record_id,pubmedID,title,authors,abstract,year,label_included,label_abstract_screening
1,10067807,"Migraine: a ""woman's disease?"".",L J Warshaw; R B Lipton; S D Silberstein,"Migraine, a chronic disorder characterized by episodes of headache, has a profound effect on the well-being and general functioning of its victims, not only during the acute attacks, but also in terms of impairment of school achievement, work performance, and family/social relationships. Despite staggering social and economic costs, it remains under-diagnosed and under-treated worldwide. Migraine has been labeled a ""woman's disease"" because it is three times more common in women than men, the attacks tend to be more severe and disabling among women and, in some women, they seem to be modulated by such hormonal ""milestones"" as menarche, menstruation, pregnancy and menopause. After a brief review of the diagnosis of migraine, this article will examine the nuances responsible for that label and their implications for treatment.",1999.0,0,0
2,10099854,Sumatriptan is effective in the treatment of menstrual migraine: a review of prospective studies and retrospective analyses.,R Salonen; J Saiers,"Menstrual migraine may be debilitating, long-lasting, and refractory to treatment. Because the efficacy and tolerability of abortive and prophylactic treatment options for menstrual migraine have generally not been evaluated in controlled clinical trials, treatment choices are often made on the basis of personal experience and anecdotal reports. This article reviews evidence from retrospective analyses and prospective studies showing that sumatriptan injection and tablets are effective and well tolerated in menstrual migraine. (1) Sumatriptan injection 6 mg was as effective in the treatment of menstrual migraine attacks as it was for nonmenstrual attacks in a retrospective analysis of data from two randomized, double-blind, placebo-controlled, parallel-group trials (n = 1104). In the menstrual migraine group, 80% of women treated with sumatriptan injection 6 mg compared with 19% of placebo-treated patients reported headache relief 1 h postdose (p < 0.001). (2) Sumatriptan injection 6 mg was effective in the acute treatment of menstrual migraine attacks in a prospective, double-blind, placebo-controlled, parallel-group, two-attack study (n = 226). Across the two attacks, 70-71% of patients treating menstrual migraine attacks with sumatriptan injection 6 mg compared with 22-24% of placebo-treated patients reported headache relief 1 h postdose (p < 0.001). (3) Sumatriptan tablets 100 mg were effective in the acute treatment of menstrual migraine attacks in a prospective, double-blind, placebo-controlled, crossover study in women diagnosed with menstrual migraine (n = 115). For menstrual migraine attacks, headache relief 4 h postdose was reported by 67% of sumatriptan-treated patients compared with 33% of placebo-treated patients. Sumatriptan injection and tablets were generally well tolerated in these studies, in which adverse events were characteristic of those typically observed in sumatriptan acute migraine clinical trials. These data demonstrate that sumatriptan injection and tablets are effective and well tolerated in the treatment of menstrual migraine.",1999.0,0,0
3,10160470,Comparing dihydroergotamine mesylate and sumatriptan in the management of acute migraine. A retrospective cost-efficacy analysis.,K Payne; C M Kozma; B J Lawrence,"The annual cost of managing migraine totals billions of US dollars. This retrospective economic analysis of a clinical trial comparing subcutaneous dihydroergotamine mesylate (DHE) with subcutaneous sumatriptan in the treatment of acute migraine is appropriate because, although each product has been shown to be efficacious, the acquisition cost of sumatriptan is over 3 times that of DHE. Total costs in each treatment group were calculated and applied independently to 11 clinical trial efficacy measures. Three of the efficacy measures showed no statistically significant difference between treatment arms, leading to a decision to use the less expensive DHE. In 4 of the efficacy measures. DHE was the obvious choice because it is more efficacious and less expensive. For the final 4 efficacy measures, where sumatriptan is more efficacious and more expensive, incremental cost-efficacy ratios were calculated to determine the additional expenditure required to achieve outcomes associated with quick relief. Depending on the efficacy variable chosen and the assumptions used in the model, the incremental cost-efficacy ratios ranged from $US4000 to $US6700 per year (1993 dollars) for each additional patient who is successfully treated with sumatriptan compared with DHE. Therefore, in a population of 100 migraineurs, an additional 13 to 22 patients would achieve these short term benefits of sumatriptan, although it would cost an additional $US88 395 annually, given the assumptions made. Because each product has unique advantages, we conclude that the more cost-efficacious product is dependent on the outcome of interest and the amount that the patient or provider is willing to pay to achieve that outcome.",1996.0,0,0
4,10166407,The impact of drug therapy on quality of life in headache and migraine.,G D Solomon; D G Litaker,"Although headache is among the most common and costly disorders in primary care, our understanding of its direct impact on the quality of life of affected individuals is incomplete. While studies evaluating the role of headache on health-related quality of life and healthcare economics are starting to appear in the medical literature, the effect of pharmacotherapy in improving quality of life is only beginning to be studied. At present, studies evaluating health-related quality of life in patients with migraine who are undergoing treatment are limited to 3 agents: sumatriptan, flurbiprofen and diclofenac. Several studies have consistently indicated that these drugs benefit patients by improving key dimensions of health-related quality of life or patients' sense of well-being to a significant extent. Given the magnitude of functional and emotional impairment associated with chronic headache disorders, assessing patients' perceptions of their quality of life makes a useful contribution to the evaluation of therapeutic interventions and should supplement traditional clinical endpoints in determining the effectiveness of new drugs.",1997.0,0,1
5,10168035,Sumatriptan. A pharmacoeconomic review of its use in migraine.,A J Coukell; H M Lamb,"Migraine is a common illness characterised by severe, often throbbing and/or unilateral headache, which may be accompanied by sensitivity to light or noise. A minority of migraine attacks are preceded by transient visual or sensory disturbances. Migraine is associated with reductions in health-related quality of life both during and between attacks. Despite methodological limitations in cost-of-illness studies, it is clear that the cost of migraine to society is substantial. Indirect costs (primarily workplace productivity losses) make up 75 to 90% of total costs. Direct costs, such as the cost of drug treatment, physician consultation, hospitalisation and emergency room treatment, make up most of the remainder. Sumatriptan is an effective and well tolerated agent in the treatment of migraine. Its main advantage over other agents used in the acute management of migraine appears to be its rapid onset of action. Sumatriptan reduces headache severity within 2 hours of oral administration in 50 to 67% of patients and within 1 hour of subcutaneous administration in 70 to 80% of patients. Headache recurs in approximately 40% of patients who initially respond to oral or subcutaneous sumatriptan; however, a second dose of the drug is effective against the symptoms of recurrence in a majority of patients. Some patients experience relief of non-headache migraine symptoms, including nausea, vomiting, photophobia and phonophobia. Adverse events reported after sumatriptan are generally mild and transient. Data from studies of patients who used their usual therapies and sumatriptan in nonblinded, sequential phases indicate that both workplace and nonworkplace productivity losses were reduced during sumatriptan therapy. A cost-benefit analysis applied to some of these workplace productivity data indicated that, including direct costs and productivity savings, sumatriptan was associated with a net reduction in total cost of migraine. In retrospective cost analyses, sumatriptan was associated with increased prescription costs: the effect of the drug on other direct treatment costs was less clear. A retrospective pharmacoeconomic model suggested that the cost-effectiveness of subcutaneous sumatriptan versus subcutaneous dihydroergotamine depended on which outcome measure was of greatest interest. For measures of rapid relief of migraine, sumatriptan was superior, but the cost of achieving rapid relief was substantial. Sumatriptan improved global quality-of-life scores compared with patients' usual therapy in a randomised crossover trial and appeared to do the same when the drugs were administered in nonblinded, sequential phases in trials which used general and migraine-specific quality-of-life instruments. Thus, sumatriptan is associated with a fast onset of action and improvements in health-related quality of life in patients with migraine. However, the cost of achieving rapid relief of migraine symptoms may be substantial. Compared with patients' usual treatments, sumatriptan appeared to reduce workplace and non-workplace productivity losses. However, few economic data from well controlled prospective comparisons of sumatriptan with other available agents are available to quantify the effect of sumatriptan on the overall cost of migraine.",1997.0,0,0
6,10168039,"A multinational investigation of the impact of subcutaneous sumatriptan. I: Design, methods and clinical findings.",J Heywood; J Bouchard; P Cortelli; C Dahlöf; J P Jansen; S Pham; J Hirsch; C E Edwards; J Adams; P Berto; B Brueggenjuergen; A L Nyth; P Lindsay; K L Price,"This report describes the design, methods and clinical results of a prospective sequential multinational (5 countries) study conducted to evaluate the effects of subcutaneous sumatriptan on health-related quality of life, workplace productivity, clinical parameters and patient satisfaction. Adult patients with moderate to severe migraine initially received customary therapy for migraine episodes for 12 weeks, followed by 24 weeks' treatment with self-administered subcutaneous sumatriptan 6 mg. Demographic, baseline, health-related quality of life and patient satisfaction rating data were collected during visits to the clinic. Data relating to migraine symptoms, migraine therapy, work productivity and non-work activity time were collected on diary cards filled out by the patients. 749 patients were recruited to the study and 637 received at least 1 dose of sumatriptan. Overall, 75.5% of migraines were successfully treated within 2 hours with sumatriptan compared with 31.9% with customary therapy; 36% of patients reported complete relief at 2 hours with sumatriptan treatment compared with 1% of patients receiving customary therapy. 69% of patients successfully treated 70% of their migraines with sumatriptan within 2 hours, compared with 12% of patients with customary therapy. No serious adverse events were reported; 50% of patients reported an adverse event during the 12-week customary therapy phase and 89% of patients during the 24-week sumatriptan phase. These clinical results, which are consistent with those reported in randomised blinded studies of subcutaneous sumatriptan, suggest that relief of migraine symptoms occurs more often, and in less time, in patients receiving subcutaneous sumatriptan rather than customary therapy as their primary medication.",1996.0,0,1
7,10168040,A multinational investigation of the impact of subcutaneous sumatriptan. II: Health-related quality of life.,C Dahlöf; J Bouchard; P Cortelli; J Heywood; J P Jansen; S Pham; J Hirsch; J Adams; D W Miller,"The aim of this prospective sequential multinational (5 countries) study was to concurrently evaluate the effects of subcutaneous sumatriptan on clinical parameters, health-related quality-of-life (HRQOL) measures, workplace productivity and patient satisfaction. This report presents the HRQOL results. 582 patients (aged 18 to 65 years) with moderate to severe migraine received their customary antimigraine therapy for 12 weeks and then subcutaneous sumatriptan for 24 weeks. The Short Form-36 Health Survey and the Migraine-Specific Quality of Life Questionnaire were completed at a screening visit (base-line), at the end of the 12-week customary therapy phase, and at 12 and 24 weeks of the sumatriptan phase. Scores for most of the Short Form-36 dimensions improved significantly (p < 0.05) after 12 and 24 weeks of sumatriptan therapy compared with 12 weeks of customary therapy, in each country. Similarly, scores on all Migraine-Specific Quality of Life Questionnaire dimensions were significantly (p < 0.05; paired t-test) improved after 12 weeks (in all countries) and 24 weeks (in 4 of 5 countries) of sumatriptan therapy compared with 12 weeks of customary therapy. This study demonstrates that, in 5 countries, treatment of migraine attacks with subcutaneous sumatriptan compared with customary therapy was associated with improvements in HRQOL, as measured by both general health status and disease-specific instruments.",1996.0,0,1
8,10168041,A multinational investigation of the impact of subcutaneous sumatriptan. III: Workplace productivity and non-workplace activity.,P Cortelli; C Dahlöf; J Bouchard; J Heywood; J P Jansen; S Pham; J Hirsch; J Adams; D W Miller,"This report presents the workplace productivity and non-workplace activity results of a multinational study of the effects of subcutaneous sumatriptan 6 mg in the acute treatment of migraine compared with patient's customary therapy. Patients diagnosed with migraine treated their symptoms for 24 weeks with subcutaneous sumatriptan after a 12-week period of treating symptoms with their customary (non-sumatriptan) therapy. Patients used diary cards to record information concerning the effects of migraine on workplace productivity and non-workplace activity time. The average workplace productivity time lost was 23.4 hours per patient during 12 weeks of customary therapy, compared with 7.2 and 5.8 hours per patient during the first and second 12-week periods of sumatriptan therapy, respectively. An average of 9.3 hours of non-workplace activity time was lost per patient during the customary therapy phase, compared with 3.2 and 2.8 hours during the first and second 12-week periods of sumatriptan therapy, respectively. Treatment of migraine with subcutaneous sumatriptan compared with customary therapy was associated with an average gain per patient of approximately 16 hours of workplace productivity time and 6 hours of non-workplace activity time, over a 3-month period.",1996.0,0,1
9,10168042,A multinational investigation of the impact of subcutaneous sumatriptan. IV: Patient satisfaction.,J Bouchard; P Cortelli; C Dahlöf; J Heywood; J P Jansen; K L Price; S Pham; A Joseph; L Babiak,"This report describes the patient satisfaction results from a prospective, sequential, multinational study. The study was conducted to concurrently evaluate the effects of sumatriptan, compared with customary therapy, on clinical parameters, health-related quality of life, productivity and patient satisfaction in adult patients with moderate to severe migraine. Patients treated migraine attacks for 12 weeks with their customary therapy, followed by 24 weeks' treatment with subcutaneous sumatriptan 6 mg. A questionnaire was conducted at the end of each study phase, or retrospectively at the end of the study, to assess patient satisfaction with customary therapy and sumatriptan. Sumatriptan was considered by most patients (67 to 85%) to be dependable and fast-acting, and to have a long duration of effect, allowing a quick return to normal activities. By comparison, 15 to 32% of patients considered that their customary therapy possessed the same attributes. However, customary therapy was considered to be easy/very easy to use by 82% of patients compared with 62% for subcutaneous sumatriptan. 89% of patients indicated that they would use sumatriptan again in the future. This study demonstrates that treatment of migraine attacks with subcutaneous sumatriptan for 24 weeks is associated with greater patient satisfaction as regards specific drug attributes than customary therapy.",1996.0,0,1
10,10169243,Cost-effectiveness of sumatriptan in a managed care population.,R F Legg; D A Sclar; N L Nemec; J Tarnai; J I Mackowiak,"We conducted an open-labeled study to determine whether sumatriptan is more cost-effective than other therapies used to treat migraine headache. We contacted by phone 220 sumatriptan users enrolled in QualMed, a health maintenance organization (HMO) in Spokane, Washington. Of these, 203 met the inclusion criteria and 164 (81%) completed our telephone survey. The main outcome measures were healthcare costs to the HMO and number of days free of migraine-related disability before and after sumatriptan treatment. Before sumatriptan treatment, 89% of patients reported severe migraine, compared with 63% after sumatriptan treatment. The number of monthly migraine disability days decreased from 6.5 days per month before sumatriptan to 3.9 days per month after sumatriptan. Healthcare utilization rates (ie, number of hospitalizations, emergency department visits) and costs were lower after the patients began taking sumatriptan. The number of different over-the-counter medicines and prescription medications (other than sumatriptan) taken for migraine disabilities decreased. Although total drug expenditures per month increased, the total migraine healthcare expenditure was 41% lower after sumatriptan was initiated. The cost-effectiveness ratio was 47% more favorable after patients started taking sumatriptan. Overall, patients reported fewer migraine-related disabilities, had lower migraine severity scores, and used fewer healthcare resources when taking sumatriptan. These changes resulted in a better cost-effectiveness ratio for migraine treatment.",1996.0,0,1
11,10179706,MSQ: Migraine-Specific Quality-of-Life Questionnaire. Further investigation of the factor structure.,P Jhingran; S M Davis; L M LaVange; D W Miller; R W Helms,"MSQ, the 16-item Migraine-Specific Quality-of-Life Questionnaire (Version 1.0), was developed by Glaxo Wellcome Inc. to assess the effect of migraine and its treatment on patients' health-related quality of life (HR-QOL). The MSQ was hypothesised to measure 3 meaningful dimensions: (i) Role Function-Restrictive; (ii) Role Function-Preventive; and (iii) Emotional Function. The objective of this research was to further investigate the number of dimensions as well as the items contained in each dimension through principal components factor analysis of clinical trial data. Secondary objectives were to determine whether the factor structure changed in post-treatment visits compared with screening visits, to make recommendations for coding the MSQ when the patient did not have a migraine in the previous 4 weeks, and to modify the MSQ if so indicated by this research. Results supported the existence of 3 distinct factors which agreed strongly with the hypothesised dimensions. The analysis of post-treatment data suggested that the underlying factor structure of the MSQ varies as a result of treatment. Based on evaluations of the 'did not have a migraine' response, it was concluded that it be dropped from the MSQ. All these changes have been incorporated into MSQ (Version 2.0) which is being evaluated in studies to determine if its psychometric properties are different than the properties of the previous version.",1998.0,0,0
12,10190654,The haemodynamic effect of the 5HT1 agonist BMS-180048: a class effect of triptans?,L Swan; S Hood; D H Birnie; D F Muir; G P McCann; W S Hillis,"To investigate the effects of an intravenous infusion of BMS-180048, a novel 5HT1-like agonist, on the systemic, pulmonary and coronary circulations in patients undergoing diagnostic cardiac catheterisation. Ten patients (mean age 55 years (range 41-65)) were studied during diagnostic cardiac catheterisation. The haemodynamic response to an intravenous (i.v.) infusion for 30 min of BMS-180048 (0.56 mg kg(-1) h(-1) for 10 min and 0.39 mg kg(-1) h(-1) for 20 min) was assessed via a 7F Swan Ganz catheter and thermodilution cardiac output system. Quantitative coronary angiography was performed at 10 min intervals. BMS-180048 caused a significant increase in systemic arterial systolic blood pressure (rise of 32.5 mmHg, 95% CI 24,44.5) P=0.009), pulmonary artery systolic (12.2 mmHg, 95% CI 6.8,18.5; P=0.009) and diastolic pressures (8.5 mmHg, 95% CI 5.0,13.8; P=0.009), right atrial pressure (4 mmHg, 95% CI 1.5,5.2; P=0.013) and pulmonary capillary wedge pressure (9.5 mmHg 95% CI 5.2,14.0; P=0.09). There was no significant change in cardiac output (0.1 l min(-1), 95% CI -0.17,0.57, P>0.05). Mean coronary artery diameter in the proximal coronary segments decreased by 0.73 mm (95% CI -1.22,-0.15; P=0.03) at 35 min. The corresponding reduction in middle segments was 0.26 mm (95% CI -0.395,-0.08; P=0.02). There was a non-significant trend to constriction in the most distal segments of 0.28 mm (95% CI -0.68,0.015); P=0.06). One patient experienced chest pain with ECG changes suggestive of ischaemia. BMS-180048 displayed a cardiovascular profile similar to that previously reported for sumatriptan. These changes appear to reflect a class effect of these agents.",1999.0,0,0
13,10209349,Sumatriptan nasal spray: a dose-ranging study in the acute treatment of migraine.,A Peikert; W J Becker; E A Ashford; C Dahlof; H Hassani; R J Salonen,"This multicentre, randomized, double-blind, placebo-controlled, parallel group dose-ranging study compared the efficacy and tolerability of four doses of sumatriptan nasal spray (2.5, 5, 10 and 20 mg) with a placebo, in the acute treatment of a single migraine attack. In total, 544 patients received the study medication as a single spray in one nostril, to treat a single migraine attack in the clinic. Efficacy assessments included the measurement of headache severity, clinical disability, and the presence/absence of associated symptoms. The incidence of headache recurrence was also assessed. The three highest doses of sumatriptan (5 mg 49%, 10 mg 46%, 20 mg 64%) were significantly better than the placebo (25%) at providing headache relief (moderate or severe headache improving to mild or none) 120 min after treatment (P </= 0. 01). Also, the 20 mg dose was significantly superior to both the 10 and 5 mg doses at this time point (P < 0.05). The proportion of patients who were headache-free 120 min after treatment, was also higher following 20 mg (42%) rather than following any other sumatriptan dose (14-24%, P < 0.005 20 vs 10 mg) or placebo (11%). Headache recurrence in patients who had responded to initial treatment was reported by 30-41% of patients who received sumatriptan, compared with 33% of patients in the placebo group. Sumatriptan nasal spray was well tolerated, the incidence of adverse events with each dose of sumatriptan being similar to the placebo (20-27 and 23%, respectively). Apart from bad/bitter taste, the events were comparable with those reported following sumatriptan treatment by other routes of administration.",2000.0,0,1
14,10214534,"A double-blind, randomized, crossover assessment of blood pressure following administration of avitriptan, sumatriptan, or placebo to patients with mild to moderate hypertension.",S S Jhee; D E Salazar; N F Ford; I E Fulmor; J J Sramek; N R Cutler,"We examined the effects of avitriptan, a 5-hydroxytryptamine 1-like (5HT1) receptor agonist for the treatment of migraine, in patients with medicated, controlled, mild to moderate hypertension relative to placebo and sumatriptan. The study was randomized, double-blinded, placebo-controlled, and 4-way crossover in design. Twenty patients (12M, 8F) participated. As required by protocol, all were stable on medications for mild to moderate hypertension, with a supine diastolic blood pressure of < 95 mmHg. Qualified subjects were randomized to receive oral administration of either 75 or 150 mg of avitriptan, 100 mg sumatriptan or placebo during the four treatment visits. Supine blood pressure and pulse rates were recorded up to 24 h after drug administration. Avitriptan 150 mg significantly increased peak diastolic and systolic blood pressure, and mean arterial pressure compared to placebo and sumatriptan 100 mg (p < 0.05). Only those hypertensive patients receiving medication for hypertension should receive anti-migraine medications, such as avitriptan, which are 5HT1-like receptor agonists.",1999.0,0,1
15,10214535,Effects of zolmitriptan (Zomig) on central serotonergic neurotransmission as assessed by active oddball auditory event-related potentials in volunteers without migraine.,A M Hughes; R Dixon; A Dane; J Kemp; L Cummings; R A Yates,"In this randomized, double-blind, three-period crossover trial, 24 healthy volunteers without migraine received zolmitriptan 5 mg, dexfenfluramine 15 mg or placebo orally. At 2, 6, and 24 h postdose, auditory stimuli of 1000 Hz (nontarget tone) and 2000 Hz (target tone) were randomly and binaurally presented in an active oddball paradigm (4:1 ratio). Cortical auditory evoked responses were recorded for 500 msec poststimulus. Plasma concentrations of zolmitriptan and a 17-lead quantitative EEG were assessed at the same timepoints. Relative to placebo, zolmitriptan reduced the maximum absolute amplitude, amplitude difference (from nontarget tone noise) and area under the curve of the cortical auditory target tone event-related potential (P300 ERP). The most dramatic effect of zolmitriptan was to diminish the point estimate of noise during the 200-400 msec poststimulus epoch. The effect of zolmitriptan appeared concentration dependent. The latency of the P300 ERP was unaffected by zolmitriptan and there was no clinically significant effect on the EEG. Modification by zolmitriptan of the cortical electrical activity evoked by auditory stimuli confirms a central action of this drug in humans, which appears to affect cortical information processing without global alteration of the quantitative EEG.",1999.0,0,0
16,10214771,Naratriptan is effective and well tolerated in the acute treatment of migraine.,P Tfelt-Hansen; P J Goadsby,,1999.0,0,0
17,10219932,Changes in resource use and outcomes for patients with migraine treated with sumatriptan: a managed care perspective.,J H Lofland; N E Johnson; A S Batenhorst; D B Nash,"Migraine headaches result in significant patient suffering and high costs to managed care organizations and employers. Studies that evaluate patient outcomes and the financial consequences of migraine treatment are important from a clinical and an economic perspective. This prospective, observational study assessed the outcomes of migraineurs in a mixed model staff/ independent practice association managed care organization for patients previously diagnosed as having migraine who received their first prescription for sumatriptan. Data collected included medical as well as pharmacy claims and patient surveys to measure changes in satisfaction, health-related quality of life, workplace productivity, and nonworkplace activity after sumatriptan therapy was initiated. A total of 178 patients completed the study. Results showed significant decreases in the mean number of migraine-related physician office visits, emergency department visits, and medical procedures in the 6 months after sumatriptan therapy compared with the 6 months before sumatriptan was used (P<.05). Four of the health-related quality-of-life dimensions and the physical component summary score measured by the SF-36 (which is a valid, reliable general health status instrument) showed significant improvements at 6 months compared with patients' scores before use of sumatriptan (P<.05). Health-related quality of life measured by the disease-specific instrument MSQ (Migraine-Specific Quality of Life Questionnaire-Version 1.0, 1992 Glaxo Wellcome Inc, Research Triangle Park, NC) showed significant improvement at 3 and at 6 months compared with baseline scores (P<.05). There were also improvements in patient satisfaction and significant reductions in time lost from workplace productivity and nonworkplace activity. In the 6 months after sumatriptan therapy was initiated, health care resource use and time lost from workplace productivity and nonworkplace activity were reduced, while health-related quality of life and patient satisfaction scores improved for the managed care migraineurs enrolled in this study.",1999.0,0,1
