; P Kunz; R Schreckenberger; B M Graf; E Martin; J Motsch,"In children, sevoflurane anaesthesia is associated with postanaesthetic agitation, which is treated mainly with opioids. We compared the effectiveness of epidural and i.v. clonidine in the prevention of this postanaesthetic agitation. Eighty children aged 3-8 yr (ASA I-II) received standardized general anaesthesia with inhaled sevoflurane and caudal epidural block with 0.175% bupivacaine 1 ml kg-1 for minor surgery. The children were assigned randomly to four groups: (I) clonidine 1 microgram kg-1 added to caudal bupivacaine; (II) clonidine 3 micrograms kg-1 added to caudal bupivacaine; (III) clonidine 3 micrograms kg-1 i.v. and caudal bupivacaine; and (IV) caudal block with bupivacaine, no clonidine (control). A blinded observer assessed the behaviour of the children during the first postoperative hour. Secondary end-points were the time to fitness for discharge from the postanaesthesia care unit, and haemodynamic and respiratory variables. The incidence of agitation was 22, 0, 5 and 39% in groups I, II, III and IV respectively (P < 0.05 for groups II and III compared with group IV). During the first hour after surgery, patients in groups II and III had significantly lower scores for agitation than group IV patients. Time to fitness for discharge did not differ between the four groups. Clonidine 3 micrograms kg-1 prevented agitation after sevoflurane anaesthesia, independently of the route of administration. The effect of clonidine appears to be dose-dependent, as an epidural dose of 1 microgram kg-1 failed to reduce it.",2002.0,0,0
347,12180276,Topiramate versus bupropion SR when added to mood stabilizer therapy for the depressive phase of bipolar disorder: a preliminary single-blind study.,Roger S McIntyre; Deborah A Mancini; Sonia McCann; Janaki Srinivasan; Doron Sagman; Sidney H Kennedy,"Antiepileptic drugs (AEDs) are commonly employed in the treatment of bipolar disorder. The efficacy and tolerability of topiramate, a novel anticonvulsant, and bupropion SR when added to mood stabilizer therapy were compared under single-blind conditions (rater-blinded) in patients meeting DSM-IV criteria for bipolar I/II depression. A total of 36 out-patients with Hamilton Depression Rating Scale (HDRS-17) scores > or = 16 were randomized to receive escalating doses of either topiramate (50-300 mg/day) or bupropion SR (100-400 mg/day) for 8 weeks. Data were analyzed on an intent-to-treat basis using the last observation carried forward method. The percentage of patients meeting a priori response criteria (> or = 50% decrease from baseline in mean HDRS-17 total score) was significant for both topiramate (56%) and bupropion SR (59%) [t(17) = 2.542, p = 0.04 and t(17) = 2.661, p = 0.03, respectively]. Baseline demographic and clinical parameters were comparable between the two treatment groups. The mean doses of study medication were 176 mg/day (SD = 102 mg/day) for the topiramate-treated group and 250 mg/day (SD = 133 mg/day) for the bupropion SR-treated group. A significant and comparable reduction in depressive symptoms was observed from baseline to endpoint following topiramate and bupropion SR treatment, according to a > or = 50% reduction in the HDRS-17. Total mean HDRS-17 scores significantly decreased from baseline to endpoint in both groups (p = 0.001), however, differences between the topiramate-treated group and the bupropion SR-treated group were not significant [t(36) = 1.754, p = 0.097]. Both topiramate and bupropion SR were generally well tolerated. Thirteen patients discontinued the study: 2 because of lack of efficacy, 1 due to withdrawal of consent and 10 following side-effects (six in the topiramate and four in the bupropion SR-treated group). There were no cases of affective switch in either arm. Weight loss was experienced by patients in both groups (mean weight loss at endpoint was 1.2 kg in bupropion SR and 5.8 kg in topiramate) [t(17) = 2.325, p = 0.061 and t(17) = 2.481, p = 0.043, respectively]. These preliminary data suggest that adjunctive topiramate may reduce depressive symptom severity in acute bipolar depression. The antidepressant efficacy of this compound requires confirmation via double-blind placebo controlled investigation.",2003.0,0,0
348,12188588,Bupropion for pharmacologic relapse prevention to smoking: predictors of outcome.,Richard D Hurt; Troy D Wolter; Nancy Rigotti; J Taylor Hays; Raymond Niaura; Michael J Durcan; David Gonzales; David P L Sachs; J Andrew Johnston; Kenneth P Offord,"The aim of this study was to identify predictors of successful relapse prevention in smokers receiving long-term sustained-release bupropion. Smokers (N= 784) who were interested in stopping smoking were enrolled in a 7-week, open-label bupropion phase. Abstinent subjects at the end of treatment and eligible to proceed (N= 429) were randomized to active bupropion or placebo through Week 52 and then followed for an additional year. The best overall predictor of less relapse to smoking was assignment to active bupropion. In aggregate, the results indicate that bupropion can be prescribed to diverse populations of smokers with expected comparable results. There was a medication effect that was independent of any predictor except older age and those who gained no or minimal weight during the open-label phase. Predictors of successful relapse prevention included lower baseline smoking rates, a Fagerström Tolerance Questionnaire score of < 6, and initiation of smoking at an older age. These data should encourage others to perform similar pharmacologic relapse prevention studies with this or other pharmacotherapies.",2003.0,0,0
349,12198064,The analgesic efficacy of bilateral combined superficial and deep cervical plexus block administered before thyroid surgery under general anesthesia.,Sophie Aunac; Marianne Carlier; Francois Singelyn; Marc De Kock,"In this study we evaluated the analgesic efficacy of combined deep and superficial cervical plexus block in patients undergoing thyroidectomy under general anesthesia. For this purpose, 39 patients undergoing elective thyroid surgery were randomized to receive a bilateral combined deep and superficial cervical block (14 mL per side) with saline (Group 1; n = 13), ropivacaine 0.5% (Group 2; n = 13), or ropivacaine 0.5% plus clonidine 7.5 microg/mL (Group 3; n = 13). Deep cervical plexus block was performed with a single injection (8 mL) at the C3 level. Superficial cervical plexus block consisted of a subcutaneous injection (6 mL) behind the lateral border of the sternocleidomastoid muscle. During surgery, the number of additional alfentanil boluses was significantly reduced in Groups 2 and 3 compared with Group 1 (1.3 +/- 1.0 and 1.1 +/- 1.0 vs 2.6 +/- 1.0; P < 0.05). After surgery, the opioid and non-opioid analgesic requirements were also significantly reduced in Groups 2 and 3 (P < 0.05) during the first 24 h. Except for one patient in Group 3, who experienced transient anesthesia of the brachial plexus, no side effect was noted in any group. We conclude that combined deep and superficial cervical plexus block is an effective technique to alleviate pain during and immediately after thyroidectomy. Combined deep and superficial cervical plexus block is an effective technique to reduce opioid requirements during and after thyroid surgery.",2002.0,0,0
350,12199263,Selegiline: a second look. Six years later: too risky in Parkinson's disease.,,"(1) The reference treatment for Parkinson's disease is levodopa plus a peripheral dopadecarboxylase inhibitor (benserazide or carbidopa). (2) In 1996, selegiline, a type B MAOI marketed in France since 1988, saw its indications extended to cover single-agent therapy of early-stage Parkinson's disease, and in combination with levodopa, before onset of complications of levodopa therapy. The initial clinical file failed to show that selegiline had any benefit in these indications. (3) Now, in 2002, new data from trials involving hundreds of untreated patients show that selegiline postpones the need for levodopa therapy for a few months but fails to substantially alter the progression of Parkinson's disease. (4) A clinical trial and a retrospective epidemiological study of patients with advanced Parkinson's disease showed excess mortality on selegiline. (5) The side effects of selegiline are similar to those of other antiparkinsonian drugs and amphetamine. Notable side effects include cardiovascular problems (postural hypotension, atrial fibrillation and arterial hypertension). (6) Selegiline can cause a serotoninergic syndrome and arterial hypertension, so must not be combined with pethidine, tramadol, bupropion, sumatriptan, zolmitriptan or naratriptan. Concurrent treatment with serotonin reuptake inhibitor antidepressants should also be avoided. (7) Given the only moderate effects of selegiline in Parkinson's disease, and the possibility of a slight increase in mortality, there is no justification for prescribing this medication in patients with Parkinson's disease. (8) Whatever the stage of Parkinson's disease, there is no justification for starting patients on selegiline. Patients who are already taking selegiline should only continue to take it if they feel a clear benefit and are free from risk factors for early mortality, especially cardiovascular disease.",2002.0,0,0
351,12200949,Anaesthetic and postoperative analgesic effects of spinal clonidine as an additive to prilocaine in the transurethral resection of urinary bladder tumours.,X Santiveri; A Arxer; I Plaja; M T Metje; B Martínez; A Villalonga; M López,"The alpha 2-adrenoceptor agonist clonidine has potent central antinociceptive properties. The study was designed to investigate the effects of the combined subarachnoid administration of clonidine and prilocaine on spinal block and postoperative analgesia for the transurethral resection of tumours in the urinary bladder. The controlled, prospective, double-blind study enrolled 40 patients scheduled for elective transurethral resection of bladder tumours under spinal anaesthesia with prilocaine. Patients were randomly assigned to receive an intrathecal injection of prilocaine 75 mg alone (control group) or in combination with clonidine 75 micrograms. We assessed haemodynamic changes (non-invasive arterial pressure, heart rate), pulse oximetry, the upper level of block, the onset and duration of sensory and motor block, postoperative analgesia and any adverse effects. There were no statistically significant differences in demographic data, heart rate, onset time or the levels of sensory or motor block. Analgesia lasted significantly longer in the clonidine group (498.4 +/- 226.9 versus 187.2 +/- 103.1 min; P < 0.05). The duration of motor block was longer in the clonidine group (165.5 +/- 30.6 min) than in the control group (139.7 +/- 40.4 min; P < 0.05) and the duration of sensory block was also longer in the clonidine group (157.3 +/- 24.5 min) than in the control group (137.2 +/- 31.2 min; P < 0.05). Fewer patients in the recovery room needed metamizol (dipyrone) in the clonidine group (5%) than in the control group (50%). Arterial pressure decreased significantly in the clonidine group 75-135 min after the block. The addition of clonidine 75 micrograms to prilocaine 75 mg for subarachnoid anaesthesia increased the duration of sensory and motor block and reduced the need for additional postoperative analgesics by providing excellent analgesia for about 8 h during recovery from transurethral resection of bladder tumours.",2003.0,0,0
352,12202454,Optimal dosing of atypical antipsychotics in adults: a review of the current evidence.,Leslie Citrome; Jan Volavka,"This review describes dosing strategies used to optimize the beneficial effects of atypical antipsychotic medications. Differences between manufacturers' recommended dosing and actual clinical practice are reconciled using evidence from pivotal double-blind randomized registration studies, other randomized clinical trials, case series, and case reports. With clozapine and perhaps olanzapine, plasma levels are correlated with therapeutic response; with risperidone, plasma levels are not correlated with therapeutic response but may be related to the occurrence of extrapyramidal symptoms. Information related to optimal dosing of quetiapine and ziprasidone is more limited. In clinical practice, the mean daily dose of risperidone has decreased, whereas that for olanzapine is increasing. The percentage of patients receiving quetiapine at doses above the manufacturer's recommended maximum is higher than would be expected, further illustrating that dosing ranges established during registration studies may not reflect the needs of day-to-day practice.",2002.0,0,0
353,12204387,Effects of caffeine on development and behavior in infancy and childhood: a review of the published literature.,F X Castellanos; J L Rapoport,"The Medline literature on the behavioral effects of caffeine in infants and children are reviewed. There has been little recent work in this area. Generally, caffeine is well tolerated in usual dietary amounts, and there is evidence that individuals differ in their susceptibility to caffeine-related adverse effects, which in turn may influence their consumption. Overall, the effects of caffeine in children seem to be modest and typically innocuous.",2002.0,0,0
354,12206448,A comparison of sustained-release bupropion and placebo for smokeless tobacco cessation.,Elbert D Glover; Penny N Glover; C Rollynn Sullivan; Connie L Cerullo; Gerald Hobbs,"To evaluate the potential efficacy of bupropion sustained release when used in combination with minimal counseling for moist snuff cessation in males. A double-blind, placebo-controlled 3-month trial. The active treatment group (n = 35) received bupropion SR at 150 mg/qd day for the first 3 days, then beginning day 4 through day 49 (7 weeks) 150 mg/ b.i.d. The placebo group (n= 35) received 1 tablet qd for 3 days and beginning day 4 through day 49, 1 tablet/b.i.d. Bupropion 300 mg/day (150 b.i.d.) produced significantly higher quit rates for smokeless tobacco cessation at the end of treatment (7 weeks) than placebo (p = 0.04) with an OR of 2.73. Bupropion SR appears to be effective for smokeless tobacco cessation.",2003.0,0,0
355,12208553,Drug treatment of conduct disorder in young people.,Priscille Gérardin; David Cohen; Philippe Mazet; Martine F Flament,"Although conduct disorder (CD) is the most common psychiatric disorder in youth from the community and encompasses one third to one half of all referrals to child and adolescent clinics, there is no licensed drug, to date, for treatment of CD, neither in Europe nor in the US. The aims of this paper are to review research data available on the use of medication for CD in young people and to identify future directions for research. We review 17 controlled studies and six open trials. Investigated compounds mainly belong to three classes of psychotropic drugs: mood stabilizers, neuroleptics and stimulants (six, five and six controlled studies, respectively). Lithium is the most documented treatment (3/4 positive studies). Conventional neuroleptics have been most commonly prescribed (3/3 positive studies), atypical neuroleptics appear promising (2/2 positive studies). Methylphenidate improves some CD symptoms, even in the absence of ADHD (6/6 positive studies). Sparse research has been conducted on response to antidepressants. The evidence for an effective role of pharmacotherapy in CD is still limited. Treatment should be multimodal and individualized to each patient's specific condition.",2002.0,0,1
356,12215063,Dexmethylphenidate.,Gillian M Keating; David P Figgitt,"Dexmethylphenidate comprises only the d-enantiomer (the pharmacologically effective isomer) of racemic methylphenidate and is indicated for the treatment of patients aged > or =6 years with attention deficit hyperactivity disorder (ADHD). In a 4-week, double-blind trial in 132 children with ADHD, significantly greater improvements from baseline in teacher-rated Swanson, Nolan and Pelham (SNAP)-ADHD scores were seen in dexmethylphenidate and methylphenidate recipients, compared with placebo recipients. In addition, significantly more dexmethylphenidate and methylphenidate recipients, compared with placebo recipients, were much improved or very much improved according to Clinical Global Impression-Improvement of Illness scale scores. In the same study, parent-rated SNAP-ADHD scores had decreased by a significantly greater extent in dexmethylphenidate recipients at 3pm and 6pm and in methylphenidate recipients at 3pm, compared with placebo recipients. Significantly fewer dexmethylphenidate than placebo recipients failed treatment in a double-blind, treatment-withdrawal trial in 75 children with ADHD (17.1 vs 61.5%). In a noncomparative study in 22 children with ADHD, symptoms of ADHD, as assessed by teachers and parents, were controlled during the entire school day in 68 and 86% of dexmethylphenidate recipients, respectively, with a median duration of effect of 6.3 and 7.5 hours, respectively. Dexmethylphenidate was generally well tolerated in children with ADHD; adverse events were consistent with those known to be associated with agents containing methylphenidate.",2002.0,0,0
357,12218435,ADHD in Brazil: the DSM-IV criteria in a culturally different population.,Luis Augusto Rohde,,2002.0,0,0
358,12222083,Somatic treatment for depressive illnesses in children and adolescents.,Robert L Findling; Norah C Feeny; Robert J Stansbrey; Denise DelPorto-Bedoya; Christine Demeter,"Numerous somatic interventions have been studied as potential treatments of depressive disorders in children and adolescents. These include antidepressant medications, light therapy, electro-convulsive therapy, and alternative therapies. The available evidence suggests that several somatic interventions hold promise as potentially safe and effective treatments for depressed youth; however, there is still much to be learned about these interventions. This article reviews what is known and what needs to be learned about the somatic treatment of pediatric depression.",2003.0,0,0
359,12223251,Switching from conventional to novel antipsychotic drugs: results of a prospective naturalistic study.,L Voruganti; L Cortese; L Owyeumi; V Kotteda; Z Cernovsky; S Zirul; A Awad,"We examined the long-term consequences of switching patients from conventional to novel antipsychotic drugs, from a patient's perspective. In a prospective, single-blinded, naturalistic study, a cohort of subjects (n=150) with schizophrenia or schizo-affective disorder (DSM-IV) were switched from conventional neuroleptic drugs to either risperidone (n=50), olanzepine (n=50) or quetiapine (n=50), and monitored for a period of 2 to 6 years. The ensuing natural history of transitions in treatments was charted, and the outcomes including symptoms, side effects, subjective tolerability of drugs and their impact on quality of life were documented with standardized rating scales. Majority (85%) of the subjects benefited from a switch to the novel antipsychotic drugs, though some preferred to return to their original neuroleptic (8%), and others eventually required clozapine (7%) therapy. Novel antipsychotic drugs were significantly tolerated better, and had a positive impact on treatment-adherence, psychosocial functioning and quality of life. Among the novel drugs, risperidone was significantly better in improving negative symptoms, while olanzepine was particularly well tolerated and effective against comorbid anxiety and depressive symptoms. Patients treated with quetiapine reported fewer side effects, and showed a significantly greater improvement in neurocognitive deficits. Novel antipsychotics emerged as the drug of choice in view of their overall effectiveness, though conventional neuroleptics and clozapine will continue to have a limited but distinct role in the management of schizophrenia. The challenge for clinicians lies in matching a patient's clinical and biochemical profile with that of a drug's pharmacological actions, in order to achieve optimum outcomes.",2002.0,0,0
360,12223254,Extrapyramidal symptom profiles in Japanese patients with schizophrenia treated with olanzapine or haloperidol.,Toshiya Inada; Gohei Yagi; Sadanori Miura,"Previous clinical trials have clearly shown the superiority of olanzapine to haloperidol in the improvement of extrapyramidal symptoms (EPS) in schizophrenic patients. The primary purpose of this study was to compare EPS profiles in Japanese schizophrenic patients treated with an atypical antipsychotic, olanzapine, or a typical antipsychotic, haloperidol, as measured by the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). The DIEPSS, which consists of eight individual parameters and one global assessment (overall severity), was used to evaluate 182 patients enrolled in this 8-week study. The primary safety analysis was maximum change (that could be either a decrease or increase) from baseline in DIEPSS total score. Secondary analyses included change from baseline to maximum in DIEPSS total score, change from baseline to endpoint (LOCF) in DIEPSS total score, and the rank sum of the maximum change (that could be either a decrease or increase) from baseline in the DIEPSS individual items. Incidence of treatment-emergent EPS adverse events using the DIEPSS scale was also analyzed. The olanzapine group showed statistically significant superiority to the haloperidol group on the primary analysis (p<0.001). Secondary analyses also demonstrated olanzapine's superiority in DIEPSS total, parkinsonism, akathisia and overall severity scores (all p< or =0.014). Categorical analysis of treatment-emergent akathisia and parkinsonism syndromes at endpoint showed improvement in the olanzapine group but worsening in the haloperidol group. The results from this study suggest that olanzapine, as in Caucasian populations, is a safe treatment in Japanese patients chronically ill with schizophrenia.",2002.0,0,0
361,12230649,Attention deficit hyperactivity disorder in children.,Paul Ramchandani; Carol Joughin; Morris Zwi,,2002.0,0,1
362,12230716,Schizophrenia.,Stephen Lawrie; Andrew McIntosh,,2002.0,0,0
363,12230782,Menopausal symptoms.,Edward Morris; Janice Rymer,,2002.0,0,0
364,12236804,Cost-effectiveness comparison of tizanidine and baclofen in the management of spasticity.,David N Rushton; Adam C Lloyd; Pippa M Anderson,"Baclofen and tizanidine are both used for the treatment of muscle spasticity of spinal origin. Their effectiveness, cost and adverse-effect profiles differ. This paper sets out to estimate the cost effectiveness of each drug, and the impact of changing from baclofen to tizanidine. A simplified but realistic model of physician behaviour and patient response was developed as a decision tree and populated with data derived from the available published clinical comparative trials. We considered patients with spasticity caused by multiple sclerosis or spinal cord injury. The outcome measure used was 'cost per successfully treated day' (STD). Costs were estimated from the perspective of the UK National Health Service at 2000 values. Expected cost for a cohort of 100 patients over 1 year was estimated to be pound 181 545 with baclofen and pound 211 930 with tizanidine. The estimated number of STDs was 20,192 with tizanidine and 17,289 with baclofen. The overall cost effectiveness of managing spasticity using baclofen and tizanidine was very similar ( pound 10.50 and pound 10.49 per STD respectively). The incremental cost effectiveness (ICE) of using tinzanidine as an alternative to baclofen for first-line treatment was pound 10.47 per STD. Sensitivity analysis found the model to be robust to changes in key parameters Drug cost should not be a determining factor in making this treatment choice, as the cost effectiveness ratios are similar for both products.",2002.0,0,0
365,12242060,Olanzapine in the treatment of dopamimetic-induced psychosis in patients with Parkinson's disease.,Alan Breier; Virginia K Sutton; Peter D Feldman; Deborah L Kadam; Iris Ferchland; Padraig Wright; Joseph H Friedman,"Studies in elderly patients demonstrate antipsychotic efficacy and favorable safety profiles for olanzapine. We report results from two placebo-controlled, double-blind studies of olanzapine for treatment of dopamimetic drug-induced psychosis in patients with Parkinson's disease (PD). Patients were treated with olanzapine or placebo for 4 weeks while dopamimetic therapy was held constant. Olanzapine was initiated at 2.5 mg/day, with 2.5-mg/day increases allowed every 3 to 4 days up to the maximum dose of 15 mg/day. Olanzapine patients showed significant improvements from baseline on positive symptoms and most efficacy measures, but no significant treatment-group differences were observed. Olanzapine performed significantly worse than placebo in both studies on the Unified Parkinson's Disease Rating Scale (UPDRS) total, Motor, and Activities of Daily Living scales, but not the UPDRS Tremor item or Complications scores. Corrected QT interval, vital signs, and body weight were not significantly different from placebo. These findings did not demonstrate superior efficacy of olanzapine for treatment of dopamimetic-induced psychosis in PD. The initial dose-titration schedule and mild baseline levels of psychosis may account for these findings. Future studies involving gradual dose titration are needed to explore further olanzapine's optimum use for patients with PD with treatment-related psychosis.",2002.0,0,0
366,12352269,Comparative efficacy of Adderall and methylphenidate in attention-deficit/hyperactivity disorder: a meta-analysis.,Stephen V Faraone; Joseph Biederman; Christine Roe,"Because methylphenidate is currently the most widely prescribed medication for attention-deficit/ hyperactivity disorder, several studies have used it as the active comparator medication for evaluating the efficacy of a newer stimulant, Adderall. These prior studies show Adderall to be superior to placebo and suggest it is at least as effective as the standard-release form of methylphenidate and has a longer duration of action. Although these initial studies provide useful information for clinicians treating children with attention-deficit/hyperactivity disorder, they are difficult to interpret because findings vary among studies and among the different types of measures used within each study. To provide a clearer picture of what conclusions can be drawn from these studies, we performed a meta-analysis. Data from the four available studies suggest that Adderall has a small but statistically significant advantage over the standard-release form of methylphenidate. This advantage was observed for both symptom measures and global ratings but was strongest for global ratings. The effect of Adderall was significant for clinician and parent ratings but not for teacher ratings and was significant for both fixed-dose and best-dose designs.",2002.0,0,1
367,12355680,Risperidone decreases craving and relapses in individuals with schizophrenia and cocaine dependence.,David A Smelson; Miklos F Losonczy; Craig W Davis; Maureen Kaune; John Williams; Douglas Ziedonis,"To examine the efficacy of atypical neuroleptics for decreasing craving and drug relapses during protracted withdrawal in individuals dually diagnosed with schizophrenia and cocaine dependence. We conducted a 6-week, open-label pilot study comparing risperidone with typical neuroleptics in a sample of withdrawn cocaine-dependent schizophrenia patients. Preliminary results suggest that individuals treated with risperidone had significantly less cue-elicited craving and substance abuse relapses at study completion. Further, they showed a trend toward a greater reduction in negative and global symptoms of schizophrenia. Atypical neuroleptics may help reduce craving and relapses in this population. Future research should include more rigorous double-blind placebo-controlled studies with this class of medications.",2002.0,0,0
368,12359687,"Adjunctive olanzapine for SSRI-resistant combat-related PTSD: a double-blind, placebo-controlled study.",Murray B Stein; Neal A Kline; Jeffrey L Matloff,"Posttraumatic stress disorder (PTSD), particularly in combat veterans with chronic illness, is often refractory to standard pharmacological interventions. There is a need to test adjunctive treatments to boost response. Subjects were 19 patients with PTSD who were minimally responsive to 12 weeks of treatment with a selective serotonin reuptake inhibitor (SSRI) at maximum tolerated dose. Outcomes were compared among subjects whose treatment was augmented with 8 weeks of double-blind olanzapine or placebo administration. Olanzapine augmentation was associated with statistically significantly greater reduction than placebo in specific measures of posttraumatic stress, depressive, and sleep disorder symptoms. Clinician-rated global response rates did not, however, significantly differ between groups. This is most likely the first double-blind, placebo-controlled study of an adjunct to SSRIs for PTSD. Despite the small group size, the findings suggest a role for olanzapine or other atypical antipsychotics in treating SSRI-resistant PTSD. Sleep symptoms may especially benefit.",2002.0,0,0
369,12360554,Olanzapine treatment for dopaminergic-induced hallucinations.,William G Ondo; Joel K Levy; Kevin Dat Vuong; Christine Hunter; Joseph Jankovic,"Atypical antipsychotic medications with lower affinities for D2 receptors are considered useful alternatives to treat drug-induced hallucinations in Parkinson's disease (PD). We conducted a double-blind, placebo-controlled, unforced titration, parallel design study (2:1 drug to placebo randomization ratio) using olanzapine (2.5-10 mg/day to effect) in 30 PD patients with drug-induced hallucinations. We performed an extensive battery of neuropsychological tests, the Unified Parkinson's Disease Rating Scale (UPDRS), assessments of on and off time at baseline and at 9 weeks after starting the medication. Sixteen patients on olanzapine (mean dose, 4.6 mg/night) and 11 on placebo completed the study. Compared with placebo, performance on the UPDRS item 2 (thought disorder), and a structured interview for hallucinations, both tended to improve on drug but neither reached statistical significance. A neuropsychological test battery did not show any significant differences. Total on UPDRS motor scores (P < 0.05) and timed tapping (P < 0.01) worsened while on drug compared to placebo. Bradykinesia (P < 0.01) and gait (P < 0.001) items on the UPDRS largely accounted for this deterioration. After completion of the study, 8 of 16 patients randomly assigned to drug continued olanzapine at a mean dose of 2.4 mg/day. However, at the last recorded visit only 5 of 24 (20.8%) of all patients exposed to drug (including those originally randomly assigned to placebo) remained on olanzapine. In patients with PD, low-dose olanzapine did not significantly improve hallucinations but did worsen motor function.",2003.0,0,0
370,12362827,[Opioid detoxication under general anesthesia].,Mikhail J Zemtsovski; Oleg Trosko; Henrik Schmidt,"Antagonist-precipitated opioid detoxification under general anaesthesia has been used extensively since its introduction in 1988. The use of antagonists was believed to shorten the detoxification period. Administration to opioid dependents is followed by a violent activation of the adrenergic system, which results in the development of an acute withdrawal syndrome in the patient. This is usually treated with clonidine. To reduce the subjective discomfort, the procedure is conducted under anaesthesia. From the existing literature, one may conclude that despite more than ten years of development there is currently no sufficient evidence of the effectiveness of antagonist-precipitated opioid detoxification under general anaesthesia conducted under modern anaesthesiological management. Randomised, clinical trials are necessary to document the advantages of this detoxification method as compared to conventional treatment.",2002.0,0,0
371,12363115,Efficacy and safety of aripiprazole and haloperidol versus placebo in patients with schizophrenia and schizoaffective disorder.,John M Kane; William H Carson; Anutosh R Saha; Robert D McQuade; Gary G Ingenito; Dan L Zimbroff; Mirza W Ali,"Aripiprazole is an investigational agent for treating schizophrenia that has a novel pharmacologic profile. The present study investigated the efficacy, safety, and tolerability of aripiprazole and haloperidol compared with placebo. A 4-week, double-blind, randomized study, conducted at 36 U.S. centers between July 1997 and June 1998, compared aripiprazole (15 mg/day, 30 mg/day) to placebo, with haloperidol (10 mg/day) as an active control. Fixed doses of each agent were administered from day 1 throughout the study. A total of 414 patients with a primary DSM-IV diagnosis of schizophrenia or schizoaffective disorder were randomized. Efficacy measures included the Positive and Negative Syndrome Scale (PANSS) total, PANSS positive, PANSS negative, PANSS-derived Brief Psychiatric Rating Scale (BPRS) core, Clinical Global Impressions (CGI)-Severity of Illness, and mean CGI-Improvement scores. Safety and tolerability evaluations included extrapyramidal symptoms (EPS), weight gain, serum prolactin level, and QTc interval. Both doses of aripiprazole and haloperidol, 10 mg, produced statistically significant (p < or = .05) improvements from baseline in PANSS total, PANSS positive, PANSS-derived BPRS core, and CGI-Severity scores and significantly lower CGI-Improvement scores at endpoint, compared with placebo. Aripiprazole, 15 mg, and haloperidol, 10 mg, significantly improved PANSS negative score compared with placebo. Both aripiprazole doses and haloperidol separated from placebo for PANSS total scores at week 2. Unlike haloperidol, aripiprazole was not associated with significant EPS or prolactin elevation at endpoint compared with placebo. There were no statistically significant differences in mean changes in body weight across the treatment groups versus placebo, and no patients receiving aripiprazole experienced clinically significant increases in QTc interval. Aripiprazole, effective against positive and negative symptoms, is a safe and well-tolerated potential treatment for schizophrenia and schizoaffective disorder.",2002.0,0,0
372,12378746,Severe ventricular arrhythmia and sudden death on neuroleptics.,,"(1) Neuroleptics prolong the QT interval, with a risk of torsades de pointes, ventricular tachycardia, syncope and sudden death. This adverse reaction is dose-dependent. (2) Most published cases have involved phenothiazines, and especially thioridazine. Most other neuroleptics have also been involved, including recent drugs such as risperidone and olanzapine. 'Hidden neuroleptics' such as cisapride and injectable domperidone carry the same risk. (3) While this effect has been known for several decades, the degree of risk associated with the various neuroleptics is still poorly known, and few epidemiological data are available. (4) The cornerstones of prevention of cardiac arrhythmia in patients treated with neuroleptics are to weigh up carefully the indications, prescribe the lowest effective dose, and monitor the ECG. All patients should also be screened for precipitating factors, such as other risk factors for torsades de pointes and combination with other drugs that favour torsades de pointes or provoke pharmacokinetic interactions.",2002.0,0,0
373,12381228,Extended-release methylphenidate (Ritalin LA).,Katherine A Lyseng-Williamson; Gillian M Keating,"An extended-release formulation of methylphenidate (Ritalin LA), a CNS stimulant that inhibits dopamine and noradrenaline (norepinephrine) reuptake into presynaptic neurons, has been developed for use in patients with attention deficit/hyperactivity disorder (ADHD). In children with ADHD and healthy male adults, extended-release methylphenidate 20mg was rapidly absorbed and demonstrated two distinct peak plasma concentrations approximately 4 hours apart. The absorption pharmacokinetics of extended-release methylphenidate 20mg, which closely mimics those of immediate-release methylphenidate 10mg given in two doses 4 hours apart, permits once-daily administration. In a 2-week randomised, double-blind, placebo-controlled trial in 134 evaluable children aged 6 to 12 years with ADHD, symptoms improved to a significantly greater extent with extended-release methylphenidate 10 to 40mg once daily than with placebo. Extended-release methylphenidate improved both inattention and hyperactivity symptoms and was effective in children with combined- (inattentive and hyperactive/impulsive) type or predominantly inattentive-type ADHD. In clinical trials, the safety and tolerability profiles of extended-release methylphenidate were consistent with that of the immediate-release formulation.",2003.0,0,0
374,12383035,Aripiprazole.,Jane K McGavin; Karen L Goa,"Aripiprazole is a quinolinone derivative and the first of a new class of atypical antipsychotics. The drug has partial agonist activity at dopamine D(2) and serotonin 5-HT(1A) receptors, and is also an antagonist at 5-HT(2A) receptors. In patients with acute relapse of schizophrenia or schizoaffective disorder, aripiprazole 15 to 30 mg/day was at least as effective as haloperidol 10 mg/day and had similar efficacy to risperidone 6 mg/day in well designed, 4-week, placebo-controlled trials. Negative symptoms improved earlier in the aripiprazole than the risperidone group. Efficacy of aripiprazole was observed at week 1 in several trials and was sustained throughout the study periods. Aripiprazole was superior to placebo in a 26-week trial in patients with stable, chronic schizophrenia. In a 52-week trial involving patients with acute relapsing disease, aripiprazole was similar to haloperidol as assessed by time to failure to maintain response and was superior in ameliorating negative and depressive symptoms. The incidence of extrapyramidal symptoms during aripiprazole therapy was similar to that with risperidone and placebo but lower than with haloperidol. Compared with placebo, the proportion of patients with increased plasma prolactin levels and QTc prolongation was similar in patients treated with aripiprazole 15 to 30 mg/day but was significantly increased with haloperidol and risperidone.",2003.0,0,0
375,12393356,Epinephrine and clonidine do not improve intrathecal sufentanil analgesia after total hip replacement.,R Fournier; E Van Gessel; A Weber; Z Gamulin,"We compared analgesia after intrathecal sufentanil alone, sufentanil with epinephrine 200 microg and sufentanil with clonidine 30 microg in patients after total hip replacement, the endpoints being onset and duration of action. We performed a randomized double-blind study of 45 patients for elective total hip arthroplasty using continuous spinal anaesthesia. As soon as a pain score higher than 3 on a 10 cm visual analogue scale was reported, sufentanil 7.5 microg alone, sufentanil 7.5 microg + epinephrine 200 microg or sufentanil 7.5 microg + clonidine 30 micro g in 2 ml normal saline was given intrathecally. Pain scores, rescue analgesia (diclofenac and morphine) and adverse effects (respiratory depression, postoperative nausea and vomiting, itching) were observed for 24 h after surgery. Time to a pain score of <3 [6 (SD 1) vs 6 (1) vs 5 (1) min], time to the lowest pain score [7 (2) vs 8 (2) vs 8 (2) min] and time to the first dose of systemic analgesic for a pain score >3 [281 (36) vs 288 (23) vs 305 (30) min] were similar in all three groups. Adverse effects and analgesic requirements during the first 24 h were also similar. After total hip replacement, all three analgesic regimens gave good analgesia with comparable onset and duration of action, and minor adverse effects.",2002.0,0,0
376,12398067,The role of magnetic resonance imaging in the assessment of patients with established multiple sclerosis.,M Filippi,,2002.0,0,0
377,12403150,"Young adult follow-up of hyperactive children: self-reported psychiatric disorders, comorbidity, and the role of childhood conduct problems and teen CD.",Mariellen Fischer; Russell A Barkley; Lori Smallish; Kenneth Fletcher,"We report on the psychiatric disorders present at young adult follow-up (Mean age 20-21 years; 13+ year follow-up) and the comorbidity among them for a large sample of hyperactive (H; N = 147) and community control (CC; N = 71) children. The H group had a significantly higher risk for any nondrug psychiatric disorders than the CC group (59% vs. 36%). More of the H group met criteria for ADHD (5%); major depressive disorder (26%); and histrionic (12%), antisocial (21%), passive-aggressive (18%), and borderline personality disorders (14%) at follow-up than the CC group. Severity of childhood conduct problems contributed to the risk for passive-aggressive, borderline, and antisocial personality disorders. But it only affected risk for antisocial personality after controlling for severity of teen conduct disorder (CD), which also contributed to the risk for these same 3 disorders. Examination for comorbidity among these disorders indicated that presence of either borderline or antisocial personality disorder significantly increased the risk for major depression and the other significant personality disorders. More of the hyperactive group had received various forms of mental health treatment during and since leaving high school than the control group. Results suggest that hyperactive children are at significant risk for at least 1 nondrug disorder in young adulthood, principally major depression and several personality disorders, and that this risk is largely mediated by severity of CD at adolescence.",2003.0,0,0
378,12404659,Re: Chan et al. A double-blind randomised comparison of risperidone and haloperidol in the treatment of behavioural and psychological symptoms in Chinese dementia patients. Int J Geriatr Psychiatry 16: 1156 - 1162.,D Onalaja; A K Jainer,,2003.0,0,0
379,12410058,Olanzapine for Huntington's disease: an open label study.,Raphael M Bonelli; Franz A Mahnert; Gerald Niederwieser,"The aim of this prospective open label study was to assess the efficacy of olanzapine for motor symptoms in Huntington's disease (HD). Olanzapine was administrated to nine patients with genetically confirmed HD in increasing doses until satisfactory clinical effect or the appearance of side effects. The patients were evaluated at baseline and after 14 days of treatment using the motor scale of the Unified HD Rating Scale (UHDRS). The patients improved significantly in most subscores of the UHDRS, including fine motor tasks, although some patients needed a rather high dose (30 mg per day). No adverse effects were reported by the patents spontaneously or were observed directly by the investigator. High-dose olanzapine seems to be useful in choreatic HD patients. A double blind, placebo-controlled trial appears warranted to definitively establish the symptomatic value of olanzapine in HD.",2003.0,0,0
380,12411225,"Once-daily atomoxetine treatment for children and adolescents with attention deficit hyperactivity disorder: a randomized, placebo-controlled study.",David Michelson; Albert J Allen; Joan Busner; Charles Casat; David Dunn; Christopher Kratochvil; Jeffrey Newcorn; F Randy Sallee; R Bart Sangal; Keith Saylor; Scott West; Douglas Kelsey; Joachim Wernicke; Nancy J Trapp; Donald Harder,"The authors assessed the efficacy of once-daily atomoxetine administration in the treatment of children and adolescents with attention deficit hyperactivity disorder (ADHD). In a double-blind study, children and adolescents with ADHD (N=171, age range=6-16 years) were randomly assigned to receive 6 weeks of treatment with either atomoxetine (administered once daily) or placebo. Outcomes among atomoxetine-treated patients were superior to those of the placebo treatment group as assessed by investigator, parent, and teacher ratings. The treatment effect size (0.71) was similar to those observed in previous atomoxetine studies that used twice-daily dosing. Parent diary ratings suggested that drug-specific effects were sustained late in the day. Discontinuations due to adverse events were low (less than 3%) for both treatment groups, and no serious safety concerns were observed. Once-daily administration of atomoxetine is an effective treatment for children and adolescents with ADHD.",2002.0,1,1
381,12413642,Serum glucose and lipid changes during the course of clozapine treatment: the effect of concurrent beta-adrenergic antagonist treatment.,Scott P Baymiller; Patricia Ball; Robert P McMahon; Robert W Buchanan,"We examined the effects of long-term clozapine treatment, concurrent treatment with beta-adrenergic antagonists, and clozapine-induced weight gain on serum glucose and lipid measures. Fifty subjects met the DSM-III-R criteria for schizophrenia or schizoaffective disorder, participated in a 10-week, double-blind comparison of haloperidol and clozapine and a 1-year, open-label clozapine trial, and had available serum glucose and lipid levels. Weight and glucose, and lipid laboratory values were measured at the baseline and throughout the double-blind and year-long study. There were significant increases in serum triglyceride, total cholesterol, and glucose levels during the course of clozapine treatment. There were no significant changes in high-density lipoprotein (HDL) or low-density lipoprotein (LDL). Propranolol and atenolol had additive effects on changes in the total cholesterol and triglycerides, with propranolol having the most pronounced effects. Propranolol and atenolol had no significant effect on the serum glucose levels. There were significant correlations between the triglyceride and HDL level changes and clozapine-associated weight gain during the study. There were no significant correlations between the change in serum total cholesterol, LDL, or glucose and weight gain. Clozapine therapy has adverse effects on glucose and lipid homeostasis, with clozapine-induced changes in serum glucose likely due to the inherent pharmacological properties of clozapine. Concurrent beta-adrenergic receptor antagonist treatment may have an additive effect on serum lipids, and clozapine-associated weight gain also plays a modest role in triglyceride increases.",2003.0,0,0
382,12416598,"Risperidone, 2 mg/day vs. 4 mg/day, in first-episode, acutely psychotic patients: treatment efficacy and effects on fine motor functioning.",Marco C G Merlo; Helene Hofer; Walter Gekle; Gregor Berger; Joseph Ventura; Ingrid Panhuber; Gabriela Latour; Stephen R Marder,"The aim of this study was to examine differences in the improvement of clinical psychopathology and in fine motor functions at 2 doses of risperidone in first-episode, acutely psychotic patients. In a double-blind, fixed-dose study, 49 acutely psychotic, neuroleptic-naive patients who were admitted for the first time and who met DSM-IV criteria for schizophrenia, schizophreniform disorder, or schizoaffective disorder were randomly assigned to 2 or 4 mg/day of risperidone. Treatment efficacy was measured using the Brief Psychiatric Rating Scale, the Scale for the Assessment of Negative Symptoms, The Clinical Global Impressions scale, and the Social and Occupational Functioning Assessment Scale. Fine motor functions were assessed using a computerized device (the Vienna Test System) and were compared with those of a control group of 20 healthy subjects who were matched for age, gender, and educational level. Treatment with doses of 2 and 4 mg of risperidone daily significantly reduced positive (p < .0001) and negative (p < .01) symptoms at 8 weeks. Although there were no significant differences in motor movements as measured using the Barnes Akathisia Scale and the Simpson-Angus Scale, computerized fine motor assessment showed significantly less motor dysfunction in the 2-mg/day group at 8 weeks. No significant correlations to plasma concentration of active moiety were found for data on psychopathology and fine motor functions. The 2 doses of risperidone did not differ in terms of clinical improvement, but the 2-mg/day dose produced fewer fine motor dysfunctions. These results suggest that a dose as low as 2 mg/day of risperidone may be effective for patients with first-episode psychosis.",2002.0,0,0
383,12417963,The effects of methylphenidate on prepulse inhibition during attended and ignored prestimuli among boys with attention-deficit hyperactivity disorder.,Larry W Hawk; Andrew R Yartz; William E Pelham; Thomas M Lock,"The present study investigated attentional modification of prepulse inhibition of startle among boys with and without attention-deficit hyperactivity disorder (ADHD). Two hypotheses were tested: (1) whether ADHD is associated with diminished prepulse inhibition during attended prestimuli, but not ignored prestimuli, and (2) whether methylphenidate selectively increases prepulse inhibition to attended prestimuli among boys with ADHD. Participants were 17 boys with ADHD and 14 controls. Participants completed a tone discrimination task in each of two sessions separated by 1 week. ADHD boys were administered methylphenidate (0.3 mg/kg) in one session and placebo in the other session in a randomized, double-blind fashion. During each series of 72 tones (75 dB; half 1200-Hz, half 400-Hz), participants were paid to attend to one pitch and ignore the other. Bilateral eyeblink electromyogram startle responses were recorded in response to acoustic probes (50-ms, 102-dB white noise) presented following the onset of two-thirds of tones, and during one-third of intertrial intervals. Relative to controls, boys with ADHD exhibited diminished prepulse inhibition 120 ms after onset of attended but not ignored prestimuli following placebo administration. Methylphenidate selectively increased prepulse inhibition to attended prestimuli at 120 ms among boys with ADHD to a level comparable to that of controls, who did not receive methylphenidate. These data are consistent with the hypothesis that ADHD involves diminished selective attention and suggest that methylphenidate ameliorates the symptoms of ADHD, at least in part, by altering an early attentional mechanism.",2003.0,0,0
384,12417966,,,,,0,0
385,12418935,An assessment of the independent effects of olanzapine and risperidone exposure on the risk of hyperlipidemia in schizophrenic patients.,Carol E Koro; Donald O Fedder; Gilbert J L'Italien; Sheila Weiss; Laurence S Magder; Julie Kreyenbuhl; Dennis Revicki; Robert W Buchanan,"The newer antipsychotic agents exhibit a superior safety profile compared with conventional antipsychotic agents in terms of extrapyramidal symptoms. Previous studies have suggested an association between olanzapine treatment and hyperlipidemia. We evaluated this association using a large health care database. The study was derived from the England and Wales-based General Practice Research Database, composed of 3.5 million subjects followed up between June 1, 1987, and September 24, 2000. A total of 18 309 individuals diagnosed as having schizophrenia were identified. A 6:1 matched nested case-control design was used. Conditional logistic regression was used to derive adjusted odds ratios (ORs), controlling for sex, age, and other medications and disease conditions influencing lipid levels. Antipsychotic drug exposure was defined as the receipt of at least 1 prescription for an antipsychotic medication within the 3 months before the date of diagnosis of hyperlipidemia. There were 1268 incident cases of hyperlipidemia in the cohort, matched to 7598 control subjects. Olanzapine use was associated with nearly a 5-fold increase in the odds of developing hyperlipidemia compared with no antipsychotic exposure (OR, 4.65; 95% confidence interval [CI], 2.44-8.85) (P<.001) and more than a 3-fold increase compared with those receiving conventional agents (OR, 3.36; 95% CI, 1.77-6.39) (P<.001). Risperidone was not associated with increased odds of hyperlipidemia compared with no antipsychotic exposure (OR, 1.12; 95% CI, 0.60-2.11) (P =.72) or conventional antipsychotic exposure (OR, 0.81; 95% CI, 0.44-1.52) (P =.52). We observed a strong association between olanzapine exposure and hyperlipidemia in schizophrenic patients. The possible metabolic consequences of olanzapine use should be given serious consideration by treating physicians.",2002.0,0,0
386,12424166,Cardiac arrest and ventricular arrhythmia in patients taking antipsychotic drugs: cohort study using administrative data.,Sean Hennessy; Warren B Bilker; Jill S Knauss; David J Margolis; Stephen E Kimmel; Robert F Reynolds; Dale B Glasser; Mary F Morrison; Brian L Strom,"To examine the rates of cardiac arrest and ventricular arrhythmia in patients with treated schizophrenia and in non-schizophrenic controls. Cohort study of outpatients using administrative data. 3 US Medicaid programmes. Patients with schizophrenia treated with clozapine, haloperidol, risperidone, or thioridazine; a control group of patients with glaucoma; and a control group of patients with psoriasis. Diagnosis of cardiac arrest or ventricular arrhythmia. Patients with treated schizophrenia had higher rates of cardiac arrest and ventricular arrhythmia than controls, with rate ratios ranging from 1.7 to 3.2. Overall, thioridazine was not associated with an increased risk compared with haloperidol (rate ratio 0.9, 95% confidence interval 0.7 to 1.2). However, thioridazine showed an increased risk of events at doses > or =600 mg (2.6, 1.0 to 6.6; P=0.049) and a linear dose-response relation (P=0.038). The increased risk of cardiac arrest and ventricular arrhythmia in patients with treated schizophrenia could be due to the disease or its treatment. Overall, the risk with thioridazine was no worse than that with haloperidol. Thioridazine may, however, have a higher risk at high doses, although this finding could be due to chance. To reduce cardiac risk, thioridazine should be prescribed at the lowest dose needed to obtain an optimal therapeutic effect.",2002.0,0,0
387,12424551,Effects of stimulant medications on the EEG of children with attention-deficit/hyperactivity disorder.,Adam R Clarke; Robert J Barry; Dominique Bond; Rory McCarthy; Mark Selikowitz,"Stimulant medications are the most commonly used treatments for attention deficit/hyperactivity disorder (ADHD) in North America and Australia, although it is still not entirely known how these medications work. This study aimed to investigate the effects of stimulant medications on the EEG of children with the Combined subtype of ADHD. An initial EEG was recorded during an eyes-closed resting condition and Fourier transformed to provide absolute and relative power estimates for the delta, theta, alpha and beta bands. Theta/alpha and theta/beta ratios were also calculated. Subjects were placed on a 6-month trial of a stimulant and a second EEG was recorded at the end of the trial. The ADHD group had significantly greater absolute delta and theta, less posterior absolute beta, more relative theta, and less relative alpha than the control group, which is typical of EEG studies of children with ADHD. The use of stimulant medications resulted in normalisation of the EEG, primarily evident in changes in the theta and beta bands. These results suggest that stimulants act to increase cortical arousal in children with ADHD, normalising their brain activity.",2003.0,0,0
388,12435529,"Psychotropic and neurotropic agents in dermatology: unapproved uses, dosages, or indications.",John Y Koo; Theresa C Ng,,2003.0,0,0
389,12444819,Depression and dysphoria in adult and adolescent patients with Tourette's disorder treated with risperidone.,Howard C Margolese; Lawrence Annable; Yves Dion,"Depression is a common comorbid condition in patients with Tourette's disorder. While risperidone is not usually known to induce dysphoria or depression in patients treated for other psychiatric disorders, previous short-term 4- to 12-week trials of risperidone for Tourette's disorder have reported a 2.6% to 30.8% incidence of depression. A retrospective study was carried out in 58 adult and adolescent patients with Tourette's disorder (Tourette Syndrome Classification Study Group diagnosis) who received risperidone between Jan. 1, 1993, and Dec. 31, 2000, at the Allan Memorial Institute, McGill University Health Centre, Montreal, Quebec, Canada. Charts of all patients were examined for evidence of, and risk factors for, DSM-IV-defined major depressive disorder (MDD) or dysphoria. Seventeen (29.3%) of 58 patients developed MDD, including 1 patient who later committed suicide and 13 patients (22.4%) who became dysphoric while taking risperidone. Nine of the 17 patients who developed MDD were relapses, i.e., patients with a history of depression prior to taking risperidone, while the remainder were new cases, i.e., patients with no previous history of depression. A positive personal history of MDD was the only factor to significantly (p <.001) predict the development of depression while taking risperidone. Seventy percent of those who developed MDD or dysphoria and discontinued risperidone did so specifically as a result of this adverse event. MDD and dysphoria commonly occurred in this cohort of adult and adolescent Tourette's disorder patients treated with risperidone, particularly in patients with a previous history of depression. Depression and dysphoria were frequent reasons for risperidone discontinuation.",2002.0,0,0
390,12452546,,,,,0,0
391,12454566,Dosing strategies of clozapine-fluvoxamine cotreatment.,Mong-Liang Lu; Hsien-Yuan Lane; Michael W Jann; Wen-Ho Chang,,2003.0,0,0
392,12462294,An economic assessment of quetiapine and haloperidol in patients with schizophrenia only partially responsive to conventional antipsychotics.,Dominic Tilden; Mike Aristides; David Meddis; Tom Burns,"Many patients with schizophrenia exhibit only a partial response to conventional antipsychotic agents, making them difficult to treat adequately. This analysis models the cost-effectiveness of quetiapine compared with haloperidol in partial responders with schizophrenia. Outcome data from the Partial Responders International schiZophrenia Evaluation (PRIZE) clinical trial comparing quetiapine and haloperidol in partial responders with schizophrenia as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition were combined with data from the literature to construct a Markov model. The model was used to calculate treatment outcomes and total direct treatment costs from the perspective of the United Kingdom National Health Service over 5 years. The PRIZE study showed that quetiapine treatment resulted in a higher response rate and better tolerability than haloperidol treatment. These benefits have the potential to improve compliance and reduce relapse rates. The model showed that the higher acquisition cost of quetiapine was offset by lower costs for other medications, hospitalization, and other medical services. The total treatment cost over 5 years was 38,106 pounds for quetiapine and 38,350 pounds for haloperidol, a cost saving of 244 pounds in favor of quetiapine. Quetiapine-treated patients also spent longer in response states and experienced fewer relapses. Sensitivity analysis showed these results to be robust across a range of conditions. Quetiapine has the potential to improve outcomes compared with haloperidol in partial responders with schizophrenia, at a slightly lower total cost. The higher acquisition cost of quetiapine was offset by savings in other medical costs. Quetiapine could significantly improve the management of this patient group, without increasing the economic burden on the health service.",2003.0,0,0
393,12463729,Pharmacokinetic and safety assessments of galantamine and risperidone after the two drugs are administered alone and together.,Fenglei Huang; Kenneth C Lasseter; Luc Janssens; Tom Verhaeghe; Henry Lau; Qinying Zhao,"To explore the steady-state pharmacokinetic profile after coadministration of galantamine and risperidone, an open-label, randomized, single-center, two-way crossover drug-drug interaction study was conducted in 16 healthy elderly subjects, ages 60 years and older. The results showed that risperidone, when administered with galantamine, did not change the bioavailability of galantamine at steady state. In addition, systemic exposure of risperidone active moiety (risperidone plus 9-hydroxyrisperidone), the most clinically relevant component of risperidone treatment, was not affected by galantamine coadministration, while systemic exposure was increased by approximately 10% for risperidone and decreased by about 10% for 9-hydroxyrisperidone (active metabolite of risperidone). Galantamine and risperidone were both safe and well tolerated administered either alone or together. Thus, no dose adjustment for either risperidone orgalantamine is necessary when these two drugs are administered together in the dose range evaluated.",2003.0,0,0
394,12464464,Amisulpride vs. risperidone in chronic schizophrenia: results of a 6-month double-blind study.,Daniel Sechter; Joseph Peuskens; Odile Fleurot; Werner Rein; Yves Lecrubier; Amisulpride Study Group,"This multicenter, double-blind, randomized study evaluated the efficacy, safety and functional effects of two atypical antipsychotics, amisulpride and risperidone, in patients with chronic schizophrenia (DSM IV) with a recent worsening of symptoms. It was planned as a non-inferiority trial. 309 patients received amisulpride (400-1,000 mg/day) or risperidone (4-10 mg/day) for six months. Amisulpride was demonstrated to be not inferior to risperidone with respect to the decrease in Positive and Negative Syndrome Scale (PANSS) total score from baseline (90% 2-sided confidence interval (-5.6; 4.0)). Symptomatic improvement measured with the Brief Psychiatry Rating Scale (BPRS), the PANSS positive subscale, and the Bech Rafaelsen Melancholia Scale was similar in both groups. Amisulpride was significantly (p <.05) superior to risperidone in terms of response (>/=50% improvement in PANSS and BPRS total scores or ""very much/much improved"" on the Clinical Global Impression Scale) and also demonstrated better functional effects and subjective response. Both treatments were well tolerated and had a similar low incidence of extrapyramidal symptoms; however, amisulpride was associated with less weight gain and endocrine/sexual symptoms.",2003.0,0,0
395,12471781,[Spinal anesthesia in children: comparative study of hyperbaric bupivacaine with or without clonidine].,O Kaabachi; A Ben Rajeb; M Mebazaa; H Safi; C Jelel; M Ben Ghachem; M Ben Ammar,"To evaluate the effect of intrathecal clonidine in children. A prospective randomised study. 45 children, 6 to 15 years old, were randomised in two groups; receiving either 0.5% hyperbaric bupivacaine or 0.5% hyperbaric bupivacaine added to clonidine 2 micrograms.kg-1. We assessed quality and length of motor and sensory blocks and side effects of clonidine: hypotension, bradycardia and sedation. Clonidine was associated with prolongation of motor block. 190 +/- 42 min vs 150 +/- 35 min (p < 0.01), but the difference was not significant. Postoperative analgesia was longer in clonidine group, 490 +/- 35 min vs 200 +/- 50 min (mean +/- SD), p < 0.001. Clonidine was associated with higher incidence of hypotension 54 vs 36% and bradycardia 30 vs 0%. These data suggest that intrathecal clonidine 2 micrograms.kg-1 is associated with extending duration of postoperative analgesia but with moderate side effects.",2003.0,0,0
396,12486650,Remifentanil-clonidine-propofol versus sufentanil-propofol anesthesia for coronary artery bypass surgery.,K Gerlach; Th Uhlig; M Hüppe; E Kraatz; L Saager; A Schmitz; V Dörges; P Schmucker,"To compare a remifentanil-clonidine-propofol regimen with conventional sufentanil-propofol anesthesia. Randomized, nonblinded trial. A single university hospital. Male patients scheduled for coronary artery bypass graft (CABG) surgery. In the control group, anesthesia was induced with 0.5 microg/kg of sufentanil and 0.2 to 0.3 mg/kg of etomidate after preoxygenation. Propofol (50 to 100 microg/kg/min) and sufentanil (0.5 to 1.0 microg/kg/h) were started after endotracheal intubation. Sufentanil was stopped after aortic decannulation. In the remifentanil-clonidine group, anesthesia was started with remifentanil (0.15 to 0.3 microg/kg/min), followed by etomidate (0.2 to 0.3 mg/kg). Propofol was started at 50 to 100 microg/kg/min, and after endotracheal intubation, clonidine infusion was started (6 to 20 microg/h). Patients received piritramide (0.15 mg/kg) and metamizole (20 mg/kg) for transitional analgesia. In both groups, propofol infusion was reduced to 30 to 60 microg/kg/min at skin closure and stopped when assisted spontaneous breathing led to adequate gas exchange. The main outcomes were recovery times; somatic variables; plasma catecholamine levels; and self-recorded pain, nausea, and vomiting. Patients in the remifentanil-clonidine group were extubated earlier and had lower plasma epinephrine and norepinephrine levels. After transitional analgesia, the remifentanil-clonidine patients had similar postoperative analgesic use and self-reported pain and side-effect scores. Compared with a sufentanil-propofol regimen, an anesthetic regimen for CABG surgery that combines remifentanil, clonidine, and propofol provides similar hemodynamics. The remifentanil-clonidine regimen reduces catecholamine levels and hastens recovery from anesthesia.",2003.0,0,0
397,12489899,"Modafinil for the treatment of daytime sleepiness in Parkinson's disease: a double-blind, randomized, crossover, placebo-controlled polygraphic trial.",B Högl; M Saletu; E Brandauer; S Glatzl; B Frauscher; K Seppi; H Ulmer; G Wenning; W Poewe,"To assess the therapeutic efficacy of modafinil in the treatment of increased daytime sleepiness in patients with Parkinson's disease (PD). Double-blind, randomized, placebo-controlled crossover study with two 2-week treatment blocks, separated by a 2-week washout phase. Tertiary Parkinson's disease care center and sleep laboratory at university hospital neurology department. Fifteen patients with idiopathic PD and daytime sleepiness (Epworth sleepiness score (ESS) 10 or more). Administration of placebo or modafinil as a single morning dose in a randomized crossover order. The modafinil dose was 100 mg in the first, and 200 mg in the second treatment week. At baseline and at the end of each treatment block, sleepiness was evaluated using subjective (perceived sleepiness with the ESS) and objective measures (maintenance of wakefulness test). Twelve patients completed the study (9 male, 3 female; mean age 65.0 +/- 7.6 years, mean disease duration 6.8 +/- 4.1 years). Epworth scores were significantly improved with modafinil (3.42 +/- 3.90) compared to placebo (0.83 +/- 1.99; p = 0.011). Latency to sleep in the maintenance of wakefulness test was not significantly altered by modafinil treatment: 10.9 (3-40)/15.1 (2.5-40) minutes before/after placebo and 12 (2.6-40)/17.8 (4.2-40) minutes before/after modafinil (p = 0.139) [data given as mean +/- standard deviation or median (range)]. The results of this study suggest that modafinil improves daytime sleepiness in PD patients, at least on a subjective or behavioral level. Modafinil treatment may be considered for EDS in PD patients, in whom otherwise treatable causes of Excessive Daytime Sleepiness (EDS) are absent.",2003.0,0,0
398,12490774,Extrapyramidal symptom profiles assessed with the Drug-Induced Extrapyramidal Symptom Scale: comparison with Western scales in the clinical double-blind studies of schizophrenic patients treated with either olanzapine or haloperidol.,Toshiya Inada; Charles M Beasley; Yoko Tanaka; Daniel J Walker,"The superiority of olanzapine to haloperidol with respect to a decreased incidence of treatment-emergent extrapyramidal syndromes (EPS) in patients with schizophrenia was demonstrated in studies conducted in both Japan and Western countries. EPS measurements used in Western countries included the Simpson-Angus, Barnes akathisia and the Abnormal Involuntary Movement Scale, while the Drug-Induced Extrapyramidal Symptom Scale (DIEPSS) was used in Japan. The aim of this study was to clarify how the DIEPSS captures EPS profiles. The baseline prevalence and treatment-emergent incidence of EPS in Japanese schizophrenic patients treated with olanzapine or haloperidol were retrospectively compared as assessed by the DIEPSS to the prevalence and incidence of EPS in primarily Caucasian schizophrenic patients who were treated with olanzapine or haloperidol. Specifically, the prevalence and incidence of dyskinesia, akathisia and parkinsonism were compared between the Japanese trial and an international trial to examine if appropriate definitions using the DIEPSS can be derived assuming that a comparable prevalence and incidence of the syndromes would be observed when any differences in residual antipsychotic exposure at the initiation of study treatment were accounted for. For the incidence of all EPS syndromes, odds ratios were observed to be similar between the two studies, indicating that appropriate criteria for the clinical diagnosis of the EPS syndromes could be established based on the DIEPSS. This preliminary and retrospective work suggests that the DIEPSS can be used to operationally define the presence or absence, and make the clinical diagnosis, of specific EPS syndromes.",2003.0,0,0
399,12496955,Effect of divalproex combined with olanzapine or risperidone in patients with an acute exacerbation of schizophrenia.,Daniel E Casey; David G Daniel; Adel A Wassef; Katherine A Tracy; Patricia Wozniak; Kenneth W Sommerville,"This double-blind, randomized, multicenter study investigated the use of divalproex with an antipsychotic agent in patients hospitalized for acute exacerbation of schizophrenia. Patients (n = 249) who met DSM-IV criteria for schizophrenia were randomly assigned to receive olanzapine monotherapy, risperidone monotherapy, divalproex plus olanzapine, or divalproex plus risperidone for 28 days. Divalproex was initiated at 15 mg/kg/day and titrated over 12 days to a maximum dosage of 30 mg/kg/day. Olanzapine and risperidone, were, respectively, initiated at 5 and 2 mg/day and were titrated over the first 6 days to respective target fixed daily dosages of 15 and 6 mg/day. Improvements from baseline were observed at all evaluation points throughout the 28-day treatment period in the two combination therapy and the two antipsychotic monotherapy groups, with statistically significant treatment differences favoring combination therapy as soon as day 3 for Positive and Negative Syndrome Scale (PANSS) total score, derived Brief Psychiatric Rating Scale (BPRSd) total score, as well as PANSS and BPRSd subscales. These findings were confirmed in post hoc repeated-measures analyses of variance in which treatment differences favoring combination therapy were observed for PANSS total (p = 0.020) and PANSS positive scale scores (p = 0.002). Both combination therapy and antipsychotic monotherapy were well tolerated. Treatment with divalproex in combination with an atypical antipsychotic agent resulted in earlier improvements in a range of psychotic symptoms among acutely hospitalized patients with schizophrenia. Further evaluation is warranted to confirm these findings.",2003.0,0,0
400,12499477,Modafinil reduces excessive somnolence and enhances mood in patients with myotonic dystrophy.,J R MacDonald; J D Hill; M A Tarnopolsky,"To evaluate the potential of modafinil in reducing excessive daytime somnolence (EDS) and enhancing indexes of quality of life and mood in patients with myotonic dystrophy (DM). Forty patients with DM were randomized to receive modafinil and placebo for 14 days each, using a double-blind, cross-over design. Before and after each trial, subjects completed handgrip strength testing, spirometry, and quality-of-life measures (RAND). On days 7 and 14, each subject completed the Epworth Sleepiness Scale (ESS), the Stanford Sleepiness Scale (SSS), and the Profile of Mood States (POMS). ESS scores were lower while taking modafinil (mean 248 mm; 95% confidence limit 220 to 276 mm) as compared with placebo (309 mm; 281 to 336 mm) (p < 0.001). Mean SSS scores were also lower during the modafinil trial (3.05; 2.77 to 3.33) than during the placebo trial (3.45; 3.18 to 3.71) (p < 0.05). The POMS indicated that modafinil decreased fatigue-inertia (p < 0.001) and increased vigor-activity and tension-anxiety (p < 0.001) indexes. The total mood disturbance score was also decreased during the modafinil trial as compared with placebo (p < 0.05). The RAND quality-of-life measures of energy (p < 0.001) and health change (p < 0.05) were both significantly enhanced during the modafinil treatment phase. No changes in maximal grip strength or forced expired volume in 1 second were detected over the course of the study. Headache was the most frequently reported adverse event. Four patients withdrew from the study, three because of side effects (two during modafinil ingestion and one during placebo ingestion). Modafinil reduces somnolence and improves mood in patients with DM.",2003.0,0,0
401,12503835,The potential cardiotoxicity of antipsychotic drugs as assessed by heart rate variability.,B Silke; C Campbell; D J King,"Most antipsychotic drugs have cardiac effects as a consequence of their pharmacological actions. Recently, thioridazine has been subjected to a restricted indications notice and sertindole had its license withdrawn because of concerns about their potential cardiotoxicity. In the development of new atypical agents, heart-rate corrected QT effects are evaluated but it is unclear how predictive these are of clinically significant cardiotoxicity or sudden death. Heart rate variability (HRV) is a potential index of cardiotoxicity which has been found to be decreased following antidepressants and clozapine. We studied acute HRV changes following antipsychotic agents. Sixteen healthy male volunteers received risperidone (4 mg), olanzapine (10 mg), thioridazine (50 mg) or placebo in a randomized cross-over design. Subjective effects and psychomotor function were assayed at 2 h and both linear (summary statistics) and non-linear (scatterplot) measures of HRV were evaluated by continuous electrocardiogram recording over 10 h. Differential effects of single doses of the three antipsychotic drugs on HRV were found, and these were independent of their sedative effects. Olanzapine increased, and thioridazine decreased HRV, while risperidone had no effect. HRV is sensitive to the acute effects of antipsychotics. It may prove to be a reliable index of their potential for cardiotoxicity. Further studies in both healthy volunteers and patients on antipsychotic medication will be valuable.",2003.0,0,0
402,12503837,Efficacy of olanzapine in social anxiety disorder: a pilot study.,Stewart D Barnett; Michelle L Kramer; Charles D Casat; Kathryn M Connor; Jonathan R T Davidson,"Based on evidence suggesting anxiolytic properties of the atypical antipsychotic olanzapine, this study was conducted to evaluate whether olanzapine may be efficacious in treating social anxiety disorder (SAD). This study was an 8-week, double-blind, placebo-controlled evaluation of olanzapine as monotherapy in which 12 patients with the DSM-IV diagnosis of SAD were randomized to either olanzapine (n = 7) or placebo (n = 5). An initial dose of 5 mg/day was titrated to a maximum of 20 mg/day. Baseline to endpoint scores from the Brief Social Phobia Scale (BSPS), Social Phobia Inventory (SPIN), Liebowitz Social Anxiety Scale and Sheehan Disability Scale, as well as Clinical Global Impression-Improvement ratings, were compared for olanzapine versus placebo. Seven subjects completed all 8 weeks of the study, four in the olanzapine group and three in the placebo group. In the intent-to-treat analysis, olanzapine yielded greater improvement than placebo on the primary measures: BSPS (p = 0.02) and SPIN (p = 0.01). Both treatments were well tolerated, although the olanzapine group had more drowsiness and dry mouth. Olanzapine and placebo were both associated with negligible weight gain. Olanzapine was superior to placebo on the primary outcome measures in this preliminary study of SAD. Additional studies of olanzapine as a treatment for SAD are warranted.",2003.0,0,0
403,12504069,Efficacy of newer generation antipsychotics in the treatment of schizophrenia.,R Tandon; M D Jibson,"The advent of the newer 'atypical' antipsychotic medications has revolutionized the pharmacologic treatment of schizophrenia and other psychotic disorders. In contrast to the older conventional antipsychotic agents, atypical medications have a broader spectrum of efficacy (greater efficacy in negative, cognitive, and mood symptoms) and a lower risk of extrapyramidal symptoms (EPS) and tardive dyskinesia. Due to concerns surrounding hematological safety and other adverse effects, clozapine is used principally in patients refractory to treatment with other antipsychotic agents. The other three universally available atypical agents (risperidone, olanzapine, and quetiapine) collectively constitute about 70% of all antipsychotic prescriptions in the USA. Despite the broad popularity of these medications and their rapid adoption in general clinical practice, there are limited data on how they compare to each other with regards to their overall efficacy and also as to their efficacy in specific symptom domains. To address this question, two separate analyses were undertaken. First, all published, short-term, randomized, controlled clinical trials of these agents in schizophrenia and schizoaffective disorder were reviewed and the extent of improvement across these agents was compared. While the amount of improvement with a particular agent across its different studies varied, the average improvement was similar for the agents for all efficacy parameters considered. Secondly, all randomized, controlled clinical trials directly comparing two or more of these agents in patients with schizophrenia or schizoaffective disorder were analyzed. Only three such trials (all industry sponsored) were identified; while there were differences in methodology and small differences in efficacy on a minority of measures on which comparisons were undertaken, the preponderance of data suggested no differences in efficacy. While data thus far do not support assertions of differential efficacy between risperidone, olanzapine, and quetiapine, there are clear differences in their side-effect profiles and these are briefly summarized.",2003.0,0,0
404,12505103,Quetiapine is not associated with increase in prolactin secretion in contrast to haloperidol.,Murad Atmaca; Murat Kuloglu; Ertan Tezcan; Halit Canatan; Omer Gecici,"Typical antipsychotic drugs frequently cause hyperprolactinemia and even galactorrhea. In addition, these side effects may result in noncompliance with antipsychotic treatment. Capacity to avoid hyperprolactinemia has been accepted as one atypical criterion. The aim of the present study was to compare effects of haloperidol, the most commonly used antipsychotic, and quetiapine, a novel antipsychotic agent used in Turkey, on serum prolactin (PRL) levels. The study consisted of 35 females diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, 4(th) ed. (DSM-IV). Thirty-five patients in a drug-free period for at least 2 weeks were included to randomized quetiapine (n = 18) and haloperidol (n = 17) treatment group. All patients were assessed by Brief psychiatric rating scale (BPRS), Positive and negative syndrome scale (PANSS), and Extrapyramidal symptoms rating scale (ESRS). PRL levels were measured both at the beginning and at the sixth week of the study. Both treatment groups exhibited significant improvements in clinical signs as evaluated by BPRS and PANSS. While there was no significant difference in PRL level between groups at the beginning of the study, control prolactin (PRL) levels were significantly lower in quetiapine compared to haloperidol group. While no quetiapine group patients exhibited galactorrhea, we observed that two patients from the haloperidol group had galactorrhea related to hyperprolactinemia. The present study revealed that quetiapine is not associated with increase in PRL secretion in contrast to the conventional antipsychotic haloperidol.",2003.0,0,0
405,12505963,The analgesic effect of interscalene block using clonidine as an analgesic for shoulder arthroscopy.,Henri Iskandar; Antoine Benard; Joelle Ruel-Raymond; Gyslaine Cochard; Bertrand Manaud,"Used as the sole analgesic, clonidine produces analgesia after central neural blockade and intraarticular injection but not after axillary block. In this study, we sought to determine whether interscalene clonidine induces analgesia for shoulder arthroscopy. Forty patients scheduled for shoulder arthroscopy were prospectively included in this double-blinded study. Using a nerve stimulator technique, an interscalene catheter was inserted. The patients were randomly divided into two groups. The interscalene group (n = 20) received clonidine 150 micro g in 15 mL of saline through the catheter and 1 mL of subcutaneous saline, and the systemic group (n = 20) received 15 mL of saline through the catheter and clonidine 150 micro g (1 mL) subcutaneously. All patients underwent general anesthesia for surgery. On completion of arthroscopy, all patients received, via a patient-controlled analgesia, on demand a bolus of 8 mL of ropivacaine 0.2% through the catheter with a 1-h lockout period. Postoperative pain was measured every 4 h using the visual analog scale (VAS) for 24 h. Additional postoperative analgesia was available with parenteral nalbuphine if required until VAS < 3. VAS scores in the recovery room were significantly higher in the systemic group compared with the interscalene group (P < 0.0001). Analgesic duration was significantly longer in the interscalene group (P < 0.00001), and ropivacaine consumption was significantly less than in the systemic group (P < 0.0001). No significant difference was observed between groups for nalbuphine consumption. Side effects were comparable in the two groups. Clonidine administered via an interscalene catheter enhanced analgesia compared with systemic administration. Nevertheless, the adverse effect of clonidine at this dose limits its use for routine management for postoperative analgesia.",2003.0,0,0
406,12507747,Placebo-controlled trials do not find association of olanzapine with exacerbation of bipolar mania.,Robert W Baker; Denái R Milton; Virginia L Stauffer; Alan Gelenberg; Mauricio Tohen,"Published case reports describe apparent induction or exacerbation of manic-like symptoms during treatment with the atypical antipsychotics olanzapine and risperidone. To date, such reports are from uncontrolled clinical experience and therefore cannot clarify whether the atypical antipsychotics caused such manic-like states or simply failed to prevent them. Presumably, bipolar patients would be at increased risk for this putative adverse event. Therefore, we evaluated the potential of olanzapine to exacerbate symptoms of mania compared to placebo during treatment of bipolar mania. Two inpatient, double-blind, randomized trials investigating the efficacy of olanzapine 5-20 mg daily versus placebo for the treatment of acute mania were combined. Two hundred and fifty-four subjects participated (placebo n=129; olanzapine n=125) in the two studies. Severity of mania was quantified with the 11-item Young-Mania Rating Scale (Y-MRS). In a post-hoc analysis, after double-blind therapy up to 3 weeks, categorical comparison of olanzapine and placebo groups was made for any worsening and worsening by 10 or 20% from baseline Y-MRS scores (LOCF). The percentage of subjects with exacerbation at endpoint were: any worsening, placebo 37.7%, olanzapine 21.8% (P=0.005); >or=10% worsening, placebo 24.6%, olanzapine 14.5% (P=0.039); >or=20% worsening, placebo 15.6%, olanzapine 8.1% (P=0.064). Mania rating scores worsened for some patients during olanzapine therapy. However, this was significantly less common with olanzapine than with placebo. These controlled data suggest that clinical case reports of occurrence of 'mania' during treatment with olanzapine, and possibly those with other atypical antipsychotics, reflect exacerbation in the natural history of bipolar illness, rather than an adverse pharmacological effect. Post-hoc analysis of pooled data from two different studies.",2003.0,0,0
407,12509561,Does the treatment of attention-deficit/hyperactivity disorder with stimulants contribute to drug use/abuse? A 13-year prospective study.,Russell A Barkley; Mariellen Fischer; Lori Smallish; Kenneth Fletcher,"To examine the impact of stimulant treatment during childhood and high school on risk for substance use, dependence, and abuse by young adulthood. A total of 147 clinic-referred hyperactive children were followed approximately 13 years into adulthood (mean: 21 years old; range: 19-25). At adolescent (age 15) and adult follow-up, probands were interviewed about their use of various substances and duration of stimulant treatment. Duration of stimulant treatment was not significantly associated with frequency of any form of drug use by young adulthood. Stimulant-treated children had no greater risk of ever trying drugs by adolescence or any significantly greater frequency of drug use by young adulthood. Stimulant treatment in high school also did not influence drug use in adulthood except for greater use of cocaine. This difference was no longer significant after controlling for severity of attention-deficit/hyperactivity disorder and conduct disorder in childhood, adolescence, and adulthood. Stimulant treatment in either childhood or high school was not associated with any greater risk for any formal Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised drug dependence or abuse disorders by adulthood. Treatment with stimulants did not increase the risk of ever having tried most illegal substances by adulthood except for cocaine. Subsequent analyses showed that this elevated risk was primarily mediated by severity of conduct disorder by young adulthood and not by stimulant treatment in childhood. This study concurs with 11 previous studies in finding no compelling evidence that stimulant treatment of children with attention-deficit/hyperactivity disorder leads to an increased risk for substance experimentation, use, dependence, or abuse by adulthood.",2003.0,0,0
408,12509574,Does stimulant therapy of attention-deficit/hyperactivity disorder beget later substance abuse? A meta-analytic review of the literature.,Timothy E Wilens; Stephen V Faraone; Joseph Biederman; Samantha Gunawardene,"Concerns exist that stimulant therapy of youths with attention-deficit/hyperactivity disorder (ADHD) may result in an increased risk for subsequent substance use disorders (SUD). We investigated all long-term studies in which pharmacologically treated and untreated youths with ADHD were examined for later SUD outcomes. A search of all available prospective and retrospective studies of children, adolescents, and adults with ADHD that had information relating childhood exposure to stimulant therapy and later SUD outcome in adolescence or adulthood was conducted through PubMed supplemented with data from scientific presentations. Meta-analysis was used to evaluate the relationship between stimulant therapy and subsequent SUD in youths with ADHD in general while addressing specifically differential effects on alcohol use disorders or drug use disorders and the potential effects of covariates. Six studies--2 with follow-up in adolescence and 4 in young adulthood--were included and comprised 674 medicated subjects and 360 unmedicated subjects who were followed at least 4 years. The pooled estimate of the odds ratio indicated a 1.9-fold reduction in risk for SUD in youths who were treated with stimulants compared with youths who did not receive pharmacotherapy for ADHD (z = 2.1; 95% confidence interval for odds ratio [OR]: 1.1-3.6). We found similar reductions in risk for later drug and alcohol use disorders (z = 1.1). Studies that reported follow-up into adolescence showed a greater protective effect on the development of SUD (OR: 5.8) than studies that followed subjects into adulthood (OR: 1.4). Additional analyses showed that the results could not be accounted for by any single study or by publication bias. Our results suggest that stimulant therapy in childhood is associated with a reduction in the risk for subsequent drug and alcohol use disorders.",2003.0,0,1
409,12521356,Bupropion for the treatment of tobacco dependence: guidelines for balancing risks and benefits.,J Taylor Hays; Jon O Ebbert,"Tobacco use, particularly cigarette smoking, is now a global pandemic. The expected morbidity and mortality from smoking-attributable diseases will continue to rise for the next 30 years. In order to reduce this negative impact on worldwide health, effective therapy to aid smoking cessation must be provided to current smokers. Treatment for tobacco dependence involves the combination of behavioural therapies and pharmacological treatment. The most common pharmacological treatments include nicotine replacement therapy and non-nicotine medications, including antidepressants. The antidepressant with the greatest weight of evidence for efficacy in the treatment of tobacco dependence is bupropion. Sustained-release bupropion is approved for the treatment of tobacco dependence in over 50 countries worldwide. The efficacy of bupropion for the treatment of tobacco dependence is attributed to the blockage of dopamine reuptake in the mesolimbic dopaminergic system. This area of the brain is believed to mediate reward for nicotine use and for other drugs of dependence. Randomised, controlled clinical trials have shown that bupropion approximately doubles abstinence rates compared with placebo. In addition, long-term treatment with bupropion may reduce or delay smoking relapse. Bupropion also appears to be effective in the treatment of smokers who have recently relapsed and smokers with other comorbid psychiatric conditions. Bupropion has a good adverse events profile, but the risk exists for serious adverse effects such as seizures. Recent postmarketing surveillance reports have raised safety concerns about bupropion, although no causal relationship between bupropion and the reported serious adverse events or death has been established.",2003.0,0,0
410,12523873,The risk of diabetes during olanzapine use compared with risperidone use: a retrospective database analysis.,J Jaime Caro; Alexandra Ward; Carey Levinton; Kimberly Robinson,"The relative risk of diabetes among patients undergoing risperidone treatment was compared with that of patients receiving olanzapine. A cohort was formed of 33,946 patients with at least 1 prescription for either olanzapine (N = 19,153) or risperidone (N = 14,793) between January 1, 1997, and December 31, 1999, recorded in the Régie de l'Assurance Maladie du Québec database. Patients were excluded if clozapine was dispensed to them during the study period or if they were diagnosed with diabetes before beginning antipsychotic therapy. New diabetes diagnoses made after the first antipsychotic prescription during the period were tabulated until December 31, 1999; censoring occurred at this date or at the last service date, if there was no record of using services during the last 6 months of follow-up. Crude hazard ratio and proportional hazard analyses were carried out. 319 patients developed diabetes on olanzapine treatment, and 217 developed diabetes on risperidone treatment; a crude hazard ratio of 1.08 (95% CI = 0.89 to 1.31, p =.43) was determined. When age, gender, and haloperidol use were controlled for using proportional hazard analysis, there was a 20% increased risk of diabetes with olanzapine relative to risperidone (95% CI = 0% to 43%, p =.05). Proportional hazard analyses adjusted for duration of olanzapine exposure indicated that the first 3 months of olanzapine treatment was associated with an increased risk of diabetes of 90% (95% CI = 40% to 157%, p <.0001), after adjusting for age, gender, and haloperidol use. Compared with risperidone, olanzapine was associated with an increased risk of developing diabetes. More studies are required to further investigate this association.",2003.0,0,1
411,12523874,"Results from 2 proof-of-concept, placebo-controlled studies of atomoxetine in children with attention-deficit/hyperactivity disorder.",Thomas Spencer; John H Heiligenstein; Joseph Biederman; Douglas E Faries; Christopher J Kratochvil; C Keith Conners; William Z Potter,"Atomoxetine is a nonstimulant drug being studied for the treatment of attention-deficit/hyperactivity disorder (ADHD). Atomoxetine is a highly specific inhibitor of the presynaptic norepinephrine transporter with minimal affinity for other noradrenergic receptors or other neurotransmitter transporters or receptors. Results of 2 proof-of-concept studies are reported that tested the hypothesis that a selective inhibitor of presynaptic norepinephrine uptake would be effective for the treatment of ADHD in school-aged children. Two identical 12-week, stratified, randomized, double-blind, placebo-controlled trials were conducted in children who met DSM-IV criteria for ADHD. The primary efficacy outcome measure was the mean change from baseline to endpoint in the Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHD RS) total score. Secondary efficacy measures included the Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S) and the Conners' Parent Rating Scale-Revised: Short Form (CPRS-R:S). A total of 291 patients were randomized in the 2 trials combined (Study 1, N = 147; Study 2, N = 144). Stimulant-naive patients were randomized to atomoxetine, placebo, or methylphenidate. Patients with prior stimulant exposure were randomized to atomoxetine or placebo. Atomoxetine significantly reduced ADHD RS total scores compared with placebo in each study (p <.001). Changes in the CGI-ADHD-S (Study 1: p =.003; Study 2: p =.001) and CPRS-ADHD Index (Study 1: p =.023; Study 2: p <.001) also showed atomoxetine to be statistically significantly superior to placebo in reducing ADHD symptoms. Atomoxetine was found to be well tolerated in this population of pediatric patients. Two studies of atomoxetine early in its development confirmed that atomoxetine, a specific and selective inhibitor of noradrenergic uptake, was effective for the treatment of children with ADHD. In addition, atomoxetine was found to be well tolerated.",2003.0,1,1
412,12523875,"A comparison of the efficacy, safety, and tolerability of divalproex sodium and olanzapine in the treatment of bipolar disorder.",John M Zajecka; Richard Weisler; Gary Sachs; Alan C Swann; Patricia Wozniak; Kenneth W Sommerville,"This study compared the efficacy, safety, and tolerability of divalproex and olanzapine in the treatment of acute mania associated with bipolar disorder. This randomized, 12-week, double-blind, parallel-group, multicenter study included DSM-IV-defined bipolar disorder type I patients hospitalized for acute mania and randomly assigned to treatment with divalproex or olanzapine. After an inpatient period of up to 21 days, subjects were followed as outpatients. Dose adjustment was permitted during the inpatient period. Efficacy was assessed using change from baseline in Mania Rating Scale (MRS) score to day 21; other efficacy measures included the Brief Psychiatric Rating Scale, the Hamilton Rating Scale for Depression, and the Clinical Global Impressions-Part I, Severity of Illness scale. The primary safety endpoint was change from baseline in weight. Other safety and tolerability endpoints included spontaneous adverse event reporting and changes from baseline in laboratory measures and vital signs. 120 subjects (N = 63 divalproex, N = 57 olanzapine) were randomly assigned to treatment. No significant differences between groups were found for any efficacy variable for change from baseline to day 21. Mean MRS score changes from baseline to day 21 were -14.8 for divalproex and -17.2 for olanzapine (p =.210). A significantly (p <.05) greater proportion of olanzapine-treated subjects experienced somnolence, weight gain, edema, rhinitis, and speech disorder (slurred speech); no adverse events were significantly greater in the divalproex group. A number of laboratory measures also demonstrated significant treatment differences, but the clinical significance of many of these is uncertain. Mean body weight changes were significantly greater in the olanzapine group (+ 8.8 lb [+ 4.0 kg]) than the divalproex group (+ 5.5 lb [+ 2.5 kg], p <.050). One death occurred during the study (olanzapine group, diabetic ketoacidosis). No significant difference in efficacy was found between treatment groups. Divalproex was associated with a more favorable adverse event profile and significantly less weight gain than olanzapine.",2003.0,0,0