18,10227648,Intranasal sumatriptan for the acute treatment of migraine in children.,M A Ueberall; D Wenzel,"Sumatriptan is a highly effective treatment for migraine in adults but its efficacy in children has not been determined. Fourteen children with migraine (6.4 to 9.8 years of age; seven girls, six with aura) participated in a randomized double-blind placebo-controlled crossover study to evaluate the efficacy of sumatriptan nasal spray. After sumatriptan, 12 of 14 (versus 6 of 14 after placebo) reported a decrease in pain intensity (p = 0.031); complete headache relief was obtained in 9 of 14 after sumatriptan versus 2 of 14 after placebo (p = 0.016). Migraine-associated symptoms were also significantly reduced by sumatriptan.",1999.0,0,0
19,10231608,"Migraine headaches: nutritional, botanical and other alternative approaches.",S Sinclair,"Migraine headaches are an increasingly common health problem with a wide range of potential etiological factors. Stress, food allergies, neuroendocrine imbalances and nutritional deficiencies all may contribute to migraine attacks. Many nutritional and botanical therapies aim to reduce migraine incidence by decreasing platelet aggregation and preventing the release of vasoactive neurotransmitters, and avoiding triggering foods. This article reviews much of the research on nutritional, botanical, dietary, and other alternative approaches to the treatment and prevention of migraines.",1999.0,0,0
20,10233200,Pharmacokinetics and tolerability of oral rizatriptan in healthy male and female volunteers.,Y Lee; J A Conroy; M E Stepanavage; C M Mendel; G Somers; D A McLoughlin; T V Olah; M De Smet; B Keymeulen; J D Rogers,"The pharmacokinetics and dose proportionality of rizatriptan single oral doses from 2.5 to 15 mg administered as solutions to healthy volunteers were studied. In a randomized, crossover study with four periods, twenty-four healthy volunteers (12 males and 12 females) took single oral doses of 2.5, 5, 10, and 15 mg rizatriptan in Periods 1-4. In a fifth period, subjects received 4 mg intravenous (i.v.) rizatriptan as a reference. Plasma and urine rizatriptan concentrations were determined at several timepoints/intervals for 12 and 24 h, respectively. The arithmetic mean AUC values following single oral doses of 2.5, 5, 10, and 15-mg rizatriptan were 16, 33, 72, and 127 ng ml-1 h, respectively, in males; and 19, 42, 97, and 161 ng ml-1 h, respectively, in females. The overall bioavailability (F ) of rizatriptan was approximately 40% in males. Following the 4 mg reference i.v. dose, the apparent plasma clearance (CL) and renal clearance (CLr ) were 1042 and 225 ml min-1, respectively, in males; and 821 and 174 ml min-1, respectively, in females. The disposition kinetics of oral rizatriptan were linear for doses of 2. 5-10 mg in males, and for doses of 2.5-5 mg in females. However, the degree of nonlinearity for higher doses was minor for both genders. The plasma concentrations of rizatriptan were slightly greater in women compared to men but the difference was not considered to be clinically meaningful. Also, the clearance of rizatriptan appeared to be mainly nonrenal.",1999.0,0,0
21,10235690,Systematic review and guide to selection of selective serotonin reuptake inhibitors.,J G Edwards; I Anderson,"A meta-analysis of 20 short term comparative studies of 5 selective serotonin reuptake inhibitors (SSRIs; citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline) has shown no difference in efficacy between individual compounds but a slower onset of action of fluoxetine. There were suggestions that fluoxetine caused more agitation, weight loss and dermatological reactions than the other SSRIs. More patients discontinued fluvoxamine and fewer patients stopped sertraline because of adverse effects than their comparator SSRIs. The most common adverse reactions to the SSRIs were gastrointestinal (especially nausea) and neuropsychiatric (particularly headache and tremor). Data from the Committee on Safety of Medicines showed more reports of suspected reactions (including discontinuation reactions) to paroxetine, and of gastrointestinal reactions to fluvoxamine and paroxetine, than the other SSRIs during their first 2 years of marketing. Prescription-event monitoring revealed a higher incidence of adverse events related to fluvoxamine than its comparators. There were higher incidences of gastrointestinal symptoms, malaise, sedation and tremor during treatment with fluvoxamine and of sedation, tremor, sweating, sexual dysfunction and discontinuation reactions with paroxetine. Fluoxetine was not associated with a higher incidence of suicidal, aggressive and related events than the other SSRIs. Patients have survived large overdoses of each of the compounds, but concern has been expressed over 6 fatalities following overdoses of citalopram. Drug interactions mediated by cytochrome P450 enzymes are theoretically less likely to occur during treatment with citalopram and sertraline, but there is a sparsity of clinical data to support this. Methodological difficulties and price changes do not allow choice for recommendations on the choice of SSRI based on pharmacoeconomic data. Taking into account the strengths and weaknesses of the methods used to compare drugs, guidelines to the selection of individual SSRIs in clinical practice are proposed. Citalopram should be avoided in patients likely to take overdoses. Fluoxetine may not be the drug of first choice for patients in whom a rapid antidepressant effect is important or for those who are agitated, but it may have advantages over other SSRIs in patients who are poorly compliant with treatment and those who have previously had troublesome discontinuation symptoms. Fluvoxamine, and possibly paroxetine, should not be used as first choice in patients especially prone to SSRI-related adverse reactions, while paroxetine should be avoided if previous discontinuation of treatment was troublesome. When in doubt about the risks of drug interactions, citalopram or sertraline should be considered given the lower theoretical risk of interactions.",2000.0,0,0
22,10329285,Intracranial vessels in trigeminal transmitted pain: A PET study.,A May; C Büchel; A Bahra; P J Goadsby; R S Frackowiak,"The underlying principle in interpreting data from positron emission tomography (PET) is that increases and decreases of synaptic activity in the brain are accompanied by equivalent changes in regional blood flow. However, given the relatively low spatial resolution of PET, regional indices of neural activity can be influenced by signals from nonneural elements in the intracranial space. We have used PET to study the functional neuroanatomy of headache syndromes, such as cluster headache and experimental headache, by observing activation in brain that is due to synaptic activity. In these studies we noted a bilateral activation in midline structures over several planes that, based on its anatomy, is likely to arise from bilateral large intracranial arteries in the region of the cavernous sinus. We have observed this activity in two different group studies and in 11 of 17 single-subject studies. The most likely explanation for this ""activation"" is the increased volume of space occupied by dilated large vessels containing H215O. We further defined the anatomy of the PET findings using magnetic resonance angiography, which showed bilateral vasodilatation of the internal carotid artery and the basilar artery in nitroglycerin-induced cluster headache attacks. While the fact that vascular structures can contaminate PET-based blood flow studies may be well known to methodological experts, the issue is less well recognized outside the immediate field.",1999.0,0,0
23,10345971,Maintenance drug therapy of chronic obstructive pulmonary disease.,T Self; K Demirkan,,1999.0,0,0
24,10358852,Focus on primary care diagnosis and management of headache in women.,D A Marcus,"Women experience unique changes in headache pattern related to changes in their reproductive cycles. Changes predictably occur in association with menarche, menstrual cycling, the use of oral contraceptives, pregnancy, and menopause. These predictable headache changes are linked to changing levels of sex hormones. This article describes important relationships between estradiol and neurotransmitters involved in the pathogenesis of headache, such as serotonin. Treatment of headache in women includes the use of acute care and preventive treatments. The effectiveness of both medication and nonmedication treatments is reviewed. Also, unique aspects of treating headache with menstruation, pregnancy, and menopause are described.",1999.0,0,0
25,10361566,"Acupuncture for migraine and headache in primary care: a protocol for a pragmatic, randomized trial.",A Vickers; R Rees; C Zollman; C Smith; N Ellis,"This paper presents the protocol for a randomized trial of acupuncture for migraine and headache. Four hundred patients with migraine or headache will be recruited from GP practices. Eighteen to 65 years old, contractable by telephone, onset at least 1 year prior at age less than 50, two headaches per month in the previous 6 months, adequate data completion and headache severity during pre-randomization baseline. Pregnancy or malignancy, cluster headache, serious pathological aetiology, cranial neuralgia, acupuncture treatment in the past year. Following a 4-week baseline, patients will be allocated to acupuncture or control by minimized randomization. Up to 12 acupuncture treatments will be provided by advanced members of the Acupuncture Association of Chartered Physiotherapists. The type of acupuncture given will be recorded. STUDY MEASURES: Outcome will be assessed by headache diary, medication diary and SF36 at 3 months and 1 year. Resource use and days off sick will be assessed by quarterly questionnaire. Adverse events will be monitored by self-report. The primary outcome measure will be the change in mean daily headache score between baseline and the 1 year follow-up. An economic evaluation will also be undertaken.",1999.0,0,0
26,10362912,Issues relating to the assessment of migraine recurrence following triptan therapy.,D Millson; S Tepper,,2000.0,0,0
27,10376167,Prospective large-scale study of the tolerability of subcutaneous sumatriptan injection for acute treatment of migraine.,S O'Quinn; R L Davis; D L Gutterman; G D Pait; A W Fox,"To investigate prospectively serious adverse events associated with sumatriptan injection, we studied 12,339 typical migraineurs for up to 12 months each. This study imitated the ordinary clinical use of sumatriptan injection except that: (a) a short, written informed consent was required, (b) there was a centralized, automated dispensing service that audited each patient's product use, (c) patients were sometimes reviewed by telephone, and (d) drug supply and medical consultation were without charge. All adverse events were recorded regardless of etiology. There were 25 fatalities during the study, none being attributable to sumatriptan injection. Of six strokes in the study, two occurred soon after treatment of a migraine attack with sumatriptan injection; whether these were migraine-related or drug-related is discussed. None of the three myocardial infarctions was due to sumatriptan injection use. We conclude that sumatriptan injection is well tolerated when used in accordance with labeling.",1999.0,0,1
28,10376168,"Acute treatment of migraine attacks: efficacy and safety of a nonsteroidal anti-inflammatory drug, diclofenac-potassium, in comparison to oral sumatriptan and placebo. The Diclofenac-K/Sumatriptan Migraine Study Group.",,"Migraine attacks are often treated with simple analgesics or with ergotamine-containing preparations alone or in combination with anti-emetics. Although also sometimes used to treat migraine, nonsteroidal anti-inflammatory drugs (NSAIDs) have not been systematically evaluated in controlled clinical trials, particularly in comparison with the newer drug sumatriptan. Sumatriptan is a specific migraine treatment which has recently become among the most widely prescribed acute migraine therapies. However, while effective, it has low oral bioavailability and some problematic adverse effects. Diclofenac-potassium is a potent NSAID available as a fast-acting oral tablet, which has been shown to be safe and effective in several other acute pain indications. In the clinical trial reported here, the efficacy and safety of diclofenac-potassium in the acute treatment of migraine attacks has been tested in comparison with oral sumatriptan and placebo. Single oral doses of 50 mg and 100 mg diclofenac-potassium were compared to a single oral dose of 100 mg sumatriptan and placebo in a double-blind randomized crossover trial in 156 adult patients suffering from migraine attacks, with or without aura, selected according to the International Headache Society diagnostic criteria. The primary efficacy criterion was migraine headache pain recorded on a visual analog scale at 2 h after dosing. Secondary endpoints included pain at other time points up to 8 h and the presence of accompanying symptoms (nausea, vomiting, photophobia, phonophobia). Diclofenac-potassium was more effective than placebo in reducing migraine headache pain at 2 h after dosing, which was the primary endpoint. Secondary analyses showed that diclofenac-potassium provided significant pain relief from 60 min after dosing and for all remaining endpoints in the 8-h observation period. Both 50 and 100 mg doses of diclofenac-potassium were similarly effective. A similar effect was shown with sumatriptan; however, significant superiority to placebo was seen only from the 90-min time point. Diclofenac-potassium was generally superior to placebo or sumatriptan in reducing accompanying symptoms, particularly nausea. Diclofenac-potassium seemed to be as well tolerated as placebo, with fewer adverse events reported than after sumatriptan treatment and with more patients assessing the overall tolerability of diclofenac-potassium better than that of sumatriptan. Compared with placebo and the reference therapy sumatriptan, diclofenac-potassium is an effective, fast-acting, and well-tolerated acute oral therapy for migraine attacks, with advantages over oral sumatriptan in terms of onset of analgesic effect, reduction of accompanying symptoms, and tolerability profile. It may therefore be useful as an alternative oral therapy for migraine attacks.",1999.0,0,1
29,10376171,Efficacy definitions for migraine studies.,D J Goldstein; W W Offen; M B Moster,,1999.0,0,1
30,10383528,"Altered oesophageal motility following the administration of the 5-HT1 agonist, sumatriptan.",J M Foster; L A Houghton; P J Whorwell; J Morris,"The 5-HT1 agonist sumatriptan, used in the treatment of migraine, can cause chest pain. To investigate the effect of a therapeutic dose of sumatriptan (6 mg s.c.) on oesophageal motility. In 16 normal healthy subjects aged 19-32 years (9 males), the manometric response of the lower oesophageal sphincter (sleeve sensor), oesophageal body (four sites), stomach and pharynx (to register swallows) to 5 mL water swallows was assessed before and after a subcutaneous injection of either sumatriptan (6 mg) or saline control. Symptoms and ECGs were also monitored. Sumatriptan 6 mg s.c. altered oesophageal motility in all subjects. This was reflected by a significant increase in the amplitude of oesophageal body contractions (change from pre- to 1 h post-injection: sumatriptan 9.9 (2.8, 17.1) mmHg vs. placebo -0.8 (-4.2, 2.6) mmHg, difference 10.8 (4.4, 17.1) mmHg; P=0.003) and a transient increase in lower oesophageal sphincter pressure (change from pre- to 5 min post-injection: sumatriptan 10.9 (5.2, 16.6) mmHg vs. placebo 5.1 (1.8, 8.4) mmHg, difference 5.8 (-0.7, 12.3) mmHg; P=0.08). Sumatriptan had no effect on the velocity of propagation of oesophageal contractions (change from pre- to 1 h post-injection: sumatriptan -0.1 (-0.3, 0.1) cm/s vs. placebo -0.1 (-0.3, 0.0) cm/s, difference 0.1 (-0.1, 0.2) cm/s; P = 0.40). One subject experienced chest symptoms following sumatriptan and, although motility was altered, this did not reach pathological levels. No ECG abnormalities were observed. Sumatriptan (6 mg s.c.) significantly alters oesophageal motor function without affecting the ECG. It is therefore possible that sumatriptan-induced chest symptoms may have an oesophageal origin. The evaluation of similar therapeutic agents for migraine on oesophageal function may be justified.",1999.0,0,0
31,10400409,Diclofenac-potassium in migraine: a review.,W McNeely; K L Goa,"The NSAID diclofenac is a potent inhibitor of prostaglandin synthesis and an established antipyretic and analgesic agent. Diclofenac-potassium was developed as an immediate-release tablet with the aim of providing rapid onset of action after oral administration. This formulation has been investigated in the acute treatment of migraine. Data from available placebo-controlled clinical trials indicate that diclofenac-potassium 50 or 100mg as an immediate-release tablet is more effective than placebo and as effective as oral sumatriptan 100mg and ergotamine plus caffeine at reducing pain intensity in patients with migraine 2 hours after initial administration. Duration of pain relief is similar for the 3 drugs but onset appears to be faster with diclofenac-potassium than with oral sumatriptan or ergotamine plus caffeine. Diclofenac-potassium appears to have favourable effects on some accompanying symptoms such as nausea and vomiting. The frequency of these symptoms was significantly lower with diclofenac-potassium than with sumatriptan in 1 study, although only a few patients had vomiting at baseline. Effects on phonophobia or photophobia did not differ between diclofenac-potassium, sumatriptan and ergotamine plus caffeine. The need for rescue medication is consistently less with diclofenac-potassium than with placebo. Data are inconsistent or scarce regarding the effects of diclofenac-potassium versus placebo on other measures such as headache recurrence and working ability. Diclofenac-potassium was generally well tolerated in clinical trials in patients with migraine. Adverse events reported most frequently (abdominal pain, tiredness and fatigue and nausea) were typically mild to moderate. Diclofenac-potassium provides rapid pain relief (within 60 to 90 minutes), is well tolerated and reduces the frequency of some of the accompanying symptoms in patients with migraine. Available trials indicate that diclofenac-potassium provides similar pain relief to sumatriptan and is at least as effective as ergotamine plus caffeine, but appears to have a greater effect on nausea and vomiting than sumatriptan and a faster onset of action than both drugs. Comparisons with other NSAIDs are lacking. Diclofenac-potassium is likely to find a role as a useful first-line option in the acute treatment of migraine.",1999.0,0,0
32,10403065,,,,,0,1
33,10403069,Efficacy and safety of rizatriptan wafer for the acute treatment of migraine. Rizatriptan Wafer Protocol 049 Study Group.,S P Ahrens; M V Farmer; D L Williams; E Willoughby; K Jiang; G A Block; W H Visser,"Rizatriptan is a potent, highly selective 5HT1B/1D agonist with rapid onset of action for acute treatment of migraine. Rizatriptan wafer is a novel, freeze-dried dosage formulation of rizatriptan which rapidly disintegrates on the tongue, is swallowed with saliva, and may be taken without liquids. The efficacy and tolerability of rizatriptan wafer were examined in a placebo-controlled, double-blind, outpatient study in 555 migraineurs. The primary efficacy endpoint was pain relief at 2 h. From 30 min onwards, significantly more patients experienced pain relief and became pain-free after rizatriptan 10-mg wafer compared to placebo. At 2 h, the percentage of patients with pain relief was significantly higher after rizatriptan 10-mg wafer (74%), 5-mg wafer (59%) compared with placebo (28%). Rizatriptan 10-mg wafer was superior to rizatriptan 5-mg wafer on pain relief at 1.5 and 2 h (p < 0.05). Significantly more patients were pain-free at 2 h after rizatriptan 10-mg wafer (42%), 5-mg wafer (35%) compared with placebo (10%). Both doses of rizatriptan wafer were well tolerated. Rizatriptan wafer is a convenient, highly effective new formulation for acute treatment of migraine.",1999.0,0,1
34,10405702,Treatment of migraine headaches.,J D Bartleson,"Migraine headaches are common and costly. Patients with migraine frequently seek medical attention from primary care physicians. Although effective therapy is available, migraine is underdiagnosed and undertreated. The 3 main forms of management are avoidance of migraine triggers, treatment of the acute attack with medications, and regular use of preventive medications. Although changes in lifestyle can help to prevent some migraine attacks, the mainstay of treatment is the use of medications taken early during the attack. A wide variety of single-ingredient and combination over-the-counter and prescription medications are now available. Especially effective are the new selective serotonin (5-hydroxytryptamine1 receptor) agonists such as sumatriptan. For patients who have frequent and severe migraine headaches despite the use of acute treatment, preventive medications, including beta-adrenergic blockers, calcium channel blockers, tricyclic antidepressants, and one anticonvulsant, should be considered. The vast majority of patients with migraine can be helped.",1999.0,0,0
35,10410185,Naratriptan: an alternative for migraine.,D A Dulli,"To critically evaluate the literature regarding naratriptan's clinical pharmacology, efficacy, safety, and indications. A MEDLINE search was conducted for the period from January 1990 to June 1998. Key words used included naratriptan, triptan, serotonin agonists, migraine, and migraine therapy. In addition, pertinent references cited in articles obtained from MEDLINE and product information for triptans were reviewed. All original and review articles and abstracts pertaining to naratriptan were reviewed, as were product information extracts. Clinical trials of naratriptan were critically reviewed and compared with pertinent clinical trials of other oral triptans. The treatment of migraine has been dramatically improved with the use of sumatriptan, other triptans, and serotonin-receptor subtype 1B and 1D agonists. Drawbacks to these medications, however, have included poorly tolerated adverse effects and the recurrence of the migraine. Naratriptan has been recently approved for acute oral migraine therapy. In two Phase III trials of naratriptan compared with placebo, relief at four hours was obtained in 60% and 68% of patients using the 2.5-mg dose, with recurrence of headache in 24 hours in 27% and 28% of patients. The data on migraine recurrence were similar to those of other oral triptans; the efficacy of naratriptan at two hours was not specifically analyzed. Adverse effects of naratriptan were similar to placebo, and its tolerability seemed superior compared with studies of other oral triptans. Naratriptan is a promising new oral therapy for acute migraine; it may successfully treat patients who poorly tolerate other triptan therapies or have longer duration migraine headaches.",1999.0,0,0
36,10413073,Effects of subcutaneous naratriptan on systemic and pulmonary haemodynamics and coronary artery diameter in humans.,S Hood; D Birnie; L Swan; L S Murray; H Whitehouse; P Winter; W S Hillis,"Naratriptan, an effective antimigraine agent, is a selective 5-hydroxytryptamine (5-HT1 )-receptor agonist with a pharmacologic profile similar to that of sumatriptan. The object of this study was to assess the haemodynamic effects of naratriptan in a clinical model previously applied to sumatriptan. Cardiac haemodynamics and coronary artery diameter were measured at baseline and after subcutaneous injections of placebo and naratriptan (1.5 mg, s.c.) in 10 patients undergoing diagnostic cardiac catheterisation. No statistically significant change in mean coronary artery diameter was observed after naratriptan [95% confidence interval (CI), -0.27-0.11 mm: p = 0.37]. Naratriptan injection was associated with statistically significant increases in systolic arterial pressure (95% CI, 7.6-22.0 mm Hg; p = 0.0015), total systemic vascular resistance (95% CI, 74-253 dyn/s/cc; p = 0.003), pulmonary artery systolic pressure (95% CI, 2.0-6.9 mm Hg; p = 0.003), pulmonary vascular resistance (95% CI, 3-34 dyn/s/cc; p = 0.025), and pulmonary artery wedge pressure (95% CI, 1.9-2.4 mm Hg; p = 0.009). Naratriptan, a selective 5-HT1-receptor agonist, caused a vasopressor response in the systemic and pulmonary arterial circulations but was not associated with coronary artery vasoconstriction.",1999.0,0,1
37,10417495,The effects of moclobemide on the pharmacokinetics of the 5-HT1B/1D agonist rizatriptan in healthy volunteers.,A D Van Haarst; J M Van Gerven; A F Cohen; M De Smet; A Sterrett; K L Birk; A L Fisher; M E De Puy; M R Goldberg; D G Musson,"The new 5-HT1B/1D agonist rizatriptan (MK-0462) has recently been registered for the treatment of migraine. Its primary route of metabolism is via monoamine oxidase-A (MAO-A). Antidepressants such as the MAO-A inhibitor moclobemide may be used in patients with chronic headache syndromes. Hence, this study aimed to investigate the interactions between rizatriptan and moclobemide. In a double-blind, randomized, placebo-controlled, two-period cross-over study 12 healthy, young volunteers (six males, six females) were treated with moclobemide (150 mg twice daily) or placebo for 4 days. On the fourth day, a single dose of rizatriptan (10 mg) was administered, and subsequently blood and urine samples were collected for assay of rizatripan and N-monodesmethyl rizatriptan. Plasma concentrates of 3,4-dihydroxyphenylglycol (DHPG), a marker of MAO-A inhibition, were also assessed. Supine and standing blood pressure were measured regularly. Both treatments were well tolerated. During moclobemide, the increase in supine diastolic blood pressure following rizatriptan administration was augmented. Inhibition of MAO by moclobemide was inferred from a persistent decrease in DHPG level (43% on average). When rizatriptan was coadministered with moclobemide, the area under the plasma drug concentration-time profiles for rizatriptan and its N-monodesmethyl metabolite increased 2.2-fold (90% CI, 1.93-2.47) and 5.3-fold (90% CI, 4.81-5.91), respectively, when compared with placebo. Peak plasma drug concentrations for rizatriptan and its n-monodesmethyl metabolite increased 1.4-fold (90% CI, 1.11-1.80) and 2.6-fold (90% CI, 2.23-3.14), respectively, and half-lives of both were prolonged. Moclobemide inhibited the metabolism of rizatriptan and its active N-monodesmethyl metabolite through inhibition of MAO-A. Thus, moclobemide may considerably potentiate rizatriptan action. Concurrent administration of moclobemide and rizatriptan is not recommended.",1999.0,0,0