413,12523876,Efficacy of quetiapine and risperidone against depressive symptoms in outpatients with psychosis.,Martha Sajatovic; Jamie A Mullen; Dennis E Sweitzer,"The treatment of psychotic symptoms in patients with mood disorders is a complex challenge. Antipsychotic medications in these individuals may be associated with extrapyramidal symptoms (EPS), worsening of depression, and functional impairment. Atypical antipsychotics such as quetiapine and risperidone are associated with a decreased incidence of adverse events such as EPS. The objective of this study was to compare the efficacy and tolerability of quetiapine and risperidone for the treatment of depressive symptoms in outpatients with psychosis. In this 4-month, multicenter, open-label trial, patients were randomly assigned in a 3:1 ratio of quetiapine to risperidone, and both drugs were flexibly dosed. Eligible patients had psychoses and demonstrated 1 of several DSM-IV diagnoses, including schizoaffective disorder, bipolar I disorder, major depressive disorder, delusional disorder, Alzheimer's dementia, schizophreniform disorder, vascular dementia, and substance abuse dementia. Patients were classified as mood disordered if they had bipolar disorder, major depressive disorder, or schizoaffective disorder. Efficacy was assessed using the Positive and Negative Syndrome Scale and the Clinical Global Impressions scale. The Hamilton Rating Scale for Depression (HAM-D) was used to assess the level of depressive symptoms. The primary tolerability assessment was presence or absence of substantial EPS, defined as EPS severe enough to require an alteration in treatment. A total of 554 patients were randomly assigned to quetiapine and 175 to risperidone. Mean doses at 16 weeks were 318 mg for quetiapine and 4.4 mg for risperidone. Although both agents produced improvements in mean HAM-D scores, quetiapine produced a greater improvement than risperidone in all patients (p =.0015). Within the mood-diagnosed population, incidences of both substantial EPS (p =.001) and at least moderate EPS (p =.0373) occurred significantly less frequently among patients taking quetiapine. For patients with non-mood diagnoses, incidences of substantial EPS were fewer for patients taking quetiapine than for those taking risperidone (p =.062); however, this was not statistically significant. These results suggest that quetiapine may be a useful agent in the management of depressive symptoms in patients with psychosis.",2003.0,0,0
414,12523877,An open study of olanzapine and fluoxetine for psychotic major depressive disorder: interim analyses.,John D Matthews; Kathryn A Bottonari; Laura M Polania; David Mischoulon; Christina M Dording; Robert Irvin; Maurizio Fava,"Although atypical antipsychotic agents are commonly used in the treatment of psychotic depression, there are no published prospective studies on their use in this condition. The aim of this study was to assess, by interim analyses, the efficacy of the atypical antipsychotic agent olanzapine in combination with the selective serotonin reuptake inhibitor antidepressant agent fluoxetine. We enrolled 27 patients (17 women [63.0%] and 10 men [37.0%]; mean +/- SD age: 41.2 +/- 14.7 years) with DSM-IV-defined major depressive disorder with psychotic features into an open trial of olanzapine, 5 to 20 mg/day, plus fluoxetine, 20 to 80 mg/day. Patients were assessed at each visit with the 17-item Hamilton Rating Scale for Depression and both the psychotic and mood modules of the Structured Clinical Interview for DSM-IV Axis I Disorders, Patient Edition. We are reporting the results of the first 6 weeks of treatment. Twenty-two (81.5%) of the 27 enrolled patients completed the 6-week open trial, and 5 (18.5%) dropped out, with only 2 (7.4%) dropping out due to side effects. Of the 27 patients, 74.1% (N = 20) met criteria for melancholic features, 14.8% (N = 4) had delusions alone, 18.5% (N = 5) had hallucinations alone, and 66.7% (N = 18) reported both delusions and hallucinations. In addition, the overall rates of response for the intent-to-treat group were as follows: depression response rate, 66.7% (N = 18); psychosis response rate, 59.3% (N = 16); psychotic depression response rate, 55.6% (N = 15); and psychotic depression remission rate, 40.7% (N = 11). The combination of olanzapine and fluoxetine appears to be a promising, safe, and effective treatment for psychotic depression. Double-blind studies are needed to confirm this impression.",2003.0,0,0
415,12532717,[Schizoaffective disorder: clinical symptoms and present-day approach to treatment].,Vita Danileviciūte,"During 20th century serious mental disorders were divided into two groups according symptomatology and course of disorder. Individuals with dominating disturbance of perception, thinking and cognition were basically diagnosed having schizophrenic. Individuals with mood disturbance were basically diagnosed having affective disorders. However, there were patients who did not fit neatly into either category. In 1933 Jocob Kasanin introduced the term ""schizoaffective psychosis"". Scientific discussions involved the possibility that schizoaffective disorder was conceptualized most accurately as following: a type of schizophrenia, a type of affective disorder, a unique disorder that was separate from both schizophrenia and bipolar disorder, an arbitrary categorization of clinical symptoms that marked a continuum between schizophrenia and affective illness, a heterogeneous collection of ""interforms"" between schizophrenia and affective disorders. However, diagnosis of schizoaffective disorder is included both in DSM-IV-TR and ICD-10. Schizoaffective disorder is listed in the category ""schizophrenia and other psychotic disorders"". The differential diagnosis includes basically either schizophrenia or affective disorder. The epidemiological status of schizoaffective disorder is somewhat uncertain compared with schizophrenia because of dilemmas related to diagnosis and classification of the disorder. Treatment of schizoaffective disorder comprises psychotropic medication, supportive psychotherapy, social care, rehabilitation. The most important groups of psychotropic medications are: antipsychotics, antidepressants and mood stabilizers. Atypical antipsychotics are the first-line medication for schizoaffective disorder due to their pharmacological properties. In the case of schizoaffective disorders combination of atypical antipsychotics with antidepressants seems to be useful. Novel antidepressants have priority for the combination mentioned above. Peculiarities of mechanism of action of antidepressant are important for combinations. Mood stabilizers seem to be useful for treatment of certain type of schizoaffective disorder as well.",2003.0,0,0
416,12544370,Quetiapine treatment in patients with posttraumatic stress disorder: an open trial of adjunctive therapy.,Mark B Hamner; Sarah E Deitsch; Peter S Brodrick; Helen G Ulmer; Jeffrey P Lorberbaum,"In this 6-week, open-label trial, combat veterans meeting DSM-IV criteria for posttraumatic stress disorder (PTSD) were treated with the atypical antipsychotic quetiapine. The starting dose was 25 mg at bedtime with subsequent titration based on tolerability and clinical response. Primary outcome was measured using the Clinician Administered PTSD Scale (CAPS). Secondary assessments of efficacy included the Positive and Negative Symptom Scale (PANSS), the Hamilton Rating Scale for Depression, and the Clinical Global Impression Scale. Safety and tolerability evaluations included neurologic ratings, vital signs, and assessment of treatment-emergent side effects. Eighteen of 20 patients enrolled in the study completed 6 weeks of open-label treatment. The dose range of quetiapine was 25 to 300 mg daily, with an average of 100+/-70 mg/d. There was significant improvement in CAPS scores, from 89.8+/-15.7 to 67.5+/-21.0 (t=4.863, df=18, <0.005), and composite PANSS ratings from baseline to endpoint. General psychopathology (PANSS) and depressive symptoms (HRSD) were also reduced at the 6-week end point. There were no serious adverse events and no clinically significant changes in vital signs or neurologic ratings. This preliminary open trial suggests that quetiapine is well tolerated and may have efficacy in reducing PTSD symptoms in patients who have not had an adequate response other medications. Studies utilizing a randomized, controlled trial design and larger sample sizes are needed to better define the potential role of quetiapine and other atypical antipsychotics in the treatment of PTSD.",2003.0,0,0
417,12547466,"Atomoxetine in adults with ADHD: two randomized, placebo-controlled studies.",David Michelson; Lenard Adler; Thomas Spencer; Frederick W Reimherr; Scott A West; Albert J Allen; Douglas Kelsey; Joachim Wernicke; Anthony Dietrich; Denái Milton,"[corrected] Attention-deficit/hyperactivity disorder (ADHD) has been less studied in adults than in children, and the treatment studies reported to date have been small, single-center trials. To assess the efficacy of atomoxetine, a new and highly selective inhibitor of the norepinephrine transporter, we conducted two large, multicenter treatment trials. Two identical studies using randomized, double-blind, placebo-controlled designs and a 10-week treatment period were conducted in adults with DSM-IV-defined ADHD as assessed by clinical history and confirmed by a structured interview (study I, n = 280; study II, n = 256). The primary outcome measure was a comparison of atomoxetine and placebo using repeated measures mixed model analysis of postbaseline values of the Conners' Adult ADHD Rating Scale. In each study, atomoxetine was statistically superior to placebo in reducing both inattentive and hyperactive and impulsive symptoms as assessed by primary and secondary measures. Discontinuations for adverse events among atomoxetine patients were under 10% in both studies. Atomoxetine appears to be an efficacious treatment for adult ADHD. Its lack of abuse potential may be an advantage for many patients.",2003.0,1,1
418,12559661,Atypical antipsychotic drugs improve cognition in schizophrenia.,Herbert Y Meltzer; Tomiki Sumiyoshi,,2003.0,0,0
419,12560305,The addition of droperidol or clonidine to epidural tramadol shortens onset time and increases duration of postoperative analgesia.,Ercan Gürses; Hülya Sungurtekin; Erkan Tomatir; Canan Balci; Mustafa Gönüllü,"To compare tramadol alone and the combinations of either tramadol-clonidine or tramadol-droperidol with regard to analgesic and adverse effects. After Ethic's Committee approval and patient informed consent were obtained, epidural catheters were inserted preoperatively at the L(3-4) interspace in 90 ASA physical status I-II adult patients undergoing lower abdominal surgery. Anesthesia was standardized. Patients were randomly assigned to one of three groups. Group I (T) patients received tramadol 75 mg, Group II (TD) patients received tramadol 75 mg plus droperidol 2.5 mg, and Group III (TC) patients received tramadol 75 mg plus clonidine 150 microg in a total volume of 10 mL administered as a single epidural injection in the postanesthesia care unit. The onset time of analgesia and duration of analgesia, visual analogue pain scores, sedation, nausea scores, vital signs and side effects were recorded. Duration of analgesia was similar in both the TD and TC groups, and significantly longer than in the T group (P < 0.001). Group TC patients displayed a significant increase in sedation scores and decrease in blood pressure and heart rate when compared with other groups (P < 0.001). No adverse effects were observed in Group TD, while nausea scores were high in both the T and TC groups (P < 0.001). Pain score, respiration rate, and SpO(2) values were similar in all study groups. We conclude that epidural tramadol in combination with droperidol or clonidine prolongs the duration of analgesia; however, droperidol appears to be a better alternative when adverse effects and antiemetic properties are taken into consideration.",2003.0,0,0
420,12562575,Changes in glucose and cholesterol levels in patients with schizophrenia treated with typical or atypical antipsychotics.,Jean-Pierre Lindenmayer; Pal Czobor; Jan Volavka; Leslie Citrome; Brian Sheitman; Joseph P McEvoy; Thomas B Cooper; Miranda Chakos; Jeffrey A Lieberman,"The association of hyperglycemia and hypercholesterolemia with use of atypical antipsychotics has been documented in case reports and uncontrolled studies. The authors' goal was to assess the effects of clozapine, olanzapine, risperidone, and haloperidol on glucose and cholesterol levels in hospitalized patients with schizophrenia or schizoaffective disorder during a randomized double-blind 14-week trial. One hundred fifty-seven patients with schizophrenia or schizoaffective disorder who were inpatients at four hospitals were originally included in the study. The 14-week trial consisted of an 8-week fixed-dose period and a 6-week variable-dose period. Planned assessments included fasting glucose and cholesterol, which were collected at baseline and at the end of the 8-week period and the following 6-week period. One hundred eight of the 157 patients provided blood samples at baseline and at least at one point after random assignment to clozapine, olanzapine, risperidone, or haloperidol during the treatment trial. Seven of these patients had diabetes; their glucose levels were >125 mg/dl at baseline. Data from 101 patients were used for statistical analyses. During the initial 8-week period there was an overall significant increase in mean glucose levels. There were significant increases in glucose levels at the end of the 8-week fixed-dose period for patients given clozapine (N=27) and those given haloperidol (N=25). The olanzapine group showed a significant increase of glucose levels at the end of the 6-week variable-dose period (N=22). Fourteen of the 101 patients developed abnormal glucose levels (>125 mg/dl) during the trial (six with clozapine, four with olanzapine, three with risperidone, and one with haloperidol). Cholesterol levels were increased at the end of the 8-week fixed-dose period for the patients given clozapine (N=27) and those given olanzapine (N=26); cholesterol levels were also increased at the end of the 6-week variable-dose period for patients given olanzapine (N=22). In this prospective randomized trial, clozapine, olanzapine, and haloperidol were associated with an increase of plasma glucose level, and clozapine and olanzapine were associated with an increase in cholesterol levels. The mean changes in glucose and cholesterol levels remained within clinically normal ranges, but approximately 14% of the patients developed abnormally high glucose levels during the course of their participation in the study.",2003.0,0,0
421,12562576,"Attenuation of olanzapine-induced weight gain with reboxetine in patients with schizophrenia: a double-blind, placebo-controlled study.",Michael Poyurovsky; Ilanit Isaacs; Camil Fuchs; Michael Schneidman; Sarit Faragian; Ronit Weizman; Abraham Weizman,"Since increased norepinephrine availability may account for the weight-reducing effect of appetite suppressants, the authors hypothesized that the addition of the selective norepinephrine reuptake inhibitor reboxetine may prevent or attenuate olanzapine-induced weight gain. Twenty-six patients hospitalized for first-episode DSM-IV schizophrenic disorder participated in the study. In addition to 6 weeks of treatment with olanzapine, 10 mg/day, patients were randomly allocated in a double-blind design to receive either reboxetine, 4 mg/day, (N=13) or placebo (N=13). Ten patients in each group completed the 6-week trial. Patients given olanzapine and reboxetine demonstrated a significantly lower increase in body weight (mean=2.5 kg, SD=2.7) than those given olanzapine and placebo (mean=5.5 kg, SD=3.1). Significantly fewer patients in the olanzapine/reboxetine group (N=2 of 10) than in the olanzapine/placebo group (N=7 of 10) gained at least 7% of their initial weight, the cutoff for clinically significant weight gain. The addition of reboxetine to olanzapine treatment was safe and well tolerated by the patients. A between-group difference in the reduction of Hamilton depression scale scores was seen that favored the olanzapine/reboxetine group (mean difference=-3.1, SD=1.25). The selective norepinephrine reuptake inhibitor reboxetine may reduce olanzapine-induced weight gain in schizophrenia patients, and activation of the adrenergic system may attenuate weight gain induced by atypical antipsychotic agents.",2003.0,0,0
422,12562742,"Mood stabilisers plus risperidone or placebo in the treatment of acute mania. International, double-blind, randomised controlled trial.",Laksami N Yatham; Fred Grossman; Ilse Augustyns; Eduard Vieta; Arun Ravindran,"Few double-blind trials have examined the efficacy of a combination of a mood stabiliser and an atypical antipsychotic in acute mania. To determine the efficacy of risperidone in combination with a mood stabiliser in acute mania. Patients taking a mood stabiliser were randomised to 3 weeks' treatment with risperidone (n=75) or placebo (n=76). Young Mania Rating Scale (YMRS) scores improved rapidly with significantly greater reductions at week 1 in the risperidone group compared with the placebo group. At end-point YMRS scores decreased by 14.5 and 10.3 points in the risperidone and placebo groups, respectively. Significant improvements v. placebo (P<0.05) were noted in the risperidone group on several other clinically meaningful measures. Additionally, a post hoc analysis excluding carbamazepine-treated patients (plasma concentrations of risperidone active moiety were 40% lower in this group) revealed significantly greater reductions (P=0.047) in YMRS scores in the risperidone group than in the placebo group. Incidence of adverse events was similar in both groups. Risperidone is superior to placebo when used in combination with lithium or divalproex in acute mania.",2003.0,0,0
423,12563038,Movement disorders in children.,Bradley L Schlaggar; Jonathan W Mink,,2003.0,0,0
424,12563049,Childhood behavior disorders and injuries among children and youth: a population-based study.,Jamie C Brehaut; Anton Miller; Parminder Raina; Kimberlyn M McGrail,"While an association between pediatric behavioral disorders and injuries is generally acknowledged, no studies have measured the risk for injury in the context of a large, population-based study that is free of cohort biases. To examine the association between childhood behavior disorders ([CBDs] as indicated by prescription for methylphenidate [MPH]) and a variety of injury outcomes, and to evaluate the risk for injury among these children after controlling for known demographic correlates. Population-based database analysis of all children in British Columbia (BC) under the age of 19 as of December 31, 1996; comparison of those who had been prescribed MPH and therefore placed in the CBD group (n = 16, 806) and those who were not (n = 1,010,067). Demographic information collected was as follows: age, sex, measures of socioeconomic status, and region of residence. Common types of childhood injury in BC: International Classification of Diseases, Ninth Revision N-codes (fractures, open wounds, poisoning/toxic effect, concussion, intracranial, burns) and E-codes (falls, postoperative complications, motor vehicle accidents, struck by object, adverse effects of drugs, suffocation, drowning). BC Linked Health Data Set and the BC Triplicate Prescription Program. After controlling for known demographic correlates, odds for injury was greater among those treated with MPH and presumed to have a behavioral disorder, when injury was characterized either by type (1.67; 99% confidence interval: 1.54-1.81) or cause (1.52; 99% confidence interval: 1.40-1.66) of injury. This increased risk extended to unexpected categories of injury such as postoperative complications and adverse effects of drugs. Children with CBDs have >1.5 times the odds of sustaining injuries of a variety of types from a variety of causes, even after controlling for known demographic correlates, than those without behavioral disorders. The risks for these children extend beyond those that might be directly associated with impulsivity and overactivity. Injury prevention strategies aimed at this group of children and youth would be beneficial. Policy-makers should account for increased risk of a wide variety of injuries in this group of children and youth.",2003.0,1,1
425,12574563,"Safety of dexamphetamine in acute ischemic stroke: a randomized, double-blind, controlled dose-escalation trial.",Louise Martinsson; Nils Gunnar Wahlgren,"Amphetamine is reported to enhance recovery after experimental stroke, but results from the first few trials in humans are inconclusive. Limited information is available on treatment safety. This study intended to investigate the safety and tolerability of dexamphetamine in patients with acute cerebral ischemia. Forty-five patients with cerebral ischemia were enrolled within 72 hours after onset of symptoms. Patients were randomized to 1 of 3 dose levels (2.5, 5, or 10 mg orally twice daily) or placebo for 5 consecutive days. Adverse events, blood pressure, heart rate, body temperature, consciousness level, and functional outcome measures were followed up daily during treatment. Follow-ups were made at day 7 and 1 and 3 months after stroke. Mean systolic and diastolic blood pressures and heart rate increased 14 mm Hg, 8 mm Hg, and 9 bpm, respectively, with dexamphetamine treatment compared with placebo (P< or =0.01). There was no difference between dexamphetamine and placebo regarding adverse events, body temperature, or consciousness level. During treatment, there was a benefit of dexamphetamine in neurological and functional outcome (P<0.05), but differences were not maintained at follow-up. Overall, dexamphetamine was safe and well tolerated by patients with acute cerebral ischemia, but blood pressure and heart rate increased during treatment in comparison to placebo. These observations may be important in the future planning of amphetamine trials because changes in these variables have been observed to interfere with clinical outcome. The suggestions of improvement in outcome must be confirmed in further studies.",2003.0,0,0
426,12578439,Development of a new once-a-day formulation of methylphenidate for the treatment of attention-deficit/hyperactivity disorder: proof-of-concept and proof-of-product studies.,James Swanson; Suneel Gupta; Andrew Lam; Ira Shoulson; Marc Lerner; Nishit Modi; Elizabeth Lindemulder; Sharon Wigal,"The duration of action of the immediate-release formulation of methylphenidate hydrochloride is short (3 to 4 hours), and 3 times daily dosing is thought to maximize effectiveness across a 12-hour day. The initial sustained-release formulations of methylphenidate had reduced efficacy compared with immediate-release methylphenidate and were not well accepted. Tachyphylaxis was hypothesized to account for the reduced effects, and an ascending drug delivery pattern was proposed to overcome this acute tolerance. Children with attention-deficit/hyperactivity disorder were evaluated in a laboratory school to characterize onset and duration of the effect of a variety of methylphenidate regimens. In a proof-of-concept study, an experimental ascending profile was established by an initial bolus followed by small increasing doses of immediate-release methylphenidate in capsules administered every 30 minutes for 8 hours. Two proof-of-product studies of a new oral once-a-day formulation to deliver methylphenidate by an osmotic pump process based on OROS (ALZA Corp, Mountain View, Calif) technology (hereafter referred to ""OROS-methylphenidate"") were conducted: a pharmacokinetic study and a pharmacodynamic study. The experimental ascending profile matched the effect of the standard regimen of methylphenidate, 3 times daily. In the pharmacokinetic study, OROS-methylphenidate treatment produced a rapid rise followed by increasing plasma concentrations that peaked 7 to 9 hours after administration. In the pharmacodynamic study, OROS-methylphenidate treatment matched the 3 times daily dosing of methylphenidate for onset and duration of efficacy. These studies demonstrate the translation of a basic science finding (acute tolerance to clinical doses of methylphenidate) into clinical application (the selection of a new drug delivery pattern for methylphenidate). This approach produced a new product (OROS-methylphenidate or Concerta), which proved to have the predicted rapid onset (with 1-2 hours) and long duration of efficacy (10-12 hours) after a single administration in the morning.",2003.0,0,0
427,12579548,Self-administered psychosocial treatments for children and families.,Frank J Elgar; Patrick J McGrath,"Self-administered psychosocial treatments for child health problems have the potential to circumvent barriers to traditional models of care. They are convenient and inexpensive to families and, for some types of problems, may be as effective as therapist-based care. In a review of past research on child- and parent-facilitated self-administered treatments, it was found that a stronger evidence base exists in support of some formats (manual- and multimedia-based treatments) than for others (inspirational literature and support groups). The practical, ethical, and legal issues associated with self-administered treatments are discussed as well as avenues for future research. How psychologists and health care systems respond to the opportunities associated with self-administered treatments for children will likely affect the face of the profession and the health of children in the future.",2003.0,0,0
428,12590630,Combination therapy: is clinical practice leading the way?,Ron Welch; Mark Snaterse,,2003.0,0,0
429,12593456,Efficacy of methylphenidate in patients with cerebral palsy and attention-deficit hyperactivity disorder (ADHD).,Varda Gross-Tsur; Ruth S Shalev; Navah Badihi; Orly Manor,"Our objective was to study the short-term efficacy and safety of methylphenidate in patients with the dual diagnosis of cerebral palsy and attention-deficit hyperactivity disorder (ADHD). Twenty-nine patients (8.0 +/- 4.0 years old) with cerebral palsy and ADHD completed the study. In a prospective, crossover, double-blind paradigm, patients were treated with methylphenidate or placebo, each for 4 weeks. Parents and teachers completed a modified Abbreviated Conners' Rating Scale at the beginning of the study and the end of the first and second months of treatment with methylphenidate or placebo. Parents were contacted weekly to report side effects. Methylphenidate treatment, as assessed by teachers' ratings, resulted in a significant improvement in ADHD symptomatology (t = 2.29, df = 27, P < .05); however, a trend for improvement was noted only on the parents' ratings. After the conclusion of the study, 12 patients continued methylphenidate for 20 +/- 10 months. Side effects were minimal, with the exception of transient hallucinations in one patient. In children with cerebral palsy and ADHD, methylphenidate is effective, rendering it a valuable adjunct to their overall medical therapy.",2003.0,0,1
430,12597703,The effect of methylphenidate on three forms of response inhibition in boys with AD/HD.,Anouk Scheres; Jaap Oosterlaan; James Swanson; Sharon Morein-Zamir; Nachson Meiran; Harry Schut; Laurens Vlasveld; Joseph A Sergeant,"The current study was aimed at (a) investigating the effect of three doses methylphenidate (MPH) and placebo on inhibition of a prepotent response, inhibition of an ongoing response, and interference control in Attention Deficit/Hyperactivity Disorder (AD/HD), and (b) studying dose-response relations for the three forms of response inhibition. To meet these aims, the following tasks were selected: two versions of the Stop Paradigm for inhibition of a prepotent response, a Circle Tracing Task and a recently developed Follow Task for inhibition of an ongoing response, and the Stroop Color-Word Test and an Eriksen Flanker Task for interference control. These tasks were administered to 23 boys with AD/HD during four treatment conditions: 5 mg MPH, 10 mg MPH, 20 mg MPH, and placebo. A pseudorandomized, multiple-blind, placebo-controlled, within-subject design was used. As hypothesized, inhibitory control in children with AD/HD improved under MPH compared to placebo. However, this effect was only significant for inhibition of a prepotent response and inhibition of an ongoing response (as measured by the Follow Task), but not for interference control. The relation between treatment condition and response was linear. However, this linear relation was due to improved inhibitory control under MPH compared to placebo, because no effects of MPH dose were observed for any of the response inhibition measures.",2003.0,0,1
431,12598277,The effect of spinal bupivacaine in combination with either epidural clonidine and/or 0.5% bupivacaine administered at the incision site on postoperative outcome in patients undergoing lumbar laminectomy.,W Scott Jellish; Adam Abodeely; Elaine M Fluder; John Shea,"Spinal anesthesia has numerous advantages over general anesthesia for patients undergoing lumbar laminectomy and microdisk surgery. In this study, we evaluated the addition of epidural clonidine and/or bupivacaine, injected at the incision site, on postoperative outcome variables in patients undergoing lower spine procedures using spinal anesthesia. One hundred twenty patients having lumbar spine surgery received bupivacaine spinal anesthesia supplemented by 150 microg of epidural clonidine with or without incisional bupivacaine, epidural placebo plus incisional bupivacaine, or placebo with incisional saline. Demographic data, intraoperative hemodynamics, blood loss, pain, nausea, urinary retention, hospital discharge, and other variables were compared by using either analysis of variance or chi(2) analysis. Demographics were similar. IV fluids, blood loss, incidence of intraoperative bradycardia, and hypotension were not different among groups. Postanesthesia care unit pain scores were lower and demand for analgesics was less in patients who received both the clonidine and subcutaneous bupivacaine. Patients who received epidural clonidine also had improved postoperative hemodynamics. Hospital discharge, urinary retention, and other variables were not different. We conclude that epidural clonidine as a supplement to spinal anesthesia produced no perioperative complications and improved postoperative pain and hemodynamic stability in patients undergoing lower spine procedures. Spinal anesthesia with supplemental epidural clonidine in combination with incision site subcutaneous bupivacaine was evaluated both intra- and postoperatively and compared with spinal anesthesia alone for lower lumbar spine procedures. Both epidural clonidine and subcutaneous incisional bupivacaine, added to spinal anesthesia for lumbar spine surgery, improves pain relief and reduces the need for postoperative opioids with their associated side effects.",2003.0,0,0
432,12600227,Intramuscular preparations of antipsychotics: uses and relevance in clinical practice.,A Cario Altamura; Francesca Sassella; Annalisa Santini; Clauno Montresor; Sara Fumagalli; Emanuela Mundo,"Intramuscular formulations of antipsychotics can be sub-divided into two groups on the basis of their pharmacokinetic features: short-acting preparations and long-acting or depot preparations. Short-acting intramuscular formulations are used to manage acute psychotic episodes. On the other hand, long-acting compounds, also called ""depot"", are administered as antipsychotic maintenance treatment to ensure compliance and to eliminate bioavailability problems related to absorption and first pass metabolism. Adverse effects of antipsychotics have been studied with particular respect to oral versus short- and long-acting intramuscular formulations of the different compounds. For short-term intramuscular preparations the main risk with classical compounds are hypotension and extrapyramidal side effects (EPS). Data on the incidence of EPS with depot formulations are controversial: some studies point out that the incidence of EPS is significantly higher in patients receiving depot preparations, whereas others show no difference between oral and depot antipsychotics. Studies on the strategies for switching patients from oral to depot treatment suggest that this procedure is reasonably well tolerated, so that in clinical practice depot antipsychotic therapy is usually begun while the oral treatment is still being administered, with gradual tapering of the oral dose. Efficacy, pharmacodynamics and clinical pharmacokinetics of haloperidol decanoate, fluphenazine enanthate and decanoate, clopenthixol decanoate, zuclopenthixol decanoate and acutard, flupenthixol decanoate, perphenazine enanthate, pipothiazine palmitate and undecylenate, and fluspirilene are reviewed. In addition, the intramuscular preparations of atypical antipsychotics and clinical uses are reviewed. Olanzapine and ziprasidone are available only as short-acting preparations, while risperidone is to date the only novel antipsychotic available as depot formulation. To date, acutely ill, agitated psychotic patients have been treated with high parenteral doses of typical antipsychotics, which often cause serious EPS, especially dystonic reactions. Intramuscular formulations of novel antipsychotics (olanzapine and ziprasidone), which appear to have a better tolerability profile than typical compounds, showed an equivalent efficacy to parenteral typical agents in the acute treatment of psychoses. However, parenteral or depot formulations of atypical antipsychotics are not yet widely available.",2003.0,0,0
433,12610718,Switching patients to aripiprazole from other antipsychotic agents: a multicenter randomized study.,Daniel E Casey; William H Carson; Anutosh R Saha; Amy Liebeskind; Mirza W Ali; Darlene Jody; Gary G Ingenito; Aripiprazole Study Group,"Switching patients from one antipsychotic to another can lead to tolerability problems or transient symptom exacerbations. It is important to compare switching strategies to determine which methods produce the best possible patient outcomes. To investigate the efficacy, safety and tolerability of three dosing strategies for switching chronic, stable patients with schizophrenia from current oral antipsychotic monotherapy to once-daily oral aripiprazole monotherapy. Patients in this 8-week, open-label, outpatient study were randomized to: 1). immediate initiation of 30 mg/day aripiprazole with simultaneous immediate discontinuation of current antipsychotic; 2). immediate initiation of 30 mg/day aripiprazole while tapering off current antipsychotic over 2 weeks; or 3). up-titrating aripiprazole to 30 mg/day over 2 weeks, while simultaneously tapering off current antipsychotic. Efficacy assessments included PANSS, CGI-S, and CGI-I scores. Safety assessments included: adverse events (AEs) recording, evaluation of extrapyramidal symptoms (EPS), vital signs, ECG, and clinical laboratory tests. Efficacy with aripiprazole was maintained during the study with numerical improvements compared with baseline in all three groups. The overall incidence of AEs was broadly comparable across all groups, and AEs were generally mild to moderate in severity and time-limited. Discontinuations due to AEs were comparable across the groups. No deterioration in EPS occurred in any group. The reduction in body weight and plasma prolactin levels following switch to aripiprazole were comparable across the three groups. Any of the three strategies evaluated can be used safely for switching patients to aripiprazole from antipsychotic monotherapy. Furthermore, patients' symptoms may continue to improve after switching to aripiprazole.",2003.0,0,0
434,12611852,Comparative effectiveness of antipsychotic drugs.,,,2003.0,0,0
435,12616671,Pharmacokinetic and safety assessments of concurrent administration of risperidone and donepezil.,Qinying Zhao; Charles Xie; Luana Pesco-Koplowitz; Xinwei Jia; Jean-Loup Parier,"Treatment of Alzheimer's disease sometimes uses combinations of drugs because dementia is frequently associated with behavioral symptoms. Risperidone and donepezil are both metabolized through cytochrome P450 2D6 and 3A4, raising the possibility of drug interactions with combination therapy. The objective of this study was to determine whether significant drug interactions occur with concomitant administration of donepezil and risperidone. In an open-label, three-way crossover study, 24 healthy men were randomly assigned to receive 0.5 mg of risperidone twice daily, 5 mg of donepezil once daily, or both drugs for 14 consecutive days, followed by a 21-day washout period. The treatment ratios of AUC and associated 90% confidence intervals (CIs) for risperidone active moiety, defined as risperidone plus 9-hydroxyrisperidone (ratio = 110.2%; 90% CI = 103.7-117.2), and for donepezil (ratio = 97.1%; 90% CI = 90.0-103.6) were within the 80% to 125% of bioequivalence range. The treatment ratios of Cmax and associated 90% CIs for risperidone active moiety (ratio = 114.6%; 90% CI = 107.0-122.8) and for donepezil (ratio = 96.1%; 90% CI = 90.0-102.6) were also within the bioequivalence range. Therefore, no significant pharmacokinetic differences occurred in either risperidone active moiety or donepezil when given alone or in combination. Adverse events (predominantly headache, nervousness, and somnolence) were minor and comparable for all treatment groups. The results indicate that no clinically meaningful drug interactions occurred between risperidone 1 mg daily and donepezil 5 mg daily at steady state, and therefore no dosage adjustment is required when both drugs are combined with the dosage regimen studied. Additional investigations are warranted to determine the potential for interactions in elderly patients with dementia who may eliminate risperidone and donepezil more slowly and thus be more vulnerable to clinical drug interactions than the young healthy subjects examined in this study.",2003.0,0,0
436,12620132,Neuropsychiatric effects of cardiovascular drug therapy.,Seth Keller; William H Frishman,"Various cardiovascular drugs have been shown to have neuropsychiatric effects that can be harmful or therapeutically beneficial to patients. As an example, both sedation and mental depression have been described in patients receiving centrally acting antihypertensive drugs and beta-adrenergic blockers, related to their antiadrenergic actions. In contrast, because of these antiadrenergic actions, agents like clonidine have been used to treat opiate, alcohol, and nicotine withdrawal, while beta blockers have been used to treat symptoms of performance anxiety, migraine, and psychocardiac disorders. Some antiarrhythmic drugs have been associated with delirium, and digitalis toxicity has been shown to cause hallucinations, mania, euphoria, and depression. The calcium-channel blocker verapamil has been used as an adjunctive treatment in patients with bipolar disorders. Since neuropsychiatric symptoms are seen in patients with cardiovascular disease, clinicians should be aware of the possible relationship between these symptoms and concurrent cardiovascular drug therapy.",2003.0,0,0
437,12621632,Randomized trial of modafinil for treating subjective daytime sleepiness in patients with Parkinson's disease.,Charles H Adler; John N Caviness; Joseph G Hentz; Marlene Lind; Judy Tiede,"We assessed the safety and efficacy of modafinil for the treatment of excessive daytime sleepiness in patients with Parkinson's disease (PD). This was a single-site, randomized, double-blind, placebo-controlled crossover study of 21 PD patients having an Epworth Sleepiness Scale (ESS) score > or =10. They received either placebo or modafinil 200 mg/day for 3 weeks, followed by a washout week, then the alternate treatment for 3 weeks. The ESS data demonstrated a carryover effect, so the changes from baseline ESS scores were compared between the two treatments for period 1 only. The ESS scores for the placebo group went from 16.0 +/- 4.2 (mean +/- SD) to 17.0 +/- 5.1 and for the modafinil group went from 17.8 +/- 4.2 to 14.4 +/- 5.7 (P = 0.039). There was no significant carryover effect for any other measure. The patient Clinical Global Impression of Change (+3 to -3) improved by 0.75 on modafinil compared with 0.15 for placebo (P = 0.07). A total of 7 of 20 (35%) of the patients reported some improvement on modafinil but not placebo. There was no significant improvement or worsening of the UPDRS subscores I-III, Timed Tap test, or time on. Vital signs, electrocardiograms, and lab tests were unchanged. Modafinil was very well tolerated. Our data demonstrate that, in a small sample size, administration of 200 mg/day of modafinil was associated with few side effects and was modestly effective for the treatment of excessive daytime sleepiness in patients with PD.",2003.0,0,0
438,12629532,Treatment of weight gain with fluoxetine in olanzapine-treated schizophrenic outpatients.,Juan R Bustillo; John Lauriello; Katherine Parker; Roger Hammond; Laura Rowland; Michael Bogenschutz; Samuel Keith,"Significant weight gain is a side effect associated with olanzapine treatment in some patients. We investigated the efficacy of high-dose fluoxetine as a weight-reducing agent for patients who develop early weight gain with olanzapine treatment. Patients that gained >/=3% of their baseline weight in the initial 8 weeks of olanzapine treatment (n=31) were randomized to double-blind treatment with placebo or fluoxetine (60 mg/day). Clinical, weight, and weight-related measures were assessed. Fluoxetine failed to demonstrate weight-reducing effects (fluoxetine group: baseline mean 80.5 kg, SD=19.1, last mean=83.5 kg, SD=19.8; placebo group: baseline mean=77.1 kg, SD=12.1, last mean=78.8 kg, SD=10.6; F=1.3; df=1, 18; p=0.3). There were no differential effects in psychopathology, extrapyramidal side effects or weight-related measures between the placebo and fluoxetine groups. Serotonin reuptake inhibitors are probably not a practical option to counteract weight gain induced by atypical antipsychotics. Atypical-induced weight gain may result from mechanisms other than 5HT reuptake blockade.",2003.0,0,0
439,12633121,"A randomized placebo-controlled trial of risperidone for the treatment of aggression, agitation, and psychosis of dementia.",Henry Brodaty; David Ames; John Snowdon; Michael Woodward; Jeff Kirwan; Roger Clarnette; Emma Lee; Ben Lyons; Fred Grossman,"This randomized, double-blind, placebo-controlled trial examined the efficacy and safety of risperidone in the treatment of aggression, agitation, and psychosis in elderly nursing-home patients with dementia. Elderly patients with a DSM-IV diagnosis of dementia of the Alzheimer's type, vascular dementia, or a combination of the 2 (i.e., mixed dementia) and significant aggressive behaviors were randomized to receive, for a period of 12 weeks, a flexible dose of either placebo or risperidone solution up to a maximum of 2 mg/day. Outcome measures were the Cohen-Mansfield Agitation Inventory (CMAI), the Behavioral Pathology in Alzheimer's Disease (BEHAVE-AD) rating scale, and the Clinical Global Impression of Severity (CGI-S) and of Change (CGI-C) scales. A total of 345 patients were randomized to treatment with risperidone or placebo, and 337 patients received at least one dose of study drug. The trial was completed by 67% of patients in the placebo group and 73% of patients in the risperidone group. The mean +/- SE dose of risperidone was 0.95 +/- 0.03 mg/day. The primary endpoint of the study, the difference from baseline to endpoint in CMAI total aggression score, showed a significant reduction in aggressive behavior for risperidone versus placebo (p <.001). A similar improvement was also seen for the CMAI total non-aggression subscale (p <.002) and for the BEHAVE-AD total (p <.001) and psychotic symptoms subscale (p =.004). At endpoint, the CGI-S and the CGI-C scores indicated a significantly greater improvement with risperidone compared with placebo (p <.001). Overall, 94% and 92% of the risperidone and placebo groups, respectively, reported at least 1 adverse event. Somnolence and urinary tract infection were more common with risperidone treatment, whereas agitation was more common with placebo. There was no significant difference in the number of patients who reported extrapyramidal symptoms between the risperidone (23%) and placebo (16%) groups. Treatment with low-dose (mean = 0.95 mg/day) risperidone resulted in significant improvement in aggression, agitation, and psychosis associated with dementia.",2003.0,0,0
440,12640221,Low-dose risperidone as adjunctive therapy for irritable aggression in posttraumatic stress disorder.,Edward P Monnelly; Domenic A Ciraulo; Clifford Knapp; Terence Keane,"Increased aggressive behavior can occur in association with posttraumatic stress disorder (PTSD). This study tested the hypothesis that low-dose risperidone reduces aggression and other PTSD-related symptoms in combat veterans. Subjects were male combat veterans with PTSD who scored 20 or higher on cluster D (hyperarousal) of the Patient Checklist for PTSD-Military Version (PCL-M). Subjects were randomly assigned to either risperidone or placebo treatment groups. Drugs were administered over a 6-week treatment period in a double-blind manner. Subjects received either risperidone (0.5 mg/day; n = 7) or matched placebo (n = 8) tablets during the first 2 weeks of the treatment period. The dose of risperidone could then be increased up to 2.0 mg/day on the basis of response. Prerandomization psychotropic regimens were continued. Subjects were evaluated with the PCL-M and the Overt Aggression Scale-Modified for Outpatients (OAS-M). In comparison with placebo treatment, reductions in scores between baseline and the last week of treatment were significantly greater for OAS-M irritability and PCL-M cluster B (intrusive thoughts) subscales and on the PCL-M total scale. These results suggest that low-dose risperidone administration reduces irritability and intrusive thoughts in combat-related PTSD.",2003.0,0,0
441,12640225,An open-label trial of modafinil augmentation in patients with partial response to antidepressant therapy.,Paul J Markovitz; Susan Wagner,,2003.0,0,0
442,12645162,Management of attention deficit/hyperactivity disorder--use of an effective paradigm.,S P Dixit; M N Pandey; G P Dubey,"The management of ADHD poses a great problem before the psychologists, psychiatrists and different behavioural scientists. The multi-model approach, combining pharmacologic with different non-pharmacologic interventions, is more effective than any form of therapy. In the present study the theta feedback, a non-pharmacologic technique, has shown beneficial role among the low medicated ADHD cases. The present study also signifies the role of multi-model intervention in the management of ADHD.",2003.0,0,0
443,12650685,What are the effects of antipsychotics on sexual dysfunctions and endocrine functioning?,H Knegtering; A E G M van der Moolen; S Castelein; H Kluiter; R J van den Bosch,"The literature is reviewed and preliminary results of new studies are presented showing that treatment with classical antipsychotics, as well as risperidone, induces sexual dysfunctions in 30-60% of the patients. These antipsychotics also frequently induce amenorrhoea and galactorrhoea. Although comparative studies are rare, it is likely that prolactin-sparing antipsychotics, as recently shown in a randomized trial of olanzapine versus risperidone, induce less sexual side effects.From these studies, it becomes apparent that prolactin elevation induced by classical antipsychotics and risperidone is probably a factor in inducing sexual dysfunctions, amenorrhoea and galactorrhoea. The role of other factors inducing sexual dysfunctions like sedation, proportional, variant -blockade, testosterone, dopamine, and serotonin is discussed. Finally, it is concluded that sexual and hormonal effects of antipsychotics, although clearly important, are often neglected in research as in clinical practice. Lowering the dosage or switching to a prolactin-sparing antipsychotic often reduces sexual side effects, amenorrhoea, and galactorrhoea.",2003.0,0,0
444,12650950,Nizatidine for prevention of weight gain with olanzapine: a double-blind placebo-controlled trial.,Patrizia Cavazzoni; Yoko Tanaka; Suraja M Roychowdhury; Alan Breier; David B Allison,"Weight gain is associated with treatment with olanzapine and other psychotropic agents. Nizatidine, a histamine H-2 receptor antagonist, has been proposed to have weight-reducing effects. This double-blind trial evaluated the efficacy of nizatidine in limiting weight gain in patients with schizophrenia and related disorders who were treated with olanzapine for up to 16 weeks. After an initial screening period, 175 patients were randomized to receive olanzapine (5-20 mg) with either placebo or nizatidine (150 mg b.i.d. or 300 mg b.i.d.). Significantly less weight gain was observed on average at weeks 3 and 4 with olanzapine+nizatidine 300 mg b.i.d. (P<0.05) compared to olanzapine+placebo, but the difference was not statistically significant at 16 weeks. Nizatidine was well-tolerated and did not adversely affect clinical outcomes. Nizatidine 300 mg b.i.d. may have an early transient effect in limiting the weight gain, but this potential early effect appeared to be diminished or eliminated by 16 weeks.",2003.0,0,0
445,12651665,Intrathecal clonidine added to a bupivacaine-morphine spinal anesthetic improves postoperative analgesia for total knee arthroplasty.,Brian D Sites; Michael Beach; Russell Biggs; Christopher Rohan; Christopher Wiley; Athos Rassias; Janice Gregory; Gilbert Fanciullo,"Postoperative pain after total knee arthroplasty (TKA) is severe and can complicate early physical therapy. We tested the hypothesis that intrathecal clonidine would improve postoperative analgesia for TKA using a hyperbaric bupivacaine spinal anesthetic. In a double-blinded, placebo-controlled protocol, 81 ASA physical status I-III patients undergoing either a single or bilateral TKA were randomized into 4 groups with the following 2-mL solutions added to 15 mg of hyperbaric bupivacaine: 1) sterile saline, 2) morphine (250 microg), 3) morphine (250 microg) with clonidine (25 microg), and 4) morphine (250 microg) with clonidine (75 microg). At 1, 2, 4, 6, 12, and 24 h postoperatively, we measured visual analog scales (VAS), cumulative IV morphine consumption, hemodynamics, nausea, ancillary drugs, and side effects. Our primary comparison was between the clonidine with morphine groups versus the morphine group. We found that the combined administration of intrathecal clonidine and morphine decreased 24 h IV morphine consumption by 13 mg (P = 0.028) when compared with intrathecal morphine alone. This corresponded to a decrease in the VAS score of 1.3 cm at 24 h postoperatively (P = 0.047). Adverse side effects were similar among all groups with the exception of more relative hypotension in the clonidine groups through postoperative hour 6. We conclude that the coadministration of intrathecal clonidine and morphine decreases the 24-h IV morphine consumption and improves the 24-h VAS score when compared with intrathecal morphine alone. In this prospective, randomized, double-blinded, and placebo-controlled trial, we identify an effective postoperative analgesic approach in total knee replacement surgery. Intrathecal morphine (250 microg) combined with clonidine (25 or 75 microg) provided superior analgesia compared with intrathecal morphine alone.",2003.0,0,0
446,12653410,Smoking withdrawal dynamics: II. Improved tests of withdrawal-relapse relations.,Thomas M Piasecki; Douglas E Jorenby; Stevens S Smith; Michael C Fiore; Timothy B Baker,"In this article, the authors assessed whether continuously scaled symptom parameters derived from growth models (T. M. Piasecki et al., 2003) are linked to smoking at long-term follow-up by using data from a large-scale clinical trial (N = 893). Results revealed that higher withdrawal intercepts, positive linear slopes, and greater volatility were all positively associated with relapse, and cigarette coefficients (indicating smoking-induced withdrawal reduction) were negatively related to relapse. In models keyed around the first lapse to smoking, those destined to lapse reported more severe withdrawal during abstinence, and withdrawal patterns discriminated groups defined according to lapse duration. The findings complement earlier heterogeneity studies in implicating the pattern of changing withdrawal symptoms over time as a factor strongly associated with smoking relapse.",2003.0,0,0
447,12653813,Evaluation of the effects of lofexidine and clonidine on naloxone-precipitated withdrawal in opioid-dependent humans.,Sharon L Walsh; Eric C Strain; George E Bigelow,"To examine the efficacy of lofexidine, an alpha2 adrenergic agonist, to suppress opioid withdrawal symptoms in opioid-dependent humans under in-patient laboratory conditions by using a naloxone challenge procedure. Randomized, within-subject, cross-over design with drug administration taking place under double-blind and triple-dummy conditions. A 14-bed in-patient hospital research unit dedicated to the conduct of behavioral pharmacology studies. Eight healthy adult volunteers (two female/six male) with histories of polysubstance abuse and current physical dependence on opioids. Participants were stabilized onto methadone and maintained on 30 mg/day, p.o. throughout the study. Oral placebo, lofexidine (0.4, 0.8 and 1.6 mg, p.o.) and clonidine (0.1 and 0.2 mg, p.o.) were each tested as pre-treatments once in combination with each of three intramuscular naloxone doses (0, 0.1 and 0.3 mg, i.m.) during 18 separate experimental sessions. An array of physiological indices (e.g. heart rate, blood pressure, pupil diameter) as well as a number of subjective and observer-rating scales sensitive to opioid withdrawal effects. As expected, lofexidine and clonidine both produced dose-related decreases in blood pressure and heart rate but few subjective effects; naloxone increased opioid withdrawal signs and symptoms in a dose- and time-dependent fashion. Although both lofexidine and clonidine reduced the cardiovascular response to naloxone challenge, close inspection of the data reveal that this occurred only to the extent that baseline physiological parameters were reduced, while neither drug significantly modified the overall magnitude of the response to naloxone. Moreover, neither lofexidine nor clonidine suppressed the subjective discomfort of opioid withdrawal or significantly reduced other autonomic signs of opioid withdrawal, such as lacrimation or rhinorrhea. These data suggest that lofexidine is well tolerated even at supratherapeutic acute doses. However, its failure to modify most signs and symptoms of opioid withdrawal suggest that its effective use in spontaneous withdrawal will require concomitant medications for improved therapeutic response.",2003.0,0,0
448,12658557,Dorzolamide X apraclonidine in the prevention of the intraocular pressure spike after Nd : YAG laser posterior capsulotomy.,Carlos Arieta; Marcela Amaral; Eliana Matuda; Cybele Crosta; Djalma de Carvalho Moreira Filho; Newton José,"To evaluate the efficacy of dorzolamide compared to apraclonidine, in the prevention of the intra-ocular pressure (IOP) spike after Nd :YAG laser posterior capsulotomy. SITE: Department of Ophthalmology, State University of Campinas (UNICAMP) General Hospital, Campinas, São Paulo, Brazil. In a double masked prospective clinical trial, 217 eyes from 217 patients were randomly assigned to receive either dorzolamide 2 h before and placebo 1 h before Nd : YAG laser capsulotomy or placebo 2 h before and apraclonidine 1 h before the procedure. Inclusion criteria were secondary cataracts with reduction in best corrected visual acuity (BCVA < 20/40), absence of manifest or suspected glaucoma and no known hypersensitivity to the study drugs. IOP was measured 2 h and 1 h before applying the laser, and 1 h, 2 h, 3 h and 7 days after. There were no statistically significant differences between the two groups regarding the IOP 2 h and 1 h before the procedure, and 1 h, 2 h, 3 h and 7 days after the laser treatment (p values, respectively: 0.077, 0.21, 0.085, 0.36, and 0.60). The results of this study suggest that dorzolamide is as safe and effective as apraclonidine in the prevention of the IOP elevation after Nd : YAG laser posterior capsulotomy. Synopsis. The efficacy of dorzolamide was compared to apraclonidine in the prevention of the intraocular pressure spike after Nd : YAG laser posterior capsulotomy in 217 patients and the results were similar with both drugs.",2003.0,0,0
449,12658913,Measurement of simple reaction time in antipsychotic treatment of patients with schizophrenia.,Blanka Kores Plesnicar; Bojan Zalar; Martina Tomori; Ivan Krajnc,"The role of simple reaction time in schizophrenia has been extensively reported to date in professional literature. However, most studies have examined basic reaction time under static conditions using a single measurement. The aim of the present study was to establish whether any changes occur in simple reaction time during treatment with risperidone or olanzapine in in-patients suffering a relapse of schizophrenia. Seventeen in-patients suffering acute relapse of schizophrenia (DSM IV criteria) and twenty matched, healthy controls participated in an eight-week, double-blind pilot study. The patients were treated with conventional antipsychotics for seven days after admission and were then randomised to the treatment arms with risperidone (4 mg/day) or with olanzapine (10 mg/day) at a fixed dosage in the first week and thereafter in flexible dosages for the remaining seven weeks. Since no differences were found between reaction times of patients treated with risperidone or olanzapine, the two treatment groups were merged in the statistical analysis before being compared with the normal controls. Psychopathological symptoms were assessed using the Positive and Negative Symptom Scale (PANSS) and extrapyramidal symptoms with the Simpson Angus Scale and Abnormal Involuntary Movement Scale. Reaction time was measured with the Alpha apparatus, connected to a personal computer. All assessments and measurements were conducted four times during the treatment phase of the study. The reaction time of patients was significantly longer than that of the healthy controls (t1 = 17.11; p1 < 0.05). After eight weeks of treatment the reaction time of patients significantly improved but did not reach that of the healthy controls (t4 = 28.18, p4 < 0.05). Furthermore, the improved reaction time in the patients did not correlate with improvement of psychopathological symptoms or with improved extrapyramidal symptoms. The results of the study suggest that simple reaction time can improve during treatment with atypical antipsychotics.",2003.0,0,0
450,12659615,Clinical trial response and dropout rates with olanzapine versus risperidone.,Benedetta Santarlasci; Andrea Messori,"In schizophrenia, comparing treatment dropouts between olanzapine and risperidone can be useful to better understand their relative effectiveness. To analyze the differences in the rates of dropout from clinical trials and response between these 2 antipsychotics. Literature search was based on MEDLINE (1966-May 2002). Analysis 1 included 4 randomized studies (838 patients), analysis 2 included 2 randomized studies (n = 716), and analysis 3 assessed 5 clinical studies for olanzapine (n = 928) and 3 for risperidone (n = 290). Odds ratios were estimated by the fixed-effect model. The risk of treatment discontinuation (analysis 1) was significantly greater for risperidone than for olanzapine (42% vs. 33%, respectively). The response rates were identical for the 2 drugs (analysis 2). A slightly better pattern of maintenance of response was found for olanzapine (analysis 3). The pattern of dropout and maintenance of remission seems to be better controlled for olanzapine than for risperidone.",2003.0,0,0
451,12661098,[AD/HD (attention deficit and hyperactivity syndrome) and methylphenidate].,M Kaga; S Miyamoto,,2003.0,0,0
452,12666001,[Can the addition of clonidine improve the analgesic efficacy of low dose intrathecal morphine? A randomised double-blind trial].,M Gehling; M Tryba; T Lüsebrink; A Zorn,"To evaluate the influence of intrathecal clonidine on spinal morphine analgesia and adverse effects after major orthopaedic surgery. The study was approved by the local Ethics Committee.After written informed consent, 45 ASA I-III patients scheduled for hip or knee replacement were included. Patients were randomly allocated to receive either placebo, 0.1 mg morphine or 0.1 mg morphine+50 microg clonidine in addition to 15 mg bupivacaine intrathecally. The primary outcome parameter was the time to first opioid request. Statistical differences were calculated with U-test or Fisher's exact test. Clonidine did not result in a significant improvement of postoperative analgesia. The mean time until first opioid request was for placebo 10.3+/-7.9 h, for 0.1 mg morphine 23.0+/-3.9 h and for 0.1 mg morphine+ 50 microg clonidine 21+/-6.9 h, respectively. Clonidine significantly increased the rate of adverse effects. Our trial did not confirm an improved analgesia with the combination of intrathecal morphine and clonidine. Due to increased adverse effects the combination of intrathecal clonidine and morphine does not seem to be a reasonable alternative in the management of postoperative pain after orthopaedic surgery.",2003.0,0,0
453,12667116,Bupropion SR for smoking cessation.,Robert West,"Cigarette dependence is recognised as a life-threatening disorder which can be treated by behavioural support and/or medication. Bupropion hydrochloride sustained-release (Zyban trade mark, GlaxoSmithKline) is licensed in many countries including the US, Canada, UK, Australia and continental Europe to aid smoking cessation. The usual recommended dose is 150 mg b.i.d. taken for 7 - 14 days prior to the quit date, and then 6 - 8 weeks afterwards (figures vary across countries). Evidence from seven double-blind, placebo-controlled, randomised trials shows that it improves success at staying off cigarettes for at least 12 months by 9 - 10 percentage points. Taking into account estimates of subsequent cessation and relapse patterns in treated and untreated smokers, and the improvement in life-expectancy of smokers who manage to stop, the estimated cost/life/year saved from an episode of use of the medication is approximately UK pound 1000 or US$1500. Bupropion has CNS stimulant properties; the common side effects are dry mouth and sleep disturbance. Rare but serious side effects are anaphylactic/hypersensitivity reaction and seizure (both estimated at 1 in a 1000). The drug is contraindicated in patients with hypersensitivity to the drug or its metabolites, any seizure disorder, eating disorder, severe hepatic cirrhosis, history of bipolar disorder or in patients taking monoamine oxidase inhibitors. Extreme caution is advised where there are any predisposing factors that may reduce the seizure threshold. Bupropion sustained-release and nicotine replacement therapies are both considered as first-line treatments to aid smoking cessation. Ideally patients should also enrol in a structured behavioural support programme to boost their chances of success.",2003.0,0,0
454,12668364,"Ziprasidone in the treatment of acute bipolar mania: a three-week, placebo-controlled, double-blind, randomized trial.",Paul E Keck; Marcio Versiani; Steven Potkin; Scott A West; Earl Giller; Kathleen Ice; Ziprasidone in Mania Study Group,"The study evaluated the efficacy and tolerability of ziprasidone, compared with placebo, in the treatment of adult patients with acute bipolar mania. Patients with a primary DSM-IV diagnosis of bipolar I disorder and a current manic or mixed episode (confirmed by the Structured Clinical Interview for DSM-IV Axis I Disorders, Patient Edition) (N=210) were randomly assigned in a 2:1 ratio to 3 weeks of double-blind treatment with ziprasidone (40-80 mg twice daily) or placebo. Efficacy was assessed with the Schedule for Affective Disorders and Schizophrenia, Change Version (which contains the Mania Rating Scale), Positive and Negative Syndrome Scale, Clinical Global Impression (CGI) severity scale, CGI improvement scale, and Global Assessment of Functioning Scale. Primary efficacy variables were differences from baseline to endpoint (last observation carried forward) in mean Mania Rating Scale and CGI severity scale scores between the ziprasidone and placebo groups. Safety evaluations included monitoring of adverse events, vital signs, electrocardiogram results, and clinical laboratory values and assessment of movement disorders and akathisia. Ziprasidone produced rapid, sustained improvements relative to baseline and placebo on all primary and most secondary efficacy measures at endpoint. Significant improvements were typically observed within 2 days after treatment commenced and were maintained throughout the 3 weeks. Ziprasidone was well tolerated and associated with a low rate of extrapyramidal symptoms; neither weight gain nor clinically significant changes in vital signs or other safety parameters were observed with ziprasidone. Ziprasidone monotherapy was significantly superior to placebo in reducing symptoms of acute mania in patients with bipolar I disorder. Onset of action was rapid, and tolerability of ziprasidone was generally comparable to that of placebo.",2003.0,0,0
455,12669177,,,,,0,0
456,12680748,A placebo-controlled study of lofexidine in the treatment of children with tic disorders and attention deficit hyperactivity disorder.,Helmut Niederhofer; Wolfgang Staffen; Alois Mair,"This study evaluated the efficacy and safety of Lofexidine in treating children with tic disorders and attention deficit hyperactivity disorder (ADHD). Subjects from a specialty tic disorders clinic were randomly assigned to receive 8 weeks of treatment with lofexidine or placebo under double-blind conditions. Follow-up visits occurred every 2 weeks for safety monitoring and dose adjustment. Fourty-four medication-free subjects (41 boys and three girls; mean age of 10.4 years) with ADHD, combined type, and a tic disorder participated. After 8 weeks of treatment, lofexidine was associated with a mean improvement of 41% in the total score on the teacher-rated ADHD Rating Scale compared to 7% improvement for placebo. Eleven of 22 subjects who received lofexidine were blindly rated on the Clinical Global Scale-Improvement as either much improved or very much improved compared to none of 22 subjects who received placebo. The mean score on the parent-rated hyperactivity index improved by 29% in the lofexidine group and 18% in the placebo group, which was not a significant difference. On the Continuous Performance Test, commission errors decreased by 25% and omission errors by 20% in the lofexidine group, compared with increases of 33% in commission errors and of 36% in omission errors in the placebo group. Tic severity decreased by 27% in the lofexidine group, compared to 0% in the placebo group. One lofexidine subject with sedation withdrew at week 4. Lofexidine was associated with insignificant decreases in blood pressure and pulse. Lofexidine appears to be a safe and effective treatment for children with tic disorders and ADHD.",2003.0,0,0
457,12682319,A placebo-controlled trial of risperidone in Tourette syndrome.,L Scahill; J F Leckman; R T Schultz; L Katsovich; B S Peterson,"To evaluate the efficacy and safety of risperidone in children and adults with Tourette syndrome. This was an 8-week, randomized, double-blind, placebo-controlled trial. The primary outcome measure was the Total Tic score of the Yale Global Tic Severity Scale (YGTSS). Thirty-four medication-free subjects (26 children and 8 adults) ranging in age from 6 to 62 years (mean = 19.7 +/- 17.0 years) participated. YGTSS Total Tic scores were similar at baseline (26.0 +/- 5.1 for risperidone vs 27.4 +/- 8.5 for placebo). After 8 weeks of treatment (mean daily dose of 2.5 +/- 0.85), the 16 subjects on risperidone showed a 32% reduction in tic severity from baseline, compared to a 7% reduction for placebo patients (n = 18) (F[2,64] = 6.07; p = 0.004). The 12 children randomized to risperidone showed a 36% reduction in tic symptoms compared to an 11% decrease in the 14 children on placebo (F[2,48] = 6.38; p = 0.004). Two children on risperidone showed acute social phobia, which resolved with dose reduction in one subject but resulted in medication discontinuation in the other. A mean increase in body weight of 2.8 kg was observed in the risperidone group compared to no change in placebo (F[2,64] = 10.68; p = 0.0001). No extrapyramidal symptoms and no clinically significant alterations in cardiac conduction times or laboratory measures were observed. Risperidone appears to be safe and effective for short-term treatment of tics in children or adults with Tourette syndrome. Longer-term studies are needed to evaluate the durability of efficacy and safety over time.",2003.0,0,0
458,12685512,Effects of nicardipine and clonidine on cognitive functions and electroencephalography in hypertensive patients.,T Denolle; P Sassano; H Allain; D Bentué-Ferrer; S Breton; I Cimarosti; B Ouatara; M Merienne; J M Gandon,"The aim of this study was to investigate the cognitive and electroencephalography (EEG) short-term effects of a calcium antagonist, nicardipine, compared to placebo and clonidine (which, having known sedative effects, acted as a negative control) for 15 days in elderly hypertensive patients with memory complaints. Nicardipine and clonidine were compared with placebo in a double-blind, randomized, three-way cross-over controlled study after a 2-week placebo run-in period. This was a phase II clinical study carried out on out-patients in a single research centre. Fifteen elderly (63 +/- 10 years) hypertensive patients, without dementia but with memory complaints, were included. Psychomotor performance and cognition were assessed using both an extensive battery of validated psychometric tests (which evaluated attention and vigilance, body sway and memory) and an EEG profile. Cardiovascular parameters measured were blood pressure and heart rate. No detrimental effects of nicardipine were found on attention, vigilance, body sway or memory. Nicardipine produced a significant increase in alpha EEG energies, which may indicate possible alerting effects. In contrast, clonidine induced well-known deleterious sedative effects in psychometric tests and in EEG analysis (decrease in alpha and increase in delta and theta waves). The two drugs produced equivalent decreases in blood pressure at steady state. In conclusion, clonidine induced well-known sedative effects, while nicardipine did not impair central nervous system activity and may have had some short-term alerting effects in elderly hypertensive patients with memory complaints. This study supports the hypothesis of a dissociation between blood pressure and direct drug effects on the central nervous system.",2003.0,0,0
459,12691600,"Reader response to, ""Effects of risperidone on aberrant behavior in persons with developmental disabilities: I. A double-blind crossover study using multiple measures"".",Andrew Levitas,,2003.0,0,0
460,12698209,Aripiprazole: efficacy and tolerability profile of a novel-acting atypical antipsychotic.,Peter F Buckley,"Aripiprazole, the latest atypical antipsychotic to come to clinical practice, has a proposed mechanism of action different to other agents, most notably in its partial agonist action at dopamine (D2) receptors and at serotonin (5HT1A) receptors. Placebo-controlled comparative trials of aripiprazole confirm efficacy for positive, negative and general psychopathology. Treatment-emergent adverse effects appear low. Aripiprazole is associated with low propensity for extrapyramidal side effects, an absence hyperprolactinemia and a low propensity for weight gain. Aripiprazole's clinical role will be determined by clinical experience, additional phase IV studies, and comparative information for this agent with respect to the efficacy and tolerability profiles of other atypical antipsychotic medications.",2003.0,0,0
461,12700715,Atypical and conventional antipsychotic drugs in treatment-naive first-episode schizophrenia: a 52-week randomized trial of clozapine vs chlorpromazine.,Jeffrey A Lieberman; Michael Phillips; Hongbin Gu; Scott Stroup; Peiyan Zhang; Lan Kong; Zhongfu Ji; Gary Koch; Robert M Hamer,"The purported advantages of second-generation or ""atypical"" antipsychotics relative to first-generation antipsychotics have not been examined in patients with a first episode of schizophrenia. This flexible-dose study examined efficacy and safety in a randomized, double-blind, 52-week trial, comparing chlorpromazine (CPZ) and clozapine (CLZ) in treatment naive patients experiencing their first episode of schizophrenia. In all, 160 inpatients with first-episode schizophrenia or schizophreniform disorder were randomized to CPZ or CLZ and followed them for 52 weeks or until dropout. The primary efficacy measure was time to first remission and proportion of time remaining in remission. The analysis was supplemented by comparisons on a profile of clinical symptoms and side effects. Of these first-episode patients, 80% achieved remission within 1 year (79% CPZ, 81% CLZ). The Kaplan-Meier estimated median time to first remission was 8 weeks for CLZ vs 12 weeks for CPZ (chi(2)(1)=5.56, p=0.02). Both the rate of first achieving remission and the odds for being in remission during the trial were almost doubled for the CLZ group in comparison with the CPZ group. At 12 weeks, CLZ was superior on many rating scale measures of symptom severity while CPZ was not superior on any. These symptom differences remained significant when controlling for EPS differences. By 52 weeks many of the symptom differences between groups were no longer significantly different. Generally, CLZ produced fewer side effects than CPZ, particularly extrapyramidal side effects. There was no significant difference between treatments in weight change or glucose metabolism. For each prior year of untreated psychosis, there was a 15% decrease in the odds of achieving remission (OR=0.85; CI 0.75-0.95). A high proportion of first-episode patients remitted within 1 year. We detected no difference in the proportion of first-episode patients receiving CLZ or CPZ that achieved remission. However, first-episode patients receiving CLZ remitted significantly faster and remained in remission longer than subjects receiving CPZ. While the CLZ group showed significantly less symptomatology on some measures and fewer side effects at 12 weeks, the two treatment groups seemed to converge by 1 year. Longer duration of untreated psychosis was associated with lower odds of achieving remission.",2003.0,0,0
462,12709775,Initiating treatment with modafinil for control of excessive daytime sleepiness in patients switching from methylphenidate: an open-label safety study assessing three strategies.,Michael J Thorpy; Jonathan R L Schwartz; Ruzica Kovacevic-Ristanovic; Roza Hayduk,"Modafinil is a first-line wake-promoting medication and a useful therapeutic alternative to psychostimulant medications for excessive daytime sleepiness. This 5-week, randomized, open-label study evaluated three strategies for switching patients from methylphenidate, a commonly used psychostimulant, to modafinil. Patients ( n=40) with excessive daytime sleepiness related to narcolepsy, who had received previous treatment with methylphenidate, were switched from methylphenidate to modafinil (200 mg/day followed by 400 mg/day) without a washout period between treatments, with a 2-day washout period between treatments, or by using a taper-down/titrate-up protocol. Adverse events were recorded throughout the study, and Epworth Sleepiness Scale scores were determined at the end of the study. The majority of patients (95%) were successfully switched to modafinil. At the study end point, mean Epworth Sleepiness Scale scores were <12 for each treatment group. All three switching strategies were well tolerated, with adverse events mild or moderate in nature. Adverse events most frequently reported during modafinil treatment were among those seen previously in large-scale, placebo-controlled studies. There were no meaningful differences among the treatment groups in the frequency or severity of adverse events or in their relationship to modafinil treatment. Only one patient discontinued modafinil treatment because of a treatment-related adverse event (i.e. moderate headache); another patient discontinued due to insufficient efficacy. Switching from methylphenidate to modafinil was well tolerated with or without a washout period or when the methylphenidate dose is gradually tapered during initiation of modafinil therapy. Daytime wakefulness was maintained in patients who have switched from methylphenidate to modafinil. These data suggest that patients with narcolepsy may be switched from methylphenidate to modafinil with few complications and inconveniences.",2003.0,0,0
463,12714026,"Bupropion SR for smoking cessation in smokers with cardiovascular disease: a multicentre, randomised study.",S Tonstad; C Farsang; G Klaene; K Lewis; A Manolis; A P Perruchoud; C Silagy; P I van Spiegel; C Astbury; A Hider; R Sweet,"To investigate the safety and efficacy of bupropion sustained release (bupropion SR) in promoting abstinence from smoking in subjects with cardiovascular disease (CVD). Six hundred twenty-nine subjects with CVD who smoked >/=10 cigarettes/day were randomised in a double-blind, multicentre study to receive bupropion SR (150 mg twice daily) or placebo for 7 weeks, with a follow-up of 52 weeks. Primary efficacy endpoint: continuous abstinence from smoking from weeks 4 to 7. Secondary endpoints: continuous abstinence (weeks 4-12, 4-26 and 4-52) and weekly point prevalence abstinence. All participants received brief motivational support. Safety was evaluated throughout the study. Continuous smoking abstinence rates from weeks 4 to 7 were significantly higher in subjects receiving bupropion SR compared with placebo (43 vs. 19%, odds ratio [OR]=3.27, 95% confidence interval [CI] 2.24-4.84; P<0.001). Continuous abstinence rates from weeks 4 to 26 and 4 to 52 continued to be more than double for bupropion SR compared with placebo (27 vs. 11%; 22 vs. 9%, P<0.001). Weekly point prevalence abstinence was significantly higher for participants who received bupropion SR compared with placebo at weeks 3, 7, 26 and 52 (P<0.001). In both groups, there were no clinically significant changes in blood pressure and heart rate throughout the treatment phase. Overall, 6% of the participants (n=36) discontinued study medication due to an adverse event (bupropion SR, n=17; placebo, n=19). After 7 weeks of bupropion SR treatment, more than twice as many smokers with CVD had quit smoking at 1 year compared with placebo. The safety profile of bupropion SR was similar to that previously observed in general smoking populations.",2003.0,0,0
464,12729864,"Aripiprazole in the treatment of schizophrenia: safety and tolerability in short-term, placebo-controlled trials.",Stephen R Marder; Robert D McQuade; Elyse Stock; Stephen Kaplita; Ronald Marcus; Allan Z Safferman; Anutosh Saha; Mirza Ali; Taro Iwamoto,"Aripiprazole is a novel antipsychotic with a unique mechanism of action. Presented here is a pooled analysis of safety and tolerability data from all completed short-term, placebo-controlled trials in schizophrenia from the aripiprazole clinical development program. Data were analyzed from five 4- to 6-week double-blind multicenter studies of patients hospitalized with acute relapse of schizophrenia or schizoaffective disorder randomized to aripiprazole (n=932), placebo (n=416), or haloperidol (n=201). Daily aripiprazole doses ranged from 2 to 30 mg. Safety assessments included adverse event (AE) reports, EPS scales, ECGs, weight, and prolactin, glucose and cholesterol levels. Aripiprazole was well tolerated, with similar AE incidence rates to placebo, and lower rates than haloperidol for akathisia, extrapyramidal syndrome and somnolence. Objective EPS assessments demonstrated no significant differences between aripiprazole and placebo on Simpson-Angus Scale (SAS) scores, no dose-dependent effects on Barnes Akathisia scores, and significant reductions in Abnormal Involuntary Movement Scale (AIMS) scores from baseline vs. placebo (p</=0.01). Haloperidol showed increased SAS and Barnes Akathisia scores over placebo (p</=0.01). There was minimal mean weight change with aripiprazole (+0.71 kg) and haloperidol (+0.56 kg), and a lack of QT(c) prolongation. Serum prolactin increased with haloperidol, but not aripiprazole. In conclusion, aripiprazole shows a favorable safety and tolerability profile with low potential for EPS, weight gain, prolactin elevation, QT(c) prolongation, and sedation. Aripiprazole's safety profile may offer benefits in schizophrenia treatment.",2003.0,0,0
465,12729866,Are patients enrolled in first episode psychosis drug trials representative of patients treated in routine clinical practice?,Jonathan Rabinowitz; Evelyn J Bromet; Michael Davidson,"Evidence on efficacy of antipsychotic medications comes primarily from controlled trials which select eligible consenting patients for experimental and regimented treatments, who do not abuse drugs, and are in good general health. Thus, it is not clear to what extent results are generalizable to most individuals treated for a psychotic illness who may not be eligible for such trials. This study compared characteristics of patients treated in a large randomized trial of persons with early psychosis to a cohort from a large epidemiological study of first episode psychosis. Included were the 535 patients enrolled in a controlled trial of antipsychotic medication and 179 similarly diagnosed persons from the Suffolk County Mental Health epidemiological study. Drug trial exclusion criteria were used to estimate the number of patients from the epidemiological study who would have been ineligible for the drug trial. The two samples were compared on key characteristics. Thirty-three percent (n=59) of the epidemiological sample did not meet inclusion criteria for the drug trial (due to antidepressant treatment, n=26; current substance abuse, n=18; recent suicide attempt, n=9; and for more than one reason, n=6). There were no significant differences between the two study samples on age of onset, age, gender and premorbid functioning. Drug trial patients had higher Brief Psychiatric Rating Scale (BPRS), slightly lower Clinical Global Impression (CGI), and less formal education than those in the epidemiological study. While some patients in the epidemiological sample would have been excluded from the drug trial, patients in the two studies were similar on several key variables.",2003.0,0,0
466,12729882,Olanzapine vs risperidone in the management of schizophrenia: a randomized double-blind trial in Australia and New Zealand.,Oye Gureje; Wayne Miles; Nicholas Keks; David Grainger; Timothy Lambert; John McGrath; Pierre Tran; Stanley Catts; Allen Fraser; Harry Hustig; Scott Andersen; Ann Marie Crawford,"Improved drug therapy for schizophrenia may represent the best strategy for reducing the costs of schizophrenia and the recurrent chronic course of the disease. Olanzapine and risperidone are atypical antipsychotic agents developed to meet this need. We report a multicenter, double-blind, parallel, 30-week study designed to compare the efficacy, safety, and associated resource use for olanzapine and risperidone in Australia and New Zealand. The study sample consisted of 65 patients who met DSM-IV criteria for schizophrenia, schizoaffective disorder, or schizophreniform disorder. Olanzapine-treated patients showed a significantly greater reduction in Positive and Negative Syndrome Scale (PANSS) total, Brief Psychiatric Rating Scale (BPRS) total, and PANSS General Psychopathology scores at endpoint compared to the risperidone-treated patients. Response rates through 30 weeks showed a significantly greater proportion of olanzapine-treated patients had achieved a 20% or greater improvement in their PANSS total score compared to risperidone-treated patients. Olanzapine and risperidone were equivalent in their improvement of PANSS positive and negative scores and Clinical Global Impression-Severity of Illness scale (CGI-S) at endpoint. Using generic and disease-specific measures of quality of life, olanzapine-treated patients showed significant within-group improvement in most measures, and significant differences were observed in favor of olanzapine over risperidone in Quality of Life Scale (QLS) Intrapsychic Foundation and Medical Outcomes Study Short Form 36-item instrument (SF-36) Role Functioning Limitations-Emotional subscale scores. Despite the relatively small sample size, our study suggests that olanzapine has a superior risk:benefit profile compared to risperidone.",2003.0,0,0
467,12734634,Relative lack of cognitive effects of methylphenidate in elderly male volunteers.,Danielle C Turner; Trevor W Robbins; Luke Clark; Adam R Aron; Jonathan Dowson; Barbara J Sahakian,"Methylphenidate, a dopaminergic and noradrenergic reuptake inhibitor, has been shown in young, healthy adult volunteers to produce pronounced effects on working memory and sustained attention. We were interested in assessing whether similar improvements could be conferred upon elderly volunteers in order to gain a more complete understanding of the effects of age on monoaminergic manipulations of working memory and attention, as well as to explore the potential for pharmacological intervention in attention and executive dysfunction disorders in this age group. The main aim of the study was to characterise the dose-related effects of methylphenidate on a range of neuropsychological functions in elderly healthy volunteers. Sixty healthy elderly adult male volunteers received either a single oral dose of placebo, 20 mg or 40 mg methylphenidate prior to performing a variety of tasks designed to assess memory, attention and executive function. A randomised double-blind, between-subjects design was used. Methylphenidate had significant cardiovascular and subjective effects. However, unlike in younger volunteers, no significant effects of drug on working memory (spatial span and spatial working memory), response inhibition (stop-signal) or sustained attention (rapid visual information processing) were seen. Subtle effects on latency similar to those in younger volunteers were identified: both doses of methylphenidate resulted in a slowing in response time during set-shifting and decision-making. The results of this study demonstrate that, in elderly subjects, the cognitive effects of methylphenidate are grossly attenuated and distinct from the profile previously described in younger volunteers. It is suggested that methylphenidate may not be appropriate as a pharmacological intervention in elderly patient groups, such as those reporting age-related cognitive decline.",2003.0,0,0
468,12734766,Methylphenidate enhances both intracortical inhibition and facilitation in healthy adults.,J Kirschner; G H Moll; U M Fietzek; H Heinrich; V Mall; S Berweck; F Heinen; A Rothenberger,"Transcranial magnetic stimulation was used to investigate the effect of the psychostimulant drug methylphenidate (MPH) on motor cortex excitability in healthy adults (n = 12) in a placebo-controlled, crossover design study. MPH caused an enhancement of intracortical inhibition as well as intracortical facilitation. Enhancement of both of these TMS parameters was unexpected and suggests that MPH exerts its action on the motor cortex not only through the dopaminergic neurotransmitter system.",2003.0,0,0
469,12747876,New generation antipsychotics versus low-potency conventional antipsychotics: a systematic review and meta-analysis.,Stefan Leucht; Kristian Wahlbeck; Johannes Hamann; Werner Kissling,"The clearest advantage of new generation, atypical antipsychotics is a reduced risk of extrapyramidal side-effects (EPS), compared with conventional compounds. These findings might have been biased by the use of the high-potency antipsychotic haloperidol as a comparator in most of the trials. We aimed to establish whether the new drugs induce fewer EPS than low-potency conventional antipsychotics. We did a meta-analysis of all randomised controlled trials in which new generation antipsychotics had been compared with low-potency (equivalent or less potent than chlorpromazine) conventional drugs. We included studies that met quality criteria A or B in the Cochrane Collaboration Handbook, and assessed quality with the Jadad scale. The primary outcome of interest was the number of patients who had at least one EPS. We used risk differences and 95% CIs as measures of effect size. We identified 31 studies with a total of 2320 participants. Of the new generation drugs, only clozapine was associated with significantly fewer EPS (RD=-0.15, 95% CI -0.26 to -0.4, p=0.008) and higher efficacy than low-potency conventional drugs. Reduced frequency of EPS seen with olanzapine was of borderline significance (-0.15, -0.31 to -0.01, p=0.07). Only one inconclusive trial of amisulpride, quetiapine, and risperidone and no investigations of ziprasidone and sertindole were identified, but some evidence indicates that zotepine and remoxipride do not lead to fewer EPS than low-potency antipsychotics. Mean doses less than 600 mg/day of chlorpromazine or its equivalent had no higher risk of EPS than new generation drugs. As a group, new generation drugs were moderately more efficacious than low-potency antipsychotics, largely irrespective of the comparator doses used. Optimum doses of low-potency conventional antipsychotics might not induce more EPS than new generation drugs. Potential advantages in efficacy of the new generation drugs should be a factor in clinical treatment decisions to use these rather than conventional drugs.",2003.0,0,0
470,12753444,Side-effects of postoperative epidural analgesia in children: a randomized study comparing morphine and clonidine.,G Cucchiaro; C Dagher; C Baujard; A M Dubousset; D Benhamou,"Morphine is widely used in association with local anaesthetics for postoperative epidural analgesia. There are no data on the prolonged use of clonidine for postoperative analgesia in children. The primary outcome of this randomized, double-blind trial was to compare the incidence of side-effects after epidural infusion of clonidine or morphine, in association with ropivacaine in children. After institutional approval, 26 children, aged 3-12 years, who were scheduled for abdominal surgery, had an epidural catheter placed after induction of general anaesthesia. Patients were then randomized to two different groups. After an initial bolus of 2.5 mg x kg-1 0.25% ropivacaine with either 40 micro g x kg-1 morphine (group M, n = 14) or 1 micro g x kg-1 clonidine (group C, n = 12), an epidural infusion was started at a rate of 0.4 ml x kg-1 x h-1. The patients in the M group received an infusion of 0.08% ropivacaine with 10 micro g.ml-1 morphine, those in the group C an infusion of 0.08% ropivacaine with 0.6 micro g.ml-1 clonidine. The two groups were similar with respect to age, sex and weight. One patient in the C group was excluded for misplacement of the epidural catheter. The incidence of vomiting and pruritus was significantly higher in the M group compared with the C group (64% and 85% versus 0%, respectively). The incidence of pain was significantly higher in the C group compared with the M group (73% versus 29%) as well as the need for rescue analgesia medications. Epidural clonidine is followed by a significantly lower incidence of side-effects. However, its analgesic effects, at least at the doses used in this study, are less potent than those of epidural morphine.",2003.0,0,0
471,12763699,Factorial validity of the Conners' Parent Rating Scale-revised: short form with psychiatric outpatients.,Geetha Kumar; Robert A Steer,"To assess the factorial validity of the 27-item Conners' Parent Rating Scale-Revised: Short Form (CPRS-R:S; Conners, 1997), 100 (50%) male and 100 (50%) female psychiatric outpatients between 5 and 16 years old were rated by a parent. A confirmatory factor analysis of the 18 item ratings from the CPRS-R:S Oppositional, Cognitive Problems, and Hyperactivity scales provided only tentative support for scoring these scales as Conners (1997) recommended. However, an exploratory principal-axis factor analysis with all 27 item ratings found 2 dimensions: 1 dimension was composed of the 6 items in the Oppositional scale, and other dimension contained the remaining 21 items. An attention deficit hyperactivity disorder (ADHD) Total Symptoms scale was constructed by summing the ratings for these 21 symptom ratings, and this scale was found to be as effective as the Hyperactivity scale was in discriminating between youth who were and were not eventually diagnosed with an ADHD. We discuss the results as providing an alternate way of scoring the CPRS-R:S to screen for an ADHD in child and adolescent psychiatric outpatients.",2003.0,0,0
472,12765489,Atomoxetine.,Dene Simpson; Caroline M Perry,"Atomoxetine, formerly tomoxetine, is a selective norepinephrine reuptake inhibitor and a new, nonstimulant treatment for attention deficit hyperactivity disorder (ADHD). In vitro, ex vivo and in vivo studies have shown that atomoxetine is a highly selective antagonist of the presynaptic norepinephrine transporter with little or no affinity for other noradrenergic receptors or other neurotransmitter transporters or receptors. In four randomized, placebo-controlled clinical trials conducted over 6-9 weeks in children and adolescents with ADHD, atomoxetine (total daily dose 1-1.8 mg/kg administered in one or two doses daily) reduced symptoms (hyperactivity, impulsiveness and inattention) as determined by the reduction in ADHD total score (34-38% with atomoxetine versus 13-15.7% with placebo [p < 0.05]). Atomoxetine also significantly improved ADHD subscale rating scores (p < 0.05 and p < 0.001), psychosocial well-being (p < 0.05) and ADHD-related problem behavior according to parent and teacher ratings (p < 0.05). Atomoxetine was well tolerated in clinical trials and discontinuation rates due to adverse events were low (<5%). The most common treatment-related adverse event was decreased appetite. Atomoxetine shows no abuse potential and is not a controlled substance in the US.",2003.0,0,0
473,12766921,"The impact upon extra-pyramidal side effects, clinical symptoms and quality of life of a switch from conventional to atypical antipsychotics (risperidone or olanzapine) in elderly patients with schizophrenia.",C W Ritchie; E Chiu; S Harrigan; K Hall; A Hassett; S Macfarlane; M Mastwyk; D W O'Connor; J Opie; D Ames,"Atypical antipsychotics are commonly used in the management of schizophrenia in late life with evidence suggesting they induce lower rates of motor disturbance, but have similar efficacy to conventional antipsychotics. Trials in the elderly have been either retrospective, small, of short duration or of a single-arm design. To demonstrate the effects upon motor side-effects, efficacy, safety and quality of life (QOL) of switching elderly patients with schizophrenia from conventional antipsychotics to olanzapine or risperidone. Elderly patients with schizophrenia were randomly allocated to olanzapine or risperidone and followed through an open-label crossover period. Between and within group intention to treat analyses were conducted. 66 patients were randomised (mean age 69.6 [SD +/- 6.2]). Four (11.8%) patients on olanzapine and 8 (26.7%) patients on risperidone failed to complete the crossover because of treatment failure [Odds Ratio (OR) = 2.73[0.73-10.2] p = 0.14]. The mean doses upon completion of switching in each arm were 9.9 mg (SD = 4.2) and 1.7 mg (SD = 1.2) for olanzapine and risperidone respectively. In both arms there was improvement in Parkinsonism, though only olanzapine was associated with a reduction in dyskinetic symptoms. The Brief Psychiatric Rating Scale, Scale for the assessment of Negative Symptoms and Montgomery and Asberg Depression Rating Scale scores all improved through the crossover period in both arms with no between group differences. Treatment with olanzapine was associated with a better response over risperidone on the psychological domain of the World Health Organisation-Quality Of Life [Brief] (WHO-QOL-BREF) scale ( p = 0.02). Patients in the olanzapine arm also demonstrated improvement from baseline in the WHO-QOL-BREF physical, psychological and health satisfaction domains, but risperidone had no effect on any Quality of Life (QOL) measure. After switching from a conventional antipsychotic, olanzapine and risperidone were associated with improvement in core symptoms of schizophrenia and motor side effects. Subjects switched to olanzapine were more likely to complete the switching process and show an improvement in psychological QOL.",2003.0,0,0
474,12774863,Motor timing deficits in community and clinical boys with hyperactive behavior: the effect of methylphenidate on motor timing.,Katya Rubia; Janet Noorloos; Anna Smith; Boudewijn Gunning; Joseph Sergeant,"In a previous paper we showed that community children with hyperactive behavior were more inconsistent than controls in the temporal organization of their motor output. In this study we investigated: (1) various aspects of motor timing processes in 13 clinically diagnosed boys with attention deficit hyperactivity disorder (ADHD) who were compared to 11 community boys with hyperactive behavior and to a control group and (2) the effect of methylphenidate on the motor timing processes in the clinical group with ADHD in a double blind, cross-over, medication-placebo design, including 4 weeks of medication. The clinical group with ADHD, like the community group with hyperactivity, showed greater variability in sensorimotor synchronization and in sensorimotor anticipation relative to controls. The clinical group was also impaired in time perception, which was spared in the community group with hyperactivity. The persistent, but not the acute dose, of methylphenidate reduced the variability of sensorimotor synchronization and anticipation, but had no effect on time perception. This study shows that motor timing functions are impaired in both clinical and community children with hyperactivity. It is the first study to show the effectiveness of persistent administration of methylphenidate on deficits in motor timing in ADHD children and extends the use of methylphenidate from the domain of attentional and inhibitory functions to the domain of executive motor timing.",2003.0,0,1
475,12774864,Selective inhibition in children with attention-deficit hyperactivity disorder off and on stimulant medication.,Anne-Claude Bedard; Abel Ickowicz; Gordon D Logan; Sheilah Hogg-Johnson; Russell Schachar; Rosemary Tannock,"Selective inhibition requires discrimination between auditory signals and is assessed using a modification of the stop-signal task. Selective inhibition was assessed in a group of 59 clinic-referred, DSM-IV-diagnosed children with attention-deficit hyperactivity disorder (ADHD) and compared to that of a community sample of 59 children. Methylphenidate (MPH) effects on selective inhibition were assessed in a subset of the ADHD sample that participated in an acute, randomized, placebo-controlled, crossover trial with 3 fixed doses of MPH. Children with ADHD performed more poorly than controls on the majority of selective stop-signal task parameters: they exhibited more anticipatory (invalid) responses, with less accurate and more variable responses on the response execution task, as well as a slower selective inhibition process. MPH improved speed of both inhibition and response execution processes; it also reduced variability of response execution and decreased nonselective inhibition. On the one hand, findings are consistent with purported inhibition deficit in ADHD, but on the other hand, suggest that neither the impairment itself, nor MPH effects, were restricted to inhibition.",2003.0,0,1
476,12777271,Long-acting injectable risperidone: efficacy and safety of the first long-acting atypical antipsychotic.,John M Kane; Mariëlle Eerdekens; Jean-Pierre Lindenmayer; Samuel J Keith; Michael Lesem; Keith Karcher,"The authors assessed the efficacy and safety of the first long-acting atypical antipsychotic (long-acting injectable risperidone) in patients with schizophrenia. In a 12-week, multicenter, double-blind, randomized study, patients received intramuscular injections every 2 weeks of placebo or long-acting risperidone (25 mg, 50 mg, or 75 mg). The primary measure of efficacy was the change in total score on the Positive and Negative Syndrome Scale. Of the 554 patients who were enrolled, 400 entered the double-blind study, and 370 received at least one postbaseline assessment. Mean changes in score of -6.2, -8.5, and -7.4 on the Positive and Negative Syndrome Scale were seen at endpoint for the 25-, 50-, and 75-mg risperidone groups, respectively; all three change scores were significantly different from that seen with placebo (+2.6). Improvements in positive and negative symptoms were also significantly greater in patients receiving risperidone. Long-acting risperidone was well tolerated. Adverse events related to extrapyramidal symptoms were spontaneously reported by 13% of patients receiving placebo and 10% of patients in the 25-mg risperidone group, with higher rates in the 50-mg and 75-mg groups. Severity of extrapyramidal symptoms was mild at baseline and throughout the trial in each treatment group. Mean weight changes were small in the 25-, 50-, and 75-mg risperidone groups (0.5 kg, 1.2 kg, and 1.9 kg, respectively). Injection site pain was rated as low by the patients, consistent with the investigators' pain ratings. Long-acting injectable risperidone was efficacious and well tolerated and provides both clinicians and patients with a new mode of treatment that can improve the outcome of long-term therapy.",2003.0,0,0
477,12777289,Randomized controlled trials.,Ashok Kumar Jainer; Mohan Chawla,,2003.0,0,0
478,12798791,Reduction in excess daytime sleepiness by modafinil in patients with myotonic dystrophy.,K Talbot; J Stradling; J Crosby; D Hilton-Jones,"Patients with myotonic dystrophy frequently suffer from excess daytime sleepiness, which can be a significant cause of disability. Previous studies have indicated that this excess daytime sleepiness is only occasionally due to obstructive sleep apnoea and may be principally of central nervous system origin. Modafinil has been successfully used to treat narcolepsy, a central disorder causing excess daytime sleepiness. We have investigated the use of this drug in myotonic dystrophy patients with excess daytime sleepiness. Patients were recruited from a clinic population on the basis of screening with the Epworth Sleepiness Scale. Patients scoring 10 and above were invited to participate in a randomized double-blind crossover trial of modafinil versus placebo, with four weeks in each arm of the study separated by a 2-week washout period. Patients were assessed by polysomnography at baseline. The primary outcome measures were change in both the Epworth Sleepiness Scale and a modified Maintenance of Wakefulness Test, which were measured at the start of each arm of the trial and in week 3 of each intervention period. In agreement with previous smaller studies, sleepiness is not correlated with CTG expansion size. Treatment with modafinil showed a non-significant reduction in median Epworth Sleepiness Scale. However, the median Maintenance of Wakefulness Test score was prolonged by treatment (31.7-40 min, P=0.006). There were no significant adverse cardiac effects of the drug in this group of patients (resting 12 lead and 24 h ECG monitoring). Selected patients with myotonic dystrophy and excess daytime sleepiness may benefit from modafinil. In this patient group the Epworth Sleepiness Scale may not be the most reliable measure of sleepiness. Despite the potential for cardiac disease in these patients, the drug was well tolerated with no adverse effects.",2003.0,0,0
479,12811711,Calming versus sedative effects of intramuscular olanzapine in agitated patients.,John Battaglia; Stacy R Lindborg; Karla Alaka; Karena Meehan; Padraig Wright,"Distinct calming rather than nonspecific sedation is desirable for the treatment of acute agitation. In 3 double-blind studies, acutely agitated patients with schizophrenia (N = 311), bipolar mania (N = 201), or dementia (N = 206) were treated with intramuscular (1-3 injections/24 hrs) olanzapine (2.5-10.0 mg), haloperidol (7.5 mg), lorazepam (2.0 mg), or placebo. The Agitation-Calmness Evaluation Scale (ACES; Eli Lilly and Co.) and treatment-emergent adverse events assessed sedation. Across all studies, 1 patient (lorazepam-treated, bipolar) became unarousable. There were no significant between-group differences in ACES scores of deep sleep or unarousable at any time across. Excluding asleep patients, agitation remained significantly more reduced with olanzapine than placebo (P <.05). The incidences of adverse events indicative of sedation were not significantly different with olanzapine versus comparators. For the treatment of acute agitation associated with schizophrenia, bipolar mania, or dementia, intramuscular olanzapine-treated patients experienced no more sedation than haloperidol- or lorazepam-treated patients and experienced distinct calming rather than nonspecific sedation.",2003.0,0,0
480,12826855,Differential modulation of remifentanil-induced analgesia and postinfusion hyperalgesia by S-ketamine and clonidine in humans.,Wolfgang Koppert; Reinhard Sittl; Karin Scheuber; Monika Alsheimer; Martin Schmelz; Jürgen Schüttler,"Experimental studies and clinical observations suggest a possible role for opioids to induce pain and hyperalgesia on withdrawal. The authors used a new experimental pain model in human skin to determine the time course of analgesic and hyperalgesic effects of the mu-receptor agonist remifentanil alone or in combination with the N-methyl-D-aspartate-receptor antagonist S-ketamine or the alpha(2)-receptor agonist clonidine. Thirteen volunteers were enrolled in this randomized, double-blind, placebo-controlled study. Transcutaneous electrical stimulation at a high current density (2 Hz, 67.3 +/- 16.8 mA, mean +/- SD) induced acute pain (numerical 11-point rating scale: 5-6 out of 10) and stable areas of mechanical hyperalgesia to punctate stimuli and touch (allodynia). The magnitude of pain and area of hyperalgesia were assessed before, during, and after drug infusion (remifentanil at 0.1 microg x kg-1 x min-1 and S-ketamine at 5 microg x kg-1 x min-1 over a period of 30 min, respectively; clonidine infusion at 2 microg/kg for 5 min). Remifentanil reduced pain and areas of punctate hyperalgesia during infusion. In contrast, postinfusion pain and hyperalgesia were significantly higher than control. During infusion of S-ketamine, pain and hyperalgesia decreased and gradually normalized after infusion. When given in combination, S-ketamine abolished postinfusion increase of punctate hyperalgesia but did not reduce increased pain ratings. Clonidine alone did not significantly attenuate pain or areas of hyperalgesia. However, when given in combination with remifentanil, clonidine attenuated postinfusion increase of pain ratings. Opioid-induced postinfusion hyperalgesia could be abolished by S-ketamine, suggesting an N-methyl-d-aspartate-receptor mechanism. In contrast, elevated pain ratings after infusion were not reduced by ketamine but were alleviated by the alpha(2)-receptor agonist clonidine. The results of this study suggest different mechanisms of opioid-induced postinfusion antianalgesia and secondary hyperalgesia.",2003.0,0,0
481,12826983,Tolerability and efficacy of clozapine combined with lithium in schizophrenia and schizoaffective disorder.,Joyce G Small; Marietta H Klapper; Frederick W Malloy; Timothy M Steadman,"The safety and tolerability of clozapine combined with lithium were investigated because of potential additive risks as well as frequent usage in clinical practice. Ten hospitalized schizophrenic and 10 schizoaffective patients receiving clozapine maintenance therapy with partial therapeutic response were studied in a randomized controlled trial. CGI and PANSS outcome ratings were employed and a cognitive battery was administered at baseline and after 4 weeks of lithium and placebo administration. Barnes and UKU side effect ratings and laboratory safety data were obtained. Combined lithium-clozapine treatment was well tolerated except for reversible neurotoxic reactions in two schizophrenic patients. Safety measures showed no significant variations, even during lithium toxicity. Total WBC and absolute granulocyte counts increased with lithium and declined with placebo. Schizoaffective patients improved with lithium on CGI and PANSS total and negative symptom scales and the cognitive measures, whereas schizophrenic patients did not. Lithium added to clozapine in treatment regimens for hospitalized, treatment-resistant, schizoaffective patients appears to afford potential benefit without harmful effects; for schizophrenic patients, however, it did not afford improvement but posed a risk of lithium toxicity.",2003.0,0,0
482,12828502,SLI-381 (Adderall XR).,Kate McKeage; Lesley J Scott,"SLI-381 is an extended-release formulation of short-acting Adderall, a racemic mixture of dextro- and levo-isomers of amphetamine salts. Drug-containing microbeads within the SLI-381 capsule give a double-pulsed delivery, similar to that achieved by two equal doses of the short-acting formulation administered 4 hours apart. In an intent-to-treat analysis of a 3-week, double-blind study in 563 children with attention-deficit hyperactivity disorder (ADHD), SLI-381 10, 20 or 30 mg once daily improved mean morning and afternoon behaviour scores compared with baseline significantly more than placebo (p < 0.001 for all comparisons), as assessed by the Connors Global Index Scale for teachers (CGIS-T). Following treatment, CGIS-T scores were similar to those reported in children without ADHD. In the same study, a dose-response relationship was observed, and increasing the dosage of SLI-381 by 10mg at weekly intervals, to a maximum of 30 mg once daily, resulted in further improvements in the scores of the CGIS-T. After early morning administration of SLI-381 in this double-blind study, late-afternoon scores of the CGIS for parents were similar to morning scores. SLI-381 was generally well tolerated in randomised trials in children with ADHD for up to 24 months. Overall, adverse events were mild to moderate in intensity.",2003.0,0,1
483,12831341,Atomoxetine: a selective noradrenaline reuptake inhibitor for the treatment of attention-deficit/hyperactivity disorder.,Christopher J Kratochvil; Brigette S Vaughan; Martin J Harrington; William J Burke,"Atomoxetine (Strattera, Eli Lilly & Co.) is a selective noradrenaline reuptake inhibitor that has been studied for use in the treatment of attention-deficit/hyperactivity disorder (ADHD). So far, two open-label and seven randomised, double-blind, placebo-controlled, clinical trials have been published, six in youths and three in adults. Each of these trials has shown a positive response as measured by the primary efficacy measures, the ADHD-IV Rating Scale (ADHD RS) or the Conners Adult ADHD Rating Scale (CAARS). Atomoxetine has generally been well tolerated. In November of 2002 the FDA approved atomoxetine for use in the US for the treatment of ADHD in children, adolescents and adults. Atomoxetine is the first nonstimulant approved by the FDA for the treatment of ADHD and the first medication approved for the treatment of adult ADHD.",2003.0,0,0
484,12832240,Olanzapine versus divalproex sodium for the treatment of acute mania and maintenance of remission: a 47-week study.,Mauricio Tohen; Terence A Ketter; Carlos A Zarate; Trisha Suppes; Mark Frye; Lori Altshuler; John Zajecka; Leslie M Schuh; Richard C Risser; Eileen Brown; Robert W Baker,"Few double-blind trials have compared longer-term efficacy and safety of medications for bipolar disorder. The authors report a 47-week comparison of olanzapine and divalproex. This 47-week, randomized, double-blind study compared flexibly dosed olanzapine (5-20 mg/day) to divalproex (500-2500 mg/day) for manic or mixed episodes of bipolar disorder (N=251). The only other psychoactive medication allowed was lorazepam for agitation. The primary efficacy instrument was the Young Mania Rating Scale; a priori protocol-defined threshold scores were > or =20 for inclusion, < or =12 for remission, and > or = 15 for relapse. Analytical techniques included mixed model repeated-measures analysis of variance for change from baseline, Fisher's exact test (two-tailed) for categorical comparisons, and Kaplan-Meier estimates of time to events of interest. Over 47 weeks, mean improvement in Young Mania Rating Scale score was significantly greater for the olanzapine group. Median time to symptomatic mania remission was significantly shorter for olanzapine, 14 days, than for divalproex, 62 days. There were no significant differences between treatments in the rates of symptomatic mania remission over the 47 weeks (56.8% and 45.5%, respectively) and subsequent relapse into mania or depression (42.3% and 56.5%). Treatment-emergent adverse events occurring significantly more frequently during olanzapine treatment were somnolence, dry mouth, increased appetite, weight gain, akathisia, and high alanine aminotransferase levels; those for divalproex were nausea and nervousness. In this 47-week study of acute bipolar mania, symptomatic remission occurred sooner and overall mania improvement was greater for olanzapine than for divalproex, but rates of bipolar relapse did not differ.",2003.0,0,0
485,12839431,Clozapine: a clinical review of adverse effects and management.,Mohammad Masud Iqbal; Atiq Rahman; Zahid Husain; Syed Zaber Mahmud; Wlliam G Ryan; Jacqueline M Feldman,"Clozapine (Clozaril) is a novel and unique prototype atypical, tricyclic, dibenzodiazepine-derivative, antipsychotic agent. It has been proven effective and significantly superior to placebo, as well as to conventional neuroleptics, in several placebo-controlled, double-blind studies in treatment-resistant schizophrenia. It has also been found to produce an incidence of extrapyramidal symptoms (EPS) as low as that found with placebo. Approximately 30-60% of all schizophrenic patients who fail to respond to typical antipsychotics may respond to clozapine. It was the first major advance that marked a turning point in the treatment of schizophrenia and other psychotic disorders since the introduction of the typical antipsychotic agents, i.e., chlorpromazine and haloperidol in the 1950s and 1960s, respectively. After its introduction in clinical studies in the United States in the early 1970s, it was withdrawn in 1974, and was not approved for clinical use in the United States until February 1990, because of the risk of agranulocytosis. Its novel pharmacological profile, lack of propensity to cause EPS in both short- and long-term uses, lack of effects on serum prolactin, and ameliorative effects on tardive dyskinesia have resulted in the expansion of its use from refractory schizophrenia to schizoaffective disorders, affective disorders, some neurological disorders, aggression, as well as psychosis in patients with dementia and parkinsonism. This review covers the history, pharmacology, management of side effects, and fetal and neonatal effects of clozapine.",2003.0,0,0
486,12850953,Neuropharmacology of TBI-induced plasticity.,Larry B Goldstein,"The purpose of this report is to review both fundamental studies in laboratory animals and preliminary clinical data suggesting that certain drugs may affect behavioural recovery after brain injury. Laboratory studies show that systemically-administered drugs that affect specific central neurotransmitters including norepinephrine and GABA influence affect recovery in a predictable manner. Although some drugs such as d-amphetamine have the potential to enhance recovery, others such as neuroleptics and other central dopamine receptor antagonists, benzodiazepines and the anti-convulsants phenytoin and phenobarbital may be detrimental. In one study, 72% of patients with traumatic brain injury received one or a combination of the drugs that may impair recovery based on both animal experiments and studies in recovering stroke patients. Until the true impact of these classes of drugs are better understood, care should be exercised in the use of medications that may interfere with the recovery process in patients with traumatic brain injury. Additional research needs to be completed before the clinical efficacy of drugs that may enhance recovery can be established.",2003.0,0,0
487,12859700,"A multicentre, randomized, double-blind, placebo-controlled, 1-year study of bupropion SR for smoking cessation.",P Tønnesen; S Tonstad; A Hjalmarson; F Lebargy; P I Van Spiegel; A Hider; R Sweet; J Townsend,"Bupropion sustained release (bupropion SR) has been shown to increase smoking cessation success rates in the US studies. To determine whether bupropion SR, in combination with counselling, is effective for smoking cessation in a multi-country study. This randomized, double-blind, placebo-controlled trial enrolled 707 smokers. A total of 527 received bupropion SR 300 mg daily for 7 weeks and 180 received placebo. A total of 11 clinic visits and 10 telephone contacts were scheduled, during the course of 1 year. Seven-week and 12-month abstinence rates were the study outcomes. Both continuous and weekly point prevalence smoking abstinence rates were significantly higher in the bupropion SR group compared with placebo. The continuous abstinence rate from weeks 4 to 7 was 46% in the bupropion SR group compared with 23% in the placebo group [odds ratio (OR) = 2.82; 95% confidence interval (CI) 1.89-4.28; P < 0.001). At month 12, the continuous abstinence rates were 21% for the bupropion SR group and 11% for the placebo group (OR = 2.19; 95% CI 1.29-3.86, P = 0.002). For most nicotine-withdrawal symptoms small changes were measured. Adverse events were higher for the bupropion SR group compared with placebo (insomnia 24% vs. 15%; dry mouth 13% vs. 5%). Bupropion SR in combination with counselling increased the abstinence rate compared with placebo, and was well tolerated.",2003.0,0,0
488,12860772,"Aripiprazole, an antipsychotic with a novel mechanism of action, and risperidone vs placebo in patients with schizophrenia and schizoaffective disorder.",Steven G Potkin; Anutosh R Saha; Mary J Kujawa; William H Carson; Mirza Ali; Elyse Stock; Joseph Stringfellow; Gary Ingenito; Stephen R Marder,"Aripiprazole is a dopamine D2 receptor partial agonist with partial agonist activity at serotonin 5HT1A receptors and antagonist activity at 5HT2A receptors. This multicenter trial examined the efficacy, safety, and tolerability of aripiprazole in patients with acute exacerbation of schizophrenia or schizoaffective disorder. In this 4-week double-blind study, 404 patients were randomized to 20 mg/d (n = 101) or 30 mg/d (n = 101) of aripiprazole, placebo (n = 103), or 6 mg/d of risperidone (n = 99). Efficacy assessments included Positive and Negative Syndrome Scale (PANSS) scores and Clinical Global Impression scores. Safety and tolerability evaluations included extrapyramidal symptoms and effects on weight, prolactin, and corrected QT (QTc) interval. Aripiprazole (20 and 30 mg/d) and risperidone (6 mg/d) were significantly better than placebo on all efficacy measures. Separation from placebo occurred at week 1 for PANSS total and positive scores with aripiprazole and risperidone and for PANSS negative scores with aripiprazole. There were no significant differences between aripiprazole and placebo in mean change from baseline in the extrapyramidal symptom rating scales. Mean prolactin levels decreased with aripiprazole but significantly increased 5-fold with risperidone. Mean change in QTc interval did not differ significantly from placebo with any active treatment group. Aripiprazole and risperidone groups showed a similar low incidence of clinically significant weight gain. Aripiprazole is effective, safe, and well tolerated for the positive and negative symptoms in schizophrenia and schizoaffective disorder. It is the first non-D2 receptor antagonist with clear antipsychotic effects and represents a novel treatment development for psychotic disorders.",2003.0,0,0
489,12862507,"Cardiovascular effects of atomoxetine in children, adolescents, and adults.",Joachim F Wernicke; Douglas Faries; Donald Girod; Jeffrey Brown; Haitao Gao; Douglas Kelsey; Humberto Quintana; Robert Lipetz; David Michelson; John Heiligenstein,"Atomoxetine is a highly specific presynaptic inhibitor of the noradrenaline (norepinephrine) transporter that was recently approved in the US for the treatment of patients with attention-deficit/hyperactivity disorder (ADHD). Adverse effects on the cardiovascular system, including abnormalities in heart rate, blood pressure, or cardiac rhythm have been associated with several noradrenergic medications. To further elucidate the magnitude and impact of blood pressure and pulse elevations in patients taking atomoxetine. Short-term cardiovascular safety in children, adolescents, and adults with ADHD was assessed in five randomised, double-blind trials (duration up to 10 weeks) with atomoxetine (n = 612) or placebo (n = 474). Long-term cardiovascular safety in children and adolescents (n = 169) was assessed in patients who entered an open-label extension or a blinded continuation following short-term treatment. Adverse events, blood pressure, sitting pulse, and electrocardiograms (ECGs) were collected throughout the trials. QT intervals were corrected for heart rate by a data-specific correction factor (QTcD; derived from baseline ECGs) as well as standard methods. Atomoxetine treatment was associated with small but statistically significant increases in mean systolic blood pressure in adults and diastolic blood pressure in children and adolescents. Mean pulse rate increased for all atomoxetine treatment groups. The increases in blood pressure and pulse tended to occur early in therapy, stabilised, and returned toward baseline upon drug discontinuation. There was no significant difference between atomoxetine and placebo treatment groups in change in QTcD interval for all study populations. Palpitations in the adult patient population were the only significant cardiovascular adverse event (p = 0.037) occurring more frequently in the atomoxetine treatment group (3.7%) than in the placebo group (0.8%). Discontinuations due to cardiovascular-related events were very uncommon in the adult group, and did not occur in the child/adolescent group. While atomoxetine has noradrenergic activity, increases in pulse and blood pressure were small and of little, if any, clinical significance. Atomoxetine was not associated with QT interval prolongation. Cardiovascular effects of atomoxetine were minimal, and atomoxetine was well tolerated in short- and long-term studies.",2003.0,1,1
490,12867218,A comparison of the efficacy and safety of olanzapine versus haloperidol during transition from intramuscular to oral therapy.,Padraig Wright; Karena Meehan; Martin Birkett; Stacy R Lindborg; Cindy C Taylor; Philip Morris; Alan Breier,"Acutely agitated patients with schizophrenia who receive intramuscular (IM) medications typically are switched to oral (PO) antipsychotic maintenance therapy. The goal of this study was to assess the efficacy and safety of olanzapine versus those of haloperidol during transition from IM to PO therapy. We used additional data from a previously reported trial to test the hypothesis that the reduction in agitation achieved by IM olanzapine 10 mg or IM haloperidol 7.5 mg would be maintained following transition to 4 days of PO olanzapine or PO haloperidol (5-20 mg/d for both). We also hypothesized that olanzapine would maintain its more favorable extrapyramidal symptom (EPS) safety profile. This was a multinational (hospitals in 13 countries), double-blind, randomized, controlled trial. Acutely agitated inpatients with schizophrenia were treated with 1 to 3 IM injections to olanzapine 10 mg or haloperidol 7.5 mg over 24 hours and were entered into a 4-day PO treatment period with the same medication (5-20 mg/d for both). The primary efficacy measurement was reduction in agitation, as measured by the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) score. Adverse events and scores on EPS rating scales were assessed. A total of 311 patients (204 men, 107 women; mean [SD] age, 38.2 [11.6] years) were enrolled (131, 126, and 54 patients in the olanzapine, haloperidol, and placebo groups, respectively). In all, 93.1% (122/131) of olanzapine-treated patients and 92.1% (116/126) of haloperidol-treated patients completed the IM period and entered the PO period; 85.5% (112/131) of olanzapine-treated patients and 84.1% (106/126) of haloperidol-treated patients completed the PO period. IM olanzapine and IM haloperidol effectively reduced agitation over 24 hours (mean [SD] PANSS-EC change, -7.1 [4.81 vs -6.7 [4.3], respectively). Reductions in agitation were sustained throughout the PO period with both study drugs (mean [SD] change from PO period baseline, -0.6 [4.8] vs -1.3 [4.4], respectively). During PO treatment, haloperidol-treated patients spontaneously reported significantly more acute dystonia than olanzapine-treated patients (4.3%[5/116] vs 0% [0/122], respectively; P = 0.026) and akathisia (5.2% [6/116] vs 0% [0/122], respectively; P = 0.013). Significantly more haloperidol-treated patients than olanzapine-treated patients met categorical criteria for treatment-emergent akathisia (18.5% [17/92] vs 6.5% [7/107], respectively; P = 0.015). In the acutely agitated patients with schizophrenia in this study, both IM olanzapine 10 mg and IM haloperidol 7.5 mg effectively reduced agitation over 24 hours. This alleviation of agitation was sustained following transition from IM therapy to 4 days of PO treatment (5-20 mg/d for both). During the 4 days of PO treatment, olanzapine-treated patients did not spontaneously report any incidences of acute dystonia, and olanzapine had a superior EPS safety profile to that of haloperidol. The combination of IM and PO olanzapine may help improve the treatment of acutely agitated patients with schizophrenia.",2003.0,0,0
491,12869813,Tics.,Tamara Pringsheim; William Jeptha Davenport; Anthony Lang,"This paper reviews the recent literature concerning Tourette syndrome and related disorders. Tourette syndrome is a common disorder in children and adolescents, with an established association with attention deficit hyperactivity disorder, obsessive compulsive disorder, and a number of other psychiatric disorders. Both autoimmune and genetic mechanisms are implicated in the pathophysiology of the syndrome, while neuroimaging studies have identified abnormalities in the composition of the basal ganglia and frontal lobe white matter, as well as alterations in dopaminergic activity. When necessary, treatment of tics can be successful with neuroleptics and alpha-2-adrenergic agonists. The use of stimulants in children with Tourette syndrome and comorbid attention deficit hyperactivity disorder does not appear to worsen tics. As a result of the recent literature, clinicians can feel comfortable treating children with co-morbid attention deficit hyperactivity disorder and Tourette syndrome with stimulant medications. It has also been established that transient tics are very common in children, and for the most part, non-disabling. In those children with persistent tics, behavioural disorders are associated which may impair success in school and psychosocial functioning. Clinicians have a number of therapeutic options, with recent double-blinded randomized trials of clonidine, risperidone, and desipramine showing benefit. Scientists continue to search for the cause of Tourette syndrome.",2003.0,0,0
492,12873248,Pilot randomized double blind placebo-controlled study of dexamphetamine for cocaine dependence.,James Shearer; Alex Wodak; Ingrid van Beek; Richard P Mattick; John Lewis,"To establish the feasibility of conducting a placebo-controlled clinical trial of dexamphetamine replacement therapy for cocaine dependence and to obtain preliminary data. Double-blind randomized placebo-controlled trial. Thirty cocaine-dependent injecting drug users. Subjects were assigned randomly to receive 60 mg/day dexamphetamine (n = 16) or placebo (n = 14) for 14 weeks. Immunoassay and mass spectrometric techniques were used to identify cocaine metabolites in urine. Subjects were screened using the Composite International Diagnostic Interview and DSM-IV. The Opiate Treatment Index, Brief Symptom Inventory, Severity of Dependence Scale and visual analogue craving scales were used to collect pre- and post-self-report data. Treatment retention was equivalent between groups; however, outcomes favoured the treatment group with no improvements observed in the placebo control group. The proportion of cocaine-positive urine samples detected in the treatment group declined from 94% to 56% compared to no change in the placebo group (79% positive). While the improvements were not significant between groups, within-group analysis revealed that the treatment group reduced self-reported cocaine use (P = 0.02), reduced criminal activity (P = 0.04), reduced cravings (P < 0.01) and reduced severity of cocaine dependence (P < 0.01) with no within-group improvements found in the placebo group. A definitive evaluation of the utility of dexamphetamine in the management of cocaine dependence is feasible and warranted.",2003.0,0,0
493,12879814,[Comparative bioavailability study of two formulations of risperidone available in the Chilean market].,Leonardo E Gaete; Jaime Solís; Pablo Venegas; Mitzy J Carrillo; Oscar Schatloff; Iván Saavedra,"Bioavailability of a particular drug can vary according to the formulation used. Therefore, studies of comparative bioavailability of different formulations of a same drug are worthwhile. To compare the bioavailability of two risperidone formulations available in the Chilean market. The bioavailability of a local risperidone formulation (Spiron) was compared with the original formulation of the drug (Risperdal) in 12 healthy volunteers, aged 19 +/- 1 years. A single dose of 3 mg was given orally, using a randomized double blind protocol in two periods. Fifteen blood samples were obtained at regular intervals, until 24 h after drug administration. Risperidone plasma levels were measured by high pressure liquid chromatography. pharmacokinetic parameters were calculated using a computer program that is independent of compartmental analysis. The area under the curve of plasma concentration versus time, from 0 to infinite (ABC0-infinity) and from 0 to 24 h (ABC0-24), early exposure (ABC from 0 to maximal time) and maximal plasma concentrations were significantly lower for Spiron. Half life time and time to achieve the maximal concentration were similar for the two formulations. According to bioequivalence tests suggested by the Food and Drug Administration (FDA) of the United States (90% confidence interval for the difference of long transformed mean pharmacokinetic parameters), the formulations Risperdal and Spiron, cannot be considered interchangeable.",2003.0,0,0
494,12887139,"A comparison of tyrosine against placebo, phentermine, caffeine, and D-amphetamine during sleep deprivation.",William F Waters; Richard A Magill; George A Bray; Julia Volaufova; Steven R Smith; Harris R Lieberman; Jennifer Rood; Mark Hurry; Tai Anderson; Donna H Ryan,"Sleep deprivation can impair alertness and cognitive and motor performance. We hypothesized that the amino acid tyrosine might reduce deleterious effects of sleep deprivation. Seventy-six healthy males, age 18-35 years, participated in a four-day protocol that included a habituation night, a baseline night, a 40.5 h period without sleep, and a recovery night. Tyrosine 150 mg/kg, caffeine 300 mg/70 kg, phentermine 37.5 mg, D-amphetamine 20 mg and placebo were administered in a double-blind, randomized fashion to compare their effects on the time it took to fall asleep, on endocrine responses during sleep deprivation, and on sleep quantity, quality and architecture as measured by polysomnography during recovery sleep. When given after 36 h without sleep, tyrosine had no significant effect on any parameter of sleep. D-amphetamine produced marked decrease in sleep drive but caused deleterious effects on many aspects of recovery sleep. Still, D-amphetamine was associated with increased alertness on the first recovery day. Phentermine and caffeine both decreased sleep drive during sleep deprivation, but phentermine impaired rapid-eye-movement (REM) recovery sleep. Tyrosine (when compared to placebo) had no effect on any sleep related measure, but it did stimulate prolactin release.",2003.0,0,0
495,12887140,"Effects of tyrosine, phentermine, caffeine D-amphetamine, and placebo on cognitive and motor performance deficits during sleep deprivation.",Richard A Magill; William F Waters; George A Bray; Julia Volaufova; Steven R Smith; Harris R Lieberman; Nancy McNevin; Donna H Ryan,"Cognitive and motor performance are critical in many circumstances and are impaired by sleep deprivation. We administered placebo, tyrosine 150 mg/kg, caffeine 300 mg/70 kg, phentermine 37.5 mg and D-amphetamine 20 mg at 15.30 h following overnight sleep deprivation and compare their effects on cognitive and motor performance in healthy young men. Tests of visual scanning, running memory, logical reasoning, mathematical processing, the Stroop task, four-choice serial reaction time, time wall take, pursuit tracking, visual vigilance, Trails (B) task and long-term memory were evaluated at standardized intervals before, during and after sleep deprivation and drugs. Performance decrements with sleep deprivation occurred in visual scanning, running memory, logical reasoning, mathematical processing, the Stroop test, the time wall test, tracking and visual vigilance. Interestingly, with sleep deprivation some tests improved and others did not deteriorate. Improvements with medication following sleep deprivation were seen in running memory, logical reasoning, mathematical processing, tracking and visual vigilance. Although less effective than D-amphetamine, tyrosine improved performance on several tests. We conclude that all drugs tested improved at least some aspects of cognitive and motor performance after sleep deprivation. As a naturally occurring amino acid, and thus amenable to nutritional strategies, tyrosine may deserve further testing.",2003.0,0,0
496,12888781,,,,,0,0
497,12895137,Comparative efficacy of two once daily methylphenidate formulations (Ritalin LA and Concerta) and placebo in children with attention deficit hyperactivity disorder across the school day.,Frank Lopez; Raul Silva; Linda Pestreich; Rafael Muniz,"The primary objective was to compare the differences in clinical efficacy of the starting dose of Ritalin LA (20mg) to the starting dose of Concerta (18mg), in a laboratory school setting for the duration of an entire school day. Secondary objectives were to compare Ritalin LA 20mg with Concerta 36mg, and Ritalin LA and both Concerta doses versus placebo across the school day. Thirty-six children (29 males, 7 females), aged 6-12 years, with attention deficit hyperactivity disorder, previously stabilized on methylphenidate (MPH), completed this four-way, randomized, single-blind crossover, analog classroom study. Patients were evaluated on day 0 and randomized to receive treatment on days 7, 14, 21, and 28 (Ritalin LA 20mg, Concerta 18mg, Concerta 36mg, or placebo). Swanson, Kotkin, Agler, M-Flynn and Pelham Rating Scale (SKAMP)-attention: The effect of Ritalin LA 20mg across the morning was statistically different from that of Concerta 18mg and 36mg, as demonstrated by the change in the area under the curve (AUC) during the first 4 hours (0-4) from pre-dose. AUC((0-4)) for RitalinLA was -2.48 versus -1.36 for Concerta 18mg (p = 0.015), and -1.55 for Concerta 36mg (p = 0.043). AUC((0-8)) change from pre-dose for Ritalin LA was -4.48 versus -2.72 for Concerta 18mg (p = 0.074), and -3.24 for Concerta 36mg (p = 0.208).SKAMP-deportment: AUC((0-4)) for Ritalin LA was -1.67 compared with -0.28 for Concerta 18mg (p < 0.001), and -0.55 for Concerta 36mg (p = 0.004). AUC((0-8)) change from pre-dose for Ritalin LA was -2.81 compared with -0.82 for Concerta 18mg (p = 0.018), and -1.34 for Concerta 36mg (p = 0.078).Combined: Mean AUC((0-4)) change from pre-dose for Ritalin LA was -2.05 compared with -0.78 for Concerta 18mg (p < 0.001), -1.01 for Concerta 36mg (p = 0.003). The mean AUC((0-8)) change from pre-dose for Ritalin LA was -3.58 compared with -1.70 for Concerta 18mg (p = 0.010), -2.22 for Concerta 36mg (p = 0.061). Math test-attempted: Mean pre-dose score for Ritalin LA was about 73 compared with 74, 90, and 81 for Concerta 18mg, 36mg, and placebo, respectively. Mean AUC((0-8)) change from pre-dose for Ritalin LA was 202 compared with 115 for Concerta 18mg (p = 0.135), 137 for Concerta 36mg (p = 0.265). Math test-correct: Mean pre-dose score for Ritalin LA was 68 compared with 64, 78, and 76 for Concerta 18mg, 36mg, and placebo, respectively. Mean AUC((0-8)) change from pre-dose for Ritalin LA was 183 compared with 100 for Concerta 18mg (p = 0.144), and 117 for Concerta 36mg (p = 0.245). One patient from each treatment group experienced a single mild adverse event that included abdominal pain, nausea, and dyspnea. While both Ritalin LA and Concerta were shown to be effective, the different release profiles of each formulation can result in distinct differences between the effects on measures of attention and deportment.",2003.0,1,1
498,12900300,"Comparative efficacy and safety of atypical and conventional antipsychotic drugs in first-episode psychosis: a randomized, double-blind trial of olanzapine versus haloperidol.",Jeffrey A Lieberman; Gary Tollefson; Mauricio Tohen; Alan I Green; Raquel E Gur; Rene Kahn; Joseph McEvoy; Diana Perkins; Tonmoy Sharma; Robert Zipursky; Hank Wei; Robert M Hamer; HGDH Study Group,"Few long-term studies have compared the efficacy and safety of typical and atypical antipsychotic medications directly in patients with a first episode of psychosis who met the criteria for schizophrenia or a related psychotic disorder. This study compared the acute and long-term effectiveness of haloperidol with that of olanzapine in patients with first-episode psychosis in a large, controlled clinical trial. Patients with first-episode psychosis (N=263) were randomly assigned under double-blind conditions to receive haloperidol or olanzapine and were followed for up to 104 weeks. Domains measured included psychopathology, psychosocial variables, neurocognitive functioning, and brain morphology and metabolism. This report presents data from clinical measures of treatment response and safety data from the 12-week acute treatment phase. Haloperidol and olanzapine were associated with substantial and comparable baseline-to-endpoint reductions in symptom severity, which did not differ significantly in last-observation-carried-forward analyses. However, in a mixed-model analysis, olanzapine-treated subjects had significantly greater decreases in symptom severity as measured by the Positive and Negative Syndrome Scale total score and negative and general scales and by the Montgomery-Asberg Depression Rating Scale but not as measured by the Positive and Negative Syndrome Scale positive scale and by the Clinical Global Impression severity rating. Olanzapine-treated patients experienced a lower rate of treatment-emergent parkinsonism and akathisia but had significantly more weight gain, compared with the haloperidol-treated patients. Overall, significantly more olanzapine-treated subjects than haloperidol-treated subjects completed the 12-week acute phase of the study (67% versus 54%). As expected on the basis of previous studies, both olanzapine and haloperidol were effective in the acute reduction of psychopathological symptoms in this group of patients with first-episode psychosis. However, olanzapine had several relative advantages in therapeutic response. Although the nature of adverse events differed between the two agents, retention in the study was greater with olanzapine. Retention in treatment is important in this patient population, given their risk of relapse. Longer-term results are needed to determine whether treatment with atypical antipsychotics results in superior outcomes for a first episode of schizophrenia.",2003.0,0,0
499,12911050,Bupropion sustained release for treatment of tobacco dependence.,J Taylor Hays; Jon O Ebbert,"Tobacco use is a global pandemic. The most common pharmacological treatments of tobacco use and dependence include nicotine replacement therapy and nonnicotine medications. Bupropion sustained release (SR) is the only first-line nonnicotine medication recommended by the US Public Health Service Clinical Practice Guideline. Randomized controlled clinical trials have shown that bupropion SR doubles abstinence rates compared with placebo. Long-term treatment with bupropion SR may reduce or delay smoking relapse. Bupropion SR has an excellent adverse effect profile, although a risk exists for serious adverse effects such as seizures. The risk of serious adverse effects associated with bupropion SR can be reduced by careful selection of patients. This article reviews the evidence of efficacy and common adverse effects of bupropion SR and delineates the clinical characteristics of patients at higher risk for adverse effects when bupropion SR is prescribed for treatment of tobacco use and dependence.",2003.0,0,0
500,12915290,Randomized trial of olanzapine versus placebo in the symptomatic acute treatment of the schizophrenic prodrome.,Scott W Woods; Alan Breier; Robert B Zipursky; Diana O Perkins; Jean Addington; Tandy J Miller; Keith A Hawkins; Eva Marquez; Stacy R Lindborg; Mauricio Tohen; Thomas H McGlashan,"The prodromal phase of schizophrenic disorders has been described prospectively. The present study aimed to determine the short-term efficacy and safety of olanzapine treatment of prodromal symptoms compared with placebo. This was a double-blind, randomized, parallel-groups, placebo-controlled trial with fixed-flexible dosing conducted at four sites. Sixty patients met prodromal diagnostic criteria, including attenuated psychotic symptoms, as determined by structured interviews. Olanzapine 5-15 mg daily or placebo was prescribed for 8 weeks. In the mixed-effects, repeated-measures analysis, the treatment x time interaction for the change from baseline on the Scale of Prodromal Symptoms total score was statistically significant, and post hoc analyses revealed that the olanzapine-placebo difference reached p<.10 by week 6 and p<.05 at week 8. Ratings of extrapyramidal symptoms remained low in each group and were not significantly different. Olanzapine patients gained 9.9 lb versus.7 lb for placebo patients (p<.001). This short-term analysis suggests olanzapine is associated with significantly greater symptomatic improvement but significantly greater weight gain than is placebo in prodromal patients. Extrapyramidal symptoms with olanzapine were minimal and similar to those with placebo. Future research over the longer term with more patients will be needed before recommendations can be made regarding routine treatment.",2003.0,0,0
501,12920408,Serum antimuscarinic activity during clozapine treatment.,Jose de Leon; Aruby Odom-White; Richard C Josiassen; Francisco J Diaz; Thomas B Cooper; George M Simpson,"This study attempts: (1) to verify that serum antimuscarinic activity is related to clozapine dose, and more importantly to clozapine plasma concentrations; (2) to explore whether norclozapine has serum antimuscarinic activity; (3) to explore whether antimuscarinic activity is related to clozapine side effects; and (4) to compare the serum antimuscarinic activities of clozapine with those of antiparkinsonian drugs and other antipsychotics. In 39 patients participating in a double-blind clozapine study, the [3H]QNB assay was used to measure serum antimuscarinic activity: (1) on baseline medications; (2) after a 4-week haloperidol trial; (3) after a 16-week clozapine trial of either 100, 300, or 600 mg/d; and (4) after 1 or 2 consecutive 16-week clozapine trials with remaining doses in nonresponders. Clozapine levels predicted serum antimuscarinic activity better than clozapine dose. At the end of the 1st clozapine trial, the correlation with the levels explained 69% of the variance of serum antimuscarinic activity (r = 0.83, P < 0.001, N = 34). Clozapine levels were good predictors of serum antimuscarinic activity only in patients taking 300 or 600 mg/d. After correcting for clozapine levels, the within-subject correlation between norclozapine levels and serum antimuscarinic activity was relatively high and significant (r = 0.54, F = 26.7, df = 1.65, P < 0.001). Constipation was significantly associated with higher serum antimuscarinic activity during the 1st clozapine trial. Clozapine was associated with clearly higher antimuscarinic activity than other antipsychotics or low doses of antiparkinsonians. In vitro studies and new clinical studies are needed to verify whether norclozapine may significantly contribute to antimuscarinic activity during clozapine treatment.",2003.0,0,0
502,12920409,Effectiveness of rapid initial dose escalation of up to forty milligrams per day of oral olanzapine in acute agitation.,Robert W Baker; Bruce J Kinon; Gerald A Maguire; Hong Liu; Angela L Hill,"Patients experiencing an acute decompensation of schizophrenia or bipolar disorder often present in an agitated state. Agitation presents a barrier to therapy, interrupting the typical physician-patient alliance and creating a disruptive, even hazardous, environment. Rapid assessment and effective treatment are necessary to manage agitation and, potentially, to shorten the time to recovery. One hundred forty-eight acutely agitated patients received either: rapid initial dose escalation (RIDE) in which up to 40 mg of oral olanzapine was allowed on days 1 and 2, up to 30 mg on days 3 and 4, and 5 to 20 mg thereafter; or usual clinical practice (UCP) in which patients received 10 mg/d olanzapine plus up to 4 mg lorazepam on days 1 and 2, up to 2 mg on days 3 and 4, and olanzapine 5 to 20 mg/d thereafter. The Positive and Negative Syndrome Scale-Excited Component (PANSS-EC: poor impulse control, tension, hostility, uncooperativeness, and excitement) measured at 24 hours was the primary measure. Secondary assessments of agitation and safety were also performed. Agitation improved significantly from baseline for both treatment groups; however, improvement with the RIDE strategy was superior to UCP. The RIDE group improvement was superior on the primary efficacy measure (PANSS-Excited) at 24 hours; it was superior on all agitation measures at the end of double-blind treatment. Both treatments were well tolerated, with no clinically significant differences in safety measures. Treatment was not limited by oversedation and attention improved from baseline in both groups. This study demonstrates the value of olanzapine in the treatment of acutely agitated patients. A new approach to olanzapine dosing that expands the initial dose range up to 40 mg/d may offer superior efficacy in rapidly and effectively controlling the symptoms of agitation.",2003.0,0,0
503,12921224,Actigraphic measurement of the effects of single-dose haloperidol and olanzapine on spontaneous motor activity in normal subjects.,Michael Kiang; Z Jeff Daskalakis; Bruce K Christensen; Gary Remington; Shitij Kapur,"To quantitatively examine the effects of haloperidol and olanzapine on spontaneous motor activity in normal subjects. Randomized, double-blind, placebo-controlled medication study. Normal volunteers (n = 30). Subjects received 1 dose of either haloperidol 2 mg (n = 9), olanzapine 10 mg (n = 10) or placebo (n = 10) and were admitted to hospital for the next 24 hours. Subjects wore an actigraphic monitor, which recorded movement in 15-second epochs. The Simpson-Angus Extrapyramidal Side Effect Scale (SAS) and the Barnes Akathisia Scale (BAS) were administered before and 7 and 24 hours after medication was given. Compared with placebo, total motor activity was decreased by 41% with olanzapine (p = 0.004) and by 12% with haloperidol (NS). There were significantly more epochs with zero movement with olanzapine than with haloperidol or placebo. For non-zero epochs, the mean activity count and the distribution of activity counts did not differ significantly among groups. There were no positive findings on the SAS or the BAS. Olanzapine decreased total motor activity by increasing the amount of time during which subjects were immobile, rather than by affecting the magnitude of movement during periods in which there was activity. This effect occurred at a dose of olanzapine low enough not to cause clinically observed extrapyramidal side effects. Our results suggest that actigraphy is useful as a sensitive, noninvasive tool for measuring the effect of antipsychotics on spontaneous motor activity.",2003.0,0,0
504,12921516,Olanzapine for psychotic and behavioral disturbances in Alzheimer disease.,Robin A Schatz,"To evaluate the efficacy and safety of olanzapine for the treatment of psychotic and behavioral disturbances in Alzheimer disease. MEDLINE (1966-January 2003) and Science Citation Index searches were performed. Key search terms included olanzapine, Alzheimer(s), and dementia. Four trials of olanzapine and subsequent post hoc analyses were reviewed. Three trials found a benefit associated with olanzapine use, but a fourth trial did not. Olanzapine appears to be effective in treating psychotic and behavioral disturbances associated with Alzheimer disease. However, the most appropriate dose remains to be determined. The benefit of olanzapine therapy must be weighed against the adverse effect profiles of olanzapine and alternative treatment options.",2003.0,0,0
505,12921918,Selegiline in the treatment of attention deficit hyperactivity disorder in children: a double blind and randomized trial.,Shahin Akhondzadeh; Reza Tavakolian; Rozita Davari-Ashtiani; Fariba Arabgol; Homayoun Amini,"Attention deficit hyperactivity disorder (ADHD) is a common disorder of childhood that affects 3% to 6% of school-age children. Conventional stimulant medications are recognized by both specialists and parents as useful symptomatic treatment. Nevertheless, approximately 30% of ADHD children treated with them do not respond adequately or cannot tolerate the associated adverse effects. Such difficulties highlight the need for alternative safe and effective medications in the treatment of this disorder. Selegiline is a type B monoamine oxidase inhibitor (MAOI) that is metabolized to amphetamine and methamphetamine stimulant compounds that may be useful in the treatment of ADHD. The authors undertook this study to further evaluate, under double-blind and controlled conditions, the efficacy of selegiline for ADHD in children. A total of 28 children with ADHD as defined by DSM IV were randomized to selegiline or methylphenidate dosed on an age and weight-adjusted basis at selegiline 5 mg/day (under 5 years) and 10 mg/day (over 5 years) (Group 1) and methylphenidate 1 mg/kg/day (Group 2) for a 4-week double-blind clinical trial. The principal measure of the outcome was the Teacher and Parent ADHD Rating Scale. Patients were assessed by a child psychiatrist at baseline, 14 and 28 days after the medication started. No significant differences were observed between the two protocols on the Parent and Teacher Rating Scale scores. Although the number of dropouts in the methylphenidate group was higher than in the selegiline group, there was no significant difference between the two protocols in terms of the dropouts. Decreased appetite, difficulty falling asleep and headaches were observed more in the methylphenidate group. The results of this study must be considered preliminary, but they do suggest that selegiline may be beneficial in the treatment of ADHD. In addition, a tolerable side effect profile may be considered as one of the advantages of selegiline in the treatment of ADHD.",2003.0,0,0
506,12927004,"An integrated analysis of acute treatment-emergent extrapyramidal syndrome in patients with schizophrenia during olanzapine clinical trials: comparisons with placebo, haloperidol, risperidone, or clozapine.",Christopher D Carlson; Patrizia A Cavazzoni; Paul H Berg; Hank Wei; Charles M Beasley; John M Kane,"The frequency and severity of extrapyramidal syndrome (EPS) were evaluated in patients with DSM-III or DSM-IV schizophrenia in the acute phase (- 8 weeks) of randomized, double-blind, controlled trials from the integrated olanzapine clinical trial database. This retrospective analysis included 23 clinical trials and 4611 patients from November 11, 1991, through July 31, 2001. Incidences of dystonic, parkinsonian, and akathisia events were compared using treatment-emergent adverse-event data. Categorical analyses of Simpson-Angus Scale and Barnes Akathisia Scale (BAS) scores, use of anticholinergic medications, and baseline-to-endpoint changes in Simpson-Angus Scale and BAS scores were compared. A significantly smaller percentage of olanzapine-treated patients experienced dystonic events than did haloperidol- (p <.001) or risperidone-treated patients (p =.047). A significantly greater percentage of haloperidol-treated patients experienced parkinsonian (p <.001) and akathisia (p <.001) events than did olanzapine-treated patients. Categorical analysis of Simpson-Angus Scale scores showed significantly more haloperidol- (p <.001) or risperidone-treated patients (p =.004) developed parkinsonism than did olanzapine-treated patients. Olanzapine-treated patients experienced significantly greater reductions in Simpson-Angus Scale scores than did haloperidol- (p <.001), risperidone- (p <.001), or clozapine-treated (p =.032) patients. Categorical analysis of BAS scores showed significantly more haloperidol-treated patients experienced treatment-emergent akathisia versus olanzapine-treated patients (p <.001). Significantly greater reductions in BAS scores were experienced during olanzapine treatment versus placebo (p =.007), haloperidol (p <.001), and risperidone (p =.004) treatments. A significantly smaller percentage of olanzapine-treated patients received anticholinergic medications compared with that of haloperidol- (p <.001) or risperidone-treated patients (p =.018). Compared with that in olanzapine-treated patients, the duration of anticholinergic cotreatment was significantly longer among haloperidol- (p <.001) or risperidone-treated patients (p =.040) and significantly shorter among clozapine-treated patients (p =.021). This analysis of available data from olanzapine clinical trials lends additional support to olanzapine's favorable EPS profile.",2003.0,0,0
507,12933373,Pharmacologic myocardial protection in patients undergoing noncardiac surgery: a quantitative systematic review.,Robert D Stevens; Haran Burri; Martin R Tramèr,"A number of drugs have been tested in clinical trials to decrease cardiac complications in patients undergoing noncardiac surgery. To compare the results of these studies, we conducted a quantitative systematic review. Medline, Embase, and Cochrane databases were searched for randomized trials that assessed myocardial ischemia, myocardial infarction, 30-day cardiac mortality, and adverse effects. Data were combined using a fixed-effect model and expressed as Peto odds ratios (OR) with 95% confidence interval (CI) and as numbers-needed-to-treat/harm (NNT/H). Twenty-one trials involving 3646 patients were included: 11 trials using beta-blockers (6 drugs; 866 patients), 6 clonidine or mivazerol (614 patients), 3 diltiazem or verapamil (121 patients), and 1 nitroglycerin (45 patients). All trials had an inactive control; there were no direct comparisons. beta-blockers decreased ischemic episodes during surgery (7.6% versus 20.2% with placebo; OR 0.32 [95% CI, 0.17-0.58]; NNT 8) and after surgery (15.2% versus 27.9% with control; OR 0.46 [95% CI, 0.26-0.81]; NNT 8). alpha(2)-agonists decreased ischemia during surgery only (19.4% versus 32.8%; OR 0.47 [95% CI, 0.33-0.68]; NNT 7). beta-blockers reduced the risk of myocardial infarction (0.9% versus 5.2%; OR 0.19 [95% CI, 0.08-0.48]; NNT 23) but only when 2 trials with high-risk patients were included. The effect of alpha(2)-agonists on myocardial infarction was not significant (6.1% versus 7.3%; OR 0.85 [95% CI, 0.62-1.14]). beta-blockers significantly decreased the risk of cardiac death from 3.9% to 0.8% (OR 0.25 [95% CI, 0.09-0.73], NNT 32). alpha(2)-agonists significantly decreased the risk of cardiac death from 2.3% to 1.1% (OR 0.50 [95% CI, 0.28-0.91], NNT 83). For calcium channel blockers and nitroglycerin, evidence of any benefit was lacking. The most common adverse effect was bradycardia, which occurred in 24.5% of patients receiving a beta adrenergic blocker versus 9.1% of controls (OR 3.76 [95% CI, 2.45-5.77], NNH 6).",2003.0,0,0
508,12934987,"The safety and early efficacy of oral-loaded divalproex versus standard-titration divalproex, lithium, olanzapine, and placebo in the treatment of acute mania associated with bipolar disorder.",Robert M A Hirschfeld; Jeffrey D Baker; Patricia Wozniak; Katherine Tracy; Kenneth W Sommerville,"Previous studies have examined the safety and tolerability of oral-loaded divalproex sodium in the treatment of acute mania, but not the early efficacy of this dosing strategy. The purpose of this study was to evaluate the early efficacy of oral-loaded divalproex. In this pooled analysis, 348 subjects from 3 randomized, double-blind, parallel-group, active- or placebo-controlled studies were used to compare the efficacy, safety, and tolerability of oral-loaded divalproex with standard-titration divalproex, lithium, olanzapine, or placebo. Subjects were inpatients diagnosed with acute mania associated with bipolar I disorder (DSM-III-R or -IV and SADS-Change Version). Patients were administered oral-loaded divalproex (20 or 30 mg/kg/day on days 1 and 2 followed by 20 mg/kg/day, and increased at physician's discretion), standard-titration divalproex initiated at 250 mg t.i.d. and titrated to 40-150 microg/mL, lithium (300 mg t.i.d. initial dose) titrated to 0.4 to 1.5 mEq/L, olanzapine (10 mg q.d. initial dose) up to 20 mg/day, or placebo. The results demonstrate an early efficacy advantage for oral-loaded divalproex compared to standard-titration divalproex at days 5, 7/8, and 10. Efficacy was improved over lithium on day 7/8. There were no efficacy differences between divalproex loading and olanzapine. Divalproex loading showed greater efficacy than placebo at all time points. Divalproex loading was as well tolerated or better tolerated than the other active treatments as measured by adverse events and changes in laboratory parameters. These results suggest the oral loading of divalproex leads to a more rapid antimanic effect when compared with standard-titration divalproex, lithium, or placebo and is better tolerated than olanzapine and as well tolerated as lithium or standard-titration divalproex.",2003.0,0,0
509,12944341,"A placebo-controlled, double-blind study of the efficacy and safety of aripiprazole in patients with acute bipolar mania.",Paul E Keck; Ronald Marcus; Stavros Tourkodimitris; Mirza Ali; Amy Liebeskind; Anutosh Saha; Gary Ingenito; Aripiprazole Study Group,"The authors compared the efficacy and safety of aripiprazole, a novel antipsychotic, to placebo for treatment of patients in an acute manic or mixed episode of bipolar disorder. This 3-week, multicenter, double-blind study randomly assigned 262 bipolar disorder patients in an acute manic or mixed episode to aripiprazole, 30 mg/day (reduced to 15 mg/day if needed for tolerability), or placebo. Patients remained hospitalized for at least 2 of the weeks. The primary efficacy measure was mean change from baseline in total score on the Young Mania Rating Scale; response was defined as a decrease in score of > or =50%. Aripiprazole produced statistically significant mean improvements in total score on the Young Mania Rating Scale compared with placebo (-8.2 versus -3.4, respectively) and produced a significantly higher response rate (40% versus 19%). For key efficacy variables (response per Young Mania Rating Scale; Clinical Global Impression-Bipolar Version scores for severity of illness [mania] and change from preceding phase [mania]), aripiprazole separated from placebo by day 4. The completion rate was significantly higher with aripiprazole than with placebo (42% versus 21%). Discontinuations due to adverse events did not differ significantly between the aripiprazole and placebo groups. There were no significant changes in body weight versus placebo, and aripiprazole was not associated with elevated serum prolactin or QTc prolongation. Aripiprazole had significantly greater efficacy than placebo for the treatment of bipolar disorder patients in acute manic or mixed episodes and was safe and well tolerated in this randomized controlled trial.",2003.0,0,0
510,14529800,"Effects of methylphenidate, desipramine, and L-dopa on attention and inhibition in children with Attention Deficit Hyperactivity Disorder.",C C E Overtoom; M N Verbaten; C Kemner; J L Kenemans; H van Engeland; J K Buitelaar; M W van der Molen; J van der Gugten; H Westenberg; R A A Maes; H S Koelega,"The objective of this study was to investigate the effects of methylphenidate (MPH) on attention and inhibition in children with Attention Deficit Hyperactivity Disorder (ADHD) and to establish what the relative contributions of the noradrenergic and dopaminergic systems to this effect were. In addition to MPH, two other drugs were administered in order to affect both transmitter systems more selectively, L-dopa (dopamine (DA) agonist) and desipramine (DMI) (noradrenaline (NA) re-uptake inhibitor). Sixteen children with ADHD performed a stop-task, a laboratory task that measures the ability to inhibit an ongoing action, in a double-blind randomized within-subjects design. Each child received an acute clinical dose of MPH, DMI, L-dopa, and placebo; measures of performance and plasma were determined. The results indicated that inhibition performance was improved under DMI but not under MPH or L-dopa. The response-time to the stop-signal was marginally shortened after intake of DMI. MPH decreased omission and choice-errors and caused faster reaction times to the trials without the stop-tone. No effects of L-dopa whatsoever were noted. Prolactin levels were increased and 5-HIAA levels were lowered under DMI relative to placebo. It is suggested that the effects of MPH on attention are due to a combination of noradrenergic and dopaminergic mechanisms. The improved inhibition under DMI could be serotonergically mediated.",2003.0,0,1
511,14562491,The effects of an educational intervention on antipsychotic-induced weight gain.,Kimberly H Littrell; Nicole M Hilligoss; Carol D Kirshner; Richard G Petty; Craig G Johnson,"To assess the effect of an educational intervention on antipsychotic-induced weight gain among patients with schizophrenia. Quasi-experimental. Seventy patients with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder entered this 6-month study condicted in the United States. All participants began receiving olanzapine treatment when they entered the study. The patients were then randomly assigned to an intervention group or a standard care group. Over the next 4-months, the intervention group participated in weekly psychoeducation classes focused on nutrition, exercise, and living a healthy lifestyle. Patients were followed for an additional 2 months to assess weight change. A statistically significant difference in weight change between the two groups was observed post-treatment and at endpoint. At endpoint, the mean weight change of the intervention group was -.06 pounds, while the mean weight change in the standard care group was 9.57 pounds. In both groups, men gained significantly more weight than did women. The results indicate that a structured educational intervention might have a positive effect on antipsychotic-induced weight gain among patients with schizophrenia.",2003.0,0,0
512,14567163,[Clozapine and pregnancy].,H N Nguyen; P Lalonde,"This article reviews the relations between clozapine and pregnancy. Six case reports are identified in the literature of pregnant patients who received clozapine. Novartis at Basle, Switzerland, through its pharmacovigilance and epidemiology, service, has data on nearly 200 cases summarized in this article. We also describe the case of a patient with paranoid schizophrenia who was hospitalized 10 times between the age of 22 to 32. She received clozapine when she was 29 years old and, with a daily dosage of 350 mg, she became asymptomatic. At the age of 33 and 37, she became pregnant and continued clozapine during her 2 pregnancies. During her first pregnancy, she received insulin due to gestational diabetes associated with a body weight mass (BWM) of 30.4 (N = 20 to 25). During her second pregnancy, the BWM was 23.7 and she did not develop diabetes. She delivered at term 2 daughters who are at the time of this report 5 and 3 years old. The two girls are doing well and have no developmental delay. Psychotic symptoms exacerbation: the plasma concentration of clozapine diminishes during pregnancy due to a higher hepatic metabolism and distribution volume. Monitoring plasma concentration of clozapine can help to adjust its dosage. In case of psychotic symptoms exacerbation, the following can be recommended: 1) Increase the clozapine dosage; 2) Add a classic antipsychotic like perphenazine, trifluoperazine or haloperidol. Diabetes: obesity, glucose intolerance or a family history of diabetes are risk factors to develop gestational diabetes. The follow-up of patients, who take an atypical antipsychotic, should include constant monitoring of the blood glucose or Hb1A and lipid dosages. Complications at labor: Clozapine increases the secretion of oxytocine and the contraction of the uterine muscle. But, no studies can explain how clozapine affects the labor exactly. Some case studies report use of forceps, vacuum or cesarean. Stoner (1997) described neonatal convulsions 8 days after birth. The mother was receiving 350 mg of clozapine, but also lorazepam and haloperidol during her pregnancy. The newborn withdrawal of lorazepam can increase the risk of convulsions and also haloperidol can diminish the convulsion threshold. Floppy infant syndrome: in the case described by Dimichele (1996), the mother received a daily dosage of 300 mg of clozapine and 2.5 mg of lorazepam 3 to 5 times a day. This can explain hypotonia. Stoner (1997) reports a second case where a mother, who received 600 mg of clozapine during pregnancy, gave birth to a child who had no convulsions neither hypotonia. The cases described concerning studies of children until age 2 to 3 years by Stoner (1997) and Dickson (1998) and until 6 years old by Barnas (1994), do not mention any developmental problem, similar to the two daughters of our patient. The pharmacovigilance service of Novarits reports 6% of malformations. But these reports must be considered with caution since they represent only the pregnancies reported spontaneously to the pharmaceutical company. This is only a portion of all pregnancies associated with clozapine. No specific risks for the mother and children can be attributed to the use of clozapine during pregnancy. However, the plasma concentration of clozapine is higher in the fetus compared to the mother (Barnas, 1994); therefore, a minimal dosage should be used. Since clozapine is present in the maternal milk, breast feeding should be avoided. The advantages to use clozapine during pregnancy must exceed the risks. It is justified to continue the use of this medication even if data on classic antipsychotics (e.g.: haloperidol) are more extensive. Because the risk of psychotic exacerbation is higher, the substitution of clozapine is not recommended. The psychosocial support and the obstetrical follow-up must be intensive too. An institutional pharmacovigilance service should complement the one provided by the industry. Also, further case-control and cohort studies are essential to better estimate the long-term risks.",2003.0,0,0
513,14581254,Effectiveness of bupropion sustained release for smoking cessation in a health care setting: a randomized trial.,Gary E Swan; Tim McAfee; Susan J Curry; Lisa M Jack; Harold Javitz; Sara Dacey; Katherine Bergman,"The efficacy of bupropion hydrochloride sustained release (SR) (Zyban) for smoking cessation has been evaluated in clinical trials that included frequent in-person behavioral counseling, but not in actual practice settings. To determine the differential effectiveness of 2 doses of bupropion SR in combination with behavioral interventions of minimal to moderate intensity in an actual practice setting. Open-label randomized trial, with 1 year of follow-up. A large health system (Group Health Cooperative) based in Seattle. Adult smokers (N = 1524) interested in quitting smoking. Participants were randomly assigned to receive 1 of 4 combinations of bupropion SR (150 or 300 mg) and behavioral counseling (minimal or moderate intensity). The primary outcome measure was self-reported point-prevalence 7-day nonsmoking status at 3 and 12 months following the target quit date. Secondary outcomes included adverse and abstinence effects reported since beginning treatment with bupropion SR. At 3 months, a significantly higher rate of nonsmoking was observed among those receiving the larger bupropion SR dose (P=.005). At 12 months, moderate intensity counseling was associated significantly with a higher rate of nonsmoking (P=.001). At 3 months, the higher dose was associated with a significantly increased frequency of self-reported symptoms such as difficulty sleeping (P=.02), difficulty concentrating (P=.02), shakiness/tremor (P=.002), and gastrointestinal problems (P=.005)and a decreased frequency of reported desire to smoke (P=.001). In this actual practice setting, the combination of bupropion SR and minimal or moderate counseling was associated with 1-year quit rates of 23.6% to 33.2%. This suggests that existing health care systems can substantially decrease tobacco use rates among their enrollees if they provide these modest interventions.",2003.0,0,0
514,14592280,Effects of modafinil on sustained attention performance and quality of life in OSA patients with residual sleepiness while being treated with nCPAP.,David F Dinges; Terri E Weaver,"Some patients with obstructive sleep apnea/hypopnea syndrome (OSA/HS) who are regular users of nasal continuous positive airway pressure (nCPAP) therapy continue to experience daytime sleepiness that impairs performance and quality of life. A randomized, double-blind, placebo-controlled, parallel-group study was conducted to determine the effect of modafinil on sustained attention performance and functional quality of life in OSA/HS patients with residual daytime sleepiness, who were regular users of nCPAP therapy. Seventy-seven patients received modafinil (200 mg/day, week 1; 400 mg/day, weeks 2-4) and 80 patients received matching placebo once daily for 4 weeks. Sustained attention performance on the psychomotor vigilance task (PVT) and functional status and quality of life using the Functional Outcomes of Sleep Questionnaire (FOSQ) were measured. The frequency of lapses of attention during PVT performance was significantly decreased, and both the median and slowest reaction times were significantly improved in patients receiving nCPAP plus modafinil compared with those receiving nCPAP plus placebo (P=0.010 for the number of lapses [transformed], P=0.023 for the median reaction time, and P=0.014 for the reciprocal of the 10% slowest reaction times). Treatment with nCPAP plus modafinil significantly improved the FOSQ total score (weeks 1 and 4), the vigilance subscale score (weeks 1 and 4), and the activity level subscale score (week 4) compared with treatment with nCPAP plus placebo (all P<0.05). Consistent with previous results for objective and subjective measures of sleepiness, modafinil used adjunctively improved performance on a test of behavioral alertness and reduced functional impairments in patients with OSA/HS who were regular users of nCPAP therapy but still experiencing sleepiness.",2003.0,0,0
515,14645311,Effectiveness and cost of olanzapine and haloperidol in the treatment of schizophrenia: a randomized controlled trial.,Robert Rosenheck; Deborah Perlick; Stephen Bingham; Wen Liu-Mares; Joseph Collins; Stuart Warren; Douglas Leslie; Edward Allan; E Cabrina Campbell; Stanley Caroff; June Corwin; Lori Davis; Richard Douyon; Lawrence Dunn; Denise Evans; Ede Frecska; John Grabowski; David Graeber; Lawrence Herz; Kong Kwon; William Lawson; Felicitas Mena; Javaid Sheikh; David Smelson; Valerie Smith-Gamble; Department of Veterans Affairs Cooperative Study Group on the Cost-Effectiveness of Olanzapine,"Although olanzapine has been widely adopted as a treatment of choice for schizophrenia, its long-term effectiveness and costs have not been evaluated in a controlled trial in comparison with a standard antipsychotic drug. To evaluate the effectiveness and cost impact of olanzapine compared with haloperidol in the treatment of schizophrenia. Double-blind, randomized controlled trial with randomization conducted between June 1998 and June 2000 at 17 US Department of Veterans Affairs medical centers. Three hundred nine patients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of schizophrenia or schizoaffective disorder, serious symptoms, and serious dysfunction for the previous 2 years. Fifty-nine percent fully completed and 36% partially completed follow-up assessments. Patients were randomly assigned to receive flexibly dosed olanzapine, 5 to 20 mg/d, with prophylactic benztropine, 1 to 4 mg/d (n = 159); or haloperidol, 5 to 20 mg/d (n = 150), for 12 months. Standardized measures of symptoms, quality of life, neurocognitive status, and adverse effects of medication. Veterans Affairs administrative data and interviews concerning non-VA service use were used to estimate costs from the perspective of the VA health care system and society as a whole (ie, consumption of all resources on behalf of these patients). There were no significant differences between groups in study retention; positive, negative, or total symptoms of schizophrenia; quality of life; or extrapyramidal symptoms. Olanzapine was associated with reduced akathisia in the intention-to-treat analysis (P<.001) and with lower symptoms of tardive dyskinesia in a secondary analysis including only observations during blinded treatment with study drug. Small but significant advantages were also observed on measures of memory and motor function. Olanzapine was also associated with more frequent reports of weight gain and significantly greater VA costs, ranging from 3000 dollars to 9000 dollars annually. Differences in societal costs were somewhat smaller and were not significant. Olanzapine does not demonstrate advantages compared with haloperidol (in combination with prophylactic benztropine) in compliance, symptoms, extrapyramidal symptoms, or overall quality of life, and its benefits in reducing akathisia and improving cognition must be balanced with the problems of weight gain and higher cost.",2003.0,0,0
516,7478682,Epidural clonidine analgesia for intractable cancer pain. The Epidural Clonidine Study Group.,J C Eisenach; S DuPen; M Dubois; R Miguel; D Allin,"Although the vast majority of patients with cancer pain receive effective analgesia from standard therapy, a few patients, particularly those with neuropathic pain, continue to experience severe pain despite large doses of systemic or intraspinal opioids. Animal studies suggest intraspinal alpha 2-adrenergic agonists may be effective in such cases. Eighty-five patients with severe cancer pain despite large doses of opioids or with therapy-limiting side effects from opioids were randomized to receive, in a double-blind manner, 30 micrograms/h epidural clonidine or placebo for 14 days, together with rescue epidural morphine. Pain was assessed by visual analog score (VAS), McGill Pain Questionnaire, and daily epidural morphine use. Success was defined as a decrease in either morphine use of VAS pain, with the alternative variable either decreasing or remaining constant. Blood pressure, heart rate, and degree of nausea and sedation were monitored. Successful analgesia was more common with epidural clonidine (45%) than with placebo (21%). This was particularly prominent in those with neuropathic pain (56% vs. 5%). Pain scores were lower at the end of the treatment period in patients with neuropathic pain treated with clonidine rather than placebo, whereas morphine use was unaffected. Clonidine, but not placebo, decreased blood pressure and heart rate. Hypotension was considered a serious complication in 2 patients receiving clonidine and in 1 patient receiving placebo. This study confirms the findings from previous animal studies which showed the effective, potent analgesic properties of intraspinal alpha 2-adrenergic agonists and suggests that epidural clonidine may provide effective relief for intractable cancer pain, particular of the neuropathic type.",1995.0,0,0
517,7486097,Epidural clonidine or sufentanil for intraoperative and postoperative analgesia.,M De Kock; F Famenne; G Deckers; J L Scholtes,"This study contrasts the efficacy and side effects of epidural clonidine and sufentanil in the perioperative period. Using a randomized, prospective, double-blind study design, 40 patients undergoing abdominal surgery under propofol/nitrous oxide anesthesia were enrolled. Before anesthesia, an epidural catheter was inserted at the L1-L2 interspace. At induction of anesthesia, the patients received epidurally either clonidine (4 micrograms/kg in 10 mL) infused in 20 min followed by a 2-micrograms.kg-1.h-1 infusion (5 mL/h) during 12 h (Group 1) or sufentanil (0.5 microgram/kg in 10 mL) in 20 min followed by a 0.25-microgram.kg-1.h-1 infusion (5 mL/h) during 12 h (Group 2). Intraoperatively, increases in arterial blood pressure and heart rate not responding to propofol bolus (0.5 mg/kg) were treated with a bolus of intravenous (IV) sufentanil 0.035 microgram/kg. Postoperatively, IV sufentanil boluses (5 micrograms) were given through a patient-controlled analgesia (PCA) device. Postoperative analgesia was assessed by recording the IV PCA sufentanil requirements and the patients' visual analog scale (VAS) at 3, 6, 12, 18, 24, 36, and 48 h. Sedation analog scales and side effects were also recorded. Plasma clonidine and sufentanil concentrations were measured after 20 min and 6, 12, and 24 h. The number of reinjections of propofol (n = 1.6 +/- 1.6 in Group 1 vs 6.5 +/- 4.0 in Group 2) and of IV sufentanil (n = 0.6 +/- 0.8 in Group 1 vs 3.8 +/- 3.7 in Group 2) was significantly reduced (P < 0.001) in the epidural clonidine group. In the early postoperative period, pain scores and rescue analgesic requirements were very low in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
518,7491385,A comparison of European and American dosing regimens of schizophrenic patients on clozapine: efficacy and side effects.,S Pollack; J A Lieberman; W W Fleischhacker; M Borenstein; A Z Safferman; M Hummer; M Kurz,"We present a comparison of the results from two studies of patients on clozapine. The American study (n = 84; Hillside Hospital, Glen Oaks, NY) and the European study (n = 63; Innsbruck University Clinics, Innsbruck, Austria) both examine efficacy and side effects in schizophrenic patients on this atypical neuroleptic. There is a very substantial difference in the dosing regimen used on both continents and this is reflected in the studies reported. A question with major clinical implications is whether the higher doses commonly used in the United States lead to a better outcome or a different profile of side effects. Outcome as a function of serum concentration will be examined. Results confirm a lower dose, lower clozapine blood level, and a lesser degree of side effects in the Austrian cohort when compared to the American sample. Surprisingly, the clinical efficacy of the lower dosing regimen was superior to the higher dose. Reasons for this anomaly are explored.",1995.0,0,0
519,7491391,Methylphenidate effects on a laboratory aggression measure in children with ADHD.,C D Casat; D A Pearson; M J Van Davelaar; D R Cherek,"This study investigated the utility of the Point Subtraction Aggression Paradigm (PSAP), a computerized laboratory analog aggression measure. We measured the effects of methylphenidate (MPH) on aggressive responding in children with a DSM-III-R diagnosis of attention deficit hyperactivity disorder (ADHD), who had high ratings on the Child Behavior Checklist Aggression Factor (CBCL; Achenbach 1991). Results are reported for 6 subjects, ages 8-11 years. All were tested at baseline in an unmedicated condition, and after double-blind administration of placebo, 0.3 mg/kg of MPH, and 0.6 mg/kg of MPH. A main effect of decreased aggressive responding with MPH was found, with a dose-related change by repeated measures ANOVA (F = 6.59, df = 2.10, p = .014). Post-hoc analysis with the Tukey HSD indicated that only the 0.6 mg/kg was significantly (p < .05) different than placebo. Implications for use of the PSAP in future investigations of medications in aggressive children are discussed.",1995.0,0,1
520,7509495,"Risperidone versus clozapine in the treatment of schizophrenic patients with acute symptoms: a double blind, randomized trial.",K Heinrich; E Klieser; E Lehmann; E Kinzler; H Hruschka,"1. In order to verify the hypothesis that risperidone is a useful therapeutic alternative to clozapine the authors carried out a randomized double blind trial in 59 patients with paranoid hallucinatory psychoses. 2. In a treatment lasting 28 days three groups of patients received either 4 mg risperidone (N = 20), 8 mg risperidone (N = 19), or 400 mg clozapine (N = 20) daily. 3. The tolerance of 4 mg risperidone was globally assessed as being better than that of 400 mg clozapine. Drop-outs under clozapine were mostly caused by side effects, whereas under risperidone they tended to occur for therapeutic inefficacy. 4. The antipsychotic effect was highly significant and clinically relevant under both risperidone and clozapine.",1994.0,0,0
521,7514366,Risperidone in the treatment of schizophrenia.,S R Marder; R C Meibach,"The purpose of this study was to investigate the safety and efficacy of risperidone in the treatment of schizophrenic patients and determine its optimal dose. This double-blind study included 388 schizophrenic patients drawn from 20 sites in the United States. Patients were randomly assigned to 8 weeks' treatment with placebo, one of four doses of risperidone (2, 6, 10, or 16 mg), or 20 mg of haloperidol daily. Clinical improvement (20% reduction in total scores on the Positive and Negative Syndrome Scale for Schizophrenia) at the study end point was shown by 35% of the patients receiving 2 mg of risperidone, 57% receiving 6 mg, 40% receiving 10 mg, and 51% receiving 16 mg; and by 30% receiving haloperidol and 22% receiving placebo. Statistically significant differences in clinical improvement were found between 6 and 16 mg of risperidone versus placebo and versus haloperidol. Positive symptom scores were significantly lower after 6, 10, and 16 mg of risperidone and 20 mg of haloperidol than placebo; negative symptom scores, however, were reduced significantly, compared with placebo, only after 6 and 16 mg of risperidone. The incidence of extra-pyramidal side effects (measured by the Extrapyramidal Symptom Rating Scale) was significantly higher in patients treated with 16 mg of risperidone or 20 mg of haloperidol than placebo. The results indicate that the optimal daily dose of risperidone for most schizophrenic patients in this study was 6 mg; this dose was as effective as 16 mg, and the incidence of extrapyramidal symptoms in patients receiving 6 mg of risperidone was no higher than that in patients receiving placebo. Risperidone is a safe antipsychotic that is effective against both the positive and negative symptoms of schizophrenia.",1994.0,0,0
522,7525394,"Methylphenidate and ADHD: influence of age, IQ and neurodevelopmental status.",S D Mayes; D L Crites; E O Bixler; F J Humphrey; R E Mattison,"Sixty-nine children with attention deficit hyperactivity disorder (ADHD) underwent blind methylphenidate trials. 36 had ADHD alone (with or without a learning disability) and 33 had additional neurodevelopmental disorders. Of the children with ADHD alone, 88 per cent improved significantly on methylphenidate. This did not differ significantly from the 69 per cent response rate for children with ADHD and other neurodevelopmental disorders. The results confirm and add to the research literature indicating that ADHD children who are of preschool age and/or who have co-existing neurological disorders may benefit from methylphenidate.",2001.0,0,1
523,7525541,Predictors of clozapine response in schizophrenia.,D Pickar; R R Owen; R E Litman; J K Hsiao; T P Su,"The introduction of the atypical neuroleptic, clozapine, has had widespread influence not only on the treatment of the seriously mentally ill patient, but also on new drug development and on hypotheses of the pathophysiology of schizophrenia. While clozapine differs from traditional neuroleptics in its lack of extrapyramidal side effects (EPS), it also is distinct in its profile of neurotransmitter receptor affinities. In our work examining the clinical and biological effects of clozapine in patients with schizophrenia, we have identified the presence of EPS during typical neuroleptic treatment as a consistent predictor of subsequent good response to clozapine. Further, our data suggest that clozapine should not be reserved for the most chronically ill patients, but rather be utilized in patients with less chronic courses of schizophrenia. Biological predictors of clozapine response are consistent with dopaminergic, serotonergic, and noradrenergic facets to its mechanism of action.",2001.0,0,0
524,7527327,Risperidone. A review of its pharmacology and therapeutic potential in the treatment of schizophrenia.,S Grant; A Fitton,"Risperidone, a benzisoxazol derivative, is a novel antipsychotic agent which combines potent serotonin (5-hydroxytryptamine) 5-HT2 and dopamine D2 receptor antagonism. Development of the drug was stimulated by reports that the selective serotonin 5-HT2 antagonist ritanserin improved the negative symptoms of schizophrenia and decreased extrapyramidal symptoms when combined with haloperidol. The relatively low incidence of extrapyramidal symptoms with risperidone may reflect a preferential action on mesolimbic rather than nigrostriatal dopaminergic pathways. Recent clinical investigation suggests that risperidone is of at least comparable efficacy to haloperidol and perphenazine in improving the symptoms of acute and chronic schizophrenia on short term administration. Advantages offered by risperidone over haloperidol include a faster onset of antipsychotic action, a lower incidence of extrapyramidal effects and possibly greater efficacy against the negative symptoms of schizophrenia. If these benefits prove to be maintained during long term therapy, risperidone is likely to make a significant contribution to the treatment of schizophrenia.",1994.0,0,0
525,7527565,Cerebrospinal fluid monoamine metabolites in boys with attention-deficit hyperactivity disorder.,F X Castellanos; J Elia; M J Kruesi; C S Gulotta; I N Mefford; W Z Potter; G F Ritchie; J L Rapoport,"Cerebrospinal fluid (CSF), plasma, and urinary monoamine metabolites were determined for 29 boys, aged 6-12, with attention-deficit hyperactivity disorder (ADHD). Levels of CSF 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG), the metabolites of serotonin, dopamine, and norepinephrine, respectively, correlated significantly with behavioral measures of aggression and impulsivity/hyperactivity. However, these correlations were in the unexpected direction; for example, CSF 5-HIAA correlated positively with the Brown-Goodwin Lifetime History of Aggression Scale. HVA in CSF was positively correlated with several measures of hyperactivity. The replicability of these findings, as well as possible socioenvironmental effects, and the predictive value of CSF monoamines in prepubertal hyperactivity are the subjects of ongoing study.",1994.0,0,0
526,7528602,Desmopressin for risperidone-induced enuresis.,J A Bennett; P E Keck; L J Wallhausser,,2001.0,0,0
527,7531355,Risperidone and clozapine in the treatment of drug-resistant schizophrenia and neuroleptic-induced supersensitivity psychosis.,G Chouinard; J L Vainer; M C Bélanger; L Turnier; P Beaudry; J Y Roy; R Miller,"1. Supersensitivity psychosis (SSP) has emerged as a potential side effect of long-term neuroleptic therapy similar to tardive dyskinesia (TD). 2. Six schizophrenic patients with SSP, considered to be drug-resistant, were treated with risperidone, while another 5 were treated with clozapine. 3. The 6 risperidone-treated patients (all women) were rated on the Clinical Global Impression Improvement Scale as at least very much improved. Among the 5 clozapine-treated patients, all 4 men were found to have a marked response to clozapine, while the female patient was judged to be minimally improved. 4. It is hypothesized that not only TD but also SSP arise from destruction of cholinergic interneurons in the striatum as a consequence of prolonged neuroleptic administration. Thus, the drug-induced parkinsonism, which was proposed as mediating the antipsychotic effect of dopamine D2 blocking drugs, depends on the integrity of these cholinergic neurons. If these neurons are destroyed, drugs such as haloperidol lose their therapeutic effect. 5. In contrast, atypical neuroleptics like clozapine and risperidone reduce dopamine release in the striatum independently of prior production of extrapyramidal symptoms and, in this way, may be effective in psychotic illnesses unresponsive to classical anti-D2 neuroleptics. 6. In the present sample of patients, it is worth noting that schizophrenic men were good responders to clozapine. In comparison, risperidone was found to be efficacious in schizophrenic women.",1994.0,0,0
528,7542829,Risperidone versus zuclopenthixol in the treatment of acute schizophrenic episodes: a double-blind parallel-group trial.,M O Huttunen; T Piepponen; H Rantanen; I Larmo; R Nyholm; V Raitasuo,"A double-blind, randomized, multi-center, parallel-group study was conducted in Finland to compare the efficacy and safety of risperidone with zuclopenthixol in patients with acute exacerbations of schizophrenia or schizophreniform disorder. Ninety-eight patients were randomly assigned to treatment with risperidone (n = 48) or zuclopenthixol (n = 50), in variable doses, for 6 weeks. The mean daily doses of risperidone and zuclopenthixol at the end of the trial were 8 mg and 38 mg respectively. Efficacy was assessed throughout by the Positive and Negative Syndrome Scale for schizophrenia and Clinical Global Impression. Safety assessments included the Extrapyramidal Symptom Rating Scale, UKU Side-Effect Rating Scale, vital signs, body weight and laboratory screening. The results indicate that risperidone is at least as effective as zuclopenthixol for the treatment of acute schizophrenic episodes, with a trend towards greater improvement in the overall severity of symptoms. The onset of action was significantly shorter with risperidone than with zuclopenthixol. Although the general tolerability of the two drugs was comparable, fewer patients experienced extrapyramidal symptoms with risperidone, so that significantly fewer risperidone-treated patients required antiparkinsonian medication.",1995.0,0,0
529,7545060,"Risperidone in the treatment of patients with chronic schizophrenia: a multi-national, multi-centre, double-blind, parallel-group study versus haloperidol. Risperidone Study Group.",J Peuskens,"This study was performed in order to evaluate the short-term efficacy and safety of fixed risperidone doses compared to haloperidol. In a multi-national, parallel-group, double-blind study, patients with chronic schizophrenia (DSM-III-R) were randomly assigned to risperidone 1, 4, 8, 12 or 16 mg or haloperidol 10 mg daily for 8 weeks. Efficacy was assessed by the Positive and Negative Syndrome Scale for schizophrenia (PANSS) and clinical global impression (CGI), and safety primarily by the Extrapyramidal Symptom Rating Scale (ESRS). One thousand three hundred and sixty-two patients were evaluated. The optimum risperidone doses were 4 mg and 8 mg, with response rates of 63.4% (56.8%; 69.7%) and 65.8% (59.2%; 71.9%) respectively. Response rate in haloperidol-treated patients was 58.7% (52.0%; 65.3%); the 95% confidence intervals (CI) of the differences between risperidone 4 mg or 8 mg and haloperidol were (- 4.3%; 13.7%) and (- 1.9%; 16.0%) respectively. There were no significant differences in CGI scores at endpoint between risperidone 4 mg, 8 mg, 12 mg and 16 mg and haloperidol (3.0, 3.0, 3.2, 3.1 and 3.1 respectively); the 95% CI of the differences between risperidone 4 mg or 8 mg and haloperidol were ( - 0.4; 0.1) and ( - 0.3; 0.2) respectively. Mean shifts to the maximum total ESRS scores versus baseline (mean (confidence interval)) were significantly greater in haloperidol-treated patients (5.1 (4.0; 6.2)) than in the risperidone 1, 4, 8 and 12 mg groups (1.1 (0.3; 1.9); 1.8 (0.9; 2.7); 2.7 (1.8; 3.6) and 3.2 (2.3; 4.1) respectively (P < 0.05)). Risperidone is an effective antipsychotic for the treatment of chronic schizophrenia; doses of 4 and 8 mg seem to be optimal and have a lower incidence of side-effects than haloperidol.",1995.0,0,0
530,7554870,Is there a relationship between clozapine and obsessive-compulsive disorder?: a retrospective chart review.,S N Ghaemi; C A Zarate; A P Popli; S S Pillay; J O Cole,"The emergence of obsessive-compulsive symptoms during clozapine treatment has been reported in recent case studies, yet the incidence and significance of this finding is still unclear pending reliable data from a larger sample of patients. Hospital records of 142 randomly selected inpatients started on clozapine treatment at McLean Hospital before July 1, 1992, were reviewed retrospectively. Based on a limited retrospective chart review, there were no definitive cases of patients who developed obsessive-compulsive disorder (OCD) or whose OCD worsened as a result of clozapine treatment. Although some fluctuation of OCD symptoms may have occurred in two cases, it is unclear whether those symptoms were related to treatment with clozapine (or other psychotropic drugs) or to undulations in the natural history of OCD. No definitive relationship between OCD symptoms and clozapine treatment could be established in this limited study. Further clarification of this matter awaits outcome research using prospective methodologies.",2001.0,0,0