38,10427351,Profiles of 5-HT 1B/1D agonists in acute migraine with special reference to second generation agents.,D Deleu; Y Hanssens,"The efficacy of 5-hydroxytryptamine 1B/1D (5-HT 1B/1D) agonists is related to their inhibitory effects on neurogenic inflammation, mediated through serotoninergic control mechanisms. Recently, a series of oral second generation 5-HT 1B/1D agonists (eletriptan, naratriptan, rizatriptan and zolmitriptan) have been developed and are reviewed in this paper. Their in vitro and in vivo pharmacological properties, clinical efficacy, drug interactions, and adverse effects are evaluated and compared to the gold standard in the treatment of acute migraine, sumatriptan.",1999.0,0,0
39,10442248,Sumatriptan and ergotamine overuse and drug-induced headache: a clinicoepidemiologic study.,S Evers; I Gralow; B Bauer; B Suhr; A Buchheister; I W Husstedt; E B Ringelstein,"Drug-induced headache, particularly ergotamine-induced headache, is a common problem in migraine treatment. Some case reports suggest that even the new serotonergic antimigraine drugs such as sumatriptan can lead to overuse and subsequent drug-induced headache. We performed a controlled study to identify the rate of sumatriptan overuse and sumatriptan-induced headache and compared it to the rate of ergotamine overuse and ergotamine-induced headache. Two thousand sixty-five consecutive heachache patients, all experienced in intake of sumatriptan (n = 631) or ergotamine (n = 620), were enrolled over a three-year study period. The rates of overuse and drug-induced headache and the clinical features of the subgroups were compared. Risk factors for sumatriptan overuse were identified. The rates of ergotamine and sumatriptan overuse were 14.2% and 3.5%, respectively (p < 0.001). Drug-induced headache could be found more frequently in cases of ergotamine overuse than in cases of sumatriptan overuse (68% versus 32%; p < 0.01). Development of sumatriptan overuse was most common in patients with previous drug-induced headache (68%), combined headache as the primary headache type (45%), and subcutaneous application of sumatriptan (45%). We conclude that sumatriptan intake can lead to overuse and subsequent drug-induced headache. The risk for overuse and drug-induced headache is significantly lower than in patients with ergotamine intake. This might be caused in part by the relatively short period of sumatriptan availability on the market. The new generation of serotonin-1B/D-receptor agonists in the treatment of headache should have a potential for overuse similar to that of traditional headache drugs.",1999.0,0,1
40,10448545,"Efficacy and safety of intravenous acetylsalicylic acid lysinate compared to subcutaneous sumatriptan and parenteral placebo in the acute treatment of migraine. A double-blind, double-dummy, randomized, multicenter, parallel group study. The ASASUMAMIG Study Group.",H C Diener,"Two-hundred-and-seventy-eight patients with acute migraine attacks with or without aura were treated in 17 centers with 1.8 g lysine acetylsalicylate i.v. (Aspisol; = 1 g acetylsalicylic acid), 6 mg sumatriptan s.c. or placebo using a double-blind, double-dummy, randomized, multicenter parallel group study design. Two-hundred-and-seventy-five of them fulfilled the criteria for efficacy analysis, corresponding to 119 patients treated with lysine acetylsalicylate (L-ASA), 114 with sumatriptan and 42 with placebo injections. Both treatments were highly effective compared to placebo (p < 0.0001) in decreasing headache from severe or moderate to mild or none (verbal rating scale, VRS, placebo = 23.8%). Sumatriptan showed a significantly (p = 0.001) better response (91.2%) compared to L-ASA (response 73.9%). Of the patients in the L-ASA-group, 43.7% were pain-free after 2 h; 76.3% after sumatriptan and 14.3% after placebo. It took patients on average 12.6 (L-ASA), 8.2 (sumatriptan), and 19.4 h (placebo) to be able to work again. There was no significant difference between treatment groups in recurrence of headache in responders within 24 h (18.2% L-ASA, 23.1% sumatriptan, 20% placebo). Accompanying symptoms (nausea, vomiting; photophobia, phonophobia, and visual disturbances) improved with both verum treatments to a similar extent. L-ASA was significantly better tolerated than sumatriptan (adverse events L-ASA 7.6%, sumatriptan 37.8%). In conclusion, subcutaneous sumatriptan and lysine acetylsalicylate i.v. are effective treatments for patients suffering from migraine attacks. Sumatriptan is more effective, but resulted in more adverse events.",1999.0,0,1
41,10453967,Migraine: a comprehensive review of new treatment options.,K W Weitzel; M L Thomas; R E Small; J V Goode,"Headaches are among the most common complaints reported to health care professionals and are classified by the International Headache Society as migraine, tension-type, or cluster, with additional subtypes. Classification and etiology of headache should be determined after thorough review of the patient's history. Once diagnosed, migraine can be treated by preventive or abortive measures. Recent developments add new options, including availability of drugs for intranasal administration (sumatriptan, dihydroergotamine) and 5-HT1B/1D agonists (rizatriptan, zolmitriptan, naratriptan, eletriptan). Although placebo-controlled trials are available, few comparative clinical trials of these agents have been conducted; however, important pharmacologic, pharmacokinetic, and clinical differences exist among the drugs.",1999.0,0,0
42,10463324,,,,,0,0
43,10463512,Symptomatic pharmacotherapy of migraine.,B L Lobo; S C Cooke; S H Landy,"This review summarizes data on the effectiveness of various symptomatic migraine pharmacotherapies and makes recommendations for treatment. A wide variety of agents are available for the symptomatic treatment of migraine headache, including over-the-counter analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), combination products, opiates, ergot alkaloids, corticosteroids, dopamine antagonists, and triptans. In the stepped-care approach, simple analgesics and NSAIDs are the recommended first step for the treatment of mild-to-moderate migraine headaches. Patients who do not respond to first-step treatments may be given ergots, combination products, dopamine antagonists, or triptans as the second step. Corticosteroids or opiates may be used as rescue treatment in patients who do not respond to second-step treatment. A stratified approach to care individualizes treatment based on the severity of the headache and other patient-specific factors. In a stratified approach, dihydroergotamine or triptans may be the first-step treatment for patients who present with a history of severe migraines that have responded poorly to previous treatments. Sumatriptan was the first triptan approved for the symptomatic treatment of migraine headache; newer triptans include zolmitriptan, naratriptan, and rizatriptan. Since sumatriptan is rapidly absorbed by the subcutaneous route, its time to onset of effect is shortest. Among triptan drugs that are administered orally, the relative time to onset may be shorter with rizatriptan than sumatriptan. Naratriptan has a longer time to onset but is associated with a lower rate of migraine recurrence than other triptans. graine headache, ergot alkaloids, triptans,",1999.0,0,0
44,10473025,Zolmitriptan: a review of its use in migraine.,C M Spencer; N S Gunasekara; C Hills,"Zolmitriptan is a selective serotonin 5-HT1B/1D receptor agonist ('triptan'). Its efficacy and tolerability have been assessed in a number of randomised, placebo-controlled, double-blind trials in large numbers of adults with moderate to severe migraine attacks. Oral zolmitriptan 2.5 and 5mg has a rapid onset of action (significant headache relief is observed at 45 minutes) and efficacy is sustained in most patients who respond at 2 hours. The drug is significantly more effective than placebo as measured by a number of parameters including 2-hour headache response rates and pain-free response rates. Other symptoms of migraine, including nausea, photophobia and phonophobia are also alleviated with zolmitriptan. Zolmitriptan is effective in the treatment of migraine associated with menses and migraine with aura. There is some evidence to support the use of zolmitriptan in patients with migraine who have had a poor response to previous therapy. The efficacy of zolmitriptan appears to be maintained, with no tachyphylaxis, following repeated administration for multiple attacks of migraine over a prolonged period of time, with high headache response rates reported over all attacks. In comparison with placebo, the incidence of persistent migraine headache is reduced by zolmitriptan and recurrent migraine headache occurs less frequently with the active treatment. Zolmitriptan has also demonstrated efficacy in the treatment of persistent and/or recurrent migraine headache. For relief of migraine headache, zolmitriptan 5mg had similar efficacy to sumatriptan 100mg for a single attack, but generally was more effective than sumatriptan 25 and 50mg for multiple attacks, in single trials. The incidence of recurrent headache with zolmitriptan was similar to that with sumatriptan. Zolmitriptan is generally well tolerated with most adverse events being mild to moderate, transient and resolving without intervention or the need for treatment withdrawal. The most common adverse events with zolmitriptan therapy are asthenia, heaviness other than that of the chest or neck, dry mouth, nausea, dizziness, somnolence, paraesthesia, warm sensation, tightness, vasodilation and chest pain. Zolmitriptan is effective across a wide range of migraine subtypes, maintains efficacy when used in the long term and is generally well tolerated. Further clinical experience is necessary to define the position of zolmitriptan among other currently or soon to be available selective 5-HT1B/1D receptor agonists. However, on the basis of available data, zolmitriptan should emerge as a useful treatment option in the management of patients with moderate to severe migraine.",1999.0,0,0
45,10500262,Vasoneuronal coupling in migraineurs after subcutaneous sumatriptan: a TCD study.,H Baezner; W Steinke; M Daffertshofer; M Hennerici,"According to the trigeminovascular model of pain in migraine, sterile neurogenic inflammation of dural vessels stimulates nociceptive fibres of the trigeminal nerve. Sumatriptan, a 5-HT1 receptor agonist, blocks this reaction and mediates vasoconstriction of meningeal arteries. However, it is uncertain, whether sumatriptan also has a vasoconstrictive effect on cerebral arteries, which may influence vasoneuronal coupling and induce secondary cerebral blood flow changes. We studied changes of cerebral blood flow velocity (CBFV) and the pulsatility index (PI) in the posterior cerebral artery (PCA) after stimulus activation before, 10 min and 30 min after subcutaneous application of 6 mg sumatriptan, in order to assess potential vasoactive effects on cerebral circulation. CBFV was recorded from both PCAs simultaneously in 27 migraineurs (twenty women, seven men, mean age 29 years), and arterial blood pressure (BP), heart rate (HR) and respiration rate (RR) were monitored. Although the mean diastolic blood pressure rose significantly from 75 mm Hg to 81 mm Hg (P<0.05) and systolic blood pressure and respiration rates remained constant, average CBFV values remained constant. Similarly, the relative increase of CBFV by visual stimulation, which is clearly higher compared to controls in other studies (55.0% before, 52.6% after 10 min, and 52.4% after 30 min), and absolute mean values for CBFV and PI did not change after visual stimulation. These results provide evidence against the hypothesis that sumatriptan produces vasoconstriction in the intracranial human arterial circulation as a potential risk of cerebral ischemia.",1999.0,0,0
46,10510143,Changes in systolic time intervals-a non-invasive marker for the haemodynamic effects of sumatriptan.,S Hood; D Birnie; L S Murray; P D MacIntyre; W S Hillis,"This study assessed the use of systolic time intervals (STI) as a potential non-invasive marker of the haemodynamic effects of sumatriptan, a 5HT1 receptor agonist. Twenty-six patients undergoing diagnostic cardiac catheterization participated. STIs were derived from haemodynamic pressure tracings at baseline, following placebo injection and following either subcutaneous (n=18) or intravenous injection (n=8) of sumatriptan. Sumatriptan (i.v. or s.c.) was associated with significant increases in mean arterial pressure (95% C.I. 9,14mmHg, P=0.0001), total electromechanical systole (95% C.I.8,36ms, P<0.0001), pre-ejection period (95%C.I. 8,21ms, P=0.0001) and left ventricular ejection time (95% C.I. 2,12ms, P=0.004). Conclusion STI responses were consistent with sumatriptan-induced changes in afterload. In summary, the measurement of STIs is a potential non-invasive method of investigating the influence of serotonergic compounds on the cardiovascular system.",1999.0,0,0
47,10524661,"Migraine polypharmacy and the tolerability of sumatriptan: a large-scale, prospective study.",G P Putnam; S O'Quinn; C P Bolden-Watson; R L Davis; D L Gutterman; A W Fox,"Polypharmacy (the prescription of more than one therapy for a single patient) and subcutaneous (s.c.) sumatriptan tolerability were prospectively studied in 12,339 migraineurs, each followed for up to 1 year. Inclusion/exclusion criteria were minimal and mirrored United States Imitrex labeling. Drug usage and compliance monitoring were automatically interfaced with prescription refill. Concomitant drugs were used by 79% of patients, with analgesics, antidepressants, and sedatives used most commonly. No adverse interactions between sumatriptan and neurological drugs were found, possibly reflecting relative inability of the former to cross the blood-brain barrier. No difference in cardiovascular adverse events was associated with oral contraceptive use, which was more common than expected. No other drug class influenced adverse event probability, although sample sizes for these comparisons was sometimes <400 patients. This study confirms the prevalence of polypharmacy in migraine, identifies the drugs used, and concludes that, on a population basis, the tolerability of s.c. sumatriptan, when used according to labeled instructions, is unaffected by these concomitant drugs.",1999.0,0,0
48,10524662,"Open-labeled long-term study of the efficacy, safety, and tolerability of subcutaneous sumatriptan in acute migraine treatment.",H Göbel; A Heinze; H Stolze; K Heinze-Kuhn; V Lindner,"In a multicenter study, a long-term analysis was made of the efficacy, safety, and tolerability of subcutaneous (s.c.) sumatriptan in the acute treatment of migraine attacks over a period of up to 18 months. A total of 2263 patients took part in the study, all able to perform their own acute treatment of migraine attacks at home by s.c. administration of 6 mg of sumatriptan. A headache diary was used by each patient to record the various migraine parameters before the injection and 1 h and 2 h after it. A total of 43,691 attacks were treated and analyzed during the study period from October 1991 to June 1993. Therapy was successful in 89.5% of attacks. Freedom from headache was achieved in 71.0% of cases. In 22.7% of the attacks a second injection was administered on recurrence of the headache; 82.9% of the patients achieved an intraindividual therapy success rate ranging from over 80% to 100%. In the course of treatment there was no change in either the therapy success rate or in the frequency of attacks. Some 4.9% of the patients withdrew from the study because of insufficient efficacy or adverse events. A total of 44.5% of patients reported adverse events, and these were rated serious in the case of 1.7%. S.c. administration of sumatriptan for acute migraine therapy is an effective treatment method, with reliable action, that can be used with good tolerability provided the contraindications are taken into account.",1999.0,0,1
49,10529545,Comparison of rizatriptan 10 mg vs. naratriptan 2.5 mg in migraine.,M Bomhof; J Paz; N Legg; C Allen; K Vandormael; K Patel,"Rizatriptan (MAXALT(TM), Merck & Co., Inc.) is a selective 5-HT(1B/1D) receptor agonist with rapid oral absorption and early onset of action for the acute treatment of migraine. This randomized, double-masked, double-dummy, placebo-controlled study compared rizatriptan 10 mg to naratriptan (NARAMIG(TM), AMERGE(TM), both Glaxo Wellcome plc) 2.5 mg in 522 patients treating a single migraine attack. Rizatriptan was more effective than naratriptan. Rizatriptan provided earlier headache relief than naratriptan (hazard ratio 1.62, p < 0.001), acting as early as 30 min. More patients were pain free at 2 h on rizatriptan than on naratriptan (44.8 vs. 20.7%, p < 0.001). Rizatriptan also provided earlier relief of associated migraine symptoms within 2 h than naratriptan and more patients had normal function at 2 h (39.3 vs. 22.6%, p < 0. 001). Both active treatments were effective compared to placebo. Both active treatments were well tolerated. The most common side effects with rizatriptan were dizziness, asthenia/fatigue, nausea and somnolence, while the most common side effects with naratriptan were dizziness and asthenia/fatigue.",1999.0,1,1
50,10551439,Rizatriptan: a review of its efficacy in the management of migraine.,M Dooley; D Faulds,"Rizatriptan is an orally active serotonin 5-HT1 receptor agonist selective for the 5-HT(1B/1D) subtypes. The efficacy of oral rizatriptan (5 or 10 mg) has been demonstrated in large (n = 309 to 1746) well designed comparative trials with placebo and oral sumatriptan. Two hours postdose, rizatriptan 5 or 10 mg was more effective than placebo at producing pain relief or a pain free status, relieving migraine-associated symptoms and normalising functional ability. In general, rizatriptan 10 mg appeared to be more effective than rizatriptan 5 mg. However, recurrence rates with rizatriptan 5 and 10 mg appeared to be similar to those with placebo. Patients were significantly more likely to achieve pain relief within 2 hours after receiving rizatriptan 5 mg than sumatriptan 25 mg and after rizatriptan 10 mg than sumatriptan 50 mg. This was also observed with rizatriptan 10 mg compared with sumatriptan 100 mg according to an age-adjusted and a prespecified per-protocol analysis. In general, rizatriptan was better than sumatriptan at relieving migraine-associated symptoms, particularly nausea, and in normalising functional ability depending on which doses were compared. The incidence of headache recurrence, time to onset of recurrence and the need for escape medication in nonresponders appeared to be similar between rizatriptan and sumatriptan. Over the 24 hours after the dose, rizatriptan 10 mg improved the quality of life of patients with migraine compared with placebo. Rizatriptan 10 mg also significantly improved work function compared with placebo and with sumatriptan 50 mg. Rizatriptan appears to be well tolerated with most adverse events being mild and transient. The most commonly experienced events included general digestive complaints, general neurological complaints, dizziness, somnolence, asthenia/fatigue and pain and pressure sensations. In clinical trials, the overall incidence of adverse events with rizatriptan 5 or 10 mg was similar to that with sumatriptan 25 or 50 mg but lower than that with sumatriptan 100 mg. Chest pain was reported by 1 to 3% of rizatriptan recipients and by 3 to 6% of patients receiving sumatriptan (25, 50 or 100 mg); clinically significant effects on ECG parameters, heart rate or blood pressure were not observed with rizatriptan. Rizatriptan produces pain relief and a pain free status, relieves associated symptoms of migraine, normalises functional ability and improves patient quality of life. Rizatriptan 10 mg appears to be more effective than rizatriptan 5 mg. In comparison with oral sumatriptan, rizatriptan may provide better relief from pain and nausea, with some evidence of a faster onset of action. Thus, rizatriptan 5 or 10 mg is likely to establish a place as an effective and well tolerated agent for the management of acute migraine.",1999.0,0,0
51,10566707,,,,,0,0
52,10570722,Unbalanced randomization influences placebo response: scientific versus ethical issues around the use of placebo in migraine trials.,H C Diener; A J Dowson; M Ferrari; G Nappi; P Tfelt-Hansen,,1999.0,0,1
53,10595285,Sumatriptan nasal spray in the acute treatment of migraine: a review of clinical studies.,C Dahlöf,"Sumatriptan nasal spray is a single-dose device that delivers 5 mg, 10 mg, or 20 mg of sumatriptan (dosage availability dependent upon country) in a 0.1 ml aqueous solution to one nostril. The efficacy and tolerability of sumatriptan nasal spray have been assessed in a number of studies. It has been demonstrated that administering sumatriptan as a divided dose in both nostrils confers no advantage over administration in a single nostril. It appears from these studies that sumatriptan nasal spray is rapidly effective (with an onset of efficacy as early as 15 min postdose). The 20 mg dose is superior to the lower doses (5 mg, 10 mg) in terms of both time to onset of efficacy and the extent of migraine symptom relief. Sumatriptan nasal spray is consistently effective in the treatment of multiple migraine attacks (with 67% of patients treated with the 20 mg dose responding in at least two of three treated attacks) and with long-term use for up to 1 year. Apart from a bitter taste, the adverse event profile of sumatriptan nasal spray is comparable to that of placebo.",1999.0,0,1
54,10621951,Single photon emission computed tomography of the brain with Tc-99m HMPAO during sumatriptan challenge in obsessive-compulsive disorder: investigating the functional role of the serotonin auto-receptor.,D J Stein; B Van Heerden; C J Wessels; J Van Kradenburg; J Warwick; H J Wasserman,"1. Symptoms of obsessive-compulsive disorder (OCD) may be acutely exacerbated by administration of certain serotonin agonists Exacerbation of OCD symptoms by sumatriptan, a 5HT1D agonist (Zohar, 1993), is consistent with pre-clinical data suggesting that the serotonin auto-receptor plays an important role in this disorder (El Mansari et al, 1995). 2. In order to investigate the functional role of the serotonin auto-receptor in OCD, the authors undertook single photon emission computed tomography in OCD patients after administration of sumatriptan and placebo. The authors hypothesized that, as in the case of m-chlorophenylpiperazine (mCPP) challenge (Hollander et al, 1995), exacerbation of OCD symptoms would be accompanied by increased cortical metabolism and thus blood flow, and more specifically by increased activity in the orbitofrontal-striatal circuit. They also expected, that as in the case of mCPP challenge (Hollander et al, 1993), exacerbation of OCD symptoms would be associated with a relatively poor response to subsequent treatment with serotonin specific reuptake inhibitors. 3. Sumatriptan (100 mg orally) and placebo were administered on separate days to 14 patients who met DSM-IV diagnostic criteria for OCD, using a randomized double-blind design. After 90 minutes, patients were injected with Tc-99m HMPAO and underwent single photon emission computed tomography (SPECT) of the brain. Activity in regions of interest was calculated, and compared using repeated measures analysis of variance. Patients were subsequently treated with a serotonin specific reuptake inhibitor (SSRI). 4. Behavioral response to sumatriptan was heterogenous, with 4 patients showing acute exacerbation, and 4 patients demonstrating a decrease in symptoms. On sumatriptan challenge, there was a significant association between symptom exacerbation and decreased activity in frontal areas. There was an association between decreased activity in an inferior frontal area with worse response to treatment, and also patients with symptom exacerbation after sumatriptan had poorer response to SSRI treatment. 5. Heterogeneity of behavioral response to sumatriptan in OCD is consistent with previous studies demonstrating conflicting and heterogenous behavioral responses to serotonergic challenges (Hollander et al, 1992), and with underlying heterogeneity in the neurobiology of this disorder. 6. It may be hypothesized that increased frontal activity in some patients with OCD is itself a compensatory mechanism. In patients with such compensatory hyperactivity, administration of a serotonin auto-receptor agonist results in decreased frontal activity and exacerbation of OCD symptoms. These patients may also be less likely to respond to treatment with a SSRI. 7. Further work combining pharmacological challenge paradigms and functional imaging techniques in OCD may be helpful in elucidating the neurobiology of this complex disorder.",2000.0,0,0
55,10631625,"Rizatriptan, a novel 5-HT1B/1D agonist for migraine: single- and multiple-dose tolerability and pharmacokinetics in healthy subjects.",M R Goldberg; Y Lee; K P Vyas; D E Slaughter; D Panebianco; S J Ermlich; C R Shadle; M J Brucker; D A McLoughlin; T V Olah,"Rizatriptan is a novel 5-HT1D/1B agonist for relief of migraine headache. The pharmacokinetics, metabolite profiles, and tolerability of rizatriptan were examined in a multiple-dose study in healthy subjects. Rizatriptan (N = 24) (or placebo, N = 12) was administered as a single 10 mg dose, followed 48 hours later by administration of one 10 mg dose every 2 hours for three doses on 4 consecutive days, corresponding to the maximum daily dose for a migraine attack. The AUC of rizatriptan and its active N-monodesmethyl metabolite after three 10 mg doses was approximately threefold greater than the plasma concentrations following a single 10 mg dose. Metabolite profiles were similar after single and multiple doses. Adverse events during rizatriptan were mild and transient; similar events occurred during placebo, with a somewhat reduced incidence. Diastolic blood pressure tended to increase compared with placebo (approximately 5 mmHg), particularly on the first multiple-dose day (p < .01 vs. placebo). In conclusion, rizatriptan is well tolerated by healthy subjects during multiple-dose administration, with no unexpected accumulation of drug in plasma.",2000.0,0,0
56,10631628,Lack of pharmacokinetic interaction between sumatriptan and naproxen.,P Srinivasu; D Rambhau; B R Rao; Y M Rao,"Sumatriptan is a 5HT1D agonist used in the treatment of migraine. Nonsteroidal anti-inflammatory drugs, beta-blockers, and calcium channel-blocking antagonists are used in the prophylaxis of migraine. Hence, there is a need to investigate the interaction of these prophylactic drugs with sumatriptan. The interaction of sumatriptan with propranolol, flunarizine, pizotifen, and butorphanol were reported earlier. Naproxen is shown to be effective in prophylactic treatment of migraine. In this study, the authors have investigated the circadian rhythm effect of naproxen on the pharmacokinetics of sumatriptan at 1000 and 2200 hours. Twelve healthy volunteers were treated with 100 mg sumatriptan succinate either alone or along with 500 mg naproxen orally at either 1000 or 2200 hours in a randomized Latin square design with a washout period of 10 days. Serum samples were collected at predetermined time intervals and analyzed for unchanged sumatriptan by high-performance liquid chromatography. The pharmacokinetic parameters were calculated by using model-independent methods. Naproxen had no statistically significant (p > 0.05) effect on any pharmacokinetic parameters of sumatriptan both at 1000 and 2200 hours treatment. The results of this study suggest that no alteration in the sumatriptan dosage will be necessary for migraine patients taking naproxen prophylactic therapy.",2000.0,0,0