531,7573299,Short-term efficacy of apraclonidine hydrochloride added to maximum-tolerated medical therapy for glaucoma. Apraclonidine Maximum-Tolerated Medical Therapy Study Group.,A L Robin; R Ritch; D H Shin; B Smythe; T Mundorf; R P Lehmann,"We determined whether the addition of topical apraclonidine hydrochloride to eyes that are receiving maximal medical therapy but still have inadequate intraocular pressure control and that are scheduled to undergo surgery could adequately decrease intraocular pressure, postponing the need for further intervention. We performed a prospective, 90-day, multicentered, placebo-controlled, double-masked parallel study. We enrolled one eye each of 174 glaucoma patients with inadequate intraocular pressure control who were on maximally tolerated medical therapy. We continued to administer maximum medical therapy for glaucoma. Study medications were either apraclonidine hydrochloride 0.5% or placebo (apraclonidine's vehicle). Patients were instructed to take the study medication every eight hours. We measured intraocular pressure, change in intraocular pressure from baseline, and the number of eyes requiring surgery after the addition of study medication. Fifty-two (60%) of 86 patients treated with apraclonidine maintained adequate intraocular pressure control throughout the study and avoided surgery, compared with 28 (32%) of 88 patients treated with placebo (P < .001). Apraclonidine treatment resulted in significantly more patients attaining an additional 20% reduction or more in intraocular pressure from baseline and an intraocular pressure less than or equal to 20 mm Hg (P < .05). The most common ocular complication was conjunctival hyperemia (11 of 86 patients, 12.8%). The most frequent nonocular problem was dry mouth (four patients, 4.7%). Apraclonidine appeared to be safe in all eyes and efficacious in some eyes. It significantly lowered intraocular pressure when used in combination with maximally tolerated medical therapy, which delayed or prevented further glaucoma surgery for at least 90 days in 52 (60%) of 86 treated patients.",1995.0,0,0
532,7575109,Clozapine-induced increase in plasma levels of soluble interleukin-2 receptors.,T Pollmächer; D Hinze-Selch; J Mullington; F Holsboer,,1995.0,0,0
533,7576677,"Epidemiology of the adverse hemodynamic events occurring during ""clonidine anesthesia"": a prospective open trial of intraoperative intravenous clonidine.",M De Kock; H Versailles; B Colinet; R Karthaeuser; J L Scholtes,"Determine the hemodynamic consequences of intraoperative clonidine during major abdominal surgery. Prospective open trial. Teaching hospital. 402 consecutive patients scheduled for major abdominal surgery. 350 consecutive patients received intravenous (IV) clonidine (loading dose of 4 micrograms/kg in 20 minutes at anesthesia induction, followed by a continuous infusion of 2 micrograms/kg/h until the end of surgery). Fifty-two additional patients served as controls. Anesthetic technique consisted of balanced anesthesia (isoflurane, fentanyl, atracurium). ECG, invasive arterial blood pressure (BP), expiratory PCO2 and pulse oximetry were continuously recorded. Hemodynamic events (HEs) were defined as moderate for a 20% reduction of the baseline systolic blood pressure (SBP) or a heart rate (HR) decreasing between 50 beats per minute (bpm) and 40 bpm. A 30% reduction of the baseline SBP or a HR below 40 bpm was considered an important HE. The rate and duration of these events were recorded from induction to recovery. HEs requiring a specific treatment were noted. Central venous pressure, volume of fluid infused, and urinary output were also recorded. 21% of control patients and 31% of clonidine patients had no adverse HEs. A moderate reduction of the baseline BP was the most common episode in both groups. The incidence of the HEs (moderate and important) was similar in both groups but the duration HEs was significantly longer in the clonidine patients (p < 0.05). 40% of the control patients and 13% of the clonidine patients required specific management for their HEs (p < 0.05), the most common of which was hypotension without bradycardia. Neither coexisting pathology nor preoperative medications influenced the incidence of HEs. IV clonidine can be used routinely during anesthesia for major abdominal surgery.",1995.0,0,0
534,7585841,"ICI 204,636, a novel, atypical antipsychotic: early indication of safety and efficacy in patients with chronic and subchronic schizophrenia.",L F Fabre; L Arvanitis; J Pultz; V M Jones; J B Malick; V B Slotnick,"We evaluated the effects of ICI 204,636 in 12 hospitalized patients with schizophrenia in a double-blind, placebo-controlled, parallel-group, rising-dose study. Patients met the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised criteria for chronic or subchronic schizophrenia and had a total score > or = 30 on the 18-item Brief Psychiatric Rating Scale (BPRS) and a score > or = 3 on the Clinical Global Impression (CGI) Severity of Illness item. Patients received 21 days of double-blind treatment with increasing doses of ICI 204,636 (25 to 250 mg/d) or placebo. Efficacy was assessed using the BPRS and CGI. Response to treatment was defined as a > or = 30% decrease in the BPRS total score from baseline. Extrapyramidal symptoms and abnormal involuntary movements were assessed using the Simpson Scale and Abnormal Involuntary Movement Scale. Changes from baseline in the BPRS and CGI were significantly greater at end point for patients who received ICI 204,636 versus placebo (BPRS, -20.9 vs -4.8; CGI, -2.9 vs -1.0; P < 0.05, analysis of covariance; P < or = 0.06, Wilcoxon rank sum test). All patients in the ICI 204,636 group responded to treatment (P < 0.10) versus only two patients in the placebo group. Mild somnolence occurred in 50% of ICI 204,636-treated patients. No treatment-emergent extrapyramidal symptoms or dystonic reactions were observed. ICI 204,636 showed efficacy in the positive and negative symptoms of schizophrenia and was well tolerated.",2001.0,0,0
535,7585844,Efficacy and safety of risperidone in the long-term treatment of patients with schizophrenia.,E Lindström; B Eriksson; A Hellgren; L von Knorring; G Eberhard,"The long-term efficacy and safety of risperidone were evaluated in patients with chronic schizophrenia in an open-label study. Thirty-two patients received risperidone for 1 year and 19 of the 32 received risperidone for 2 years. The mean dose of risperidone was 9.4 mg/d in the 1-year follow-up. At the end of 1 and 2 years, improvements were found in total scores on the Positive and Negative Syndrome Scale (PANSS), on four PANSS factors (positive, negative, excited, and cognitive), and the Clinical Global Impression scale. Severity of extrapyramidal symptoms (based on scores on the Extrapyramidal Symptom Rating Scale) was also reduced. Clinical improvement (defined as a 20% or more reduction in total PANSS scores) was shown by 54% of the patients at end point. Social functioning (as assessed by using the modified Strauss/Carpenter scale) was significantly improved after 2 years. Number of days spent in hospitals was significantly reduced during the 2 years of treatment, and the number of days in treatment (group) homes significantly increased. It is concluded that treatment with risperidone for 1 and 2 years is associated with significant reductions in symptoms of schizophrenia, improved social functioning, and reduction in days spent in the hospital.",1995.0,0,0
536,7591493,Male sexual side effects associated with antidepressants: a descriptive clinical study of 32 patients.,J H Hsu; W W Shen,"This is a retrospective study to add to the existing body of clinical information regarding male sexual side effects associated with antidepressants. From the chart review, thirty-four out of eighty male patients were identified to have reported loss of libido, erectile difficulty, anorgasmia, and delayed ejaculation while receiving pharmacotherapy of selective serotonin reuptake blockers (fluoxetine, paroxetine, and sertraline); tricyclic antidepressants (nortriptyline, imipramine, amitriptyline, desipramine, and clomipramine); and a monoamine oxidase inhibitor (phenelzine). The authors also discussed the management of these sexual side effects by waiting for spontaneous remission, reducing the dosage level, and substituting the offending drug with other antidepressants. This article underscores the underreported nature of antidepressant-associated sexual dysfunction, the high incidence of SSRI-associated sexual side effects, equal potentials in causing sexual side effects among the three SSRI's, the low incidence rate of sexual adverse effects from bupropion, and the minimal need to add an antidote if the side effects are to be managed systematically. Finally, male sexual side effects can occur randomly and involve any sexual phase randomly, and the treatment approaches are similar, regardless of the types of sexual dysfunction associated with antidepressants.",1995.0,0,0
537,7593710,Pharmacotherapy of adult attention deficit/hyperactivity disorder: a review.,T E Wilens; J Biederman; T J Spencer; J Prince,"Adult attention deficit/hyperactivity disorder (ADHD) is an increasingly recognized disorder with associated psychiatric comorbidity and impairment. Although pharmacotherapy serves an important role in treating ADHD and other concurrent psychiatric disorders in children and adolescents, the use of pharmacotherapeutics for adults with ADHD remains less established. In this report, the effectiveness and dosing parameters of the various agents investigated for adult ADHD are reviewed. A systematic review of the available literature identified 7 studies (N = 193 subjects) of psychostimulants and 10 studies of nonstimulant medications (N = 167 subjects) including antidepressants, antihypertensives, and amino acids for the treatment of ADHD in adults. The majority of double-blind investigations were with the psychostimulants, with the nonstimulant agents, generally antidepressants, studied under open conditions. There was considerable variability in diagnostic criteria, dosing parameters, and response rates between the various studies. Under controlled conditions, the aggregate literature shows that the stimulants had a clinically and statistically significant effect on reducing ADHD symptoms. Open studies on the nonserotonergic antidepressants (tricyclics, bupropion, and monoamine oxidase inhibitors) also show a moderate anti-ADHD effect. The literature appears to support the use of robust doses of both stimulants and antidepressants for ADHD in adults. Further controlled studies applying stringent diagnostic criteria and outcome methodology are necessary to define the range of pharmacotherapeutic options for adults with ADHD.",1995.0,0,1
538,7605757,Epidural clonidine combined with bupivacaine for analgesia in labor. Effects on mother and neonate.,I Cigarini; A Kaba; F Bonnet; E Brohon; F Dutz; F Damas; P Hans,"A double-blind study was conducted to assess the efficacy and the safety of epidural clonidine combined with bupivacaine for analgesia during labor. Two groups of pregnant healthy women were allocated randomly to receive either 10 mL 0.125% bupivacaine plain solution (group B, n = 10) or with 75 micrograms clonidine (group B + C, n = 12). Visual analog scale (VAS) scores were measured over 30 minutes after each epidural injection. Patients were monitored with an automated blood pressure device (Dinamap and a pulse oximeter), and fetal heart rate was measured with a cardiotocograph. Plasma clonidine concentrations were measured at birth in mothers and in the umbilical cord by radioimmunoassay. Visual analog scale scores were significantly lower in patients who received clonidine. Patients required a second epidural injection after 55 +/- 9 minutes in group B and 127 +/- 11 minutes in group B + C (P < .05). Visual analog scale scores were also significantly lower in group B + C than in group B, after the second injection. Decreases in arterial blood pressure were comparable in the two groups, and no patient experienced arterial oxygen desaturation or bradycardia. Fetal heart rate was decreased in group B + C at the time of the second injection. The duration of labor after epidural administration was prolonged in group B + C patients compared to group B (282 +/- 43 minutes and 169 +/- 26 minutes, respectively, P < .05). Apgar scores at 1 and 5 minutes were similar in both groups. Plasma clonidine concentrations were, respectively, 0.31 +/- 0.16 ng/mL 60 minutes after the first injection and 0.62 +/- 0.13 ng/mL at birth in mothers while plasma umbilical cord concentrations were 0.56 +/- 0.12 ng/mL. The study documents that clonidine improves epidural bupivacaine analgesia during labor and demonstrates transfer of the drug across the placenta. Therefore, a more extensive study is required to determine the incidence of possible side effects of clonidine in neonates.",1995.0,0,0
539,7619979,Clozapine decreases smoking in patients with chronic schizophrenia.,J McEvoy; O Freudenreich; M McGee; C VanderZwaag; E Levin; J Rose,,1995.0,0,0
540,7630692,Effects of late-afternoon methylphenidate administration on behavior and sleep in attention-deficit hyperactivity disorder.,J D Kent; J C Blader; H S Koplewicz; H Abikoff; C A Foley,"This study evaluated the effects on behavior and sleep of methylphenidate (MPH) administered at 4 PM to children with attention-deficit hyperactivity disorder (ADHD). Twelve children admitted to a child psychiatric inpatient service with ADHD participated in a double-blind, crossover study in which they received a 4 PM dose of either 15 mg of MPH, 10 mg of MPH, or a placebo in random order for 12 consecutive days. Ratings of behavior, including ADHD symptoms, pertaining to the period from dose administration until sleep onset, were supplied nightly by hospital staff. Sleep latency and sleep adequacy were also assessed for each night. MPH resulted in markedly improved behavioral control compared with placebo; there was no difference between 15-mg and 10-mg MPH doses. MPH did not alter sleep latencies observed with the placebo. Children were more often rated as less tired on awakening after nights that they received 10 mg of MPH compared with 15 mg of MPH and the placebo. Weight loss was apparent among 83% of the patients, but dinner intake did not vary with third-dose condition. Morning and noon administration of stimulants to children with ADHD is a near-universal practice, but many clinicians avoid a third, late-afternoon administration for fear of inducing insomnia. This study's findings show that children with ADHD derive substantial symptom reduction from MPH administered in late afternoon, with no untoward effects on sleep. Therefore, three-times-a-day dosing should be considered for those children exhibiting ADHD symptoms in the evening. Adverse effects on sleep latency were not apparent in the sample overall. Nonetheless, monitoring for possible aggravation of sleep problems and weight loss remains sound treatment practice.",1995.0,0,1
541,7639365,An isobolographic study of epidural clonidine and fentanyl after cesarean section.,J C Eisenach; R D'Angelo; C Taylor; D D Hood,"Although the epidural administration of clonidine and fentanyl provides pain relief after surgery, the interaction between the two drugs has not been examined formally. This study used an isobolographic method to determine whether epidurally administered fentanyl and clonidine interact in an additive or synergistic manner. Ninety women with moderate to severe pain after elective cesarean section under epidural anesthesia were studied. Using a randomized, double-blind protocol, we assigned each patient to receive a single epidural injection of one of three doses of fentanyl, clonidine, or a fixed ratio combination. Pain relief, blood pressure (BP), heart rate (HR), and sedation were measured 15 min after injection. Each drug alone and in combination produced analgesia, as measured by pain relief scores, and reduced need for intravenous morphine. Although the effective dose producing analgesia in 50% of patients (ED50) for the mixture was only 52% of that predicted by an additive interaction, this did not differ significantly from additivity, likely due to large variability. Clonidine, alone or in combination with fentanyl, produced a minor reduction in BP, but did not affect HR or cause more sedation than fentanyl. Unlike studies in rodents, this clinical study did not demonstrate synergy between fentanyl and clonidine. This could reflect a true species difference or differences in methodologies used. Nonetheless, a reduced dose of fentanyl and clonidine can be combined for excellent analgesia.",1994.0,0,0
542,7642836,Methylphenidate and cognitive flexibility: dissociated dose effects in hyperactive children.,R Tannock; R Schachar; G Logan,"A randomized, double-blind, placebo-controlled trial was conducted to assess the acute effects of placebo and three doses of methylphenidate (MPH) (0.3, 0.6, 0.9 mg/kg) on cognitive flexibility and overt behavior in 28 children with a confirmed diagnosis of attention deficit-hyperactivity disorder. Two underlying cognitive processes (response inhibition and response reengagement) were assessed by measuring the probability and speed with which subjects could inhibit responses to a primary task (forced-choice letter discrimination) and immediately execute a response to a secondary task (simple reaction time) when given a signal to do so. Results indicated that MPH enhanced cognitive flexibility, although the high dose was less effective than lower doses in enhancing response inhibition. Dissociations of dose effects on cognitive function and behavior were demonstrated: Dose-response functions for changes in behavior were linear, whereas the function for response inhibition was U-shaped. Findings argue against the typical clinical practice of determining the response to stimulant treatment from a single measure such as parent report of child behavior.",1995.0,0,1
543,7649718,Effects of methylphenidate in HIV-related depression: a comparative trial with desipramine.,F Fernandez; J K Levy; H R Samley; F J Pirozzolo; D Lachar; J Crowley; S Adams; B Ross; P Ruiz,"This report is a randomized, double-blind, comparative trial of desipramine with the psychomotor stimulant methylphenidate. Twenty HIV antibody-positive patients with depressive symptoms were randomly assigned to either drug. After individual dose titration, the mean daily dose of desipramine was 150 mg. and methylphenidate 30 mg. daily. The differences in responses between desipramine and methylphenidate were not statistically significant on various measures of depression. The antidepressant effect of methylphenidate did not occur any faster than that of desipramine. Both significantly reduced depressive and anxious symptomatology over the blinded portion of the treatments. Thus, methylphenidate relieves depressive symptomatology with efficacy similar to that of desipramine, offering an alternative to patients who are unable to tolerate standard tricyclic antidepressant therapy. The dopaminergic effects of methylphenidate are likely to mediate its antidepressant effects.",1995.0,0,0
544,7669311,The efficacy of guanfacine in reducing perioperative hemodynamic changes and volatile anesthetic requirement.,K Nishina; K Mikawa; N Maekawa; H Obara,"To evaluate the efficacy of guanfacine, an alpha 2-adrenergic agonist, for attenuating hemodynamic changes associated with tracheal intubation or extubation, providing intraoperative hemodynamic stability, and reducing inhalation anesthetic requirement in patients undergoing gynecologic surgery. Randomized, double-blind, placebo-controlled study. Inpatient gynecology at a university hospital. 45 women (ASA I) undergoing elective abdominal hysterectomy. Guanfacine and placebo supplementation. Oral guanfacine at 0.5 or 1 mg or a placebo (control) 3 hours before induction of anesthesia. Anesthesia was induced with thiamylal 5 mg/kg and vecuronium 0.2 mg/kg, and maintained with isoflurane and 50% nitrous oxide (N2O) in oxygen. The inspired isoflurane concentration was maintained at 1% during the first 5 minutes following induction of anesthesia and titrated to the concentration required to maintain hemodynamic stability [defined as +/- 10% of systolic blood pressure (SBP)]. The end-tidal concentration of isoflurane was monitored throughout anesthesia. On completion of surgery, N2O and isoflurane were discontinued. Following confirmation of recovery from anesthesia and muscle relaxation, the endotracheal tube was removed. Patients in the control group showed significant increases in SBP and diastolic blood pressure (DBP) and heart rate (HR) associated with tracheal intubation 50 +/- 5, 57 +/- 6.3, and 45 +/- 4.6 (%, mean +/- SEM, p < 0.05 for any variables), respectively. Plasma norepinephrine and epinephrine concentrations increased to 382 +/- 40 pg/ml and 49 +/- 4.2 pg/ml, respectively (p < 0.05 compared with basal values). These changes were attenuated in patients receiving 1 mg of guanfacine (29 +/- 4.2, 33 +/- 4.5, 25 +/- 3.2, 210 +/- 32, and 22 +/- 3.5, respectively (p < 0.05 for any variables compared with placebo group). Higher inspired concentrations of isoflurane (%) were required in the control and 0.5 mg guanfacine-treated groups (1.2 +/- 0.05 and 1.0 +/- 0.04, respectively) than in the 1 mg guanfacine-treated group (0.62 +/- 0.03) for hemodynamic stability (p < 0.05). Coefficient of variation in HR changes during surgery was 17.2, 13.9, and 8.8 in the placebo, guanfacine 0.5 mg, and guanfacine 1 mg treated groups, respectively. Compared with placebo, guanfacine 1 mg reduced the maximum changes (mean +/- SEM) in SBP (7 +/- 1.2 vs. 18 +/- 2.2) and in HR (23 +/- 2.1 vs. 44 +/- 3.6) occurring during tracheal extubation. The incidence of perioperative complications was similar among the three groups. Guanfacine 1 mg administered orally proved to be an effective premedicant for providing intraoperative hemodynamic stability, attenuating the increase in BP and HR associated with tracheal intubation and extubation, and reducing anesthetic requirements without increasing the incidence of perioperative complications.",1995.0,0,0
545,7701277,Childhood-onset schizophrenia: an NIMH study in progress.,C T Gordon; J A Frazier; K McKenna; J Giedd; A Zametkin; T Zahn; D Hommer; W Hong; D Kaysen; K E Albus,"An ongoing study of the phenomenology, genetics, neuropsychology, physiology (eye tracking, autonomic responsivity), neuroimaging, biochemistry, and pharmacology of childhood-onset schizophrenia is described, and pilot data are presented for the first 22 subjects. Differentiation from autism ""spectrum"" disorders and other poorly defined, severe neurodevelopmental disorders is needed. Eye tracking and autonomic results are similar to patterns seen in later-onset schizophrenia and possibly more striking. Magnetic resonance imaging showed larger left frontal ventricular horn area for the schizophrenia subjects, larger left caudate, and lack of normal caudate asymmetry. Fluorodeoxyglucose positron emission tomography during an auditory continuous performance task revealed decreased right parietal/occipital glucose metabolic rate in the schizophrenia subjects, which may be secondary to poor attentional performance, and increased glucose metabolic rate in three left frontal regions, a left parietal region, and the right putamen. Clozapine has been effective and well tolerated in an open trial with 12 adolescents who responded poorly to typical neuroleptics; 16 subjects have been enrolled in a double-blind comparison of haloperidol and clozapine. Longitudinal study of this narrowly defined and possibly more homogeneous group of very early-onset schizophrenia subjects will be relevant to current neurodevelopmental theories addressing the role of puberty, progression of pathology, and continuity or discontinuity with later-onset schizophrenia.",1994.0,0,0
546,7718678,Do anticonvulsants hinder clozapine treatment?,W H Wilson,,1995.0,0,0
547,7726818,Differential effects of methylphenidate and self-reinforcement on attention-deficit hyperactivity disorder.,O Ajibola; P W Clement,"Six boys aged 9 to 12 years attended a tutoring class focusing on reading for 30 minutes each morning. The investigators employed a modified Latin-square design in which each child began with a 5-day baseline phase followed by six 10-day treatment phases that used drug placebo, noncontingent reinforcers, 0.3 mg/kg methylphenidate, 0.7 mg/kg methylphenidate, and self-reinforcement in various combinations. Amount of academic performance was the major measure of outcome and the target behavior of self-reinforcement. Drug placebo and noncontingent reinforcers had no systematic impact. Methylphenidate had differential effects across the recorded behaviors. Self-reinforcement improved the target behavior; the mean effect size for self-reinforcement was 2.66. The combined effects of methylphenidate and self-reinforcement on academic performance were greater than either of the treatments given alone (mean effect size = 2.89).",1995.0,0,1
548,7727330,Addition of clonidine to epidural morphine enhances postoperative analgesia after cesarean delivery.,G Capogna; D Celleno; A Zangrillo; P Costantino; S Foresta,"The randomized, double-blind, dose-response study was designed to evaluate the effects of the addition of clonidine to epidural morphine on postoperative analgesia and side effects in patients undergoing cesarean delivery. Sixty patients, undergoing cesarean delivery under epidural anesthesia, were randomly divided in three equal groups to receive, at the end of surgery, an epidural analgesic mixture consisting of 10 mL solution containing 2 mg of morphine diluted with 0.125% bupivacaine plus 1:800,000 epinephrine and 0, 75, or 150 micrograms of clonidine. Duration of analgesia was assessed as the pain-free interval between the end of surgery and patient's first analgesic request. The analgesic mixture was repeated, on patient's request, to 36 hours after the operation. Arterial blood pressure, heart rate, respiratory rate, and side effects were noted. The total amount of morphine and clonidine delivered was also noted. The addition of clonidine (0, 75, or 150 micrograms) to morphine significantly increased the duration of postoperative analgesia (P < .0001) (6.27 versus 13.25 and versus 21.55 hours) and reduced the mean total dose of morphine (9.40 mg versus 5.0 mg versus 3.60 mg) (P < .0001). No significant differences in side effects were noted. A low dose of clonidine such as 75 micrograms doubled the duration of analgesia produced by 2 mg of morphine and a dose of 150 micrograms further increased the duration of postoperative complete analgesia without increasing the incidence of side effects. The morphine requirements during the postoperative period (36 hours) was greatly reduced by the addition of clonidine to the analgesic epidural mixture.",1995.0,0,0
549,7746398,Common drugs may influence motor recovery after stroke. The Sygen In Acute Stroke Study Investigators.,L B Goldstein,"Studies in laboratory animals indicate that certain centrally acting drugs (eg, the antihypertensives clonidine and prazosin, neuroleptics and other dopamine receptor antagonists, benzodiazepines, and the anticonvulsants phenytoin and phenobarbital) impair behavioral recovery after focal brain injury. Even single doses may have long-term harmful effects. To determine whether these medications have a similar negative impact in humans, we analyzed the recoveries of control patients who were enrolled in the Sygen in Acute Stroke Study, a multicenter study of the effects of GM1 ganglioside after ischemic stroke. Motor impairments were measured by the motor subscores of the Toronto Stroke Scale at baseline and 7, 14, 21, 28, 56, and 84 days after stroke. Using these data, we compared motor recovery between patients with initial motor deficits who received at least one of the drugs that interfere with recovery in laboratory studies (""detrimental"" drug group, n = 37) and patients who did not receive these drugs (""neutral"" drug group, n = 59). The groups were well balanced with regard to the frequency of comorbid conditions and other prognostic factors. For upper-extremity motor function, repeated-measures ANOVA showed a significant interaction between drug group and time after stroke [F(6,528) = 2.38; p = 0.03], with a significant (p < 0.001) difference between the groups beginning 7 days after the stroke. A similar trend was present for the lower extremity, but the overall difference between the groups was not significant [ANOVA F(6,498) = 1.22; p = 0.29]. Drug group did influence the degree of independence in activities of daily living as measured with the Barthel Index.(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
550,7752296,Clonidine and opiate receptor antagonists in the treatment of heroin addiction.,G Gerra; A Marcato; R Caccavari; B Fontanesi; R Delsignore; G Fertonani; P Avanzini; P Rustichelli; M Passeri,"Good results in detoxification methods have been reached using both together clonidine and opiate receptors antagonists. One hundred fifty-two heroin-abusing patients were studied evaluating withdrawal symptoms after therapy with (a) clonidine only, (b) clonidine and naltrexone, (c) clonidine and naloxone, and (d) placebos. Treatment results, emotional and behavioral changes, and involvement in psychosocial programs were evaluated after a 6-month follow-up. Although opiate antagonists were able to induce slight and transient withdrawal signs and symptoms, there was, in the group of patients treated with clonidine and naltrexone together, a low percentage of catabolites in urine and an improvement in mood and family relationships. Furthermore, the patients that underwent longer naltrexone treatment showed a stronger involvement in psychosocial programs, and even their relatives demonstrated more interest in the recovery program. A decrease in the difficulties of accepting an opiate antagonists treatment and a different evaluation of withdrawal syndrome were the results of an early use of naltrexone.",1995.0,0,0
551,7759787,Growth rate and growth hormone response to growth hormone-releasing hormone challenge in slowly growing children during chronic administration of clonidine.,F Orio; N Padovano; L Cinquanta; A Colao; B Merola; S Longobardi; E Rossi; V Esposito; F Orio; G Lombardi,"In this study the effects of chronic administration of clonidine, an alpha-2-adrenergic agonist, on the growth rate and GH response to GHRH in 12 ""slowly growing"" children were reported. Clonidine was administered at the dose of 0.04 mg/m2 body surface twice daily along 12 months. The protocol of the study consisted in five periods of growth rate, insulin-like growth factor-1, basal and GHRH-stimulated GH level evaluation: 1) 6-month pretreatment (P1); 2) 6-month placebo administration (PO); 3) after 4 months of therapy (P1); 4) after 4 months of clonidine withdrawal (P2); 5) after 4 months of therapy reinstatement (P3). No difference was observed between P-1 and P0 when all the parameters were considered. During P1 a significant increase of linear growth (p < 0.05 vs P0 and P-1) was observed while standard deviation of height was not modified. At the end of P2, the growth rate and standard deviation of height were similar to those recorded in P0 and P-1. After reinstatement of clonidine therapy a new but less pronounced rise of the growth rate was found (p < 0.05 vs P1, p < 0.01 vs P0 and P-1). GH, insulin-like growth factor-1, GHRH-stimulated GH levels had significantly increased during P1 than P0 and P-1 (p < 0.05), while during P2 they were similar to P0 and P-1. During P3 a new increase of insulin-like growth factor-I baseline and GHRH-stimulated GH levels were observed. However, these were significantly lower than those observed during P1.(ABSTRACT TRUNCATED AT 250 WORDS)",2001.0,0,1
552,7760256,Amphetamine on Rorschach measures in normal subjects.,W Perry; J Sprock; D Schaible; A McDougall; A Minassian; M Jenkins; D Braff,"Twenty-two normal undergraduate men were administered either d-amphetamine (0.2 mg/kg or 0.4 mg/kg) or placebo in a double-blind, counterbalanced design. The test sessions were exactly three weeks apart and included, among other measures, the Rorschach test. Rorschach anxiety and thought disorder variables were measured under drug and placebo conditions. The results suggest that amphetamine causes an increase in Rorschach anxiety indices but does not elevate Rorschach indices of thought disorder. The observed dissociation of anxiety and thought disorder on the Rorschach has implications for the role of the Rorschach in studying anxiety disorders and schizophrenic disorders.",1995.0,0,0
553,7761553,Effect of dextroamphetamine and methylphenidate on calcium and magnesium concentration in hyperactive boys.,M E Schmidt; M J Kruesi; J Elia; B G Borcherding; R J Elin; J M Hosseini; K E McFarlin; S Hamburger,"Levels of calcium in plasma, red blood cells, and mononuclear blood cells, levels of calcium in plasma, and the plasma calcium-to-magnesium ratio were measured at baseline and after 3 weeks of each drug phase of a double-blind, placebo-controlled study of methylphenidate and dextroamphetamine in hyperactive boys. Levels of magnesium in plasma were significantly higher after 3 weeks of dextroamphetamine treatment, and the calcium-to-magnesium ratio was significantly lower after 3 weeks of either drug compared with the baseline or placebo condition. There was no change in magnesium levels in red blood cells or mononuclear blood cells. These measures were obtained 30 minutes before the morning dose and at 9 a.m., 9:30 a.m., 10:30 a.m., 11:00 a.m., and noon on the last day of each 3-week phase. Analysis of variance revealed a drug effect on plasma magnesium and on the calcium-to-magnesium ratio but no drug x time interaction. Although these changes were not correlated with the time course of acute symptomatic response to stimulant therapy, the decrease in the ratio may be relevant to side effects and treatment resistance associated with stimulant use.",1994.0,0,1
554,7770313,The treatment of attention-deficit hyperactivity disorder in Tourette's syndrome: a double-blind placebo-controlled study with clonidine and desipramine.,H S Singer; J Brown; S Quaskey; L A Rosenberg; E D Mellits; M B Denckla,"Because psychostimulants can exacerbate preexisting motor/phonic tics in individuals with Tourette's syndrome (TS), a clinical trial was performed to examine the ability of clonidine and desipramine to modify attention-deficit hyperactivity disorder (ADHD) behaviors in children with TS + ADHD. A double-blind, placebo-controlled protocol was used in which each subject served as his or her own control and received, in a randomly assigned fashion, 6-week medication cycles with clonidine (0.05 mg four times daily), desipramine (25 mg four times daily), and placebo. Thirty-seven children with TS+ADHD between the ages 7 to 13 years and of normal intellect were recruited, and 34 (31 males, 3 females) completed the entire protocol. Outcome measures for ADHD included Parent and Teacher Child Behavior Checklists (CBCL), continuous performance tests, and neuropsychologic tests of executive function. Several markers for ADHD were shown to improve significantly (P < .05) after treatment with desipramine (parent linear analogue rating, parent CBCL ""hyperactivity"" subscale, and teacher CBCL subscales ""nervous/overactive,"" ""anxious,"" and ""unpopular""). Improvement with desipramine was always superior to that noted with clonidine. Clinical improvement did not correlate with drug blood levels. On measures of tic severity, neither drug made tics worse. Desipramine showed a statistically significant improvement on a global linear analogue scale, but not on the Hopkins Motor/Vocal Tic Severity Scale, the Tourette Syndrome Severity Scale, or the Yale Global Tic Severity Scale. Clonidine did not significantly alter tic severity on any measure. The results of this study suggest that desipramine may be a useful alternative for the treatment of symptoms of ADHD in children with TS.",1995.0,0,1
555,7771913,"A double-blind, crossover comparison of methylphenidate and placebo in adults with childhood-onset attention-deficit hyperactivity disorder.",T Spencer; T Wilens; J Biederman; S V Faraone; J S Ablon; K Lapey,"There are few controlled studies of methylphenidate hydrochloride in adults with attention-deficit hyperactivity disorder (ADHD), and their results have been equivocal. The discrepancies among these studies may be related to low doses, diagnostic uncertainties, and lack of attention to comorbid disorders. We conducted a randomized, 7-week, placebo-controlled, crossover study of methylphenidate in 23 adult patients with DSM-III-R ADHD using standardized instruments for diagnosis, separate assessments of ADHD and depressive and anxiety symptoms, and a robust daily dose of methylphenidate hydrochloride, 1.0 mg/kg per day. We found a marked therapeutic response for methylphenidate treatment of ADHD symptoms that exceeded the placebo response (78% vs 4%, P < .0001). Response to methylphenidate was independent of gender, psychiatric comorbidity with anxiety or moderate depression, or family history of psychiatric disorders. Robust doses of methylphenidate are effective in the treatment of adult ADHD.",1995.0,1,1
556,7771914,Efficacy of methylphenidate for attention-deficit hyperactivity disorder in children with tic disorder.,K D Gadow; J Sverd; J Sprafkin; E E Nolan; S N Ezor,"The findings from case reports and patient questionnaire surveys have been interpreted as indicating that administration of stimulants is ill-advised for the treatment of attention-deficit hyperactivity disorder in children with tic disorder. Thirty-four prepubertal children with attention-deficit hyperactivity disorder and tic disorder received placebo and three dosages of methylphenidate hydrochloride (0.1, 0.3, and 0.5 mg/kg) twice daily for 2 weeks each, under double-blind conditions. Treatment effects were assessed using direct observations of child behavior in a simulated (clinic-based) classroom and using rating scales completed by the parents, teachers, and physician. Methylphenidate effectively suppressed hyperactive, disruptive, and aggressive behavior. There was no evidence that methylphenidate altered the severity of tic disorder, but it may have a weak effect on the frequency of motor (increase) and vocal (decrease) tics. Methylphenidate appears to be a safe and effective treatment for attention-deficit hyperactivity disorder in the majority of children with comorbid tic disorder.",1995.0,0,1
557,7791061,Effectiveness of apraclonidine and acetazolamide in preventing postoperative intraocular pressure spikes after extracapsular cataract extraction.,R M Feist; D J Palmer; R Fiscella; J T Ernest; R Tripathi; E Torczynski; M Farber,"We studied the effectiveness of two prophylactic agents in controlling early postoperative intraocular pressure (IOP) increases after cataract surgery. Fifty-four nonglaucomatous patients received either topical 1% apraclonidine, one drop before and after surgery, or sustained-release acetazolamide, 500 mg, or no medication at the completion of planned extracapsular cataract extraction (ECCE). Mean baseline IOPs were similar among patients randomized to the apraclonidine, acetazolamide, and control groups: 15.29 mm Hg, 15.33 mm Hg, and 14.26 mm Hg, respectively. At 3 hours postoperatively, IOPs were significantly lower in the apraclonidine group (11.13 mm Hg, P = .035), nonsignificantly lower in the acetazolamide group (13.3 mm Hg, P = .17), and significantly increased in the control group (21.32 mm Hg, P = .003). One eye in the apraclonidine group and six in the control group had IOPs greater than 30 mm Hg. At 24 hours, the only statistically significant difference was in the control group, whose mean IOPs remained elevated (21.83 mm Hg, P = .0008). One eye in the apraclonidine group, two in the acetazolamide group, and five in the control group had IOPs greater than 30 mm Hg. We found a significant early IOP reduction with apraclonidine given topically preoperatively and at the completion of planned ECCE.",1995.0,0,0
558,7802307,Postoperative analgesia after co-administration of clonidine and morphine by the intrathecal route in patients undergoing hip replacement.,D Grace; H Bunting; K R Milligan; J P Fee,"Postoperative analgesia after intrathecal co-administration of clonidine hydrochloride (75 micrograms) and morphine sulfate (0.5 mg) was compared with analgesia produced after either intrathecal morphine (0.5 mg) or 0.9% sodium chloride in 90 patients undergoing total hip replacement under bupivacaine spinal anesthesia. Patient-controlled morphine requirements were significantly reduced (P < 0.001) postoperation by both clonidine/morphine (median 5 mg/24 h) and morphine (median 7 mg/24 h) compared with control (saline) (median 28 mg/24 h). However, no significant additional reduction in postoperative analgesic requirements was shown with the clonidine/morphine combination compared with morphine alone. Visual analog pain scores, although good in all groups at all times, were significantly poorer in the control group at 2 h (P < 0.04) and 4 h (P < 0.001) after operation compared with both treatment groups, and significantly poorer than the clonidine/morphine group at 6 h (P < 0.002) and 24 h (P < 0.009) postoperation. Mean arterial blood pressure was significantly lower in the clonidine/morphine group than in the two other groups (P < 0.001) between 2 and 5 h after operation. The incidence of emesis was similar in the clonidine/morphine and morphine groups and was significantly more than in the control group.",1995.0,0,0
559,7804386,The cardiovascular effects of bupropion and nortriptyline in depressed outpatients.,A Kiev; H L Masco; T L Wenger; J A Johnston; S R Batey; L C Holloman,"The cardiovascular effects of bupropion hydrochloride and nortriptyline were compared in a double-blind, randomized, 6-week trial in adult outpatients with major depression. After a 1-week placebo phase, 58 patients were randomized to treatment with bupropion (225-450 mg/day) and 57 to nortriptyline (75-150 mg/day). Nortriptyline-treated patients had statistically significant heart rate increases at each assessment as determined by RR intervals on electrocardiogram (14.5-18 bpm). Bupropion-treated patients had small but statistically significant increases in supine diastolic blood pressure of 5.6 mm Hg on day 7 and 7.5 mm Hg on day 28. A few patients in each treatment group had orthostatic changes, but only nortriptyline-treated patients had symptomatic orthostatic hypotension. A slowing of cardiac conduction and possibly of rate-corrected repolarization occurred in patients treated with nortriptyline that did not occur in patients treated with bupropion. Compared to nortriptyline, bupropion appears to have a wider safety margin with regard to cardiovascular effects. This may be particularly true in the elderly, in patients with preexisting cardiovascular disease, or in overdose.",1994.0,0,0
560,7822629,Methylphenidate influences on both early and late ERP waves of ADHD children in a continuous performance test.,M N Verbaten; C C Overtoom; H S Koelega; H Swaab-Barneveld; R J van der Gaag; J Buitelaar; H van Engeland,"Although it has frequently been reported that hyperactive children have abnormally small P3 amplitudes of the event-related potential (ERP), which are normalized by the stimulant drug methylphenidate (MPH), the literature is inconsistent concerning earlier ERP waves. The aim of the present study was to investigate whether the normalizing effect of a 10-mg dose of MPH was also apparent on earlier waves, such as the N1, the P2, and the N2, besides the P3. Twelve attention deficit with hyperactivity disorder (ADHD) children performed a Continuous Performance Test involving a button-press response to the letter X (CPT-X) under the influence of MPH in a double-blind placebo controlled acute dosage design. ERPs were recorded at Oz, Pz, Cz, and Fz. The expected increase of the parietal P3, both to targets and nontargets, was apparent, as well as a significant increase in percentage of hits. There also was a significant increase of an earlier, negative going, wave, the N2, with a frontal maximum, under the influence of MPH. This wave was probably a manifestation of an increase in processing negativity for target stimuli only, after the intake of the stimulant drug. No effect of MPH was found on the N1 or the P2.",1994.0,0,0
561,7822630,Observations and ratings of tics in school settings.,E E Nolan; K D Gadow; J Sverd,"This paper describes the findings of a school-based tic assessment procedure (direct observations, teacher rating scales) for hyperactive children with comorbid tic disorder. Rates of motor tic frequency were found to be moderately stable across both days and school settings. Correlations between direct observations of tics and clinician rating scales were generally in the low to moderate range as were correlations between teacher and clinician rating scales. Overall rates of hyperactive/disruptive behaviors were not associated with rates of motor tic occurrence, and the behavioral symptoms of both disorders were also independent for specific intervals of time.",1994.0,0,0
562,7831459,Effects of intravenous dextroamphetamine on brain metabolism in adults with attention-deficit hyperactivity disorder (ADHD). Preliminary findings.,M Ernst; A J Zametkin; J A Matochik; L Liebenauer; G A Fitzgerald; R M Cohen,"The effects on brain metabolism of the intravenous (i.v.) administration of dextroamphetamine was assessed by positron emission tomography (PET) with [18F]-fluorodeoxyglucose (18-FDG) in 8 adults with attention-deficit hyperactivity disorder (ADHD). During the 3-hour 18-FDG PET session, each adult underwent the initial scan following i.v. infusion of placebo and a second scan following i.v. infusion of 0.15 mg/kg dextroamphetamine in a single-blind design. All subjects showed increased systolic/diastolic blood pressure and improved continuous performance task scores after dextroamphetamine. Global and regional metabolic rates were not significantly altered by the stimulant. When regional and global rates were normalized, the metabolic rates of only three cortical regions differed significantly between conditions. Individually, global metabolism increased in 4 subjects, was unchanged in 2, and decreased in 2 after stimulant infusion. No clinical characteristics differentiated these patients. I.V. infusion of dextroamphetamine did not significantly alter brain metabolism in ADHD adults in this preliminary study.",1994.0,0,0
563,7849498,Sympathetic suppression attenuates anomalous responses to morphine in unexplained pain after cholecystectomy.,I C Roberts-Thomson; J R Jonsson; D B Frewin,"Anomalous responses to morphine are common in patients with unexplained pain in the upper abdomen after cholecystectomy and may be linked to activation of the sympathetic nervous system. The hypothesis that sympathetic suppression would attenuate anomalous responses to morphine was tested by a randomized, cross-over trial using a standard challenge with morphine, with and without pretreatment with clonidine (300 micrograms orally, 1 h prior to the administration of morphine). In 13 of the 15 patients who completed the study, pre-treatment with clonidine decreased plasma concentrations of noradrenaline, dopamine and adrenaline by 56, 15 and 25% respectively. This was associated with a significant reduction in morphine-induced pain (p = 0.02) and nausea (p = 0.04) and attenuated increases in plasma aspartate aminotransferase (AST) activity (p = 0.03). Clonidine attenuates anomalous responses to morphine, perhaps through effects on sympathetic nervous activity or plasma concentrations of catecholamines.",1994.0,0,0
564,7869468,Efficacy of methadone versus methadone and guanfacine in the detoxification of heroin-addicted patients.,L San; T Fernandez; J Cami; M Gossop,"In a randomized double-blind study, the clinical efficacy of methadone vs. methadone and guanfacine was assessed in terms of evolution of opioid withdrawal symptoms during inpatient detoxification. A total of 144 patients were included and randomly allocated to three different treatment groups: methadone alone, and two combined treatment schedules (methadone plus 3 or 4 mg of guanfacine). No differences were observed among the three groups with regard to retention rate throughout the study period. Both therapies, methadone and methadone plus guanfacine, determined a slight increase in withdrawal scores when methadone was discontinued. However, guanfacine was unable to effectively control methadone-associated withdrawal symptoms. These results indicate that guanfacine does not effectively reduce the opioid withdrawal symptoms.",1994.0,0,0
565,7875111,[Clozapine and refractory schizophrenia. Long-term prospective study of 20 patients].,I Jalenques; A J Coudert,"Clozapine, a dibenzodiazepine derivative, has potent antipsychotic activity. But bone marrow suppression resulting in agranulocytosis has been associated with clozapine treatment; thus its clinical development has been delayed and the administration of this drug has been restricted to treatment-resistant schizophrenic patient. This report describes an open prospective study of the effects of clozapine on symptomatology of patients who are refractory to neuroleptics. Authors prospectively followed up until 36 months, 20 DSM III-R schizophrenic patients who had failed to respond to various neuroleptics (7.7 +/- 3.0). When clozapine treatment was initiated, the mean duration of the illness was 17 +/- 10 years. Various scales were used for evaluation: total BPRS, BPRS ""positive symptoms"", BPRS ""negative symptoms"", PANSS positive and PANSS negative were realized at days 0 and 15, months 1, 2 and 3 and then every 3 months. Significative improvements in total BPRS, BPRS positive symptoms and PANSS positive were noted at day 15 (p < 0.005, p < 0.026, p < 0.02, respectively); clozapine produced significant improvement on the BPRS negative symptoms and the PANSS negative at 1 month (p < 0.03 and p < 0.008, respectively). Side effects were studied: dry mouth was more prominent in the first month after wash-out (15%), while salivation was more and more prevalent (20% within the first month; 53% beyond). There was no agranulocytosis in this cohort; 2 cases (10%) of eosinophilia occurred during the first month; 20% of the patients experienced an increase in total white blood cell count (> 12.000/mm3). Weight gain (> 5 kg) affected 32% of patients.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
566,7887841,The efficacy of apraclonidine as an adjunct to timolol therapy. Apraclonidine Adjunctive Therapy Study Group.,W C Stewart; R Ritch; D H Shin; R P Lehmann; C E Shrader; E M van Buskirk,"To compare the intraocular pressure (IOP) lowering efficacy of 0.5% and 1.0% apraclonidine hydrochloride when used adjunctively with 0.5% timolol maleate in 129 patients. A multicenter, randomized, double-masked clinical trial. Adult patients of either sex diagnosed as having either open-angle glaucoma or ocular hypertension were enrolled in the study. Patients using only 0.5% timolol maleate twice daily for at least 4 weeks and who had 8 AM IOPs of at least 22 mm Hg and no greater than 30 mm Hg 12 hours after dosing were eligible for the study. After 8 AM baseline IOPs were obtained while patients were taking timolol only, they were then randomized to receive either 0.5% or 1.0% apraclonidine twice daily in addition to their timolol. Intraocular pressures were measured at 8 AM (before morning dosing) and at 11 AM (3 hours after dosing) on days 14 and 90 and at 8 AM only on day 45. Both concentrations of apraclonidine produced significant IOP reductions from baseline at all visits (P < .001). At 8 AM, after the nighttime dose, the additional mean IOP reduction from the timolol baseline ranged from 2.5 to 3.3 mm Hg (10.3% to 13.6% reduction, respectively). At 11 AM, 3 hours after the morning dose, the additional IOP reduction from the timolol baseline ranged from 4.7 to 5.2 mm Hg (20.0% to 21.7%, respectively). No difference in IOP reduction was observed between the 0.5% and 1.0% apraclonidine concentrations and no loss of IOP efficacy was observed for either concentration for the duration of the study. Sensitivity to 0.5% and 1.0% apraclonidine was observed in nine (13.8%) and 13 (20.3%) patients, respectively. Overall, therapy was discontinued owing to ocular or nonocular side effects with 0.5% and 1.0% apraclonidine in 14 (21.5%) and 16 (25%) patients, respectively. We believe that 0.5% apraclonidine is equally effective as 1.0% apraclonidine when used twice daily as the first adjunctive drug to timolol. The drug effect is maintained for at least 90 days.",1995.0,0,0
567,7906539,Influence of apraclonidine and pilocarpine alone and in combination on post laser trabeculoplasty pressure rise.,R B Dapling; I A Cunliffe; S Longstaff,"Apraclonidine and pilocarpine have been shown to be effective in reducing the incidence of intraocular pressure (IOP) spikes following argon laser trabeculoplasty. An additional reduction in the incidence of acute pressure rise might theoretically be expected by combining these two effective agents. In a prospective randomised study we compared the ability of apraclonidine and pilocarpine alone and in combination to prevent post laser pressure spikes. Patients receiving regular pilocarpine to either eye were excluded. Seventy five eyes received either apraclonidine (26 eyes), pilocarpine (23 eyes), or both drugs (26 eyes). Apraclonidine 1% was instilled 1 hour before and immediately after, and pilocarpine 4% immediately after trabeculoplasty. IOP was measured before and at 1, 2, and 3 hours following trabeculoplasty. In only two (8%) eyes receiving combined treatment was a pressure rise observed. This frequency was significantly lower than that seen in eyes treated with apraclonidine alone (38%), or pilocarpine alone (39%). The mean fall in IOP at 1, 2, and 3 hours was significantly greater in those eyes receiving combined treatment than in the other two groups.",1994.0,0,0
568,7909410,Attention deficit hyperactivity disorder in adults.,D Shaffer,,1994.0,0,0
569,7929019,A double-blind trial of bupropion versus desipramine for bipolar depression.,G S Sachs; B Lafer; A L Stoll; M Banov; A B Thibault; M Tohen; J F Rosenbaum,"Although treatment of bipolar depression is a frequent clinical problem, double-blind studies of the treatment of bipolar depression are scarce. Some case series and uncontrolled data suggest antidepressants may differ in their propensity to induce mania or their efficacy for bipolar depression. The authors conducted a prospective double-blind trial to assess efficacy and rate of treatment-emergent mood elevation in depressed bipolar patients when bupropion or desipramine was added to an ongoing therapeutic regimen of lithium or an anticonvulsant. Results were assessed after 8 weeks of acute treatment and during maintenance treatment up to 1 year. No difference was found for acute efficacy between the two drugs. Mania/hypomania was observed in 5 of 10 desipramine-treated patients, but only 1 of 9 bupropion-treated patients. The occurrence of hypomania or mania was correlated with treatment group (Kendall's tau correlation = 0.42; Z = -2.5, p < .012). These pilot findings suggest that bupropion is less likely to induce mood elevation than desipramine. For treatment of bipolar depression, bupropion and desipramine appear to have similar antidepressant efficacy.",1994.0,0,0
570,7931253,Pharmacodynamics of MDL 72974A: absence of effect on the pressor response to oral tyramine.,C Hinze; M Kaschube; J Hardenberg,"MDL 72974A, a new irreversible selective inhibitor of monoamine oxidase (MAO)-B which is not metabolized to amphetamine-like compounds, is currently being developed for the treatment of Parkinson's disease. In this double blind, placebo controlled randomized study 24 healthy volunteers (n = 6/dose) received single oral doses of placebo, 1, 12 or 24 mg of MDL 72974A qd over two weeks. Sensitivity to orally administered tyramine was determined under fasting conditions before and after drug administration and the doses of tyramine yielding a 30 mmHg increase of SBP (PD30) compared. The 2-fold increase of tyramine sensitivity at end of treatment seen at all MDL 72974A dose levels, however, is within the variability range of the tyramine pressor response. MDL 72974A selectively inhibits MAO-B at doses up to 24 mg orally and has a favourable safety profile.",1994.0,0,0
571,7946257,Opioid antagonist effects on self-injury in adults with mental retardation: response form and location as determinants of medication effects.,T Thompson; T Hackenberg; D Cerutti; D Baker; S Axtell,"The opioid antagonist naltrexone was administered to 8 adults with severe or profound mental retardation and extensive histories of self-injurious behavior. Five-minute behavioral samples were observed randomly out of every hour from 8 a.m. through 3 p.m., Monday through Friday, for four 2-week phases (baseline, placebo, 50 mg, and 100 mg). During naltrexone administration, there were fewer days with frequent head-banging and self-biting, whereas there were more days on which blows to the head or self-biting were infrequent. Self-injurious participants slept 1.38 hours less per night during baseline, which was unaffected by naltrexone.",1994.0,0,0
572,7948457,Stability of neurological signs with clozapine treatment.,R W Buchanan; P Koeppl; A Breier,,1994.0,0,0
573,7949510,Hydrocortisone cream in clonidine patch dermatitis.,G R Tom; M Premer,,1994.0,0,0
574,7961550,Clozapine in tardive dyskinesia: observations from human and animal model studies.,C A Tamminga; G K Thaker; M Moran; T Kakigi; X M Gao,"Clozapine has long been considered a useful treatment in patients who have schizophrenia with the neuroleptic-induced delayed-onset side effect tardive dyskinesia. We present data in support of the clinical impression using both an animal model of the disorder and dyskinetic patients themselves. Clozapine produces a lower rate of oral dyskinesia in laboratory rats after 6 months of chronic treatment than does haloperidol (8.6 +/- 1.3 vs. 13.6 +/- 1.4 vacuous chewing movements every 5 minutes, respectively), suggesting a lower propensity to cause tardive dyskinesia. In the human, when clozapine was compared with haloperidol in the treatment of patients with tardive dyskinesia, clozapine produced significantly greater benefit for motor symptoms after 12 months of treatment than did haloperidol (p < .001). Moreover, the dyskinesia rebound, which occurred equally in both drug groups at the beginning of the study, was sustained in the haloperidol group but lost in the clozapine-treated patients. These data suggest that dyskinetic patients lose their symptoms of tardive dyskinesia, along with dopaminergic hypersensitivity, with long-term clozapine treatment.",1994.0,0,0
575,7961579,"Clozapine, negative symptoms, and extrapyramidal side effects.",J M Kane; A Z Safferman; S Pollack; C Johns; S Szymanski; M Kronig; J A Lieberman,"The importance of persistent negative symptoms in schizophrenia as a limiting factor in psychosocial and vocational rehabilitation has been increasingly emphasized. As a result, treatment trials and new drug development programs are focusing more attention on negative symptoms. Unfortunately, there is enormous phenomenological overlap between negative symptoms and neuroleptic-induced parkinsonism. We report data from a cohort of 56 clozapine-treated patients demonstrating significant correlations between measures of akinesia and anergia. Despite an average drug washout of over 2 weeks, the persistence of drug-induced parkinsonism can confound the assessment of therapeutic drug effects on negative symptoms.",1994.0,0,0
576,7978435,Dosing interval for prolongation of tetracaine spinal anesthesia by oral clonidine in humans.,K Ota; A Namiki; H Iwasaki; I Takahashi,"This study was designed to evaluate the optimal administration time of oral clonidine as premedication for the prolongation of tetracaine spinal anesthesia in humans. Forty male patients scheduled for urologic surgery were studied. Patients were allocated randomly into four groups given 15 mg of 0.5% isobaric tetracaine. Group 1 was given 250 micrograms triazolam orally 1 h before anesthesia. Groups 2, 3, and 4 were administered 150 micrograms oral clonidine just before anesthesia or 1 h and 3 h before anesthesia respectively. Sensory block was assessed by pinprick. Groups 2 and 3 had a significantly prolonged time of sensory block (74%-94%, P < 0.01) when compared with Group 1. However, the prolonging effect of oral clonidine was not apparent in Group 4. We conclude that, when administered within 1 h before anesthesia, oral clonidine, at a dose of 150 micrograms, produced a significant prolongation of tetracaine spinal anesthesia without adverse effects.",1994.0,0,0
577,7978436,Dose-related prolongation of tetracaine spinal anesthesia by oral clonidine in humans.,K Ota; A Namiki; H Iwasaki; I Takahashi,"The prolonging effects of oral clonidine on sensory block during tetracaine spinal anesthesia were studied in 47 healthy patients scheduled for urologic or gynecologic surgery. All patients received 15 mg tetracaine intrathecally in isobaric saline. The patients were randomly allocated into four groups. Group 1 (n = 13) was administered 0.25 mg triazolam orally. Group 2 (n = 12), Group 3 (n = 12), and Group 4 (n = 10) received 75 micrograms, 150 micrograms, and 300 micrograms of oral clonidine, respectively. These drugs were administered 1 h before anesthesia. Sensory block was evaluated by pinprick. All regression times in Groups 2, 3, and 4 were significantly longer than those in Group 1. The prolonging effect of oral clonidine increased in a dose-dependent manner and reached a maximal effect at 150 micrograms. Four patients in Group 4 developed bradycardia (heart rate < 45 bpm), suggesting that the dose of 300 micrograms of oral clonidine may promote bradycardia during spinal anesthesia.",1994.0,0,0
578,7978437,Balanced postoperative analgesia: effect of intravenous clonidine on blood gases and pharmacokinetics of intravenous fentanyl.,J M Bernard; D Lagarde; R Souron,"Agonist interactions in antinociceptive effects between clonidine and opioids can be used to reduce opioid requirements in surgical patients. However, clonidine can cause marked sedation and associated respiratory dysfunction. Thus, the benefit of using clonidine to reduce opioid use on respiration is questionable. This double-blind randomized study compared the analgesic efficacy, arterial blood gases, and pharmacokinetics of an intravenous (IV) infusion of fentanyl 75 micrograms/h and a mixture of fentanyl 25 micrograms/h plus clonidine 0.3 micrograms.kg-1.h-1 in 32 healthy young adults after surgery for scoliosis correction. Oxygen saturation (FIO2: 0.21) and respiratory rate were monitored as well as supplemental analgesia demands (IV ketoprofen via a patient-controlled device), pain, sedation, and hemodynamics. Oxygen and naloxone (5 micrograms.kg-1.min-1) were administered, respectively, if more than three episodes of oxygen saturation less than 90% were observed within 10 min and if PaCO2 was higher than 50 mm Hg. Pain relief, sedation, and ketoprofen requirements were similar in both groups. The number of episodes of arterial desaturation less than 90% (> 20 s) was 106 for four patients in the fentanyl group (versus none in the clonidine-fentanyl group). Naloxone was required in six patients and oxygen in two patients of the fentanyl group (versus none in the group receiving clonidine). Dopamine, 10 micrograms.kg-1.min-1, was required in one patient of the clonidine-fentanyl group to correct hypotension. Mean arterial blood pressure, plasma clearance, and the elimination rate constant of fentanyl were lower in the clonidine-fentanyl group than in the fentanyl group.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
579,7978438,Premedication with oral and transdermal clonidine provides safe and efficacious postoperative sympatholysis.,J E Ellis; G Drijvers; S Pedlow; S P Laff; M J Sorrentino; J F Foss; M Shah; J R Busse; S Mantha; J F McKinsey,"We studied 61 patients undergoing elective major non-cardiac surgery in a randomized, double-blind, placebo-control clinical trial to test the hypothesis that the addition of clonidine to a standardized general anesthetic could safely provide postoperative sympatholysis for patients with known or suspected coronary artery disease. Patients were allocated randomly to receive either placebo (n = 31) or clonidine (n = 30). The treatment group received premedication with a transdermal clonidine system (0.2 mg/d) the night prior to surgery, which was left in place for 72 h, and 0.3 mg oral clonidine 60-90 min before surgery. Clonidine reduced enflurane requirements, intraoperative tachycardia, and myocardial ischemia (1/28 clonidine patients vs 5/24 placebo, P = 0.05). However, clonidine decreased heart rates only during the first five postoperative hours; the incidence of postoperative myocardial ischemia (6/28 clonidine vs 5/26 placebo) did not differ between the two groups. Patients who experienced postoperative myocardial ischemia tended to have higher heart rates after surgery. Clonidine significantly reduced the plasma levels of epinephrine (P = 0.009) and norepinephrine (P = 0.026) measured on the first postoperative morning. There were no differences in the need for intravenous fluid therapy or antihypertensive therapy after surgery. The number of hours spent in an intensive care setting and the number of days spent in hospital were not different between the two groups. These results suggest that larger doses of clonidine should be investigated for their ability to decrease postoperative tachycardia and myocardial ischemia.",1994.0,0,0
580,7979074,"Prevention of phantom pain after major lower limb amputation by epidural infusion of diamorphine, clonidine and bupivacaine.",M Jahangiri; A P Jayatunga; J W Bradley; C H Dark,"Phantom limb pain may appear in up to 85% of patients after amputation. There is no effective treatment. Perioperative epidural infusion of morphine and bupivacaine, alone or in combination, is effective in preventing phantom limb pain in patients with pre-existing limb pain. Serious side-effects, however, make them difficult to manage on a general ward. Clonidine has been shown to be an effective postoperative analgesia when applied epidurally. To mitigate the potentially serious side-effects of all these drugs, we have studied their combined efficiency in preventing phantom limb pain in a prospective controlled study of 24 patients undergoing lower limb amputation. In the study group (n = 13), an epidural infusion containing bupivacaine 75 mg, clonidine 150 micrograms and diamorphine 5 mg in 60 ml normal saline was given at 1-4 ml/h 24-48 h preoperatively and maintained for at least 3 days postoperatively. The control group (n = 11) received on-demand opioid analgesia. Pain was assessed by visual analogue scale at 7 days, 6 months and 1 year. At 1 year follow-up, one patient in the study group and eight patients in the control group had phantom pain (P < 0.002) and two patients in the study group versus eight patients in the control group had phantom limb sensation (P < 0.05). There was no significant improvement in stump pain. We conclude that perioperative epidural infusion of diamorphine, clonidine and bupivacaine is safe and effective in reducing the incidence of phantom pain after amputation.",1994.0,0,0
581,7980374,Efficacy of methylphenidate and behavioral intervention on classroom behavior in children with ADHD and mental retardation.,C R Johnson; B L Handen; M J Lubetsky; K A Sacco,"Using a combination of an alternating treatment and double-blind placebo-controlled drug design, the independent and combined effects of two behavioral interventions and two doses of methylphenidate (MPH) in 3 children with Attention Deficit Hyperactivity Disorder (ADHD) and mental retardation (MR) were assessed. In this single subject design, 2 of the 3 subjects responded positively to medication as measured by increased on-task behavior. The first behavioral intervention, a token economy for on-task behavior, was ineffective for increasing either on-task behavior or work accuracy when combined with placebo. However, improvement in work accuracy was realized with implementation of a second behavioral intervention that specifically targeted accuracy independent of drug conditions. The current findings highlight both the positive effects and limitations of the two commonly used treatment modalities for ADHD. Future studies should continue to extend this area of investigative efforts to produce more data-based knowledge as to the appropriate doses of treatment, both pharmacological and behavioral, with children with both ADHD and mental retardation.",1994.0,0,0
582,7986770,"Effects of clozapine, fluphenazine, and placebo on reaction time measures of attention and sensory dominance in schizophrenia.",T P Zahn; D Pickar; R J Haier,"Two reaction time (RT) paradigms were used to study clozapine's effects on sustained and selective attention compared to fluphenazine and placebo in 25 chronic schizophrenic patients. Sensory dominance was studied via simple and choice RTs to lights and tones, and on double-stimulus trials in which the two stimuli were presented simultaneously. Although 8 of the 25 patients could not perform the RT tasks when taking placebo, there were no effects of clozapine on simple or choice RT compared to placebo or fluphenazine. Subjects on all 3 treatments showed visual dominance: faster RT to lights than to tones on choice and double-stimulus trials. However, clozapine reduced this by means of a selective increase in RT to lights. Clozapine reduced failures to respond to the tone on double-stimulus trials. This was shown to be due to reductions in hallucinations. Clozapine does not generally improve attention, but it may increase the ability of schizophrenic persons to process nondominant or unattended stimuli possibly by increasing the efficiency of resource allocation. This may be partially mediated by a reduction in hallucinations.",1994.0,0,0
583,7992901,Clonidine and lidocaine inhibition of isoflurane-induced tachycardia in humans.,S Tanaka; H Tsuchida; H Namba; A Namiki,"A rapid increase in isoflurane concentration can induce tachycardia and hypertension and increase plasma catecholamine concentrations. To investigate a possible mechanism, we measured hemodynamic responses to isoflurane administered via mask; we also administered clonidine for premedication, lidocaine topically to the nasal mucosa, or lidocaine intravenously to evaluate the effect of these drugs on the hemodynamic responses. Forty ASA physical status 1 patients (aged 20-30 yr) scheduled for elective oral surgery participated in the study. Thirty patients were randomly allocated to one of three groups: a control group, a group receiving 3-4 micrograms.kg-1 of oral clonidine for premedication, and a group receiving 2 ml of 4% lidocaine spray to the nasal mucosa. Ten patients were assigned nonrandomly to a group receiving intravenous lidocaine continuously (0.4 mg.kg-1 bolus followed by 30 micrograms.kg-1.min-1) after the initial randomized experiments were done to test whether systemic lidocaine blunts the responses to inhaled isoflurane. Anesthesia was induced with thiamylal, after which inhalation of 1% isoflurane in 100% oxygen via mask was begun. The inspired concentration of isoflurane was increased by 1% every 5 min to a maximum of 4%. During normocapnia and without surgical stimulation, heart rate and systolic blood pressure were measured every minute for 20 min before and during isoflurane inhalation. Plasma catecholamine concentrations were measured before and at each isoflurane concentration. In the control and intravenous lidocaine groups, an increase in isoflurane concentration from 2% to 3% significantly increased systolic blood pressure (peak changes of 16 +/- 5 and 15 +/- 6 mmHg, respectively) and heart rate (peak changes of 23 +/- 3 and 13 +/- 4 beats.min-1, respectively). A change in concentration to 4%, however, did not significantly alter hemodynamics. Blood pressure and heart rate responses to a change to 3% isoflurane were significantly blunted in the groups receiving clonidine (peak changes of 4 +/- 4 mmHg and 8 +/- 3 beats.min-1, respectively) or nasal lidocaine (peak changes of 2 +/- 1 mmHg and 4 +/- 2 beats.min-1, respectively) compared with the control group. In all groups, plasma epinephrine and norepinephrine concentrations increased after administration of 2% and 1% isoflurane, respectively. Plasma lidocaine concentrations were 0.3-1.3 micrograms.kg-1 in the nasal lidocaine group and 0.6-1.5 micrograms.kg-1 in the intravenous lidocaine group. Stepwise increases in isoflurane concentration elicited hypertension and tachycardia as well as increments in plasma catecholamine concentrations during mask anesthesia. Nasal administration of lidocaine and clonidine premedication significantly blunted the circulatory responses to isoflurane. Intravenous lidocaine did not significantly weaken the responses to changes in isoflurane concentration.",1994.0,0,0
584,7994508,Clonidine is not a useful adjunct to methadone gradual detoxification in opioid addiction.,H Ghodse; J Myles; S E Smith,"The role of clonidine in the management of opioid-dependent individuals undergoing gradual detoxification. A double-blind placebo-controlled trial was conducted on 86 voluntary in-patients (59 male, 27 female) aged 18-47 years, at a specialist drug-dependence treatment unit. Patients entered the trial when on 40 mg of methadone daily or less, and were randomised to receive incremental doses of clonidine (increasing from 0.2 mg daily to 1.2 mg daily) during a 14-day period of gradual methadone detoxification and for four weeks thereafter. Blood pressure was monitored and severity of opioid abstinence was assessed by questionnaire and by clinical examination. Half the subjects were withdrawn or defaulted from the trial by the end of two weeks, those receiving clonidine earlier than those receiving dummy medication (9 of the former and only one of the latter because of systemic hypotension). Similar proportions of subjects completed detoxification in the two groups. In those who completed detoxification, clonidine did not significantly reduce either the symptoms or objective signs of opioid withdrawal. These findings suggest that clonidine has no place as an adjunct to a programme of gradual opioid detoxification.",1994.0,0,0
585,8010365,Trazodone for antidepressant-associated insomnia.,A A Nierenberg; L A Adler; E Peselow; G Zornberg; M Rosenthal,"The authors investigated trazodone as a hypnotic for depressed patients who had persistent, exacerbated, or new insomnia while taking either fluoxetine or bupropion. Seventeen depressed patients who had insomnia while taking fluoxetine or bupropion were given either trazodone or placebo in a double-blind crossover trial. Sleep was assessed by self-report with the Pittsburgh Sleep Quality Index and the sleep items of the Yale-New Haven Hospital Depressive Symptom Inventory. Improvement with trazodone, but not with placebo, was shown by the total Pittsburgh index scores and Yale-New Haven inventory total sleep scores and by the Pittsburgh index measures of sleep duration and Yale-New Haven inventory measures of early morning awakening, and there was a trend toward improvement in the Yale-New Haven inventory item regarding middle of the night awakenings. Subjective sleep quality and sleep latency also showed a trend toward improvement, but the Pittsburgh index measures of sleep efficiency and disturbances and the Yale-New Haven inventory item regarding difficulty falling asleep were unaffected by trazodone. One patient dropped out because of excessive daytime sedation with trazodone, and another dropped out because of nonresponse to placebo. Of the completers, 67% experienced overall improvement in sleep with trazodone according to a priori criteria, whereas only 13% experienced improvement with placebo. Trazodone is an effective hypnotic for patients with antidepressant-associated insomnia.",1994.0,0,0
586,8021335,"Comparison of the pharmacokinetics, pharmacodynamics, and safety of oral (Catapres) and transdermal (M-5041T) clonidine in healthy subjects.",A Fujimura; A Ebihara; K Ohashi; T Shiga; Y Kumagai; H Nakashima; T Kotegawa,"The pharmacokinetic as well as pharmacodynamic properties of a transdermal clonidine, M-5041T (M) and its safety were compared with those of oral clonidine, Catapres (Nippon Boehringer Ingelheim, Hyogo, Japan). One patch of M containing 6 mg of clonidine was applied on the right chest for 3 days or one tablet of Catapres (.075 mg) was given orally every 12 hours for 3 days in eight healthy subjects. The study was conducted by a crossover design with 14 to 16 days' interval between the cross-over. Blood and urine samples for clonidine concentration were obtained, and blood pressure (BP) was measured for a 168-hour period after application of M and for a 96-hour period after initiation of Catapres therapy. Plasma concentration of clonidine increased gradually after application of M and decreased gradually after removal, whereas this parameter increased rapidly during the absorption phase and decreased rapidly in the elimination phase after each dosage of Catapres. Elimination half-life of clonidine after removal of M was significantly greater than that after the final dosage of Catapres. No significant difference was observed in maximum plasma concentration or area under the plasma concentration-time curve between the two trials. The BP lowering effects of M and Catapres did not differ significantly. Adverse symptoms occurred more frequently during Catapres therapy than during treatment with M. Most of these symptoms were observed when plasma clonidine concentration was relatively higher in each trial. These results suggest that M is effective for the treatment of hypertension with a lower incidence of adverse symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
587,8022532,Platelet alpha 2-adrenergic receptor binding and the effects of d-amphetamine in boys with attention deficit hyperactivity disorder.,W O Shekim; D B Bylund; K Hodges; R Glaser; C Ray-Prenger; G Oetting,"Presynaptic inhibitory alpha-adrenergic receptors are involved in regulating the release of norepinephrine (NE) through a negative feedback mechanism mediated by NE. Increased alpha2-adrenergic receptor activity suggests decrease NE release and activity, while decreased alpha2-adrenergic activity suggests increase NE release and activity. A large body of evidence suggests the involvement of a disturbance in NE activity in the pathophysiology of attention deficit hyperactivity disorder (ADHD) in childhood. Platelet alpha2-adrenergic receptor binding was compared in 23 boys aged 7-12 with the diagnosis of ADHD and 11 normal controls. The ADHD boys tended to have lower levels of alpha2-binding than controls. The administration of d-amphetamine in a double-blind placebo-controlled crossover design did not have any effect on alpha2-receptor binding in ADHD boys. Nonresponders to d-amphetamine had the lowest alpha2-receptor binding compared to responders and controls. These findings suggest a normal alpha2-adrenergic activity in ADHD boys responders to d-amphetamine and a possible increase in NE release in ADHD boys nonresponders to d-amphetamine due to decreased alpha2-adrenergic receptors.",1994.0,0,0
588,8027413,Comparison of bupropion and trazodone for the treatment of major depression.,R H Weisler; J A Johnston; C G Lineberry; B Samara; R J Branconnier; A A Billow,"Bupropion and trazodone were compared in a two-center, double-blind clinical trial of outpatients with moderate to severe major depression. After a 1-week placebo lead-in, 124 patients were randomly assigned to receive either bupropion (N = 63) or trazodone (N = 61) for 6 weeks; data from 111 patients were used in the efficacy analysis. Dosing ranged from 225 to 450 mg/day for bupropion and 150 to 400 mg/day for trazodone. The overall efficacy for each of the two drugs was similar; although improvement in the trazodone treatment group was significantly greater on day 7 because of the effects on sleep. At the end of treatment, 58% of the bupropion-treated patients and 46% of the trazodone-treated patients were considered much or very much improved. Weight measurements at the time of discontinuation indicated a 2.5-lb mean weight loss for the bupropion treatment group and a 1.2-lb mean weight gain for the trazodone treatment group. The adverse experience profiles for bupropion and trazodone were consistent with their known pharmacologic profiles (i.e., activating versus sedating). Anorexia and anxiety were reported significantly more often for the bupropion treatment group, whereas somnolence, appetite increase, and edema were reported significantly more often for the trazodone treatment group.",1994.0,0,0
589,8033025,N of 1 study: methylphenidate in a patient with borderline personality disorder and attention deficit hyperactivity disorder.,R van Reekum; P S Links,,1994.0,0,0
590,8040490,Clinical and cognitive effects of methylphenidate on children with attention deficit disorder as a function of aggression/oppositionality and age.,R Klorman; J T Brumaghim; P A Fitzpatrick; A D Borgstedt; J Strauss,"Children diagnosed with attention deficit disorder (ADD; n = 44), ADD plus aggression/oppositionality (ADD/O; n = 34), and as not meeting ADD criteria (NC; n = 29) received methylphenidate and placebo for 21 consecutive days each. Parents and teachers rated all groups improved under medication, but teachers reported less improvement for NC than for ADD/O children. Methylphenidate and chronological age had generally similar effects in a Sternberg task: greater accuracy and speed (especially for nontargets at low memory loads), larger P3b waves of event-related potentials, more pronounced slowing of P3b latency by memory load, and a greater trend of earlier peaks for targets than for nontargets. Both methylphenidate and maturation promoted more efficient strategies involving differentiated evaluation of targets and nontargets. These results were comparable among ADD groups.",1994.0,0,1
591,8043227,"HIV seroconversion in intravenous drug users in San Francisco, 1985-1990.",A R Moss; K Vranizan; R Gorter; P Bacchetti; J Watters; D Osmond,"To examine the HIV seroconversion rate, risk factors for seroconversion, and changes in risk behavior over time in intravenous drug users (IVDU) in San Francisco, 1985-1990. Observational study. All methadone maintenance and 21-day methadone detoxification programs in San Francisco. A total of 2351 heterosexual IVDU, of whom 681 were seronegative at first visit and seen at least twice ('repeaters'). HIV seroconversion rates, risk factors for seroconversion, and changes in behavior. The HIV seroconversion rate in repeaters was 1.9% per person-year (ppy) of follow-up [2.1% in women versus 1.7% in men (not significant); 4% in African Americans versus 1% in whites (P = 0.006); 3.9% ppy in the first third of the study, 1.2% in the second (P = 0.007), and 1.9% in the last (not significant)]. Risk factors for seroconversion were five or more sexual partners per year [hazard ratio (HR) = 2.6; P = 0.02], use of shooting gallery ever (HR = 2.9; P = 0.02), and less than 1 year (lifetime) in methadone maintenance (HR = 2.7; P = 0.02). Self-reported intravenous cocaine use fell from 33 to 15% over 5 years, shooting gallery use fell from 19 to 6%, and the proportion with five or more sexual partners fell from 25 to 10%. Bleach use rose to 75% of needle-sharers. The 1985-1990 HIV seroconversion rate in IVDU (1.9% ppy) was comparable to that in San Francisco cohorts of homosexual men (1.4% ppy). A decline in HIV seroconversion coincided with changes in risk behavior. Stable attendance of methadone maintenance was highly protective: the seroconversion rate in subjects with 1 year or more in methadone was 12% ppy.",1994.0,0,0
592,8043521,Quantitative effects of typical and atypical neuroleptics on smooth pursuit eye tracking in schizophrenia.,R E Litman; D W Hommer; A Radant; T Clem; D Pickar,"Smooth pursuit eye movement (SPEM) gain, total saccades, and subtypes of saccades were quantified from the visual pursuit tracking of 26 fluphenazine-treated patients with schizophrenia and 42 normal controls. Tracking was repeated in 16 patients who underwent a placebo-controlled, double-blind crossover comparison of fluphenazine and clozapine. Fluphenazine-treated patients showed significant reduction in SPEM gain and significant increases in both total, intrusive, and anticipatory saccades and in saccadic amplitude, when compared to controls. Clozapine significantly reduced SPEM gain and significantly increased total and catch-up saccades, when compared to placebo or fluphenazine. High amplitude of intrusive saccades in drug-free patients predicted poor response to clozapine, suggesting that intact frontal cortical function may enable optimal clozapine response.",1994.0,0,0
593,8044265,Tics and dyskinesias associated with stimulant treatment in attention-deficit hyperactivity disorder.,P H Lipkin; I J Goldstein; A R Adesman,"To determine the incidence of tics or dyskinesias (T/D) and examine associated clinical factors in children treated with stimulant medications for attention-deficit hyperactivity disorder. Cross-sectional analysis of a clinic cohort with chart review. Hospital-based clinical service within a division of developmental and behavioral pediatrics. One hundred twenty-two children with attention-deficit hyperactivity disorder treated with stimulant medication. All children currently or recently treated were included. None. Determinations were made of medication used, medication dosage, presence or absence of T/D, time of T/D onset, and history and family history of T/D. Incidence of T/D was 9.0% of children or 8.2% of medication trials. One child (0.8%) had development of Tourette's syndrome. Age, medication, dosage, history of tics, or family history of tics was not related to onset of T/D. Approximately 9% of children with attention-deficit hyperactivity disorder treated with stimulant medication had development of T/D, predominantly transient in nature, with less than 1% having development of chronic tics or Tourette's syndrome. Personal or family tic history, medication selection, or dosage was not related to onset of T/D.",1994.0,0,1
594,8071267,Seizures associated with clozapine treatment in a state hospital.,W H Wilson; A M Claussen,"The seizures associated with the atypical antipsychotic medication clozapine represent a serious side effect of treatment. In premarketing studies, seizures occurred at a crude rate of 3.5%. It is possible that the rate and character of seizures would vary in clinical settings because of differences in patient populations or differences in the manner in which treatment is administered. We studied the seizures that occurred during clozapine treatment in a state psychiatric hospital. We reviewed the medical charts and pharmacy records of 100 sequential patients who were to start clozapine treatment. The review period covered 6 months pretreatment through 1 year of follow-up. The patients were 55 men and 45 women, aged 20 to 61 years. Ten (5 men, 5 women) had at least one seizure during clozapine treatment. Seizures occurred at all dose ranges (0-299 mg/day, N = 6; 300-599 mg/day, N = 2; 600-900 mg/day, N = 2). Of 12 patients with histories of previous seizures, 4 (33%) had a seizure while taking clozapine and anticonvulsants. Of 9 patients with histories of head trauma but no seizures, 1 (11%) had a seizure. Of 79 patients without seizure disorder or a history of head trauma, 5 (6.3%) had a seizure. Nine of the patients who had a seizure continued on clozapine treatment with temporary dose reduction and/or addition of an anticonvulsant, 2 having one additional seizure. Clozapine-associated seizures were more frequent in this group of state hospital patients than they were in premarketing studies. Clozapine-related seizures did not preclude successful treatment with clozapine.",1994.0,0,0
595,8079014,[Clonidine in the treatment of tobacco withdrawal. A comparison with nicotine chewing gum].,M Aparici; A L Fernández González; E Alegría,The objective of our work was to carry out a prospective study on the effectiveness of clonidine and nicotine gum in the treatment of tobacco withdrawal. Sixty smokers were randomly distributed in two groups and were included in a tobacco withdrawal program. One group received oral clonidine treatment while the other group was given nicotine gum. Adjuvant therapy such as group therapy or psychotherapy was not performed. At the end of one year there were no significant differences between the two groups with regards to the number of subjects who have continued to stop smoking. There were also no significant differences between the two groups with regards to the symptoms of tobacco abstinence. When we studied the relation between treatment fulfillment and tobacco withdrawal we observed that the clonidine treated group had a significantly greater number of success compared to the nicotine group (p < 0.01).,1994.0,0,0
596,8092504,Hemodynamic and analgesic profile after intrathecal clonidine in humans. A dose-response study.,K S Filos; L C Goudas; O Patroni; V Polyzou,"Epidural clonidine produces effective postoperative analgesia in humans. Observed side effects include hypotension, bradycardia, sedation, and dryness of the mouth. A recent clinical study demonstrated that 150 micrograms intrathecal clonidine administered postoperatively as the sole analgesic agent was effective but produced hypotension and sedation. Animal studies have provided evidence of a biphasic effect on blood pressure after intrathecal clonidine administration, but no data concerning this effect in humans currently exist. This study was performed to evaluate the dose-response hemodynamic and analgesic profiles of intrathecal clonidine administered after a standard surgical intervention, without perioperative administration of additional analgesics, local anesthetics, or tranquilizers. In a randomized prospective double-blind study, 30 women who underwent elective cesarean section during general anesthesia with thiopental, nitrous oxide, and halothane were studied. Forty-five minutes after tracheal extubation, a lumbar intrathecal puncture was performed, and the patients received 150 (group 1), 300 (group 2), or 450 (group 3) micrograms clonidine. Postoperative analgesia was assessed on a visual analog scale at rest and after deep cough at standard time points up to 24 h. At the same time points, blood pressure, heart rate, sedation, and respiratory rate also were recorded. Intrathecal clonidine decreased pain in all three groups both at rest and with coughing very shortly after injection, in a dose-dependent fashion. Clonidine 450 and 300 micrograms reduced pain scores significantly earlier (3rd and 6th min after intrathecal injection respectively), compared with 150 micrograms clonidine. Pain relief, defined as the time to first request for supplemental analgesic by patients, lasted 402 +/- 75 min in group 1, 570 +/- 76 min in group 2, and 864 +/- 80 min in group 3; significant differences among all groups; P < 0.01-0.001). Clonidine reduced mean arterial pressure compared with baseline only in group 1 (21 +/- 13%, P < 0.05). Delayed hypotension or bradycardia were not encountered after any of the three dose studies. Sedation was evident in all groups, but group 3 patients were significantly more sedated than group 1 and 2 patients. Respiratory rate and motor activity of the lower extremities were unaffected in all three groups (differences not significant). These results demonstrate dose-dependent analgesia after intrathecal clonidine at doses as great as 450 micrograms. The nearly immediate analgesic effect observed after intrathecal injection of 300 and 450 micrograms clonidine strongly argues for a spinal rather than a systemic site of action of this alpha 2-adrenergic agonist. After 300 and 450 micrograms intrathecal clonidine a relative hemodynamic stability is observed, suggesting a pressor effect at peripheral sites.",1994.0,0,0
597,8126317,Malleability of social impressions of hyperactive children.,D A Granger; C K Whalen; B Henker,"The role of adults' social cognitions in mediating judgments of hyperactive children's medication-related behavior change was explored. Two hundred eight-eight undergraduates observed two videotaped excerpts of a hyperactive ""target"" boy playing a group game with two peers. Each target was taking either methylphenidate (0.6 mg/kg) during both excerpts, placebo during both excerpts, methylphenidate first followed by placebo, or placebo first followed by methylphenidate. Adults' cumulative social evaluations of the child were assessed after they viewed both video segments. Results indicated that observers combined their perceptions of the two behavior samples into composite impressions using an equal-weight averaging algorithm. Even for children whose behavior improved, adults' ratings of undercontrolled behaviors continued to meet or, in some cases exceed, research cutoff scores used to identify hyperactive children. The findings suggest that the actual behaviors of children with attention-deficit hyperactivity disorder (ADHD) play a more influential role in shaping interpersonal impressions than do perceiver social-cognitive processes such as primacy, recency, or integration biases.",1993.0,0,0
598,8130041,Comparison of a bupivacaine-clonidine mixture with plain bupivacaine for caudal analgesia in children.,J J Lee; A P Rubin,"In a randomized, double-blind study in children undergoing elective orthopaedic surgery, we have assessed the clinical value of combining clonidine with bupivacaine for caudal analgesia. Forty-six children, aged 1-10 yr, were allocated randomly to two equal groups to receive 0.25% bupivacaine 1 ml kg-1 combined with either normal saline 1 ml (group A) or clonidine 2 micrograms kg-1 in normal saline 1 ml (group B). Mean (SD) duration of caudal analgesia for groups A and B were 5.2 (1.2) h and 9.8 (2.1) h, respectively (P < 0.0001). Group B required significantly less supplementary analgesia after operation (P < 0.01). There was no significant difference in the incidence of side effects between the two groups. The longer duration of sedation in group B (9.1 (2.5) h) resulted partly from the sedative effect of clonidine and partly from the longer duration of analgesia provided by clonidine. We conclude that, when added to bupivacaine, clonidine improves the efficacy of caudal analgesia in children.",1994.0,0,0
599,8132186,Clozapine treatment of outpatients with schizophrenia: outcome and long-term response patterns.,A Breier; R W Buchanan; D Irish; W T Carpenter,"The purpose of the study was to examine the effects of clozapine in treating moderately ill schizophrenic outpatients and to determine the length of medication trial needed to identify responders and nonresponders. Rates of clinical responses, relapses and hospitalizations, and levels of symptomatology and functioning were assessed for 30 chronic schizophrenic outpatients who received clozapine for one year. For some patients, data on relapse and hospitalization during treatment were compared with data from the year before treatment. Eighteen of the 30 patients met criteria for sustained response; 17 of the responders were identified within the first four months of treatment. Patients experienced significantly fewer relapses and hospitalizations during treatment than in the previous year. Improvement in positive symptoms, general symptomatology, and levels of functioning reached a plateau during the first six months of treatment and remained at that level during the second six months. Negative symptoms and quality of life showed nonsignificant improvements at 12 months. Results support the use of clozapine in treating chronic, residually symptomatic schizophrenic outpatients. A four-month clozapine trial may be adequate to detect clinical responders in this population.",2001.0,0,0
600,8138866,"Methods of evaluating methylphenidate in children with attention deficit hyperactivity disorder: acceptability, satisfaction, and compliance.",C Johnston; S Fine,"Compared two methods of evaluating methylphenidate (MPH) on measures of parental acceptance, satisfaction, and compliance with the treatment. Twenty-four 6- to 10-year-old children with Attention Deficit Hyperactivity Disorder (ADHD) were randomly assigned to either a blind, placebo-controlled medication trial (MT) or to a typical clinical procedures (TCP) evaluation that was nonblind and without a placebo control. Ratings of satisfaction were significantly higher in the MT condition than in the TCP condition; however, all parents became more accepting of MPH after participating in an evaluation. Both during the evaluation and at 6-week and 3-month follow-ups, approximately 20% of cases were not complying with treatment. However, rates of compliance did not differ between the MT and TCP conditions.",1993.0,0,1
601,8164820,Attention deficit in Alzheimer's disease is not simulated by an anticholinergic/antihistaminergic drug and is distinct from deficits in healthy aging.,B S Oken; S S Kishiyama; J A Kaye; D B Howieson,"To evaluate attention deficit in Alzheimer's disease (AD) and its relationship to attention deficits associated with aging and with medications altering alertness. Ten patients with probable AD, 10 healthy old controls, and 15 young controls performed a covert orienting of spatial attention task. Young controls performed the task an additional time after ingestion of diphenhydramine 1 mg/kg. Reaction times were obtained following valid, neutral, and invalid cues. In all groups, the reaction times were shortest for the validly cued stimuli and longest for the invalidly cued stimuli. Additionally, the AD patients performed disproportionately worse following the invalid cue than did the control groups. Young controls given diphenhydramine had decreased subjective alertness, performed worse than they did before drug but better than the old controls or AD patients, and had no disproportionate impairment with the invalid cue. AD patients have disproportionate problems shifting spatial attention compared with age-matched controls. Impaired attentional performance in AD cannot be simulated in young subjects by ingestion of a combined antihistamine/anticholinergic agent at a dose sufficient to produce significant changes in alertness.",1994.0,0,0
602,8188554,The utility of curriculum-based measurement for evaluating the effects of methylphenidate on academic performance.,G Stoner; S P Carey; M J Ikeda; M R Shinn,"Two case studies were conducted to investigate the utility of curriculum-based measurement of math and reading for evaluating the effects of methylphenidate on the academic performance of 2 students diagnosed with attention deficit hyperactivity disorder. Following baseline measurement, double-blind placebo-controlled procedures were employed to evaluate each student's response to three levels (5 mg, 10 mg, and 15 mg) of the medication. Results of the first study suggest that the curriculum-based measures were sensitive indicators of the student's response to medication. This finding was replicated in the second study. In the second study, when the student's follow-up dose of medication was based on trial-phase data, follow-up performance was improved compared to baseline performance. These case studies suggest that further research is warranted on the utility of curriculum-based measurements for monitoring and evaluating stimulant medication interventions with children with this disorder.",1994.0,0,0
603,8193426,Oral antihypertensives for hypertensive urgencies.,M A Gales,"To review the data describing the use of oral antihypertensive agents in the treatment of hypertensive urgencies (HU). A MEDLINE search of the English-language literature and fan searches of papers evaluating oral antihypertensives in HUs and emergencies were conducted. Controlled and uncontrolled studies in humans are reviewed. Emphasis was placed on recent trials evaluating individual agents and comparative trials. Comparative trials have demonstrated that four currently available oral agents can lower blood pressure rapidly and predictably. Nifedipine, the most extensively studied, and clonidine have served traditionally as the oral agents of choice for the treatment of HUs. All the agents can lower blood pressure effectively within the first few hours after dosing, but their use also has been associated with adverse effects. Nifedipine and captopril are the two agents with the most rapid onset, within 0.5-1 hour, and may treat hypertensive emergencies as well as urgencies. Clonidine and labetalol have maximal blood pressure lowering effects at 2-4 hours. Captopril, clonidine, labetalol, and nifedipine are all effective agents for the treatment of HUs. Agent selection should be based on the perceived need for urgent blood pressure control, the cause of HU, and concomitant conditions. A definite benefit from acute blood pressure lowering in HUs has yet to be demonstrated, especially in asymptomatic patients. More controlled trials with less aggressive dosing regimens and placebo controls need to be performed to assess the most appropriate treatment for HUs with the fewest adverse effects.",1994.0,0,0
604,8205301,Effect of isradipine on cyclosporin A-related hypertension.,M A van den Dorpel; R Zietse; J N Ijzermans; M A Schalekamp; W Weimar,"There is evidence that calcium antagonists may have a beneficial effect on cyclosporin A (CyA)-induced hypertension after organ transplantation. In a double-blind controlled trial, 50 consecutive non-diabetic first kidney-transplant recipients were randomized to receive either isradipine, a dihydropyridine calcium antagonist, or placebo. There were no significant differences in age, weight, gender, warm and cold ischaemic periods, and original renal disease between treatment groups. Treatment was started intravenously 2 h before the transplantation procedure and was subsequently continued orally for 3 months. The immunosuppressive treatment included oral CyA from day 5 after a short course of anti-T-lymphocyte immunoglobulins. Hypertension was treated with oral labetolol in combination with guanfacine if necessary. Antihypertensive medication was prescribed significantly more often (16 vs 7 patients; p < 0.05) in the placebo group. Standing systolic blood pressure was significantly lower in the isradipine group. The standing diastolic and both systolic and diastolic sitting blood pressures were similar in both groups. After 3 months, patients' mean serum creatinine was significantly lower with isradipine than with placebo (142.0 +/- 11.9 vs 164.0 +/- 10.8 mumol/l; p < 0.05). With isradipine, a significantly higher dose of CyA was needed to achieve adequate plasma levels (8.0 +/- 0.5 vs 6.2 +/- 0.5 mg/kg/day; p < 0.01). It can be concluded that isradipine is an effective antihypertensive agent after kidney transplantation and may have an influence on CyA metabolism. Furthermore, isradipine appears to ameliorate CyA-induced nephropathy.",1994.0,0,0
605,8249952,Effects of methylphenidate on sleep in children with attention-deficient hyperactivity disorder. An activity monitor study.,E Tirosh; A Sadeh; R Munvez; P Lavie,"To assess the effects of methylphenidate hydrochloride on sleep patterns in children diagnosed as having attention-deficit hyperactivity disorder (ADHD). A double-blind, controlled drug-placebo cross-over design. Home. Ten children (aged 6 years 9 months to 12 years & months) diagnosed as having ADHD were consecutively recruited and compared with age- and sex-matched normal controls. Methylphenidate hydrochloride (0.3 to 0.4 mg/kg) or placebo was administered at 7:30 AM. Each child underwent activity monitoring at home during 6 days of no treatment (baseline) followed by placebo and methylphenidate treatment. The results of the three trial stages, as well as those of the 20 age- and sex-matched normal controls, were compared. A shorter total sleep duration was evident during the methylphenidate treatment compared with that of baseline and placebo treatment. The amount of quiet sleep was lower (however, not significantly) among the study group compared with controls, whereas no such difference was noted during methylphenidate treatment. Night-to-night sleep pattern stability was found. No other differences were found either between children with ADHD and controls or between on and off stages of methylphenidate treatment. These results support the notion that ADHD is a centrally generated disorder attributable to hypoarousal, which subsequently stimulates motor overactivity. Methylphenidate does not appear to affect sleep patterns adversely and possibly normalizes them in patients with ADHD.",1993.0,0,1
606,8251275,Comparison of the analgesic effects of intrathecal clonidine and intrathecal morphine after spinal anaesthesia in patients undergoing total hip replacement.,D J Fogarty; U A Carabine; K R Milligan,"We have studied the anaesthetic and analgesic properties of intrathecal clonidine and intrathecal morphine in patients undergoing total hip replacement under spinal anaesthesia. After routine spinal anaesthesia with 0.5% plain bupivacaine 2.75 ml, patients were allocated randomly to receive intrathecal clonidine, morphine or saline (control) as adjuvant to the bupivacaine. Postoperative analgesic effects were measured by consumption of morphine via patient-controlled analgesia and visual analogue pain scores. Both intrathecal clonidine and intrathecal morphine prolonged the time to first analgesia compared with saline (mean 278 (SD 93.2) min, 498 (282.4) min and 54 (61.9) min, respectively) (P < 0.001). Total morphine consumption on the first night after operation was significantly less in the intrathecal morphine group. There were no differences between the clonidine and the control group. Intrathecal clonidine prolonged the duration of spinal analgesia, but was markedly inferior to the intrathecal morphine in providing subsequent postoperative analgesia.",1993.0,0,0
607,8251276,"Single-dose, randomized, double-blind, double-dummy cross-over comparison of extradural and i.v. clonidine in chronic pain.",D Carroll; A Jadad; V King; P Wiffen; C Glynn; H McQuay,"We studied 10 patients with chronic back pain who had claimed benefit with a previous extradural dose of clonidine 150 micrograms combined with local anaesthetic. We compared a single dose of clonidine 150 micrograms given by either the extradural or i.v. route in a double-blind, randomized, double-dummy and cross-over fashion, with 80% power to detect a difference in the analgesic effect of the two routes. Pain intensity, pain relief, adverse effects, mood, sedation and vital signs were assessed by a nurse observer. I.v. clonidine produced significantly (P < 0.04) greater analgesia than extradural clonidine in one of the five analgesic outcome measures. Clonidine given by either route produced statistically significant sedation and significant decreases in arterial pressure and heart rate. In this study, extradural clonidine had no significant clinical advantages compared with i.v. clonidine; clonidine 150 micrograms by either route produced a high incidence of adverse effects.",1993.0,0,0
608,8251696,Pharmacoepidemiology of clozapine in 202 inpatients with schizophrenia.,J M Zito; J Volavka; T J Craig; P Czobor; S Banks; J Vitrai,"To evaluate clozapine in a field trial for hospitalized patients with treatment-resistant schizophrenia. The setting consisted of a large, state-operated, public psychiatric system. The protocol called for the treating psychiatrist to provide symptom- and adverse-effect ratings at four times following the start of drug therapy. The outcome criteria included the Sandoz study outcome measure of symptom improvement as well as discharge status for one year of follow-up. To assess the validity of the ratings, several measures of internal consistency were determined. Clozapine therapy was started in 227 patients, and symptom data are available for 202. Overall, 33 percent (n = 66) of the patients were improved at the end of one year of treatment; 12 percent (n = 24) maintained symptom improvement at all three evaluation times. Modest, statistically significant improvement after 12 weeks compared with baseline Brief Psychiatric Rating Scale (BPRS) total scores was observed for the patients continuing medication (n = 152); the emergence of a previously unimproved group (n = 26) explains this modest improvement. However, in the analysis of all patients (n = 202), (including dropouts), there was no significant symptom improvement after 12 weeks. Lower baseline BPRS scores predicted significant symptom improvement after 12 weeks of treatment. Among those medicated for one year, the pattern of symptom improvement showed that the probability of late improvement was 0.26 for those previously unimproved, and the probability of a 12-week responder losing improvement was 0.23, resulting in a net group gain of 3 cases in 100. By the end of one year, 8 percent (n = 17) of the cohort was discharged, and 3 percent (n = 7) was transferred to another facility while continuing to receive clozapine. Of the 227 original patients started on clozapine therapy, medication was discontinued for adverse effects in 11 percent (n = 25): white blood cell count (WBC) decrease (but no agranulocytosis) in 5 percent (n = 12), seizures in 1 percent (n = 3), one patient with seizures and decreased WBC count, and other events (e.g., cardiovascular changes, fever, or possible neuroleptic malignant syndrome) in 4 percent (n = 9). Patient refusal was reported for 6 percent (n = 13) of those starting treatment. Although only 19 percent of the patients exhibited improvement at 6 weeks, the response rate at 12 weeks (29 percent) for this naturalistic study cohort was similar to that in the major, double-blind, six-week, controlled, clinical trial of clozapine. The impersistence of response as symptoms were followed for up to one year is a finding that deserves rigorous evaluation.",1993.0,0,0
609,8260445,Changes in psychopathology and dyskinesia after neuroleptic withdrawal in a double-blind design.,L Dixon; G Thaker; R Conley; D Ross; N Cascella; C Tamminga,"The goal of this study was to assess the time course of change in psychopathology and dyskinesia after neuroleptic withdrawal. Fifteen DSM-III schizophrenic patients were abruptly withdrawn in a double-blind fashion from stable haloperidol treatment. Weekly ratings of dyskinesia and psychopathology were performed for 4 weeks post-withdrawal. There was an overall increase in dyskinesia ratings over the 4-week period (p < 0.05) beginning in week 2, with dyskinetic movements of the fingers showing the most significant increase (p < 0.001). There were no overall changes in psychopathology, though the group appeared to be bimodal with 6 of the 15 patients showing a significant relapse in psychotic symptoms. Neither baseline TD nor psychotic relapse significantly interacted with change in TD over time. These schizophrenic patients showed an increase in global dyskinesia rating early within four weeks of neuroleptic withdrawal. This time course did not appear to be associated with reemergence of psychopathology which occurred later. A significant minority of patients relapsed within this time period. This suggests the relative safety of brief periods of neuroleptic withdrawal for carefully selected patients in a controlled setting with specific goals (e.g., for evaluation or in preparation for clozapine) and the need to further understand who is at risk for rapid relapse.",1993.0,0,0
610,8260563,Changes in event-related potentials with stimulant medication in children with attention deficit hyperactivity disorder.,M J Taylor; J G Voros; W J Logan; M A Malone,"Thirty-two children with attention deficit hyperactivity disorder (ADHD) undergoing a 4 week double-blind medication assessment (methylphenidate) and 32 normal controls were studied using event-related potentials (ERPs). The ERPs were recorded from 13 active electrodes during a visual feature detection task. Significant age effects were found in N2, P3a and P3b latencies, that did not interact with group. The P3a and P3b latencies were significantly longer in the ADHD children on baseline testing; there were no latency differences between the groups of children when the normal controls were compared with the ADHD children on their optimal drug dosage (as determined by extensive behavioural and cognitive assessments). There were no significant distributional effects either between groups, or with the ADHD children as a function of medication; there were also no significant differences in reaction time measures. Thus, only the ERPs reflected slowed processing in the ADHD children that normalized on appropriate medication.",1993.0,0,0
611,8267190,Epidural clonidine treatment for refractory reflex sympathetic dystrophy.,R L Rauck; J C Eisenach; K Jackson; L D Young; J Southern,"Intraspinally administered alpha 2-adrenergic agonists may relieve pain in sympathetically maintained pain (SMP) syndromes, such as reflex sympathetically dystrophy (RSD), by spinal, peripheral, and central nervous system actions. This study examined analgesic efficacy and side effects of epidurally administered clonidine in patients with severe, refractory RSD. Twenty-six patients with severe chronic pain consistent with RSD were studied in a randomized, blinded, placebo-controlled design. Cervical or lumbar epidural catheters were inserted for patients with upper or lower extremity RSD, respectively, and patients received, in random order on three consecutive days, epidural injection of clonidine, 300 or 700 micrograms, or placebo. Pain (by visual analog score (VAS) and McGill Pain Questionnaire), sedation, blood pressure, and heart rate were monitored at specified intervals for 6 h after injection. Patients who responded to clonidine, but not placebo, then entered a trial of open-label, continuous epidural infusion of clonidine (10-50 micrograms/h). Clonidine, but not placebo, caused pain relief, sedation, and decreased blood pressure and heart rate after bolus epidural injection. The smaller clonidine dose (300 micrograms), produced pain relief and decreases in blood pressure and heart rate similar to those of the 700 micrograms dose, but with less sedation. Epidural clonidine was infused for a mean of 43 days in 19 patients at a mean rate of 32 micrograms/h for sustained analgesia. Transdermal clonidine has been demonstrated to produce analgesia in the area surrounding its application site in patients with SMP. The current study indicates that extensive analgesia may be obtained by epidural administration. Sedation and hypotension may limit bolus epidural clonidine administration for RSD. The role for chronic epidural infusion of clonidine has not yet been established.",1993.0,0,0
612,8270972,Transdermal clonidine for ameliorating tamoxifen-induced hot flashes.,R M Goldberg; C L Loprinzi; J R O'Fallon; M H Veeder; A W Miser; J A Mailliard; J C Michalak; A M Dose; K M Rowland; N L Burnham,"To determine the efficacy of transdermal clonidine for alleviating tamoxifen-induced hot flashes in women with a history of breast cancer. A randomized, double-blind, crossover design was used in this prospective study. Women with a history of breast cancer who were receiving tamoxifen and suffering from hot flashes were potentially eligible for this protocol study. Clonidine did reduce hot-flash frequency to a degree that was statistically impressive (P < .0001), but clinically moderate (20% reduction from baseline). It also decreased hot-flash severity (P = .02, 10% reduction from baseline). Clonidine was related to increased mouth dryness (P < .001), constipation (P < .02), itchiness under the patch (P < .01), and drowsiness (P < .05). Better means are needed to alleviate hot flashes among patients in whom estrogen therapy is contraindicated.",2001.0,0,0
613,8290087,"Epilepsy, psychosis, and schizophrenia: clinical and neuropathologic correlations.",C J Bruton; J R Stevens; C D Frith,"This study examines the relationship between epilepsy and psychosis. It compares clinical, EEG, and neuropathologic data from a group of subjects who had both epilepsy and psychosis with similar information from another group of patients who had epilepsy but no evidence of psychotic illness. We examined, blind to clinical diagnosis, gross and microscopic material from whole-brain specimens from 10 patients diagnosed with epilepsy plus schizophrenia-like psychosis, nine subjects diagnosed with epilepsy plus ""epileptic psychosis,"" and 36 individuals with epilepsy (21 from an epileptic colony and 15 from the community at large) who had no history of psychosis (n = 10 + 9 + 21 + 15 = 55). We abstracted case histories without knowledge of pathologic findings. Epileptic colony patients had an earlier age at onset of seizures, while epileptic colony and epileptic psychosis patients had more frequent seizures. Epileptic individuals in the community died at a younger age than did epileptic patients in long-stay hospital care. Psychotic epileptic patients had larger cerebral ventricles, excess periventricular gliosis, and more focal cerebral damage compared with epileptic patients who had no psychotic illness. Epileptic patients with schizophrenia-like psychosis were distinguished from all other groups by a significant excess of pinpoint perivascular white-matter softenings. We found that mesial temporal sclerosis and temporal lobe epilepsy occurred with equal frequency in the psychotic and nonpsychotic groups; generalized seizures occurred more frequently in the psychotic epileptics and the epileptic colony epileptics than in the community epileptic controls.",1994.0,0,0
614,8290095,Long-term botulinum toxin treatment of focal hand dystonia.,B I Karp; R A Cole; L G Cohen; S Grill; J S Lou; M Hallett,"We treated focal hand dystonia in 53 patients with botulinum toxin injections for up to 6 years. Eighty-one percent of the patients improved with at least one injection session. Sixty-five percent of the injections produced transient weakness. We followed 37 of the patients for at least 2 years from the start of treatment, 24 of whom discontinued treatment because of inadequate response, loss of response, inaccessibility of a treatment provider, or the expense of the toxin. Women, who had a greater extent and longer duration of benefit than men, were more likely to continue treatment. The mean interval between injection sessions was 6 months. In most patients, we injected the toxin into the same combination of muscles at each session. The dose of toxin generally fluctuated within a range of 20 units. Side effects were mild and transient and unrelated to the long-term use of botulinum toxin. Botulinum toxin injection is safe and effective for the long-term management of focal hand dystonia.",1994.0,0,0
615,8308937,Methadone combined with clonidine versus clonidine alone in opiate detoxification.,R S Wilson; W S DiGeorge,"The availability and use of a methadone/clonidine combination versus clonidine alone in opiate detoxification were studied. In Phase I of the study, a sequential combination of methadone followed by clonidine was utilized in those patients presenting with a primary diagnosis of opiate dependence. During the Phase II of the study, only clonidine was available. Medications were administered only if the history and clinical findings indicated impending or acute opiate withdrawal syndrome. Overall, there was no difference between the Phase I and Phase II groups when the number of opiate dependent admissions, patients completing detoxification, and the patients completing a follow-up rehabilitation program were compared. However, the patients in Phase I whose clinical symptomatology warranted the use of methadone were more likely to complete the detoxification program when compared to the patients in Phase II who received clonidine only. There was no difference between the two groups in completion of a follow-up rehabilitation. Detoxification with clonidine alone was more likely to be successful if the patient has had prior detoxification experience with methadone or if there was a secondary dependence of alcohol, sedative, or tranquilizer present coexisting with the primary opiate dependence diagnosis.",1993.0,0,0
616,8308973,Transdermal clonidine for ameliorating post-orchiectomy hot flashes.,C L Loprinzi; R M Goldberg; J R O'Fallon; S K Quella; A W Miser; L A Mynderse; L D Brown; L K Tschetter; M B Wilwerding; M Dose,"To determine the efficacy of transdermal clonidine for alleviating post-orchiectomy hot flashes, a randomized, double-blind, crossover clinical trial was designed including 70 men with a history of prostate cancer who had undergone a medical or surgical orchiectomy and were suffering from hot flashes. The results of this study demonstrated that clonidine did not significantly decrease hot flash frequency or severity. Future research is necessary to find effective means of alleviating hot flashes in post-orchiectomy patients.",1994.0,0,0
617,8524989,Spatial orienting and focused attention in attention deficit hyperactivity disorder.,G P Novak; M Solanto; H Abikoff,"Seventeen children with attention deficit disorder (ADHD) and 10 normal controls performed two tasks while event-related potentials were recorded. ADHD subjects took part in two more sessions under methylphenidate (MP) or placebo. In the spatial orienting task, invalidly cued targets elicited a longer reaction time (RT) and a P3 that was longer in latency and greater in amplitude than did validly cued targets. Performance was similar for both groups, but the early portion of P3 (300-400 ms) was lower in amplitude for invalidly cued targets in ADHD subjects. MP increased accuracy without affecting RT and shortened P3 peak latency and increased the amplitude of its early portion. In the focused attention task, accuracy was greater for controls and MP, but there were no RT differences. Attended stimuli elicited greater amplitude P1, N1, and P3 than did nonattended stimuli, but these measures were unaffected by diagnosis or medication.",1995.0,0,0
618,8529164,One vs. two doses of 1.0% apraclonidine for prophylaxis of intraocular pressure spike after argon laser trabeculoplasty.,C M Birt; D H Shin; S Y Reed; B McCarty; C Kim; R E Frenkel,,1995.0,0,0
619,8560050,[Comparative study of clonidine and lidocaine on the attenuation of the intraocular pressure increase associated with laryngoscopy and endotracheal intubation].,M Núñez; A Figueira; V Guerra; G Baños; M L Alvarez; M Rodríguez,"To verify and compare the efficacy of clonidine and lidocaine for attenuating the ocular hypertensive response generated by manipulation of the laryngoscope and endotracheal intubation (EIT). In this prospective double blind study 45 patients undergoing non-ocular surgery were divided into 3 groups according to pretreatment protocol: A, approximately 3 micrograms/kg clonidine orally 90-120 min before surgery; B, 1.5 mg/kg intravenous lidocaine 1 min before EIT and C, control group. On all patients we recorded intraocular pressure (IOP), mean arterial pressure and heart rate at the following times: basal, just before EIT, immediately after EIT, 5 minutes later and 10 minutes later. The patients pretreated with clonidine had significantly lower IOP levels than did the control group at all measurements times; patients pretreated with lidocaine had lower IOP after induction and after intubation. IOP was significantly lower in patients who received lidocaine than in control group patients after EIT, although IOP levels with lidocaine were higher than with clonidine. Pretreatment with oral clonidine is an effective method for preventing increases in IOP after EIT, is more effective than pretreatment with lidocaine, and should therefore be used for that end. Intravenous lidocaine represents a valid alternative in emergency cases when the approximate wait time of 2 hours is contraindicated.",1995.0,0,0
620,8561324,Postoperative alpha 2-adrenergic stimulation attenuates protein catabolism.,N Mertes; C Goeters; M Kuhmann; J F Zander,"The metabolic effects of continuous intravenous (IV) application of the alpha 2 agonist clonidine were evaluated by assessment of nitrogen economy and postaggression endocrine patterns. Twenty-four patients undergoing abdominothoracic esophageal cancer resection were studied. Thirteen of these patients with alcohol abuse were treated postoperatively with IV clonidine for prevention of alcohol withdrawal syndrome. Eleven patients who were not treated with clonidine served as controls. All patients were treated in a standardized manner in regard to surgical technique, balanced anesthesia, and postoperative intensive care treatment, including thoracic epidural analgesia with bupivacaine and fentanyl. Isonitrogenous and isocaloric nutrition was comparable in all patients. A significantly improved cumulated 6-day nitrogen balance was found in clonidine-treated patients (-1.5 +/- 4.9 g nitrogen) compared to the control group (-17.6 +/- 4.2 g nitrogen) (P < 0.05). The main reason for improved nitrogen economy may be clonidine-induced growth hormone (GH) release. The pattern of insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein 3 (IGFBP-3) concentrations could support this hypothesis.",1996.0,0,0
621,8565000,The cognitive and psychomotor effects of opioid drugs in cancer pain management.,W M O'Neill,"The time has come to evaluate critically our practice of cancer pain management and the assumptions on which it is based. We owe it to our patients to maximize the quality of their lives and to provide evidence for them that is based on a scientific approach rather than anecdotal experience. From the information available, opioids do have effects on cognitive and psychomotor function, and although many of these effects diminish once the patient is on a stable dose, the evidence suggests that baseline pretreatment levels are not achieved. In addition, the relationship between measurable effects and the performance of everyday tasks such as driving is unclear. The challenge we now face is to continue the improvements in cancer pain control achieved over the last 25 years. The management of the central adverse effects of opioids must be focused on accurate assessment and careful titration of opioids against pain. Adjuvant analgesic drugs and non-drug measures should be used whenever possible, and drugs should be chosen that will not contribute to existing difficulties. The appropriate use of psychostimulants has yet to be established as has the relative benefit of one opioid over another in cancer pain.",1994.0,0,0
622,8610833,Different side effect profiles of risperidone and clozapine in 20 outpatients with schizophrenia or schizoaffective disorder: a pilot study.,D G Daniel; T E Goldberg; D R Weinberger; J E Kleinman; D Pickar; L J Lubick; T S Williams,"The purpose of this study was to compare the side effect +profiles of clozapine and risperidone. The subjects were 20 outpatients with schizophrenia or schizoaffective disorder who were clinically stable on a regimen of clozapine at the time of screening. They underwent a randomized-order crossover comparison of 6 weeks of risperidone treatment and 6 weeks of clozapine treatment. Clinical and neurocognitive variables were assessed by raters blind to medication status, and severity of side effects was determined from patients' self-reports. Side effect measures, but not clinical ratings, were significantly different after 6 weeks of treatment with the two drugs. Patients required more benztropine for motor effects and complained of more insomnia with risperidone and more sedation with clozapine. Body weight was higher at the end of clozapine treatment than at the end of risperidone treatment. In this exploratory study, the side effect profiles of clozapine and risperidone were consistent with the different pharmacodynamic profiles of the two drugs.",1996.0,0,0
623,8624187,A prospective 4-year follow-up study of attention-deficit hyperactivity and related disorders.,J Biederman; S Faraone; S Milberger; J Guite; E Mick; L Chen; D Mennin; A Marrs; C Ouellette; P Moore; T Spencer; D Norman; T Wilens; I Kraus; J Perrin,"Previous cross-sectional data showed that children and adolescents with attention-deficit hyperactivity disorder (ADHD) are at increased risk of comorbid conduct, mood, and anxiety disorders as well as impairments in cognitive, social, family, and school functioning. However, longitudinal data were needed to confirm these initial impressions. Using DSM-III-R structured diagnostic interviews and raters blinded as to diagnosis, we reexamined psychiatric diagnoses at 1- and 4-year follow-ups in children with ADHD and controls. In addition, subjects were evaluated for cognitive, achievement, social, school and family functioning. Analyses of follow-up findings revealed significant differences between children with ADHD and controls in rates of behavioral, mood, and anxiety disorders, with these disorders increasing markedly from baseline to follow-up assessments. In addition, children with ADHD had significantly more impaired cognitive, family, school, and psychosocial functioning than did controls. Baseline diagnosis of conduct disorder predicted major depression and bipolar disorder at follow-up, and anxiety disorders at baseline predicted anxiety disorders at follow-up. These results confirm and extend previous retrospective results indicating that children with ADHD are at high risk of developing a wide range of impairments affecting multiple domains of psychopathology such as cognition, interpersonal, school, and family functioning. These findings provide further support for the value of considering psychiatric comorbidity in both clinical assessment and research protocols involving children with ADHD.",1996.0,0,0
624,8625628,"Therapy of alcohol withdrawal syndrome in intensive care unit patients following trauma: results of a prospective, randomized trial.",C D Spies; N Dubisz; T Neumann; S Blum; C Müller; H Rommelspacher; G Brummer; M Specht; C Sanft; L Hannemann; H W Striebel; W Schaffartzik,"To assess the effect of three different alcohol withdrawal therapy regimens in traumatized chronic alcoholic patients with respect to the duration of mechanical ventilation and the frequency of pneumonia and cardiac disorders during their intensive care unit (ICU) stay. A prospective, randomized, blinded, controlled clinical trial. A university hospital ICU. Multiple-injured alcohol-dependent patients (n=180) transferred to the ICU after admission to the emergency room and operative management. A total of 180 patients were included in the study; however, 21 patients were excluded from the study after assignment. Patients who developed actual alcohol withdrawal syndrome were randomized to one of the following treatment regimens: flunitrazepam/clonidine (n=54); chlormethiazole/haloperidol (n=50); or flunitrazepam/haloperidol (n=55). The need for administration of medication was determined, using a validated measure of the severity of alcohol withdrawal (Revised Clinical Institute Withdrawal Assessment for Alcohol Scale). The duration of mechanical ventilation and major intercurrent complications, such as pneumonia, sepsis, cardiac disorders, bleeding disorders, and death, were documented. Patients did not differ significantly between groups regarding age, Revised Trauma and Injury Severity Score and Acute Physiology and Chronic Health Evaluation II score on admission. In all except four patients in the flunitrazepam/clonidine group, who continued to hallucinate, the Revised Clinical Institute Withdrawal Assessment for Alcohol Scale decreased to <20 after initiation of therapy. ICU stay did not significantly differ between groups (p=.1669). However, mechanical ventilation was significantly prolonged in the chlormethiazole/haloperidol group (p=.0315) due to an increased frequency of pneumonia (p=.0414). Cardiac complications were significantly (p=.0047) increased in the flunitrazepam/clonidine group. There was some advantage in the flunitrazepam/clonidine regimen with respect to pneumonia and the necessity for mechanical ventilation. However, four (7%) patients had to be excluded from the study due to ongoing hallucinations during therapy. Also, cardiac complications were increased in this group. Thus, flunitrazepam/haloperidol should be preferred in patients with cardiac or pulmonary risk. Further studies are required to determine which therapy should be considered.",1996.0,0,0
625,8633697,Differential effect of clozapine on weight: a controlled study.,J R Bustillo; R W Buchanan; D Irish; A Breier,This study examined whether clozapine induces more weight gain than haloperidol and whether weight gain is related to clinical improvement. The weight and symptoms of 39 outpatients with schizophrenia who were randomly assigned to double-blind treatment with either clozapine or haloperidol were assessed. The weight and symptoms of 33 of the patients who chose to take clozapine during a 1-year follow-up after the study ended were also assessed. The patients treated with clozapine gained significantly more weight over baseline (7%) than the haloperidol-treated patients (1%). Weight gain was not significantly correlated with improvements in either positive or negative symptoms. Fifty-eight percent of the patients followed for 1 year gained at least 10% over their baseline weight. Weight gain is an important side effect of clozapine and is unrelated to the drug's differential antipsychotic efficacy.,1996.0,0,0
626,8672322,Prophylaxis of alcohol withdrawal syndrome in alcohol-dependent patients admitted to the intensive care unit after tumour resection.,C D Spies; N Dubisz; W Funk; S Blum; C Müller; H Rommelspacher; G Brummer; M Specht; L Hannemann; H W Striebel,"Prophylaxis of alcohol withdrawal syndrome (AWS) in alcohol-dependent patients shortens the duration of stay in the intensive care unit (ICU). The objective of this study was to assess the effect of four different prophylactic regimens on the duration of ICU stay, prevention of AWS and rate of major intercurrent complications in alcohol-dependent patients admitted to the ICU after tumour resection. A total of 197 alcohol-dependent patients, diagnosed by the Diagnostic and Statistical Manual of Mental Disorders (third revised edition) with a daily ethanol intake of 60 g, were allocated randomly to one of the following regimens which were commenced on admission to the ICU: flunitrazepam-clonidine, chlormethiazole-haloperidol, flunitrazepam-haloperidol or ethanol. The duration of ICU stay, prevention of AWS, incidence of tracheobronchitis and major intercurrent complications such as pneumonia, sepsis, cardiac disorders, bleeding disorders and death were documented. On admission, patients did not differ significantly in age, APACHE II and multiple organ failure scores. ICU stay, incidence of AWS, severity of AWS (revised clinical institute withdrawal assessment for alcohol scale > 20) and major intercurrent complication rate did not differ significantly between groups. Although there was no advantage in any of the four regimens with respect to the primary outcome measures, pulmonary and cardiac patients were not included in the study. Patients in the chlormethiazole-haloperidol group had a significantly increased incidence of tracheobronchitis (P = 0.0023), probably because of an increased incidence of hypersecretion.",1995.0,0,0
627,8678284,[Patient-controlled analgesia with clonidine and piritramide].,R Sümpelmann; H Büsing; D Schröder; M Rekersbrink; S Krohn; J M Strauss,"Following parenteral administration, clonidine has analgesic effects at both cerebral and spinal levels. Patient-controlled analgesia (PCA) makes it possible to determine equipotent dosages of analgesics by relating analgesic consumption per time to the levels of analgesia obtained in comparable patient populations. Therefore, we studied the equipotency ratios of clonidine and piritramide and the incidence of undesired side effects in the treatment of postoperative pain in patients undergoing maxillo-facial surgery. After approval of the local ethics committee and informed consent 40 patients (age > 18 year, ASA I-III) were studied. Following randomization, the patients each received a PCA device containing either clonidine (bolus 30 micrograms), or piritramide (bolus 1.5 mg) for treatment of postoperative pain (lockout interval 5 min in both groups). During the postoperative period, pain was determined using a visual analogue scale, while analgesic consumption, sedation, haemodynamic parameters, respiration rate, and the occurrence of undesired side effects were documented additionally. The groups had comparable distributions of biometric data, duration of anaesthesia, and ASA classification. Pain level decreased significantly (P < 0.0001) in both groups during the first 2 h of PCA. Mean arterial pressure and heart rate were lower (P < 0.05) in the clonidine group 4 and 6 h after PCA onset, while the degree of sedation after 2 (P < 0.01) and 6 (P < 0.05) h was higher than in the piritramide group. Nausea and vomiting were more frequent (P < 0.05) in the piritramide group. Both groups showed a wide interpatient variation in analgesic requirement. The equipotency ratio clonidine/piritramid was 1:63.7. Intravenous clonidine is a potent analgesic and is suitable or the treatment of postoperative pain following maxillo-facial surgery. The analgesic potency of 150 micrograms clonidine i.v. was equivalent to that of 9.56 mg piritramide i.v. Nausea and vomiting occurred more rarely in the clonidine group, while deeper sedation was observed more frequently than in the piritramide group. Owing to the wide interindividual variation of analgesic consumption, clonidine dosages have to be adjusted to the actual requirements.",1996.0,0,0
628,8679366,Spinal clonidine produces less urinary retention than spinal morphine.,M Gentili; F Bonnet,"We have conducted a double-blind, randomized study in two groups of 20 patients each, undergoing hip surgery during spinal anaesthesia, to compare the incidence of urinary retention after spinal morphine or clonidine. Patients received 0.5% spinal bupivacaine 15 mg combined with either clonidine 75 micrograms or morphine 0.2 mg. After operation, patients were examined for micturition, bladder distension, or both; when they failed to void, they received naloxone 0.2 mg, and if bladder distension persisted, a catheter was inserted. At 12 h, all patients in the morphine group but only five in the clonidine group had bladder distension, and at 24 h this was present in seven and one patient in the morphine and clonidine groups, respectively (P < 0.001). Naloxone was given in 16 and one, and a catheter was placed in one and six patients in the morphine and clonidine groups, respectively (P < 0.001). We conclude that spinal clonidine impaired bladder function to a lesser extent than morphine.",1996.0,0,0
629,8685657,Clozapine eligibility among state hospital patients.,S M Essock; W A Hargreaves; F A Dohm; J Goethe; L Carver; L Hipshman,"Connecticut State Hospital's entire resident population (n = 1,300) was screened on an arbitrary target day to determine eligibility for clozapine. Sixty percent of 803 patients with schizophrenia or schizoaffective disorder diagnoses met Food and Drug Administration (FDA)- approved criteria for clozapine use as judged by review of past medication trial records and by the responsible physicians. Eighty-eight percent of these patients were medically cleared, and of those cleared, 63 percent agreed to clozapine treatment. Of the patients who began a clozapine trial, 76 percent were still taking the drug 12 months later. Preliminary findings from a randomized trial of clozapine versus usual care (n = 227) indicate that discharge rates associated with clozapine and usual care do not differ. Once discharged, however, patients assigned to clozapine are less likely to be readmitted. Hence, clozapine may be more cost-effective than usual care. However, before savings can be realized, State governments will have to make up-front investments of approximately $140 million simply to give patients hospitalized on a single day a year's access to clozapine.",1996.0,0,0
630,8687199,Effect of lazabemide on the progression of disability in early Parkinson's disease. The Parkinson Study Group.,,"Lazabemide (Ro 19-6327) is a relatively short-acting, reversible, and selective type B monoamine oxidase inhibitor that is not metabolized to amphetamines or other active compounds. We previously found lazabemide to be safe and well tolerated at dosages of up to 400 mg/day during a 6-week study of 201 patients with early untreated Parkinson's disease (PD). We now assess whether or not lazabemide influences the progression of disability in untreated PD. Patients (N = 321) were assigned by randomization to one of five treatment groups (placebo, 25 mg, 50 mg, 100 mg, or 200 mg/day) and followed systematically for up to 1 year. The risk of reaching the primary end point (the onset of disability sufficient to require levodopa therapy) was reduced by 51% for the patients who received lazabemide compared with placebo-treated subjects. This effect was consistent among all dosages. The frequency of adverse experiences did not differ among the treatment groups. At dosages ranging from 25 to 200 mg/day, lazabemide was well tolerated and delayed the need for levodopa in early, otherwise untreated PD. The magnitude and pattern of benefits were similar to those observed after 1 year of deprenyl (selegiline) treatment in the DATATOP clinical trial.",1996.0,0,0
631,8690831,"ICI 204,636, an atypical antipsychotic: efficacy and safety in a multicenter, placebo-controlled trial in patients with schizophrenia. U.S. SEROQUEL Study Group.",R L Borison; L A Arvanitis; B G Miller,"ICI 204,636 is a new, potentially atypical antipsychotic. In early phase II trials, the antipsychotic was well tolerated and results suggested efficacy in the treatment of the positive and negative symptoms of schizophrenia. The efficacy and safety of ICI 204,636 were evaluated on a larger scale in a 6-week, multicenter, double-blind trial. Hospitalized patients who met DSM-III-R criteria for chronic or subchronic schizophrenia with acute exacerbation, as well as other criteria, were randomized to ICI 204,636 (75 to 750 mg daily) (N = 54) or placebo (N = 55). Patients were assessed weekly by use of the Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Negative Symptoms (SANS), and Clinical Global Impression Scale (CGI) for efficacy and the Simpson Scale and Abnormal Involuntary Movement Scale for extrapyramidal side effects (EPS). Significant differences (p < or = 0.05) between treatment groups, which favored ICI 204,636, were identified throughout the trial. Endpoint differences were significant (by analysis of covariance) for BPRS factor IV (activation) and SANS scores and were marginally significant for total BPRS, BPRS factor III (thought disturbance), BPRS positive-symptom cluster, and CGI Severity of Illness item scores (p = 0.07, 0.09, 0.06, and 0.09, respectively). ICI 204,636 was well tolerated, although it was associated with mild transient increases in alanine aminotransferase and a higher incidence of somnolence and anticholinergic effects compared with placebo. In the dose range studied, treatment with ICI 204,636 did not induce EPS as determined by analysis of Simpson Scale total scores and lack of treatment-emergent acute dystonic reactions. Furthermore, ICI 204,636 did not produce sustained levels of prolactin; the mean change from baseline at endpoint (-7.2 micrograms/L) was comparable (p = 0.44) to that for placebo (-8.2 micrograms/L). These findings distinguish ICI 204,636 from standard antipsychotics and confirm preclinical predictions that ICI 204,636 is an atypical antipsychotic.",1996.0,0,0
632,8694728,A 90-day study of the efficacy and side effects of 0.25% and 0.5% apraclonidine vs 0.5% timolol. Apraclonidine Primary Therapy Study Group.,W C Stewart; R Laibovitz; B Horwitz; R H Stewart; R Ritch; M Kottler,"To compare long-term intraocular pressure (IOP)-lowering efficacy of 0.25% and 0.5% apraclonidine hydrochloride with 0.5% timolol maleate. Multicenter, randomized, double-masked trial. Adult patients of either sex diagnosed as having open-angle glaucoma or ocular hypertension were enrolled following appropriate washout from all ocular hypotensive medications. Morning IOPs of 22 to 35 mm Hg were required for entry. Patients received 0.25% or 0.5% apraclonidine 3 times a day or 0.5% timolol twice a day for 90 days. Intraocular pressure was measured at 8 AM (before morning dosing) and at 4 PM (8 hours after dosing) on days 1, 30, and 90, and only at 8 AM on day 14. All 3 medications significantly reduced IOP from baseline at all observation times (P < .001): 0.5% apraclonidine reduced IOP more than 0.25% apraclonidine; no significant difference was observed between 0.5% apraclonidine and 0.5% timolol 8 hours after dosing on days 1, 30, and 90; and a significant difference (P < .05) in favour of 0.5% timolol over 0.25% apraclonidine was observed 8 hours after dosing on day 30. At all morning visits following evening dosing, 0.5% timolol significantly reduced IOP more than both concentrations of apraclonidine. Both 0.25% and 0.5% apraclonidine significantly reduce IOP when used as primary ocular hypotensive medication. Although 0.25% and 0.5% apraclonidine reduce IOP to a similar degree as 0.5% timolol 8 hours after morning dosing, neither concentration is as effective for reducing morning IOP after evening dosing.",1996.0,0,0
633,8695127,,,,,0,0
634,8712447,Interaction between intrathecal neostigmine and epidural clonidine in human volunteers.,D D Hood; K A Mallak; J C Eisenach; C Tong,"alpha 2-Adrenergic agonists are thought to produce analgesia, in part, by activating spinal acetylcholine release. The purpose of the current study was to examine the interaction between intrathecal neostigmine and epidural clonidine for analgesia and side effects in humans. A total of 58 volunteers received an intrathecal injection of 5% dextrose in normal saline (D5NS) or neostigmine (50, 100, or 200 micrograms in D5NS), followed in 1 h by epidural saline or clonidine (computer-controlled infusion targeted to 50, 100, 200, or 400 ng/ml in cerebrospinal fluid) using an isobolographic design. Visual analog scale pain to a noxious cold stimulus, nausea, weakness, sedation, and other safety variables was measured before and at specified intervals after drug administration. The first 21 volunteers randomized to receive intrathecal hyperbaric neostigmine rather than D5NS received the drug while in the sitting position, and had none-to-minimal analgesia 1 h later. The remaining volunteers received the drug while in the lateral position, and demonstrated dose-dependent analgesia in the foot 1 h later. Epidural clonidine also caused dose-dependent analgesia. The combination of neostigmine and clonidine resulted in an additive enhancement for analgesia, but no enhancement of each drug's side effects, and a reduction in clonidine-induced hypotension. Neostigmine injected into subjects in the lateral position diminished clonidine-induced reductions in blood pressure and plasma norepinephrine. These results support enhancement of alpha 2-adrenergic analgesia by intrathecal neostigmine, but do not demonstrate synergy, as observed in animals. Lack of enhancement of side effects suggests this combination may be clinically useful.",1996.0,0,0
635,8714324,Carbamazepine use in children and adolescents with features of attention-deficit hyperactivity disorder: a meta-analysis.,R R Silva; D M Munoz; M Alpert,"In the United States approximately 750,000 children receive psychostimulants to treat attention-deficit hyperactivity disorder (ADHD); up to 25% may not respond. The purpose of this study was to evaluate the reports in the international literature concerning the efficacy of carbamazepine (CBZ) in children with ADHD features by means of meta-analysis. A review of the world literature located 29 reports that dealt with behavior problems, activity levels, and CBZ in children. Of these, only 10 reports provided sufficient or pertinent information for the meta-analysis. In all seven open studies, therapeutic responses were significant (ranging from p = .05 to .0001, two-tailed t test). Meta-analysis using weighted variables revealed a significant positive correlation (r = .88; p < .02) between duration of treatment and positive outcome. In three double-blind placebo-controlled studies, treatment effects for CBZ's superiority over placebo ranged from p = .07 to .0001. A meta-analysis of these three studies revealed that CBZ was significantly (p = .018) more effective than placebo at controlling target symptoms. Despite the general lack of attention that CBZ has received for treating ADHD, there is preliminary evidence that CBZ may be an effective alternate treatment in children with features of ADHD.",1996.0,0,0
636,8719690,Topical apraclonidine hydrochloride in eyes with poorly controlled glaucoma. The Apraclonidine Maximum Tolerated Medical Therapy Study Group.,A L Robin; R Ritch; D Shin; B Smythe; T Mundorf; R P Lehmann,"We determined whether the addition of topical apraclonidine hydrochloride to eyes receiving maximal medical therapy, with inadequate intraocular pressure (IOP) control, and scheduled to undergo surgery, could adequately lower IOP, postponing the need for surgical intervention. A prospective 90 day, multi-centered, placebo-controlled, doublemasked parallel study. We enrolled 174 glaucoma patients with inadequate IOP control on maximally tolerated medical therapy. All were candidates for either laser trabeculoplasty or invasive surgical intervention. We enrolled only one eye per patient. We continued to administer maximum-tolerated medical therapy for glaucoma. Patients took the study medication every eight hours. Study medications were either apraclonidine hydrochloride 0.5% or placebo (apraclonidine's vehicle). We evaluated IOP, IOP change from baseline, and the number of eyes requiring surgery after the addition of study medication. Sixty one percent of patients treated with apraclonidine maintained adequate IOP control throughout the study, avoiding additional surgery compared to 33.9% patients treated with placebo (P < .001). Apraclonidine treatment resulted in significantly more patients achieving either an additional > or = 20% reduction in IOP from baseline (resulting in an IOP < or = 20 mm Hg) (P < 0.05). The most common ocular complications were conjunctival hyperemia (12.6%), itching and foreign body sensation (6.8%), and tearing (4.5%). The most frequent non-ocular adverse events related to apraclonidine were dry mouth (4.5%) and unusual taste perception (2.2%). Apraclonidine appears safe and efficacious. It significantly lowered IOP when used in combination with a patient's maximum tolerated medical therapy. This delayed or prevented further glaucoma surgery for at least 90 days in approximately 60% of treated patients.",1995.0,0,0
637,8725991,Efficacy and safety of risperidone in psychotic patients: an open study.,T K Daradkeh; F Reda; L Karim,"This open prospective study was undertaken to determine the efficacy and safety of a fixed dose (6 mg) of risperidone in psychotic patients. Hospital in-patients who fulfilled DSM-111-R criteria for schizophrenia, schizoaffective and bipolar disorders were eligible for entry into the study (n = 15). Patients who were on other antipsychotics had a washout period of 1 week before they were started on the drug. A fixed dose of risperidone was administered (6 mg). The Brief Psychiatric Rating Scale (BPRS), Negative Symptom Rating Scale (NSRS) and Abnormal Involuntary Movement Scale were used to measure psychopathology and extrapyramidal side-effects. Five patients dropped out of the study. Two patients became very agitated and potentially aggressive, one patient became very restless and did not respond to benzodiazepines, and one dropped out because of restlessness that did not respond to clonazepam. Of the 10 patients who completed the study, 50 per cent reduction on BPRS and NSRS was achieved by five and six patients respectively. There was a marginally significant trend towards a greater reduction in the magnitude of negative symptoms. Four patients required treatment with anticholinergic drugs. Risperidone was effective in resistent psychotic patients, but agitated and impulsive psychotic patients with positive symptoms may not be best candidates for treatment with risperidone. On average, negative symptoms respond better than positive symptoms.",1996.0,0,0
638,8730971,Comparison of the effects of clonidine on tyramine- and methoxamine-evoked mydriasis in man.,P Bitsios; R W Langley; E Szabadi; C M Bradshaw,"1. It has been reported previously that clonidine can potentiate tyramine-evoked mydriasis on the pain-free side of cluster headache patients. We examined whether a single oral dose of clonidine (200 micrograms) can also potentiate tyramine-evoked mydriasis in healthy subjects, using mydriasis to methoxamine, a directly acting sympathomimetic amine, as a control. 2. Eight healthy male volunteers participated in four weekly sessions. In the first two sessions (Experiment 1) the effect of clonidine or placebo on the mydriasis to tyramine hydrochloride eyedrops (75 mM; 2 x 10 microliters), and in the last two sessions (Experiment 2) the effect of clonidine or placebo on the mydriasis to methoxamine hydrochloride eyedrops (20 mM; 2 x 10 microliters) was examined. In both experiments subjects were allocated to drugs and sessions according to a double-blind balanced design. In both experiments, pupil diameter of both the treated and the untreated eyes was recorded in standard ambient light and in the dark, before, and 2 h after clonidine/placebo, via binocular infrared television pupillometry. Salivation (dental roll technique), systolic and diastolic blood pressure (sitting), heart rate, and self-ratings of mood and feelings (visual analogue scales), were also measured before, and 2 h after the ingestion of clonidine or placebo. 3. Both tyramine and methoxamine produced a significant mydriasis, which was more prominent in the light condition (change in resting pupil size; mm +/- s.e.mean: tyramine/light 1.05 +/- 0.28; tyramine/dark: 0.73 +/- 0.15; methoxamine/light: 1.65 +/- 0.28; methoxamine/dark: 0.85 +/- 0.15). Clonidine produced a significant miosis in the untreated eye which was more prominent in the light condition (change in resting pupil size; mm +/- s.e.mean: Experiment 1, light: -1.34 +/- 0.19; Experiment 1, dark: -0.46 +/- 0.1; Experiment 2, light -0.97 +/- 0.18; Experiment 2, dark: -0.29 +/- 0.17). Clonidine had no significant effect on either tyramine- or methoxamine-evoked mydriasis. 4. In agreement with previous reports, clonidine significantly reduced salivation (g, mean +/- s.e.mean; Experiment 1: -0.84 +/- 0.22; Experiment 2: -0.55 +/- 0.11), systolic blood pressure (mm Hg; Experiment 1: -17.5 +/- 3.76; Experiment 2: -23.38 +/- 4.67), diastolic blood pressure (mm Hg; Experiment 2: -12.38 +/- 2.05), alertness (mm; Experiment 2: -24.19 +/- 5.40), and anxiety (mm; Experiment 1: -13.82 +/- 4.60), indicating the presence of pharmacodynamically effective tissue levels of the drug. 5. These results show that a single oral dose (200 micrograms) of clonidine causes significant miosis in human subjects, and fails to potentiate tyramine-evoked mydriasis. This indicates that the pupil on the asymptomatic side of cluster headache patients is affected differently from the pupils of healthy volunteers by tyramine and/or clonidine.",1996.0,0,0
639,8740612,"A double-blind randomised comparison of the effects of epidural clonidine, lignocaine and the combination of clonidine and lignocaine in patients with chronic pain.",C Glynn; K O'Sullivan,"Twenty patients with chronic pain who previously had obtained analgesia from epidural clonidine and lignocaine agreed to participate in a double-blind crossover study of lumbar epidural clonidine (150 micrograms), lignocaine (40 mg) and the combination of clonidine (150 microgram) and lignocaine (40 mg), all drugs were given in a volume of 3 ml. There were 11 women and 9 men with a mean age 53 years (range: 23-78 years); 9 patients had low back and leg pain, 9 had neuropathic pain, 1 had pelvic pain and 1 Wegner's granulomatosis. Pain intensity and pain relief, as well as sensory and motor blockade, were assessed for 3 h following each injection. The combination was reported as the best pain relief by 12 of the 17 patients who completed all three arms of the study; 4 patients reported that clonidine was the best, 1 patient reported that none of the injections provided any analgesia and no patient reported that lignocaine was the best. SPID analysis revealed a significant difference between the combination and lignocaine (P < 0.05) but no other significant difference. TOTPAR analysis revealed no significant difference between any of the injections. All 3 injections produced evidence of neurological blockade; clonidine produced sensory blockade in 3 patients and motor blockade in 3 patients. Lignocaine produced sensory blockade in 6 patients and motor in 8 patients, while the combination produced evidence of neurological blockade in all 17 patients, sensory in 6 and motor in 11 patients. Overall there was no relationship between neurological blockade and analgesia. The reported side effects appeared to be related to clonidine. These data indicate that in these patients with chronic pain epidural clonidine had a supra-additive effect and behaved more like a co-analgesic than a pure analgesic.",1996.0,0,0
640,8743243,What they want and what they get: the social goals of boys with ADHD and comparison boys.,S M Melnick; S P Hinshaw,"Twenty-seven boys diagnosed with attention-deficit hyperactivity disorder (ADHD) and 18 comparison boys participated in a competitive tetradic interaction task. Boys were individually interviewed before the game about their goals for the interaction, and adult observers inferred boys' social goals from videotapes of the interaction. Social acceptance was determined by combining positive and negative sociometric nominations collected through individual interviews at the end of the summer research program in which the interaction was held. In their self-reports, ADHD-high aggressive boys prioritized trouble-seeking and fun at the expense of rules to a greater extent than did both ADHD-low aggressive and comparison boys. Observers judged ADHD-high aggressive boys to seek attention more strongly and seek fairness less strongly than of the other two groups. Self-reported goals of defiance and cooperation predicted boys' end-of-program social standing, even with interactional behaviors and subgroup status controlled statistically. Observer-inferred goals were differentially associated with social acceptance for ADHD and comparison boys, suggesting discontinuities in peer interaction processes. Differentiation of goals from behavior and the integral role of children's goals in peer acceptance are discussed.",1996.0,0,0
641,8749887,Risperidone: efficacy and safety.,D Umbricht; J M Kane,This article reviews the evidence for the efficacy and effectiveness of risperidone in persons with schizophrenia. Nine published double-blind studies compare risperidone with another antipsychotic medication and/or placebo. All were conducted in the acute phase of illness. Risperidone's antipsychotic efficacy is shown to be consistently superior to that of placebo and at least comparable to that of haloperidol and perphenazine for patients in the acute phase of schizophrenia. Further research is necessary to determine the effectiveness of risperidone and its efficacy both as a maintenance treatment and in treatment-refractory and deficit-state patients.,1995.0,0,0
642,8768938,[Efficacy and tolerance of risperidone in various doses (report of a study)].,E Cesková; J Svestka,Risperidone was compared in 2 double blind studies with haloperidol and perphenazine in schizophrenic psychoses. According to the maximal daily dose achieved the risperidone group was divided in 4 subgroups and the risperidone efficacy and tolerability in these groups were compared both mutually and in relation to the baseline. With all doses a good global antipsychotic efficacy has been observed. There were no statistically significant differences in influencing of productive or negative symptoms with exception of significantly more pronounced reduction of productive catatonic symptoms with 2 < max < or = 5 mg in comparison with doses higher than 15 mg daily. Extrapyramidal symptoms were less frequent with lower doses: with 2 < max < or = 5 mg significantly lower occurrence of increased muscle tonus and tremor was found than with higher doses. With maximal daily doses above 10 mg antiparkinson drugs had to be applied in more patients and in the case of trihexyphenidyl this difference reached a statistically significant level.,1996.0,0,0
643,8822534,Olanzapine versus placebo and haloperidol: acute phase results of the North American double-blind olanzapine trial.,C M Beasley; G Tollefson; P Tran; W Satterlee; T Sanger; S Hamilton,"Olanzapine is a potential new ""atypical"" antipsychotic agent. The double-blind acute phase of this study compared three dosage ranges of olanzapine (5 +/- 2.5 mg/day [Olz-L], 10 +/- 2.5 mg/day [Olz-M], 15 +/- 2.5 mg/day [Olz-H]) to a dosage range of haloperidol (15 +/- 5 mg/day [Hal]) and to placebo in the treatment of 335 patients who met the DSM-III-R criteria for schizophrenia. In overall symptomatology improvement (Brief Psychiatric Rating Scale [BPRS]-total), Olz-M, Olz-H, and Hal were significantly superior to placebo. In positive symptom improvement (BPRS-positive), Olz-M, Olz-H, and Hal were comparable and significantly superior to placebo. In negative symptom improvement (Scale for the Assessment of Negative Symptoms [SANS]-composite), Olz-L and Olz-H were significantly superior to placebo and Olz-H was also significantly superior to Hal. The most common treatment-emergent adverse events included somnolence, agitation, asthenia, and nervousness. No acute dystonia was observed with olanzapine. Treatment-emergent parkinsonism occurred with Olz-H at approximately one-third the rate of Hal, and akathisia occurred with Olz-H at approximately one-half the rate of Hal. Prolactin elevations associated with olanzapine were not significantly greater than those observed with placebo and were also significantly less than those seen with haloperidol.",2001.0,0,0
644,8822535,Cerebrospinal fluid homovanillic acid predicts behavioral response to stimulants in 45 boys with attention deficit/hyperactivity disorder.,F X Castellanos; J Elia; M J Kruesi; W L Marsh; C S Gulotta; W Z Potter; G F Ritchie; S D Hamburger; J L Rapoport,"Central dopaminergic activity has been assumed to play a role in the efficacy of stimulant drugs in attention deficit/hyperactivity disorder (ADHD), although supporting evidence has been scant. This study examined baseline cerebrospinal fluid (CSF) of boys with ADHD in relation to response to three different stimulant drugs. Forty five boys with DSM-III-R-diagnosed ADHD had a lumbar puncture before double-blind trials of methylphenidate, dextroamphetamine, and placebo. Sixteen also received pemoline as part of a subsequent open trial. Stepwise linear regressions determined significant predictors of drug response. Our prior report of a positive significant correlation between CSF homovanillic acid (HVA) and ratings of hyperactivity on placebo was replicated in a new sample of 20 boys. After baseline symptom severity, CSF HVA was the best predictor of stimulant drug response, with significant independent contribution to four of the ten measures of hyperactivity that changed significantly with medication. Higher HVA predicted better drug response, and lower HVA was associated with worsening on some measures. This supports the mediating role of central dopaminergic activity in stimulant drug efficacy in childhood hyperactivity.",1996.0,0,0
645,8822770,Cocaine and cigarettes: a comparison of risks.,N Kistin; A Handler; F Davis; C Ferre,"In order to provide additional data and perspective to current clinical, policy, and legal debates surrounding the prenatal use of cocaine in the USA, a retrospective cohort study was conducted to examine effects of cocaine on selected perinatal outcomes, and to compare the relative risks of adverse perinatal outcomes among users of cocaine and users of cigarettes. Using data from a large urban perinatal registry, relative risks of selected perinatal outcomes were determined for maternal cocaine users who were non-smokers of cigarettes, and used no marijuana, heroin, amphetamines, or alcohol (n = 64), and for cigarette smokers who do not use illicit drugs or alcohol during pregnancy (n = 3209). When compared with women with no recorded prenatal exposure to drugs or cigarettes (n = 13,043), cocaine users had higher risks than smokers for the following adverse outcomes: low birthweight [Relative Risk (RR) 5.3, 95% Confidence Interval (CI) 3.0-9.3], small-for-gestational age (SGA) [RR 4.2, 95% CI 2.4-7.3], prematurity [RR 4.0, 95% CI 2.3-7.0], abruptio placentae [RR 10.0, 95% CI 3.5-29.0], placenta praevia [RR = 2.4, 95% CI 0.3-17.8] and perinatal death [RR = 5.3, 95% CI 1.9-15.2]. Smokers who did not use any drugs experienced most of the same adverse perinatal outcomes as cocaine users, but the magnitude of risk was greater in cocaine users than in smokers for all outcomes. However, given the greater numbers of cigarette smokers than cocaine users in the population the numbers of infants in the population suffering these adverse outcomes is likely to be greater among offspring of cigarette smokers. The data support the current concern about the risk of cocaine, and current efforts to provide treatment to pregnant cocaine users. The data also underline the continued substantial risks of cigarette smoking to large numbers of pregnant women.",1996.0,0,0
646,8830068,Clonidine plus haloperidol in the treatment of schizophrenia/psychosis.,J W Maas; A L Miller; J L Tekell; L Funderburg; J A Silva; J True; D Velligan; N Berman; C L Bowden,"Because of the evidence for increased norepinephrine (NE) production in psychotic patients, we studied the effects of combining the alpha 2-adrenergic agonist clonidine with haloperidol for the treatment of schizophrenic psychosis. Twelve hospitalized schizophrenic patients were taken off their antipsychotic medication for 2 to 4 weeks before double-blind treatment with haloperidol (20 mg/day) combined with either clonidine or placebo. The group receiving clonidine was significantly more improved on the thought disorder subscale of the Brief Psychiatric Rating Scale (p = 0.02). The groups differed initially in the level of negative symptoms, but not controlling for this difference statistically by analysis of covariance did not change the finding with regard to the superiority of combining clonidine with haloperidol. We conclude that larger treatment trials of combining haloperidol with clonidine are warranted.",1995.0,0,0
647,8831317,Postoperative analgesia after peripheral nerve block for podiatric surgery: clinical efficacy and chemical stability of lidocaine alone versus lidocaine plus clonidine.,D J Reinhart; W Wang; K S Stagg; K G Walker; P L Bailey; E B Walker; S E Zaugg,"Postoperative analgesia may be prolonged by the addition of clonidine to local anesthetic solutions used for regional anesthesia. The purpose of this study was to test this hypothesis in a clinical trial of patients undergoing podiatric surgery. The study design was prospective, double-blinded, and randomized. Ninety ASA physical status I or II patients scheduled for bunionectomy or hammer toe repair were randomized to receive ankle or metatarsal blocks with plain 1.73% lidocaine (Group L), 1.73% lidocaine with 10 micrograms/mL of clonidine added (Group C10), or 1.73% lidocaine with 20 micrograms/mL clonidine (Group C20). Time from the performance of the block to 1) loss of sensation to pinprick, 2) return of sensation to pinprick, 3) onset of postsurgical pain, and 4) time of first oral pain medication intake were recorded. Beginning at 1 h after the completion of the block, visual analog scale (VAS) and verbal pain scores were recorded every 30 min. Additional postoperative oral pain medication required in the first 9 h after the block was also recorded. Analysis of variance (ANOVA) was used to analyze intergroup differences in the VAS and verbal pain scores, the time to first reported pain, the time to first oral pain medication, and the total amount of oral pain medications required. Repeated-measures ANOVA was used to analyze the VAS and verbal pain scores overall and integrated assessment of pain scores and rescue medication was per-formed. Adverse events were also recorded for each group. There were no differences among the three groups with regard to overall VAS pain scores although Group C10 had significantly better verbal pain scores after the first 3 h (P < 0.05). There was also no difference in time to loss or return of pinprick sensation. Group C10 had a longer time to first reported pain (P < 0.01), a longer time to first oral pain medication (P < 0.01), a lower average total dose of oral pain medication required (P < 0.05), and a lower integrated assessment of pain and medication (P < 0.01) than Group L. More patients in Group C10 reported no pain postoperatively (P < 0.01) and no pain medication taken (P < 0.01) than Group L. Group C20 results suggested no statistically significant improvement over plain lidocaine. One patient in Group C20 experienced significant hypotension postoperatively. pH determinations and chemical analysis by capillary electrophoresis showed no significant change in composition of the solutions when clonidine was mixed with lidocaine and stored at 4 degrees C for 1 wk. Compared to 1.73% lidocaine, combining clonidine (10 micrograms/mL) with lidocaine for local anesthetic block for foot surgery significantly increases the duration and quality of postoperative analgesia.",1996.0,0,0
648,8834417,"Antipsychotic and anxiolytic properties of risperidone, haloperidol, and methotrimeprazine in schizophrenic patients.",O Blin; J M Azorin; P Bouhours,"The subjects were 62 patients hospitalized for acute exacerbations of schizophrenia and were randomly assigned to receive risperidone (mean dose, 7.4 mg/day), haloperidol (7.6 mg/day), or methotrimeprazine (100 mg/day) for 4 weeks. Clinical improvement, defined a priori as a 20% reduction in total Positive and Negative Syndrome Scale (PANSS) scores at end point, was attained by 81% of the risperidone patients, 60% of the haloperidol patients, and 52% of the methotrimeprazine patients (p < 0.05). The reductions in total PANSS and Clinical Global Impression Scale severity scores from baseline to end point were significantly greater in the risperidone patients than in the other two groups. Reductions in scores on the Psychotic Anxiety Scale were significantly greater in the risperidone patients than the methotrimeprazine patients; the difference between haloperidol and methotrimeprazine was not significant. Extrapyramidal symptoms (scores on the Extrapyramidal Symptom Rating Scale) were more severe in the haloperidol patients than in the other two groups, but few differences were apparent between risperidone and methotrimeprazine patients. It is concluded that risperidone is an effective antipsychotic and anxiolytic agent in schizophrenic patients.",1996.0,0,0
649,8836273,The efficacy of clonidine for reducing perioperative haemodynamic changes and volatile anaesthetic requirements in children.,K Nishina; K Mikawa; N Maekawa; H Obara,"Oral clonidine given as a premedicant in adults has been shown to reduce intraoperative inhalation anaesthetic requirements and provide perioperative haemodynamic stability. We conducted the current study to ascertain whether or not these beneficial effects of clonidine can be reproduced in children. In a prospective, randomized, double-blind, controlled clinical trial, 60 children (ASA I) aged 5-11 yr, received placebo (control), 2 micrograms kg-1 clonidine, or 4 micrograms kg-1 clonidine orally 105 min before induction of anaesthesia. Anaesthesia was induced with halothane, nitrous oxide in oxygen via mask and maintained with halothane and 60% nitrous oxide in oxygen. The halothane concentration was titrated to the concentration required to maintain haemodynamic stability (defined as 20% of blood pressure (BP) and heart rate (HR)) for maintenance of anaesthesia. The end-tidal concentration of halothane was monitored throughout anaesthesia. On completion of surgery, nitrous oxide and halothane were discontinued. Following confirmation of recovery from anaesthesia and muscle relaxation, the endotracheal tube was removed. Higher inspired concentrations of halothane (%) were required in the control and 2 micrograms kg-1 clonidine-treated groups (mean SD: 1.1 +/- 0.2 and 1.0 +/- 0.2, respectively) than in the 4 micrograms kg-1 clonidine-treated group (0.6 +/- 0.1) for haemodynamic stability (P < 0.05). Clonidine, 4 micrograms kg-1, significantly reduced the intraoperative lability (coefficient of variation) of systolic and diastolic BP and HR compared with the other two regimens. Oral clonidine premedication at a dose of 4 micrograms kg-1 provided intraoperative haemodynamic stability and reduced anaesthetic requirements in children. However, we are unable to extrapolate these observations to younger children and infants.",1996.0,0,0
650,8853219,Does haloperidol block methylphenidate? Motivation or attention?,F Levy; G Hobbes,"The effect of methylphenidate preceded by a moderate dose of haloperidol on reaction times over the duration of a continuous performance test (CPT), was investigated in ten male children, with a DSM-III diagnosis of attention deficit disorder with hyperactivity disorder (ADDH). Using a within-subject double-blind design, the effects of methylphenidate preceded by haloperidol on reaction time during the first and second blocks of CPT test were compared. Methylphenidate maintained a significantly improved reaction time in the second block of the CPT test. When methylphenidate, preceded by placebo, was preceded by haloperidol this effect was not observed, suggesting opposing effects on attentional systems by methylphenidate versus haloperidol. The study is the first to examine the ""blocking"" effect of haloperidol over the course of a CPT. The results suggest that dopamine systems are involved in the maintenance of the CPT response, and support an ""incentive motivation"" theory of sustained attention.",1996.0,0,1
651,8864326,Clonidine and or adrenaline decrease lignocaine plasma peak concentration after epidural injection.,J X Mazoit; D Benhamou; Y Veillette; K Samii,"Clonidine is an alpha 2-adrenoceptor agonist increasingly used in combination with lignocaine for spinal or epidural anaesthesia because of a prolonged analgesic effect. Life adrenaline, it may decrease lignocaine peak concentration (Cmax), thus leading to decreased toxicity. However, the effects of clonidine on resorption of lignocaine into the systemic circulation from the epidural space remain to be established. We studied the pharmacokinetics of lignocaine after epidural injection of lignocaine with or without clonidine, adrenaline and both drugs. Total body clearance and apparent volume of distribution were similar in the four groups, but the maximum observed concentration (Cmax) was markedly increased in the plain solution group as compared with the other groups; (plain lignocaine: 7.15 +/- 2.04 micrograms ml-1, lignocaine + adrenaline: 3.11 +/- 136 micrograms ml-1, lignocaine + clonidine: 4.48 +/- 1.26 micrograms ml-1, lignocaine + adrenaline + clonidine: 4.06 +/- 1.42 micrograms ml-1 [mean +/- s.d.]). Our results show that, clonidine decreases lignocaine Cmax to the same extent as adrenaline.",1996.0,0,0
652,8866934,Mechanical lesions of the fimbria fornix in rat brain studied by 1H-magnetic resonance imaging. Evidence for long-lasting dynamic alterations in the ipsilateral ventricular system.,R M Dijkhuizen; H J Muller; M Josephy; B M Spruijt; K Nicolay,"In vivo 1H-NMR imaging was employed to study dynamic changes in the status of tissue water as a function of time after mechanical brain injury induced by partial unilateral transection of the fimbria fornix (FF) in the rat brain and was correlated with histology. Changes in the brain tissue were reproducibly found in distinct regions which were exclusively located in the lesioned hemisphere. The most pronounced changes concerned the lateral ventricle. Ventricular enlargement became evident posterior to the site of transection after a few hours and was maximal after 2-4 days. At later time points the posterior ventricular expansion was reduced. The lateral ventricle anterior to the site of transection was significantly enlarged from day 1 and continued to expand for up to 7 months. Tissue response at the site of transection, mainly involving the hippocampal formation and the thalamus, was first manifested after 24 h, while signs of progressive tissue degeneration were apparent in the long term.",1996.0,0,0
653,8872973,Mechanism of angiotensin converting enzyme inhibitor-related anemia in renal transplant recipients.,J Gossmann; P Thürmann; T Bachmann; S Weller; H G Kachel; W Schoeppe; E H Scheuermann,"To delineate the pathogenesis of the reduction in hemoglobin occurring in renal transplant patients treated with angiotensin converting enzyme inhibitors (ACEI) and azathioprine (AZA) a controlled, prospective trial of ACEI withdrawal was conducted. The ACEI was replaced by nifedipine or clonidine in 15 kidney transplant patients immunosuppressed with AZA and prednisone (enalapril in 14 and captopril in 1). Before and during 10 to 12 weeks after withdrawal of the ACEI, AZA metabolites, renal function parameters and hematological parameters including erythropoietin and reticulocytes were evaluated. Enalaprilat levels were measured and compared with 15 similar patients matched for transplant function and enalapril dosage immunosuppressed with cyclosporine and prednisone. AZA metabolites did not differ significantly in the presence or absence of the ACEI. Enalaprilat levels also showed no significant difference between the two patient groups treated with AZA or cyclosporine. Hematocrit and hemoglobin increased significantly from 37.5 +/- 6.4 to 39.7 +/- 3.6% (mean +/- SD, P = 0.02) and 12.8 +/- 2.2 to 13.5 +/- 1.2 g/dl, P = 0.04, respectively, 10 to 12 weeks after ACEI treatment had been discontinued. Simultaneously numbers of reticulocytes and erythropoietin concentrations rose significantly after 2, 4 and 10 weeks, with a peak at two weeks (from 14.1 +/- 3.8 to 20.6 +/- 8.0/1000, P < 0.05 and from 14.3 +/- 12.4 to 29.3 +/- 54.5 mU/ml, P < 0.05, respectively). In conclusion, ACEI-related anemia in renal transplant recipients seems to be due to the erythropoietin-lowering effect of this group of drugs. A pharmacokinetic interaction between AZA and enalapril is not likely since plasma enalaprilat levels were independent of the immunosuppressive regimen and AZA metabolite levels were unchanged in the presence and absence of the ACEI. Several mechanisms by which angiotensin converting enzyme blockade may cause a decrease in circulating erythropoietin are discussed.",1996.0,0,0
654,8873539,"Small, oral dose of clonidine reduces the incidence of intraoperative myocardial ischemia in patients having vascular surgery.",K D Stühmeier; B Mainzer; J Cierpka; W Sandmann; J Tarnow,"Most new perioperative myocardial ischemic episodes occur in the absence of hypertension or tachycardia. The ability of alpha 2-adrenoceptor agonists to inhibit central sympathetic outflow may benefit patients with coronary artery disease by increasing the myocardial oxygen supply and -demand ratio. A randomized double-blind study design was used in 297 patients scheduled to have elective vascular surgical procedures to evaluate the effects of 2 micrograms/kg-1 oral clonidine (n = 145) or placebo (n = 152) on the incidence of perioperative myocardial ischemic episodes, myocardial infarction, and cardiac death. Continuous real-time S-T segment trend analysis (lead II and V5) was performed during anesthesia and surgery and correlated with arterial blood pressure and heart rate before and during ischemic events. Dose requirements for vasoactive and antiischemic drugs to control blood pressure and heart rate as well as episodes of myocardial ischemia (i.e., catecholamines, beta-adrenoceptor antagonists, nitrates, and systemic vasodilators) and fluid volume load were recorded. Administration of clonidine reduced the incidence of perioperative myocardial ischemic episodes from 39% (59 of 152) to 24% (35 of 145) (P < 0.01). Hemodynamic patterns, percentage of ischemic time, and the number of ischemic episodes per patient did not differ. Nonfatal myocardial infarction developed after operation in four patients receiving placebo compared with none receiving clonidine (day 2 to 21; P = 0.07). The incidence of fatal cardiac events (1 vs. 2) was not different. Dose requirements for vasoactive and antiischemic drugs did not differ between the groups, but the amount of presurgical fluid volume was slightly greater in patients receiving clonidine (951 +/- 388 vs. 867 +/- 381 ml; P < 0.03). A small oral dose of clonidine, given prophylactically, can reduce the incidence of perioperative myocardial ischemic episodes without affecting hemodynamic stability in patients with suspected or documented coronary artery disease.",1996.0,0,0
655,8875814,Methylphenidate and attentional training. Comparative effects on behavior and neurocognitive performance in twin girls with attention-deficit/hyperactivity disorder.,M D Rapport; S Loo; P Isaacs; S Goya; C Denney; S Scanlan,"The effectiveness of four doses (5-mg, 10-mg, 15-mg, 20-mg) of methylphenidate (MPH) and attentional training (AT) were evaluated using neurocognitive instruments (Continuous Performance Test; Matching Unfamiliar Figures Test), narrow- and broad-band rating scales in the context of a double-blind, placebo-control, within-subject reversal design for dizygotic twin girls with Attention-Deficit/Hyperactivity Disorder (ADHD). Both interventions proved effective for improving neurocognitive test performance and behavior, although broad-band ratings revealed dose-response curves different from those obtained from the neurocognitive tests. Implications for clinical management of girls with ADHD are discussed.",1996.0,0,1
656,8885956,Methylphenidate dosing: twice daily versus three times daily.,M A Stein; T A Blondis; E R Schnitzler; T O'Brien; J Fishkin; B Blackwell; E Szumowski; N J Roizen,"To evaluate the short-term efficacy and side effects associated with two methylphenidate hydrochloride (MPH) dosing patterns. Twenty-five boys with attention deficit hyperactivity disorder (ADHD) participated in a 5-week, triple-blind, placebo-controlled, crossover evaluation of MPH administered twice (b.i.d.) versus thrice (t.i.d.) per day (mean dose = 8.8 +/- 5 mg, .30 +/- .1 mg/kg/dose). Four dosing conditions (placebo, titration [gradual increase to target dose], b.i.d., and t.i.d.) were used. Dependent measures obtained on a weekly basis included: parent and teacher ratings of child behavior, parent-child conflicts, parent report of stimulant side effects, child self-report of mood symptoms, a sleep log, laboratory measures of attention, and actigraphic recording of sleep activity. All dosing conditions resulted in significant effects on ADHD symptoms when compared with baseline. Relative to placebo, t.i.d. dosing was characterized by improvement on the greatest number of behavioral measures, and both b.i.d. and t.i.d. were generally more effective than titration. Direct comparisons of b.i.d. and t.i.d. dosing revealed that t.i.d. was associated with greater improvement on the Conners Parent Rating Scale Impulsivity/Hyperactivity factor, with a similar marginally significant effect for the ADD-H Teacher Rating Scale Hyperactivity factor. The analysis of clinically significant change favored a three-times-a-day dosing schedule over placebo on both parent and teacher ratings of impulsivity/hyperactivity and attention. Compared with placebo, appetite suppression was rated, on average, as more severe in the t.i.d. and titration conditions, but not in the b.i.d. condition. However, the number of subjects who exhibited any or severe appetite suppression did not differ significantly between the b.i.d. and t.i.d. schedules. Although there was no difference in sleep duration for children on b.i.d. and t.i.d. schedules, total sleep time appeared to decrease slightly on t.i.d. relative to placebo according to both parent ratings and actigraphic assessment. There were no significant differences between b.i.d. and t.i.d. on any other side effects or sleep variables. For many children with ADHD, t.i.d. dosing may be optimal. There are few differences in acute side effects between b.i.d. and t.i.d. MPH dosing. The dosing schedule should be selected according to the severity and time course of ADHD symptoms rather than in anticipation of dosing schedule-related side effects.",1996.0,0,1
657,8895283,A minimum dose of clonidine added to mepivacaine prolongs the duration of anesthesia and analgesia after axillary brachial plexus block.,F J Singelyn; J M Gouverneur; A Robert,"This study assessed the minimum dose of clonidine required to prolong the duration of both anesthesia and analgesia after axillary brachial plexus blockade. Eighty patients scheduled for elective hand surgery were divided into eight groups in a randomized, double-blind fashion. An axillary brachial plexus block was performed with 40 mL 1% mepivacaine plus 1:200,000 epinephrine. The control group received no clonidine. In the other groups, increasing doses of clonidine (0.1, 0.2, 0.3, 0.4, 0.5, 1, and 1.5 micrograms/kg) were added to the local anesthetic solution. Onset time, duration of anesthesia and analgesia, postoperative pain score, intake of analgesics, and adverse effects were recorded. The eight groups were comparable in terms of onset time, postoperative pain score, and analgesic requirement. The minimum dose of clonidine required to significantly prolong the duration of analgesia and anesthesia was, respectively, 0.1 and 0.5 microgram/kg. No side effects (sedation, drowsiness, bradycardia, arterial hypotension) were reported. We conclude that the dose of clonidine required to prolong significantly the duration of both anesthesia and analgesia after axillary brachial plexus blockade is 0.5 microgram/kg and that, at this dose, clonidine may be used without important reported side effects even in outpatients.",1996.0,0,0
658,8916595,A comparative evaluation of pilocarpine 1% and clonidine 0.125% versus timolol 0.5%.,R Sihota; H C Agarwal; Y L Rajashekar,"All the presently available antiglaucoma medications have either local or systemic adverse effects. Combinations of drugs are being used not only to increase the effectivity and compliance but also to decrease the incidence and magnitude of side effects. The single dose response of open angle glaucoma eyes to pilocarpine 1%, clonidine 0.125%, a combination of pilocarpine 1% and clonidine 0.125%, and timolol 0.5% was studied in a double blind, masked, cross over study. Over a period of twelve hours the effectivity of the combination of pilocarpine 1% and clonidine 0.125% was significantly more than that of either drug alone and was found to be similar to that of timolol 0.5%. No local or systemic adverse effects were seen.",1996.0,0,0
659,8926223,Separate and combined effects of methylphenidate and a behavioral intervention on disruptive behavior in children with mental retardation.,N J Blum; J E Mauk; J J McComas; F C Mace,"We investigated the separate and combined effects of a behavioral intervention and methylphenidate (Ritalin) on disruptive behavior and task engagement in 3 children with severe to profound mental retardation. The behavioral intervention involved differential reinforcement of appropriate behavior and guided compliance. All 3 children demonstrated decreased disruptive behavior and improved task engagement in response to the response to the behavioral intervention. Two of the 3 children demonstrated similar improvement in response to methylphenidate. Although both interventions were highly effective for these 2 participants, the relative efficacy of the interventions varied between the 2 children. There was no evidence of an additive or synergistic effect of the two interventions, but the high efficacy of each intervention alone limited our ability to detect such effects.",1996.0,0,0
660,8927677,Nicotine and attention in adult attention deficit hyperactivity disorder (ADHD).,C K Conners; E D Levin; E Sparrow; S C Hinton; D Erhardt; W H Meck; J E Rose; J March,"Nicotine, like the psychostimulants methylphenidate and dextroamphetamine, acts as an indirect dopamine agonist and improves attention and arousal. Adults and adolescents with attention deficit hyperactivity disorder (ADHD) smoke much more frequently than normal individuals or those with other psychiatric conditions, perhaps as a form of self-medication for ADHD symptoms. Nicotine might therefore have some value as a treatment for ADHD. The present study is an acute double-blind crossover administration of nicotine and placebo with smokers (n = 6) and nonsmokers (n = 11) diagnosed with adult ADHD. The drug was delivered via a transdermal patch at a dosage of 7 mg/day for nonsmokers and 21 mg/day for smokers. Results indicate significant clinician-rated global improvement, self-rated vigor and concentration, and improved performance on chronometric measures of attention and timing accuracy. Side effects were minimal. These acute results indicate the need for a longer clinical trial and a comparison with other stimulants in adult ADHD treatment.",1996.0,0,0
661,8935812,"Olanzapine versus placebo: results of a double-blind, fixed-dose olanzapine trial.",C M Beasley; T Sanger; W Satterlee; G Tollefson; P Tran; S Hamilton,"Olanzapine is a potential new ""atypical"" antipsychotic agent. This double-blind, acute phase study compared two doses of olanzapine [1 mg/day (Olz1.0); 10 mg/day (Olz10.0)] with placebo in the treatment of 152 patients who met the DSM-III-R criteria for schizophrenia and had a Brief Psychiatric Rating Scale (BPRS)-total score (items scored 0-6) > or = 24. In overall symptomatology improvement [BPRS-total score and Positive and Negative Syndrome Scale (PANSS)-total score], Olz10.0 was statistically significantly superior to placebo. In positive symptom improvement (PANSS-positive score, BPRS-positive score), Olz10.0 was statistically significantly superior to placebo. In negative symptom improvement (PANSS-negative score), Olz10.0 was statistically superior to placebo. Olz 1.0 was clinically comparable to placebo in all efficacy comparisons. The only adverse event to show an overall statistically significant incidence difference was anorexia (reported for 10% of placebo-treated and 0% of Olz10.0-treated patients). The Olz10.0-treated patients improved over baseline with respect to parkinsonian and akathisia symptoms, and these changes were comparable with those observed with placebo. There were no dystonias associated with Olz10.0 treatment. At endpoint, the incidence of patients with elevated prolactin values did not differ statistically significantly between placebo-treated and Olz10.0-treated patients. Olanzapine appears to be not only safe and effective, but a promising atypical antipsychotic candidate.",2001.0,0,0
662,8935814,Relapse following clozapine withdrawal: effect of neuroleptic drugs and cyproheptadine.,H Y Meltzer; M A Lee; R Ranjan; E A Mason; P A Cola,"The objective of this study was to report the effect of the slow withdrawal of clozapine from 19 patients with neuroleptic-responsive schizophrenia at the end of a 2-year clinical trial of clozapine and to compare this with the results of naturalistic discontinuation of clozapine treatment in 64 neuroleptic-resistant schizophrenic patients. Nineteen neuroleptic-responsive schizophrenic patients who received clozapine were withdrawn from clozapine by tapering it over 3-week period with and without the addition of a typical neuroleptic. Fifteen of the 19 neuroleptic-responsive patients experienced the return of psychotic symptoms during or after the clozapine taper, which were most severe in the ten patients in whom the withdrawal of clozapine was carried out without prior addition of neuroleptic treatment. Addition of a neuroleptic prior to clozapine withdrawal prevented the emergence of positive symptoms during clozapine withdrawal in each of eight patients. Nevertheless, psychotic symptoms emerged, usually within a week after discontinuing clozapine, in six of the eight patients. Neuroleptic treatment, with or without an anticholingergic drug, was much less effective in treating positive symptoms in these patients immediately after the clozapine withdrawal than it had been 2 years previously. Cyproheptadine, a non-selective serotonin receptor antagonist, augmented the antipsychotic effect of neuroleptics in each of four patients who relapsed following withdrawal from clozapine and relieved extrapyramidal symptoms in a fifth patient. The frequency of relapse following withdrawal of clozapine in 64 neuroleptic-resistant patients was significantly lower (25/64, 39.1%) than in the neuroleptic-responsive patients.",1996.0,0,0
663,8935815,Clozapine versus typical antipsychotics. A retro- and prospective study of extrapyramidal side effects.,L Peacock; T Solgaard; H Lublin; J Gerlach,"Schizophrenic patients in long-term neuroleptic monotherapy with clozapine (n = 100) and perphenazine, flupenthixol or zuclopentixol (controls, n = 100) were evaluated for extrapyramidal side effects (EPS) (blind) as well as other side effects and mental condition (non-blind). In both groups the patients had received neuroleptic treatment for a total of 14 years (median) and the present antipsychotic (clozapine or control drug) for 5 years. Thus the clozapine-treated patients had previously received traditional neuroleptics for 9 years (median). The study was both retrospective (0.3-19 years for clozapine, 0.3-24 years for control drug, by means of chart information) and prospective (1 year, with video-controlled evaluation of EPS). There was a significantly lower prevalence of tardive dyskinesia (TD) in clozapine treated patients than control patients, although prior to this treatment there were more TD patients in the clozapine group (P < 0.05). This lower level of TD in the clozapine group was related to a lower induction of new cases (P < 0.001) and a tendency towards greater disappearance of TD in the clozapine than in the control group (P = 0.07). Clozapine treated patients without TD had started clozapine and ceased traditional neuroleptics at an earlier age than those with TD. Parkinsonian signs were seen in 33% of the clozapine patients versus 61% of the control patients, mainly as hypokinesia; tremor in 3% versus 11% and rigidity in 0 versus 19%. Psychic akathisia was found in 14% versus 40% and motor akathisia in 7% versus 29% of the patients, all differences significantly in favor of clozapine. Clozapine treated patients also had less neuroleptic-induced emotional indifference and depression, but more autonomic side effects than controls.",1996.0,0,0