57,10636142,"Eletriptan in acute migraine: a double-blind, placebo-controlled comparison to sumatriptan. Eletriptan Steering Committee.",P J Goadsby; M D Ferrari; J Olesen; L J Stovner; J M Senard; N C Jackson; P H Poole,"To compare the efficacy, safety, and tolerability of oral eletriptan (20 mg, 40 mg, and 80 mg) with that of oral sumatriptan (100 mg) and placebo for the acute treatment of migraine. Eletriptan is a potent and selective agonist at human recombinant 5HT1B/1D receptors, with efficacy in animal models that predict antimigraine activity. In healthy volunteers, the pharmacokinetics of eletriptan are characterized by linear and rapid oral absorption. Randomized, double-blind, parallel-group study conducted in 857 outpatients with a diagnosis of migraine according to the International Headache Society (IHS) criteria. Of these, 692 took study medication for one acute migraine attack and provided on-drug efficacy data. Subjects received either placebo, 100 mg of sumatriptan or 20 mg, 40 mg, or 80 mg of eletriptan for the treatment of an acute migraine attack. The primary endpoint was the percentage of patients with a headache response (improvement in pain intensity from moderate or severe to mild or none) at 2 hours after treatment. At the primary endpoint (2 hours after dosing), headache response rates were 24% (30/126) for placebo; 55% (63/115) for sumatriptan, 100 mg; 54% (70/129) for eletriptan, 20 mg; 65% (76/117) for eletriptan, 40 mg; and 77% (91/118) for eletriptan, 80 mg. There was a difference compared with placebo (p<0.001) for all doses of eletriptan, and at 2 hours there was a difference between sumatriptan, 100 mg, and eletriptan, 80 mg (p<0.001). Headache-free rates at 2 hours were superior to placebo (6%; p<0.001) for both the 80-mg dose of eletriptan (37%) and the 40-mg dose (29%), with the 80-mg dose also being superior to 100 mg of sumatriptan (23%; p<0.05). Eletriptan and sumatriptan were well tolerated, and the majority of adverse events were mild or moderate in intensity and transient. In this placebo-controlled trial, eletriptan, at selected doses, demonstrated superior efficacy, onset of action and patient acceptability in the acute treatment of migraine when compared with oral sumatriptan and placebo.",2000.0,1,1
58,10643958,Newer intranasal migraine medications.,C D Logemann; L M Rankin,"Two new intranasal migraine medications, sumatriptan and dihydroergotamine mesylate, may offer specific advantages for patients who are seeking alternatives to various oral or parenteral migraine abortive therapies. Placebo-controlled clinical studies demonstrate that both intranasal forms are effective in relieving migraine headache pain, but published clinical trial information comparing these two intranasal medications with current abortive therapies is lacking. Both agents are generally well tolerated by patients, with the exception of mild, local adverse reactions of the nose and throat.",2000.0,0,0
59,10649829,The relationship between repetitive behaviors and growth hormone response to sumatriptan challenge in adult autistic disorder.,E Hollander; S Novotny; A Allen; B Aronowitz; C Cartwright; C DeCaria,"Autism is heterogeneous with respect to clinical symptoms and etiology. To sort out this heterogeneity in autism, we investigated whether specific neurobiological markers vary in parallel to core symptomatology. Specifically, we assessed growth hormone response to the 5-HT 1d agonist, sumatriptan, and linked this measure of serotonergic function to the severity of repetitive behaviors in adult autistic patients. Eleven adult patients with autism or Asperger's disorder were randomized to single dose sumatriptan (6 mg SQ) and placebo challenges, separated by a one-week interval. In adult autistic disorders, severity of repetitive behaviors at baseline, as measured by YBOCS-compulsion score, significantly positively correlated with both peak delta growth hormone response and area under the curve growth hormone response to sumatriptan. Thus, the severity of a specific behavioral dimension in autism (repetitive behaviors) parallels the sensitivity of the 5-HT 1d receptor, as manifest by sumatriptan elicited GH response.",2000.0,0,0
60,10652116,Influence of a 5HT1 receptor agonist on gastric accommodation and initial transpyloric flow in healthy subjects.,S Vingerhagen; T Hausken; O H Gilja; A Berstad,"Sumatriptan, a 5HT1 receptor agonist, inhibits antral motor activity, delays gastric emptying and relaxes the gastric fundus. The aim of this study was to characterize the effect of sumatriptan on transpyloric flow and gastric accommodation during and immediately after ingestion of a liquid meal using duplex sonography. Ten healthy subjects were investigated twice on separate days. In random order either sumatriptan 6 mg (Imigran 0.5 mL) or a placebo were given s.c. 15 min before ingesting 500 mL of a meat soup. The subjects were examined during the 3-min period before ingestion of the liquid meal, the 3-min spent drinking the meal and 10 min postprandially. Sumatriptan caused a significant widening of both the gastric antrum (P=0.02) and the proximal stomach (P=0.01) 10 min postprandially as compared with placebo. It caused no significant differences in time to initial gastric emptying (P=0.2), but significantly delayed commencement of peristaltic-related transpyloric flow (P=0.04). Sumatriptan had no significant effect on mean abdominal symptom scores, but after sumatriptan there was a significant negative correlation between width of postprandial antral area and postprandial nausea and between width of postprandial antral area and postprandial bloating. We therefore conclude that sumatriptan causes a postprandial dilatation of both the distal and the proximal stomach with no change in dyspeptic symptoms nor in length of time to first gastric emptying. Time to commencement of peristaltic-related emptying is delayed.",2000.0,0,0
61,10669900,"Efficacy and safety of sumatriptan 50 mg in patients not responding to standard care, in the treatment of mild to moderate migraine. The Sumatriptan 50 mg Italian Study Group.",L A Pini; L Fabbri; L Cavazzuti,"The tolerability and efficacy of oral sumatriptan 50 mg for the treatment of mild to moderate migraine attacks were assessed in a double-blind, multicenter placebo-controlled study on a group of patients who had not responded sufficiently to analgesic preparations. Three-hundred-and-twenty-eight migraine sufferers treated a first migraine attack with a nontriptan standard care medication: a mixture containing phenazone, butalbital and caffeine (optalidon) or indomethacin plus prochlorperazine plus caffeine (difmetre) or paracetamol 100 mg (tachipirine), depending on their habits. Of these patients, 32.6% reported headache relief with this treatment and were not included in phase II of the study. The 219 patients not reporting relief during the first phase of the study entered the second phase and were randomized to sumatriptan 50 mg or to placebo; 167 of these patients treated a second attack according to the protocol and were evaluated for efficacy. Of the patients with migraine taking sumatriptan, 58% reported headache relief compared with 35% of placebo-treated patients (p = 0.008). The reduction of nausea and vomiting was significantly better in the sumatriptan group. No differences were detected for the recurrence rate, while rescue medication was used more by the placebo group. The safety profile of sumatriptan 50 mg was confirmed. This study demonstrates the usefulness of this dose of oral sumatriptan against the pain and the accompanying symptoms of mild and moderate migraine.",2000.0,0,1
62,10690725,Percutaneous retrogasserian glycerol rhizolysis for treatment of chronic intractable cluster headaches: long-term results.,D R Pieper; J Dickerson; S J Hassenbusch,"To analyze the long-term effectiveness and safety of percutaneous retrogasserian glycerol rhizolysis (PRGR) in the treatment of medically refractive chronic cluster headache (CH). The current mainstay of surgical intervention for these patients is percutaneous radiofrequency retrogasserian rhizotomy (PRFR). However, when performed for V1 distribution pathology, PRFR can lead to corneal anesthesia, which places the patient at risk for future visual loss. It also increases the risk of facial dysesthesia. In a prospective, consecutive series, 18 patients with intractable CH were followed for a mean of 5.2 years (range, 40-78 mo) after they had undergone PRGR, performed using a standard technique. The significance of this technique as an alternative to PRFR is that it should result in a lower rate of both corneal and facial anesthesia and provide an acceptable degree of pain relief. Fifteen patients (83%) obtained immediate pain relief after one or two injections; the majority of them experienced relief after the first injection. CH recurred in seven patients (39%) over the course of the study. Two of these patients received a second injection, and both met with equal success. Two other patients underwent PRFR. Excluding those who underwent PRFR, the overall daily headache frequency decreased from 3.5 +/- 0.3 attacks per day preoperatively to 0.6 +/- 0.2 attacks per day at last follow-up. The severity of these headaches, as assessed by verbal pain scales, also decreased from 10 preoperatively to 4.4 +/- 1.4 at follow-up. None of the patients, including those who required a second procedure, experienced corneal anesthesia or facial dysesthesia. This study provides the first long-term evaluation of PRGR for the treatment of medically refractive chronic CH and lends support to both the safety and long-term efficacy of this procedure. Further investigations are needed to compare directly the relative efficacy and safety of PRGR and PRFR.",2000.0,0,0
63,10692716,Defining optimal dosing for sumatriptan tablets in the acute treatment of migraine.,N T Mathew; R Salonen,"Oral sumatriptan, which is a well tolerated, effective acute treatment for migraine, and is selectively available in different countries in 100 mg, 50 mg, and 25 mg tablets. The first large dose-ranging study compared the 100 mg dose to higher doses (200 mg and 300 mg) and found it to be just as efficacious and better tolerated. The first studies comparing the 100 mg dose to lower doses (25 mg and 50 mg) found them all to be similar in effectiveness and tolerability. However, a larger definitive study found that the 100 mg and 50 mg doses offered better efficacy than the 25 mg dose, whereas the 25 mg and 50 mg doses were better tolerated than the 100 mg dose. Thus the 50 mg dose appears to offer the best ratio of efficacy to tolerability. Many patients, though, prefer or require the 100 mg dose and tolerate it well. Allowed to select dosing themselves, patients tend to migrate to the 100 mg dose.",2000.0,0,0
64,10692717,A double-blind placebo-controlled study assessing the efficacy and tolerability of 50 mg sumatriptan tablets in the acute treatment of migraine. Sumatriptan Tablets S2CM07 Study Group.,N Savani; N J Brautaset; M Reunanen; I Szirmai; E A Ashford; H Hassani; J Saiers,"Oral sumatriptan 50 mg has been found to have good efficacy and tolerability in the acute treatment of migraine but has been less well studied than the 100 mg dose. This was a double-blind, parallel-group study (Glaxo Wellcome protocol number S2CM07) comparing the efficacy and safety of sumatriptan 50 mg tablets with placebo in the acute treatment of migraine. Patients treated three migraine attacks with study medication; a second, optional dose was available for treating recurrent headache. Of the 560 patients randomized, 485 treated at least one attack, 411 at least two attacks, and 362 three attacks. The primary efficacy measure was the proportion of patients who had obtained complete or almost complete headache relief at 4 h after dosing. For all attacks, a significantly greater proportion of patients experienced headache relief at 4 h with sumatriptan 50 mg tablets than with placebo (59% to 62% versus 32% to 42%; P = 0.005). The same was true at 3 h across all attacks, and at 2 h for attacks 1 and 2 (49% versus 23% and 45% versus 29%, respectively). Although sumatriptan and placebo were associated with similar incidences of recurrence, sumatriptan was associated with a longer time to recurrence. The incidence of adverse events with sumatriptan was similar to that with placebo, and there was no increase in adverse events associated with use of a second dose to treat recurrence. Sumatriptan 50 mg tablets are well tolerated and efficacious in relieving migraine headache.",2000.0,0,1
65,10692718,"Patient preference for oral sumatriptan 25 mg, 50 mg, or 100 mg in the acute treatment of migraine: a double-blind, randomized, crossover study. Sumatriptan Tablets S2CM11 Study Group.",R Salonen; E A Ashford; M Gibbs; H Hassani,"Dosing recommendations for oral sumatriptan have ranged from 25 mg to 100 mg. Patient dose preferences are clinically relevant (perhaps moreso than traditional efficacy endpoints) and deserve study. A multinational randomized double-blind crossover study was conducted over 18 weeks to assess patient dose preference, efficacy, and tolerability for oral sumatriptan (25 mg, 50 mg, and 100 mg) in the acute treatment of migraine; 257 patients treated three attacks, using a different dose for each. The 100 mg dose was preferred by 35% of patients, 31% the 50 mg dose, and 25% the 25 mg dose. Efficacy and speed of action were the two main reasons given for preferring the higher doses. Compared with the 25 mg dose, the 100 mg and 50 mg doses were significantly more likely to provide headache relief at 2, 3, and 4 h after dosing and complete headache resolution at 3 and 4 h after dosing (P < 0.027). Recurrence rates were similar for the three doses, ranging from 33% to 38%, though the median time to recurrence increased with dose, from 8.5 to 11.8 h. The 25 mg, 50 mg, and 100 mg doses were all well tolerated, with adverse event incidences of 19%, 21%, and 30%, respectively. Patients preferred the 50 mg and 100 mg doses of oral sumatriptan to the 25 mg dose, and the higher doses were more effective against migraine; however, the 25 mg and 50 mg doses were better tolerated than the 100 mg dose. Though the 50 mg dose probably has the best effectiveness-to-tolerability ratio, some patients clearly prefer a higher dose.",2000.0,0,1
66,10692719,Patient-selected dosing in a six-month open-label study evaluating oral sumatriptan in the acute treatment of migraine. Sumatriptan Tablets S2CM10 Study Group.,A J Dowson; E A Ashford; S Prendergast; H Hassani; G W Roberts; T Flöter; A Szczudlik,"Dosing recommendations for oral sumatriptan as acute treatment for migraine have ranged from 25 mg to 100 mg. Patient dose preferences have not been studied in a setting mimicking clinical practice. In an open-label study evaluating patient acceptance and the relative efficacy and safety of 25 mg, 50 mg, and 100 mg doses of oral sumatriptan over a period of six months, 338 patients treated three migraine attacks with 50 mg sumatriptan and then were allowed to double or halve the dose. After treating another three attacks, they were again allowed to adjust the dose by one level. After migraine attack 3, 37% of patients chose to continue with the 50 mg dose, 50% increased the dose to 100 mg, and 12% decreased it to 25 mg. After attack 6, 8%, 33%, and 58% of patients chose the 25 mg, 50 mg, and 100 mg doses, respectively; only 3% of those taking the 100 mg dose chose to reduce it. Overall, the mean percentages of attacks per patient in which headache relief had been obtained 4 h after dosing were 71%, 71%, and 80% for the 25 mg, 50 mg, and 100 mg doses, respectively. Patients who decreased the dose to 25 mg after attack 3 experienced decreases both in adverse events and percentage of attacks with headache relief, whereas in those who increased the dose to 100 mg, likelihood of headache relief increased but the incidence of adverse events did not. More patients chose the 50 mg or 100 mg dose than the 25 mg dose. All three doses had similar efficacy and tolerability.",2000.0,0,0
67,10692752,A dose-defining study of sumatriptan suppositories in the acute treatment of migraine.,L Bertin; N Brion; M Färkkilä; H Göbel; P Wessely,"In this dose-ranging, randomised, multinational, multicentre, double-blind, placebo-controlled, parallel group study, 431 patients treated a single migraine attack with study medication: sumatriptan suppository 6 mg, 12.5 mg, 25 mg, 50 mg, 100 mg, or placebo. Patients were treated in the clinic with a single dose in suppository form. All doses of sumatriptan, except 6 mg, were significantly better than placebo (p < 0.004) and achieved similar rates of headache relief within two hours of dosing. The highest response rate was in the 25 mg group (72%) compared with placebo (37%) (p < 0.001). Fewer patients required rescue medication in the active groups (1% 100 mg to 13% 6 mg) compared with placebo (17%), and more patients were able to work and function normally two hours after dosing (41%, 100 mg; 20%, placebo). The overall incidence of adverse events was similar in the placebo, 6 mg and 12.5 mg groups (14-17%) but higher in the 25 mg, 50 mg and 100 mg groups (25%, 32% and 29% respectively). Analysis of plasma sumatriptan levels indicated rapid rectal absorption for all doses (median tmax = 1.0 hr). It is concluded that sumatriptan, in doses above 6 mg, is an effective and well tolerated treatment for acute migraine. From this study doses of 12.5 mg and 25 mg sumatriptan were identified as having the best efficacy/safety profile and were evaluated further.",2000.0,0,0
68,10709161,"A double-blind, placebo-controlled evaluation of the effect of oral doses of rizatriptan 10 mg on oral contraceptive pharmacokinetics in healthy female volunteers.",C R Shadle; G Liu; M R Goldberg,"Rizatriptan (MAXALT), a potent, oral 5-HT1B/1D agonist with a rapid onset of action, is available now for the acute treatment of migraine. This study examined the pharmacokinetic and clinical interaction between rizatriptan 10 mg and the components (ethinyl estradiol [EE] 35 micrograms and norethindrone [NET] 1.0 mg) of a well-established oral contraceptive combination product, ORTHO-NOVUM 1/35. Levels of sex hormone binding globulin (SHBG), a protein increased by EE to which NET binds, were also examined. In this two-period crossover study, 20 healthy young female subjects received a coadministration of 8 days of rizatriptan treatment (6 days of single-dose 10 mg rizatriptan and 2 days of multiple-dose rizatriptan, 10 mg q 4 hours for three doses, giving a total daily dose of 30 mg on Days 7 and 8) or matching placebo along with their daily dose (one tablet) of ORTHO-NOVUM 1/35 within their oral contraceptive cycle. Plasma was sampled for EE, NET, and SHBG concentrations. Safety evaluations included routine laboratory safety studies, physical examinations, and monitoring for ECG, vital signs, and adverse events. There were no statistically significant differences in any of the pharmacokinetic parameters of EE or NET between the rizatriptan and placebo treatment periods, thus indicating that rizatriptan had no meaningful effect on the disposition of either the EE or the NET component of ORTHO-NOVUM 1/35. The SHBG concentration did not change throughout the entire study. Clinically, coadministration of rizatriptan with ORTHO-NOVUM 1/35 was well tolerated. Blood pressure, heart rate, and temperature showed no consistent trend or clinically important changes. Adverse events following coadministration of rizatriptan with ORTHO-NOVUM 1/35 were similar to those reported when placebo was given with ORTHO-NOVUM 1/35. The findings of this study indicate that there is little potential for dosages as high as 30 mg/day, the maximum recommended dosing schedule, of rizatriptan to alter the plasma concentrations of oral contraceptives.",2000.0,0,0
69,10716674,Influence of sumatriptan on gastric fundus tone and on the perception of gastric distension in man.,J Tack; B Coulie; A Wilmer; A Andrioli; J Janssens,"In animals, activation of 5-HT(1) like receptors causes a relaxation of the gastric fundus through the activation of intrinsic inhibitory neurones. To investigate the effect of sumatriptan, an agonist at enteric neuronal 5-HT(1) receptors, on fasting fundus tone and sensitivity to gastric distension in man. A gastric barostat was used to study the effect of placebo and sumatriptan, 6 mg subcutaneously, on basal fundic tone in healthy subjects. In addition, stepwise isobaric and isovolumetric gastric distensions were performed and perception was measured before and after the administration of placebo and sumatriptan. Placebo had no significant effects on gastric tone and on perception. Sumatriptan induced an immediate relaxation of the gastric fundus, reflected by an intragastric volume increase of 209 (39) ml (p<0.0005). After sumatriptan, intragastric pressures at the thresholds for perception or discomfort were not significantly altered. However, the intragastric volumes and the corresponding calculated wall tensions at perception and discomfort thresholds were significantly increased. Administration of the 5-HT(1) receptor agonist sumatriptan induces a relaxation of the gastric fundus in man, allowing larger intragastric volumes before thresholds for perception or discomfort are reached. The effects of sumatriptan on the gastric fundus may have therapeutic potential in the treatment of patients with functional dyspepsia.",2000.0,0,0
70,10746617,Verapamil in the prophylaxis of episodic cluster headache: a double-blind study versus placebo.,M Leone; D D'Amico; F Frediani; F Moschiano; L Grazzi; A Attanasio; G Bussone,"The authors performed a double-blind, double-dummy study to compare the efficacy of verapamil with placebo in the prophylaxis of episodic cluster headache. After 5 days' run-in, 15 patients received verapamil (120 mg tid) and 15 received placebo (tid) for 14 days. The authors found a significant reduction in attack frequency and abortive agents consumption in the verapamil group. Side effects were mild. These findings provide objective evidence for the effectiveness of verapamil in episodic cluster headache prophylaxis.",2000.0,0,0
71,10752697,Triptans and migraine.,D N Bateman,,2001.0,0,0
72,10759911,A comparative trial of zolmitriptan and sumatriptan for the acute oral treatment of migraine.,R M Gallagher; G Dennish; E L Spierings; R Chitra,"This randomized, double-blind, parallel group multicenter study compared response rates and tolerability of zolmitriptan with sumatriptan in the acute treatment of migraine. A sample consisting of 1445 outpatients with an established diagnosis of migraine was randomized to zolmitriptan, 2.5 mg or 5 mg, or sumatriptan, 25 mg or 50 mg. Patients took 1 tablet for moderate/severe migraine and a second identical tablet, if necessary, for recurrent headache of moderate/severe intensity 4 to 24 hours after the initial dose. Up to six attacks were treated during a 6-month period. The primary outcome measure was headache response 2 hours after the initial dose. Secondary end points included 1-hour and 4-hour headache response and pain relief over 24 hours. A headache response at 2 hours was noted in 67.1% of patients taking zolmitriptan, 2.5 mg, and 64.8% of those taking zolmitriptan, 5 mg, versus 59.6% of patients taking sumatriptan, 25 mg, and 63.8% of those taking sumatriptan, 50 mg. At 2 and 4 hours, the differences between zolmitriptan, 2.5 mg, and sumatriptan, 25 mg, were statistically significant (odds ratio=1.49 and 1.67, respectively; both P<.001). Statistically significant differences between zolmitriptan, 2.5 mg, and sumatriptan, 50 mg, were seen at 2 and 4 hours post dose (odds ratio=1.21 and 1.23, respectively; both P<.05). At 1 hour post dose, the headache response rate for zolmitriptan, 2. 5 mg, was numerically higher than response rates for sumatriptan, 25 mg and 50mg (odds ratio=1.16, odds ratio=1.06, though they failed to reach statistical significance; P=.061, P=.461 respectively). Differences between zolmitriptan, 5 mg, and sumatriptan, 25 mg, were statistically significant at 1, 2, and 4 hours (odds ratio=1.43, 1. 46, and 1.78, respectively; all P<.001) and at 1 and 4 hours versus sumatriptan, 50 mg (odds ratio=1.28, P=.002; odds ratio=1.29, P=.012, respectively). Although not statistically significant at 2 hours, more patients responded to zolmitriptan, 5 mg, than to sumatriptan, 50 mg (odds ratio=1.16, P=.064). Patients receiving zolmitriptan, 2. 5 mg or 5 mg, achieved more pain relief over 24 hours than patients receiving sumatriptan, 25 mg (odds ratio=1.47, and 1.54 respectively, both P<.001) or sumatriptan, 50 mg (odds ratio=1.17, P=.021; odds ratio=1.22, P=.005, respectively). All treatments were well tolerated. Zolmitriptan, 2.5 mg and 5 mg, was at least as effective as sumatriptan, 25 mg or 50 mg, for all parameters studied. Zolmitriptan, 2.5 mg, was significantly more effective than sumatriptan, 50 mg, in terms of headache response at 2 and 4 hours. Patients taking zolmitriptan were significantly more likely to have pain relief over 24 hours than those taking sumatriptan.",2000.0,1,1
73,10759937,Sumatriptan in patients with postdural puncture headache.,N R Connelly; R K Parker; A Rahimi; C S Gibson,"To determine the efficacy of sumatriptan in the management of patients presenting for an epidural blood patch for the management of postdural puncture headache. Postdural puncture headache can be quite severe, requiring invasive therapy (ie, epidural blood patch). Sumatriptan has been used successfully in patients with postdural puncture headache, however, its use has not been investigated in a controlled fashion. Ten patients with postdural puncture headache presenting for an epidural blood patch were given either saline or sumatriptan subcutaneously. The severity of the headache was evaluated at baseline and 1 hour following injection. If the headache remained severe, an epidural blood patch was performed. Only one patient in each group received relief from the injection. We do not recommend sumatriptan in patients who have exhausted conservative management of postdural puncture headache.",2000.0,0,0
74,10787112,Placebo effect in the acute treatment of migraine: subcutaneous placebos are better than oral placebos.,A J de Craen; J G Tijssen; J de Gans; J Kleijnen,"We carried out a meta-analysis of 22 trials to determine the comparative placebo effect of (a) subcutaneous vs. oral and (b) in-hospital vs. at-home administration in the treatment of migraine. The headache relief rates were combined from the placebo arms of these randomised clinical trials assessing the value of sumatriptan in acute treatment of migraine. The main outcome measure was the proportion of patients reclassified from severe or moderate headache severity to no or mild headache severity 2 h after the beginning of treatment. In the oral regimen 222 of 865 patients (25.7%) reported no or mild headache severity after 2 h, compared to 279 of 862 patients (32.4%) of those receiving subcutaneous placebo (6.7% difference; 95% CI 2.4-11.0%). Adjusting for treatment setting and severity of headache at baseline did not change the observed difference. After placebo treatment at home 285 of 1,054 patients (27.0%) reported no or mild headache severity after 2 h, compared to 216 of 673 patients (32.1%) among those receiving placebo in hospital (5.1 % difference; 95% CI 0.6-9.5%). When adjusted for route of administration and severity of headache at baseline, the difference in relief rates between home and hospital setting disappeared. These findings indicate that subcutaneous administration enhances the placebo effect of acute treatment of migraine. Future trials of antimigraine drugs assessing the relative efficacy of various routes of administration should use a double-dummy technique. The interpreting of placebo-controlled trial results must therefore consider that the effect in the drug arm of the trial depends in part on the route of administration.",2000.0,0,1
75,10802793,Oral zolmitriptan is effective in the acute treatment of cluster headache.,A Bahra; M J Gawel; J E Hardebo; D Millson; S A Breen; P J Goadsby,"To evaluate the efficacy and tolerability of oral zolmitriptan 5 mg and 10 mg and placebo in cluster headache. A multicenter, double-blind, randomized, three-period, crossover, outpatient study. Adult patients received placebo and zolmitriptan 5 mg and 10 mg orally for the acute treatment of episodic or chronic cluster headache. Headache intensity was rated by a five-point scale: none, mild, moderate, severe, or very severe. Patients only treated moderate to very severe headaches. The primary efficacy measure was headache response (two-point or greater reduction from baseline in the cluster headache rating scale) at 30 minutes. Secondary efficacy measures included proportion of patients with initial headache relief within 15 and 30 minutes, mild or no pain at 30 minutes, meaningful headache relief, and use of escape medication. A total of 124 patients took at least one dose of study medication, with 73% having episodic and 27% chronic cluster headache. For the primary endpoint, there was a treatment-by-cluster-headache-type interaction (p = 0.0453). Therefore, results are presented separately for chronic and episodic cluster headache. In patients with episodic cluster headache, the difference between zolmitriptan 10 mg and placebo at 30 minutes reached significance (47% versus 29%; p = 0.02). Mild or no pain at 30 minutes was reported by 60%, 57%, and 42% patients treated with zolmitriptan 10 mg, zolmitriptan 5 mg, and placebo (both p </= 0.01 versus placebo). For all other secondary endpoints, zolmitriptan 10 mg was significantly superior to placebo in episodic cluster headache patients, whereas zolmitriptan 5 mg was significantly superior to placebo for three of the four secondary endpoints. In patients with chronic cluster headache, response rates following zolmitriptan 5 mg or 10 mg were not significantly different from placebo at any endpoint. Zolmitriptan 5 mg and 10 mg were well tolerated. Oral zolmitriptan is efficacious in episodic cluster headache.",2000.0,0,1
76,10808042,,,,,0,0
77,10814600,Sumatriptan reduces exercise capacity in healthy males: a peripheral effect of 5-hydroxytryptamine agonism?,G P McCann; H Cahill; S Knipe; D F Muir; P D MacIntyre; W S Hillis; W S Hills,"5-Hydroxytryptamine (5-HT; serotonin) has been implicated in the perception of exercise-induced fatigue. Sumatriptan is a selective 5-HT(1B/D) receptor agonist which does not cross the blood-brain barrier. The aim of the present study was to determine the effect of sumatriptan on exercise capacity. Ten healthy male subjects (mean age 28.4+/-10.8 years) performed a maximal treadmill exercise test according to the Bruce protocol with expired gas analysis on two occasions. Either 6 mg of sumatriptan or placebo was administered subcutaneously in a randomized, double-blind, placebo-controlled, cross-over design. Exercise time was greater after placebo compared with sumatriptan [914 and 879 s respectively; 95% confidence interval (CI) of difference 12.1 s, 59.1 s; P = 0.008]. There was no significant effect on peak oxygen consumption (placebo, 50.6+/-6.3 ml.min(-1).kg(-1); sumatriptan, 51.7+/-7.6 ml.min(-1).kg(-1)). Sumatriptan administration resulted in decreases in both heart rate (sumatriptan, 188+/-14 beats/min, placebo, 196+/-12 beats/min; 95% CI of difference 12.6, 2.6; P = 0.008) and respiratory exchange ratio (sumatriptan, 1.23+/-0.06; placebo, 1.26+/-0.07; 95% CI of difference 0.05, 0.01; P = 0.01) at peak exercise. There were no significant differences in blood pressure, heart rate or submaximal oxygen consumption between sumatriptan and placebo treatments at any stage of exercise. Thus sumatriptan reduces maximal exercise capacity in normal males. The failure to demonstrate any haemodynamic or cardiorespiratory effect suggests that sumatriptan enhances perception of fatigue by a peripheral mechanism affecting 5-HT modulation.",2000.0,0,0
78,10817444,Comparison of the efficacy of zolmitriptan and sumatriptan: issues in migraine trial design.,G Geraud; J Olesen; V Pfaffenrath; P Tfelt-Hansen; R Zupping; H C Diener; R Sweet,"In this international, multicentre, double-blind, placebo-controlled, single attack study, 'triptan naive' migraine patients were randomized in an 8:8:1 ratio to receive zolmitriptan 5 mg, sumatriptan 100 mg or placebo. The all-treated analysis included 1058 patients who took study medication. The primary endpoint, complete headache response, was reported by 39%, 38% and 32% of patients treated with zolmitriptan, sumatriptan and placebo, respectively, with no significant difference between treatment groups. In patients with moderate headache at baseline, complete response was significantly greater following zolmitriptan than after placebo (48% vs. 27%; P=0.01); there was no significant difference between sumatriptan and placebo groups (40% vs. 27%). In patients with severe baseline headache (where a greater reduction in headache intensity is required for a headache response), there was no significant difference between any groups in complete headache response rates. For secondary endpoints, active treatment groups were significantly superior to placebo for: 1-, 2- and 4-h headache response (e.g. 2-h headache response rates: zolmitriptan 59%; sumatriptan 61%; placebo 44%; P < 0.01 vs. placebo); pain-free response rates at 2 and 4 h; alleviation of nausea and vomiting; use of escape medication and restoration of normal activity. The incidence of adverse events was similar between zolmitriptan and sumatriptan groups but was slightly lower in the placebo group. The lack of difference between active treatments and placebo for complete response probably reflects the high placebo response obtained, which is probably a result of deficiencies in trial design. For example, the randomization ratio may result in high expectation of active treatment. Thus, while ethically patient exposure to placebo should be minimized, this must be balanced against the scientific rationale underpinning study design.",2000.0,1,1
79,10817445,Effects of the anti-migraine drug sumatriptan on muscle energy metabolism: relationship to side-effects.,M D Boska; K M Welch; L Schultz; J Nelson,"Sumatriptan succinate (Imitrex) is a 5-HT (5-hydroxytryptamine) agonist used for relief of migraine symptoms. Some individuals experience short-lived side-effects, including heaviness of the limbs, chest heaviness and muscle aches and pains. The effects of this drug on skeletal muscle energy metabolism were studied during short submaximal isometric exercises. We studied ATP flux from anaerobic glycolysis (An Gly), the creatine kinase reaction (CK) and oxidative phosphorylation (Ox Phos) using 31P nuclear magnetic resonance spectroscopy (31P MRS) kinetic data collected during exercise. It was found that side-effects induced acutely by injection of 6 mg sumatriptan succinate s.c. were associated with reduced oxygen storage in peripheral skeletal muscle 5-20 min after injection as demonstrated by a transient reduction in mitochondrial function at end-exercise. These results suggest that mild vasoconstriction in peripheral skeletal muscle is associated with the action of sumatriptan and is likely to be the source of the side-effects experienced by some users. Migraine with aura patients were more susceptible to this effect than migraine without aura patients.",2000.0,0,0
80,10830342,Are the triptans for migraine therapy worth the cost?,W J Becker,The triptans represent a major advance in migraine therapy but their cost per dose greatly exceeds that of many older treatments. There is evidence that for a significant proportion of migraine patients these new drugs can show a positive cost benefit and also improve quality of life. Cost benefit would be expected to be greatest in patients with more severe migraine attacks.,2000.0,0,0
81,10840172,Low dose zolmitriptan as a 5-HT neuroendocrine challenge agent in humans.,F G Moeller; J M Bjork; D M Dougherty; L D Van de Kar; D M Marsh; A C Swann,"The 5-HT1B/D agonist sumatriptan has been used in a number of studies as a neuroendocrine challenge agent. Whether its neuroendocrine effects are centrally mediated is unclear, however, since sumatriptan shows minimal penetration of the central nervous system. Zolmitriptan shows a greater penetration into the central nervous system than sumatriptan, and has recently been shown to be an effective challenge agent. In order to determine the neuroendocrine, temperature and side effects of a 2.5 mg oral dose of zolmitriptan, 17 healthy volunteers underwent a placebo controlled, repeated measures, double blind neuroendocrine challenge. Zolmitriptan or placebo were administered, and cortisol, growth hormone, prolactin, blood pressure and temperature, were measured over four hours after the dose of zolmitriptan. Zolmitriptan at this dose was well tolerated by all subjects, with minimal side effects and only minor effects on blood pressure. There was a significant increase in serum growth hormone after zolmitriptan compared to placebo, however there were no significant effects on cortisol, prolactin or oral temperature. The neuroendocrine effects of 2.5 mg of orally administered zolmitriptan are similar to previously reported effects of sumatriptan, with minimal side effects.",2000.0,0,0
82,10848058,Zolmitriptan: new product.  Similar to sumatriptan.,,"(1) Zolmitriptan is an antimigraine drug similar to sumatriptan. (2) The clinical file mainly comprises placebo-controlled dose-finding studies recommending an optimal oral dose of 2.5 mg. (3) Zolmitriptan has been compared with sumatriptan in a trial that showed no difference in efficacy.  In particular, the recurrence rate of headache after initial relief was not lower on zolmitriptan than on sumatriptan. (4) The safety profile of zolmitriptan is similar to that of sumatriptan.  The contraindications relating to a history of cardiovascular disease must be respected because of the vasoconstrictive effect of the drug. (5) Zolmitriptan has the same drug interactions as sumatriptan.  Moreover, zolmitriptan should not be used during migraine attacks by patients on propranolol.",2000.0,0,0
83,10849030,Rizatriptan tablet versus wafer: patient preference.,J U Adelman; L K Mannix; R L Von Seggern,"After taking both conventional oral rizatriptan tablets and oral disintegrating rizatriptan tablets in the treatment of migraine with or without aura, patients were permitted to select their formulation preference. All adult patients who had requested continuation of rizatriptan during a 6-month period were included in the study. Of the 367 patients studied, 188 selected the oral disintegrating tablet, while 179 preferred the conventional tablet. Although individual patients had strong preferences for one preparation over the other, no group preference was found.",2000.0,0,1
84,10849042,Treatment of nonresponders to oral sumatriptan with zolmitriptan and rizatriptan: a comparative open trial.,N T Mathew; J Kailasam; P Gentry; O Chernyshev,"In order to study the effect of zolmitriptan and rizatriptan in oral sumatriptan nonresponders (defined as lack of response in three or more of five attacks), 56 patients were studied in an open trial in a crossover fashion. Both zolmitriptan, 5 mg, and rizatriptan, 10 mg, were effective in the majority of sumatriptan nonresponders. The response to rizatriptan, 10 mg, appeared to be better than to zolmitriptan, 5 mg. Approximately 19% of sumatriptan nonresponders remained nonresponders to both zolmitriptan and rizatriptan.",2000.0,0,0
85,10869781,The pharmacology of headache.,P J Goadsby,"Headache is a common problem which besets most of us at some time or the other. The pharmacology of headache is complex in an overall sense but can be understood in terms of the anatomy and physiology of the pain-producing structures. Migraine can be used as a template to understand the activation of nociceptive systems in the head and thus their neurotransmitter mediation and modulation. In recent years, the role of serotonin (5-HT) in headache pharmacology has been unravelled in the context of both understanding its role in the nociceptive systems related to headache and by exploiting its 5-HT1 receptor subtypes in headache therapeutics. The pharmacology of the head pain systems, as they are known and as they might evolve, are explored in the context of both, the anatomy and physiology of trigeminovascular nociception and in the context of clinical questions, such as those of efficacy, headache recurrence and adverse events.",2001.0,0,0
86,10881257,Sleep disordered breathing in patients with cluster headache.,R D Chervin; S N Zallek; X Lin; J M Hall; N Sharma; K M Hedger,"To study subjects with active or inactive cluster headache (CH) for occult sleep disordered breathing (SDB). CH frequently occurs during sleep. The authors previously found that symptoms of SDB predicted reported occurrence of CH in the first half of the night, which suggested that CH could be triggered in some cases by unrecognized SDB. The authors performed polysomnography in 25 adults (22 men) with CH. Subjects were not selected for any sleep-related complaint. In addition to standard measures, studies included monitoring of end-tidal carbon dioxide (n = 22), and esophageal pressure (n = 20). The rate of apneas and hypopneas per hour of sleep was >5 in 20 subjects (80%; 95% CI, 64% to 96%), minimum oxygen saturation was <90% in 10 subjects, maximum negative esophageal pressure ranged from -13 to -65 cm H2O, and maximum end-tidal carbon dioxide was > or =50 mm Hg in eight subjects. The eight subjects with active (versus inactive) CH at the time of study had higher maximum end-tidal carbon dioxide levels (50 +/- 3 versus 44 +/- 5 mm Hg; p = 0.0007). More severe oxygen desaturation was associated with reports that CH typically occurred in the first half of the nocturnal sleep period (p = 0.008). SDB occurred in the majority of patients with CH. Evaluation of a patient with CH should include consideration that SDB may be present.",2000.0,0,0
87,10881915,Migraine revolution and sumatriptan.,J B Palmer; R Salonen,,2000.0,0,0
88,10890255,Rizatriptan in the treatment of migraine.,C G Dahlof; A M Rapoport; F D Sheftell; C R Lines,"Rizatriptan is a selective 5-hydroxytriptamine1B/1D receptor agonist that was launched in 1998 for the acute treatment of migraine in adults. Based on data from 6 large clinical trials in patients > or =18 years of age in whom migraine was diagnosed according to International Headache Society criteria, the marketed 10-mg and 5-mg oral doses of rizatriptan are effective in relieving headache pain and associated migraine symptoms. The 10-mg dose is more effective than the 5-mg dose. At 2 hours after dosing, up to 77% of patients taking rizatriptan 10 mg had pain relief compared with 37% of those taking placebo, up to 44% were completely pain free compared with 7% of those taking placebo, and up to 77% were free of nausea compared with 58% of those taking placebo (P < 0.05 for all 3 comparisons). Both doses of rizatriptan are generally well tolerated. In placebo-controlled studies involving treatment of a single migraine attack, the most common side effects (incidence > or =2%) occurred in <10% of patients, typically were transitory (2 to 3 hours), and were mild or moderate. Rizatriptan is an effective and well-tolerated acute treatment for migraine.",2000.0,0,0
89,10891894,Treatment of myasthenia gravis: A call to arms.,J T Kissel; G M Franklin,,2000.0,0,0
90,10891904,Autoantibodies to glutamic acid decarboxylase in patients with therapy-resistant epilepsy.,J Peltola; P Kulmala; J Isojärvi; A Saiz; K Latvala; J Palmio; K Savola; M Knip; T Keränen; F Graus,"Autoantibodies to glutamic acid decarboxylase (GAD-A) are present in type 1 diabetes and stiff man syndrome (SMS), and have also been reported in cerebellar ataxia. Epilepsy was present in 4 of 19 patients with SMS and GAD-A, implying that epilepsy sometimes is associated with anti-GAD autoimmunity. The authors investigated the prevalence of GAD-A in patients with therapy-resistant localization-related epilepsy (n = 51) and generalized epilepsy (n = 49) by a radiobinding assay. The positive samples were confirmed by immunohistochemistry and immunoblotting of recombinant human GAD65. GAD-A were found in eight patients with localization-related epilepsy, whereas none of the patients with generalized epilepsy, other neurologic disorders (n = 38), or the control subjects (n = 48) had GAD-A. Two patients had high levels of GAD-A, similar to SMS, whereas six patients had significantly lower titers, characteristic of type 1 diabetes. The two patients with high levels of GAD-A had GAD-A both in serum and CSF by immunohistochemistry and immunoblotting. Both of them had longstanding therapy-resistant temporal lobe epilepsy but did not have diabetes. One had a history of autoimmune disease, whereas the other had serologic evidence of multiple autoantibodies without any clinical signs of autoimmune disease. GAD autoimmunity may be associated with refractory localization-related epilepsy.",2000.0,0,0
91,10891912,Effect of naratriptan on myocardial blood flow and coronary vasodilator reserve in migraineurs.,T Gnecchi-Ruscone; X Bernard; P Pierre; D Anderson; N Legg; H Enahoro; P D Winter; A Crisp; J A Melin; P G Camici,"Migraine drugs can produce adverse cardiac effects. The authors have demonstrated previously that ergotamine can lead to a significant reduction of hyperemic myocardial blood flow, but little is known about the effect of the newer serotonin analogues. Coronary artery constriction caused by serotonin or its analogues is mediated mainly by 5HT2 receptors. The selective 5HT1B/1D agonist naratriptan has no significant activity at 5HT2 receptors; however, like all 5HT1B/1D agonists developed for the acute treatment of migraine, naratriptan could potentially constrict coronary arteries by activation of 5HT1B receptors. The effects on myocardial blood flow of subcutaneous naratriptan 1.5 mg compared with placebo were assessed under resting and hyperemic conditions with PET using oxygen-15 labeled water during two separate visits. This study was a randomized, double-blind, placebo-controlled crossover trial in 34 migraine subjects with no evidence of ischemic heart disease, studied outside a migraine attack. Naratriptan did not differ significantly from placebo in its effects on resting myocardial blood flow, but did evoke a small, significant fall in hyperemic myocardial blood flow (-13% versus placebo) and an increase in hyperemic coronary resistance (+19% versus placebo) without any signs or symptoms suggestive of myocardial ischemia. Naratriptan did not significantly affect the coronary vasodilator reserve (hyperemic/resting blood flow) compared with placebo. These results show that at therapeutic doses, naratriptan exerts only a minor effect on myocardial blood flow, coronary vasodilator reserve, or coronary resistance among subjects with no evidence of ischemic heart disease. These results should not be extrapolated to patients with coronary artery disease, in whom all 5HT1 agonists for migraine are contraindicated.",2000.0,0,0
92,10899408,,,,,0,0
93,10908770,Rizatriptan in the treatment of menstrual migraine.,S D Silberstein; H Massiou; C Le Jeunne; L Johnson-Pratt; K A McCarroll; C R Lines,"To determine the efficacy of oral rizatriptan 10 mg and 5 mg for treating menstrually associated migraine attacks. Data from two large clinical trials with identical designs were included in a retrospective analysis. The studies were randomized, double-masked, placebo-controlled, incomplete block, two-period, crossover designs. Women with migraines were randomly assigned to one of five treatment sequences for the treatment of two migraine attacks. Only data from the first attack in women with migraines who were treated with rizatriptan or placebo were included in the analysis. A menstrually associated attack was defined as one that occurred within 3 days before or after the onset of the last menstrual period. In the subgroup of 335 women with menstrually associated migraine, rizatriptan was effective compared with placebo. At 2 hours after dosing, 68% of 139 women taking rizatriptan 10 mg and 70% of 115 women taking rizatriptan 5 mg with a menstrually associated migraine had pain relief compared with 44% of 81 patients taking placebo (P <.05). In all women, rizatriptan was as effective in treating menstrual as well as nonmenstrual migraine: 68% of 139 patients taking rizatriptan 10 mg with a menstrually associated migraine had pain relief at 2 hours after dosing compared with 69% of 393 patients with nonmenstrually associated attacks (test of menstrual association = nonsignificant; the analysis had 80% power to detect a difference of six percentage points between groups). Similar results were found for rizatriptan 5 mg (menstrual = 70%, nonmenstrual = 66%; not statistically significant). Rizatriptan is effective in the treatment of menstrually associated migraine attacks.",2000.0,0,1
94,10920403,Naproxen sodium decreases migraine recurrence when administered with sumatriptan.,A V Krymchantowski,"Forty to 78% of the patients using sumatriptan for the acute treatment of migraine may present recurrence at least occasionally. The concomitant use of a NSAID (nonsteroidal anti-inflammatory drug) has been recommended to decrease the recurrence rate. Sixty seven patients that treated successfully 8 migraine attacks with 100 mg of sumatritpan PO and presented recurrence in at least 5 attacks were studied prospectively. The patients received 100 mg of sumatriptan and 550 mg of naproxen sodium PO to treat 4 consecutive moderate or severe migraine attacks. The recurrence rate, once at least 62.5% (5 out of 8 attacks), decreased to 14.2% (38 out of 268 attacks) with the combination of compounds (p<0.0001). We then studied two groups of 13 patients made randomicaly from the 67 initially evaluated, that were given sumatriptan 100 mg plus naproxen sodium 550 mg or placebo, in a double-blind design, to treat 3 other consecutive migraine attacks. Each group of patients treated 39 attacks. The recurrence among the patients taking sumatriptan plus placebo was 59% (23 out of 39 attacks) and the recurrence presented by the group taking sumatriptan plus naproxen was 25.5% (10 out of 39 attacks) (p<0.0003). We concluded that the combination of sumatriptan plus naproxen sodium decreases significantly migraine recurrence presented by patients taking sumatriptan alone.",2000.0,0,0
95,10927717,Evaluation of migraineurs' preferences for naratriptan over conventional first-line agents.,C Powers; S Szeto; D Pangtay; T Bort; M Cervi; R Cady,"To assess patient satisfaction with and preference for naratriptan hydrochloride therapy over previous ""nontriptan"" therapy for migraines. Open-label study conducted at 15 primary care clinics. One hundred forty-three adults meeting International Headache Society diagnostic criteria for migraine who were not using triptans as first-line therapy for migraines were enrolled; 115 completed the study. INTERVENTION AND OUTCOME ASSESSMENTS: At baseline, satisfaction with current migraine therapy was assessed. Patients were provided with naratriptan hydrochloride, 2.5 mg, to treat 3 migraines and diaries to record headache symptoms and response to treatment. After treating 3 migraines, satisfaction with naratriptan therapy and preference for either previous or naratriptan therapy were assessed. Eighty-nine (62%) of 143 patients had previous exposure to triptans, with lack of prescribing (55%) as the primary reason for not continuing their use as first-line therapy. Medications used for first-line therapy included simple analgesics (59%), combination products (46%), and narcotics (13%). After treating 3 migraines with naratriptan, satisfaction with migraine therapy increased from 47% to 75%. Sixty-three percent of patients preferred naratriptan therapy over their previous nontriptan therapy, 27% preferred their previous therapy, and 10% had no preference. The main reasons for preference for naratriptan therapy were ""relieves pain effectively"" (86%) and ""restores ability to function/perform task"" (81%). Naratriptan for first-line migraine therapy was preferred by most patients over previous nontriptan therapy.",2000.0,0,0
96,10935837,Pharmacological and behavioral treatment of pediatric migraine and tension-type headache.,L Grazzi; D D'Amico; M Leone; F Moschiano; G Bussone,"The problem concerning the treatment of pediatric headache has been the object of several recent reports. Some of the same medications used to treat adult headache problems are also utilized with children but usually at smaller dosages and in different combinations. The recent application of behavioral approaches, in particular biofeedback, for treatment of children's headaches has been an effective alternative to drugs without the problematic and dangerous side effects of pharmacological treatments. The purpose of this review is to give some indications about the most common pharmacological therapies for migraine and tension-type headache in children, and also to discuss the use of behavioral therapies, in particular biofeedback, as excellent alternatives to drugs.",2000.0,0,0
97,10940089,Naratriptan efficacy in migraineurs who respond poorly to oral sumatriptan.,S Stark; E L Spierings; S McNeal; G P Putnam; C P Bolden-Watson; S O'Quinn,"To determine whether 347 patients would respond to a 50-mg oral dose of sumatriptan, even though they considered themselves poor responders to this acute therapy for migraine, and to investigate whether oral naratriptan can be an effective acute therapy for migraine in the subset of patients who did not respond to sumatriptan under double-blind, well-controlled conditions. Although most migraineurs respond to sumatriptan, there remains a need for an effective alternative for those who do not respond. Naratriptan is a more potent and more lipophilic member of this class of agent and could prove beneficial in such patients. This is the first well-controlled study to assess the value of another 5-HT1B/1D agonist in this difficult patient subset. This study comprised two migraine attacks. The first (attack 1) was a single-blind assessment of the efficacy of sumatriptan (50 mg orally) in patients with a history of poor response to the drug. The second (attack 2) was a randomized, parallel group, double-blind, placebo-controlled trial of naratriptan (2.5 mg orally) in nonresponders to oral sumatriptan. Attack 1: About two thirds of this selected migraine population did not respond to sumatriptan. Attack 2: Naratriptan was statistically superior to placebo for headache relief at 2 hours and 4 hours, as well as for most other features of migraine attacks. These data suggest an intrinsic efficacy of naratriptan in this patient subset and not a coincidental response. No unexpected tolerability issues arose. Naratriptan is an alternative therapy for migraineurs who respond poorly to oral sumatriptan. No response to one ""triptan"" does not necessarily predict no response to them all.",2001.0,0,1
98,10940090,Comparative tolerability of oral 5-HT1B/1D agonists.,A W Fox,"To compare the relative tolerability of 5-HT1B/1D agonists and to investigate the relationships (if any) among systemic exposure, lipophilicity, and clinical tolerability for 5-HT1B/1D agonists. Post hoc correlations were sought among the following variables: absolute dose (= administered dose x oral bioavailability), Cmax, LogDpH7.4 (LogD), frequencies of all, neurological and dizziness/somnolence/drowsiness adverse events, adjusted for corresponding placebo-associated frequencies. For effective doses of all drugs with available data, absolute dose-response relationships exist for adverse event frequencies. The overall rank order of the frequency of adverse events was as follows: naratriptan < sumatriptan = rizatriptan < zolmitriptan. With the exception of eletriptan, 5-HT1B/1D agonists exhibit correlations between absolute dose, Cmax (R = 0.97), and LogD (R = 0. 71). For neurological and dizziness/somnolence/drowsiness adverse event frequencies, the overall rank order was sumatriptan < naratriptan < rizatriptan < zolmitriptan. Neither LogD nor absolute dose size predicted adverse event frequencies. Triptans may be distinguished in terms of their tolerability. Effectiveness, absolute dose size, and lipophilicity are related for the 5-HT1B/1D agonists considered here, except eletriptan. Adverse event frequencies cannot be predicted from in vitro measures of lipophilicity, in vivo estimates of absolute bioavailability, dose size, or any combination of these variables. Since these drugs are all agonists at 5-HT1B/1D receptors in the low nanomolar range, but differ in their tolerability profiles, adverse effects are not likely to be mediated through 5-HT1B/1D receptors. Drugs of this class must be studied individually and on a reasonably large scale in clinical development programs.",2001.0,0,0