664,8938913,Cholinergic rebound and rapid onset psychosis following abrupt clozapine withdrawal.,T M Shiovitz; T L Welke; P D Tigel; R Anand; R D Hartman; J J Sramek; N M Kurtz; N R Cutler,"Following the conduct of a 28-day inpatient bioequivalence study of clozapine in schizophrenia patients, withdrawal effects after abrupt discontinuation from clozapine were assessed. Thirty patients who met DSM-III-R criteria for schizophrenia, residual type, or schizophrenia in remission were enrolled in the study. Patients were evaluated for symptoms of withdrawal effects for 7 days after clozapine 200 mg/day was abruptly withdrawn. Of 28 patients who completed the study, 11 had no withdrawal symptoms; 12 had mild withdrawal adverse events of agitation, headache, or nausea; four patients experienced moderate withdrawal adverse events of nausea, vomiting, or diarrhea; and one patient experienced a rapid-onset psychotic episode requiring hospitalization. Cholinergic rebound is a likely explanation for the mild to moderate withdrawal symptoms and is easily treated with an anticholinergic agent. Mesolimbic supersensitivity, as well as specific properties of clozapine, are discussed as likely causes for rapidonset psychosis. Our findings are consistent with previous reports of withdrawal reactions associated with clozapine, further reminding clinicians to monitor patients closely following abrupt discontinuation of clozapine.",1996.0,0,0
665,8956088,Methylphenidate slows reactions of children with attention deficit disorder during and after an error.,D A Krusch; R Klorman; J T Brumaghim; P A Fitzpatrick; A D Borgstedt; J Strauss,"A Sternberg memory search task was administered under placebo and methylphenidate to 42 children with cross-situational attention deficit disorder (ADD), 31 children with cross-situational ADD plus oppositional features, and 25 patients with marginal ADD. Overall, stimulant medication enhanced accuracy and speed. In addition, patients reacted faster on correct responses not preceded by an error than on errors (especially false alarms) or on correct responses following an error. The slowness during error reactions may reflect decreased confidence or confusion during stimulus classification. This uncertainty may also lead subjects to respond with greater caution, hence more slowly, on correct responses following errors. Notably, methylphenidate increased the slowing of reactions on error trials as well as on correct reactions following an error. Stimulant medication may augment subjects' persistence when they are uncertain or confused, thereby heightening caution and promoting accuracy on succeeding trials. Consistent with previous reports of the generality of enhancement of performance by stimulant medication, the impact of methylphenidate was comparable for the three subtypes of ADD studied.",1996.0,0,1
666,8956674,Childhood-onset schizophrenia. A double-blind clozapine-haloperidol comparison.,S Kumra; J A Frazier; L K Jacobsen; K McKenna; C T Gordon; M C Lenane; S D Hamburger; A K Smith; K E Albus; J Alaghband-Rad; J L Rapoport,"Childhood-onset schizophrenia is a rare but severe form of the disorder that is often treatment-refractory. In this study, the efficacy and adverse effects of clozapine and haloperidol were compared for children and adolescents with early-onset schizophrenia. Twenty-one patients (mean [+/-SD] age, 14.0 +/- 2.3 years) with onset of Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition-defined schizophrenia that began by age 12 years and who had been nonresponsive to typical neuroleptics participated in the study. Patients were randomized to a 6-week double-blind parallel comparison of clozapine (mean [+/-SD] final dose, 176 +/- 149 mg/d), or haloperidol, (16 +/- 8 mg/d). Clozapine was superior to haloperidol on all measures of psychosis (P = .04-.002). Positive and negative symptoms of schizophrenia improved. However, neutropenia and seizures were major concerns. To date, one third of the group has discontinued using clozapine. Clozapine has striking superiority for positive and negative symptoms in treatment-refractory childhood-onset schizophrenia. However, due to possibly increased toxic effects in this pediatric population, close monitoring for adverse events is essential.",1996.0,0,0
667,8958487,Potentiation of sufentanil by clonidine in PCEA with or without basal infusion.,M P Vercauteren; V Saldien; P Bosschaerts; H A Adriaensen,"Sufentanil or a sufentanil-clonidine combination was evaluated to determine whether the basal rate in patient-controlled epidural analgesia (PCEA) might affect the daily consumption, quality of analgesia or incidence of side effects. Following Caesarean section delivery, 60 patients were randomly assigned to receive one of the four following PCA regimens (15 patients per group) for the relief of post-operative pain by the epidural route: sufentanil 2 micrograms mL-1 in 0.9% NaCl, demand dose 5 micrograms i.e. 2.5 mL, (group S+ with, group S without an infusion at 2.5 mL hr-1) or sufentanil 2 micrograms mL-1 + clonidine 3 micrograms mL-1, demand dose 5 micrograms sufentanil + 7.5 micrograms clonidine i.e. 2.5 mL (group SC+ with and SC without an infusion of 2.5 ml hr-1). The other PCA settings (Bard I PCA pump) were a lock out of interval of 10 min and a 1 h limit of 20 micrograms sufentanil and 30 micrograms clonidine i.e. 10 mL. The parameters measured were the analgesic drug consumption and number of dose demands during the first 24 h, pain scores at 6 h intervals, side effects and quality of sleep. The concurrent infusion increased the dose requirements regardless of the content of the syringe. Consumption of sufentanil was the highest in those patients receiving the plain solution with a basal infusion. Clonidine addition reduced the dose requirements but only significantly in those receiving the background infusion. Patients treated with the mixture tended to reach lower pain scores than those receiving sufentanil only without basal rate. Patients receiving the mixture with basal rate requested significantly fewer additional demands compared with the three other groups, but this did not influence the quality of sleep. Since side effects were more frequently registered in the patients in this group, it was concluded that the optimum regimen was the sufentanil-clonidine combination but with deletion of the basal rate.",1996.0,0,0
668,8959478,Effects of 'Seroquel' (quetiapine) on platelet serotonin-2 binding in schizophrenia.,W O Faustman; D L Ringo; J Lauriello; K O Lim; A Pfefferbaum,,1996.0,0,0
669,8965185,Cerebral glucose metabolism during pharmacologic studies: test-retest under placebo conditions.,M E Schmidt; M Ernst; J A Matochik; J M Maisog; B S Pan; A J Zametkin; W Z Potter,"The reliability of serial [18F]fluorodeoxyglucose (FDG) PET scans for psychopharmacologic studies was tested by using placebo infusions. FDG scans were obtained before and after a 30 min placebo infusion (n = 10; Group 1) or after each of two bolus infusions with placebo (n = 8; Group 2). Subjects performed a continuous performance task (CPT) during each scan. Cardiovascular measures and ratings of anxiety were obtained in all subjects. Samples for determination of plasma norepinephrine (NE) were taken at multiple time points in Group 1. A slight increase in apparent global metabolism occurred between scans in both Groups 1 and 2. A few regions significantly increased in both groups. While an apparent increase in sympathetic activity occurred during the placebo infusion, neither NE levels, anxiety ratings nor cardiovascular measures correlated with global or regional FD6 uptake. Test-retest differences of global and regional glucose metabolism were highly consistent across two experimental designs. While increases in cerebral glucose metabolism appeared to occur during the second scan, differences between scans were small. This method may offer advantages for selected psychopharmacologic studies.",1996.0,0,0
670,8973026,Effects of an educational intervention on mothers of male children with attention deficit hyperactivity disorder.,S E Odom,"An experimental research study was done to determine whether an educational intervention about attention deficit hyperactivity disorder (ADHD) would improve a mother's knowledge about ADHD and her feelings of competence as a parent. 20 low socioeconomic status mothers who had a male child between the ages of 5 and 11 diagnosed with ADHD and placed on methylphenidate were randomly selected for the study. An experimental group of 10 mothers was given a 5-week educational intervention on ADHD; the remaining 10 mothers served as a control group. Differences between the experimental and non-experimental mothers in knowledge and opinions about ADHD and parental sense of competency were measured. Scores improved in parental satisfaction and parental sense of competency in mothers who participated in the educational intervention. The research findings support the idea that nurses can assist a family in learning and dealing with their child's ADHD, a chronic condition.",1996.0,0,0
671,8984849,,,,,0,0
672,8988795,Minimal effects of dextroamphetamine on scopolamine-induced cognitive impairments in humans.,R Martinez; S E Molchan; B A Lawlor; K Thompson; H Martinson; G Latham; H Weingartner; T Sunderland,"The central anticholinergic drug scopolamine has been used to model aspects of the memory impairment that occurs in Alzheimer's disease and in aging. To determine whether nonspecific stimulant effects can attenuate the cognitive impairment induced by scopolamine, we studied the effects of scopolamine and the stimulant dextroamphetamine in 17 young normal volunteers. After a baseline day of cognitive testing, subjects participated in two study days, in which they received dextroamphetamine (d-AMP) (0.25 mg/kg p.o.) + scopolamine (0.5 mg i.v.) and placebo + scopolamine, in randomized order under double-blind conditions. There were no statistically significant differences in cognitive test performance between the two drug conditions with the exception of one of the category retrieval tasks. Stimulant effects were documented to occur by other measures. We conclude that d-AMP at the dose used does not attenuate the memory impairment induced by scopolamine.",1997.0,0,0
673,8993091,Therapeutic effect and safety of adjunctive risperidone in refractory obsessive-compulsive disorder (OCD).,L Ravizza; G Barzega; S Bellino; F Bogetto; G Maina,"It has been well established that more than 40 percent of patients with obsessive-compulsive disorder (OCD) do not improve after an adequate trial with serotonin uptake inhibitors (SUIs). The first purpose of this trial was to compare the short-term efficacy and safety of two different strategies in a sample of treatment-refractory OCD patients: dose increase of the ongoing treatment versus the addition of another SUI. The second purpose was to investigate the short-term efficacy and safety of adjunctive risperidone in SUI-refractory OCD patients. Thirty-three OCD patients who were unimproved after a short-term treatment with clomipramine (150 mg/day) were admitted to the study. In the first part of the study, the dose increase of clomipramine was compared with sertraline addition, in an open-label manner. The addition of sertraline to the ongoing treatment appeared to be more effective and tolerable than the clomipramine dose increase. Seven (50%) of the 14 patients who were considered nonresponders after the first part of the study, showed good clinical improvement and good tolerability after risperidone augmentation. These results suggest that risperidone addition to ongoing SUIs may be useful in augmenting pharmacologic response in OCD.",1996.0,0,0
674,8998394,Weight gain induced by clozapine.,M Hummer; G Kemmler; M Kurz; I Kurzthaler; H Oberbauer; W W Fleischhacker,"Patients were investigated to gain more insight into the incidence and time course of clozapine induced weight gain (n = 81) and to compare weight gain in patients treated with clozapine (n = 31) with that of patients treated with standard antipsychotics (haloperidol, n = 11). 35.7% of the patients treated with clozapine gained weight according to our definition. If patients gained weight on clozapine this side effect was apparent within the first 12 weeks of treatment. Deviation from normal body weight at the beginning of treatment showed a significant influence on weight gain. Sex, severity of illness, comedication, mean clozapine dose and degree of improvement did not show an influence on this side effect. Weight increase was significantly higher in patients treated with clozapine than in patients treated with haloperidol.",1995.0,0,0
675,9003849,Epilepsy and attention deficit hyperactivity disorder: is methylphenidate safe and effective?,V Gross-Tsur; O Manor; J van der Meere; A Joseph; R S Shalev,"To study the safety and efficacy of methylphenidate in children with the dual diagnosis of epilepsy and attention deficit hyperactivity disorder (ADHD). Thirty children, aged 6.4 to 16.4 years, with epilepsy and ADHD were studied during a 4-month period. During the initial 2 months of the study, the children were treated with antiepileptic drugs (AEDs) only, and for the remaining 2 months, methylphenidate was added at a morning dose of 0.3 mg/kg. They underwent neurologic assessment, brain computed tomography, IQ testing, and assessment with the Childhood Behavior Checklist at baseline before methylphenidate therapy. Electroencephalography, AED determinations, and the continuous-performance task (CPT) test were done at baseline and after 2 months of methylphenidate therapy. A double-blind, crossover design was used to compare the effects of methylphenidate versus placebo on an electroencephalogram, AED levels, and the CPT. On the 2 days of testing, the child received AEDs and a capsule containing either placebo or methylphenidate. None of the 25 children of this sample who were seizure free had attacks while taking methylphenidate. Of the 5 children with seizures, 3 had an increase in attacks, whereas the other 2 showed no change or a reduction. There were no significant changes in AED levels or electroencephalographic findings. Methylphenidate benefited 70% of children according to parental report; methylphenidate also enhanced performance on the CPT. Side effects of methylphenidate were mild and transient. Methylphenidate is effective in treating children with epilepsy and ADHD and safe in children who are seizure free. Caution is warranted for those still having seizures while receiving AED therapy.",1997.0,1,1
676,9004057,The effects of clozapine on symptom clusters in treatment-refractory patients.,G Abraham; C Nair; J I Tracy; G M Simpson; R C Josiassen,"Preliminary results of a double-blind clozapine study in a population of chronic psychotic patients at a state psychiatric facility are reported. Thirty ""treatment-refractory"" schizophrenic patients given a diagnosis according to DSM-III-R criteria (mean age of 44 +/- 9.1 years and a duration of illness of 24.9 +/- 8.8 years) who received 300 mg or 600 mg of clozapine and randomized in a double-blind fashion were analyzed. Subjects were evaluated using the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impression (CGI) Scale on a weekly basis for 16 weeks. Based on the changes in their CGI scores at week 16 of clozapine treatment, subjects were retrospectively categorized as ""improvers"" (N = 12) and ""nonimprovers"" (N = 18). The two groups were compared for changes in total BPRS and BPRS factor scores. In terms of total BPRS scores, we expected a difference between the two groups because they were categorized based on changes in their CGI scores. However, the total BPRS scores in improvers showed a significant decrease by week 6 of clozapine treatment. On analyzing the four BPRS factors, the improvers showed improvement in the thinking disturbance factor by week 1 that remained steady from week 7. On the hostility-suspiciousness factor, the improvers showed an improvement across time when compared with nonimprovers. The withdrawal-retardation factor showed improvement in both groups across time, whereas the anxiety-depression factor was least influenced by clozapine. These observations suggested that all BPRS symptom factors did not uniformly contribute to improvement in overall psychopathology, which was observed as a decrease in total BPRS scores.",1997.0,0,0
677,9004341,"Clozapine eligibility: the effect of stringent criteria on ethnic, gender and age subgroups of schizophrenic patients.",M G Juarez-Reyes; M Shumway; C Battle; P Bacchetti; M S Hansen; W A Hargreaves,"1. The purpose of this retrospective chart review study was to determine whether broad and stringent criteria differentially impact clozapine eligibility in ethnic, gender, and age subgroups of schizophrenic patients. 2. 505 patients charts were selected from a random cluster sample of mental health patients known to the city and county of San Francisco. Information related to clozapine eligibility was abstracted by trained non-clinical personnel. The impact of subgroup membership on eligibility was examined using logistic regression procedures. 3. Even under the broadest interpretation of FDA requirements for clozapine use, Asian patients were less likely to be eligible, since fewer Asian patients met clozapine treatment requirements. Under more stringent eligibility criteria, older patients were more likely to be excluded from eligibility when TD does not automatically satisfy treatment criteria, and younger patients were more likely to lose eligibility if the number of required adequate medication trials increases to three. 4. Broad eligibility criteria tend to differentially exclude Asian patients while more stringent criteria differentially exclude younger and older patients.",1996.0,0,0
678,9010121,Predictive value of eosinophilia for neutropenia during clozapine treatment.,D Ames; W C Wirshing; R W Baker; D S Umbricht; A B Sun; J Carter; N R Schooler; J M Kane; S R Marder,Myelotoxicity continues to hinder the widespread use of clozapine in the United States. It has been theorized that eosinophilia predicts later agranulocytosis and that agranulocytosis occurs due to an immunologic mechanism. Our study compares the rates of these dyscrasias in clozapine-treated patients and a control group. Forty-one patients taking clozapine and 29 patients taking haloperidol were monitored for a period of 6 months. Rates of eosinophilia and neutropenia were compared between the two treatment groups. Treatment-emergent eosinophilia occurred frequently in both haloperidol- and clozapine-treated patients. No significant difference was seen between groups in the incidence of eosinophilia and neutropenia. We find no statistical difference between the rates of eosinophilia or neutropenia in haloperidol- and clozapine-treated patients. This study does not support the use of eosinophilia as a reliable predictor of neutropenia.,1996.0,0,0
679,9025120,"Covert visual spatial attention in boys with attention deficit hyperactivity disorder: lateral effects, methylphenidate response and results for parents.",J T Nigg; J M Swanson; S P Hinshaw,"We report three related studies of covert visual spatial orienting in child attention deficit hyperactivity disorder (ADHD). In Study 1, we examined covert visual spatial orienting in ADHD and comparison boys, Study 2 comprised a dose-response study of methylphenidate for the ADHD group, and Study 3 was an investigation of biological and adoptive parents. In contrast with comparison subjects (n = 17). ADHD boys aged 6-12 (n = 27) showed both slower reaction times overall and within-condition (lateral) asymmetries in reaction times. Specifically, boys with ADHD reacted more slowly to uncued targets in the left visual field than in the right visual field. Responses to stimuli in the two visual fields were differentially affected by methylphenidate for the ADHD group. Medication equalized visual field responses to the uncued targets, resulting in a significant cue x dose x visual field interaction. Further, medication altered the relative cue responsivity in the two visual fields, resulting in a significant dose x visual field interaction for the Validity Effect. Biological parents of ADHD boys (n = 16) also showed slower reaction times to uncued left visual field targets than to right visual field targets; in addition they showed slower response to invalidity cued targets in the right visual field. These literal effects were not observed in adoptive parents of ADHD boys (n = 12) or biological parents of comparison boys (n = 14). Possible abnormal hemispheric asymmetry of attention functions in boys with ADHD and their biological parents is discussed.",1997.0,0,0
680,9041905,The agitated brain injured patient. Part 2: Pathophysiology and treatment.,W J Mysiw; M E Sandel,"The management of agitation after brain injury remains uncertain because of a lack of a consistent definition and a poor understanding of the underlying mechanism. Part 1 of this review focused on definitions, differential diagnosis, and assessment. Part 2 reviews potential mechanisms for posttraumatic agitation and common intervention strategies. The intent of this two-part series is to advocate for a consistent definition for posttraumatic agitation, to encourage the use of appropriate assessment and monitoring strategies, and to recommend that intervention decisions are based on at least a theoretical understanding of the relationship between specific target behaviors and probable brain-behavior relationships.",1997.0,0,0
681,9044395,Pemoline-associated hepatic failure: a critical analysis of the literature.,M Shevell; R Schreiber,"Pemoline is a central nervous system (CNS) stimulant approved for use as part of the comprehensive medical management of attention deficit hyperactivity disorder (ADHD). An increased risk of acute hepatic failure is believed to be associated with pemoline usage, raising concerns about its prescription. A descriptive meta-analysis of the existing scientific literature and drug reporting databases was undertaken to provide more accurate understanding of this possible risk. The analysis appears to indicate that current assumptions of the risk of acute hepatic failure posed by pemoline usage alone are overestimates. Several recommendations regarding hepatic monitoring in the setting of pemoline prescription are provided.",1997.0,0,1
682,9052312,Late intraoperative clonidine administration prevents postanesthetic shivering after total intravenous or volatile anesthesia.,E P Horn; C Werner; D I Sessler; M Steinfath; J Schulte am Esch,"Postoperative administration of clonidine is an effective treatment for shivering. However, the ability of this drug to stop postanesthetic shivering when administered intraoperatively remains controversial. Furthermore, the relative efficacy of clonidine during isoflurane and propofol anesthesia remains unknown. We therefore evaluated the incidence of postanesthetic shivering in patients given clonidine during nitrous oxide/isoflurane or propofol anesthesia. Because clonidine is an analgesic, we also evaluated postoperative pain and analgesic requirements. We studied 60 patients undergoing elective ear or nose surgery. General anesthesia was induced with 2.0 mg/kg propofol, 1.5 micrograms/kg fentanyl, and 0.1 mg/kg vecuronium. General anesthesia was maintained with isoflurane and 70% nitrous oxide in one group of patients; in the other, a continuous infusion of propofol (8 mg.kg-1.h-1) was administered (without nitrous oxide). Five minutes before tracheal extubation, patients in each group were randomly assigned to receive saline, placebo, or 3 micrograms/kg clonidine intravenously. Postanesthetic shivering was evaluated by a blind investigator. Postoperative pain was assessed using a visual analog scale. Postoperative shivering was observed in 53% of the patients given isoflurane without clonidine and in 13% of the patients given propofol without clonidine. No patient given clonidine shivered. Clonidine administration significantly reduced postoperative pain. The incidence of postanesthetic shivering was significantly less after propofol anesthesia than after isoflurane/nitrous oxide anesthesia. However, a late intraoperative bolus administration of 3 micrograms/kg clonidine prevents postoperative shivering in patients given either type of anesthesia.",1997.0,0,0
683,9054253,Perioperative sympatholysis. Beneficial effects of the alpha 2-adrenoceptor agonist mivazerol on hemodynamic stability and myocardial ischemia. McSPI--Europe Research Group.,,"Mivazerol hydrochloride is a new alpha 2-adrenoceptor agonist. In vitro and animal studies have demonstrated both sympatholytic and antiischemic properties. To evaluate the safety and efficacy of mivazerol in patients during perioperative stress, this multicenter phase II clinical trial studied hemodynamic stability and myocardial ischemia in patients with coronary artery disease undergoing noncardiac surgery. Three hundred patients, from twenty-three European medical institutions, participated in this placebo-controlled, double-blind, randomized, parallel-group trial. Ninety-eight were given high-dose mivazerol (1.5 micrograms.kg-1.h-1); 99, low-dose mivazerol (0.75 microgram.kg-1.h-1); and 103, placebo, continuously intraoperatively and for 72 h postoperatively. Blood pressure and heart rate were monitored for 96 h. Myocardial ischemia was assessed by Holter electrocardiography for at least 8 h before induction of anesthesia until 96 h after surgery. Twelve-lead electrocardiograms and creatine kinase myocardial band isoenzyme levels were obtained before and serially after surgery. Adverse cardiac events were assessed for the intraoperative, early postoperative (0-24 h), and late postoperative (24-72 h) periods. The incidence of tachycardia was significantly lower with high-dose mivazerol (vs. placebo) during the intraoperative (30% vs. 51%; P = 0.002), early postoperative (29% vs. 50%; P = 0.002), and late postoperative periods (46% vs. 70%; P = 0.001). Also, the percentage of patients treated for tachycardia was significantly lower with the high dose (vs. placebo) during the early (10% vs. 20%; P = 0.043) and late (6% vs. 15%; P = 0.024) postoperative periods. The incidence of hypertension was significantly lower with both high and low doses (vs. placebo) during the intraoperative period (46% and 43%, respectively, vs. 63%; P = 0.010); treatment was similar at both high and low doses (33% and 34%, respectively, vs. 46%; P = 0.066). The incidence of bradycardia was significantly higher at both dose levels than with placebo during and after drug administration (intraoperatively-3%, 7%, and 9%; early postoperative-0%, 5%, and 6%; late postoperative-0%, 4%, and 6%; after drug-0%, 6%, and 6%; placebo, low-dose, high-dose, respectively), but the need for treatment did not differ for the groups. The incidence of, and treatment for, hypotension were similar for the three groups. Intraoperative myocardial ischemia was significantly lower with high-dose mivazerol than with placebo (20% vs. 34%, respectively, P = 0.026). When intraoperative data were subdivided into emergence vs. nonemergence periods (post boc analysis), the incidence of myocardial ischemia was significantly lower with high-dose mivazerol than with placebo during emergence (11% vs. 30%; P = 0.001). Regarding blood pressure, heart rate, and ischemia, no rebound response occurred in the 12 h after discontinuation of mivazerol. The high-dose, low-dose, and placebo groups did not differ in the incidence of adverse cardiac outcomes (3%, 2%, and 8%, respectively) or the diagnosis of myocardial infarction (2%, 1%, and 6%, respectively). Continuous, 72-h perioperative administration of mivazerol to high-risk patients appears to be relatively safe, producing no significant hypotension or adverse events but some evidence of bradycardia not associated with adverse clinical events. Mivazerol decreased the incidence of, and treatment for, tachycardia, hypertension, and myocardial ischemia, particularly during high stress periods. Therefore, these salutary effects of mivazerol indicate further study in large-scale trials that assess mivazerol's effects on adverse cardiac outcomes, including death and myocardial infarction.",1997.0,0,0
684,9066993,Effects of methylphenidate on event-related potentials and performance of attention-deficit hyperactivity disorder children in auditory and visual selective attention tasks.,L M Jonkman; C Kemner; M N Verbaten; H S Koelega; G Camfferman; R J vd Gaag; J K Buitelaar; H van Engeland,"Attention-deficit hyperactivity disorder (ADHD) children participated in a double-blind placebo-controlled study in which the effects of a dosage of 15 mg methylphenidate (MPH) on auditory and visual selective attention tasks was determined by presenting frequent (90%) and infrequent (10%) stimuli in both relevant and irrelevant input channels. The subject's task was to respond to the infrequent tones in the relevant input channel. Processing activity (negativity and positivity) was assessed for both tasks. N1, P2, N2, and P3b peaks were scored in the auditory task and N1, P1, N2, P2, P3(1), and P3b peaks were scored in the visual task. Effects of MPH were more prevalent in the visual than in the auditory condition. In the visual condition MPH enhanced the percentage of hits, caused higher central, parietal, and occipital P3b amplitudes to attended stimuli (both standards and deviants), and also enhanced the frontal processing negativity (PN). In the auditory task MPH did not influence performance, but it enhanced the frontal PN as well as the parietal and occipital P3b amplitudes to all stimulus types. In ADHD children, MPH ameliorates some, but not all, deficits and also improves processing where no differences with normal children are present.",1997.0,0,1
685,9067044,Clonidine at induction reduces shivering after general anaesthesia.,D Buggy; P Higgins; C Moran; F O'Donovan; M McCarroll,"Postanaesthetic shivering occurs in 5-65% of patients. In addition to causing discomfort, it is associated with deleterious consequences. Our objective was to investigate the effect of 150 micrograms clonidine, at induction of anaesthesia, on perioperative core and peripheral temperature, incidence of postanaesthetic shivering and patients' perception of cold. Sixty ASA 1 or 2 patients scheduled for elective orthopaedic limb surgery were randomly allocated to group 1, who received 150 micrograms clonidine iv, or group 2, who received a saline bolus iv, before induction. In all patients, anaesthesia was induced with fentanyl and propofol and maintained by spontaneous respiration (via a laryngeal mask airway) of oxygen, nitrous oxide and enflurane. Core (nasopharyngeal) and peripheral (dorsal hand) temperatures were recorded at induction and 15-min intervals. Nurses, unaware of the treatment groups, recorded visible shivering in the recovery room. When cognitive function returned, patients were asked to grade their perception of cold on a 10 cm linear analogue scale, higher scores indicating heat discomfort. While core temperature decreased and peripheral temperature increased in both groups, there was no difference between the groups at any time. However, there was a lower incidence of shivering in the clonidine group (20% vs 66.7%, P < 0.001). Patients receiving clonidine felt warmer; thermal comfort score (median interquartile range) 5.9 (5.0-7.2) vs 5.0 (4.5-6.0), P < 0.05). Clonidine 150 g iv at induction of anaesthesia reduces the incidence of shivering and patients' subjective perception of cold on emergence from general anaesthesia.",1997.0,0,0
686,9075040,Effects of intravenous and oral clonidine on hemodynamic and plasma-catecholamine response due to endotracheal intubation.,M P Zalunardo; A Zollinger; D R Spahn; B Seifert; M Radjaipour; K Gautschi; T Pasch,"To investigate the effects of intravenous (IV) versus oral clonidine on alterations of heart rate (HR), mean arterial pressure (MAP), cardiac output (CO), and plasma-catecholamines due to endotracheal intubation. Randomized, double-blind, placebo-controlled study. University hospital surgery operating room. 33 ASA physical status I patients were randomly assigned to either receive clonidine 3 micrograms/kg IV immediately prior to anesthesia induction, clonidine 4 micrograms/kg orally 90 minutes prior to anesthesia induction, or placebo. Insertion of a 14 G cannula in a large cubital vein for the determination of plasma-catecholamines using local anesthesia. Insertion of a radial artery catheter for measuring blood pressure (BP) using local anesthesia. Transthoracic echocardiography determined CO. Heart rate, MAP, CO, and plasma-catecholamine concentrations were measured. Measurements were performed prior to induction, during intubation, and 10 minutes after intubation. During endotracheal intubation, MAP was significantly lower in the IV clonidine group compared with the placebo and the oral clonidine groups. Cardiac output was significantly lower in the IV clonidine group only. In contrast to the placebo group, norepinephrine plasma concentrations did not increase in either clonidine group. Significant alterations of epinephrine plasma concentrations due to intubation were not observed in either group. Hemodynamics after intubation were not impaired by clonidine treatment. In conclusion, IV clonidine reduced stress response to endotracheal intubation compared with placebo. Oral clonidine at the dose used was less effective in blunting hemodynamic stress response than IV clonidine.",1997.0,0,0
687,9083608,Fenfluramine and methylphenidate in children with mental retardation and borderline IQ: clinical effects.,M G Aman; R A Kern; P Osborne; R Tumuluru; J Rojahn; V del Medico,"A double-blind, placebo-controlled, crossover study of methylphenidate (0.4 mg/kgday) and different doses of fenfluramine (1.0, 1.5, or 2.0 mg/g/day) in children with mental retardation or borderline IQ and ADHD was conducted. Parents, teachers, examiners, and physicians rated the children. There were relatively few significant drug effects by condition. When the optimal fenfluramine dose for each child was compared with placebo and methylphenidate, significant improvements occurred for fenfluramine on several parent and teacher subscales; teachers rated the children as somewhat improved with methylphenidate. The highest dose of fenfluramine produced more behavior compliance but apparently at the cost of cognitive efficiency. Most side effects (drowsiness, dizziness, anorexia) occurred with fenfluramine. Both drugs appear to be effective treatments for children with ADHD and mental retardation, although there is a possible neurotoxic action with fenfluramine. We recommend a gradual phase-in of fenfluramine dosage, up to 1.5 mg/kg/day, for most children.",1997.0,0,1
688,9088819,Cardiovascular and metabolic responses to clonidine and midazolam premedication.,M Taittonen; O Kirvelä; R Aantaa; J Kanto,"In this double-blind placebo controlled study the preoperative cardiovascular and metabolic effects of intramuscular (i.m.) clonidine and midazolam are assessed. Forty-five ASA Grade I patients (n = 15 per group) undergoing plastic surgical procedures were randomly allocated to receive either placebo, clonidine 4 micrograms kg-1 or midazolam 70 micrograms kg-1. Drugs were administered into the deltoid muscle approximately 90 min prior to the scheduled induction of anaesthesia. The metabolic measurements were performed using an indirect calorimetry device. Heart rate and blood pressure were measured noninvasively. Pre-operative subjective anxiety, dryness of mouth and tiredness were assessed using visual analogue scales (VAS). Clonidine increased subjective tiredness significantly more than placebo. Clonidine also induced moderate decreases in blood pressure and heart rate. Oxygen consumption (VO2), CO2 production and energy expenditure (EE) decreased significantly after clonidine and midazolam. The decrease in VO2 and EE was maximally 11-14% on average from the base-lines after clonidine and midazolam. These effects were of longer duration after clonidine and lasted until the end of the 90 min study period. In conclusion, both clonidine and midazolam are effective as a means of decreasing pre-operative VO2 and EE.",1997.0,0,0
689,9090331,Olanzapine versus haloperidol in the treatment of schizophrenia and schizoaffective and schizophreniform disorders: results of an international collaborative trial.,G D Tollefson; C M Beasley; P V Tran; J S Street; J A Krueger; R N Tamura; K A Graffeo; M E Thieme,"This international, multicenter double-blind trial was designed to compare the therapeutic profile of an atypical antipsychotic, olanzapine, with that of a conventional dopamine D2 antagonist, haloperidol. A total of 1,996 patients at 174 sites in Europe and North America were randomly assigned to treatment with olanzapine (N = 1,336) or haloperidol (N = 660) over 6 weeks. The primary efficacy analysis involved the mean change from baseline to endpoint in total scores on the Brief Psychiatric Rating Scale (BPRS). Secondary analyses included comparisons of the mean change in positive and negative symptoms, comorbid depression, extrapyramidal symptoms, and overall drug safety. Olanzapine demonstrated clinical results superior to those of haloperidol on overall improvement according to the BPRS and on every secondary measure, including depression. Olanzapine was also associated with significantly fewer discontinuations of treatment due to lack of drug efficacy or adverse events. Substantially more olanzapine-treated patients (66.5%) than haloperidol-treated patients (46.8%) completed 6 weeks of therapy. Statistically significant advantages of olanzapine treatment were related to 1) change in negative symptoms, 2) extrapyramidal symptom profile, 3) effect on prolactin levels, and 4) response rate. Olanzapine shows a superior and broader spectrum of efficacy in the treatment of schizophrenic psychopathology, with a substantially more favorable safety profile, than haloperidol. It meets several of the criteria for a novel atypical antipsychotic agent.",2001.0,0,0
690,9097768,Apraclonidine and anterior segment laser surgery. Comparison of 0.5% versus 1.0% apraclonidine for prevention of postoperative intraocular pressure rise.,L F Rosenberg; T Krupin; J Ruderman; D L McDaniel; C Siegfried; D P Karalekas; R K Grewal; D K Gieser; R Williams,"To compare the efficacy of 0.5% and 1.0% apraclonidine in preventing laser-induced intraocular pressure (IOP) elevation after trabeculoplasty, neodymium: YAG (Nd: YAG) iridotomy, and capsulotomy. This is a prospective, masked, and randomized study of 83 patients undergoing trabeculoplasty, 62 patients undergoing iridotomy, and 57 patients undergoing capsulotomy. Surgical eyes received one drop of 0.5% or 1.0% apraclonidine immediately after surgery. Intraocular pressure reduced 2 hours after trabeculoplasty in the 0.5% (P = 0.028) and 1.0% (P = 0.004) groups. Intraocular pressure was higher than baseline in a greater number of eyes treated with 0.5% (12 of 39 eyes, 31%) compared with 1.0% apraclonidine (5 of 44 eyes, 11%) (P = 0.032). Intraocular pressure in eyes with a narrow chamber angle was reduced in 16 (85%) of 19 eyes treated with 0.5% and in 10 (84%) of 12 eyes treated with 1.0% apraclonidine after iridotomy. Of patients with chronic angle-closure glaucoma, IOP was similar to prelaser values in 11 (69%) of 16 eyes treated with 0.5% (P > 0.7) and 12 (80%) of 15 eyes treated with 1.0% apraclonidine (P > 0.3). In patients undergoing capsulotomy, pressure was significantly lowered in the 0.5% group (P = 0.04) but not in the 1.0% apraclonidine group. After capsulotomy, both treatment groups had similar (P > 0.3) numbers of eyes with an IOP less than baseline (83% for 0.5% apraclonidine and 81% for 1.0% apraclonidine). The single postoperative administration of 0.5% apraclonidine is as effective as the 1.0% concentration in preventing IOP elevation immediately after trabeculoplasty, iridotomy, or capsulotomy.",1995.0,0,0
691,9097896,Risperidone in the treatment of schizophrenia: a meta-analysis of randomized controlled trials.,F Song,"This study evaluates the relative effectiveness and side-effects of risperidone as compared with conventional neuroleptics in the treatment of schizophrenia, by meta-analysis of 11 double-blind, randomized controlled trials. The proportion of patients showing clinical improvement; use of medications for extrapyramidal side-effects (EPS); the treatment drop-out rates; and the changes in negative PANSS scores were measured. Compared with conventional neuroleptics, slightly more patients in the risperidone group showed clinical improvement [57 vs 52%; odds ratio 1.27, 95% confidence interval (CI): 1.04, 1.56]. The use of concomitant medications for EPS was significantly less in the risperidone group than in the conventional neuroleptic group (22.8 vs 38.4%; odds ratio 0.51, 95% CI: 0.41, 0.63). The overall drop-out rate was lower in the risperidone group than in other neuroleptic group (29.1 vs 33.9%; odds ratio 0.75, 95% CI: 0.61, 0.94). The difference in changes in negative PANSS score between the risperidone and the haloperidol group was -0.74 (95% CI: -1.50, 0.02). Weight gain and tachycardia are more common in patients treated with risperidone. Sensitivity analysis of different analytic approaches did not materially change the main estimates. It was concluded that the short-term efficacy of risperidone is comparable to other neuroleptics in the treatment of schizophrenia. It is associated with significantly fewer EPS than conventional neuroleptics (mainly haloperidol).",1997.0,0,0
692,9108812,Clozapine and associated diabetes mellitus.,A P Popli; P E Konicki; G J Jurjus; M A Fuller; G E Jaskiw,"Clozapine is an effective therapy for the treatment of refractory psychosis. Clozapine-associated adverse effects include sedation, weight gain, sialorrhea, palpitations, seizures, and hematologic changes such as agranulocytosis. We present a four-case series in which clozapine use was associated with either a de novo onset or severe exacerbation of preexisting diabetes mellitus. The change in glycemic control was not significantly related to weight gain. Three of the patients have been able to continue on clozapine therapy and have experienced a reduction in psychotic symptoms. Patients with a family history of diabetes mellitus or with preexisting diabetes mellitus may need to have blood sugar monitored closely during initiation of clozapine treatment.",1997.0,0,0
693,9109903,Benztropine versus clozapine for the treatment of tremor in Parkinson's disease.,J H Friedman; W C Koller; M C Lannon; K Busenbark; E Swanson-Hyland; D Smith,"Four open-label studies have reported beneficial effects of clozapine on the tremor of idiopathic Parkinson's disease (PD). We performed a double-blind crossover trial with a 2-week washout, comparing low-dose clozapine to benztropine for the treatment of tremor in PD. Twenty-two subjects enrolled and 19 completed the study. Benztropine and clozapine were equally effective in improving tremor and the motor score of the United Parkinson's Disease Rating Scale at mean doses of 3.0 and 39 mg/day, respectively. Significant adverse events were experienced with each drug, but leukopenia was not encountered. We conclude that the atypical antipsychotic drug clozapine is helpful in the treatment of tremor in PD and should be considered when all other drug therapies fail.",1997.0,0,0
694,9138438,Adverse effects of risperidone on eye movement activity: a comparison of risperidone and haloperidol in antipsychotic-naive schizophrenic patients.,J A Sweeney; K S Bauer; M S Keshavan; G L Haas; N R Schooler; P D Kroboth,"Risperidone is a novel and clinically effective atypical antipsychotic medication with a unique biochemical profile. To contrast the neurophysiological effects of this new medication with those of a typical antipsychotic medication, we performed quantitative measurements of saccadic eye movements in a series of antipsychotic-naive schizophrenic patients treated with either risperidone or haloperidol. Patients were tested before and after 1 month of treatment, and a matched group of healthy subjects was tested twice over a similar time interval. Risperidone, but not haloperidol, was associated with prolonged latency and decreased peak velocity and accuracy of saccadic eye movements that was detectable 4 weeks after treatment initiation. The adverse effects of risperidone may be due to the lack of development of acute tolerance to its powerful serotonergic (5-HT2A) antagonism, which could be responsible for the disruption of brainstem physiology in regions controlling saccadic eye movements.",1997.0,0,0
695,9154590,Nursing home research from industry's perspective.,M Brecher,,1996.0,0,0
696,9157096,A preliminary analysis of interactive effects between common classroom contingencies and methylphenidate.,J Northup; K Jones; C Broussard; G DiGiovanni; M Herring; I Fusilier; A Hanchey,"To assess the drug-behavior interaction effects with an 8-year-old boy wih attention deficit hyperactivity disorder, common classroom antecedent (e.g., seating arrangement) and consequent (e.g., peer prompts) stimuli were alternated within a school day while drug conditions (methylphenidate vs. placebo) were alternated across days. The results suggested that peer attention maintained disruptive behavior when methylphenidate was absent but not when it was present.",1997.0,0,0
697,9161888,Effects of methylphenidate in children with attention deficit hyperactivity disorder: a comparison of event-related potentials between medication responders and non-responders.,G A Sunohara; J G Voros; M A Malone; M J Taylor,"Event-related potentials (ERPs) were compared among three groups, each with 13 subjects: (1) ADHD non-responders to methylphenidate treatment; (2) ADHD responders to methylphenidate treatment; and (3) normal control children. Response to methylphenidate was determined through extensive psychoeducational and cognitive assessments during a 4-week double-blind medication assessment. ERPs were recorded each week from 13 active electrodes during a visual feature detection task and a semantic classification task. Significant group effects were found for N2 and P3b latencies due to longer latencies for the ADHD children. Off medication, there were no differences between responders and non-responders. However, on methylphenidate non-responders had significantly longer P3b latencies than responders. Cognitive testing also revealed differential performance on medication between non-responders and responders on the paired-associate learning (PAL) task. Thus, both cognitive and ERP measures were found to differentiate ADHD non-responders and responders to methylphenidate treatment.",1997.0,0,0
698,9165565,Risperidone: effects of formulations on oral bioavailability.,R Gutierrez; P I Lee; M L Huang; R Woestenborghs,"The bioavailability of risperidone was evaluated in an open-label, randomized, two-way, crossover study comparing a 1-mg tablet with a 1-mg/ml oral solution. Both formulations were administered as a single 1-mg dose with a 10-day washout period between treatments. Of 26 healthy men who entered the study, 23 completed both treatment periods. Plasma concentrations of risperidone and the active moiety (risperidone plus its active metabolite, 9-hydroxyrisperidone) were determined by radioimmunoassays. For key pharmacokinetic values (Cmax, AUC), the 90% CIs on the relative bioequivalence of risperidone, 9-hydroxyrisperidone, and the active moiety were contained within the equivalence range of 80-120% (80-125% for log-transformed data). The results demonstrate that the 1-mg/ml oral solution and the 1-mg tablet are bioequivalent.",1997.0,0,0
699,9169300,Olanzapine versus haloperidol: acute phase results of the international double-blind olanzapine trial.,C M Beasley; S H Hamilton; A M Crawford; M A Dellva; G D Tollefson; P V Tran; O Blin; J N Beuzen,"A 6-week acute phase of an international 1-year double-blind study was conducted comparing three dose ranges of olanzapine (5 +/- 2.5 mg/day, 10 +/- 2.5 mg/day, and 15 +/- 2.5 mg/day) with a fixed dose of olanzapine (1.0 mg/day) and with a dose range of haloperidol (15 +/- 5 mg/day) in the treatment of 431 patients with schizophrenia. The purpose was to determine whether olanzapine demonstrated a dose-related ability to decrease overall psychopathology with minimal associated extrapyramidal symptoms in patients with schizophrenia. The high-dose olanzapine group showed statistically significantly greater improvement in overall psychopathology based on mean change in the CGI Severity score and statistically significantly greater improvement in positive psychotic symptoms based on mean change in both the BPRS positive score and the PANSS positive score compared with the 1.0-mg/day olanzapine group. Analyses indicated that an increasing dose-response curve was observed across the range of all olanzapine dose groups. Acute extrapyramidal syndromes were reported less frequently among all olanzapine groups compared with the haloperidol group. Endpoint mean change on both the Simpson-Angus Scale and the Barnes Akathisia Scale reflected improvement for all olanzapine treatment groups compared with worsening for the haloperidol group. Olanzapine was associated with weight gain but did not appear to have any clinically meaningful effect on vital signs. Although olanzapine was associated with some increase in prolactin concentrations, increases were transient, occurred less often, and were of lesser magnitude than those observed with haloperidol.",2001.0,0,0
700,9169965,Extrapyramidal symptoms in patients treated with risperidone.,G M Simpson; J P Lindenmayer,"Data on extrapyramidal symptoms (EPS) from both arms of the North American multicenter comparative study of risperidone, placebo, and haloperidol were analyzed. The subjects were 523 patients with chronic schizophrenia who, after a 1-week washout period, received placebo, risperidone (2, 6, 10, or 16 mg/day), or haloperidol (20 mg/day) for 8 weeks; the trial was completed by 253 patients. Severity of EPS was assessed by means of the Extrapyramidal Symptom Rating Scale (ESRS). Mean changes (increases) in ESRS scores from baseline to worst score were significantly lower in each risperidone group than the haloperidol group on the total ESRS (parkinsonism + dystonia + dyskinesia), total parkinsonism, hypokinetic symptoms, and on the questionnaire (p < 0.001). On several of the subscales (dyskinesia, buccolinguomasticatory, and Clinical Global Impression severity of dyskinesia), mean change scores were significantly lower in some of the risperidone groups than in the placebo group (p < 0.05). At the clinically most effective risperidone dose (6 mg/day), the mean ESRS change score was not significantly different from that of the placebo group. A significant linear relationship was noted between mean change scores and increasing risperidone dose on 4 of the 12 ESRS subscales; nevertheless, even at 16 mg/day of risperidone, mean change scores were lower than in the haloperidol group. A linear relationship between increasing risperidone dose and use of antiparkinsonian medications was also apparent. Acute dystonic reactions occurred both in patients receiving risperidone and haloperidol. Patients with severe baseline EPS were at higher risk of EPS during the study than patients with low or moderate baseline EPS. It is concluded that low doses of risperidone cause few or no EPS and recommendations for initiation of risperidone treatment are made.",1997.0,0,0
701,9184614,Extrapyramidal symptoms and tolerability of olanzapine versus haloperidol in the acute treatment of schizophrenia.,P V Tran; M A Dellva; G D Tollefson; C M Beasley; J H Potvin; G M Kiesler,"A relative lack of extrapyramidal symptoms (EPS, i.e., the syndromes of dystonia, parkinsonism, akathisia, dyskinesia) is one criterion used to determine whether an antipsychotic is ""atypical."" The extrapyramidal symptom profiles of the novel antipsychotic olanzapine and the conventional antipsychotic haloperidol were compared in a population of 2606 patients from three well-controlled prospective clinical trials. Extrapyramidal symptom data were analyzed for 1796 patients treated with olanzapine (5 to 20 mg/day) and 810 patients treated with haloperidol (5 to 20 mg/day) for up to 6 weeks of therapy. Patients were monitored weekly by three methods of extrapyramidal symptom assessment: (1) detection of extrapyramidal adverse events (signs and symptoms) by casual observation, nonprobing inquiry, and spontaneous report; (2) objective rating scale scores: and (3) use of concomitant anticholinergic medications. Emergence of EPS was assessed by (1) analysis of the incidence of extrapyramidal syndrome categories based on adverse events, (2) the incidence of extrapyramidal syndromes based on categorical analysis of rating scale scores, (3) analysis of mean maximum change in rating scale scores, and (4) categorical analysis of anticholinergic medication use. Outcome of EPS was assessed by (1) analysis of mean change in rating scale scores at endpoint and (2) mean anticholinergic use at endpoint. Olanzapine was statistically significantly (p = .014, p < .001) superior to haloperidol in all four analyses related to emergence of EPS and in the two analyses related to outcome. Furthermore, during acute treatment, statistically significantly fewer patients treated with olanzapine (0.3%) discontinued the study because of any extrapyramidal adverse event than patients treated with haloperidol (2.7%, p < .001). Olanzapine exhibited a statistically significantly lower extrapyramidal symptom profile than the conventional antipsychotic haloperidol at comparably effective antipsychotic doses. The lower extrapyramidal symptom profile with olanzapine was evident despite statistically significantly more frequent use of anticholinergic drugs among haloperidol-treated patients. Fewer olanzapine-treated than haloperidol-treated patients discontinued because of EPS, suggesting that olanzapine should contribute to better compliance with longer term maintenance treatment, with minimal anticholinergic-associated events.",2001.0,0,0
702,9193196,Quetiapine in patients with schizophrenia. A high- and low-dose double-blind comparison with placebo. Seroquel Study Group.,J G Small; S R Hirsch; L A Arvanitis; B G Miller; C G Link,"Quetiapine fumarate (Seroquel [ICI 204,636]) is an atypical dibenzothiazepine antipsychotic with a greater affinity for 5-hydroxytryptamine2 (5-HT2) receptors than for D2 dopamine receptors; its efficacy in patients with schizophrenia was shown in early phase 2 trials (maximum dose, 750 mg/d). In this multicenter, double-blind, placebo-controlled trial, 286 patients hospitalized with chronic or subchronic schizophrenia (DSM-III-R) were randomized to 6 weeks of treatment with high-dose quetiapine fumarate (< or = 750 mg/d), n = 96; low-dose quetiapine fumarate (< or = 250 mg/d), n = 94; or placebo, n = 96. The Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression Severity of Illness item scores were the primary efficacy variables. Secondary efficacy variables included the BPRS positive-symptom cluster score, the Modified Scale for the Assessment of Negative Symptoms summary score (United States only), and the total score from the negative scale of the Positive and Negative Syndrome Scale (Europe only). Scores were analyzed using an analysis of covariance for change from baseline at end point with last observations carried forward. The model included baseline score (covariate), center, and treatment. Extrapyramidal symptoms were assessed using the Simpson-Angus Scale and the Barnes Akathisia Scale; abnormal involuntary movements were assessed using the Abnormal Involuntary Movement Scale. Frequency distributions of grouped change-from-baseline scores were analyzed using chi 2 tests. Of 280 patients in whom the efficacy of quetiapine was evaluated, 159 (42% of those receiving high-dose treatment; 57%, low-dose treatment; and 59%, placebo) withdrew before trial completion, primarily because of treatment failure. Significant (P < .001, BPRS; P = .003, Clinical Global Impression Severity of Illness item; and P = .003, BPRS positive-symptom cluster) differences were identified between patients receiving high-dose quetiapine and placebo for both primary efficacy variables, with end point differences in the BPRS positive-symptom cluster score showing quetiapine's consistency in reducing positive symptoms. The reduction of negative symptoms was less consistent; high-dose quetiapine was superior on the Modified Scale for the Assessment of Negative Symptoms but not on the negative scale of the Positive and Negative Syndrome Scale. Quetiapine was well tolerated and did not induce extrapyramidal symptoms, sustained elevations of prolactin, or clinically significant changes in hematologic parameters. Quetiapine is an effective antipsychotic with a favorable safety profile. The optimum dose is probably greater than 250 mg/d.",1997.0,0,0
703,9193208,Relationship of the antispasticity effect of tizanidine to plasma concentration in patients with multiple sclerosis.,P W Nance; W A Sheremata; S G Lynch; T Vollmer; S Hudson; G S Francis; P O'Connor; J A Cohen; R T Schapiro; R Whitham; M K Mass; J W Lindsey; K Shellenberger,"Spasticity is a serious problem in multiple sclerosis (MS) and many patients do not achieve a satisfactory response to currently available oral antispasticity drugs. Tizanidine hydrochloride, an alpha 2-noradrenergic agonist, has been shown to have an antispasticity effect in single center trials of patients with MS. To compare plasma concentrations of tizanidine with objective measures of muscle tone in patients with MS with moderate to severe spasticity. Ten centers, all tertiary referral centers for the specialized treatment of patients with MS, in the United States and Canada. A randomized, double-blind, placebo-controlled, dose-response study of tizanidine hydrochloride (8 or 16 mg). One hundred forty-two patients with spastic MS who were not taking any interfering medication, such as an antispasticity drug or other alpha-noradrenergic agonist, entered the trial. Tizanidine treatment reduced muscle tone significantly, as shown by improved Ashworth scores and increased knee swing amplitude recorded by the pendulum test, both of which correlated significantly with plasma concentration. Placebo had no significant effect on muscle tone. Dizziness, drowsiness, dry mouth, and fatigue were reported most often in the group treated with tizanidine at peak plasma concentration. Tizanidine reduces spasticity in MS, and both therapeutic effects and side effects are related to the plasma drug levels.",1997.0,0,0
704,9196923,Psychopharmacologic treatment of pathologic aggression.,M Fava,"Several drugs are apparently effective in treating pathologic anger and aggression. Because many of the studies on aggressive populations allowed the use of concomitant medications, it is unclear whether the efficacy of each drug in a particular population is dependent on the presence of other medications, such as antipsychotic agents. Finally, one needs to be circumspect in inferring efficacy of a particular drug in aggressive patients with neuropsychiatric conditions other than the ones in which some efficacy has been established. Lithium appears to be an effective treatment of aggression among nonepileptic prison inmates, mentally retarded and handicapped patients, and among conduct-disordered children with explosive behavior. Certainly, lithium would be the treatment of choice in bipolar patients with excessive irritability and anger outbursts, and it has been shown to be effective in this population. Anticonvulsant medications are the treatment of choice for patients with outbursts of rage and abnormal EEG findings. The efficacy of these drugs in patients without a seizure disorder, however, remains to be established, with the exception perhaps of valproate and carbamazepine. In fact, dyphenylhydantoin did not appear to be effective in treating aggressive behavior in children with temper tantrums and was found to be effective in only a prison population. There is some evidence for the efficacy of carbamazepine and valproate in treating pathologic aggression in patients with dementia, organic brain syndrome, psychosis, and personality disorders. As Yudofsky et al point out in their review of the literature, although traditional antipsychotic drugs have been used widely to treat aggression, there is little evidence for their effectiveness in treating aggression beyond their sedative effect in agitated patients or their antiaggressive effect among patients whose aggression is related to active psychosis. Antipsychotic agents appear to be effective in treating psychotic aggressive patients, conduct-disordered children, and mentally retarded patients, with only modest effects in the management of pathologic aggression in patients with dementia. Furthermore, at least in one study, these drugs were found to be associated with increased aggressiveness in mentally retarded subjects. On the other hand, atypical antipsychotic agents (i.e., clozapine, risperidone, and olanzapine) may be more effective than traditional antipsychotic drugs in aggressive and violent populations, as they have shown efficacy in patients with dementia, brain injury, mental retardation, and personality disorders. Similarly, benzodiazepines can reduce agitation and irritability in elderly and demented populations, but they also can induce behavioral disinhibition. Therefore, one should be careful in using this class of drugs in patients with pathologic aggression. Beta-blockers appear to be effective in many different neuropsychiatric conditions. These drugs seem effective in reducing violent and assaultive behavior in patients with dementia, brain injury, schizophrenia, mental retardation, and organic brain syndrome. As pointed out by Campbell et al in their review of the literature, however, systematic research is lacking, and little is known about the efficacy and safety of beta-blockers in children and adolescents with pathologic aggression. Although widely used in the management of pathologic aggression, the use of this class of drugs has been limited partially by marked hypotension and bradycardia, which are side effects common at the higher doses. The usefulness of the antihypertensive drug clonidine in the treatment of pathologic aggression has not been assessed adequately, and only marginal benefits were observed with this drug in irritable autistic and conduct disorder children. Psychostimulants seem to be effective in reducing aggressiveness in brain-injured patients as well as in violent adolescents with oppositional or conduct disorders, particu",1997.0,0,0
705,9203234,"A clinical evaluation of risperidone in the treatment of schizophrenia: a 10-week, open-label, multicenter trial. ARCS Study Group. Assessment of Risperdal in a Clinical Setting.",D V Jeste; M Klausner; M Brecher; C Clyde; R Jones,"The efficacy and safety of risperidone have previously been demonstrated in controlled clinical trials in hospitalized chronic schizophrenia patients who met strict research criteria. The present study was designed to evaluate the efficacy and safety of risperidone in a heterogeneous patient population. Patients were enrolled in the study if they had a diagnosis of schizophrenia (DSM-III-R) with or without acute exacerbation. Of the 945 patients from 158 psychiatric centers who entered this phase IV study, 558 completed the 10-week trial. During week 1, the dose of risperidone was titrated to 6 mg/day, maintained there for 1 week, and then adjusted over a 4-week period as clinically necessary; the dose was then fixed for the final 4-week period. The mean dose of risperidone at endpoint was 5.9 mg/day. Patients were evaluated at baseline and at weeks 2, 6, and 10, using Clinical Global Impression scale, Psychotic Symptoms Assessment scale, and Global Assessment of Functioning scale. Significant improvement in mean scores was found on each of these measures at endpoint. Comparable results were obtained at week 10 in treatment-resistant and non-treatment-resistant patients. Risperidone was generally well tolerated and the severity of extrapyramidal symptoms was significantly reduced at endpoint.",1997.0,0,0
706,9209730,Clozapine-induced electroencephalogram changes as a function of clozapine serum levels.,O Freudenreich; R D Weiner; J P McEvoy,"Specific electroencephalogram (EEG) changes during clozapine therapy were prospectively studied in a cohort of 50 chronic state hospital patients with schizophrenia who were randomly assigned to one of three nonoverlapping clozapine serum level ranges (50-150 ng/mL, 200-300 ng/mL, and 350-450 ng/mL). EEGs were obtained before clozapine was instituted, and after 10 weeks of treatment. Fifty-three percent of patients showed EEG changes during the 10-week study period. We observed three seizures (6%), one in a patient on 900 mg (serum level 320 ng/mL) clozapine, and two in patients with lower clozapine serum levels (200-300 ng/mL) who had prior histories of seizures and inadequate valproate coverage. Thirteen percent of patients developed spikes with no relationship to dose or serum level of clozapine. Fifty-three percent of patients developed slowing on EEG. Compared to plasma levels below 300 ng/mL, a clozapine serum level between 350 and 450 ng/mL led to more frequent and more severe slowing. The EEG slowing correlated with observed sleepiness, although this factor was not sufficient to explain the severity of high-dose effects.",1997.0,0,0
707,9214531,Pharmacological management of alcohol withdrawal. A meta-analysis and evidence-based practice guideline. American Society of Addiction Medicine Working Group on Pharmacological Management of Alcohol Withdrawal.,M F Mayo-Smith,"To provide an evidence-based practice guideline on the pharmacological management of alcohol withdrawal. English-language articles published before July 1, 1995, identified through MEDLINE search on ""substance withdrawal--ethyl alcohol"" and review of references from identified articles. Articles with original data on human subjects. Structured review to determine study design, sample size, interventions used, and outcomes of withdrawal severity, delirium, seizures, completion of withdrawal, entry into rehabilitation, adverse effects, and costs. Data from prospective controlled trials with methodologically sound end points corresponding to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, were abstracted by 2 independent reviewers and underwent meta-analysis. Benzodiazepines reduce withdrawal severity, reduce incidence of delirium (-4.9 cases per 100 patients; 95% confidence interval, -9.0 to -0.7; P=.04), and reduce seizures (-7.7 seizures per 100 patients; 95% confidence interval, -12.0 to -3.5; P=.003). Individualizing therapy with withdrawal scales results in administration of significantly less medication and shorter treatment (P<.001). beta-Blockers, clonidine, and carbamazepine ameliorate withdrawal severity, but evidence is inadequate to determine their effect on delirium and seizures. Phenothiazines ameliorate withdrawal but are less effective than benzodiazepines in reducing delirium (P=.002) or seizures (P<.001). Benzodiazepines are suitable agents for alcohol withdrawal, with choice among different agents guided by duration of action, rapidity of onset, and cost. Dosage should be individualized, based on withdrawal severity measured by withdrawal scales, comorbid illness, and history of withdrawal seizures. beta-Blockers, clonidine, carbamazepine, and neuroleptics may be used as adjunctive therapy but are not recommended as monotherapy.",1997.0,0,0
708,9219046,Response to clozapine in acute mania is more rapid than that of chlorpromazine.,B Barbini; P Scherillo; F Benedetti; G Crespi; C Colombo; E Smeraldi,"The purpose of the present study was to compare the efficacy of clozapine with that of chlorpromazine in an open label manner (both given in association with lithium salts) in the treatment of acute mania. Thirty hospitalized manic patients were entered into the study. All patients met DSM-IV criteria for bipolar disorder, Manic Episode; 27 patients completed the study and three patients dropped for noncompliance. The duration of the study was 3 weeks. Patients were randomly assigned to two treatment groups; group 1 (n = 15) was treated with clozapine at a mean dose of 166 mg/day and group 2 (n = 12) was treated with chlorpromazine at a mean dose of 310 mg/day. Manic symptomatology was rated on Young Rating Scale for Mania (YRSM) each week; side effects were recorded on dosage records and treatment emergent symptoms; extrapyramidal acute side effects were rated on the Simpson-Angus Rating Scale performed at the beginning of the study and after 3 weeks of treatment. A two-way repeated measures analysis of variance on YRMS scores showed a significant time effect (p < 0.0001) and a significant time-group interaction (p < 0.0001). Post-hoc comparison between the two groups showed a significant difference after 2 weeks of treatment (p = 0.0001), with clozapine treated patients showing lower YRSM scores than chlorpromazine treated patients. YRSM scores at the end of the study were not significantly different. Patients treated with clozapine showed a more rapid trend toward amelioration. No clinically relevant side effect was observed during the study.",1997.0,0,0
709,9219047,"Diltiazem, a calcium antagonist, partly attenuates the effects of dextroamphetamine in healthy volunteers.",J E Fabian; P H Silverstone,"Calcium antagonists have previously been shown to be effective in the treatment of mania. In the present study we used dextroamphetamine administered to humans as a model of mania, to determine whether the calcium antagonist diltiazem would prevent dextroamphetamine-induced changes. This may help determine whether diltiazem is likely to be useful in the treatment of mania. Ten healthy volunteers were enrolled in this double-blind, placebo-controlled, balanced crossover study. Subjects received either oral diltiazem (60 mg) and placebo, placebo and dextroamphetamine (20 mg), diltiazem and dextroamphetamine, or placebo alone. Subjective and sleep changes were measured using visual analogue scales. Attentiveness and visual reaction times were measured repeatedly as were diastolic and systolic blood pressure. The results showed that dextroamphetamine alone produced a number of subjective changes, cardiovascular changes and changes in reaction time. Diltiazem significantly attenuated the cardiovascular changes, but not the subjective or reaction time changes. It is hypothesized that these findings may represent effects of diltiazem on noradrenergic neurotransmission. The results are tentatively supportive of suggestions that diltiazem may be clinically useful in the treatment of mania, as is another calcium channel antagonist, verapamil.",1997.0,0,0
710,9233740,Effects of clonidine on prolonged postoperative sympathetic response.,T Dorman; K Clarkson; B A Rosenfeld; C Shanholtz; P A Lipsett; M J Breslow,"Surgical trauma results in diffuse sympathoadrenal activation which is thought to contribute to perioperative cardiovascular complications in high-risk patients. Regional anesthetic and analgesic techniques can attenuate this ""stress response"" and reduce the occurrence rate of adverse perioperative events; however, their use in the postoperative period is logistically difficult and costly. The present study was undertaken to evaluate whether transdermal administration of the alpha2 adrenergic-receptor agonist, clonidine, can be used as a pharmacologic means of blunting the stress response throughout the perioperative period. Double-blind, placebo-controlled clinical trial in patients undergoing pancreatico-biliary surgery. Operating rooms and surgical intensive care unit of a major university teaching hospital. Forty patients scheduled for major upper abdominal surgery. Patients received either clonidine (0.2 mg orally and a clonidine TTS-3 patch the evening before surgery and 0.3 mg orally on call to the operating room) or matched oral and transdermal placebo. Heart rate, systemic arterial blood pressure, plasma catecholamine, clonidine, interleukin-6 concentrations, and 24-hr urine cortisol and nitrogen excretion were measured the day before surgery and daily thereafter for 72 hrs postoperatively. Preoperative transdermal (and oral) clonidine administration resulted in therapeutic plasma clonidine concentrations throughout the perioperative period (1.54 +/- .07 [SEM] microg/mL). Clonidine reduced preoperative epinephrine and norepinephrine concentrations by 65%. Plasma catecholamine concentrations increased in both groups following surgery but were markedly lower throughout the postoperative period in patients receiving clonidine. Patients receiving clonidine had a reduced frequency rate of postoperative hypertension. Clonidine had no effect on plasma interleukin-6 concentration, urine cortisol excretion, or urine nitrogen excretion. No adverse effects of clonidine administration were observed. The combined administration of oral and transdermal clonidine effectively attenuated the catecholamine response to surgical stress throughout the postoperative study period. Clonidine administration produced specific sympatholytic effects, since other elements of the stress response were not attenuated. Undesirable side effects were not noted. The sustained sympatholytic effects we observed suggest that alpha2 adrenergic-receptor agonists may offer a pharmacologic means of modifying the sympathoadrenal response to injury, and may be useful in reducing perioperative complications.",1997.0,0,0
711,9241004,"Comparison of fluoxetine, bupropion, and placebo in the treatment of premenstrual dysphoric disorder.",T B Pearlstein; A B Stone; S A Lund; H Scheft; C Zlotnick; W A Brown,"Serotonergic antidepressants have been shown to be effective treatments for premenstrual dysphoric disorder (PMDD). The efficacy of nonserotonergic antidepressants is less well studied. This study was a two-center, parallel design, placebo-controlled, randomized trial of fluoxetine, bupropion, and placebo in women with PMDD. Thirty-four women with PMDD completed 1 month of single-blind placebo and 2 months of fluoxetine 20 mg/day (N = 10), bupropion 100 mg three times daily (N = 12), or placebo (N = 12). Clinical Global Impressions (CGI) Scale, an expanded form of the Hamilton Rating Scale for Depression (HAM-D), and Global Assessment Scale (GAS) ratings were obtained premenstrually in each of the three treatment cycles. The three treatment groups differed significantly in efficacy by CGI ratings. Fluoxetine was superior to both bupropion and placebo. Comparison of posttreatment to pretreatment HAM and GAS scores demonstrated significant superior efficacy of fluoxetine compared with placebo. Posttreatment HAM and GAS scores for bupropion were intermediate between but not significantly different from fluoxetine or placebo. In summary, fluoxetine was significantly superior to bupropion and placebo as an effective treatment for PMDD. Although some improvement with bupropion was noted, and both medications were well tolerated, patient satisfaction was far greater with fluoxetine.",1997.0,0,0
712,9241010,Economic and health state utility determinations for schizophrenic patients treated with risperidone or haloperidol.,G Chouinard; P S Albright,"The current study uses utility analysis to assess economic and quality-of-life benefits of risperidone in patients with chronic schizophrenia. A retrospective analysis was performed on Positive and Negative Syndrome Symptoms (PANSS) data obtained from the published Canadian multicenter risperidone trial (part of the North American trial). Cluster analysis applied to endpoint PANSS scores, including all patients (N = 135), identified three clusters representing 130 patients with mild, moderate, and severe symptomatology. A narrative health state profile was written for each cluster, and 100 psychiatric nurses from Washington, DC, were asked to assign preference ratings to each one using linear analog and standard gamble (SG) methods. Mean utility values (confidence interval 95%) obtained from the SG ratings for the three health state profiles were 0.61 +/- 0.069 (mild); 0.36 +/- 0.073 (moderate); and 0.29 +/- 0.071 (severe). The mild health state (including the majority of risperidone 6 mg-treated patients) was rated by nurses to have a 0.25 +/- 0.0501 greater utility than the moderate health state (composed of the majority of haloperidol-treated patients). The results of these utility evaluations (SG) by the nurses were related to the clinical outcome for three of the six drug treatment groups (N = 65) by multiplying the percentage of patients in each of the three clusters, both at baseline and end-point, who were receiving risperidone 6 mg/day, haloperidol, or placebo, by the utility value for the health state assigned to that cluster. The gain in utility for risperidone-treated patients was 2.6 times higher (0.125) compared with haloperidol-treated patients (0.049), and 7 times higher compared with placebo (-0.021). After multiplying the gain in utility of each treatment by the remaining expected life span for men and women, it was found that risperidone-treated patients obtained more than twice as many quality-adjusted years as haloperidol patients. The incremental drug treatment cost divided by the incremental benefit of risperidone versus haloperidol was found to yield a favorable, generally accepted cost-utility ratio.",1997.0,0,0
713,9241012,Hepatotoxicity of clozapine.,M Hummer; M Kurz; I Kurzthaler; H Oberbauer; C Miller; W W Fleischhacker,"Two hundred thirty-eight patients treated with either haloperidol or clozapine were investigated to shed more light on the incidence and severity of antipsychotic-induced liver enzyme increase. Serum glutamic-pyruvic transaminase (SGPT) increase was most frequently seen in both treatment groups. When analyzing the incidence rates for patients with increased liver enzyme values (serum glutamic-oxaloacetic transaminase, SGPT, gamma-glutamyl transpeptidase) that were higher than twice the upper limit of the normal range, clozapine-treated patients showed an SGPT increase (37.3%) significantly more frequently than patients treated with haloperidol (16.6%). Both patients with higher clozapine plasma levels and male patients were at a higher risk for an SGPT increase. At least 60% of the increase of the different enzymes remitted within the first 13 weeks of treatment. In general, the authors conclude that clozapine-induced liver enzyme elevation seems to be a common and mostly transient phenomenon.",1997.0,0,0
714,9243353,"Desmethylselegiline, a metabolite of selegiline, is an irreversible inhibitor of monoamine oxidase type B in humans.",E H Heinonen; M I Anttila; H L Karnani; L M Nyman; J A Vuorinen; K A Pyykkö; R A Lammintausta,"Selegiline, an irreversible and selective inhibitor of monoamine oxidase type B (MAO-B), is metabolized into desmethylselegiline, levomethamphetamine, and levoamphetamine. In animal experiments, desmethylselegiline also has been shown to be an irreversible inhibitor of MAO-B. This study investigated the inhibitory potential of MAO-B and the pharmacokinetics of desmethylselegiline in humans. A double-blind, crossover trial was performed to compare the effects of a single dose (10 mg) of selegiline or desmethylselegiline on MAO-B platelet activity. The urinary excretion of phenylethylamine, which is considered to be a parameter of MAO-B inhibition, also was measured. The concentrations of selegiline, desmethylselegiline, and their metabolites were measured in plasma after administration of the two compounds. Ten healthy volunteers participated in the study. There was a clear inhibition of platelet MAO-B by both compounds. Desmethylselegiline caused a 63.7 +/- 12.7% inhibition of platelet MAO-B compared with 96.4 +/- 3.9% caused by selegiline. The maximal inhibition by desmethylselegiline was reached significantly later after desmethylselegiline (time to reach maximal inhibition [tmax], 27 +/- 20 hours) than after selegiline administration (tmax, 1.4 +/- 1.4 hours). The platelet MAO-B activity returned to baseline levels within 2 weeks, thus reflecting the irreversible nature of the inhibition by both compounds. The cumulative 48-hour excretion of phenylethylamine was 33% lower after desmethylselegiline than after selegiline administration. All three major metabolites of selegiline could be detected in plasma after selegiline administration. Levoamphetamine was the only metabolite of desmethylselegiline. The area under the concentration-time curve from time 0 to 24 hours (AUC0-24) of desmethylselegiline was 33 times higher than that of selegiline, suggesting a better bioavailability of desmethylselegiline. Desmethylselegiline is an orally active, irreversible inhibitor of MAO-B and could possibly be used to treat Parkinson's disease in the same way as selegiline.",1997.0,0,0
715,9248867,A double-blind comparative study of clozapine versus chlorpromazine on Chinese patients with treatment-refractory schizophrenia.,C J Hong; J Y Chen; H J Chiu; C B Sim,"Clozapine has been shown to have superior effectiveness compared with classic neuroleptics in treating refractory schizophrenia in Caucasians, but its efficacy and safety in Chinese have not been adequately studied. Forty Chinese schizophrenic patients were recruited in a 12-week, double-blind, comparative trial. Twenty-one patients were randomly assigned to clozapine treatment and 19 to chlorpromazine treatment. The average dose was 543 +/- 157 and 1163 +/- 228 mg/day for clozapine and chlorpromazine, respectively. The results showed that six clozapine-treated patients (28.6%) had more than 20% improvement in Brief Psychiatric Rating Scale score and were classified as responders, whereas none of the chlorpromazine-treated patients was classified as a responder. The degree of improvement in positive symptoms, negative symptoms and Brief Psychiatric Rating Scale scores in the clozapine group was inversely correlated with the severity of negative symptoms at entry into the trial. Two clozapine-treated patients were withdrawn from the study, one because of leukopenia and nausea, and the other because of vomiting and hypotension. Chlorpromazine treatment was prematurely discontinued in two patients, because of jaundice and over sedation in one, and because of severe weight loss in the other (9 kg). The rate of moderate-to-severe sialorrhea was high in clozapine-treated patients (28.6%). Two clozapine-treated patients and two chlorpromazine-treated patients showed significant improvement in previously existing tardive dyskinesia and one chlorpromazine-treated patient exhibited aggravation of tardive dyskinesia. The results of this study indicate that clozapine treatment might have advantages over chlorpromazine for Chinese schizophrenic patients who are refractory to typical neuroleptic treatment.",1997.0,0,0
716,9257090,,,,,0,1
717,9260445,"Sense of time in children with ADHD: effects of duration, distraction, and stimulant medication.",R A Barkley; S Koplowitz; T Anderson; M B McMurray,"A recent theory of ADHD predicts a deficiency in sense of time in the disorder. Two studies were conducted to test this prediction, and to evaluate the effects of interval duration, distraction, and stimulant medication on the reproductions of temporal durations in children with ADHD. Study I: 12 ADHD children and 26 controls (ages 6-14 years) were tested using a time reproduction task in which subjects had to reproduce intervals of 12, 24, 36, 48, and 60 s. Four trials at each duration were presented with a distraction occurring on half of these trials. Control subjects were significantly more accurate than ADHD children at most durations and were unaffected by the distraction. ADHD children, in contrast, were significantly less accurate when distracted. Both groups became less accurate with increasing durations to be reproduced. Study II: Tested three doses of methylphenidate (MPH) and placebo on the time reproductions of the 12 ADHD children. ADHD children became less accurate with increasing durations and distraction was found to reduce accuracy at 36 s or less. No effects of MPH were evident. The results of these preliminary studies seem to support the prediction that sense of time is impaired in children with ADHD. The capacity to accurately reproduce time intervals in ADHD children does not seem to improve with administration of stimulant medication.",1997.0,0,0
718,9265916,Dosing the antipsychotic medication olanzapine.,C B Nemeroff,"Olanzapine is a new antipsychotic agent with serotonin/dopamine antagonism action. Efficacy in treating overall psychopathology in acute schizophrenia as measured by the BPRS0-6 total score was demonstrated at 10 mg/day versus placebo; at doses in a 5-20 mg/day range, olanzapine was comparable or superior to haloperidol. Superior efficacy for negative and depressive symptoms was shown in comparison to haloperidol. Olanzapine has a favorable acute and tardive extrapyramidal symptom profile relative to haloperidol and caused substantially less elevation of serum prolactin. Dose-related weight gain and asymptomatic mild transaminase elevations occurred in olanzapine-treated patients.",1997.0,0,0
719,9270575,"Randomized, double-blind, placebo-controlled crossover trial of modafinil in the treatment of excessive daytime sleepiness in narcolepsy.",R J Broughton; J A Fleming; C F George; J D Hill; M H Kryger; H Moldofsky; J Y Montplaisir; R L Morehouse; A Moscovitch; W F Murphy,"Seventy-five patients meeting international diagnostic criteria for narcolepsy enrolled in a 6-week, three-period, randomized, crossover, placebo-controlled trial. Patients received placebo, modafinil 200 mg, or modafinil 400 mg in divided doses (morning and noon). Evaluations occurred at baseline and at the end of each 2-week period. Compared with placebo, modafinil 200 and 400 mg significantly increased the mean sleep latency on the Maintenance of Wakefulness Test by 40% and 54%, with no significant difference between the two doses. Modafinil, 200 and 400 mg, also reduced the combined number of daytime sleep episodes and periods of severe sleepiness noted in sleep logs. The likelihood of falling asleep as measured by the Epworth Sleepiness Scale was equally reduced by both modafinil dose levels. There were no effects on nocturnal sleep initiation, maintenance, or architecture, nor were there any effects on sleep apnea or periodic leg movements. Neither dose interfered with the patients' ability to nap voluntarily during the day nor with their quantity or quality of nocturnal sleep. Modafinil produced no changes in blood pressure or heart rate in either normotensive or hypertensive patients. The only significant adverse effects were seen at the 400-mg dose, which was associated with more nausea and more nervousness than either placebo or the 200-mg dose. As little as a 200-mg daily dose of modafinil is therefore an effective and well-tolerated treatment of excessive daytime somnolence in narcoleptic persons.",1997.0,0,0
720,9270900,"Multiple fixed doses of ""Seroquel"" (quetiapine) in patients with acute exacerbation of schizophrenia: a comparison with haloperidol and placebo. The Seroquel Trial 13 Study Group.",L A Arvanitis; B G Miller,"Five fixed doses of the atypical antipsychotic ""Seroquel"" (quetiapine) were evaluated to delineate a dose-response relationship, as measured by changes from baseline in Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression (CGI), and Modified Scale for the Assessment of Negative Symptoms (SANS) summary scores, and to compare efficacy and tolerability opposite placebo and haloperidol. Three hundred sixty-one patients from 26 North American centers entered this double-blind, placebo-controlled trial with acute exacerbation of chronic schizophrenia (DSM-III-R). Patients who completed a single-blind, placebo washout phase were randomized to double-blind treatment with quetiapine (75, 150, 300, 600, or 750 mg daily), haloperidol (12 mg daily), or placebo and evaluated weekly for 6 weeks. At end point, significant differences (p < 0.05, analysis of covariance) in adjusted mean changes from baseline were identified between the four highest doses of quetiapine and placebo for BPRS total, BPRS positive-symptom cluster, and CGI Severity of Illness item scores and between quetiapine 300 mg and placebo for SANS summary score. Differences between quetiapine and haloperidol were not significant. Dose-response modeling showed significant linear and quadratic functions of quetiapine dose for all primary efficacy variables. Notably, no significant safety concerns were identified as dose increased. Quetiapine was no different from placebo across the dose range studied regarding incidence of extrapyramidal symptoms or change in prolactin concentrations. Quetiapine is well tolerated and clinically effective in the treatment of schizophrenia. It is both superior to placebo and comparable to haloperidol in reducing positive symptoms at doses ranging from 150 to 750 mg/day and in reducing negative symptoms at a dose of 300 mg/day.",1997.0,0,0
721,9283512,Clozapine withdrawal: serotonergic or dopaminergic mechanisms?,H Y Meltzer,,1997.0,0,0
722,9285079,,,,,0,0
723,9286184,"Blind, controlled, long-term study of the comparative incidence of treatment-emergent tardive dyskinesia with olanzapine or haloperidol.",G D Tollefson; C M Beasley; R N Tamura; P V Tran; J H Potvin,"Tardive dyskinesia is a serious and common complication of neuroleptic treatment. Olanzapine is a novel antipsychotic agent exhibiting regional mesolimbic dopaminergic selectivity and a broad-based pharmacology encompassing serotonin, dopamine, muscarinic, and adrenergic receptor binding affinities. The authors' goal was to compare the incidence of tardive dyskinesia among patients receiving olanzapine and those receiving the conventional dopamine 2 antagonist haloperidol. Data were analyzed from three actively controlled and blind long-term responder studies of subjects meeting DSM-III-R criteria for schizophrenia, schizophreniform disorder, or schizoaffective disorder treated with olanzapine (N = 707, up to 20 mg/day, 237 median days of exposure) or haloperidol (N = 197, up to 20 mg/day, 203 median days of exposure) who did not have evidence of tardive dyskinesia at baseline. All of the subjects had a chronic disease course (mean greater than 10 years), and there were no significant between-treatment group differences in demographic or disease characteristics. The Abnormal Involuntary Movement Scale and research diagnostic criteria for tardive dyskinesia were used to define the comparative incidence rates of long-term treatment-emergent tardive dyskinesia. The incidence of newly emergent tardive dyskinesia at any visit after baseline, at the final visit, and at the final two clinical assessments was statistically significantly lower among olanzapine-treated patients than among haloperidol-treated patients. These findings support an atypical extrapyramidal symptom profile and the potential of a significantly lower risk of tardive dyskinesia with olanzapine than with haloperidol among patients requiring maintenance antipsychotic treatment.",2001.0,0,0
724,9286892,Oral clonidine premedication does not alter the efficacy of simulated intravenous test dose containing low dose epinephrine in awake volunteers.,M Tanaka; T Nishikawa,"Clonidine premedication modifies the hemodynamic responses to sympathomimetics. The present study was designed to test whether clonidine altered the response to a small intravenous dose of epinephrine, such as that which might be used in an epidural test dose. In 18 healthy volunteers, four series of determinations were performed in random order and were separated by a minimum 72 h: (1) no premedication followed by intravenous saline 3 ml, (2) no premedication followed by intravenous test dose containing 3 ml of 1.5% lidocaine + 15 microg epinephrine, (3) oral clonidine (5 microg/kg 1.5 h before hemodynamic determinations) followed by intravenous saline, and (4) oral clonidine followed by intravenous epinephrine-containing test dose. Systolic blood pressure (SBP) and heart rate (HR) were measured continuously, and symptoms associated with central nervous system toxicity were noted. After the test dose injections, HR and SBP increased with or without clonidine premedication. The 95% confidence intervals for the maximum HR increases with and without clonidine were 49-61 and 44-54 beats/min, respectively, indicating that one could not be absolutely certain that everyone would develop a positive HR response. The HR increase was > or = 20 beats/min in 18 of 18 volunteers given epinephrine with or without clonidine and in 0 of 18 volunteers given saline. Calculated sensitivities, specificities, and positive and negative predictive values were all 100% based on the conventional HR criterion and were unaltered by clonidine. Subjective symptoms were not affected by clonidine. Oral clonidine does not alter the efficacy of epinephrine-containing test doses used for detecting intravascular injection.",1997.0,0,0
725,9293649,Comparison of epidural butorphanol plus clonidine with butorphanol alone for postoperative pain relief.,P H Tan; A K Chou; J S Perng; H C Chung; C C Lee; M S Mok,"Epidural butorphanol has been shown to produce effective analgesia with less side effects than that of morphine but relatively short duration. Clonidine, an alpha 2-adrenergic agonist, has been reported to provide [corrected] pain relief by epidural administration. Furthermore, epidural clonidine has been shown to potentiate the analgesic effect of epidural morphine. The present study was undertaken to evaluate the analgesic and side effects of epidural administration (Ep) of butorphanol and clonidine. After giving their consents, 60 adult patients scheduled for abdominal surgeries were enrolled in this study. Prior to anesthesia induction, indwelling lumbar epidural catheters were placed in all patients who then received general anesthesia with inhalation anesthetic without narcotic analgesics. In the postoperative period, when the patients first complained of pain, they were divided into 2 equal groups of 30 patients each in a randomized and double blinded fashion with Group I receiving Ep butorphanol 0.5 mg and Group II receiving Ep butorphanol 0.5 mg plus clonidine 75 micrograms. All patients were observed for pain relief, sedation, vital signs, arterial blood gas studies and adverse effects for 12 h. Onset of pain relief with epidural butorphanol began at 5 min and peaked at 20-30 min with a duration of action lasting 4-6 h. The combination of butorphanol and clonidine had numerically superior pain relief than that of butorphanol for the first 30 min but it did not attain statistical significant difference. The duration of action with the combination group was similar to that of butorphanol alone. Incidence of adverse effects were similar in both groups except that hypotension and more pronounced sedation were observed in Group II. Our study showed that the addition of clonidine to epidural butorphanol did not enhance its analgesic effect in any significant manner nor did it reduce the adverse effects. This combination does not seem to offer any advantage for clinical use.",1997.0,0,0
726,9294377,"Long-term stimulant treatment of children with attention-deficit hyperactivity disorder symptoms. A randomized, double-blind, placebo-controlled trial.",C Gillberg; H Melander; A L von Knorring; L O Janols; G Thernlund; B Hägglöf; L Eidevall-Wallin; P Gustafsson; S Kopp,"We wanted to study the effects of amphetamine on symptoms of attention-deficit hyperactivity disorder (ADHD) over a longer period than has been reported in previous studies of central stimulants in this condition. Sixty-two children, aged 6 to 11 years, meeting DSM-III-R symptom criteria for ADHD participated in a parallel-group design, randomized, double-blind, placebo-controlled study of amphetamine treatment. Treatment was not restricted to children with ""pure"" ADHD, ie, some had comorbid diagnoses. In the amphetamine group, children received active treatment for 15 months. Amphetamine was clearly superior to placebo in reducing inattention, hyperactivity, and other disruptive behavior problems and tended to lead to improved results on the Wechsler Intelligence Scale for Children--Revised. Treatment failure rate was considerably lower and time to treatment failure was longer in the amphetamine group. Adverse effects were few and relatively mild. The results of this long-term, placebo-controlled study of the central stimulant amphetamine in the treatment of ADHD indicate that there are remaining positive effects of the drug 15 months after starting treatment.",1997.0,0,1