99,10940093,Further development and testing of the migraine-specific quality of life (MSQOL) measure.,D L Patrick; B C Hurst; J Hughes,"To evaluate the longitudinal performance of the migraine-specific quality of life (MSQOL) instrument. Psychometric tests evaluated data obtained from 1383 migraineurs who completed the 20-item MSQOL questionnaire during a noncomparative, long-term, observational study of zolmitriptan (Zomig), 5 mg, for the acute treatment of migraine attacks of any intensity. There was a relationship between a history of a high frequency of migraine attacks and low baseline MSQOL scores, indicating a lower quality of life. Principal components analyses confirmed three domains and an overall score. Cronbach alpha coefficients for the overall score (.93) indicated high internal consistency. Responsiveness analysis over 180 days of treatment indicated a significantly greater improvement in MSQOL scores (P <.05) in treatment responders compared with nonresponders. The average effect size (0.25) and Guyatt responsiveness statistic (0.46) for the MSQOL instrument exceeded those for the eight domains of the Medical Outcomes Study Short Form Health Survey (MOS SF-36) (-0.05 to 0.14 and 0.01 to 0.12, respectively). Change from baseline for responders in MSQOL total score was 4.7 to 5.4 compared with 1.1 to 2.7 for nonresponders. Cumulative evidence for the MSQOL instrument meets established criteria for validity, consistency, and reproducibility and shows moderate responsiveness to treatment. This instrument fulfils the need for an MSQOL measure to be used as an adjuvant measure in the assessment of long-term outcomes of therapy.",2001.0,0,1
100,10943229,Triptans to the rescue: effective therapy for migraine headaches in the workplace.,J D Bartleson,,2000.0,0,0
101,10943230,"Effectiveness of sumatriptan in reducing productivity loss due to migraine: results of a randomized, double-blind, placebo-controlled clinical trial.",E A Schulman; R K Cady; D Henry; A S Batenhorst; D G Putnam; C B Watson; S O O'Quinn,"To determine the effect of sumatriptan on migraine-related workplace productivity loss. In this randomized, double-blind, placebo-controlled, parallel-group trial, adult migraineurs self-injected 6 mg of sumatriptan or matching placebo to treat a moderate or severe migraine within the first 4 hours of a minimum of an 8-hour work shift. Outcome measures included productivity loss and number of patients returning to normal work performance 2 hours after injection and across the work shift, time to return to normal work performance, and time to headache relief. A total of 206 patients underwent screening, 140 (safety population) of whom returned for clinic treatment. Of these 140 patients, 119 received migraine treatment in the workplace (intent-to-treat population), 116 of whom comprised the study population. Of these 116 patients, 76 self-administered sumatriptan, and 40 self-administered placebo. Sumatriptan treatment tended to reduce median productivity loss 2 hours after injection compared with placebo (25.2 vs 29.9 minutes, respectively; P = .14). Significant reductions in productivity loss were obtained across the work shift after sumatriptan treatment compared with placebo (36.8 vs 72.6 minutes, respectively; P = .001). Significantly more sumatriptan-treated patients vs placebo-treated patients experienced shorter return to normal work performance at 2 hours (53/76 [70%] vs 12/40 [30%], respectively) and across the work shift (64/76 [84%] vs 23/40 [58%], respectively; P < .001). Significantly more sumatriptan-treated patients experienced headache relief 1 hour after injection compared with placebo-treated patients (48/76 [63%] vs 13/40 [33%], respectively; P = .004). Across an 8-hour work shift, sumatriptan was superior to placebo in reducing productivity loss due to migraine.",2000.0,0,1
102,10954953,A clinical comparison of sumatriptan nasal spray and dihydroergotamine nasal spray in the acute treatment of migraine.,F Boureau; L Kappos; J Schoenen; P Esperanca; E Ashford,"A multinational, multicentre, randomised, double-blind, double-dummy, crossover study (368 patients treating two attacks) was conducted to compare the efficacy and tolerability of sumatriptan nasal spray (20 mg) with dihydroergotamine (DHE) nasal spray (1 mg plus optional 1 mg). At the primary efficacy time point of 60 minutes after dosing, significantly more patients obtained headache relief (change from moderate or severe to none or mild) after treatment with sumatriptan than with DHE (53% sumatriptan, 41% DHE, p < 0.001). Significantly more patients reported relief of nausea after sumatriptan than after DHE at 60 minutes (64% sumatriptan, 49% DHE, p = 0.006). A significant difference between the two treatments was first observed at 45 minutes with respect to both headache relief (38% sumatriptan, 31% DHE, p = 0.037) and relief of nausea (55% sumatriptan, 40% DHE, p = 0.014). There were no significant differences between the two treatments for other measures of efficacy. Both treatments were well tolerated, with only 10% of patients in each group reporting one or more adverse events. The most frequently reported adverse event after sumatriptan was a bad or bitter taste, which was reported by 5% of patients. After DHE, 4% of patients reported symptoms of the nasal cavity/sinuses and 3% reported nausea and/or vomiting as adverse events. It is concluded that sumatriptan nasal spray is superior to DHE nasal spray in the relief of pain and nausea associated with acute migraine headache.",2000.0,0,1
103,10961763,The effect of intranasal cocaine and lidocaine on nitroglycerin-induced attacks in cluster headache.,A Costa; E Pucci; F Antonaci; G Sances; F Granella; G Broich; G Nappi,"The administration of nitroderivatives in cluster headache (CH) sufferers is the most reproducible experimental paradigm to induce spontaneous-like pain attacks. Previous uncontrolled studies have reported that the local use of anaesthetic agents in the area of the sphenopalatine fossa is able to extinguish nitroglycerin (NTG)-induced pain in CH. The present study, carried out according to a double-blind placebo-controlled design, included 15 CH patients, six with episodic CH (mean +/- SD age of 36.8+/-5.6 years), and nine with chronic CH (37.8+/-10.4 years). Patients had undergone a standard NTG test (0.9 mg sublingually), during which the intensity of pain was scored using a visuoanalogic scale (VAS, range 0-10). Nine patients (two with the episodic form, seven with the chronic form) experienced a typical, spontaneous-like attack on the usual side, occurring in all cases within 45 min. In these patients, the test was repeated with an interval of 2 days, and once pain intensity reached 5 on the VAS, a 10% solution of cocaine hydrochloride (1 ml, mean amount per application 40-50 mg), or 10% lidocaine (1 ml), or saline was applied using a cotton swab in the area corresponding to the sphenopalatine fossa, under anterior rhinoscopy. This was done in both the symptomatic and the non-symptomatic side, for 5 min. Treatments were always performed randomly, in separate sessions. All patients responded promptly to both anaesthetic agents, with complete cessation of induced pain occurring after 31.3+/-13.1 min for cocaine and 37.0+/-7.8 min for lidocaine (M+/-SD). In the case of saline application, pain severity increased thereafter, and extinction of the provoked attacks occurred with a latency of 59.3+/-12.3 min (P<0.01 and P<0.01 vs. cocaine and lidocaine, respectively, Mann-Whitney U-test). While further suggesting that the sphenopalatine ganglion participates in the mechanisms of pain, these findings indicate that the local administration of the anaesthetic agents cocaine and lidocaine is effective on NTG-induced CH attacks, and may be used in the symptomatic treatment of this disorder.",2001.0,0,0
104,10961773,Sumatriptan nasal spray in the acute treatment of migraine: a review of clinical studies.,P Tfelt-Hansen,,2001.0,0,0
105,10972633,Efficacy of naratriptan tablets in the acute treatment of migraine: a dose-ranging study. Naratriptan S2WB2004 Study Group.,H Havanka; C Dahlöf; P H Pop; H C Diener; P Winter; H Whitehouse; H Hassani,"This study sought to compare the efficacy of several doses of naratriptan tablets with that of sumatriptan tablets and placebo in the acute treatment of a single migraine attack. This was a randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study. Patients received either naratriptan tablets (1, 2.5, 5, 7.5, or 10 mg), sumatriptan tablets (100 mg), or placebo. A total of 643 patients took part in the study. Two hours after dosing, headache relief was reported by significantly more patients treated with any dose of naratriptan (52%-69%) or sumatriptan (60%) than with placebo (31%) (P < 0.05). Four hours after dosing, headache relief was reported by significantly more patients treated with any dose of naratriptan (63%-80%) or sumatriptan (80%) than with placebo (39%) and by significantly more patients treated with sumatriptan 100 mg (80%) than with naratriptan 1 mg (64%), 2.5 mg (63%), or 5 mg (65%) (P < 0.05). Twenty-four-hour overall efficacy (headache relief maintained through 24 hours postdose with no worsening, no use of rescue medication, and no recurrence) was reported by more patients treated with any dose of naratriptan (39%-58%) or sumatriptan (44%) than with placebo (22%). Headache recurrence was reported in 17% to 32% of naratriptan-treated patients, 44% of sumatriptan-treated patients, and 36% of placebo recipients. The overall incidence of adverse events was similar in patients treated with naratriptan 1 mg (20%), naratriptan 2.5 mg (21%), and placebo (23%). For naratriptan 5, 7.5, and 10 mg, the incidence of adverse events was 32%, 37%, and 35%, respectively, and for sumatriptan 100 mg it was 26%. Our results suggest that the 2.5-mg dose of naratriptan tablets offers the optimal efficacy-to-tolerability ratio at the dose range between 1 and 10 mg. Although naratriptan 2.5 mg was less effective than sumatriptan 100 mg at 4 hours after dosing, the 2 medications showed similar efficacy at 24 hours.",2001.0,1,1
106,10972634,Comparison of naratriptan and sumatriptan in recurrence-prone migraine patients. Naratriptan International Recurrence Study Group.,H Göbel; P Winter; D Boswell; A Crisp; W Becker; T Hauge; B Mihout; J Niewold; J Tørring,"This randomized, double-blind, crossover study was undertaken to compare the incidence of headache recurrence after treatment with naratriptan or sumatriptan in migraine patients with a history of frequent headache recurrence (recurrence in > or =50% of successfully treated attacks). Although the selective 5-hydroxytryptamine, (5-HT1) agonist sumatriptan is effective and well tolerated for acute treatment of migraine in most patients, headache recurrence within 24 hours of initial successful treatment with sumatriptan and other medications has been reported in approximately 35% of patients. The novel 5-HT1 agonist naratriptan possesses pharmacologic and pharmacokinetic characteristics that may address the issue of headache recurrence. Men and women aged 18 to 65 years with a > or =1-year history of migraine with or without aura were randomly assigned to treat 1 moderate or severe migraine attack in a nonclinical setting with one 2.5-mg naratriptan tablet and 1 attack with one 100-mg sumatriptan tablet. A pain-free interval of > or =24 hours was required between attacks. At 4 hours, patients not using rescue medication and experiencing headache recurrence could take a second, identical dose of study medication to treat recurrence. No more than 2 tablets of study medication were permitted in any 24-hour period. A total of 253 patients treated > or =1 migrane attack and were included in the safety analysis; the 225 patients who treated both attacks were included in the efficacy analysis. Of the 164 naratriptan-treated and 181 sumatriptan-treated patients experiencing headache relief after > or =1 attack, headache recurrence 4 to 24 hours after treatment was reported by 74 naratriptan-treated patients (45%) and 101 sumatriptan-treated patients (57%; not statistically significant). (One naratriptan- and 3 sumatriptan-treated patients who experienced headache relief did not record recurrence status and were not included in the denominator for the percentage calculation.) In a subset of patients experiencing headache relief after 2 attacks, headache recurrence 4 to 24 hours after initial dosing was reported by 55 naratriptan- and 77 sumatriptan-treated patients (41% and 57%, respectively; P = 0.005). The overall incidence of adverse events was 22% after treatment with naratriptan and 33% after treatment with sumatriptan. This incidence did not increase after use of a second dose of naratriptan (20%) or sumatriptan (31%). These data suggest that naratriptan is a long-acting and well-tolerated addition to currently available medications for the treatment of acute migraine.",2001.0,0,1
107,10986188,Migraine: pharmacotherapy in the emergency department.,A M Kelly,"Migraine can be a disabling condition for the sufferer. For the small number of patients for whom home therapy fails and who seek treatment in an emergency department, several therapeutic options are available. I review the evidence regarding the effectiveness and safety of the following therapies: the phenothiazines, lignocaine (lidocaine), ketorolac, the ergot alkaloids, metoclopramide hydrochloride, the ""triptans,"" haloperidol, pethidine (meperidine hydrochloride), and magnesium sulfate. Based on available evidence, the most effective agents seem to be prochlorperazine, chlorpromazine and sumatriptan, each of which has achieved greater than 70% efficacy in several studies.",2001.0,0,0
108,10993131,Serotonergic targets in the treatment of antidepressant induced sexual dysfunction: a pilot study of granisetron and sumatriptan.,M Berk; D J Stein; A Potgieter; C M Maud; C Els; M L Janet; E Viljoen,"Antidepressant induced sexual dysfunction is a common adverse event that is particularly evident with serotonergic antidepressants. There is a paucity of clinical trial evidence on the treatment of this problem. While there is some evidence of involvement of the serotonin (5-HT2) receptor subtype in this phenomenon, other serotonergic receptor systems are not well studied. In this trial, 35 patients on maintenance therapy with a variety of serotonergic antidepressants, who reported antidepressant induced sexual dysfunction, were enrolled. Patients were given both granisetron 1 mg, and sumatriptan 100 mg, in a crossover design, to be used 1 h before intercourse. Sexual dysfunction was measured using the Feiger scale. There was a high dropout rate in the trial, reflecting both embarrassment with the pharmacological treatment of sexual dysfunction and difficulties with planning and timing the medication. Nevertheless, there was a significant effect of granisetron in this study, with scores decreasing from 23.7 (SD 2.52) to 16.0 (SD 6.42) on the Feiger scale (n = 14, P = 0.001, Wilcoxon sign rank test). Sumatriptan failed to show a significant change from baseline at the 0.01 level of significance. While the small sample size, high dropout rates and open label design are limitations to this study, it suggests efficacy of the granisetron in antidepressant induced sexual dysfunction and the role of the 5-HT3 receptor in this phenomenon.",2001.0,0,0
109,10999671,Effects of subcutaneous sumatriptan on plasma growth hormone concentrations in migraine patients.,L Pinessi; I Rainero; L Savi; W Valfrè; P Limone; P Calvelli; P Del Rizzo; L Gianotti; M Taliano; E Ghigo; E Arvat,"The purpose of this study was to assess the sensitivity of 5-HT1D receptors in migraine using sumatriptan as a pharmacological probe. The drug stimulates the release of growth hormone (GH) and this effect may be used to explore the function of cerebral serotonergic systems in vivo. We administered sumatriptan and placebo to 15 migraineurs and to 10 controls. Blood samples were collected -15, 0, 15, 30, 45, 60 and 90 min after injection. Placebo had no effect on hormone concentrations. Sumatriptan induced a significant (P<0.01) increase in GH concentrations both in migraine patients and healthy controls. The GH increase was not significantly different in the two groups. Our results suggest that cerebral serotonergic functions mediated by 5-HT1D receptors are not altered in migraine. Sumatriptan overuse could lead to adverse effects mediated by its neuroendocrine activity.",2001.0,0,0
110,10999677,A comment on time-to-event analysis for headache relief.,P Tfelt-Hansen,,2001.0,0,0
111,11032200,Is oral zolmitriptan efficacious in the acute treatment of cluster headache?,J R Encarnacion; M R Ellis; E J Lindbloom,,2001.0,0,0
112,11037740,Induction of nitrate tolerance is not a useful treatment in cluster headache.,I Christiansen; H K Iversen; J Olesen,"The aims of the present study were to investigate whether induction of nitrate tolerance is a useful treatment in cluster headache and to correlate any changes in attack frequency of cluster headache and nitrate-induced headache to the vascular adaptation during continuous nitrate administration. The results were compared to results obtained from studies of nitrate tolerance in healthy subjects. 5-isosorbide-mononitrate (5-ISMN) 30 mg was administered orally three times daily for 4 weeks in nine sufferers of chronic cluster headache in a double-blind, randomized placebo-controlled cross-over design. Blood velocity in the middle cerebral artery was measured with transcranial Doppler and the diameters of the temporal and radial arteries were measured with high frequency ultrasound. The haemodynamic data were compared to changes in the frequency of cluster headache attacks and interval headaches over time. Tolerance was complete within 24 h in the middle cerebral arteries and after 7 days in the symptomatic temporal artery, while tolerance of the radial artery was not observed within this period. The time profiles of tolerance were almost identical to the time profiles observed in healthy subjects. A close temporal association between the disappearance of nitrate-induced headache and tolerance of the temporal artery was observed but tolerance had no effect on cluster headache attack frequency. Induction of tolerance to nitrates cannot be used to treat cluster headache. If pain is related to arterial dilatation the results point to extracerebral rather than cerebral arteries as the site of nociception. However, other peripheral and central pain-modulating effects of nitric oxide, the time courses of which are unknown, should also be taken into consideration.",2001.0,0,0
113,11037741,Comparison of rizatriptan 10 mg vs. zolmitriptan 2.5 mg in the acute treatment of migraine. Rizatriptan-Zolmitriptan Study Group.,J Pascual; P Vega; H C Diener; C Allen; F Vrijens; K Patel,"The efficacy and tolerability of rizatriptan (MAXALT) and zolmitriptan (ZOMIG) were compared in a randomized, double-blind, double-dummy, stratified (on prior use of rizatriptan and/or zolmitriptan), placebo-controlled, single attack study in 766 patients. Rizatriptan tended to provide freedom from pain sooner than zolmitriptan (hazard ratio 1.26, P = 0.075), acting within 60 min following dosing. More patients were pain free at 2 h on rizatriptan than on zolmitriptan (43.2% vs. 35.6%, P=0.041), while headache relief at 2 h was similar (70.5% vs. 66.8%). At 2 h, fewer patients on rizatriptan had symptoms of photophobia (35.6% vs. 43.5%, P = 0.029) and nausea (25.2% vs. 32.5%, P=0.046), and more patients on rizatriptan had normal function (45.4% vs. 37.0%, P=0.025) than zolmitriptan. Headache recurred in 28% of patients taking rizatriptan, 29% taking zolmitriptan and 26% taking placebo. Both active treatments were effective compared to placebo and were well tolerated. The most common side-effects with rizatriptan were asthenia/fatigue, somnolence and dizziness, while the most common side-effects with zolmitriptan were asthenia/fatigue and dizziness.",2001.0,1,1
114,11037743,Tolerability and efficacy of naratriptan tablets in the acute treatment of migraine attacks for 1 year. Naratriptan Long-Term Study Group.,J Heywood; M A Bomhof; A Pradalier; L Thaventhiran; P Winter; H Hassani,"This open-label study was conducted to evaluate the tolerability and efficacy of the 5HT1 agonist naratriptan with repeated use in the acute treatment of migraine attacks for 1 year. Four hundred and seventeen (417) migraine patients treated 15,301 migraine attacks over the course of the study. The results show that 84% of attacks treated with a single 2.5 mg dose of naratriptan were not associated with the occurrence of an adverse event. The percentage of attacks associated with an adverse event did not increase with number of doses used to treat a given attack (1 vs. 2) or duration of use (0-6 months vs. > 6-12 months). The only adverse events experienced in > 2% of attacks throughout the 1-year study were nausea (3% of attacks), hyposalivation (2% of attacks), and drowsiness/sleepiness (2% of attacks). Headache relief 4 h post-dose was reported in a median 70% of moderate or severe attacks and a median 86% of mild attacks treated with naratriptan tablets 2.5 mg. The percentages of patients reporting headache relief did not diminish as a function of increased duration of treatment (0-6 months vs. > 6-12 months) or frequency of use (for > 36 vs. < 36 attacks). The mean number of tablets taken per attack was 1.2. A second naratriptan 2.5 mg tablet was taken for headache recurrence in a mean 16% (median 8%) of attacks. The results of this study demonstrate that naratriptan tablets 2.5 mg taken for acute migraine attacks over a 1-year period are well-tolerated and effective.",2001.0,0,1
115,11041318,Zolmitriptan (a 5-HT1B/1D receptor agonist with central action) does not increase symptoms in obsessive compulsive disorder.,M L Boshuisen; J A den Boer,"Non-selective serotonin (5-HT) receptor agonists like meta-chlorophenylpiperazine and MK-212 have been used to explore the role of 5-HT in obsessive compulsive disorder (OCD). The results of these studies and the findings of autoradiography and neuroimaging studies, pointed to a possible role of the 5-HT1B/1D receptor in the pathophysiology of OCD. Recently the selective 5-HT1B/1D receptor agonist sumatriptan was used to further explore the role of the 5-HT1B/1D receptor in OCD. Equivocal results with respect to the increase of obsessive compulsive symptoms in patients with OCD were reported. In one study a significant increase in plasma growth hormone (GH) concentration was observed, although sumatriptan does not pass the blood-brain barrier. In order to further explore the role of the 5-HT1B/1D receptor in the pathophysiology of OCD, we performed this study, following the same design as Ho Pian et al. (Psychopharmacology 140:365-370). In the present study we performed a randomized, double-blind, placebo-controlled, cross-over design with zolmitriptan (5 mg per os), a selective 5-HT1B/1D receptor agonist with better brain penetrating properties than sumatriptan. We could not detect any changes in obsessive compulsive symptoms, mood, or anxiety levels, although we found a (nonsignificant) increase in plasma GH levels. Based upon these findings, no evidence was found for a specific role of the 5-HT1B/1D receptor in OCD. It should be noted, however, that challenge studies in OCD are difficult to perform. Perhaps in the future better challenge paradigms will make it possible to further explore the role of specific receptor types in OCD.",2001.0,0,0
116,11048903,Effect of early intervention with sumatriptan on migraine pain: retrospective analyses of data from three clinical trials.,R K Cady; F Sheftell; R B Lipton; S O'Quinn; M Jones; D G Putnam; A Crisp; A Metz; S McNeal,"This study assessed the efficacy of sumatriptan 50- and 100-mg tablets in the treatment of migraine attacks while the pain is mild rather than moderate/severe. Results from The Spectrum Study suggested that early treatment of migraine attacks with sumatriptan 50-mg tablets while the pain is mild might enhance pain-free response and reduce headache recurrence. Retrospective analyses of headaches treated during mild pain were performed using data from 3 studies of sumatriptan tablets (protocols S2CM09, S2BT25, and S2BT26). Our primary interest was pain-free response 2 and 4 hours after dosing; secondary interests were use of a second dose of medication, clinical disability (as measured on a 4-point disability scale), migraine-associated symptoms, meaningful pain relief (patient defined), time to meaningful relief, sustained pain-free response, and proportion of attacks in which pain had worsened 2 and 4 hours after dosing, all of which were compared in headaches treated during mild versus moderate/severe pain. In S2CM09, 92 patients treated 118 headaches during mild pain. Rates of pain-free response were higher 2 hours after dosing with sumatriptan 50 mg (51%) or 100 mg (67%; P < 0.05) compared with placebo (28%), and were higher with early treatment of mild pain compared with treatment of moderate/severe pain at 2 hours (sumatriptan 50 mg: mild pain, 51%; moderate/severe pain, 31%; P < 0.05; sumatriptan 100 mg: mild pain, 67%; moderate/severe pain, 36%) and 4 hours (50 mg: 75% vs 56%; 100 mg: 90% vs 61%; P < 0.05). Early intervention also resulted in less redosing than when moderate/severe pain was treated (50 mg: 21% vs 32%; 100 mg: 20% vs 29%). More attacks treated early with sumatriptan 50 or 100 mg were associated with normal function 4 hours after dosing compared with placebo (70% and 93% vs 46%, respectively). Sustained pain-free response rates 2 to 24 hours after early dosing with sumatriptan 50 or 100 mg were also higher (34% and 53%, respectively) compared with treatment of moderate/severe pain (19% and 24%, respectively). Early treatment with sumatriptan 100 mg produced significantly higher pain-free rates at 2 hours after dosing (P < 0.001) than did ergotamine plus caffeine (S2BT25: 69% vs 34%, respectively) or aspirin plus metoclopramide (S2BT26: 73% vs 25%, respectively). Sumatriptan 50- and 100-mg tablets are effective whether pain is mild or moderate/severe. However, treatment with sumatriptan while pain is mild provides high pain-free response rates while reducing the need for redosing, benefits not seen with ergotamine plus caffeine or aspirin plus metoclopramide.",2001.0,0,1
117,11061765,"A randomized, double-blind, placebo-controlled study of sumatriptan nasal spray in the treatment of acute migraine in adolescents.",P Winner; A D Rothner; J Saper; R Nett; M Asgharnejad; A Laurenza; R Austin; M Peykamian,"To compare the efficacy and tolerability of sumatriptan nasal spray (NS; 5 mg, 10 mg, and 20 mg) with placebo for the treatment of acute migraine in adolescents. A randomized, double-blind, placebo-controlled, single-attack study was conducted in 653 US adolescents (12-17 years of age). Patients with at least a 6-month history of migraine, who met International Headache Society criteria for migraine (with or without aura) were eligible for participation. Headache relief 2 hours postdose, complete relief, presence or absence of associated symptoms, headache recurrence, and use of rescue medications were recorded. The primary efficacy endpoint was headache relief 2 hours postdose sumatriptan NS (20 mg) versus placebo. Safety and tolerability were assessed by examining adverse events, changes in electrocardiograms, vital signs, physical examinations, and clinical laboratory tests. Headache relief 1 hour postdose was significantly greater for patients using 10 mg (56%) and 20 mg (56%) of sumatriptan NS compared with placebo (41%). Headache relief 2 hours postdose was significantly greater for patients using 5 mg of sumatriptan NS (66%) compared with placebo (53%), and approached statistical significance for 20 mg (63%) compared with placebo (53%). Complete relief 2 hours postdose was significantly greater for patients using 20 mg of sumatriptan NS compared with placebo (36% vs 25%, respectively). Each dose of sumatriptan (5 mg, 10 mg, and 20 mg) was superior to placebo with respect to the cumulative percentages of patients first reporting headache relief within 2 hours of dosing (Kaplan-Meier). The sumatriptan 20-mg dose was superior to placebo with respect to the cumulative percentages of patients first reporting complete relief within 2 hours of dosing (Kaplan-Meier). Photophobia and phonophobia were significantly reduced 2 hours postdose for sumatriptan NS (20 mg), compared with placebo (36% vs 48% and 25% vs 44%, respectively). Taste disturbance was the most commonly reported adverse event (2%, 19%, 30%, and 26% for placebo, 5 mg, 10 mg, and 20 mg, respectively). No drug-related serious adverse events or clinically relevant changes in laboratory parameters, electrocardiograms, or vital signs were reported. Sumatriptan NS is effective and well-tolerated for the treatment of acute migraine in adolescents, with the 20-mg dose providing the best overall efficacy and tolerability profiles.",2001.0,0,1
118,11062845,"Sumatriptan overuse in episodic cluster headache: lack of adverse events, rebound syndromes, drug dependence and tachyphylaxis.",V Centonze; A Bassi; V Causarano; L Dalfino; M A Cassiano; A Centonze; L Fabbri; O Albano,"This observational study was designed to examine the pattern of sumatriptan use in patients with cluster headache using more than the recommended daily dose of subcutaneously injected (s.c.) sumatriptan. Thirteen patients suffering from episodic cluster headache were asked to record the characteristics of their attacks and drug intake for 1 year. All reported a high daily frequency of attacks (more than 3 per day) and the related overuse of s.c. sumatriptan. The results show that the overall incidence of adverse events among patients receiving sumatriptan injections for the treatment of cluster headache is low. The extended administration of this drug in episodic cluster headache did not result in tolerance problems or tachyphylaxis. Only 4 patients experienced minor adverse events and recovered more slowly than the others. They suffered from migraine without aura and cluster headache, and showed a family history of migraine. Even though they must be viewed with caution, due to the observational nature of the study and the low number of patients included, these results suggest that the profile of sumatriptan may differ in cluster headache compared with migraine.",2001.0,0,1
119,11070573,Zolmitriptan provides effective migraine relief in adolescents.,S L Linder; A J Dowson,"Data from a subgroup of adolescents (12-17 years) entered into a one-year open-label phase of a large international study were analysed to evaluate response rates and tolerability of zolmitriptan for the acute treatment of migraine. In the open-label phase of this study, the first two migraine attacks were treated with zolmitriptan 2.5 mg and subsequent attacks with zolmitriptan 2.5 mg or 5 mg, at the patient's discretion, for up to 12 months. Two-hour headache and pain-free responses were evaluated and adverse events were recorded. Thirty-eight adolescents treated 276 migraine attacks of any intensity. The overall headache response at 2 hours was 80% (88% and 70% with zolmitriptan 2.5 mg and 5 mg, respectively), and the pain-free response was 66% (76% and 52% for zolmitriptan 2.5 mg and 5 mg, respectively). Response rates were independent of whether or not migraine was associated with aura or menses. During prolonged use, patients learned to adjust the dose of zolmitriptan to effectively manage their migraine. Treatment was well tolerated. In conclusion, preliminary data indicate that zolmitriptan is effective in the acute treatment of migraine in adolescents and is well tolerated.",2001.0,0,0
120,11075838,Determinants of patient satisfaction with migraine therapy.,G M Davies; N Santanello; R Lipton,"Determinants of patient satisfaction with migraine treatment are not well understood. The objective of this study was to evaluate which treatment outcomes influence patient satisfaction with treatment. Analyses were performed on data from 1506 migraineurs from two clinical trials of rizatriptan for treatment of migraine. Satisfaction with treatment was assessed 2 h after initial treatment and prior to use of rescue therapy. Over 90% of patients who were pain-free at 2 h were at least somewhat satisfied with treatment compared with <10% of patients with moderate or severe pain. Only 60-70% of patients with mild pain at 2 h experienced some level of satisfaction with treatment. For patients with mild pain at 2 h, results showed subjects who reported severe pain at baseline, absence of associated symptoms at 2 h and pain relief within the first 90 min had at least a 76% probability of being at least somewhat satisfied. This probability decreased with the presence of associated symptoms, slower pain relief and moderate baseline pain intensity. Fast, complete pain relief is one important factor in determining short-term patient satisfaction with treatment.",2001.0,0,1
121,11075843,Rizatriptan wafer--sublingual vs. placebo at the onset of acute migraine.,J A Klapper; S O'Connor,"Rizatriptan wafer is a 5HT1B/1D agonist for use in the acute treatment of migraine. It is a freeze-fried formulation, approved for oral administration, which dissolves on the tongue and is swallowed with saliva. In this study the efficacy of sublingually administered rizatriptan 10-mg wafer was evaluated in a randomized, double-blind, placebo-controlled, out-patient study involving 39 migraineurs. Patients were instructed to treat a migraine at the onset of pain in order to evaluate time of onset of pain relief and pain relief at 1 h. The average time to onset of relief was 25 min for patients treated with rizatriptan wafer and 27 min for patients treated with placebo. At 1 h, 50% of the patients receiving rizatriptan wafer and 50% of the patients receiving placebo experienced significant relief. Implications and potential reasons for a high placebo response are discussed.",2001.0,0,1
122,11075844,"Consistent efficacy and tolerability of almotriptan in the acute treatment of multiple migraine attacks: results of a large, randomized, double-blind, placebo-controlled study.",J Pascual; R M Falk; F Piessens; A Prusinski; P Docekal; M Robert; P Ferrer; X Luria; R Segarra; J M Zayas,"In this double-blind study, the efficacy and tolerability of a single dose of almotriptan (6.25 or 12.5 mg) was compared with placebo in the treatment of three consecutive migraine attacks of moderate or severe intensity. Of 1013 randomized patients, 722 evaluable patients completed the study. The total number of attacks relieved (severe or moderate pain reduced to mild or no pain) at 2 h post-dose was significantly higher (P < 0.001) after treatment with almotriptan 6.25 or 12.5 mg compared with placebo (60% and 70% vs. 38%, respectively). Moreover, a consistent response was achieved across and within patients for almotriptan 6.25 or 12.5 mg compared with placebo (pain relief in at least two out of three attacks within 2 h for 64% and 75% vs. 36%, respectively) and less than one-third of the patients relapsed within 24 h. Almotriptan was well tolerated with no significant differences between the almotriptan and placebo treatment groups in the percentage of patients reporting adverse events. Overall, the 12.5-mg dose was associated with the most favourable efficacy/tolerability ratio and is, therefore, the recommended dose.",2001.0,0,1
123,11078006,Rizatriptan: a new milestone in migraine treatment. Closing remarks.,J Pascual,,2001.0,0,0
124,11079284,Cost-benefit analysis of sumatriptan tablets versus usual therapy for treatment of migraine.,A K Biddle; Y C Shih; W J Kwong,"We performed a systematic assessment of the costs and benefits of sumatriptan and usual therapy for migraine from society's perspective. A decision tree was constructed with probability estimates based on data from an open-label clinical trial assessing the economic and human impacts of sumatriptan and usual therapy on nursing personnel. Direct medical care costs including costs for drug, physician, and emergency room visits were considered. Benefits were estimated using the human capital approach based on the national average of weekly earnings and productivity loss estimated from a migraine clinical trial. The net benefits of sumatriptan and usual therapy for the treatment of a single migraine attack were estimated to be $50 and $20, respectively. The annual incremental net benefit of sumatriptan over usual therapy was estimated to be $114-540/patient. The price difference was offset by benefits of sumatriptan in reducing use of health care resources and productivity loss.",2001.0,0,0
125,11086366,Stratified care vs step care strategies for migraine: the Disability in Strategies of Care (DISC) Study: A randomized trial.,R B Lipton; W F Stewart; A M Stone; M J Láinez; J P Sawyer; Disability in Strategies of Care Study group,"Various guidelines recommend different strategies for selecting and sequencing acute treatments for migraine. In step care, treatment is escalated after first-line medications fail. In stratified care, initial treatment is based on measurement of the severity of illness or other factors. These strategies for migraine have not been rigorously evaluated. To compare the clinical benefits of 3 strategies: stratified care, step care within attacks, and step care across attacks, among patients with migraine. Randomized, controlled, parallel-group clinical trial conducted by the Disability in Strategies Study group from December 1997 to March 1999 in 88 clinical centers in 13 countries. A total of 835 adult migraine patients with a Migraine Disability Assessment Scale (MIDAS) grade of II, III, or IV were analyzed as the efficacy population; the safety analysis included 930 patients. Patients were randomly assigned to receive (1) stratified care (n = 279), in which patients with MIDAS grade II treated up to 6 attacks with aspirin, 800 to 1000 mg, plus metoclopramide, 10 mg, and patients with MIDAS grade III and IV treated up to 6 attacks with zolmitriptan, 2.5 mg; (2) step care across attacks (n = 271), in which initial treatment was with aspirin, 800 to 1000 mg, plus metoclopramide, 10 mg. Patients not responding in at least 2 of the first 3 attacks switched to zolmitriptan, 2.5 mg, to treat the remaining 3 attacks; and (3) step care within attacks (n = 285), in which initial treatment for all attacks was with aspirin, 800 to 1000 mg, plus metoclopramide, 20 mg. Patients not responding to treatment after 2 hours in each attack escalated treatment to zolmitriptan, 2.5 mg. Headache response, achieved if pain intensity was reduced from severe or moderate at baseline to mild or no pain at 2 hours; and disability time per treated attack at 4 hours for all 6 attacks, compared among the 3 groups. Headache response at 2 hours was significantly greater across 6 attacks in the stratified care treatment group (52.7%) than in either the step care across attacks group (40.6%; P<.001) or the step care within attacks group (36.4%; P<.001). Disability time (6 attacks) was significantly lower in the stratified care group (mean area under the curve [AUC], 185.0 mm. h) than in the step care across attacks group (mean AUC, 209.4 mm. h; P<.001) or the step care within attacks group (mean AUC, 199.7 mm. h; P<.001). The incidence of adverse events was higher in the stratified care group (321 events) vs both step care groups (159 events in across-attack group; 217 in within-attack group), although most events were of mild-to-moderate intensity. Our results indicate that as a treatment strategy, stratified care provides significantly better clinical outcomes than step care strategies within or across attacks as measured by headache response and disability time. JAMA. 2000;284:2599-2605.",2001.0,0,1
126,11087191,,,,,0,0
127,11094106,Within-patient consistency of response of rizatriptan for treating migraine.,C G Dahlöf; R B Lipton; K A McCarroll; M S Kramer; C R Lines; M D Ferrari,"To determine the within-patient consistency of response for rizatriptan, a 5-HT(1B/1D) receptor agonist for the acute treatment of migraine. Post hoc analysis was performed on data from a randomized, double-blind, placebo-controlled clinical trial. Four hundred seventy-three patients with migraine diagnosed according to the criteria of the International Headache Society were randomly assigned to one of five sequence groups in which each patient was scheduled to treat four separate moderate or severe migraine attacks. Patients in four groups received 10 mg of rizatriptan for three of four attacks and placebo for the remaining attack; patients in the fifth group received 10 mg of rizatriptan for all four attacks. Headache severity, functional disability, and associated migraine symptoms were measured immediately before dosing and at regular intervals up to 4 hours after the dose. The analysis was based on efficacy at 2 hours after dosing, the last time point before escape medications were allowed. The percentages of patients who responded in a specified number of attacks after treatment with rizatriptan were calculated. The analysis was descriptive, and no formal statistical testing was performed. Of the evaluable patients who treated three migraine attacks with 10 mg of rizatriptan (with an additional interspersed placebo-treated attack in most patients), 216 of 252 (86%) had pain relief (reduction of pain to mild or none), 122 of 252 (48%) were pain free, 211 of 250 (84%) had no nausea, 163 of 251 (65%) had no photophobia, 182 of 252 (72%) had no phonophobia, 136 of 249 (55%) had no functional disability, and 233 of 252 (92%) had no need for escape medications at 2 hours after dosing in at least two of three attacks. The response to 10 mg of oral rizatriptan within individual patients was consistent over three attacks on a range of measures.",2001.0,0,1
128,11098098,Validity of the Migraine Disability Assessment (MIDAS) score in comparison to a diary-based measure in a population sample of migraine sufferers.,W F Stewart; R B Lipton; K B Kolodner; J Sawyer; C Lee; J N Liberman,"The Migraine Disability Assessment (MIDAS) questionnaire is a brief, self-administered questionnaire designed to quantify headache-related disability over a 3 month period. The MIDAS score has been shown to have moderately high test-retest reliability in headache sufferers and is correlated with clinical judgment regarding the need for medical care. The aim of the study was to examine the validity of the MIDAS score, and the five items comprising the score, compared to data from a 90 day daily diary used, in part, to record acute disability from headache. In a population-based sample, 144 clinically diagnosed migraine headache sufferers were enrolled in a 90 day diary study and completed the MIDAS questionnaire at the end of the study. The daily diary was used to record detailed information on headache features as well as activity limitations in work, household chores, and non-work activities (social, family and leisure activities). The MIDAS score was the sum of missed work or school days, missed household chores days, missed non-work activity days, and days at work or school plus days of household chores where productivity was reduced by half or more in the last 3 months. Validity was assessed by comparing MIDAS items and the MIDAS score with equivalent measures derived from the diary. The MIDAS items for missed days of work or school (mean 0.96, median 0) and for missed days of household work (mean 3.64, median 2.0) were similar to the corresponding diary-based estimates of missed work or school (mean 1.23, median 0) and of missed household work (mean 3.93, median 2.01). Values for missed days of non-work activities (MIDAS mean 2.6 and median 1 versus diary mean 2.22 and median 0.95) were also similar. Responses to MIDAS questions about number of days where productivity was reduced by half or more in work (mean 3.77, median 2.00) and in household work (mean 3.92, median 2.00) significantly overestimated the corresponding diary-based measures for work (mean 2.94, median 1.06) and household work (mean 2.22, median 0.98). Nonetheless, the overall MIDAS score (mean 14.53, median 9.0) was not significantly different form the reference diary-based measure (mean 13.5, median 8.4). The correlation between the MIDAS summary score and an equivalent diary score was 0.63. The group estimate of the MIDAS score was found to be a valid estimate of a rigorous diary-based measure of disability. The mean and median values for the MIDAS score in a population-based sample of migraine cases were similar to equivalent diary measures. The correlation between the two measures was in the low moderate range, but expected given that two very different methods of data collection were compared.",2001.0,0,1
129,11127957,Functional bowel disease: roles of sensation and motility.,M Camilleri,"Functional bowel disorders are collections of symptoms attributable to the mid or lower gastrointestinal tract. The two most common disorders, irritable bowel syndrome and functional dyspepsia, have common etiopathogenetic features, notably psychosocial disturbances, dysmotility and heightened sensitivity. The control mechanisms, pathophysiology, investigation and potential pharmacotherapies of these disorders are reviewed. Serotonergic and adrenergic agents are among the novel approaches that may have a significant impact on these disorders.",2001.0,0,0
130,11135021,2000 Wolfe Award. Sumatriptan for the range of headaches in migraine sufferers: results of the Spectrum Study.,R B Lipton; W F Stewart; R Cady; C Hall; S O'Quinn; T Kuhn; D Gutterman,"Migraineurs experience a spectrum of headaches: migraine, migrainous, and episodic tension-type as defined by the International Headache Society (IHS). To evaluate the effectiveness of sumatriptan, 50-mg tablets, in treating the spectrum of headaches in IHS-diagnosed migraineurs. Migraineurs with severe disability (Headache Impact Questionnaire score 250 or greater) were enrolled in a randomized, double-blind, placebo-controlled, crossover study. Patients treated up to 10 headaches with sumatriptan, 50 mg, or placebo (4:1). Headache features, recorded prior to treatment, were used to classify each headache using IHS criteria. Headache response (moderate or severe pain reduced to mild or no pain) and pain-free response were recorded at 2 and 4 hours postdose (primary endpoint). Because patients treated multiple attacks, statistical methods controlling for within-subject correlation were used. Two hundred forty-nine migraineurs treated 1576 moderate or severe headaches: migraine (n = 1110), migrainous (n = 103), and tension-type (n = 363). Sumatriptan was superior to placebo for headache response 4 hours postdose (primary endpoint) across all headache types (migraine, 66% versus 48%; P<.001; migrainous, 71% versus 39%; P<.01; tension-type, 78% versus 50%, P<.001). Sumatriptan was also superior to placebo for pain-free response 4 hours postdose for migraine (41% versus 24%, P<.001) and tension-type headaches (56% versus 36%, P =.001). Sumatriptan provided superior pain-free response 2 hours postdose for migraine (18% versus 7%, P<.0001) and tension-type headache (28% versus 14%, P =.0005) compared with placebo. Sumatriptan, 50-mg tablets, are effective for the full spectrum of headaches experienced by patients with disabling migraine due to a sumatriptan-responsive mechanism.",2001.0,0,1
131,11135022,Treatment of mild headache in disabled migraine sufferers: results of the Spectrum Study.,R K Cady; R B Lipton; C Hall; W F Stewart; S O'Quinn; D Gutterman,"To evaluate the effectiveness of sumatriptan, 50-mg tablets, versus placebo for early intervention while head pain was mild in patients with disabling migraine. A post hoc analysis was performed in a subgroup of patients from a large, randomized, placebo-controlled study of patients with disabling headache who treated while pain was mild. Pain-free response 2 and 4 hours postdose, headache recurrence, and safety were examined. Significance tests were performed only for the first-treated attacks. Twenty-six patients with disabling headache treated 46 mild and 166 moderate or severe headaches. For the first-treated headaches while pain was mild, pain-free rates were significantly higher for sumatriptan than placebo 4 hours postdose (78% versus 0%, P =.02), but not 2 hours postdose (52% versus 0%, P =.22). Across all headaches treated while pain was mild, pain-free responses were higher for sumatriptan than placebo 4 hours (85% versus 17%) and 2 hours (50% versus 0%) postdose compared with placebo. When the same patients treated headaches while pain was moderate or severe, pain-free rates were lower than that reported for treatment during mild pain. There was a trend toward lower headache recurrence in headaches treated while pain was mild compared with moderate or severe pain (13% versus 18%). No drug-related adverse events were reported in the headaches treated while pain was mild. Patients with disabling migraine may benefit from early intervention with sumatriptan, 50 mg, while pain is mild.",2001.0,0,1
132,11135028,Hypnic headache: another indomethacin-responsive headache syndrome?,D W Dodick; J M Jones; D J Capobianco,"Hypnic headache syndrome is a benign, recurrent, late-onset headache disorder that occurs exclusively during sleep. Lithium has been reported to be an effective treatment, but the side effects of this medication are sometimes prohibitive, particularly in the elderly. Other drugs have been reported to be effective in this disorder, including caffeine, flunarizine, and verapamil. Recently, indomethacin has been reported to effectively suppress hypnic headaches. We report the response of seven patients with hypnic headache who were treated with indomethacin. Hypnic headache syndrome appears to represent yet another headache disorder in which there is sometimes an impressive response to indomethacin.",2001.0,0,0
133,11135422,A clinical trial on a plate? The potential of 384-well format solid phase extraction for high-throughput bioanalysis using liquid chromatography/tandem mass spectrometry.,R A Biddlecombe; C Benevides; S Pleasance,The application of 384-well format solid phase extraction (SPE) for bioanalysis using liquid chromatography/tandem mass spectrometry (LC/MS/MS) is reported and a 384-well SPE method for the 5-HT agonist sumatriptan in human plasma described. Plasma samples were extracted on a prototype low-density polyethylene 384-well SPE block using a packed bed of 5 mg Oasistrade mark HLB. Liquid handling was automated by a combination of a robotic sampler processor and a 96/384 multi-channel dispensing station. Samples and SPE reagents were drawn through the SPE block by centrifugation. The extracts were analysed by LC/MS/MS with thermally and pneumatically assisted electrospray ionisation and selected reaction monitoring. The method is used to illustrate and discuss the feasibility and viability of sample preparation techniques in high-density microtitre plate format for routine bioanalysis.,2001.0,0,0
134,11145638,New avenues in treatment of paediatric migraine: a review of the literature.,A Pakalnis,"Headaches are a common problem in paediatric practice. Recurrent headaches can be a significant source of stress for patient and parents, and disruptive regarding school obligations and parental work responsibilities. Most treatment interventions are developed from research data extrapolated from adult studies, with resultant concerns of safety and efficacy when utilizing these therapeutic conclusions in children. This paper incorporates current treatment strategies in paediatric migraine utilizing a Medline search of English language studies from January 1988 to December 1999, with a literature search referencing the terms of paediatrics, migraines, headaches, therapy and treatment. Reference sections of the articles were reviewed for pertinent information prior to January 1988. Articles were evaluated systematically to formulate concise terms for diagnosis of paediatric migraine and applicability to clinical treatment studies. Particular emphasis was placed on newer options with relevance in adult treatment such as triptans and anti-epileptic drugs, and their benefit in therapy of paediatric migraine. Non-pharmacological options were also subjected to organized review to determine relevance in treatment of paediatric migraine. The review of the literature indicates that although migraine in childhood and adolescence appears to be increasing in prevalence, few clinical studies are available, with most current treatment recommendations utilizing data from adult studies. Further headache treatment studies in the paediatric population are necessary in order to ascertain safety and efficacy of pharmaco-therapeutics in these children. Also, much current interest in treatment in adults with recurrent headaches involves non-pharmacological areas-dietary modification and stress management. Application of these avenues especially warrants further clarification with regard to relevance in paediatric migraine treatment.",2001.0,0,1
135,11147249,New abortive agents for the treatment of migraine.,S Potrebic; N H Raskin,,2001.0,0,0
136,11152011,"Triptans in migraine: a comparative review of pharmacology, pharmacokinetics and efficacy.",P Tfelt-Hansen; P De Vries; P R Saxena,"Triptans are a new class of compounds developed for the treatment of migraine attacks. The first of the class, sumatriptan, and the newer triptans (zolmitriptan, naratriptan, rizatriptan, eletriptan, almotriptan and frovatriptan) display high agonist activity at mainly the serotonin 5-HT1B and 5-HT1D receptor subtypes. As expected for a class of compounds developed for affinity at a specific receptor, there are minor pharmacodynamic differences between the triptans. Sumatriptan has a low oral bioavailability (14%) and all the newer triptans have an improved oral bioavailability and for one, risatriptan, the rate of absorption is faster. The half-lives of naratriptan, eletriptan and, in particular, frovatriptan (26 to 30h) are longer than that of sumatriptan (2h). These pharmacokinetic improvements of the newer triptans so far seem to have only resulted in minor differences in their efficacy in migraine. Double-blind, randomised clinical trials (RCTs) comparing the different triptans and triptans with other medication should ideally be the basis for judging their place in migraine therapy. In only 15 of the 83 reported RCTs were 2 triptans compared, and in 11 trials triptans were compared with other drugs. Therefore, in all placebo-controlled randomised clinical trials, the relative efficacy of the triptans was also judged by calculating the therapeutic gain (i.e. percentage response for active minus percentage response for placebo). The mean therapeutic gain with subcutaneous sumatriptan 6mg (51%) was more than that for all other dosage forms of triptans (oral sumatriptan 100mg 32%; oral sumatriptan 50mg 29%: intranasal sumatriptan 20mg 30%; rectal sumatriptan 25mg 31%; oral zolmitriptan 2.5mg 32%; oral rizatriptan 10mg 37%; oral eletriptan 40mg 37%; oral almotriptan 12.5mg 26%). Compared with oral sumatriptan 100mg (32%), the mean therapeutic gain was higher with oral eletriptan 80mg (42%) but lower with oral naratriptan 2.5mg (22%) or oral frovatriptan 2.5mg (16%). The few direct comparative randomised clinical trials with oral triptans reveal the same picture. Recurrence of headache within 24 hours after an initial successful response occurs in 30 to 40% of sumatriptan-treated patients. Apart from naratriptan, which has a tendency towards less recurrence, there appears to be no consistent difference in recurrence rates between the newer triptans and sumatriptan. Rizatriptan with its shorter time to maximum concentration (tmax) tended to produce a quicker onset of headache relief than sumatriptan and zolmitriptan. The place of triptans compared with non-triptan drugs in migraine therapy remains to be established and further RCTs are required.",2001.0,0,0