727,9294378,National Institute of Mental Health Collaborative Multimodal Treatment Study of Children with ADHD (the MTA). Design challenges and choices.,L E Arnold; H B Abikoff; D P Cantwell; C K Conners; G Elliott; L L Greenhill; L Hechtman; S P Hinshaw; B Hoza; P S Jensen; H C Kraemer; J S March; J H Newcorn; W E Pelham; J E Richters; E Schiller; J B Severe; J M Swanson; D Vereen; K C Wells,"The Collaborative Multimodal Treatment Study of Children with Attention Deficit Hyperactivity Disorder (ADHD), the MTA, is the first child multisite cooperative agreement treatment study of children conducted by the National Institute of Mental Health, Rockville, Md. It examines the long-term effectiveness of medication vs behavioral treatment vs both for treatment of ADHD and compares state-of-the-art treatment with routine community care. In a parallel-groups design, 576 children (age, 7-9 years) with ADHD (96 at each site) are thoroughly assessed and randomized to 4 conditions: (1) medication alone, (2) psychosocial treatment alone, (3) the combination of both, (4) or community comparison. The first 3 groups are treated for 14 months and all are reassessed periodically for 24 months. Designers met the following challenges: framing clinically relevant primary questions; defining the target population; choice, intensity, and integration and combination of treatments for fair comparisons; combining scientific controls and standardization with clinical flexibility; and implementing a controlled clinical trial in a nonclinical setting (school) controlled by others. Innovative solutions included extensive decision algorithms and manualized adaptations of treatments to specific needs.",1997.0,0,1
728,9295240,A comparison of clozapine and haloperidol in hospitalized patients with refractory schizophrenia. Department of Veterans Affairs Cooperative Study Group on Clozapine in Refractory Schizophrenia.,R Rosenheck; J Cramer; W Xu; J Thomas; W Henderson; L Frisman; C Fye; D Charney,"Clozapine, a relatively expensive antipsychotic drug, is widely used to treat patients with refractory schizophrenia. It has a low incidence of extrapyramidal side effects but may cause agranulocytosis. There have been no long-term assessments of its effect on symptoms, social functioning, and the use and cost of health care. We conducted a randomized, one-year, double-blind comparative study of clozapine (in 205 patients) and haloperidol (in 218 patients) at 15 Veterans Affairs medical centers. All participants had refractory schizophrenia and had been hospitalized for the disease for 30 to 364 days in the previous year. All patients received case-management and social-rehabilitation services, as clinically indicated. In the clozapine group, 117 patients (57 percent) continued their assigned treatment for the entire year, as compared with 61 (28 percent) of the patients in the haloperidol group (P<0.001). As judged according to the Positive and Negative Syndrome Scale of Schizophrenia, patients in the clozapine group had 5.4 percent lower symptom levels than those in the haloperidol group at all follow-up evaluations (mean score, 79.1 vs. 83.6; P=0.02). The differences on a quality-of-life scale were not significant in the intention-to-treat analysis, but they were significant among patients who did not cross over to the other treatment (P=0.003). Over a one-year period, patients assigned to clozapine had fewer mean days of hospitalization for psychiatric reasons than patients assigned to haloperidol (143.8 vs. 168.1 days, P=0.03) and used more outpatient services (133.6 vs. 97.9 units of service, P=0.03). The total per capita costs to society were high -- $58,151 in the clozapine group and $60,885 in the haloperidol group (P=0.41). The per capita costs of antipsychotic drugs were $3,199 in the clozapine group and $367 in the haloperidol group (P<0.001). Patients assigned to clozapine had less tardive dyskinesia and fewer extrapyramidal side effects. Agranulocytosis developed in three patients in the clozapine group; all recovered fully. For patients with refractory schizophrenia and high levels of hospital use, clozapine was somewhat more effective than haloperidol and had fewer side effects and similar overall costs.",1997.0,0,0
729,9304445,Long-term follow-up of children with mental retardation/borderline intellectual functioning and ADHD.,B L Handen; J Janosky; S McAuliffe,"Fifty-two children (ages 7 to 14 years) with moderate retardation to borderline intellectual functioning were recontacted 12 to 65 months following participation in a double-blind, placebo-controlled trial of methylphenidate (MPH). Sixty-nine percent of subjects continued to be prescribed medication for behavior control at follow-up. While 72% of the sample evidenced improvement, over two-thirds continued to be rated at or above the 98th percentile on the Hyperactivity Index of the Parent Conners. In fact, 22% of subjects had received inpatient psychiatric treatment between the time of the initial MPH trial and follow-up. Finally, subjects with high initial ratings on the Parent Conners Conduct Problems scale were more likely to be suspended from school or receive inpatient psychiatric treatment than subjects with low initial ratings. The results suggested that children with ADHD and mental retardation of borderline intellectual functioning continued to exhibit significant symptoms associated with attention deficit hyperactivity disorder (ADHD) at follow-up and that early conduct problems were predictive of continuing behavioral difficulties.",1997.0,0,1
730,9306050,Safety issues in the use of methylphenidate. An American perspective.,M D Rappley,"Methylphenidate is the most widely use psychotropic medication in children in the US. It is both well tolerated and efficacious in the treatment of attention deficit hyperactivity disorder, and is associated with few serious adverse effects. However, the abuse of methylphenidate for the purpose of experiencing a 'high' is hazardous. The use of methylphenidate in combination with other medications increases the risk of adverse effects and drug interactions. Good communication between the physician, patient and family, together with monitoring, increases the likelihood that methylphenidate therapy will be effective and have no adverse consequences.",1997.0,0,0
731,9315985,Bupropion and sexual function: a placebo-controlled prospective study on diabetic men with erectile dysfunction.,D L Rowland; L Myers; A Culver; J M Davidson,"Many antidepressant agents interfere with sexual function. The purpose of this single-blind, prospective study was to determine sexual side effects, both positive and negative, of the amino-ketone antidepressant bupropion in a group of nondepressed diabetic men with somatic erectile dysfunction. Fourteen men participated in a 10-week protocol consisting sequentially of 2 weeks of baseline testing, 2 weeks of placebo, and 6 weeks of bupropion. Participants also completed daily and weekly questionnaires concerning sexual functioning, and a team of investigators rated various dimensions of sexual function every 2 weeks. In addition, a variety of physiologic measures, relevant either to erectile function or to neural/vascular systems that underlie sexual response, were assessed during baseline and bupropion treatment. Results indicated that neither subjective nor objective measures of erectile and overall sexual functioning worsened during bupropion. In fact, several measures suggested a trend toward improved sexual functioning. Furthermore, diabetic control was unaffected by bupropion administration. Given the lack of adverse effects on sexual function, along with the potential for improved erectile response, bupropion may provide an attractive choice for the treatment of depression in diabetic men or others for whom sexual dysfunction is a concern.",1997.0,0,0
732,9315992,Double-blind comparison of olanzapine versus risperidone in the treatment of schizophrenia and other psychotic disorders.,P V Tran; S H Hamilton; A J Kuntz; J H Potvin; S W Andersen; C Beasley; G D Tollefson,"Olanzapine and risperidone, both second-generation antipsychotic agents, represent two different pharmacologic strategies. Although they share some in vitro properties, they differ by virtue of their chemical structure, spectrum of receptor binding affinities, animal neuropharmacology, pharmacokinetics, and in vivo neuroimaging profile. Based on such differences, it was hypothesized that the two compounds would show distinct safety and/or efficacy characteristics. To test this hypothesis, an international, multicenter, double-blind, parallel-group, 28-week prospective study was conducted with 339 patients who met DSM-IV criteria for schizophrenia, schizophreniform disorder, or schizoaffective disorder. Results of the study indicated that both olanzapine and risperidone were safe and effective in the management of psychotic symptoms. However, olanzapine demonstrated significantly greater efficacy in negative symptoms (Scale for Assessment of Negative Symptoms summary score), as well as overall response rate (> or = 40% decrease in the Positive and Negative Syndrome Scale total score). Furthermore, a statistically significantly greater proportion of the olanzapine-treated than risperidone-treated patients maintained their response at 28 weeks based on Kaplan-Meier survival curves. The incidence of extrapyramidal side effects, hyperprolactinemia, and sexual dysfunction was statistically significantly lower in olanzapine-treated than risperidone-treated patients. In addition, statistically significantly fewer adverse events were reported by olanzapine-treated patients than by their risperidone-treated counterparts. Thus, the differential preclinical profiles of these two drugs were also evident in a controlled, clinical investigation. Olanzapine seemed to have a risk-versus-benefit advantage.",2001.0,0,0
733,9325559,Clozapine blunts N-methyl-D-aspartate antagonist-induced psychosis: a study with ketamine.,A K Malhotra; C M Adler; S D Kennison; I Elman; D Pickar; A Breier,"Several lines of evidence suggest that the glutamatergic N-methyl-D-aspartate (NMDA) receptor is involved in the antipsychotic efficacy of the atypical antipsychotic agent clozapine. Clinical data on the interaction between clozapine's mechanism of action and NMDA receptor function have been lacking secondary to a paucity of pharmacologic probes of the NMDA system. We have utilized a double-blind, placebo-controlled infusion paradigm with subanesthetic doses of the NMDA antagonist ketamine to test the hypothesis that clozapine would blunt ketamine-induced psychotic symptoms in schizophrenic patients. Ten schizophrenic patients underwent ketamine infusions while antipsychotic drug free and also during treatment with clozapine. Antipsychotic drug-free patients experienced increases in ratings of positive and negative symptoms. Clozapine treatment significantly blunted the ketamine-induced increase in positive symptoms. These data suggest that NMDA receptor function may be involved in the unique antipsychotic efficacy of clozapine.",1997.0,0,0
734,9335081,"Influence of clonidine on psychopathological, endocrine and respiratory effects of cholecystokinin tetrapeptide in patients with panic disorder.",M Kellner; A Yassouridis; H Jahn; K Wiedemann,"The influence of clonidine pretreatment on psychopathological, endocrine and respiratory effects of cholecystokinin tetrapeptide (CCK-4) was characterized. Patients with panic disorder (DSM-III-R) were given 50 micrograms CCK-4 i.v. at 1100 hours on 2 separate study days. In a randomized double-blind design they were additionally infused with 150 micrograms clonidine or placebo from 1040 to 1110 hours. After CCK-4 all patients experienced symptom attacks. No effects of clonidine on panic psychopathology or blood gas parameters were observed. After CCK-4, in the clonidine condition the pituitary release of adrenocorticotropin (ACTH) and prolactin was seemingly enhanced compared to placebo. Our results suggest that CCK-4-induced panic attacks are not suppressible by presynaptic alpha-2 receptor stimulation. Moreover, they point to a synergistic postsynaptic action of clonidine to CCK-4 upon pituitary hormone secretion. The diverging sites of action might possibly explain the discrepancies of psychopathological alterations and stress hormone secretion.",1997.0,0,0
735,9337378,A comparison of sustained-release bupropion and placebo for smoking cessation.,R D Hurt; D P Sachs; E D Glover; K P Offord; J A Johnston; L C Dale; M A Khayrallah; D R Schroeder; P N Glover; C R Sullivan; I T Croghan; P M Sullivan,"Trials of antidepressant medications for smoking cessation have had mixed results. We conducted a double-blind, placebo-controlled trial of a sustained-release form of bupropion for smoking cessation. We excluded smokers with current depression, but not those with a history of major depression. The 615 subjects were randomly assigned to receive placebo or bupropion at a dose of 100, 150, or 300 mg per day for seven weeks. The target quitting date (or ""target quit date"") was one week after the beginning of treatment. Brief counseling was provided at base line, weekly during treatment, and at 8, 12, 26, and 52 weeks. Self-reported abstinence was confirmed by a carbon monoxide concentration in expired air of 10 ppm or less. At the end of seven weeks of treatment, the rates of smoking cessation as confirmed by carbon monoxide measurements were 19.0 percent in the placebo group, 28.8 percent in the 100-mg group, 38.6 percent in the 150-mg group, and 44.2 percent in the 300-mg group (P<0.001). At one year the respective rates were 12.4 percent, 19.6 percent, 22.9 percent, and 23.1 percent. The rates for the 150-mg group (P=0.02) and the 300-mg group (P=0.01) -- but not the 100-mg group (P=0.09) -- were significantly better than those for the placebo group. Among the subjects who were continuously abstinent through the end of treatment, the mean absolute weight gain was inversely associated with the dose (a gain of 2.9 kg in the placebo group, 2.3 kg in 100-mg and 150-mg groups, and 1.5 kg in the 300-mg group; P= 0.02). No effects of treatment were observed on depression scores as measured serially by the Beck Depression Inventory. Thirty-seven subjects stopped treatment prematurely because of adverse events; the frequency was similar among all groups. A sustained-release form of bupropion was effective for smoking cessation and was accompanied by reduced weight gain and minimal side effects. Many participants in all groups were smoking at one year.",1997.0,0,0
736,9350955,A comparison of quetiapine and chlorpromazine in the treatment of schizophrenia.,J Peuskens; C G Link,"A 6-week, double-blind, randomized, multicentre, parallel-group study was conducted to compare the efficacy of quetiapine ('Seroquel') (n=101) with that of chlorpromazine (n=100) in hospitalized patients with acute exacerbation of subchronic or chronic schizophrenia, or schizophreniform disorder. The tolerabilities of the two treatments were also compared. The mean daily doses of quetiapine and chlorpromazine at the end of the study were 407 mg and 384 mg, respectively. Both treatments were effective in the treatment of positive and negative symptoms, with a trend towards superior efficacy for quetiapine. The quetiapine group had a lower incidence of adverse events than the chlorpromazine group, and a low incidence of treatment-emergent extrapyramidal symptoms. Quetiapine was not associated with a sustained increase in serum prolactin. These clinical data support the preclinical profile of quetiapine as an atypical antipsychotic agent.",1997.0,0,0
737,9357879,Epidural epinephrine and clonidine: segmental analgesia and effects on different pain modalities.,M Curatolo; S Petersen-Felix; L Arendt-Nielsen; A M Zbinden,"It is not known whether epidural epinephrine has an analgesic effect per se. The segmental distribution of clonidine epidural analgesia and its effects on temporal summation and different types of noxious stimuli are unknown. The aim of this study was to clarify these issues. Fifteen healthy volunteers received epidurally (L2-L3 or L3-L4) 20 ml of either epinephrine, 100 microg, in saline; clonidine, 8 microg/kg, in saline; or saline, 0.9%, alone, on three different days in a randomized, double-blind, cross-over fashion. Pain rating after electrical stimulation, pinprick, and cold perception were recorded on the dermatomes S1, L4, L1, T9, T6, T1, and forehead. Pressure pain tolerance threshold was recorded at S1, T6, and ear. Pain thresholds to single and repeated (temporal summation) electrical stimulation of the sural nerve were determined. Epinephrine significantly reduced sensitivity to pinprick at L1-L4-S1. Clonidine significantly decreased pain rating after electrical stimulation at L1-L4 and sensitivity to pinprick and cold at L1-L4-S1, increased pressure pain tolerance threshold at S1, and increased thresholds after single and repeated stimulation of the sural nerve. Epidural epinephrine and clonidine produce segmental hypoalgesia. Clonidine bolus should be administered at a spinal level corresponding to the painful area. Clonidine inhibits temporal summation elicited by repeated electrical stimulation and may therefore attenuate spinal cord hyperexcitability.",1997.0,0,0
738,9370898,Randomised controlled trial of growth effect of hydrocortisone in congenital adrenal hyperplasia.,I N Silva; C E Kater; C F Cunha; M B Viana,"The influence of 15 or 25 mg/m2 of daily oral hydrocortisone with fludrocortisone 0.1 mg/day on growth and laboratory findings was evaluated in a prospective randomised crossover trial over 12 months in 26 children with 21-hydroxylase deficiency. Nine non-salt losers had fludrocortisone stopped for a further six month period. Height velocity was significantly decreased during treatment with 25 mg/m2 as compared with 15 mg/m2. This was the most sensitive indicator of corticosteroid treatment excess. A dose dependent effect upon plasma concentrations of 17-hydroxyprogesterone, testosterone, and androstenedione was found but increased values were still detected in more than half of the determinations made during the 25 mg/m2 period. Height velocity and 17-hydroxyprogesterone concentrations were positively correlated. Growth hormone response to clonidine stimulation and insulin-like growth factor-1 concentrations were both within reference values and there was no difference between treatment periods. Withdrawal of fludrocortisone did not result in any difference for the non-salt losers. It was concluded that 25 mg/m2 of hydrocortisone depressed growth in children with congenital adrenal hyperplasia, and that full suppression, or even normalisation, of plasma concentrations of 17-hydroxyprogesterone and androgens should not be considered a treatment goal, but instead an indication of corticosteroid treatment excess.",1997.0,0,0
739,9376336,The acute and long-term effect of olanzapine compared with placebo and haloperidol on serum prolactin concentrations.,A M Crawford; C M Beasley; G D Tollefson,"Prolactin elevation is both a common and a persistent event with the currently marketed antipsychotics, excluding clozapine. Elevations have been associated with both acute (galactorrhea, amenorrhea) and chronic (predisposition to osteoporosis) treatment-emergent adverse events. One of the defining criteria for an atypical antipsychotic is the relative lack of persistent prolactinemia. A double-blind, placebo- (N = 68) and haloperidol- (Hal: 15 +/- 5 mg/day, N = 69) controlled trial of three dose ranges of olanzapine (Olz-L: 5 +/- 2.5 mg/day, N = 65; Olz-M: 10 +/- 2.5 mg/day, N = 64; Olz-H: 15 +/- 2.5 mg/day, N = 69) in the treatment of schizophrenia afforded the opportunity to assess the temporal course of the influence of olanzapine and haloperidol on serum prolactin concentration. Consistent with its potent D2 antagonism, haloperidol was associated with a statistically significantly higher incidence of treatment-emergent prolactin elevation (72%) than seen with placebo (8%; p < 0.001) at week 2 of therapy. Expectedly, this elevation was also persistent at weeks 4 and 6. In contrast, olanzapine-associated treatment-emergent prolactin elevations were both lower in magnitude and transient. At week 2, 38% of the Olz-H, 24% of the Olz-M, and 13% of the Olz-L treatment groups exhibited a treatment-emergent prolactin elevation, with a mean increase of 0.35, 0.52, and 0.61 nmol/l, respectively; for haloperidol the mean increase was 1.23 nmol/l. For only the Olz-M and the Olz-H treatment groups did the week 2 incidence of treatment-emergent prolactin elevations differ statistically significantly from placebo. Both the incidence of elevations and the mean increase, in prolactin concentration were less than that seen with haloperidol. Furthermore, by treatment week 6, all three olanzapine groups exhibited incidences of treatment-emergent prolactin elevation that were comparable to placebo and were statistically significantly less than observed with haloperidol. Rapid adaptation was observed in the temporal course of prolactin elevations associated with olanzapine based on both the categorical analysis of treatment-emergent high values and the analyses of temporal change in mean concentrations. In contrast to haloperidol, the magnitudes of the treatment-emergent elevations associated with olanzapine were minimal. The rates of elevation were approximately one-half to one-third those observed with haloperidol and were significantly more transient. Olanzapine, even at the highest doses (15 +/- 2.5 mg/day) used, was not associated with persistent elevations of prolactin, consistent with an 'atypical' pharmacologic profile.",2001.0,0,0
740,9384909,Attention-deficit hyperactivity disorder and substance abuse: relationships and implications for treatment.,F R Levin; H D Kleber,"Attention-deficit hyperactivity disorder (ADHD) and substance-use disorders are related to each other in a variety of ways. Although within the child-psychiatry literature earlier investigations were inconsistent regarding such a link, recent prospective studies that followed hyperactive children and normal controls into adulthood have found that hyperactive adults with a history of ADHD are more likely than controls to have substance-use disorders. The substance-abuse literature is less consistent regarding the potential association between ADHD and substance abuse. However, recent studies suggest that persons with a substance-use disorder, and particularly those with a cocaine-use disorder, may be more likely than the general population to have a childhood history of ADHD. Some of the inconsistency regarding this association is due to differences in diagnostic criteria, type of assessments used, and reliability of information obtained. Each of the potential relationships that may exist between ADHD and substance abuse has treatment implications for the clinician. Pharmacological as well as nonpharmacological approaches deserve further investigation. Because pharmacotherapy is a central component in the treatment of childhood ADHD, clinicians designing a strategy to treat both a substance-use disorder and ADHD need to consider pharmacological interventions. At present, the literature on pharmacological treatment for childhood ADHD is extensive and that for adult ADHD is growing; information regarding the treatment of cocaine abuse and concomitant ADHD symptoms remains limited.",1998.0,0,0
741,9384911,Beta-blockers and the treatment of aggression.,T Haspel,"This review assesses the usefulness of beta-blockers in the treatment of aggression and describes the parameters for their clinical use. A Medline search using the terms ""beta-blockers,"" ""aggression,"" ""propranolol,"" and ""brain injury"" identified relevant journal articles published in English between 1977 and 1993. Open, prospective and double-blind, placebo-controlled studies, as well as case reports, were included. Beta-blockers appear to be effective in decreasing the frequency and intensity of aggressive outbursts associated with a wide variety of conditions, such as dementias, attention-deficit disorder, personality disorders, Korsakoff's psychosis, posttraumatic stress disorder, schizophrenia, profound mental retardation, autism, and brain injury. A general discussion attempts to resolve some of the issues surrounding the possible mechanisms of beta-blocker effects, reviews the anatomic and neurochemical bases of aggression, and explores implications of the clinical use of beta-blockers.",1998.0,0,0
742,9400342,Clinical efficacy of methylphenidate in conduct disorder with and without attention deficit hyperactivity disorder.,R G Klein; H Abikoff; E Klass; D Ganeles; L M Seese; S Pollack,"Stimulants are not considered appropriate for the treatment of children with conduct disorders (CDs). The postulated differences in stimulant effect between children with attention deficit hyperactivity disorder (ADHD) and CD led to the hypothesis that methylphenidate hydrochloride, which is effective in ADHD, would not significantly improve symptoms of CD. We randomly assigned 84 children with CD, between the ages of 6 and 15 years, to receive methylphenidate hydrochloride (up to 60 mg/d) or placebo for 5 weeks. Behavior was evaluated by parent, teacher, and clinician reports and by direct classroom observations. Two thirds of the children also met criteria for ADHD. Contrary to prediction, ratings of antisocial behaviors specific to CD were significantly reduced by methylphenidate treatment. The magnitude of methylphenidate effect indicated meaningful clinical benefit. Partialling out severity of ADHD did not alter the significant superiority of methylphenidate on CD ratings specifically (P < .001). Methylphenidate has short-term positive effects on children and adolescents with CD. Key aspects of antisocial adjustment appear to be treatment responsive. This effect was independent of severity of the children's initial ADHD symptoms.",1997.0,0,0
743,9408812,Replacement medication for cocaine dependence: methylphenidate.,J Grabowski; J D Roache; J M Schmitz; H Rhoades; D Creson; A Korszun,"Agonists, or ""replacement medications,"" are useful adjuncts in treatment of opiate and nicotine dependence. They have not been systematically examined in cocaine dependence. Results of early open trials with methylphenidate for treatment of cocaine dependence were equivocal. Twenty-four cocaine-dependent subjects were enrolled in an 11-week double-blind, placebo-controlled study of methylphenidate. Assignment was random. Intake included a 2-day human laboratory procedure in which subjects received initial doses of methylphenidate or placebo. Subjects attended the clinic Monday through Friday and received oral doses of methylphenidate (5 mg plus 20-mg sustained release) or placebo at 8:00 a.m., with afternoon and weekend take-home doses (20 mg sustained-release or placebo) provided in Medication Events Monitoring System bottles to monitor compliance. Clinic visits included therapy sessions, electrocardiograms, self-report measures, and twice-weekly urine screens. The two groups were equivalent in terms of retention (methylphenidate 48% and placebo 42%) and had similar cocaine use outcomes (40% benzoylecgonine-positive urine screens). There were no significant adverse effects. The doses were sufficient to permit detection of psychoactive effects (""stimulant,"" ""more energy"") and side effects (""jitteriness,"" ""eating less"") without increased ""craving."" Additional medications with different effects profiles are being studied to further evaluate the replacement model in cocaine dependence.",1997.0,0,0
744,9428851,The efficacy and safety of a clonidine/bupivacaine combination in caudal blockade for pediatric hernia repair.,W Klimscha; A Chiari; A Michalek-Sauberer; E Wildling; A Lerche; C Lorber; H Brinkmann; M Semsroth,"We evaluated the analgesic efficacy and hemodynamic and respiratory safety of clonidine when added to bupivacaine for caudal blocks in 58 children aged 38 +/- 2 mo (mean +/- SEM). Patients scheduled for ambulatory hernia repair were randomly given a caudal injection (0.75 mL/kg) of either saline placebo (P group), bupivacaine, 0.25% (B group), bupivacaine plus epinephrine 1:200,000 (BE group), bupivacaine plus clonidine 1 microgram/kg (BC1 group), or bupivacaine plus clonidine 2 micrograms/kg (BC2 group). Postoperative measurements included duration of analgesia, hemodynamics, and respiratory monitoring for 6 h. Thereafter, parents assessed their child's analgesic requirements at home every 3 h for 18 h. The duration of analgesia (median [range]) was significantly longer (P < 0.05) in the BC1 and BC2 groups (360 [270-360] min and 360 [355-360] min, respectively) compared with the P (77[45-190]), B (346[105-360]), or BE group (300[75-360]). Similarly, the BC1 and BC2 groups required less additional analgesic within the first 24 h. All groups showed a significant decrease in mean arterial pressure compared with baseline values, but the differences among the groups were not significant. Bradycardia and respiratory depression were not observed. Clonidine 1 and 2 micrograms/kg can be safely added to bupivacaine caudal blockade in small children for ambulatory hernia repair to achieve an increased duration of analgesia compared with bupivacaine alone or bupivacaine plus epinephrine. The addition of clonidine, an antihypertensive drug with analgesic properties, to local anesthetics in caudal blocks prolongs postoperative pain relief and reduces the need for additional pain treatment in children after hernia operation.",1998.0,0,0
745,9431261,"Effects of methylphenidate on attentional function after traumatic brain injury. A randomized, placebo-controlled trial.",J Whyte; T Hart; K Schuster; M Fleming; M Polansky; H B Coslett,"Attention deficits after traumatic brain injury (TBI) are common and disabling. Many pharmacologic agents have been used to ameliorate attention deficits, and considerable interest has focused on methylphenidate (MP) because of its documented efficacy in attention deficit disorder. However, clinical studies of MP in subjects with TBI have yielded mixed results. We examined the effects of MP on attentional function in individuals with TBI referred specifically for attentional assessment and treatment. Subjects were studied in a double-blind, placebo-controlled, repeated crossover design, using five different tasks designed to measure various facets of attentional function. MP produced a significant improvement in the speed of mental processing. Orienting to distractions, most aspects of sustained attention, and measures of motor speed were unaffected. These results suggest that MP may be a useful treatment in TBI but is primarily useful for symptoms that can be attributed to slowed mental processing.",1998.0,0,0
746,9432523,Epilepsy and attention deficit hyperactivity disorder: is methylphenidate safe and effective?,V Gross-Tsur; O Manor; J van der Meere; A Joseph; R S Shalev,"To study the safety and efficacy of methylphenidate in children with the dual diagnosis of epilepsy and attention deficit hyperactivity disorder (ADHD). Thirty children, aged 6.4 to 16.4 years, with epilepsy and ADHD were studied during a 4-month period. During the initial 2 months of the study, the children were treated with antiepileptic drugs (AEDs) only, and for the remaining 2 months, methylphenidate was added at a morning dose of 0.3 mg/kg. They underwent neurologic assessment, brain computed tomography, IQ testing, and assessment with the Childhood Behavior Checklist at baseline before methylphenidate therapy. Electroencephalography, AED determinations, and the continuous-performance task (CPT) test were done at baseline and after 2 months of methylphenidate therapy. A double-blind, crossover design was used to compare the effects of methylphenidate versus placebo on an electroencephalogram, AED levels, and the CPT. On the 2 days of testing, the child received AEDs and a capsule containing either placebo or methylphenidate. None of the 25 children of this sample who were seizure free had attacks while taking methylphenidate. Of the 5 children with seizures, 3 had an increase in attacks, whereas the other 2 showed no change or a reduction. There were no significant changes in AED levels or electroencephalographic findings. Methylphenidate benefited 70% of children according to parental report; methylphenidate also enhanced performance on the CPT. Side effects of methylphenidate were mild and transient. Methylphenidate is effective in treating children with epilepsy and ADHD and safe in children who are seizure free. Caution is warranted for those still having seizures while receiving AED therapy.",1998.0,1,1
747,9433359,Olanzapine on trial.,J A Mattes,,1998.0,0,0
748,9433787,An evaluation of methylphenidate as a potential establishing operation for some common classroom reinforcers.,J Northup; I Fusilier; V Swanson; H Roane; J Borrero,"We conducted reinforcer assessments for 3 boys with a diagnosis of attention deficit hyperactivity disorder who alternately received either placebo or previously prescribed methylphenidate. Our purpose was to evaluate whether methylphenidate altered the relative reinforcing effectiveness of various stimuli that are often used in classroom-based behavioral treatment programs (e.g., activities, tangible items). Results showed clear differences for some stimuli between reinforcer assessments conducted when participants had received methylphenidate compared to placebo. Results suggest that methylphenidate might act as an establishing operation for some common classroom reinforcers. Implications for the development and evaluation of behavioral treatments are discussed.",1998.0,0,1
749,9433788,Comprehensive school-based behavioral assessment of the effects of methylphenidate.,V Gulley; J Northup,"Individualized assessments of the effects of three doses of methylphenidate (MPH) were conducted for 2 students with attention deficit hyperactivity disorder within each child's classroom using behavioral, academic, and social measures. A double-blind, placebo-controlled, multielement design was used to evaluate the results. Results suggested that at least one or more dosages of MPH were associated with some degree of improvement for both children in each area of functioning as compared to placebo. However, the degree of improvement at times varied substantially across dosage and area of functioning. Results suggest that MPH dosage and area of child functioning are critical assessment parameters and that controlled clinical trials are necessary to optimize the effectiveness of treatment with MPH for the individual child.",1998.0,0,1
750,9435993,Selective serotonin reuptake inhibitors and CNS drug interactions. A critical review of the evidence.,B A Sproule; C A Naranjo; K E Brenmer; P C Hassan,"The potential for drug-drug interactions in psychiatric patients is very high as combination psychopharmacotherapy used to treat comorbid psychiatric disorders, to treat the adverse effects of a medication, to augment a medication effect or to treat concomitant medical illnesses. Interactions can be pharmacodynamic or pharmacokinetic in nature. This paper focuses on the metabolic kinetic interactions between selective serotonin reuptake inhibitors (SSRIs) and other central nervous system (CNS) drugs. The evidence for and clinical significance of these interactions are reviewed, with special emphasis on antipsychotics, tricyclic antidepressants and benzodiazepines. Many psychotropic medications have an affinity for the cytochrome P450 (CYP) enzymes which promote elimination by transforming lipid soluble substances into more polar compounds. SSRIs serve both as substrates and inhibitors of these enzymes. In vitro studies provide a screening method for evaluating drug affinities for substrates, inhibitors or inducers of CYP enzymes. Although in vitro data are important as a starting point for predicting these metabolic kinetic drug interactions, case reports and controlled experimental studies in humans are required to fully evaluate their clinical significance. Several factors must be considered when evaluating the clinical significance of a potential interaction including: (a) the nature of each drugs' activity at an enzyme site (substrate, inhibitor or inducer); (b) the potency estimations for the inhibitor/inducer; (c) the concentration of the inhibitor/inducer at the enzyme site; (d) the saturability of the enzyme; (e) the extent of metabolism of the substrate through this enzyme (versus alternative metabolic routes); (f) the presence of active metabolites of the substrate; (g) the therapeutic window of the substrate; (h) the inherent enzyme activity of the individual, phenotyping/genotyping information; (i) the level of risk of the individual experiencing adverse effects (e.g. the elderly) and (j) from an epidemiological perspective, the probability of concurrent use. This paper systematically reviews both the in vitro and in vivo evidence for drug interactions between SSRIs and other CNS drugs. As potent inhibitors of CYP2D6, both paroxetine and fluoxetine have the potential to increase the plasma concentrations of antipsychotic medications metabolised through this enzyme, including perphenazine, haloperidol, thioridazine and risperidone in patients who are CYP2D6 extensive metabolisers. Controlled studies have demonstrated this for perphenazine with paroxetine and haloperidol with fluoxetine. Fluvoxamine, as a potent inhibitor of CYP1A2, can inhibit the metabolism of clozapine, resulting in higher plasma concentrations. Drug interactions between the SSRIs and tricyclic antidepressants (TCAs) can occur. Fluoxetine and paroxetine, as potent inhibitors of CYP2D6, can increase the plasma concentrations of secondary and tertiary tricyclic antidepressants. Sertraline and citalopram are less likely to have this effect. Fluvoxamine can increase the plasma concentrations of tertiary TCAs. Fluvoxamine inhibits, via CYP3A. CYP2C19 and CYP1A2, the metabolism of several benzodiazepines, including alprazolam, bromazepam and diazepam. Fluoxetine increases the plasma concentrations of alprazolam and diazepam by inhibiting CYP3A and CYP2C19, respectively. The clinical importance of the interaction with diazepam is attenuated by the presence of its active metabolite. Sertraline inhibits these enzymes only mildely to moderately at usual therapeutic doses. Therefore the potential for interactions is less; however, the in vivo evidence is minimal. Paroxetine and citalopram are unlikely to cause interactions with benzodiazepines. The evidence is conflicting for an interaction between carbamazepine and the SSRIs fluoxetine and fluvoxamine. These combinations should be used cautiously, and be accompanied by monitoring for adverse events and carb",1998.0,0,0
751,9442340,Differential effect of haloperidol and clozapine on plasma homovanillic acid in elderly schizophrenic patients with or without tardive dyskinesia.,I Andia; M Zumarraga; M J Zabalo; A Bulbena; R Davila,"Plasma homovanillic acid (HVA) changes in response to a challenge of several days with haloperidol have been found to be predictive of the therapeutic response to haloperidol over a longer period of treatment. Twenty-six elderly women who gave informed consent were divided into two groups, with or without tardive dyskinesia, and subjected to an 80-day washout, after which both the dyskinetic and nondyskinetic group was divided, and half of each group given haloperidol or clozapine. The nondyskinetic group had a brief rise in plasma HVA, then a decline. The dyskinetic group had no change in plasma HVA. Neither group challenged with clozapine had any change in plasma HVA.",1998.0,0,0
752,9447863,Physostigmine prevents postanesthetic shivering as does meperidine or clonidine.,E P Horn; T Standl; D I Sessler; G von Knobelsdorff; C Büchs; J Schulte am Esch,"Postanesthetic shivering develops in as many as one half of patients recovering from isoflurane anesthesia. Cholinergic stimulation of the hypothalamic-pituitary-adrenal axis and adrenal medulla by physostigmine enhances secretion of arginine vasopressin, epinephrine, and norepinephrine. Because the hypothalamus is the dominant thermoregulatory controller in mammals, and these neurotransmitters may be involved in body temperature control, physostigmine administration may influence the incidence of shivering. Accordingly, the authors tested the hypothesis that physostigmine administration inhibits postanesthetic shivering. Its efficacy was compared with that of saline (negative control) and meperidine and clonidine (positive controls). Sixty patients having surgery of the ear or nose were tested. General anesthesia was induced with 2 mg/kg propofol, 0.1 mg/kg vecuronium, and 1.5 microg/kg fentanyl and maintained with isoflurane (1.5 +/- 0.4%) in 70% nitrous oxide. At the end of surgery, the patients were randomly assigned to receive an intravenous bolus of 0.04 mg/kg physostigmine, isotonic saline, 0.5 mg/kg meperidine, or 1.5 microg/kg clonidine. Heart rate, mean arterial blood pressure, oxygen saturation, visual analog pain score, temperature, and postanesthetic shivering were measured during recovery. Postanesthetic shivering occurred in 6 of 15 (40%) patients given saline. In contrast, postanesthetic shivering was significantly reduced in physostigmine-treated patients (1 of 15, or 7%) and was absent in patients given clonidine or meperidine. Physostigmine inhibited shivering as well as did two established treatments, meperidine and clonidine. These data suggest that cholinergic systems contribute to the genesis and control of postanesthetic shivering.",1998.0,0,0
753,9448656,Double-blind comparison of bupropion sustained release and sertraline in depressed outpatients.,R J Kavoussi; R T Segraves; A R Hughes; J A Ascher; J A Johnston,"A sustained-release formulation of bupropion (bupropion SR), developed with an improved pharmacokinetic profile to permit less frequent dosing than the immediate-release form, has not been evaluated in active comparator trials. This randomized, double-blind, parallel-group trial was conducted to compare the efficacy and safety of bupropion SR and sertraline. Outpatients with moderate to severe major depressive disorder (DSM-IV) received bupropion SR (100-300 mg/day) or sertraline (50-200 mg/day) for 16 weeks. Psychiatric evaluations, including the Hamilton Rating Scale for Depression (HAM-D), the Hamilton Rating Scale for Anxiety (HAM-A), the Clinical Global Impressions scale for Severity of Illness (CGI-S), and for Improvement (CGI-I) were completed, and adverse events were assessed in the clinic periodically throughout treatment. Patients' orgasm function was also assessed. Mean HAM-D, HAM-A, CGI-I, and CGI-S scores improved over the course of treatment in both the bupropion SR group and the sertraline group; no between-group differences were observed on any of the scales. Orgasm dysfunction was significantly (p < .001) more common in sertraline-treated patients compared with bupropion SR-treated patients. The adverse events of nausea, diarrhea, somnolence, and sweating were also experienced more frequently (p < .05) in sertraline-treated patients. No differences were noted between the two treatments for vital signs and weight. This double-blind comparison of bupropion SR and sertraline demonstrates that bupropion and sertraline are similarly effective for the treatment of depression. Both compounds were relatively well tolerated, and orgasm dysfunction, nausea, diarrhea, somnolence, and sweating were reported more frequently in sertraline-treated patients.",1998.0,0,0
754,9448657,The effects of risperidone on the five dimensions of schizophrenia derived by factor analysis: combined results of the North American trials.,S R Marder; J M Davis; G Chouinard,"In two double-blind trials conducted in North America, 513 patients with chronic schizophrenia received risperidone, haloperidol, or placebo. In the present study, combined data from the two trials were analyzed. Patients were randomly assigned to receive placebo, fixed doses of risperidone (2, 6, 10, and 16 mg/day) or 20 mg/day of haloperidol for 8 weeks. Factor analysis of scores on the Positive and Negative Syndrome Scale (PANSS) produced five dimensions (negative symptoms, positive symptoms, disorganized thought, uncontrolled hostility/excitement, and anxiety/depression), similar to the five dimensions of previous factor-analytic studies of PANSS data. Mean changes (symptom reductions) in PANSS factor scores from baseline to treatment Weeks 6 and 8 were significantly greater in patients receiving 6-16 mg/day of risperidone than in patients receiving placebo or haloperidol. The advantages of risperidone were greatest for negative symptoms, uncontrolled hostility/excitement, and anxiety/depression. Even at the lowest dose, 2 mg/day, risperidone was significantly (p < or = .05) superior to haloperidol in reducing negative symptoms. The differences in outcomes between risperidone and haloperidol on PANSS scores were not related to extrapyramidal symptoms. Risperidone produced significantly (p < or = .05) greater improvements than haloperidol on all five dimensions. The large between-group differences on negative symptoms, hostility/excitement, and anxiety/depression suggest that risperidone and other serotonin/dopamine antagonists have qualitatively different effects from those of conventional antipsychotic agents.",1998.0,0,0
755,9450772,Randomized trial of modafinil for the treatment of pathological somnolence in narcolepsy. US Modafinil in Narcolepsy Multicenter Study Group.,,"Narcolepsy is a central nervous system disorder characterized by excessive daytime sleepiness and cataplexy. This placebo-controlled, double-blind, randomized, parallel-group, 18-center study assessed the efficacy and safety of modafinil, a new wake-promoting drug for treating sleepiness in narcolepsy. Subjects with narcolepsy (n = 283) received daily modafinil, 200 or 400 mg, or placebo, for 9 weeks, followed by an open-label treatment period. Subjective sleepiness was measured with the Epworth Sleepiness Scale. Objective sleepiness was assessed with the Multiple Sleep Latency Test and the Maintenance of Wakefulness Test. Level of illness was measured with the Clinical Global Impression of Change. Modafinil significantly reduced all measures of sleepiness and was associated with significant improvements in level of illness. Medication-related adverse experiences were few, dose-dependent, and mostly rated mild to moderate. Modafinil taken once daily was a very well tolerated and effective wake-promoting agent in the treatment of excessive daytime somnolence associated with narcolepsy. Modafinil demonstrated an excellent safety profile for up to 40 weeks of open-label treatment and efficacy was maintained, suggesting that tolerance will not develop with long-term use. Modafinil is a pharmacologically and clinically promising compound for the treatment of pathological daytime somnolence.",1998.0,0,0
756,9468109,"A new self-report scale for assessment of adolescent psychopathology: factor structure, reliability, validity, and diagnostic sensitivity.",C K Conners; K C Wells; J D Parker; G Sitarenios; J M Diamond; J W Powell,"This paper describes four studies on self-reported problems in 2,243 adolescent males and females, 12 to 17 years of age. In Study 1, principal-axis factoring of 102 items covering 11 problem domains revealed six factors comprising 49.5% of the variance. Study 2 used confirmatory factor analysis of a 64-item reduced set on a new sample of 408 adolescents. Goodness-of-fit indicators suggested that the six-factor model had excellent fit to the data. Study 3 used data from the 2,157 adolescents used in the first two studies. Coefficient alphas ranged from .83 to .92. Median test-retest reliability for the six factors was .86. There was a consistent structure of the correlation matrix across age and gender. Study 4 was a study of criterion validity, using an additional sample of 86 children with attention-deficit hyperactivity disorder (ADHD). Sensitivity and specificity were high, with an overall diagnostic efficiency of 83%. This new self-report scale, the Conners/Wells Adolescent Self-Report of Symptoms (CASS), may provide a useful component of a multimodal assessment of adolescent psychopathology.",1998.0,0,0
757,9475768,Patients with alcohol problems.,P G O'Connor; R S Schottenfeld,,1998.0,0,0
758,9481807,Modification of the Clinical Global Impressions (CGI) Scale for use in bipolar illness (BP): the CGI-BP.,M K Spearing; R M Post; G S Leverich; D Brandt; W Nolen,"The Clinical Global Impressions Scale (CGI) was modified specifically for use in assessing global illness severity and change in patients with bipolar disorder. Criticisms of the original CGI were addressed by correcting inconsistencies in scaling, identifying time frames for comparison, clarifying definitions of illness severity and change, and separating out assessment of treatment side effects from illness improvement during treatment. A Detailed User's Guide was developed to train clinicians in the use of the new CGI-Bipolar Version (CGI-BP) for rating severity of manic and depressive episodes and the degree of change from the immediately preceding phase and from the worst phase of illness. The revised scale and manual provide a focused set of instructions to facilitate the reliability of these ratings of mania, depression, and overall bipolar illness during treatment of an acute episode or in longer-term illness prophylaxis. Interrater reliability of the scale was demonstrated in preliminary analyses. Thus, the modified CGI-BP is anticipated to be more useful than the original CGI in studies of bipolar disorder.",1998.0,0,0
759,9497467,Effects of 0.5% apraclonidine on optic nerve head and peripapillary retinal blood flow.,T W Kim; D M Kim,"To examine the effects of 0.5% apraclonidine on optic nerve head (ONH) and peripapillary retinal blood flow by scanning laser Doppler flowmetry (SLDF). ONH and peripapillary retinal blood flow of 17 healthy subjects were measured by SLDF before and 1 hour and 3 hours after unilateral administration of 0.5% apraclonidine. The fellow eyes were treated with balanced salt solution and the examiners were masked as to which eye was treated with apraclonidine. On each occasion, three scans were obtained and haemodynamic variables (volume, flow, and velocity) were analysed at eight locations, four in the neural rim and four in the peripapillary retina, avoiding ophthalmoscopically visible vessels. The statistical significance of changes from the baseline value of variables and the differences in the measured quantities between apraclonidine treated eyes and fellow eyes at each time point were evaluated using Wilcoxon signed rank test. The intraocular pressure was reduced significantly in apraclonidine treated eyes by 15.0% (p = 0.001) at 1 hour and 30.0% (p = 0.000) at 3 hours after administration. In the volume, flow, or velocity of ONH and peripapillary retinal blood flow, there were no significant changes from the baseline values at 1 hour and 3 hours after apraclonidine administration in either apraclonidine treated eyes (p > 0.4) or fellow eyes (p > 0.2). Also, no significant differences were found in the measured quantities between apraclonidine treated eyes and fellow eyes at each time point (p > 0.1). A single dose of topical apraclonidine 0.5% in healthy subjects does not have adverse effects on the ONH and peripapillary retinal blood flow.",1998.0,0,0
760,9498885,"[Postoperative peridural analgesia. Continuous versus patient-controlled administration of a low-dose mixture of sufentanil, clonidine and bupivacaine].",R Hering; T Schumacher; H Müller,"The purpose of our study was to find out whether patient-controlled epidural administration (PCEA) of a mixture containing a low-dose local anaesthetic, opioid and alpha 2-agonist provides as good or better postoperative analgesia as continuous epidural administration of the same analgetic solution. 30 patients (ASA I-III), scheduled for major abdominal surgery, were randomly divided into 2 groups. 90 minutes after induction of general anaesthesia all patients received a continuous epidural infusion of 5 ml/h of the analgetic solution (50 micrograms sufentanil + 150 micrograms clonidine in 50 ml 0.125% bupivacaine) until the end of surgery. Immediately postoperatively the patients of group A received a continuous infusion of the study solution (5-8 ml/h), the patients of group B received a baseline continuous epidural infusion (3 ml/h), additionally they could self-administer 5 ml boli via a PCEA device. Measurements included the total dose of infused drug solution, pain at rest and on exercise by a visual analogue scale, cardiorespiratory data and side effects within the first 24 hours postoperatively. A standardised interview on analgesia and side effects was held 2 days after surgery. The PCEA group demanded less epidural analgesics (gr. B: 112 +/- 33 ml vs. gr. A: 135 +/- 20 ml) p < 0.01). Both continuous epidural infusion and patient-controlled administration provided very good analgesia at rest (gr. A: VAS 0.4 +/- 0.4 and gr. B: VAS 0.4 +/- 0.5) (n.s.). On exercise continuous epidural infusion of analgesics resulted in significantly lower pain scores (gr. A: 1.9 +/- 1.1) than patient-controlled application (gr. B: 3.4 +/- 1.1) (p < 0.01). We did not notice severe side effects such as respiratory depression or drop of heart rate or blood pressure. In patients at rest both continuous and patient-controlled epidural administration of analgesics provides excellent analgesia after major abdominal surgery. Contrariwise, patients on exercise who could use a PCA-device experienced more pain compared to those with a continuous epidural infusion technique. On the other hand the patients of the PCA-group consumed less epidural analgesics. We did not notice any severe side effects such as respiratory depression or cardiovascular instability during the study.",1998.0,0,0
761,9503259,Blood biogenic amines during clozapine treatment of early-onset schizophrenia.,E Schulz; C Fleischhaker; H W Clement; H Remschmidt,"The aims of this investigation were to evaluate long-term and short-term effects of clozapine-treatment on plasma biogenic amines and psychopathology measures in adolescents with schizophrenia (DSM-III-R criteria). The long-term study was conducted in a study sample of 40 young patients (age 14-22 years) following a mean of 3.4 years of neuroleptic treatment. During the study, 20 patients received clozapine, and the other 20 patients were treated with standard neuroleptic medications. At the beginning of the open clinical trials, the patients had already been receiving clozapine treatment for 24 +/- 15 months. Assessment of the biochemical and psychopathological measures was performed on six occasions at consecutive 6-week intervals during maintenance treatment with clozapine or conventional neuroleptics. Blood levels of serotonin, 3-methoxy-4-hydroxy-phenylglycol (MHPG), norepinephrine, and epinephrine were significantly higher in clozapine-treated patients than in conventionally treated patients. During long-term treatment, higher serotonin levels were associated with significantly fewer negative symptoms of schizophrenia, whereas higher MHPG levels were correlated with less depression. The short-term effects of clozapine were assessed in a second and independent study sample. After failing on conventional neuroleptics in clinical trials lasting a mean of 1.6 years, 15 inpatients (aged 11-20 years) received clozapine. Weekly ratings of psychopathological symptoms using standard rating scales were performed in parallel to blood samplings for measurements of biogenic amines and serum levels of clozapine. These measures were obtained for 6 weeks during conventional neuroleptic treatment and for 6 weeks during the open-label clozapine trial. Serum levels of serotonin and plasma norepinephrine levels were significantly higher during treatment with clozapine than during pretreatment with typical neuroleptics. A comparison of plasma epinephrine levels in responders (n = 7) and nonresponders (n = 8) to clozapine revealed that response to clozapine can be predicted by epinephrine levels prior to initiation of treatment with clozapine (responders ranging from 32.2 to 90.3 pg/ml; nonresponders ranging from 92.5 to 473.5 pg/ml). Additionally, subjects who responded to clozapine showed increased mean plasma concentrations of MHPG and epinephrine during treatment with this drug in comparison to the levels measured during pretreatment with typical neuroleptic medication. Nonresponders to clozapine failed to show this increase. Finally, in responders to clozapine a negative linear relationship between negative symptoms of schizophrenia and the concentrations of plasma norepinephrine and serum serotonin were observed. In conclusion, our results demonstrate that plasma epinephrine levels prior to initiation of clozapine therapy predict response to this atypical neuroleptic. Our findings derived from short-term and maintenance treatment with clozapine suggest involvement of norepinephrine, epinephrine and serotonin in the therapeutic actions of the atypical neuroleptic clozapine.",1998.0,0,0
762,9505989,Olanzapine: interaction study with imipramine.,J T Callaghan; B J Cerimele; K J Kassahun; E H Nyhart; P J Hoyes-Beehler; G V Kondraske,"Olanzapine is an ""atypical"" antipsychotic agent with a high affinity for serotonin 5HT2A/C, 5HT3, 5HT6, and dopamine D1, D2, D3, D4 receptors. Depressed patients with psychotic disorders frequently require treatment with concomitant antipsychotic and antidepressant medications. Imipramine pharmacokinetics serve as a marker for hepatic CYP2D6, CYP1A2, CYP3A activity. An open-label, three-way randomized crossover study was done to determine the safety, pharmacokinetics, and potential for a drug interaction between olanzapine (5 mg) and imipramine (75 mg). Each drug was administered alone and in combination. Nine healthy men, ages 32 to 54 years, enrolled in the study. Psychomotor performance capacities, plasma olanzapine, imipramine, desipramine concentrations, and clinical laboratory tests were measured. Pharmacokinetic variables, vital signs, subjective tests for liveliness, and psychomotor outcomes were analyzed using a two-way ANOVA. Olanzapine was safe. Sedation, postural hypotension, and minor vital sign alterations occurred during all treatments. On the liveliness questionnaire, patients generally reported poorer (less lively) scores with olanzapine alone or coadministered with imipramine versus baseline scores. These effects disappeared within 24 hours after administration. Olanzapine alone and in combination decreased motor-speed tasks (finger tapping and visual-arm random reach) compared with baseline or imipramine treatment. Peak 6-hour changes were statistically significant but clinical importance was only marginal. Olanzapine concentrations were < 19% greater than with imipramine. But olanzapine did not affect the kinetics of imipramine or desipramine and, therefore, did not show a metabolic drug interaction involving CYP2D6.",2001.0,0,0
763,9509290,New atypical antipsychotics. Experience and utility in the elderly.,R A Sweet; B G Pollock,"The atypical antipsychotics are a new class of agents with great promise for use in the elderly because of their reduced propensity to cause acute extrapyramidal adverse effects. Treatment of older patients with these agents, however, needs to take into consideration age-related changes in pharmacokinetics and the risks of drug-drug interactions. Additionally, current evidence of their efficacy in late-life psychoses is derived largely from case series and from the extrapolation of results obtained in studies of younger patients with schizophrenia. Controlled clinical studies of atypical antipsychotics in elderly patients are urgently needed.",1998.0,0,0
764,9511946,The effects of clozapine on negative symptoms in patients with schizophrenia with minimal positive symptoms.,J S Brar; K N Chengappa; H Parepally; A R Sandman; S B Kreinbrook; S A Sheth; R Ganguli,"The effectiveness of clozapine in the treatment of the negative symptoms of schizophrenia remains controversial, as improvements in negative symptoms are invariably accompanied by improvements in positive symptoms and neurological side effects. We examined the effectiveness of treatment with clozapine on negative symptoms in a cohort of patients with minimal positive symptoms. Improvements in positive and negative symptoms were measured by BPRS ratings in a subgroup of schizophrenic patients (n=17, from a state hospital cohort of 75) with minimal positive symptoms, who had received clozapine for 6 months. In this subgroup, significant improvements were noted by a composite score on the three negative symptom items of emotional withdrawal, blunted affect, and motor retardation. Positive and depressive symptoms remained unchanged. The remaining cohort (n=58) showed improvements in overall psychopathology including positive, negative, and depressive symptoms. Interestingly, nearly 50% of each group were discharged from the hospital. These findings suggest that clozapine may be beneficial in the treatment of core negative symptoms, even in the absence of other improvements in psychopathology. This effect of clozapine may be a function of its unique pharmacological profile.",1998.0,0,0
765,9519099,"Sulpiride augmentation in people with schizophrenia partially responsive to clozapine. A double-blind, placebo-controlled study.",R Shiloh; Z Zemishlany; D Aizenberg; M Radwan; B Schwartz; P Dorfman-Etrog; I Modai; M Khaikin; A Weizman,"We hypothesised that a combined regimen of clozapine, a relatively weak D2-dopaminergic antagonist, and sulpiride, a selective D2 blocker, would demonstrate a greater antipsychotic efficacy by enhancing the D2 blockade of clozapine. Twenty-eight people with schizophrenia, previously unresponsive to typical antipsychotics and only partially responsive to current treatment with clozapine, received, double-blind, 600 mg/day sulpiride or placebo, in addition to an ongoing clozapine treatment. The clinical status was evaluated before, during, and at the end of 10 weeks of sulpiride addition using the Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Positive Symptoms (SAPS), Scale for the Assessment of Negative Symptoms, and Hamilton Rating Scale for Depression. The clozapine-sulpiride group exhibited substantially greater and significant improvements in positive and negative psychotic symptoms. About half of them, characterised by a younger age and lower baseline SAPS scores, had a mean reduction of 42.4 and 50.4% in their BPRS and SAPS scores, respectively. A subgroup of patients with chronic schizophrenia may substantially benefit from sulpiride addition to clozapine.",1998.0,0,0
766,9522104,Risperidone versus haloperidol: I. Meta-analysis of efficacy and safety.,A Davies; M A Adena; N A Keks; S V Catts; T Lambert; I Schweitzer,"Haloperidol is widely considered a reference standard in antipsychotic therapy and is commonly used in comparative studies of the efficacy and safety of antipsychotic medication. Comparative clinical trials have shown that the novel antipsychotic agent risperidone tends to have greater efficacy (i.e., clinical response defined as a > or = 20% reduction in total scores on the Positive and Negative Syndrome Scale) than haloperidol in patients with chronic schizophrenia and poses less risk of extrapyramidal symptoms (EPS). We used DerSimonian and Laird's random-effects model to analyze pooled patient data from available randomized, double-masked, comparative trials of risperidone and haloperidol in patients with schizophrenia treated for at least 4 weeks at recommended doses. The purpose of the analysis was to determine whether there are significant overall differences in the rates of patient clinical response, prescription of anticholinergic agents, and treatment dropout. Six of the nine trials revealed in a literature search met all criteria for inclusion in the meta-analysis. The meta-analysis showed that in patients with chronic schizophrenia, risperidone therapy is associated with significantly higher response rates, significantly less prescribing of anticholinergic medication, and significantly lower treatment dropout rates than haloperidol. These results demonstrate the greater treatment efficacy associated with risperidone compared with haloperidol and suggest both a lower incidence of EPS and improved treatment compliance.",1998.0,0,0
767,9522320,Neuroendocrine effects of different estradiol-progestin regimens in postmenopausal women.,M Stomati; C Bersi; S Rubino; M Palumbo; G Comitini; A D Genazzani; M Santuz; F Petraglia; A R Genazzani; M Santre,"New regimens and routes of administration of hormonal replacement therapy (HRT) in climateric women are becoming available. Since there is no information on the neuroendocrine effects of sequential combined treatment with 17 beta-estradiol and a progestin, the present study evaluated the neuroendocrine, clinical vasomotor and psychological changes before and after different sequential combined HRT regimens (17 beta-estradiol plus nomegestrol acetate, or cyproterone acetate, or vaginal progesterone). Vasomotor and behavioral effects were evaluated by using the Kupperman score, while changes in plasma endorphin (beta-END) levels were used as marker of neuroendocrine effects. Postmenopausal women (n = 30) were randomly divided into three groups (ten women for each group); all women received continuous 17 beta-estradiol (50 mg, transdermal) and each group was sequentially treated with different progestins for 12 days/month: group A, cyproterone acetate (5 mg p.o.); group B, nomegestrol acetate (5 mg p.o.); and group C, progesterone (100 mg, vaginal cream). A group of healthy fertile women (n = 8) served as control. Before and after 6 months of HRT, postmenopausal women underwent an evaluation of subjective Kupperman score and two neuroendocrine tests: (a) naloxone (4 mg i.v.) and (b) clonidine (1.25 mg i.v.). Plasma beta-END levels were measured before and at 15, 30, 45, 60 and 90 min after drug injection. Control women were studied by administering the two neuroendocrine tests only once. Postmenopausal women before HRT showed a pathological Kupperman and no changes of plasma beta-END levels in response to the clonidine and naloxone tests score. On the contrary the increase was significant in healthy women. In each of the three groups of treated women both naloxone and clonidine tests induced a significant increase in plasma beta-END levels (P < 0.01). After 6 months of HRT, an improvement of vasomotor and psychological symptoms was shown by a decrease of Kupperman score. The present study indicates that sequential treatment with transdermal 17 beta-estradiol and progestin, no matter which progestin was used, restores the beta-END release, improves vasomotor and psychological symptoms.",1998.0,0,0
768,9523808,Intrathecal clonidine combined with sufentanil for labor analgesia.,P E Gautier; M De Kock; L Fanard; A Van Steenberge; J L Hody,"Intrathecal sufentanil provides rapid-onset and complete analgesia for the first stage of labor. The dose required to produce this effect can be associated with maternal respiratory depression, hypotension, nausea, or pruritus. Because clonidine potentiates the analgesic effects of opioids without increasing their side effects, the authors wanted to determine the efficacy of low doses of intrathecal clonidine (15 and 30 microg) combined with sufentanil. Ninety-eight parturient requesting labor analgesia were studied. In a combined spinal-epidural technique, patients were randomly assigned to receive one of the following intrathecal solutions: either 15 microg clonidine (n = 10); 30 microg clonidine (n = 10); 2.5 microg sufentanil (n = 13); 5 microg sufentanil (n = 13); 2.5 microg sufentanil and 15 microg clonidine (n = 13); 2.5 microg sufentanil and 30 microg clonidine (n = 13); 5 microg sufentanil and 15 microg clonidine (n = 13); or 5 microg sufentanil and 30 microg clonidine (n = 13). Visual analog scores for pain, blood pressure, heart rate, sensory levels, incidence of nausea and pruritus, and motor blockade, and maternal and cord blood concentrations of clonidine were recorded. Patients receiving 30 microg intrathecal clonidine with 2.5 or 5 microg intrathecal sufentanil had significantly longer-lasting analgesia (145 +/- 36 and 145 +/- 43 min vs. 104 +/- 35 for those receiving 5 microg intrathecal sufentanil alone). Clonidine levels were undetectable in maternal serum. Thirty micrograms of intrathecal clonidine combined with 2.5 or 5 microg intrathecal sufentanil significantly increased the duration of analgesia during the first stage of labor without adverse maternal or fetal effects.",1998.0,0,0
769,9545995,,,,,0,0
770,9546570,"Diagnosis and treatment of attention-deficit/hyperactivity disorder in children and adolescents. Council on Scientific Affairs, American Medical Association.",L S Goldman; M Genel; R J Bezman; P J Slanetz,"To deal with public and professional concern regarding possible overprescription of attention-deficit/hyperactivity disorder (ADHD) medications, particularly methylphenidate, by reviewing issues related to the diagnosis, optimal treatment, and actual care of ADHD patients and of evidence of patient misuse of ADHD medications. Literature review using a National Library of Medicine database search for 1975 through March 1997 on the terms attention deficit disorder with hyperactivity, methylphenidate, stimulants, and stimulant abuse and dependence. Relevant documents from the Drug Enforcement Administration were also reviewed. All English-language studies dealing with children of elementary school through high school age were included. All searched articles were selected and were made available to coauthors for review. Additional articles known to coauthors were added to the initial list, and a consensus was developed among the coauthors regarding the articles most pertinent to the issues requested in the resolution calling for this report. Relevant information from these articles was included in the report. Diagnostic criteria for ADHD are based on extensive empirical research and, if applied appropriately, lead to the diagnosis of a syndrome with high interrater reliability, good face validity, and high predictability of course and medication responsiveness. The criteria of what constitutes ADHD in children have broadened, and there is a growing appreciation of the persistence of ADHD into adolescence and adulthood. As a result, more children (especially girls), adolescents, and adults are being diagnosed and treated with stimulant medication, and children are being treated for longer periods of time. Epidemiologic studies using standardized diagnostic criteria suggest that 3% to 6% of the school-aged population (elementary through high school) may suffer from ADHD, although the percentage of US youth being treated for ADHD is at most at the lower end of this prevalence range. Pharmacotherapy, particularly use of stimulants, has been extensively studied and generally provides significant short-term symptomatic and academic improvement. There is little evidence that stimulant abuse or diversion is currently a major problem, particularly among those with ADHD, although recent trends suggest that this could increase with the expanding production and use of stimulants. Although some children are being diagnosed as having ADHD with insufficient evaluation and in some cases stimulant medication is prescribed when treatment alternatives exist, there is little evidence of widespread overdiagnosis or misdiagnosis of ADHD or of widespread overprescription of methylphenidate by physicians.",2001.0,0,0
771,9549666,Single-dose pharmacokinetics of modafinil and methylphenidate given alone or in combination in healthy male volunteers.,Y N Wong; S P King; W B Laughton; G C McCormick; P E Grebow,"Modafinil is a novel wake-promoting agent being developed for treatment of excessive daytime sleepiness associated with narcolepsy. An open, 3 x 3 Latin square, randomized, cross-over study was performed in healthy males to compare the pharmacokinetics of single-dose oral modafinil (200 mg) and methylphenidate (40 mg) administered alone or in combination. Blood samples were obtained for analysis of d- and l-threo-methylphenidate and modafinil and its acid and sulfone metabolites. Pharmacokinetic parameters were determined by noncompartmental methods, but could not be evaluated for modafinil sulfone due to plasma levels that were close to the assay quantitation limit. Although sporadic differences in plasma concentrations were observed between treatments, coadministration of modafinil and methylphenidate did not significantly alter the plasma concentrations of modafinil, modafinil acid, modafinil sulfone, or methylphenidate enantiomers compared with administration of these agents alone. Half-life (t1/2), maximum concentration (Cmax), area under the concentration-time curve (AUC0-infinity), total clearance (Cl/F), and apparent volume of distribution (Vd/F) for modafinil and t1/2, Cmax, and AUC0-infinity for modafinil acid were not affected by concomitant administration of methylphenidate. Small but statistically significant increases in time to Cmax (tmax) were observed for modafinil and modafinil acid after methylphenidate coadministration compared with modafinil alone. Modafinil coadministration did not significantly alter the pharmacokinetics of d- or l-threo-methylphenidate, except for a small decrease in Vd/F of l-threo-methylphenidate. Concomitant methylphenidate may cause a delay in the oral absorption of modafinil, but this delay might not be relevant clinically. Coadministration did not alter the extent of oral absorption and disposition of either agent. Therefore, a pharmacokinetic interaction between modafinil and methylphenidate would be unlikely.",1998.0,0,0
772,9555595,Therapeutic equivalence of risperidone given once daily and twice daily in patients with schizophrenia. The Risperidone Study Group.,N P Nair,"A study was conducted to determine whether once-daily administration of risperidone was as effective and safe as twice-daily administration. In a double-blind 6-week trial, 211 patients with acute exacerbation according to DSM-III-R criteria were randomly assigned to receive risperidone at 8 mg once daily or 4 mg twice daily. The primary efficacy measure was the treatment response rate, defined as a 20% or greater reduction in total Positive and Negative Syndrome Scale (PANSS) scores. Severity of extrapyramidal symptoms was assessed by the Extrapyramidal Symptom Rating Scale. The percentage of patients who showed a treatment response at endpoint was not significantly different between groups (76%, once-daily; 72%, twice-daily), nor was the median time to first treatment response (14 days, both groups). Significant reductions in PANSS total and subscale scores and PANSS-derived Brief Psychiatric Rating Scale were observed in both groups, with no significant between-group differences. Extrapyramidal Symptom Rating Scale scores did not differ significantly between groups. There were no clinically relevant changes in vital signs, electrocardiograms, or clinical laboratory test results in either group. Gradual dosage titration over the first 3 days of treatment was well-tolerated in both groups. The median trough plasma concentrations of risperidone, 9-hydroxyrisperidone, and risperidone plus 9-hydroxyrisperidone were significantly lower with once-daily than with twice-daily administration; median plasma concentrations measured within the first 8 hours after administration tended to be higher with once-daily administration. These differences did not affect the safety and efficacy of risperidone. Risperidone given once daily at 8 mg is as effective as twice-daily administration of 4 mg in the treatment of acute exacerbations of schizophrenia. Both regimens were equally well-tolerated.",1998.0,0,0
773,9555596,Risperidone versus haloperidol and amitriptyline in the treatment of patients with a combined psychotic and depressive syndrome.,F Müller-Siecheneder; M J Müller; A Hillert; A Szegedi; H Wetzel; O Benkert,"In a multicenter, double-blind, parallel group trial, the efficacy of risperidone (RIS) was compared with a combination of haloperidol and amitriptyline (HAL/AMI) over 6 weeks in patients with coexisting psychotic and depressive symptoms with either a schizoaffective disorder, depressive type, a major depression with psychotic features, or a nonresidual schizophrenia with major depressive symptoms according to DSM-III-R criteria. A total of 123 patients (62 RIS; 61 HAL/AMI) were included; the mean daily dosage at endpoint was 6.9 mg RIS versus 9 mg HAL combined with 180 mg AMI. Efficacy results for those 98 patients (47 RIS; 51 HAL/AMI) who completed at least 3 weeks of double-blind treatment revealed in both treatment groups large reductions in the Positive and Negative Syndrome Scale-derived Brief Psychiatric Rating Scale (RIS 37%; HAL/AMI 51%) and the Bech-Rafaelsen Melancholia Scale total scores (RIS 51%; HAL/AMI 70%). The reductions in the Brief Psychiatric Rating Scale and the Bech-Rafaelsen Melancholia Scale scores in the total group were significantly larger in the HAL/AMI group than in the RIS group (p < 0.01), mostly because of significant differences in the subgroup of patients suffering from depression with psychotic features, whereas treatment differences in the other diagnostic subgroups were not significant. The incidence of extrapyramidal side effects as assessed by the Extrapyramidal Symptom Rating Scale was slightly higher under RIS (37%) than under HAL/AMI (31%). Adverse events were reported by 66% of RIS and 75% of HAL/AMI patients. The results of this trial suggest that the therapeutic effect of HAL/AMI is superior to RIS in the total group of patients with combined psychotic and depressive symptoms. However, subgroup differences have to be considered.",1998.0,0,0
774,9555605,"Comments on article by Tran and colleagues, ""Double-blind comparison of olanzapine versus risperidone in treatment of schizophrenia and other psychotic disorders"".",N R Schooler,,1998.0,0,0
775,9555606,"Comments on article by Tran and associates, ""Double-blind comparison of olanzapine versus risperidone in treatment of schizophrenia and other psychotic disorders"".",J Gheuens; J A Grebb,,1998.0,0,0
776,9555778,,,,,0,0
777,9564198,Reliability and validity of the SKAMP rating scale in a laboratory school setting.,S B Wigal; S Gupta; D Guinta; J M Swanson,"In children with attention deficit hyperactivity disorder (ADHD), the effects of methylphenidate were investigated in a pharmacodynamic comparison of placebo and the standard b.i.d. administration of methylphenidate. In each of these conditions, teachers completed ratings in classroom settings at times chosen to coincide with expected ""peaks"" and ""troughs"" of serum concentrations in the b.i.d. condition. Analyses of variance (ANOVAs) revealed the expected differences between the two conditions in the laboratory classroom setting using standard rating scales (Conners and the IOWA Conners) and a new rating scale (the SKAMP), which specifically measures the classroom manifestation of ADHD. The psychometric properties of the SKAMP were evaluated by calculating test-retest reliability and by calculating correlations with the standard rating scales to establish concurrent validity.",1998.0,0,1
778,9564199,Objective and subjective measures of the pharmacodynamic effects of Adderall in the treatment of children with ADHD in a controlled laboratory classroom setting.,J Swanson; S Wigal; L Greenhill; R Browne; B Waslick; M Lerner; L Williams; D Flynn; D Agler; K L Crowley; E Fineberg; R Regino; M Baren; D Cantwell,"In a randomized double-blind crossover study of children with attention deficit hyperactivity disorder (ADHD), the time course effects of four doses of Adderall (5, 10, 15, and 20 mg) and an inactive (placebo) control, and an active (Ritalin) control were evaluated. A laboratory classroom setting was established in which subjective (teacher ratings of deportment and attention) and objective (scores on math tests) measurements were taken every 1.5 hours across the day. In addition to significant time and dose effects of Adderall, significant time-of-day effects were documented in the placebo condition for the subjective measure of deportment and objective measures of performance. Regression analyses were used to estimate the magnitude of these baseline effects. Correlations across time were used to evaluate the test-retest reliability of each measure in the face of these time-dependent placebo effects. After placebo/time adjustments, within-subject correlations between pairs of measures were used to evaluate the validity of the math test as a measure of response to stimulant medication.",1998.0,0,1
779,9582180,Recovery in pediatric brain injury: is psychostimulant medication beneficial?,S E Williams; M D Ris; R Ayyangar; B K Schefft; D Berch,"To assess the effects of methylphenidate on attention, memory, behavior, processing speed, and psychomotor skills of children with closed head injuries. Double-blind, placebo-controlled, crossover design. An outpatient facility of a children's hospital medical center. Ten pediatric subjects identified through chart review. Subjects met baseline scores for hyperactivity (Conner's Hyperactivity Index greater than or equal to 60) and intellectual functioning (Verbal Intelligence Quotient greather than or equal to 70) and achieved minimal scores on two psychometric tests. All subjects evidenced head injury by focal lesions on computed tomography scan and/or sequelae reported at the time of injury. Severity of injury ranged from mild to severe. All subjects were medically stable at the time of testing. Mean time post injury was 2 years, 8 months. Administration of methylphenidate and placebo. Percentage change in scores was calculated to assess differences between baseline and end of methylphenidate/placebo trials. No significant differences between methylphenidate and placebo on measures assessing behavior, attention, memory, and processing speed. The results of the study call into question the effectiveness of methylphenidate in the pediatric head injury population.",1998.0,0,0
780,9585725,Effectiveness and tolerability of tomoxetine in adults with attention deficit hyperactivity disorder.,T Spencer; J Biederman; T Wilens; J Prince; M Hatch; J Jones; M Harding; S V Faraone; L Seidman,"The authors assessed the experimental noradrenergic compound tomoxetine as an alternative treatment for adult attention deficit hyperactivity disorder (ADHD). They conducted a double-blind, placebo-controlled, crossover study of tomoxetine in 22 adults with well-characterized ADHD. Treatment with tomoxetine at an average oral dose of 76 mg/day was well tolerated. Drug-specific improvement in ADHD symptom was highly significant overall and sufficiently robust to be detectable in a parallel-groups comparison restricted to the first 3 weeks of the protocol. Eleven of 21 patients showed improvement after receiving tomoxetine, compared with only two of 21 patients who improved after receiving placebo. Significant tomoxetine-associated improvement was noted on neuropsychological measures of inhibitory capacity from Stroop tests. This preliminary study showed that tomoxetine was effective in treating adult ADHD and was well tolerated. These promising results provide support for further studies of tomoxetine over an extended period of treatment.",1998.0,0,0
781,9589514,The membrane phospholipid hypothesis as a biochemical basis for the neurodevelopmental concept of schizophrenia.,D F Horrobin,"The neurodevelopmental hypothesis of schizophrenia is becoming an important feature of research in the field. However, its major drawback is that it lacks any biochemical basis which might draw the diverse observations together. It is suggested that the membrane phospholipid hypothesis can provide such a biochemical basis and that the neurodevelopmental phospholipid concept offers a powerful paradigm to guide future research.",1998.0,0,0
782,9589713,Short-term clinical trial evaluating the efficacy of the combination of apraclonidine 0.5% solution and betaxolol 0.25% suspension.,G Lamberti; B Pignalosa; R Fusco; G Pignalosa; A Di Govanni; A Sebastiani,,1998.0,0,0
783,9609675,,,,,0,0
784,9611669,"A double-blind, controlled comparison of the novel antipsychotic olanzapine versus haloperidol or placebo on anxious and depressive symptoms accompanying schizophrenia.",G D Tollefson; T M Sanger; C M Beasley; P V Tran,"Depressive symptoms are a common feature of schizophrenia and may represent a core part of the illness. Where present, it has been associated with greater overall morbidity and mortality. Monotherapy with conventional dopamine antagonists may either worsen or bestow a limited therapeutic benefit. Accordingly the use of adjunctive thymoleptics has been explored. In contrast, olanzapine (OLZ), an atypical antipsychotic agent, offers a distinctive and pleotropic pharmacology suggestive of a broader efficacy profile than conventional neuroleptic agents. In a 6-week placebo- and haloperidol (HAL)-controlled trial with 335 randomized subjects with chronic schizophrenia in an acute exacerbation, three fixed dose ranges of OLZ (5, 10, or 15 +/- 2.5 mg) were evaluated versus HAL (10-20 mg) or placebo. Baseline to endpoint change in the Brief Psychiatric Rating Scale including the anxiety-depression cluster (items 1, 2, 5, 9) was analyzed. Two dose ranges of OLZ (10 +/- 2.5, 15 +/- 2.5) were superior to placebo (p < 05) in improving mood status, whereas HAL was not. Contributions from a more selective mesolimbic dopaminergic profile, D1 or D4 activity, the release of dopamine/norepinephrine in the prefrontal cortex, and/or serotonin 5-HT2A,C antagonism may explain the differential benefit seen with OLZ in the treatment of comorbid anxious and depressive symptoms in schizophrenia.",1998.0,0,0
785,9622044,Clonidine does not potentiate the antipsychotic effects of neuroleptics in chronically ill patients.,S Hedges; R S El-Mallakh; F Issa; A Elkashef; L B Bigelow; R J Wyatt,"Clonidine is a centrally acting antihypertensive and has been prescribed widely for more than 20 years. Because it decreases central norepinephrine activity, clonidine has been investigated as an antipsychotic. In most of the preliminary studies, clonidine was tested as the sole antipsychotic agent. We performed a double-blind, placebo-controlled, crossover study to compare a placebo plus a neuroleptic to clonidine plus a neuroleptic in a group of 16 chronically psychotic patients. Of these 16, 3 dropped out secondary to side effects of the clonidine and 1 withdrew from the study. The clonidine dosage varied from 0.2 to 0.6 mg per day. The concurrent neuroleptic (one of the following: haloperidol, thiothixene, thioridazine, mesoridazine, or fluphenazine) averaged 34 mg per day of haloperidol equivalents. Symptoms were monitored using the Psychiatric Symptoms Assessment Scale. The data provided evidence that a clonidine/neuroleptic combination was not more effective than a neuroleptic alone in this group of patients. These data suggest that the central antinorepinephrine activity of a neuroleptic is not potentiated further by clonidine.",1998.0,0,0
786,9629412,[Use of drugs in attention deficit hyperactivity disorders].,A Guardiola; A R Terra; K R Pereira; N T Rotta,"Attention deficit hyperactivity disorder (ADHD) is a neurological disorder which is common in the childhood and can be caused by exogenous and endogenous factors, that are responsible for cerebral disorder. This disorder presents a functional alteration of the motor, perceptive, cognition systems and conduct disorders compromising the learning of children with an adequate intellectual potential. The authors study the action of stimulants and antidepressive drugs in the ADHD, using as measure of efficacy the motor persistence tests.",1998.0,0,0
787,9630000,A comparison of bd and tid dose regimens of quetiapine (Seroquel) in the treatment of schizophrenia.,D J King; C G Link; B Kowalcyk,"Quetiapine (Seroquel, ICI 204,636) is an atypical antipsychotic that is effective in the treatment of both positive and negative symptoms of schizophrenia, and has a low propensity to cause extrapyramidal symptoms. The compound has a relatively short plasma elimination half-life (approximately 7 h). However, since dopamine D2 receptor occupancies correlate poorly with plasma concentrations of antipsychotics, plasma elimination half-life may not predict either duration of clinical effect or dosing frequency. Accordingly, the efficacy and tolerability of three dosing regimens (450 mg/day given in two or three divided doses daily, and 50 mg/day given twice daily) were compared in a 6-week, double-blind, randomized, multicentre, parallel-group study. The study recruited hospitalized men and women aged 18-65 years meeting DSM-IIIR criteria for acute exacerbation of chronic or subchronic schizophrenia. Six hundred and eighteen patients were randomly assigned to treatment with quetiapine 150 mg tid (n = 209), 225 mg bd (n = 200), or a comparator dose of 25 mg bd (n = 209). At day 42, the last day of randomized treatment and the primary timepoint for efficacy, quetiapine 450 mg/day was more effective than 50 mg/day: 225 mg bd was consistently superior to 25 mg bd in all measures of efficacy (total BPRS, P = 0.006; CGI severity, CGI improvement and SANS, P < 0.03), and 150 mg tid was statistically significantly superior to 25 mg bd with respect to BPRS total score (P = 0.05). The 225 mg bd and 150 mg tid groups were not significantly different from each other with respect to any efficacy measure. Quetiapine was generally well tolerated. Extrapyramidal symptom (EPS) adverse events were generally rare, and occurred with similar frequencies in the two 450 mg/day groups. Quetiapine was not associated with sustained increases in plasma prolactin at any dose. These data support the atypical profile developed from preclinical studies and show that quetiapine is an effective, well tolerated antipsychotic that can be given twice daily.",1998.0,0,0
788,9633833,"Psychomotor slowing, negative symptoms and dopamine receptor availability--an IBZM SPECT study in neuroleptic-treated and drug-free schizophrenic patients.",A Heinz; M B Knable; R Coppola; J G Gorey; D W Jones; K S Lee; D R Weinberger,"Anhedonia and psychomotor slowing in schizophrenia have been attributed to a dysfunction of dopaminergic neurotransmission. To differentiate between disease and drug-induced negative symptoms, we examined eight drug-free and eight neuroleptic-treated schizophrenic patients. Positive and negative symptoms and extrapyramidal side effects were assessed using standardized rating scales (PSAS, AMDP, SANS). 'Reaction time' and 'motor speed' were measured using a computer-aided system and striatal dopamine D2/D3 receptor availability was assessed using [I-123]IBZM SPECT. Psychomotor reaction time, parkinsonism, affective flattening and avolition were increased in treated patients relative to the untreated cohort and were negatively correlated with dopamine D2/D3 receptor availability. Significant positive correlations were found between parkinsonism and affective flattening and between psychomotor slowing and avolition. Positive symptoms were not significantly associated with striatal IBZM binding. These findings support the hypothesis that neuroleptic-induced dopamine D2/D3 blockade in the striatum can mimic certain negative symptoms, such as affective flattening and avolition, and indicates that psychomotor testing may be helpful in differentiating between disease and drug-induced negative symptoms.",1998.0,0,0
789,9659857,Olanzapine compared with chlorpromazine in treatment-resistant schizophrenia.,R R Conley; C A Tamminga; J J Bartko; C Richardson; M Peszke; J Lingle; J Hegerty; R Love; C Gounaris; S Zaremba,"The purpose of this study was to compare the efficacy of olanzapine with that of chlorpromazine plus benztropine in patients with treatment-resistant schizophrenia. One hundred three previously treatment-resistant patients with schizophrenia diagnosed according to the DSM-III-R criteria were given a prospective 6-week trial of 10-40 mg/day of haloperidol. Eighty-four of them failed to respond to that trial and agreed to be randomly assigned to an 8-week fixed-dose trial of either 25 mg/day of olanzapine alone or 1200 mg/day of chlorpromazine plus 4 mg/day of benztropine mesylate. Fifty-nine (70%) of the 84 subjects completed the trial. The primary outcome measures were Brief Psychiatric Rating Scale total score and positive symptom score, Scale for the Assessment of Negative Symptoms global score, and Clinical Global Impression score. An analysis of variance for the subjects who completed the study showed no difference in efficacy between the two drugs. Seven percent of the olanzapine-treated patients responded according to a priori criteria; no chlorpromazine-treated patients responded. The olanzapine-treated patients had fewer motor and cardiovascular side effects than the chlorpromazine-treated patients. Extrapyramidal symptoms and akathisia were similar in the two groups, although no antiparkinsonian drugs were used in the olanzapine group. Olanzapine and chlorpromazine showed similar efficacy, and the total amount of improvement with either drug was modest. Olanzapine-treated patients had fewer side effects than chlorpromazine-treated patients.",1998.0,0,0
790,9661556,Clonidine added to the anesthetic solution enhances analgesia and improves oxygenation after intercostal nerve block for thoracotomy.,E M Tschernko; H Klepetko; E Gruber; M Kritzinger; W Klimscha; O Jandrasits; W Haider,"We evaluated the effect of adding clonidine to bupivacaine on postoperative pain control and oxygenation after intercostal nerve blockade (ICB) for thoracotomy, and attempted to distinguish a systemic from a local effect of clonidine. ICB with 2 mg/kg 0.5% bupivacaine was performed in 36 patients undergoing thoracotomy. Patients were randomized to one of three groups: 1) a control group that received bupivacaine with saline for ICB and an IM injection of saline, 2) an IM group that received bupivacaine with saline for ICB and an IM injection of 2 micrograms/kg clonidine, and 3) a block group that received bupivacaine with 2 micrograms/kg clonidine for ICB and an IM injection of saline. Blood gases, visual analog scale (VAS) scores, and analgesic demand were determined hourly for 8 h after arrival in the postoperative care unit (PCU). Patients in the block group had significantly lower VAS scores, higher arterial oxygen tension, and lower analgesic demand for the first 4 h in the PCU, compared with the two other groups. No difference was noted thereafter. We conclude that the addition of clonidine to bupivacaine for ICB leads to a short-term effect enhancing postoperative pain control and improving arterial oxygenation, probably mediated by a direct effect on the nerves. Severe pain after thoracotomy can lead to impaired ventilation. We studied the effect of adding clonidine to bupivacaine for intercostal nerve blockade after thoracotomy. Clonidine administered directly on the nerves enhanced analgesia and improved oxygenation for a short time compared with systemic administration or control.",1998.0,0,0
791,9661567,The effect of clonidine or midazolam premedication on perioperative responses during ketamine anesthesia.,M T Taittonen; O A Kirvelä; R Aantaa; J H Kanto,"The use of ketamine as a sole anesthetic induces marked central sympathetic stimulation, causing increased heart rate, blood pressure (BP), and oxygen consumption (VO2). Both alpha 2-agonists and benzodiazepines have been used to attenuate these potentially harmful ketamine-induced responses. This double-blind, randomized, placebo-controlled study was designed to compare the perioperative metabolic, hemodynamic, and sympathoadrenal responses to IM clonidine (2 micrograms/kg) and midazolam (70 micrograms/kg) premedication during ketamine anesthesia. VO2 was measured continuously using indirect calorimetry in 30 ASA physical status I patients. The patients received ketamine, mivacurium, and fentanyl for the induction of anesthesia. Anesthesia was maintained using a ketamine infusion and fentanyl boluses i.v. Preoperatively, both VO2 and BP decreased significantly after the administration clonidine and midazolam compared with placebo (P < 0.01). Intraoperatively, VO2 was higher in the midazolam group than in the placebo and clonidine groups (P < 0.05). Postoperatively, there were no significant differences in BP and VO2, although they stayed at lower level in the clonidine group during the whole postoperative period. Clonidine decreased pre- and postoperative plasma catecholamine concentrations (P < 0.05). Our results indicate that a midazolam-ketamine combination may induce potentially harmful metabolic stimulation, whereas the sympatholytic effects of clonidine on ketamine-anesthetized patients may be beneficial, as perioperative VO2 was decreased. Ketamine causes sympathetic stimulation with an ensuing increase in oxygen consumption. Anticipating that clonidine might attenuate this response, we measured oxygen consumption in patients undergoing surgery during ketamine anesthesia. Patients treated with a clonidine-ketamine combination had lower intra- and postoperative oxygen consumption than those treated with a midazolam-ketamine combination.",1998.0,0,0
792,9661568,Clonidine does not impair redistribution hypothermia after the induction of anesthesia.,J M Bernard; J P Fulgencio; L Delaunay; F Bonnet,"Clonidine is commonly given for premedication, and it impairs normal thermoregulatory responses to warm and cold stimuli while depressing sympathetic tone. We studied the effect of premedication by clonidine on redistribution hypothermia induced by the induction of anesthesia. Sixteen ASA physical status I or II patients were randomly assigned to receive either clonidine 150 micrograms or a placebo. Anesthesia was induced 45 min later by thiopental, fentanyl, and vecuronium i.v. and was maintained by the administration of 0.6% isoflurane. We monitored central core (tympanic) temperature and skin surface temperatures at the forearm and the fingertip during the 2 h after the induction of anesthesia before surgery. We estimated skin blood flow at the level of the forearm by using laser Doppler during the same period. The core temperature decreased comparably in the two groups of patients, from 37.1 +/- 0.2 degrees C to 35.3 +/- 0.4 degrees C and from 37.1 +/- 0.2 degrees C to 35.5 +/- 0.3 degrees C in the clonidine and placebo groups, respectively. The forearm-fingertip surface temperature gradient decreased similarly in the two groups. There was no evidence of cutaneous vasoconstriction. The laser Doppler index at the fingertip increased similarly in the two groups, as did the forearm-fingertip temperature gradient. We conclude that premedication with clonidine does not significantly impair the profile of central hypothermia induced by heat redistribution after the induction of anesthesia. The induction of general anesthesia is associated with redistribution hypothermia. This study shows that premedication with oral clonidine does not worsen the decrease in core temperature resulting from general anesthesia.",1998.0,0,0
793,9663366,A multicenter evaluation of the efficacy and safety of 150 and 300 mg/d sustained-release bupropion tablets versus placebo in depressed outpatients.,F W Reimherr; L A Cunningham; S R Batey; J A Johnston; J A Ascher,"This multicenter, randomized, double-masked, placebo-controlled, parallel-group study compared the antidepressant efficacy and safety of bupropion sustained-release (SR) tablets (150 mg QD or 150 mg BID) with placebo in outpatients with moderate-to-severe depression. The study consisted of a 1-week placebo phase followed by 8 weeks of active treatment with bupropion SR 150 mg/d (150 mg QD, n = 121) or 300 mg/d (150 mg BID, n = 120) or placebo (n = 121). Efficacy was measured by changes in scores on the 17-item Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impressions for Severity of Illness (CGI-S) and Clinical Global Impressions for Improvement of Illness (CGI-I) scales. Safety was monitored by regular assessment of vital signs and adverse events as well as by pretreatment and posttreatment physical and clinical laboratory examinations. By day 56, both bupropion SR treatments were more effective in relieving the symptoms of depression than was placebo. Compared with those receiving placebo, patients in the bupropion SR 150- and 300-mg/d groups had significantly reduced symptoms by treatment day 56, as measured on the 17-item HAM-D, CGI-S, and CGI-I scales (P < 0.05). Bupropion SR was well tolerated, with no serious adverse events reported by bupropion-treated patients; 95% of all reported adverse events were of mild or moderate intensity. No clinically significant changes in vital signs, laboratory test results, or physical findings were observed. A greater mean weight loss was observed at the end of treatment in both the bupropion SR 150-mg (0.5 kg) and bupropion SR 300-mg (1.0 kg) group compared with placebo (0.2 kg). We found that bupropion SR 150 mg administered either once or twice daily was more effective than placebo in treating depression and that once-daily dosing appears to be at least as effective as twice-daily dosing. Should this prove true, depressed patients may be able to benefit from the convenience and improved tolerability associated with once-daily dosing.",1998.0,0,0
794,9664766,Effect of oral clonidine premedication on hemodynamic response during sedated nasal fiberoptic intubation.,S Yokota; T Komatsu; K Yano; K Taki; Y Shimada,"Although oral clonidine premedication is known to reduce the hemodynamic response under general anesthesia, effects of the hemodynamic response during sedated fiberoptic nasal intubation have not yet been examined. Our aim was to compare the effects of clonidine premedication on hemodynamic responses with those of atropine and hydroxyzine premedication during sedated fiberoptic nasal intubation. Thirty adult patients were randomly assigned to one of two groups: Group 1 patients (n = 15) were premedicated with atropine sulfate (0.01 mg/kg) and hydroxyzine hydrochloride (1mg/kg) intramuscularly, and group 2 patients (n = 15) were premedicated with clonidine (5 micrograms/kg) orally. We compared the hemodynamic response and sedation level in fiberoptic nasal intubation between the two groups. there were no significant differences in sedation levels and postoperative complaints between the two groups. But the oral clonidine premedication (Group 2) blunted hemodynamic changes during the fiberoptic intubation. No profound hypotension or marked bradycardia was noted in group 2. We concluded that the oral clonidine premedication might contribute to hemodynamic stability during sedated fiberoptic nasal intubation.",1998.0,0,0
795,9667273,"Methylphenidate therapy improves cognition, mood, and function of brain tumor patients.",C A Meyers; M A Weitzner; A D Valentine; V A Levin,"Patients with malignant glioma develop progressive neurobehavioral deficits over the course of their illness. These are caused both by the effects of the disease and the effects of radiation and chemotherapy. We sought to determine whether methylphenidate treatment would improve these patients' neurobehavioral functioning despite their expected neurologic deterioration. Thirty patients with primary brain tumors underwent neuropsychologic assessment before and during treatment with methylphenidate. Ability to function in activities of daily living and magnetic resonance imaging (MRI) findings were also documented. Patients were assessed on 10, 20, and 30 mg of methylphenidate twice daily. Significant improvements in cognitive function were observed on the 10-mg twice-daily dose. Functional improvements included improved gait, increased stamina and motivation to perform activities, and in one case, increased bladder control. Adverse effects were minimal and immediately resolved when treatment was discontinued. There was no increase in seizure frequency and the majority of patients on glucocorticoid therapy were able to decrease their dose. Gains in cognitive function and ability to perform activities were observed in the setting of progressive neurologic injury documented by MRI in half of the subjects. This study demonstrated improved patient function in the setting of a progressive neurologic illness. Methylphenidate should be more widely considered as adjuvant brain tumor therapy.",1998.0,0,0
796,9671342,Methylphenidate treatment for cocaine abusers with adult attention-deficit/hyperactivity disorder: a pilot study.,F R Levin; S M Evans; D M McDowell; H D Kleber,"Attention-deficit/hyperactivity disorder (ADHD) is common among cocaine abusers seeking treatment. This open trial was carried out to assess the efficacy of sustained-release methylphenidate for the treatment of cocaine abuse among individuals with ADHD. Twelve patients who met DSM-IV diagnostic criteria for adult ADHD and cocaine dependence were entered into a 12-week trial of divided daily doses of sustained-release methylphenidate ranging from 40 to 80 mg. In addition to the pharmacotherapy, patients also received individual weekly relapse prevention therapy. Individuals were assessed weekly for ADHD symptoms; vital signs and urine toxicologies were obtained 3 times a week. Of the 12 patients entered, 10 completed at least 8 weeks of the study and 8 completed the entire study. Using both a semistructured clinical interview and a self-report assessment, patients reported reductions in attention difficulties, hyperactivity, and impulsivity. Self-reported cocaine use and craving decreased significantly. More importantly, cocaine use, confirmed by urine toxicologies, also decreased significantly. These preliminary data suggest that under close supervision, the combined intervention of sustained-release methylphenidate and relapse prevention therapy may be effective in treating individuals with both adult ADHD and cocaine dependence.",1998.0,0,0
797,9672054,"A double-blind, placebo-controlled study of risperidone in adults with autistic disorder and other pervasive developmental disorders.",C J McDougle; J P Holmes; D C Carlson; G H Pelton; D J Cohen; L H Price,"Neurobiological research has implicated the dopamine and serotonin systems in the pathogenesis of autism. Open-label reports suggest that the serotonin2A-dopamine D2 antagonist risperidone may be safe and effective in reducing the interfering symptoms of patients with autism. Thirty-one adults (age [mean+/-SD], 28.1+/-7.3 years) with autistic disorder (n=17) or pervasive developmental disorder not otherwise specified (n=14) participated in a 12-week double-blind, placebo-controlled trial of risperidone. Patients treated with placebo subsequently received a 12-week open-label trial of risperidone. For persons completing the study, 8 (57%) of 14 patients treated with risperidone were categorized as responders (daily dose [mean+/-SD], 2.9+/-1.4 mg) compared with none of 16 in the placebo group (P<.002). Risperidone was superior to placebo in reducing repetitive behavior (P<.001), aggression (P<.001), anxiety or nervousness (P<.02), depression (P<.03), irritability (P<.01), and the overall behavioral symptoms of autism (P<.02). Objective, measurable change in social behavior and language did not occur. Nine (60%) of 15 patients who received treatment with open-label risperidone following the double-blind placebo phase responded. Other than mild, transient sedation, risperidone was well tolerated, with no evidence of extrapyramidal effects, cardiac events, or seizures. Risperidone is more effective than placebo in the short-term treatment of symptoms of autism in adults.",1998.0,0,0
798,9673473,Effects of 0.5% and 0.25% apraclonidine on postoperative intraocular hypertension after cataract extraction.,S Simşek; A Demirok; T Yaşar; A Cinal; A Bayram; O F Yilmaz,"We conducted a double-masked, prospective study to evaluate the effect of 0.5% and 0.25% apraclonidine on postoperative intraocular pressure (IOP) in patients undergoing extracapsular cataract extraction (ECCE) with intraocular lens (IOL) implantation. Fifty-four patients scheduled for ECCE were randomly divided into three groups of 18. The first group received one drop of 0.50% apraclonidine topically one hour before surgery and immediately after the end of the procedure. The second group received the same regimen but with 0.25% apraclonidine. The third group received artificial tears as the control group. IOP was measured 12 h preoperatively and 6 and 24 h postoperatively. All the measurements were made using the same Goldmann applanation tonometer by the same surgeon who did not know to which group the patient belonged. Preoperative mean IOP was 13.66 +/- 2.76 mmHg in the first group, 14.27 +/- 2.24 mmHg in the second and 14.5 +/- 1.34 mmHg in the control group. The differences were not significant (p = 0.398). Mean IOP at the early postoperative visit (6 h) was significantly lower in the first group (17.44 +/- 4.95 mmHg) than the second (21.78 +/- 7.19 mmHg) and the control group (24.55 +/- 5.65 mmHg) (p < 0.001). Mean postoperative IOP at 24 h was again significantly lower in the first group (14.33 +/- 3.75 mmHg) than the second (17.11 +/- 4.16 mmHg) and the control group (19.61 +/- 3.20 mmHg) (p, 0.001). Our findings indicate that topical 0.5% apraclonidine controlled early postoperative intraocular hypertension after cataract extraction without any side effects, while the 0.25% drops were not effective.",1998.0,0,0
799,9685452,Response to growth hormone in attention deficit hyperactivity disorder: effects of methylphenidate and pemoline therapy.,J K Rao; J R Julius; T J Breen; S L Blethen,"To determine whether treatment of attention deficit hyperactivity disorder (ADHD) with methylphenidate hydrochloride or pemoline diminishes the response to growth hormone (GH) therapy in patients with idiopathic GH deficiency (IGHD) or idiopathic short stature (ISS). The National Cooperative Growth Study database was used to identify patients between 3 and 20 years of age with IGHD or ISS and those within these groups who were treated with methylphenidate or pemoline for ADHD. Their growth in response to GH treatment (change in height standard deviation score [SDS]) was compared with that of patients with IGHD or ISS who were not treated for ADHD, by using a stepwise multiple regression analysis. In the IGHD cohort, there were 184 patients who were being treated for ADHD and 2313 who were not. In the ISS cohort there were 117 patients who were being treated for ADHD and 1283 who were not. There was a higher percentage of males being treated for ADHD in both cohorts. In the IGHD cohort, the change in height SDS was positively associated with the number of years of GH treatment, parents' heights, body mass index, and GH injection schedule, and was negatively associated with height SDS at the initiation of GH therapy, age, and maximum stimulated GH level. The use of methylphenidate or pemoline had a negative effect on the change in height SDS, but the magnitude of the effect was small. Similar effects were noted in the ISS cohort, but body mass index and the use of methylphenidate or pemoline had no effect on the change in height SDS. Concurrent ADHD therapy is associated with a slight decrease in the change in height SDS during GH treatment in patients with IGHD but not in those with ISS. Even in IGHD, the magnitude of the effect is small and should not deter the use of such concurrent therapy.",1998.0,0,1
800,9690334,Medical-claims databases in the design of a health-outcomes comparison of quetiapine ('Seroquel') and usual-care antipsychotic medication.,W W Hong; I W Rak; V T Ciuryla; A M Wilson; J W Kylstra; H Y Meltzer; W T Carpenter; A Lehman; L A Arvanitis,"Treating schizophrenia is expensive. Preventing rehospitalization of patients with schizophrenia provides an attractive opportunity for cost savings, especially for patients with 'revolving-door' or multiple-episode schizophrenia. Reducing the occurrence of extrapyramidal symptoms and other adverse events associated with standard antipsychotic agents may increase compliance and reduce the rate of rehospitalization of patients with schizophrenia. Quetiapine ('Seroquel', ICI 204,636, Zeneca Pharmaceuticals) is a new dibenzothiazepine antipsychotic agent with a low propensity for extrapyramidal symptoms. We describe here a unique methodology to compare quetiapine with usual-care medications in real-world treatment settings. The trial objective is to determine if therapy with this new atypical antipsychotic agent can reduce the rate of rehospitalization and, therefore, treatment costs. Using two secondary medical-claims databases, we defined the minimal threshold for revolving-door status as 1.0 admission per year; this definition allows our trial to focus on the subpopulation of schizophrenic patients with the greatest potential for cost savings by either the new atypical antipsychotic quetiapine or usual-care therapy. We describe here the approach used in our trial.",2001.0,0,0
801,9690695,An exploratory haloperidol-controlled dose-finding study of ziprasidone in hospitalized patients with schizophrenia or schizoaffective disorder.,D C Goff; T Posever; L Herz; J Simmons; N Kletti; K Lapierre; K D Wilner; C G Law; G N Ko,"Ninety patients with schizophrenia or schizoaffective disorder according to DSM-III-R criteria participated in this double-blind, exploratory, dose-ranging trial. After a single-blind washout period of 4 to 7 days, patients were randomly assigned to receive one of four fixed doses of the new antipsychotic, ziprasidone 4 (N = 19), 10 (N = 17), 40 (N = 17), or 160 (N = 20) mg/day or haloperidol 15 mg/day (N = 17) for 4 weeks. A dose-response relationship among ziprasidone groups was established for improvements in Clinical Global Impression Severity (CGI-S) score (p = 0.002) but not in Brief Psychiatric Rating Scale (BPRS) total score (p = 0.08). The intent-to-treat analysis of mean changes from baseline in the BPRS total, BPRS Psychosis core, and CGI-S scores demonstrated that ziprasidone 160 mg/day was comparable with haloperidol in reducing overall psychopathology and positive symptoms and was superior to ziprasidone 4 mg/day. Despite the small sample size and short duration of the trial, the improvement in CGI-S with both ziprasidone 160 mg/day and haloperidol 15 mg/day was statistically significantly greater than with ziprasidone 4 mg/day (p = 0.001 andp = 0.005, respectively). The percentage of patients classified as responders on both the BPRS total (> or = 30% improvement) and CGI-Improvement (score of 1 or 2) scales in the ziprasidone 160 mg/day group was similar to that in the haloperidol group and nonsignificantly greater than that in the ziprasidone 4 mg/day group. On all assessments of clinical efficacy, the improvements associated with ziprasidone 4 mg/day, 10 mg/day, and 40 mg/day were similar. Concomitant benztropine use at any time during the study was less frequent with ziprasidone 160 mg/day (15%) than with haloperidol (53%). Haloperidol was associated with a sustained hyperprolactinemia, unlike ziprasidone, where only transient elevations in prolactin that returned to normal within the dosing interval were observed. Ziprasidone was well tolerated, and the incidence of adverse events was similar in all groups. The results of this study suggest that ziprasidone 160 mg/day is as effective as haloperidol 15 mg/day in reducing overall psychopathology and positive symptoms of an acute exacerbation of schizophrenia or schizoaffective disorder but has a lower potential to induce extrapyramidal symptoms.",1998.0,0,0
802,9690708,Olanzapine-induced reversible priaprism: a case report.,J M Deirmenjian; S M Erhart; D A Wirshing; B J Spellberg; W C Wirshing,,1998.0,0,0
803,9700516,Methylphenidate does not modify the impact of response frequency or stimulus sequence on performance and event-related potentials of children with attention deficit hyperactivity disorder.,J A Smithee; R Klorman; J T Brumaghim; A D Borgstedt,"Twenty-six children with attention deficit/hyperactivity disorder (ADHD) participated in a double-blind trial consisting of 2 consecutive weeks each of placebo and methylphenidate (M = 26.92 mg/day = 0.78 mg/kg/day). As expected, stimulant therapy resulted in moderate weight loss, increased somatic complaints, and teacher and parent reports of reduced inattentiveness, aggression, and oppositionality. In both phases of the trial, patients were tested in a choice reaction time task assessing two aspects of the task that presumably affect response selection: response frequency (ratio of targets/nontargets = 25/75 vs. 50/50) and stimulus sequence (alternations vs. repetitions). Both manipulations yielded expected results on performance and event-related potentials (ERPs). Stimulant treatment increased accuracy and speed among younger children and curtailed variability of reaction time for the sample as a whole. However, methylphenidate did not affect ERPs. In combination, the results imply that the enhancement of performance by methylphenidate does not involve the demands of response selection examined in this study.",1998.0,0,0
804,9700518,"The revised Conners' Parent Rating Scale (CPRS-R): factor structure, reliability, and criterion validity.",C K Conners; G Sitarenios; J D Parker; J N Epstein,"The Conners' Parent Rating Scale (CPRS) is a popular research and clinical tool for obtaining parental reports of childhood behavior problems. The present study introduces a revised CPRS (CPRS-R) which has norms derived from a large, representative sample of North American children, uses confirmatory factor analysis to develop a definitive factor structure, and has an updated item content to reflect recent knowledge and developments concerning childhood behavior problems. Exploratory and confirmatory factor-analytic results revealed a seven-factor model including the following factors: Cognitive Problems, Oppositional, Hyperactivity-Impulsivity, Anxious-Shy, Perfectionism, Social Problems, and Psychosomatic. The psychometric properties of the revised scale appear adequate as demonstrated by good internal reliability coefficients, high test-retest reliability, and effective discriminatory power. Advantages of the CPRS-R include a corresponding factor structure with the Conners' Teacher Rating Scale-Revised and comprehensive symptom coverage for attention deficit hyperactivity disorder (ADHD) and related disorders. Factor congruence with the original CPRS as well as similarities with other parent rating scales are discussed.",1998.0,0,0
805,9700520,"Revision and restandardization of the Conners Teacher Rating Scale (CTRS-R): factor structure, reliability, and criterion validity.",C K Conners; G Sitarenios; J D Parker; J N Epstein,"The Conners Teacher Rating Scale (CTRS) is a commonly used research and clinical tool for assessing children's behavior in the classroom. The present study introduces the revised CTRS (CTRS-R) which improves on the original CTRS by (1) establishing normative data from a large, representative North American sample, (2) deriving a factor structure using advanced statistical techniques, and (3) updating the item content to reflect current conceptualizations of childhood disorders. Using confirmatory factor analysis, a six-factor structure was found which includes Hyperactivity-Impulsivity, Perfectionism, Inattention/Cognitive Problems, Social Problems, Oppositionality, and Anxious/Shy factors. The reliability of the scale, as measured by test-retest correlations and internal consistency, is generally satisfactory. Using all of the scale factors to discriminate between attention deficit hyperactivity disordered and normal children, 85 percent of children were correctly classified, supporting the validity of the scale and indicating excellent clinical utility. Similarities and differences between the original CTRS factor structure and the CTRS-R factor structure are discussed.",1998.0,0,0
806,9718222,Psychotropic medication use and risk of epithelial ovarian cancer.,B L Harlow; D W Cramer; J A Baron; L Titus-Ernstoff; E R Greenberg,"Long-term use of psychotropic medication may increase the risk for epithelial ovarian cancer through increased gonadotropin secretion or direct ovarian stimulation of adrenergic receptors, effects which may affect ovarian cancer pathogenesis. An earlier case-control study found that prior use of antidepressants or benzodiazepine tranquilizers was associated with a 2-fold increase in risk of epithelial ovarian cancer. However, that study lacked details on all types of psychotropic medications, length of use, and the categorization of the specific action of these medications on the hypothalamic-pituitary-ovarian axis. In a new case-control study conducted in eastern Massachusetts (MA) and all of New Hampshire (NH), we identified all women with newly diagnosed ovarian cancer between May 1992 and March 1997. We interviewed 563 women diagnosed with malignant or borderline epithelial ovarian tumors and 523 controls identified through random digit dialing and the use of Town Books (residential listings by name, age, and precinct). Participants were asked to provide the name of medications used for 6 months or longer, the age at first use, and total months or years of use. Psychotropic medications included amphetamines, sedatives, barbiturates/anticonvulsants, antidepressants, and antipsychotics. Self-reported use of psychotropic medication for 6 months or longer was associated with a statistically significant increase in risk of invasive ovarian cancer [odds ratio (OR), 1.6; 95% confidence interval (CI), 1.1-2.3]. Relative to nonusers, risk was greatest in those whose first use occurred premenopausally for more than 2 years (OR, 2.9; CI, 1.3-6.6). The association was largely confined to use of medications that operate through dopaminergic mechanisms (OR, 2.9; CI, 1.3-6.4) or gabaergic pathways (OR, 1.5; CI, 0.9-2.5) as opposed to serotoninergic pathways (OR, 1.0; CI, 0.4-2.1). These results are consistent with the hypothesis that psychotropic medications induce gonadotropin secretion, which in turn may increase ovarian cancer risk. However, until other studies confirm our findings and determine whether they apply to medications with specific neuroendocrine actions, it is premature to advise a change in clinical practice and conclude that these medications indeed play a role in the etiology of ovarian cancer.",1998.0,0,0
807,9728835,"Intrathecal, but not intravenous, clonidine reduces experimental thermal or capsaicin-induced pain and hyperalgesia in normal volunteers.",J C Eisenach; D D Hood; R Curry,"Clonidine is approved for intraspinal administration in the treatment of neuropathic cancer pain. Some studies have suggested an analgesic effect after systemic clonidine administration. The purpose of this study was to compare the analgesic effects of intrathecal and IV clonidine with acute noxious stimulation and with hyperalgesia from intradermal capsaicin injection in volunteers. Sixteen healthy volunteers received intradermal injections of capsaicin (100 microg) before and after the IV or intrathecal injection of clonidine 50 or 150 microg in a randomized, double-blind manner. Pain and areas of mechanical hyperalgesia and allodynia were determined at specified intervals. In addition, pain to noxious heat stimulation was determined. The capsaicin injection produced pain, followed by hyperalgesia and allodynia. The intrathecal, but not IV, injection of 150 microg of clonidine reduced capsaicin-induced pain and area of hyperalgesia. Intrathecal clonidine (150 microg) reduced pain to heat stimulation, whereas IV clonidine did not. The groups did not differ in hemodynamic or sedative effects from clonidine. These data support the value of intraspinal administration of clonidine for the treatment of acute pain and of pain states associated with hyperalgesia. Similarly, they suggest that analgesia from the systemic administration of this alpha2-adrenergic agonist, if any, is weak in doses that produce sedation and reduce blood pressure. To the extent that the experimental pain conditions used in this study reflect those in patients with acute and chronic pain, these data support the spinal rather than IV injection of clonidine for analgesia.",1998.0,0,0
808,9730078,Prediction of stimulant response in children with attention-deficit/hyperactivity disorder.,J B Thomson; C K Varley,"Discrimination of stimulant-responding and nonresponding groups of children with attention-deficit/hyperactivity disorder (ADHD) on the basis of demographic, neurophysiologic, or behavioral variables would be beneficial for clinical and theoretical reasons. Previous researchers have identified many predictor variables, but relationships between predictor and criterion variables generally have been subtle. In addition, few investigations have considered the relative predictive power of the variables. The present study evaluated the multivariate relationship between several predictor variables and response to medication in 336 children with ADHD. Neurologic status, inattention, and overactivity were found to be most likely to predict good response to psychostimulants, whether rated by parents or teachers. Although a number of variables predicted a positive psychostimulant response, the strength of the predictive associations suggests only minimal clinical usefulness.",1998.0,0,0
809,9740930,[Dose-response relationship of clonidine with epidural administration of ropivacaine in orthopedic procedures of the lower extremities].,J M Engel; R Hussmann; K H Gürtler; T Menges; G Hempelmann,"The aim of this study was to investigate preliminarydose-range effects of clonidine added to ropivacaine for epidural analgesia in elective orthopedic surgery of the lower limbs with doses, causing a minimum of cardiovascular side effects. 60 patients were randomly assigned to receive in a double-blind fashion a mixture of 1 mg/cm height ropivacaine plus saline or 1 mg/cm ropivacaine plus 25 micrograms, 50 micrograms, 75 micrograms, 100 micrograms or 150 micrograms clonidine for epidural analgesia. The sensory and motor function were determined at defined time intervals for 30 minutes. Heart rate and blood pressure were controlled and sedation score was judged. The postoperative 2-segment-regression of pin-prick and the onset of pain were recorded. The six groups were comparable in demographic data and in term of onset time. The prolongation of analgesia reached 513 +/- 92 min (p = 0.002) for 150 micrograms clonidine, 460 +/- 148 min (p = 0.073) for 100 micrograms clonidine, 440 +/- 86 min (p = 0.057) for 75 micrograms clonidine compared with 347 +/- 114 min for saline. In an equal manner, 2-segment-regression for pin-prick was extended to 251 +/- 47 min (p = 0.018) for 150 micrograms clonidine, 238 +/- 33 min (p = 0.034) for 100 micrograms clonidine, 229 +/- 29 min (p = 0.027) for 75 micrograms clonidine and 178 +/- 43 min for saline. Heart rate dropped down in all groups. Mean arterial pressure decreased significantly in the groups with 75, 100 and 150 micrograms clonidine. Sedation score increased continuously from 0.6 +/- 0.5 (saline) to 1.8 +/- 0.8 (150 micrograms clonidine). We conclude that 150 micrograms clonidine significantly enhances the duration of analgesia of epidurally administered ropivacaine in a mean of 171 mg. This time interval is longer than the one with 200 mg ropivacaine alone. But, there are side effects in form of decrease of arterial pressure. Cardiovascular monitoring seems to be essential. Because of the enhanced analgesia duration, the time interval for reloading epidural anaesthesia are increased.",1998.0,0,0
810,9766762,Dopamine transporter occupancies in the human brain induced by therapeutic doses of oral methylphenidate.,N D Volkow; G J Wang; J S Fowler; S J Gatley; J Logan; Y S Ding; R Hitzemann; N Pappas,"The therapeutic effects of methylphenidate in the treatment of attention deficit disorder have been attributed to its ability to increase the synaptic concentration of dopamine by blocking the dopamine transporters. However, the levels of dopamine transporter blockade achieved by therapeutic doses of methylphenidate are not known. This study measured, for the first time, dopamine transporter occupancy by orally administered methylphenidate in the human brain and its rate of uptake in the brain. Positron emission tomography (PET) and [11C]cocaine were used to estimate dopamine transporter occupancies after different doses of oral methylphenidate in seven normal subjects (mean age=24 years, SD=7). In addition, the pharmacokinetics of oral methylphenidate were measured in the baboon brain through use of PET and [11C]methylphenidate administered through an orogastric tube. At 120 minutes after administration, oral methylphenidate produced a dose-dependent blockade of dopamine transporter; means=12% (SD= 4%) for 5 mg, 40% (SD=12%) for 10 mg, 54% (SD=5%) for 20 mg, 72% (SD=3%) for 40 mg, and 74% (SD=2%) for 60 mg. The estimated dose of oral methylphenidate required to block 50% of the dopamine transporter corresponded to 0.25 mg/kg. Oral methylphenidate did not reach peak concentration in brain until 60 minutes after its administration. Oral methylphenidate is very effective in blocking dopamine transporters, and at the weight-adjusted doses used therapeutically (0.3 to 0.6 mg/kg), it is likely to occupy more than 50% of the dopamine transporters. The time to reach peak brain uptake for oral methylphenidate in brain corresponds well with the reported time course to reach peak behavioral effects.",1998.0,0,0
811,9768566,Failure of clonidine to stimulate feeding in healthy humans.,S Crow; W Meller; B Praus; S Raatz; J Mitchell,"The alpha2-adrenergic system is involved in the regulation of food intake in animals but its effects on feeding in humans are unknown. We hypothesized that clonidine administration would stimulate food intake in healthy human subjects. Ten men and 4 women, all physically and psychiatrically healthy, received clonidine 3 microg/kg or placebo, orally, in blinded, balanced, randomized order. Consumption of a liquid test meal was measured; also, serum growth hormone levels were used as a secondary measure of clonidine effects. Visual analog scale ratings of hunger, satiety, and sedation were obtained before, during, and after the test meal. A subset of five subjects also received 1.5 microg/kg clonidine, in addition to the two trials described above. Test meal consumption was greater following placebo than following clonidine. Sedation ratings were substantially higher at all time points after clonidine and correlated with meal consumption (correlation coefficient r = -0.584; p = 0.028). Hunger and satiety ratings did not differ. The 1.5 microg/kg dose did not provide different effects on feeding from that seen with placebo. Contrary to our hypothesis, clonidine did not stimulate food intake in humans. Sedation associated with clonidine administration may have suppressed any effects on feeding.",1998.0,0,0
812,9771298,Effects of premedication on dose requirements for propofol: comparison of clonidine and hydroxyzine.,J Guglielminotti; C Descraques; S Petitmaire; L Almenza; O Grenapin; J Mantz,"The influence of a single dose of clonidine (5 micrograms kg-1) or hydroxyzine (1 mg kg-1) on intraoperative propofol requirements was determined in 28 male patients (ASA I) undergoing elective orthopaedic surgery. Patients were randomly allocated to receive either clonidine or hydroxyzine orally 2 h before induction of anaesthesia. After a loading dose of propofol (2.5 mg kg-1), mivacurium (0.2 mg kg-1) and alfentanil (15 micrograms kg-1), anaesthesia was maintained with a standardized propofol infusion supplemented with nitrous oxide (66%) in oxygen. During surgery, additional propofol boluses (1 mg kg-1) were administered when heart rate or mean arterial pressure increased by more than 10% compared with preinduction values. The clonidine group demonstrated a 14.5% decrease in total propofol requirements (P < 0.05) and a 52.2% reduction in additional propofol boluses (P < 0.02) in comparison with the hydroxyzine group. intraoperative heart rate and mean arterial pressure were significantly lower in the clonidine group but no patients needed treatment with ephedrine for hypotension or bradycardia. Recovery of psychomotor function and discharge from the recovery room were not delayed in the clonidine group. This study indicates that 5 micrograms kg-1 clonidine given as premedication in ASA I patients reduces intraoperative propofol requirements in comparison with 1 mg kg-1 hydroxyzine without inducing adverse effects on recovery or haemodynamic stability.",1998.0,0,0
813,9773134,"Epidural fentanyl, adrenaline and clonidine as adjuvants to local anaesthetics for surgical analgesia: meta-analyses of analgesia and side-effects.",M Curatolo; S Petersen-Felix; P Scaramozzino; A M Zbinden,"The risk/benefit ratio of adding fentanyl, adrenaline and clonidine to epidural local anaesthetics for improving intraoperative analgesia is unclear. This meta-analysis was performed to clarify this issue. Trials retrieved by search were considered if they were prospective, controlled, epidural analgesia (without combining general anaesthesia) was planned and occurrence of pain during surgery or side-effects were reported. Papers entered meta-analysis if they reached a predefined minimum quality score. Pooled odds ratios (OR) and confidence intervals (CI) were computed. P < 0.05 was considered as significant. Eighteen trials were included in the analysis for fentanyl. Fentanyl decreased the likelihood of pain (OR = 0.21, 95% CI = 0.15-0.30, P < 0.001) and increased the incidence of pruritus (OR = 5.59, 95% CI = 3.12-10.05, P < 0.001) and sedation (OR = 1.88, 95% CI = 1.19-2.98, P = 0.003), compared to control (local anaesthetic without fentanyl). Fentanyl had no effect on respiratory depression, nausea, vomiting and Apgar score. One case of respiratory depression of a newborn was observed. Because of the very low number of trials selected, evaluation of adrenaline and clonidine was not feasible. The analysis of current literature shows that the addition of fentanyl to local anaesthetics for intraoperative epidural analgesia is safe and advantageous. The reduction in the incidence of pain during surgery is quantitatively high and therefore clinically significant. Side-effects are mild. Randomized, controlled trials have to be performed in order to clarify the role of adrenaline and clonidine as epidural adjuvants for surgical analgesia.",1998.0,0,0
814,9778664,Chronic olanzapine or sertindole treatment results in reduced oral chewing movements in rats compared to haloperidol.,X M Gao; K Sakai; C A Tamminga,"Chronic haloperidol treatment typically produces late-onset, purposeless oral chewing movements in laboratory rats with a prevalence of 40 to 60%. Chronic clozapine does not produce these movements. Based on the phenomenologic and pharmacologic similarities between these rat chewing movements and human tardive dyskinesia (TD), the animal movements are often used as a model of tardive dyskinesia (TD). Here we report results of the association of oral chewing movements in rats with chronic administration of two new antipsychotic drugs, olanzapine and sertindole. Because each of these antipsychotic drugs has a very low incidence of acute Parkinsonism in human studies, they are candidates for showing a low tardive dyskinesia risk. Neither new drug produced a significant incidence of haloperidol-like chewing in rats, nor did movement ratings after their chronic administration differ from placebo; whereas, haloperidol produced a 60% prevalence of purposeless chewing and a prevalence significantly increased from placebo. This low rate of oral dyskinesias in rats is consistent with several of the preclinical characteristics of the drugs and correlates with their low acute motor side effects in clinical trials. We propose, although have not yet tested in humans, that these animal results will predict low TD liability of these drugs.",1998.0,0,0
815,9785160,"""Saturday night fever"": ecstasy related problems in a London accident and emergency department.",H Williams; L Dratcu; R Taylor; M Roberts; A Oyefeso,"To report on the extent and nature of acute MDMA (ecstasy) related problems presenting to a large London hospital's accident and emergency (A&E) department. The computerised attendance records for all patients attending the A&E department over a 15 month period were retrospectively screened. Potential cases thus identified had their case notes systematically reviewed to confirm the history of MDMA use and to extract other relevant data. Forty eight consecutive MDMA related cases were identified. All were in the 15-30 year age group with the majority presenting in the early hours at weekends and having consumed the drug at a night club. The mean number of tablets consumed was two and almost 40% had taken MDMA before. Polydrug use was common with half of the sample having concurrently taken another illicit substance--most commonly other stimulants (amphetamines and cocaine). A wide range of adverse clinical features was found. The most common symptoms were vague and non-specific such as feeling strange or unwell, however many patients had collapsed or lost consciousness. The most common signs elicited were related to sympathetic overactivity, agitation/disturbed behaviour, and increased temperature. The more serious complications of delirium, seizures, and profound unconsciousness (coma) were commoner when MDMA was used in combination with other substances. For young adults presenting late at night at weekends and exhibiting symptoms of sympathetic overactivity, disturbed behaviour, and increased temperature (""Saturday night fever"") the use of stimulant dance drugs especially MDMA should be suspected. As MDMA use does not appear to occur in isolation, the clinical picture is likely to be complicated by multiple rather than single drug ingestion. This poses increased diagnostic and management challenges for A&E staff who typically represent the front line response to dance drug related problems.",1998.0,0,0
816,9789193,Effects of methylphenidate on aggressive urban children with attention deficit hyperactivity disorder.,O G Bukstein; D J Kolko,"Determined the efficacy of methylphenidate (MPH) in a clinical population of aggressive, urban children diagnosed with attention deficit hyperactivity disorder (ADHD). In previous studies of prepubertal children with ADHD, MPH has been shown to be effective when compared with placebo. Eighteen inner-city children (ages 6 to 12 years), diagnosed with ADHD and attending a summer treatment program for youth with disruptive behavior disorders, participated in a double-blind placebo trial with assessment data obtained from staff in the program and parents at home. Based on staff ratings of the children's behavior in the program and an academic classroom, the children displayed significant improvements in ADHD symptoms and aggressive behavior with low- and high-dose MPH conditions. At home, parents and guardians reported few significant differences between placebo and MPH on behavior ratings. In both settings, MPH was well tolerated with few side effects found during active drug conditions.",1998.0,0,1
817,9789907,Attentional improvement following quetiapine fumarate treatment in schizophrenia.,K W Sax; S M Strakowski; P E Keck,"This study examined changes in attentional performance in patients with schizophrenia during the 2 months after initiating treatment with quetiapine fumarate. Prior to treatment, attentional performance in patients with schizophrenia (n = 10) was significantly (p < 0.01) worse than in matched controls (n = 12). During treatment with quetiapine, performance in patients with schizophrenia improved, and by 2 months, did not differ significantly from that of the controls. These results suggest that quetiapine produces a significant improvement in attentional functioning in patients with schizophrenia.",2001.0,0,0
818,9793771,The effect of 0.25% apraclonidine in preventing intraocular pressure elevation after Nd:YAG laser posterior capsulotomy.,S Simsek; H Ertürk; A Demirok; A Cinal; T Yasar; C Karadenizli,"The efficacy and adverse effects of 0.25% apraclonidine on intraocular pressure (IOP) after Nd:YAG laser posterior capsulotomy were investigated, and the results were compared with placebo, 0.50% timolol maleate and 1% apraclonidine. Eighty eyes were randomly assigned to four groups of 20 eyes. In a double-masked design, the groups were treated with placebo (group 1), 0.50% timolol maleate (group 2), 1% apraclonidine (group 3), 0.25% apraclonidine (group 4) one hour before and five minutes after Nd:YAG laser posterior capsulotomy. IOP was measured by applanation tonometry 1 hour before (baseline IOP) and 1, 3, 24 hours after capsulotomy. The average baseline IOP increased respectively 3.90 +/- 5.35, 5.95 +/- 5.32, 1.15 +/- 3.20 mmHg in the first group 1, 3 and 24 hours post-treatment. There were significant differences between baseline IOP and 1 and 3 hours but not at 24 hours (p = 0.004, p = 0.001, p = 0.13). IOP increased 0.40 +/- 4.08, 0.75 +/- 5.33, 0.80 +/- 6.03 mmHg in the second group at the same times. The differences between the average baseline IOP and the 1, 3 and 24 h measurement were not significant (p = 0.83, p = 0.65, p = 0.93). In the third group, IOP decreased 3.70 +/- 2.40, 3.30 +/- 2.47, 2.65 +/- 1.56 mmHg at the measurement times, with significant differences between the average baseline IOP and the 1, 3 and 24 hour measurements (p = 0.001, p = 0.0001, p = 0.01). In the fourth group IOP increased 0.35 +/- 3.32 mmHg at 1 hour, but decreased 1.25 +/- 3.41, 0.90 +/- 2.07 mmHg at 3 and 24 hours. The differences were not significant (p = 0.94, p = 0.16, p = 0.08). When the 0.25% and 1% apraclonidine groups were compared, there were significant differences between the average IOP at 1 hour in both groups but not at 3 and 24 hours (p = 0.01, p = 0.17, p = 0.21). Similarly, there were no significant differences between the average IOP at the same times when the 0.25% apraclonidine group was compared with the timolol group (p = 0.30, p = 0.08, p = 0.16). Some systemic and local side effects were seen in the timolol and 1% apraclonidine groups, but none with 0.25% apraclonidine. It was concluded that 0.25% apraclonidine is effective in preventing the early elevation of IOP after Nd:YAG laser posterior capsulotomy and may offer an alternative to 0.50% timolol maleate and 1% apraclonidine.",1998.0,0,0
819,9796240,Incidence of hypotension and bradycardia during integrated epidural/general anaesthesia. An epidemiologic observational study on 1200 consecutive patients. Italian Study Group on Integrated Anaesthesia.,G Fanelli; A Casati; M Berti; L Rossignoli,"Combined epidural/general anaesthesia might theoretically emphasise the cardiovascular effects of epidural block alone. The goal of the present investigation was to evaluate the incidence of both hypotension and bradycardia during integrated epidural/general anaesthesia in a multicentric, observational study. The incidence of clinical hypotension (systolic arterial blood pressure decrease by 30% or more from baseline), and bradycardia (heart rate < 50 beats/min) and other side effects have been evaluated in 1200 consecutive patients receiving integrated epidural/general anaesthesia. The time from induction of epidural anaesthesia to induction of general anaesthesia was considered as preoperative; while the time after general anaesthesia induction was considered as intraoperative. Preoperatively hypotension developed in 85 patients (2.8%), and bradycardia in 54 patients (4.5%). Intraoperatively, hypotension was observed in 380 patients (31.6%), and bradycardia in 153 patients (12.7%). Hypotension and bradycardia were not influenced by the type of surgical procedure, the type of maintenance of general anaesthesia (inhalational versus total intravenous general anaesthesia) and the level of epidural block (lumbar versus thoracic); but they were more frequent in patients with ASA physical status II and III-IV compared to patients with ASA physical status I (p < 0.05). Prophylactic volume preload decreased the incidence of hypotension from 41.5% to 22.4% (p < 0.0001), while prophylactic atropine before epidural block did not affect the incidence of bradycardia. Patients receiving epidural clonidine showed an increased incidence of intraoperative bradycardia compared to those who did not receive it (p < 0.0001). Randomized, controlled studies should be advocated in order to compare the incidence of hypotension and bradycardia during integrated anaesthesia and during epidural block alone. Our results demonstrated that the use of integrated epidural/general anaesthesia produces an incidence of perioperative hypotension and bradycardia similar to that reported when central blocks are used alone.",1998.0,0,0
820,9809953,Hemodynamic changes induced by laparoscopy and their endocrine correlates: effects of clonidine.,J L Joris; J D Chiche; J L Canivet; N J Jacquet; J J Legros; M L Lamy,"We investigated endocrine correlates of the hemodynamic changes induced by carbon dioxide pneumoperitoneum (PNO). We then studied whether clonidine might modulate the hemodynamic changes induced by PNO by reducing release of catecholamines and vasopressin. Both mechanical and neurohumoral factors contribute to the hemodynamic changes induced by carbon dioxide PNO. Several mediators have been proposed, but no study has correlated hemodynamic changes with changes in levels of these potential mediators. We conducted two studies, each including 20 healthy patients scheduled for elective laparoscopic cholecystectomy. In the first study serial measurements of hemodynamics (thermodilution technique) were done during laparoscopy and after exsufflation. Plasma concentrations of cortisol, catecholamines, vasopressin, renin, endothelin and prostaglandins were measured at the same time points. In the second study patients were randomly allocated to receive 8 microg/kg clonidine infused over 1 h or placebo before PNO. Hemodynamics and plasma levels of cortisol, catecholamines and vasopressin were measured during PNO and after exsufflation. Peritoneal insufflation resulted in a significant reduction of cardiac output (18+/-4%) and increases in mean arterial pressure (39+/-8%) and systemic (70+/-12%) and pulmonary (98+/-18%) vascular resistances. Laparoscopy resulted in progressive and significant increases in plasma concentrations of cortisol, epinephrine, norepinephrine and renin. Vasopressin plasma concentrations markedly increased immediately after the beginning of PNO (before PNO 6+/-4 pg/ml; during PNO 129+/-42 pg/ml; p < 0.05). The profile of vasopressin release paralleled the time course of changes in systemic vascular resistance. Prostaglandins and endothelin did not change significantly. Clonidine significantly reduced mean arterial pressure, heart rate and the increase in systemic vascular resistance. Clonidine also significantly reduced catecholamine concentrations but did not alter vasopressin and cortisol plasma concentrations. Vasopressin and catecholamines probably mediate the increase in systemic vascular resistance observed during PNO. Clonidine before PNO reduces catecholamine release and attenuates hemodynamic changes during laparoscopy.",1998.0,0,0
821,9813512,I.v. clonidine prevents post-extradural shivering.,S Sia,"We have studied the efficacy of i.v. clonidine to prevent shivering in 100 healthy patients who received extradural block for knee arthroscopy. Patients were randomly allocated to two groups. Just before extradural anaesthesia (0 min = baseline), group I (n = 50) received i.v. clonidine 1 microgram kg-1, group II (n = 50) received a saline bolus. Systolic arterial pressure (SAP), heart rate (HR), oxygen saturation (SpO2), cutaneous temperature and level of sedation, were all recorded at baseline and after 10, 20, 30, 45, 60 min. Shivering was evaluated by a blinded investigator for a period of 90 min and was graded as moderate or severe. Three patients in group I shivered compared with 19 in group II (P < 0.001). Patients with severe shivering were seen only in group II. There were no significant differences between the groups during the study period in SAP, HR, SpO2, cutaneous temperature or level of sedation. We conclude that preventive use of i.v. clonidine 1 microgram kg-1 provides a significant reduction in the incidence of post-extradural shivering without clinically relevant adverse side effects.",1998.0,0,0
822,9813951,Prospective study of tobacco smoking and substance dependencies among samples of ADHD and non-ADHD participants.,N M Lambert; C S Hartsough,"This study focused on an audience at high risk for heavy use of licit and illicit substances: young adults who as children had attention-deficit/hyperactivity disorder (ADHD). The participants in this study were part of a longitudinal study of the life histories of 492 children, one third of whom were identified as hyperactive in 1974 and whose childhood symptom ratings and medical histories were used to establish Diagnostic and Statistical Manual of Mental Disorders (3rd ed., revised; DSM-III-R) ADHD diagnoses (American Psychiatric Association, 1987). The objectives of the study centered on describing (a) developmental history of tobacco use among ADHD and non-ADHD participants in a longitudinal sample, (b) the characteristic adult patterns of tobacco use from early adolescence through early adulthood, and (c) the relationship between ADHD status and tobacco and substance dependence outcomes. Adult data were obtained for 81% of the original 492 participants (77% of the ADHD and 86% of the controls). Lifetime and current tobacco use were assessed from child, adolescent, and adult data, yielding eight measures of smoking status. The study showed that participants with and without ADHD did not differ in age of initiation to smoking, but there was a significant difference in the age they began smoking regularly. By age 17, 46% of all participants with ADHD, as contrasted with 24% of the age-mate controls, reported smoking cigarettes daily. In adulthood, the proportion of participants with ADHD who were current smokers (42%) continued to exceed that of the age-mate controls (26%). Among current adult smokers, 35% with ADHD smoked daily as compared to 16% of the age-mate controls. There were significantly different lifetime tobacco dependence rates--40% compared to 19% for age-mate controls. The rates for cocaine dependence were 21% for participants with ADHD and 10% for age-mate controls. We reported a significant difference in rates of daily smoking and tobacco dependence for those with ADHD who had used stimulant medication in childhood in contrast to controls. Results were interpreted to support a possible link between ADHD treatment histories and levels of tobacco smoking and tobacco dependence in adulthood.",1998.0,0,0
823,9813955,Sleep disturbances in children with attention-deficit/hyperactivity disorder: a comparative study with healthy siblings.,A Ring; D Stein; Y Barak; A Teicher; J Hadjez; A Elizur; A Weizman,"The sleep profiles of 13 children with attention-deficit/hyperactivity disorder (ADHD) who were treated with a fixed dose of methylphenidate for at least 1 month were compared with those of 16 healthy siblings. Sleep disturbances were assessed according to a structured sleep questionnaire, and the severity of ADHD was evaluated via the Conners Parents Teachers Rating Scale. The results indicated that significantly more children with ADHD demonstrated single or multiple sleep disturbances as well as higher rates of specific sleep disorders, such as initial and middle insomnia, compared with their siblings. No correlation was found between the severity of ADHD and disturbed sleep. Sleep duration and satisfaction with sleep were similar in the two groups. These findings raise important questions regarding the association between ADHD and disturbed sleep.",1998.0,0,0
824,9813957,School-based methylphenidate placebo protocols: methodological and practical issues.,I A Hyman; A Wojtowicz; K D Lee; M E Haffner; C A Fiorello; J J Storlazzi; J Rosenfeld,"Around 1990, psychologists and educators began to notice increasing use of methylphenidate by students. Diagnosis of attention-deficit/hyperactivity disorder by family physicians and pediatricians was most commonly based on brief behavioral descriptions by parents and, infrequently, by use of rating scales. At that time, the present researchers began to explore the development of a school-based, methodologically sound, and inexpensive method of assessing the efficacy of stimulant medications, which would ensure reasonable compliance by teachers, parents, and students in monitoring the effects of medications and placebos. This article focuses on the methodological issues involved in choosing instruments to monitor behavior, once a comprehensive evaluation has suggested trials on Ritalin. Case examples illustrate problems of teacher compliance in filling out measures, supplying adequate placebos, and obtaining physician cooperation, and with the practical issue of providing adequate data without overwhelming the time and resources of participants. Emerging school-based methodologies are discussed with recommendations for future efforts.",1998.0,0,0
825,9813958,"Evaluating medication response in ADHD: cognitive, behavioral, and single-subject methodology.",J B Hale; J A Hoeppner; M B DeWitt; D L Coury; D G Ritacco; B Trommer,"Although evidence supports the use of double-blind placebo medication trials to evaluate methylphenidate (MPH) effects on the core behavioral symptoms of attention-deficit/hyperactivity disorder (ADHD), few studies have demonstrated their utility in examining MPH effects on the cognitive deficits associated with ADHD. This article presents a technique for evaluating behavioral and cognitive dose-response relationships at the single-subject level of analysis. Case study results and multivariate analyses suggest that systematic evaluation of behavioral and cognitive MPH dose-response relationships could lead to more accurate MPH titration and greater long-term multimodal treatment efficacy.",1998.0,0,0
826,9813959,Use of the restricted academic task in ADHD dose-response relationships.,M Fischer; R F Newby,"Behavioral assessment techniques have been shown to make a significant contribution in the evaluation of stimulant medication response in children with attention-deficit/hyperactivity disorder. This article examines the role of a behavioral measure consisting of standardized observation of a child while he or she performs an academic-like task (Restricted Academic Task). This technique is reliable and valid for repeated administrations across medication dosages and placebo. It can assist in optimizing medication dosage for individual children, given its sensitivity to dosage effects. It also allows the capture of medication-related changes in an area of functioning that is not directly assessed by parent and teacher judgments and ratings. In this way the Restricted Academic Task may have greater ecological validity than the results of other, more traditional in-clinic measures. Finally, given the idiosyncratic nature of stimulant medication effects on individual children, it contributes to the explication of a specific child's behavioral dose-response relationship.",1998.0,0,1
827,9818340,Medical control of intraocular pressure after cataract surgery.,S Byrd; K Singh,"To compare the effectiveness of 2 medications commonly used to prevent intraocular pressure (IOP) elevation in the early period after cataract surgery. Palo Alto Veterans Affairs Health Care System, Palo Alto, California, USA. This prospective study comprised 202 eyes of patients scheduled for cataract extraction who agreed to participate. Patients were randomized to receive oral acetazolamide, 500 mg 1 hour preoperatively; oral acetazolamide, 500 mg immediately postoperatively; apraclonidine hydrochloride 1%, 2 drops 1 hour preoperatively; or artificial tears (control group). Intraocular pressure was measured preoperatively and 4 to 6 and 24 hours postoperatively. Preoperative IOP was not significantly different among the 4 groups. At 4 to 6 hours postoperatively, only preoperative acetazolamide was significantly more effective than the control medication (P = .038); at 24 hours there were no significant differences among the 4 groups. Postoperative IOP elevation in excess of 35 mm Hg at 6 or 24 hours decreased significantly in the preoperative acetazolamide group (3/46 eyes) compared with the control group (14/54 eyes). There was no statistically significant difference in IOP elevation between eyes having extracapsular cataract extraction and those having phacoemulsification, independent of treatment group. The results favor preoperative acetazolamide to control postcataract IOP elevation. The method of cataract removal did not affect postoperative IOP elevation.",2000.0,0,0
828,9818633,Clinical and neurocognitive effects of clozapine and risperidone in treatment-refractory schizophrenic patients: a prospective study.,J P Lindenmayer; A Iskander; M Park; F S Apergi; P Czobor; R Smith; D Allen,"Few controlled studies have compared the efficacy of clozapine and risperidone in treatment-refractory schizophrenic patients. The present study investigates the efficacy of both clozapine and risperidone on psychopathologic and neurocognitive measures in a prospective 12-week open-label trial in treatment-refractory schizophrenic patients from state psychiatric hospitals. Thirty-five DSM-IV schizophrenic patients with a documented history of nonresponse to typical neuroleptics were treated with either clozapine or risperidone. Response was assessed every 2 weeks by independent raters with the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions (CGI) scale, neurologic rating scales, and plasma drug levels. Neurocognitive tests were administered at baseline and week 12. Both clozapine and risperidone brought about significant (p < .003) overall improvement in psychopathology. However, clozapine was numerically superior to risperidone on PANSS total scores and PANSS positive, negative, excitement, and cognitive factors. Extrapyramidal side effects were minimal for clozapine, whereas some were present for risperidone. Patients taking risperidone improved significantly in the beginning stages of the study and remained stable thereafter. Patients taking clozapine showed a gradual improvement that occurred over the entire length of the trial. Neurocognitive measures showed minimal improvement and did not differentiate between the 2 medication groups. Both clozapine and risperidone were comparably effective across a wide spectrum of psychopathologic measures. While the efficacy of clozapine was only numerically superior to that of risperidone, it was associated with fewer extrapyramidal side effects and with progressive improvement over the 12-week treatment period, suggesting that in longer trials clozapine may prove to be superior to risperidone in neuroleptic-refractory patients.",1998.0,0,0
829,9824875,Clozapine effects on force control in schizophrenic patients.,P B Vrtunski; P E Konicki; G E Jaskiw; D W Brescan; K Y Kwon; G Jurjus,"We previously reported significant differences in force control (FC) function between schizophrenics treated with typical antipsychotic drugs (APD) and those treated with clozapine. Clozapine treatment was associated with an attenuation of the capacity for fine motor control. We now report that a test-retest study with 41 treatment-refractory patients confirms our earlier finding; the FC deficit is due primarily to clozapine treatment. An additional comparison was made with 10 patients who were administered the FC test repeatedly through the initial clozapine titration interval of 6-8 weeks. The results suggest that two distinct clozapine effects can be distinguished, an initial transient stage characterized by 'drowsiness' and a subsequent stage with dose-dependent emerging myoclonic features.",1998.0,0,0
830,9825948,Post-marketing studies: the work of the Drug Safety Research Unit.,F J Mackay,"The Drug Safety Research Unit (DSRU) is the centre for prescription-event monitoring (PEM) in England. PEM studies are noninterventional observational cohort studies which monitor the safety of newly marketed drugs. The need for post-marketing surveillance is well recognised in the UK and general practice is an ideal source of data. PEM studies are general practitioner (community)-based and exposure is based on dispensed prescription data in England. To date, 65 PEM studies have been completed with a mean cohort size of 10 979 patients and the DSRU database has clinical information on over 700000 patients prescribed new drugs. Unlike spontaneous reporting schemes, PEM produces incidence rates for events reported during treatment. Comparative studies can be conducted for drugs in the same class. The DSRU aggregates outcome data for pregnancies exposed to new drugs. Data for children and the elderly can also be specifically examined. PEM data have a number of advantages over data from computerised general practice databases in the UK. PEM is the only technique within the UK capable of monitoring newly marketed drugs in such a comprehensive and systematic way.",1998.0,0,0
831,9838263,,,,,0,1
832,9842823,Oral clonidine premedication enhances the pressor response to ephedrine during spinal anesthesia.,T Goyagi; M Tanaka; T Nishikawa,"Clonidine premedication enhances the pressor effects of ephedrine in awake and anesthetized patients. To test the hypothesis that clonidine augments the pressor response to ephedrine during spinal anesthesia, 48 ASA physical status I or II patients were randomly assigned to either the clonidine group (n = 23), receiving oral clonidine approximately 5 microg/kg 90 min before spinal anesthesia, or the control group (n = 25), receiving no clonidine. Spinal anesthesia was performed at either the L2-3 or the L3-4 interspace using 0.5% hyperbaric tetracaine solution 1.4-3.0 mL. Blood pressure (BP), heart rate, and the upper dermatomal level of analgesia were determined at 1-min intervals with the patient in the supine position after tetracaine injections. When systolic BP decreased to <80% of the prespinal value or <100 mm Hg, IV ephedrine 0.2 mg/kg was administered as a bolus. There were no differences in the duration until the first dose of ephedrine after tetracaine injections, and the upper level of analgesia between groups (control group 8.5+/-3.7 min, T5; clonidine group 7.7+/-2.7 min, T6). Although prespinal and preephedrine BP values were higher in the control group, the magnitude of increases in mean BP after ephedrine was significantly greater in the clonidine group (P < 0.05). We conclude that oral clonidine premedication augments the pressor response to IV ephedrine during spinal anesthesia. The pressor effect of ephedrine is enhanced in patients given oral clonidine premedication during spinal anesthesia.",1998.0,0,0
833,9857806,[Central stimulants in adults with AD/HD. Do they help?].,N Lie,"This article is a review of five controlled studies of the efficacy of methylphenidate in adults with attention deficit/hyperactivity disorder (AD/HD). All five had a placebo cross-over design. In one of the studies, patients noted from the side-effects whether they were taking methylphenidate or placebo, and it is, in fact, unlikely that any of the studies were blind. The diagnostic criteria used in two of the studies were not appropriate according to present knowledge, leaving three samples of subjects meeting the present criteria for AD/HD. In one study, the patient material was extremely selective: 74% of subjects belonged to social class 1 and 2, and only 35% of those who came for treatment were eligible. Only one study has an acceptable (though not perfect) design. In this study of patients in a psychiatric clinic, no difference was found between methylphenidate and placebo. In two studies, subjects who improved on methylphenidate were followed up. Of the total of 24 subjects in these two samples, only four continued with methylphenidate after 3-12 months; two of them suffered from narcolepsy and one was a substance abuser. Thus, the efficacy of methylphenidate on AD/HD in adults has not been demonstrated. Present research is more against than in favour of its existence.",1998.0,0,0
834,9859115,[Significance of hepatic cytochrome P450 enzymes for psychopharmacology].,C Normann; B Hesslinger; J Bauer; M Berger; J Walden,"Nearly all psychotropic drugs are metabolized by hepatic cytochrome P450-enzymes. In humans, there are 5 isoenzymes involved in this process. The activity of these enzymes can be modulated by a number of commonly used drugs, yielding potentially hazardous interactions. Most of the recently introduced selective serotonin reuptake inhibitors are potent inhibitors of cytochrome P450 enzymes. Thus, the plasma concentrations of tricyclic antidepressants or clozapine might be elevated into toxic levels. In contrast, carbamazepine induces most of the isoenzymes. This potentiates the elimination of tricyclics and antipsychotics and might cause a serious risk for the recurrence of depressive or psychotic symptoms. Moreover, 5-10% of the population are slow metabolizers of CYP2D6. This group is prone to increased adverse effects of moderately dosed medication. This review systematically points out the reported or predicted pharmacokinetic drug interactions in psychopharmacology focussing on clinical significance.",1998.0,0,0
835,9860108,Ziprasidone 40 and 120 mg/day in the acute exacerbation of schizophrenia and schizoaffective disorder: a 4-week placebo-controlled trial.,P Keck; A Buffenstein; J Ferguson; J Feighner; W Jaffe; E P Harrigan; M R Morrissey,"A double-blind, placebo-controlled, multicenter study, was performed to evaluate the efficacy and safety of ziprasidone in 139 patients with an acute exacerbation of schizophrenia or schizoaffective disorder. Patients were randomized to receive ziprasidone 40 mg/day, 120 mg/day or placebo for 28 days. Ziprasidone 120 mg/day was significantly more effective than placebo in improving the BPRS total, CGI-S. BPRS depression cluster and BPRS anergia cluster scores (all P < 0.05). Similarly, the percentages of patients classified as responders on the BPRS (> or = 30% reduction) and the CGI improvement (score < or = 2) were significantly greater with ziprasidone 120 mg/day compared with placebo (P < 0.05). The number of patients who experienced an adverse event was similar in all three treatment groups, and discontinuation due to adverse events was rare (five of 91 ziprasidone-treated patients). The most frequently reported adverse events, that were more common in either ziprasidone group than in the placebo group, were dyspepsia, constipation, nausea and abdominal pain. There was a notably low incidence extrapyramidal side-effects (including akathisia) and postural hypotension and no pattern of laboratory abnormalities or apparent weight gain. Ziprasidone-treated patients were not clinically different from placebo-treated patients on the Simpson-Angus Rating scale, Barnes Akathisia scale and AIMS assessments. These results indicate that ziprasidone 120 mg/day is effective in the treatment of the positive, negative and affective symptoms of schizophrenia and schizoaffective disorder with a very low side-effect burden.",2001.0,0,0
836,9860152,A pharmacokinetic interaction between carbamazepine and olanzapine: observations on possible mechanism.,R A Lucas; D J Gilfillan; R F Bergstrom,"Olanzapine is a novel antipsychotic, which is effective against both the positive and negative symptoms of schizophrenia and causes fewer extrapyramidal adverse effects than conventional antipsychotics. The purpose of the present study was to assess the potential for a pharmacokinetic interaction between olanzapine and carbamazepine, since these agents are likely to be used concomitantly in the treatment of manic psychotic disorder. The pharmacokinetics of two single therapeutic doses of olanzapine were determined in 11 healthy volunteers. The first dose of olanzapine (10 mg) was taken alone and the second dose (10 mg) after 2 weeks of treatment with carbamazepine (200 mg BID). Measurement of urinary 6beta-hydroxycortisol/cortisol excretion was used as an endogenous marker to confirm that induction of CYP3A4 by carbamazepine had occurred. The dose of olanzapine given after a 2-week pretreatment with carbamazepine was cleared more rapidly than olanzapine given alone. Olanzapine pharmacokinetic values for Cmax and AUC were significantly lower after the second dose, the elimination half-life was significantly shorter, and the clearance and volume of distribution were significantly increased. Carbamazepine has been shown to induce several P450 cytochromes including CYP3A4 and CYP1A2. Since CYP1A2 plays a role in the metabolic clearance of olanzapine, the interaction may be attributed to induction of CYP1A2 by carbamazepine, leading to increased first-pass and systemic metabolism of olanzapine. The interaction is not considered to be of clinical significance because olanzapine has a wide therapeutic index, and the changes in plasma concentration of olanzapine are within the fourfold variation that occurs without concern for safety in a patient population.",1998.0,0,0
837,9865219,Multiple outcome assessment in a study of the cost-effectiveness of clozapine in the treatment of refractory schizophrenia. Department of Veterans Affairs Cooperative Study Group on Clozapine in Refractory Schizophrenia.,R Rosenheck; J Cramer; W Xu; J Grabowski; R Douyon; J Thomas; W Henderson; D Charney,"To develop new methods for combining results from multiple outcome domains and to demonstrate their application in a study of the cost-effectiveness of clozapine in treating hospitalized patients with refractory schizophrenia. Interview assessments, and administrative utilization and cost data, concerning 423 patients with refractory schizophrenia who had been hospitalized for 30-364 days during the year before study entry, at 15 VA medical centers. A 12-month double-blind trial compared clozapine (n = 205) and haloperidol (n = 218) in the treatment of refractory schizophrenia. Data from standard assessment instruments, gathered at baseline and at 6 weeks, and at 3, 6, 9, and 12 months, were used to develop a Composite Health Index for Schizophrenia, a measure that addresses outcome in six domains, weighted by patient or provider preferences. Cumulative improvement was estimated by computing the area under the improvement curve. This measure was then combined with cost data, reflecting consumption of societal resources to estimate incremental cost-effectiveness ratios. Clozapine was significantly more effective than haloperidol on measures of symptoms (p = .02) and side effects (p < .0001), with nonsignificant trends in the positive direction on community role functioning (p = .06), family relationships (p = .23), social relationships (p = .30), and daily activities (p = .20). Clozapine was also more effective than haloperidol on the one-year cumulative Composite Health Index for Schizophrenia (p < .0001 for all weighting schemes). After converting this measure to a 0-1 Worst Health-Good Health Scale analogous to Quality Adjusted Life Years, clozapine was found to yield a small improvement of .049 Worst Health-Good Health Units as compared to an improvement of only .027 Units for haloperidol (p < .0001). Average annual costs were $2,733 lower for clozapine (95% C.I. = -$9,220 to $3,754). Although clozapine was significantly more effective than haloperidol, the summary cost-effectiveness ratio had a wide 95 percent confidence interval ranging from -$431,585 to $177,352. Methods demonstrate an approach to using conventional disease-specific measures to evaluate the cumulative effectiveness of novel treatments for psychotic disorders and for expressing their economic effect as cost-effectiveness ratios. Among high hospital users with refractory schizophrenia, clozapine is more cost-effective than standard treatment, although the magnitude of its effect is small and there is considerable uncertainty about the cost estimates.",1998.0,0,0
838,9874861,Pre-anesthetic oral clonidine is effective to prevent post-spinal shivering.,C C Mao; M Y Tsou; Y Y Chia; L H Chow; K H Chan; T Y Lee,"Shivering is a common event during spinal anesthesia. Customarily we just treat it rather than prevent it. This study was designed to evaluate the efficacy of oral clonidine as a premedication to prevent post-spinal shivering. One hundred males of ASA physical status I-III, aged above 40, scheduled for elective urological surgery under spinal anesthesia, were included in this study. All participants were randomly divided into the clonidine and control groups. They received either oral clonidine 150 micrograms (n = 48) or placebo (n = 52) 90 min before spinal anesthesia in a double-blind fashion. Spinal blockade was induced with heavy bupivacaine to a dermatomal level near T10. The shivering was graded as: none, no perceptible tension of muscles observed; mild, slight muscle tonus (masseter muscle); moderate, real shivering (proximal muscles); and severe, generalized shivering (whole body). The tympanic membrane temperature was recorded 30 min after spinal anesthesia. Data were expressed as mean +/- standard deviation. Chi-square and Student's t-test were used. A p value less than 0.05 was considered statistically significant. The incidence of post-spinal shivering, which was graded as none, mild, moderate, and severe, showed statistically significant differences (p < 0.05) between clonidine 150 micrograms and placebo (83% vs. 42%, 10% vs. 6%, 10% vs. 19%, 0% vs. 33%, respectively) during the 30 min immediately after spinal anesthesia. The respective mean tympanic temperature in oral clonidine and placebo groups showed no difference (clonidine vs. control = 35.9 +/- 0.8 degrees C vs. 35.9 +/- 0.7 degrees C). Pre-anesthetic medication with oral clonidine 150 micrograms is effective to prevent post-spinal shivering in patients undergoing elective urological surgery.",1999.0,0,0
839,9875725,Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action.,F X Vollenweider; M F Vollenweider-Scherpenhuyzen; A Bäbler; H Vogel; D Hell,"Psilocybin, an indoleamine hallucinogen, produces a psychosis-like syndrome in humans that resembles first episodes of schizophrenia. In healthy human volunteers, the psychotomimetic effects of psilocybin were blocked dose-dependently by the serotonin-2A antagonist ketanserin or the atypical antipsychotic risperidone, but were increased by the dopamine antagonist and typical antipsychotic haloperidol. These data are consistent with animal studies and provide the first evidence in humans that psilocybin-induced psychosis is due to serotonin-2A receptor activation, independently of dopamine stimulation. Thus, serotonin-2A overactivity may be involved in the pathophysiology of schizophrenia and serotonin-2A antagonism may contribute to therapeutic effects of antipsychotics.",1999.0,0,0
840,9884676,The use of psychostimulants in the pediatric patient.,S R Pliszka,"The psychostimulant drugs have a long history of safe and effective usage in the treatment of ADHD. They remain the drugs of first choice in this condition. Children with ADHD should be aggressively treated with at least two different classes of psychostimulants before moving to nonpsychostimulant agents. As long as side effects are not troublesome, higher dosages may be used to adequately control the ADHD symptoms, and such high dosages do not impair learning. No evidence shows long-term effects of psychostimulants on growth. Effective use of the psychostimulants is essential for any clinician involved in the treatment of children with ADHD.",1999.0,0,0
841,9884677,"Alpha 2 adrenergic agonists. Neurochemistry, efficacy, and clinical guidelines for use in children.",J H Newcorn; K Schulz; M Harrison; M D DeBellis; J K Udarbe; J M Halperin,"The alpha 2 adrenergic agonists are used to treat a variety of psychiatric disorders and their usage has been increasing. This article presents the rationale and neurochemical basis for treatment of psychiatric disorders with alpha 2 agents, reviews studies examining clinical efficacy, and develops guidelines for usage. Case vignettes are presented to illustrate how the alpha 2 agents can successfully be used in practice.",1999.0,0,0
842,9884683,The antipsychotics. A pediatric perspective.,R L Findling; S C Schulz; M D Reed; J L Blumer,"As can be discerned from this article, antipsychotics are commonly prescribed, and they are not used to treat only psychosis. Although some data support the use of typical antipsychotics in pediatric patients with a variety of psychiatric syndromes, concerns about the safety and tolerability of these agents often complicated their use and probably even interfered with case identification. A fundamentally new group of medications, the atypicals, have now become available and may not only have improved tolerability but also may have greater ability to reduce some target symptoms. Because of their superior side-effect profile in adults, some of these atypical treatments probably will be commonly prescribed despite a relative paucity of data about their use in the young. Moreover, although frequently prescribed in this age group, the overall prescription rate for antipsychotics will probably increase because of the putative improved safety profile of the newer agents. However, it is possible that serious side effects, such as tardive dyskinesia or neuroleptic malignant syndrome, may occur with these atypical agents. For this reason, the enthusiasm for prescribing these newer treatments should be tempered with the understanding that these agents, although they may in some ways be superior to their predecessors, still possess the potential for significant adverse events. Four atypical antipsychotics are currently marketed in the United States (see Table 2). One additional agent, ziprasodone, is undergoing clinical investigation. Ziprasodone has been shown to be superior to placebo in adults suffering from schizophrenia. Ziprasodone will probably be marketed in the United States in the near future. Whether all of these atypical drugs will have a place in the clinical armamentarium of the pediatric psychopharmacologist remains to be determined. Because the receptor binding profile of the atypical agents differ, it is not possible to assume that what is true for one of these agents is true for the others. Although results from most preliminary studies with atypical antipsychotics indicate that these are promising agents for pediatric patients, further research is needed to define just how these medications may be most judiciously used.",1999.0,0,0
843,9892301,Olanzapine versus haloperidol treatment in first-episode psychosis.,T M Sanger; J A Lieberman; M Tohen; S Grundy; C Beasley; G D Tollefson,"It has been hypothesized that the morbidity and mortality associated with schizophrenia can be prevented by providing effective treatment during the first episode of psychosis. Hence, the authors examined patients with first-episode psychosis to determine the efficacy and safety of olanzapine and haloperidol treatment. A subpopulation of first-episode patients (N=83) from a large prospective, multicenter, international, double-blind, 6-week acute treatment study was evaluated. These patients were selected from a pool of 1,996 patients who had a DSM-III-R diagnosis of schizophrenia, schizoaffective disorder, or schizophreniform disorder and who also met the following criteria: 1) the length of their current psychotic episode had to be 5 or fewer years, and 2) patients had to be 45 years of age or younger at onset of first psychotic symptoms. Compared to haloperidol, olanzapine showed a statistically significantly greater reduction in the Brief Psychiatric Rating Scale (BPRS) total and negative scores and in the Positive and Negative Syndrome Scale total and positive scores. Clinical response (defined as 40% or greater improvement in BPRS total score from baseline) was also statistically significantly higher in olanzapine-treated patients (67.2%) than in haloperidol-treated patients (29.2%). Olanzapine-treated patients further showed statistically significant improvements in the Simpson-Angus scale and Barnes Akathisia Scale scores, while haloperidol-treated patients showed a worsening on both measures. Compared to olanzapine-treated multiple-episode patients in the parent study, olanzapine-treated first-episode patients achieved an even statistically significantly higher response. Haloperidol-treated first-episode patients experienced statistically significantly more extrapyramidal symptoms than haloperidol-treated multiple-episode patients. In patients experiencing first-episode psychosis, olanzapine had a risk-benefit profile significantly superior to that of haloperidol. The study results suggest that novel antipsychotic agents such as olanzapine should be considered as a preferred option in first-episode psychosis, on the basis of both safety and efficacy advantages.",2001.0,0,0
844,9892314,Effect of clozapine and adjunctive high-dose glycine in treatment-resistant schizophrenia.,S G Potkin; Y Jin; B G Bunney; J Costa; B Gulasekaram,"The focus of this study was the systematic evaluation of the clinical effects of glycine as an adjunct to the atypical antipsychotic clozapine in the treatment of schizophrenia. In a double-blind, placebo-controlled study, 19 patients with chronic, treatment-resistant schizophrenia who were maintained on optimal doses of clozapine (400-1200 mg/day) were administered either 30 g/day of glycine (N=9) or placebo (N=10) for 12 weeks. Clinical evaluations with the Brief Psychiatric Rating Scale, the Scale for the Assessment of Negative Symptoms, and the Simpson-Angus movement scale were completed biweekly. The use of glycine as an adjunct to clozapine was not effective in decreasing positive or negative symptoms. In contrast, the patients treated with clozapine without glycine had a 35% reduction in positive symptoms. These preliminary data suggest that glycine may interfere with the antipsychotic efficacy of atypical neuroleptics such as clozapine.",1999.0,0,0
845,9924877,Order of onset of substance abuse and depression in a sample of depressed outpatients.,H D Abraham; M Fava,"Drug abuse has been thought to cause depression, or to serve as a form of self-medication for depression. Our objective was to examine whether specific types of drug abuse preceded or followed the onset of depression. A retrospective, blinded case-controlled assessment of the drug and depressive history of depressed outpatients was conducted. Three hundred seventy-five patients with major depressive disorder were evaluated for comorbid drug dependence using the Structured Clinical Interview for DSM-III-R (SCID). They were selected from the psychiatric outpatient department of a metropolitan teaching hospital and grouped into homogeneous classes of drug dependence including alcohol, cannabis, cocaine, amphetamine, LSD, hypnosedative, opiate, and polysubstance use. We determined the percent of depressed patients with each specific type of drug abuse, their age of onset of depression and onset of specific drug abuse, and the mean number of lifetime depressive episodes for each patient. We found that alcohol dependence followed the onset of first life depression by 4.7 years (P = .02, two-tailed). Among polydrug-dependent patients, each drug abused followed the onset of depression, except for LSD, which coincided with the onset of depression. Among polydrug users, cocaine dependence occurred 6.8 years after the first major depressive episode (P = .007) and alcohol dependence 4.5 years after the onset of depression (P = .007). Opiate and sedative users had the least number of lifetime depressive episodes (3.7), and LSD and cocaine users had the greatest number (12.2). We conclude that alcohol and cocaine use in this sample of depressed outpatients conformed to a pattern of self-medication.",1999.0,0,0
846,9928923,Combination treatment with clozapine and paroxetine in schizophrenia: safety and tolerability data from a prospective open clinical trial.,I Anghelescu; A Szegedi; S Schlegel; H Weigmann; C Hiemke; H Wetzel,"Clozapine is a drug with many side effects, some of them with potentially hazardous outcome (e.g. seizures, agranulocytosis), if not carefully monitored. It has been shown that the metabolism of clozapine may be affected by concomitant treatment with selective serotonin reuptake inhibitors (SSRIs), while there have been reports of improved efficacy on negative symptomatology of clozapine in combination with SSRIs. Therefore, this prospective open clinical trial was performed to investigate the safety and tolerability of the coadministration of clozapine and paroxetine under control of serum concentrations of clozapine and its metabolites and the effect of this combination treatment on psychopathological outcome was evaluated. A total of 14 patients suffering from schizophrenia or schizodepressive disorder with predominant negative symptomatology were included. The duration of the study was at least 6 weeks for each patient. Initial treatment was a monotherapy with clozapine at a daily dose of 2.5 mg/kg weight. After two measurements of serum concentrations of clozapine and metabolites during steady state conditions, an add-on therapy with 20 mg paroxetine was initiated. No concomitant medication was allowed. The main finding of our prospective study was that addition of paroxetine to a monotherapy with clozapine was a well tolerated medication that did not give rise to new clinically relevant side effects. After addition of paroxetine the serum concentrations of clozapine and its major metabolites remained virtually constant. The results of the psychopathological measurements indicated a further clinical improvement, although the small open study could not test for efficacy.",1999.0,0,0
847,9934944,Prolactin levels and adverse events in patients treated with risperidone.,D L Kleinberg; J M Davis; R de Coster; B Van Baelen; M Brecher,"Hyperprolactinemia is a common clinical disorder that may lead to sexual dysfunction or galactorrhea. It may arise from a variety of etiologies, including the use of antipsychotic agents, presumably because of a dopamine receptor blockade. This analysis was designed to characterize the relationship between risperidone, serum prolactin levels, and possible clinical sequelae. All data from randomized, double-blind studies of risperidone in patients with chronic schizophrenia were analyzed. The two largest studies (the North American and multinational trials) included 841 patients (259 women, 582 men) with paired prolactin level data and 1,884 patients (554 women, 1,330 men) with data on six adverse events possibly associated with increased prolactin levels (amenorrhea, galactorrhea, and decreased libido in women; erectile dysfunction, ejaculatory dysfunction, gynecomastia, and decreased libido in men). Both risperidone and haloperidol produced dose-related increases in plasma prolactin levels in men and women. Among women, the risperidone dose was not correlated with adverse events, nor were the adverse events correlated with endpoint prolactin levels. Among men, the incidence of adverse events was positively correlated with risperidone dose; however, at risperidone doses of 4 to 10 mg/day the incidence of adverse events was not significantly higher than that observed in patients receiving placebo. Furthermore, adverse events in men were unrelated to plasma prolactin levels. Risperidone-associated increase in serum prolactin levels was not significantly correlated to the emergence of possible prolactin-related side effects.",1999.0,0,0
848,9952147,Dexmedetomidine failed to block the acute hyperdynamic response to electroconvulsive therapy.,W Fu; P F White,"Orally administered clonidine (0.2-0.3 mg) has been reported to decrease the acute hypertensive response to electroconvulsive therapy (ECT) without prolonging early recovery. This preliminary study was designed to evaluate the acute hemodynamic effects of the investigational alpha2-adrenergic agonist, dexmedetomidine, in patients undergoing a series of ECT treatments. Six patients undergoing a series of three to six consecutive ECT treatments were studied according to a randomized, double-blind, placebo-controlled protocol All patients received either saline or dexmedetomidine, 0.5 or 1.0 microg/kg intravenously, 10-30 min before induction of anesthesia for ECT using a standardized anesthesia protocol. In addition to assessing the cardiovascular variables, the duration of seizure activity, degree of sedation, and time to discharge from the Phase I recovery unit were assessed. Although dexmedetomidine produced dose-related increases in the level of sedation before the ECT procedure, it failed to decrease the peak blood pressure and heart rate responses after the ECT treatment. The 0.5 and 1.0 microg/kg doses of dexmedetomidine prolonged the times to orientation and to discharge from the Phase I unit. The results of this pilot study suggest that dexmedetomidine (0.5-1.0 microg/kg given intravenously) is not beneficial in controlling the acute hyperdynamic response after ECT.",1999.0,0,0
849,9987698,"A double-blind, placebo-controlled, ascending-dose evaluation of the pharmacokinetics and tolerability of modafinil tablets in healthy male volunteers.",Y N Wong; D Simcoe; L N Hartman; W B Laughton; S P King; G C McCormick; P E Grebow,"A randomized, double-blind, placebo-controlled, ascending-dose study was conducted to evaluate the pharmacokinetic and safety profiles of increasing modafinil doses (200 mg, 400 mg, 600 mg, 800 mg) administered orally over a 7-day period in normal healthy male volunteers. Eight subjects (six modafinil; two placebo) were randomized to each of the four dose groups. Modafinil or a placebo was administered once daily for 7 days. Serial blood samples were obtained following administration of the day 1 and day 7 doses for characterization of pharmacokinetics, and trough samples were obtained prior to dosing on days 2 through 6 to assess the time to reach the steady state. Pharmacokinetic parameters were calculated using noncompartmental methods. Modafinil steady state was reached after three daily doses. Modafinil pharmacokinetics were dose and time independent over the range of 200 mg to 800 mg. Steady-state pharmacokinetics of modafinil were characterized by a rapid oral absorption rate, a low plasma clearance of approximately 50 mL/min, a volume of distribution of approximately 0.8 L/kg, and a long half-life of approximately 15 hr. Modafinil was primarily eliminated by metabolism. Modafinil acid was the major urinary metabolite. Stereospecific pharmacokinetics of modafinil were demonstrated. The d-modafinil enantiomer was eliminated at a threefold faster rate than 1-modafinil. Modafinil 200 mg, 400 mg, and 600 mg doses were generally well tolerated. The modafinil 800 mg dose panel was discontinued after 3 days of treatment due to the observation of increased blood pressure and pulse rate. The safety data from this study suggest that the maximum tolerable single daily oral modafinil dose, without titration, may be 600 mg.",1999.0,0,0
850,9988841,"Efficacy and extrapyramidal side-effects of the new antipsychotics olanzapine, quetiapine, risperidone, and sertindole compared to conventional antipsychotics and placebo. A meta-analysis of randomized controlled trials.",S Leucht; G Pitschel-Walz; D Abraham; W Kissling,"The objective of this meta-analysis is to summarize the efficacy and tolerability of the new antipsychotics risperidone, olanzapine, sertindole and quetiapine in schizophrenia compared to placebo and conventional antipsychotics. The main results are: (1) All of the 4 new drugs are more effective than placebo, but the magnitude of the effect is only moderate [mean effect size, r, of all antipsychotics vs. placebo = 0.25, with a 95% confidence interval (CI) = 0.22-0.28, n = 2477]. (2) According to the studies published to date, sertindole and quetiapine are as effective as haloperidol, and risperidone and olanzapine are slightly more effective than haloperidol in the treatment of global schizophrenic symptomatology. (3) With respect to negative symptoms, all new antipsychotics are more effective than placebo. However, contrary to widespread opinion, so is the 'conventional' antipsychotic haloperidol. Risperidone and olanzapine are slightly superior, sertindole is as effective and--according to the only study fully published to date--quetiapine is even slightly less effective than haloperidol in this regard. (4) All new antipsychotics are associated with less frequent use of antiparkinson medication than haloperidol, with risperidone appearing to have a slightly less favourable EPS-profile than the other new antipsychotics. The methodological limitations of this review, the generalizability of the results and expectations from future research are discussed.",1999.0,0,0
851,9989566,"Clozapine and risperidone in chronic schizophrenia: effects on symptoms, parkinsonian side effects, and neuroendocrine response.",A F Breier; A K Malhotra; T P Su; D A Pinals; I Elman; C M Adler; R T Lafargue; A Clifton; D Pickar,"Clozapine and risperidone were the first two ""second-generation"" antipsychotic drugs approved for schizophrenia. There is currently little information about their comparative efficacy from head-to-head clinical trials. The purpose of this study was to examine the comparative efficacy of clozapine and risperidone for positive and negative symptoms, depression, parkinsonian side effects, and indexes of neuroendocrine function in schizophrenic patients who met a priori criteria for partial response to traditional neuroleptic agents. After a baseline fluphenazine treatment period, 29 patients participated in a 6-week, double-blind, parallel-group comparison of the effects of these agents. Clozapine was superior to risperidone for positive symptoms and parkinsonian side effects, but there were no significant differences between the drugs on two measures of negative symptoms, Brief Psychiatric Rating Scale total scores, and depression scores. The clozapine patients, but not the risperidone patients, demonstrated significant reductions from the fluphenazine baseline in positive symptoms, total symptoms, and depression. In addition, clozapine produced fewer effects on plasma prolactin than risperidone or fluphenazine. The mean daily doses during week 6 of the trial were 403.6 mg of clozapine and 5.9 mg of risperidone. The findings from this study indicate that these drugs have both important differences and similarities in their comparative efficacy in chronically ill, partially responsive patients with schizophrenia. Further research on second-generation antipsychotic drugs in this patient population that addresses key methodological issues, such as optimal dose and treatment duration, are needed.",2000.0,0,0