137,11167896,Tolerability of sumatriptan: clinical trials and post-marketing experience.,K M Welch; N T Mathew; P Stone; W Rosamond; J Saiers; D Gutterman,"Through December 1998, sumatriptan had been used to treat more than 236 million migraine attacks world-wide. In clinical trials alone, more than 88000 migraine patients had treated more than 300000 migraine attacks with sumatriptan, and 2000 normal healthy volunteers had been exposed to the drug. This paper describes the safety and tolerability profile of sumatriptan in three sections: adverse events reported in clinical trials, special issues, and spontaneous post-marketing reports of adverse reactions. Data from the extensive clinical trials programme coupled with information from nearly 10 years of experience in clinical practice demonstrate that sumatriptan is generally well-tolerated, with an acceptable benefit-risk ratio when used properly. Significant cardiovascular and cerebrovascular events are rare but have been observed. This fact highlights the need for careful patient selection and vigilant adherence to the prescribing recommendations for sumatriptan. The wealth of clinical trials and post-marketing information for sumatriptan may be useful in guiding prescribing decisions for members of this class of drugs.",2001.0,0,1
138,11167903,Are triptans with enhanced lipophilicity used for the acute treatment of migraine associated with an increased consulting rate for depressive illness?,D Millson; M Frischer; P Croft; P J Goadsby,"1997, sumatriptan-treated migraineurs had significantly higher depression PCRs (22.3%) compared with non-triptan users (19.3%), a difference of 6.4% (95% confidence interval (CI) 4.6-8.4%, P < 0.001). In the year (April 1997 to March 1998) following the launch of the TELs, depression PCRs were significantly higher among patients using these compounds compared with sumatriptan-treated patients (5.1%, CI 1.8-12.0%, P < 0.05). However, after taking account of prior depression (odds ratio (OR) 6.45, 95% CI 3.63-11.43), TELs were not significantly associated with depression (OR 0.27, 95% CI 0.03-2.13). Furthermore, rates of newly diagnosed depression after treatment were similar in the two triptan groups (sumatriptan 4.2%; TELs 3.9%). Although, the TELs are being prescribed to patients with higher pre-existing rates of depression, they are not associated with subsequently increased consulting for depressive illness compared with patients taking sumatriptan. This study highlights the potential to use GPRD to test targeted hypotheses exploring pharmacovigilance issues for patients using new medicines.",2001.0,0,0
139,11167913,Work and productivity loss in the rizatriptan multiple attack study.,E J Dasbach; G W Carides; W C Gerth; N C Santanello; J G Pigeon; ,"The objective of this study was to measure the self-reported effect of acute migraine and its treatment on paid work and productivity loss. Patients self-administered a questionnaire in which the impact of a recent migraine on paid work and productivity activities was assessed. We included the questionnaire in a randomized, double-blind, placebo-controlled, crossover, out-patient study designed to examine the safety and efficacy of rizatriptan (5-HT1B/1D receptor agonist) 10 mg p.o. in patients treating four separate migraine attacks. A total of 407 patients, aged 18-65 years, suffering from moderate to severe migrainous headaches was studied. Patients receiving rizatriptan compared with placebo reported 0.7 fewer hours (P < 0.01) of paid worked missed due to absenteeism, 0.4 fewer hours (P < 0.05) of productive time lost on the job, and 1.1 fewer total hours (P < 0.01) of work loss per migraine attack. Rizatriptan compared with placebo significantly reduced migraine-related work loss associated with absenteeism and decreased effectiveness on the job.",2001.0,0,1
140,11168604,Long-term efficacy and safety of oral almotriptan: interim analysis of a 1-year open study.,X Cabarrocas; R Esbri; F Peris; P Ferrer,"To assess the long-term tolerability and safety of a single, oral 12.5-mg dose of almotriptan and its efficacy in alleviating pain associated with consecutive migraine episodes occurring during a 12-month period. While sumatriptan appears to be effective for treatment of migraine, the drug has several properties that limit its use. Almotriptan, a new selective 5-HT1B/1D agonist, may be better tolerated over the long term. This 1-year study was conducted on 806 adults between the ages of 18 and 65 years suffering from migraine, either with or without aura. The patients met the criteria for study as outlined by the International Headache Society and were instructed on drug use. Oral almotriptan 12.5 mg was used to treat the attack of any pain severity and a second dose was permitted in case of relapse of pain during the first 24 hours. Rescue medication was provided. Efficacy and tolerability were assessed by a combination of patient reporting and clinical visit evaluations. Overall, almotriptan was well tolerated. At 2 hours, 81% of attacks were relieved; 56% of the subjects were entirely free of pain. These efficacy data are similar for the first as well as the last attack studied. At analysis, 534 patients had treated their migraines for at least 6 months. About half of all patients experienced at least one adverse event, with 87% of the events being mild or moderate in nature. The most frequent adverse events were back pain (7.23% of patients), bronchitis (5.76%), and influenzalike symptoms (5.62%). Seventy-one percent of the adverse events were not related to almotriptan use. Almotriptan at an oral dose of 12.5 mg is safe antimigraine treatment. The safety profile results are similar to those obtained in other controlled triptan clinical studies. Almotriptan is efficacious in moderate-to-severe migraine pain and can be used repeatedly in recurrent episodes. The long-term safety data will be reanalyzed when full data become available.",2001.0,0,1
141,11192144,"One-year tolerability and efficacy of sumatriptan nasal spray in adolescents with migraine: results of a multicenter, open-label study.",A D Rothner; P Winner; R Nett; M Asgharnejad; A Laurenza; R Austin; M Peykamian,"The objective of this study was to determine the 1-year tolerability and efficacy of sumatriptan nasal spray (NS) at doses of 5, 10, and 20 mg for the treatment of acute migraine in adolescents. This was a prospective, multicenter, open-label, 1-year, multiple-attack study. Adolescents (aged 12-17 years) with a > or =6-month history of migraine with or without aura, 2 to 8 moderate or severe migraines per month, and a typical migraine duration of > or =4 hours were eligible for participation. After initial treatment with sumatriptan 10 mg, the dose could be adjusted down to 5 mg or up to 20 mg at the investigator's discretion to optimize tolerability or efficacy. Patients could treat an unlimited number of moderate or severe migraine attacks, provided there was a 24-hour headache-free period between treated attacks and a 2-hour period between doses of sumatriptan NS. A second dose of sumatriptan NS was available for headache recurrence 2 to 24 hours after initial treatment; no more than 2 doses could be used within a 24-hour period. Adverse events, vital signs, electrocardiographic and physical findings, and laboratory variables were assessed. Headache response (reduction of moderate/severe predose pain to mild/no pain) and pain-free response (reduction of moderate/severe predose pain to no pain) were reported by patients 2 hours after dosing. A total of 437 patients treated > or =1 migraine; 3272 total attacks were treated, with 3675 drug exposures (mean, 1.1 dose/attack). Patients had a mean age of 14.1 years, 91% were white, and 53% were female. Seven patients used the 5-mg dose; meaningful conclusions concerning this dose could not be made. Drug-related adverse events were reported in 33% of attacks with the 10-mg dose and 31% with the 20-mg dose; most were related to taste disturbance. Adverse events did not increase with a second dose or over time. Four percent (16/437) of patients withdrew due to drug-related adverse events. One serious adverse event, a facial-nerve ischemic event (10-mg dose), was considered drug related. No drug-related changes in vital signs or electrocardiographic findings were observed. Headache response 2 hours after dosing was reported by 76% of patients taking the 10-mg dose and 72% of those taking the 20-mg dose. Pain-free response 2 hours after dosing was reported by 43% and 40% of patients in the 10- and 20-mg groups, respectively. Based on these results, sumatriptan NS at doses of 10 and 20 mg was well tolerated and effective in the 1-year treatment of multiple migraine attacks in adolescents.",2001.0,0,1
142,11200789,Rational migraine management: optimising treatment with the triptans.,D S Millson,"In the last two years, a number of 5-HT1B/1D agonist triptans with enhanced lipophilicity (TELs) relative to the first drug of this class, sumatriptan, have been approved for marketing in most countries of the world (naratriptan, rizatriptan and zolmitriptan). In addition, at least three others are in advanced stage of clinical development (almotriptan, eletriptan, and frovatriptan). This paper sets out to review the recent data with the aim of identifying: 1) What are the critical differences between the TELs and sumatriptan? 2) How do the currently licensed TELs compare? 3) Is it possible to provide a rational approach to migraine therapy based on objective differences in the clinical profile of these new drugs? Recent randomised controlled and comparator data were reviewed, including the independent FDA assessment of rizatriptan. Critical differences for the new TELs (naratriptan, rizatriptan and zolmitriptan) which may lead to more rational migraine management: Both rizatriptan (10 mg) and zolmitriptan (2.5 mg and 5.0 mg) have demonstrated superior efficacy to sumatriptan 100 mg, and 25 and 50 mg respectively. Therefore, for first line use either rizatriptan or zolmitriptan would be appropriate for moderate and severe headache. Rizatriptan has a more rapid onset of action than sumatriptan 100 mg. Both rizatriptan and zolmitriptan have a more rapid onset of action than naratriptan. Therefore, for a rapid onset of action either rizatriptan or zolmitriptan would be appropriate. Naratriptan would appear to have a lower recurrent headache rate than sumatriptan, rizatriptan or zolmitriptan. However, 24-hour efficacy rates for zolmitriptan 2.5 mg were significantly greater than for sumatriptan 25 mg and 50 mg and were not significantly different from naratriptan. Therefore, for headaches of long duration and with a tendency to recur (e.g. menstrual headaches) either naratriptan or zolmitriptan would be appropriate. Naratriptan has lower reported adverse event rates comparable with placebo. This would support the use of naratriptan 2.5 mg in patients who have demonstrated poor tolerance to the ""triptan type"" adverse events.",2001.0,0,0
143,11200792,The effectiveness of combined oral lysine acetylsalicylate and metoclopramide (Migpriv) in the treatment of migraine attacks. Comparison with placebo and oral sumatriptan.,P Tfelt-Hansen,"In two, double-blind, randomised, clinical, trials (RCTs), oral lysine acetylsalicylate (1620 mg, equivalent to 900 mg aspirin) combined with metoclopramide (10 mg) (LAS + MTC) was compared with placebo, and with oral sumatriptan (100 mg) in one of these RCTs. In both RCTs the LAS + MTC combination was superior to placebo with therapeutic gains (percentage relief after active treatment minus percentage relief after placebo) of 30% and 31% for the first treated attack. These therapeutic gains are in the same range as those found for 100 mg oral sumatriptan, and in the comparative RCT the LAS + MTC combination was quite comparable to 100 mg sumatriptan, with success rates for the first attack of 57% and 53%, respectively.",2001.0,0,1
144,11200793,NSAIDs: behind the mechanisms of action.,F C Tulunay,"Non-steroidal anti-inflammatory drugs (NSAIDs) are a heterogeneous group of compounds. These heterogeneous agents have a similar therapeutic action for the treatment of pain, fever and inflammation. The major mechanism of action of NSAIDs is the inhibition of cyclooxygenase (COX), the enzyme catalysing the synthesis of prostaglandins (PGs). Appropriate and effective treatment for migraine depends upon an accurate diagnosis. The goals of treatment are amelioration of the symptoms of an acute attack and prevention of further attacks.",2001.0,0,0
145,11200800,Pharmacology of emesis and gastrointestinal motility: implications for migraine.,F De Ponti,"This paper outlines the physiopharmacology of emesis and its gastrointestinal motor correlates in relation to the possible treatment strategies of a migraine attack. The gastrointestinal motor correlates of vomiting consist of a stereotyped motor response to diverse stimuli and basically include gastric relaxation and a series of events (intestinal motor inhibition and disruption of slow wave activity) in preparation for the occurrence of a retrograde giant contraction that propagates orally and empties intestinal contents into the stomach. These motor correlates always accompany vomiting, but may also appear as an independent phenomenon. Antidopaminergic agents, such as metoclopramide and domperidone, have antiemetic/prokinetic properties, block the gastrointestinal motor correlates of vomiting and may speed up absorption of antimigraine agents. The use of 5-HT4 receptor agonists may be an alternative strategy to achieve prokinesia during a migraine attack, although this issue still needs to be fully addressed by controlled studies. Sumatriptan was found to induce gastric relaxation and delay gastric emptying, but the impact of these effects during a migraine attack remains to be determined.",2001.0,0,0
146,11206865,Evidence-based migraine therapy: learning needs and knowledge assessment.,R A Purdy,"One of the primary goals of continuing medical education (CME) is to enhance the learners' performance, and a major goal of evidence-based medicine (EBM) is to improve knowledge of current best care. This paper overviews the use of a Learning Needs and Knowledge Assessment tool to highlight the potential learning needs and knowledge of neurologists and to focus the issues, interest and interactions of neurologists in a workshop on EBM migraine therapy. Virtually all neurologists felt they used evidence-based medicine in their daily practice. Surprisingly, 50% of neurologists agreed that they were uncertain which triptan to use. The great majority of neurologists felt that the triptans were not all equally efficacious. Our survey identified significant knowledge gaps among neurologists regarding how to appraise the validity of evidence from a randomized clinical trial, and with regard to what are the most clinically useful measures of benefit in clinical trials.",2001.0,0,0
147,11210397,Pharmacokinetics of naratriptan in adolescent subjects with a history of migraine.,M L Christensen; S K Eades; E Fuseau; R D Kempsford; S J Phelps; L J Hak,"Naratriptan is a novel 5-HT1 agonist developed to treat acute migraine. The study objective was to characterize the pharmacokinetics of oral naratriptan in adolescent migraine patients outside a migraine attack. Subjects received a single 2.5 mg naratriptan tablet. Serial serum samples for naratriptan concentrations were collected over 24 hours. Blood pressure, pulse rate, and 12-lead ECG were recorded at baseline and at regular intervals after dosing. Seven patients--3 males and 4 females, 12 to 16 years of age--received drug and completed the study. The geometric mean and 95% confidence interval maximum concentration (Cmax) was 8.0 ng/mL (5.9-10.7), elimination half-life (t1/2) was 4.9 hours (4.5-5.4), area under the concentration-time curve (AUC) was 74.6 ng.h/mL (56.6-98.2), and apparent total clearance (Cl/F) was 558.8 mL/min (424.3-735.9). The median time to maximal concentration (tmax) was 4 hours, with a range of 1.5 to 4. Blood pressure, pulse rate, and ECG parameters did not change significantly from baseline. No serious adverse events or subject withdrawal after drug administration occurred. Oral naratriptan pharmacokinetic parameters in adolescents were similar to values reported in adults. Naratriptan doses for adolescents older than 12 years of age would be expected to be similar to adult doses.",2001.0,0,0
148,11210405,Evaluation of the potential pharmacokinetic interaction between almotriptan and fluoxetine in healthy volunteers.,J C Fleishaker; K K Ryan; B J Carel; N E Azie,"This study was designed to assess the pharmacokinetics of almotriptan, a 5HT1B/1D agonist used to treat migraine attacks, when administered in the presence and absence of fluoxetine. Healthy male (n = 3) and female (n = 11) volunteers received (1) 60 mg fluoxetine daily for 8 days and 12.5 mg almotriptan on Day 8 and (2) 12.5 mg almotriptan on Day 8, according to a two-way crossover design. Plasma and urinary almotriptan concentrations were measured by HPLC methods. Treatment effects on pharmacokinetic parameters were assessed by analysis of variance. Mean almotriptan Cmax was significantly higher following combination treatment with fluoxetine (52.5 +/- 11.9 ng/ml vs. 44.3 +/- 10.9 ng/ml, p = 0.023). Mean AUC0-infinity was not significantly affected by fluoxetine coadministration (353 +/- 55.7 ng.h/ml vs. 333 +/- 33.6 ng.h/ml, p = 0.059). Confidence interval analysis (90%) of log-transformed pharmacokinetic parameters showed that the confidence interval for AUC0-infinity was within the 80% to 125% limit for equivalence, but Cmax was not (90% CI 106%-134% of the reference mean). Adverse events were mild to moderate in intensity, and no clinically significant treatment effects on vital signs or ECGs were observed. The results show that fluoxetine has only a modest effect on almotriptan Cmax. Concomitant administration of the two drugs is well tolerated, and no adjustment of the almotriptan dose is warranted.",2001.0,0,0
149,11219473,"Treatment satisfaction, functional status, and health-related quality of life of migraine patients treated with almotriptan or sumatriptan.",S S Colman; M I Brod; A Krishnamurthy; C R Rowland; K J Jirgens; B Gomez-Mancilla,"Patient-reported outcomes, such as treatment satisfaction, functional status, and health-related quality of life (HRQOL) are essential components of migraine research. Almotriptan is a new selective serotonin 1B/1D agonist triptan migraine treatment. The purpose of this double-blind, multicenter, randomized, parallel-group study was to compare treatment satisfaction, functional status, and HRQOL of patients treated with oral almotriptan versus sumatriptan, the leading triptan on the market. Migraine patients, aged 18 to 71 years, took equivalent oral doses of 12.5 mg almotriptan or 50 mg sumatriptan for the abortive treatment of a migraine headache. Treatment satisfaction differences between study groups were assessed using a 6-item measure to determine patients' satisfaction with pain relief and satisfaction with side effects 48 hours after drug administration. Functional status was assessed by analyzing the change in patients' ability to perform normal activities during the course of the migraine. HRQOL was compared between treatment groups at 24 hours using the Migraine Quality of Life Questionnaire. End points were assessed using entries from patients' 48-hour diaries. A total of 1173 patients were treated with almotriptan or sumatriptan. There were no significant differences between the 2 treatment groups in terms of satisfaction with pain relief; however, patients in the almotriptan group were significantly more satisfied (less bothered) with side effects than those receiving sumatriptan (P = 0.016). Functional status and HRQOL outcomes were not significantly different between groups. In this study, migraine patients treated with almotriptan were significantly more satisfied with the side-effect profile of the drug than patients treated with sumatriptan. The results of this study may help inform practicing physicians and neurologists about the potential treatment satisfaction advantages of almotriptan.",2001.0,0,1
150,11221281,Pharmacology and efficacy of eletriptan for the treatment of migraine attacks.,H C Diener; A McHarg,"Sumatriptan, a 5-HT 1B/1D agonist, was introduced 10 years ago and was the most effective therapy for migraine attacks at that time. Eletriptan is a new 5-HT 1B/1D agonist with high potency and selectivity at 5-HT 1B/1D receptors. It is effective in animal models in which the vascular and neurogenic mechanisms implicated in migraine were measured. Eletriptan is selective for the intracranial blood vessels over other extracranial vasculature, in particular coronary arteries. Eletriptan has a rapid and complete oral absorption and a good oral bioavailability in migraineurs. In comparative trials 20 mg, 40 mg and 80 mg eletriptan, 100 mg sumatritpan and placebo were compared for the treatment of migraine attacks. All three doses of eletriptan were statistically superior to placebo for headache response and headache-free patients. The 80 mg dose of eletriptan was also superior to sumatriptan 100 mg. Headache recurrence, defined as return of moderate or severe headache within 24 hours of dosing and following a headache response at two hours after initial dosing, occurred in 33% of the patients following 100 mg sumatriptan and in 28%, 34% and 32% after 20 mg, 40 mg and 80 mg eletriptan. In another large trial, headache response rates were significantly higher for both doses of eletriptan (64% for 40 mg and 67% for 80 mg) than for two doses of sumatriptan (50% for 50 mg and 53% for 100 mg). Eletriptan 40 mg or 80 mg was also superior to ergotamine plus caffeine (Cafergot). In summary, eletriptan is a highly effective and fast-acting drug for the treatment of acute migraine attacks.",2001.0,0,1
151,11227394,Effectiveness of eletriptan in reducing time loss caused by migraine attacks.,N E Wells; T J Steiner,"The growing literature on the economics of migraine and its treatment generally indicates that the direct healthcare costs of managing the disorder are relatively low compared with the personal and societal burdens resulting from the disruption to normal functioning caused by migraine attacks. To investigate the effectiveness of eletriptan, a new selective serotonin (5-hydroxytryptamine; 5-HT)5-HTIB/ID agonist, in reducing both the patient-focused burden of migraine and the amount of work time foregone during a single attack. In a phase III, multinational, randomised clinical trial, 692 patients treated a migraine attack with eletriptan 40 mg or 80 mg, or placebo. Patients responded to a questionnaire seeking information concerning the amount of time lost from usual activities during the attack. Time loss assessments were made 24 hours after the last dose taken and recorded in a diary. Patients receiving either dose of the active compound were unable to perform their usual activities for a median period of 4 hours compared with 9 hours experienced by those taking placebo. This difference was highly statistically significant (p < 0.001). The time saving associated with eletriptan usage reflected the differences in efficacy findings in the clinical component of the study. In this placebo-controlled trial, eletriptan produced a significant reduction in the loss of usual functioning time associated with a migraine attack. This gain clearly represents a substantial benefit to patients with migraine irrespective of how it might most appropriately be valued in monetary terms. Further methodological progress in this area is warranted.",2001.0,0,1
152,11243418,Hemodynamic and electrocardiographic effects of almotriptan in healthy volunteers.,M Boyce; K Dunn; S Warrington,"We studied the possible cardiovascular effects of single oral doses of 12.5, 25, and 50 mg of almotriptan, a new triptan for treatment of migraine, in a randomized, double-blind, four-way crossover, placebo-controlled study in 24 healthy volunteers aged 18 to 35 years. Doses were given at 1-week intervals. Cardiovascular effects were assessed by frequent recording of blood pressure and heart rate, 12-lead electrocardiogram (ECG) (recorded at 25 mm/s paper speed and 1 cm/mV and at 50 mm/s and 2 cm/mV), and continuous ECG monitoring for 12 h after each dose. ECG variables, PR, QRS, QT interval, and QT dispersion, were measured. QT intervals were adjusted for heart rate using Bazett's formula. None of the doses of almotriptan differed significantly from placebo with respect to PR, QRS, or QTc intervals, QTc dispersion, heart rate, or continuous ECG monitoring. Almotriptan 12.5 mg did not differ significantly from placebo with respect to systolic or diastolic blood pressure, but almotriptan 25 and 50 mg raised systolic blood pressure by a mean of 2.78 and 4.17 mm Hg, and diastolic blood pressure by 3.77 and 6.11 mm Hg, respectively, during 0 to 4 h after dosing. Thus none of the doses of almotriptan affected the ECG, and the 12.5-mg dose (the expected therapeutic dose) had no hemodynamic effects. Almotriptan in doses of 25 and 50 mg caused a small, dose-related increase in systolic and diastolic blood pressure, as seen with other triptans.",2001.0,0,0
153,11249525,Migraine pharmacotherapy with oral triptans: a rational approach to clinical management.,D S Millson; S J Tepper; A M Rapoport,"The recent clinical development of a number of migraine specific 5-HT1B/1D agonist triptans with enhanced lipophilicity (TELs), relative to the first drug of this class sumatriptan, and with a range of different metabolic, pharmacokinetic and receptor affinity profiles, provides the potential for critically different clinical profiles. Eletriptan, naratriptan, rizatriptan and zolmitriptan display both increased stability to first pass metabolic inactivation by monoamine oxidase (MAO-A) and enhanced lipophilicity (4- to > 120-fold more than sumatriptan), leading to increased oral bioavailability (2- to 5-fold more than the 14% reported for oral sumatriptan). Central penetration and increased receptor affinity and selectivity for the neuronal (5-HT1D) receptor also combine to allow for lower total oral dosing (i.e., unit doses of 15 mg or less compared with 50-300 mg doses of sumatriptan) and reduced peripheral exposure to the coronary vasoconstrictor (5-HT1B) receptor. The notable exception being eletriptan, where an active P-glycoprotein blood-brain barrier efflux system effectively negates these benefits and requires an 80 mg oral dose. Differences in the metabolic balance between hepatic P450 (especially CYP 1A2) and MAO-A inactivation lead to potential drug interactions for all TELs with the oral contraceptive pill (OCP), fluvoxamine and the quinilone antibiotics (with increased triptan levels). An important but complex MAO-A interaction between a metabolite of propranolol and rizatriptan mandates dosage reduction (to 5 mg) for rizatriptan in the presence of propranolol treatment. There is also an absolute contraindication for the concurrent administration of the MAO-A inhibitor moclobemide and rizatriptan. All the new-marketed TELs have potential clinical benefits and were well-tolerated relative to sumatriptan. Both rizatriptan (10 mg) and zolmitriptan (2.5 mg and 5 mg) demonstrate at least equivalent efficacy to sumatriptan 25, 50 and 100 mg, respectively, making them suitable first line agents for moderate or severe migraine headaches. Rizatriptan has the fastest onset of effect of the TELs. Naratriptan would appear to have lower recurrent headache rate than sumatriptan, rizatriptan or zolmitriptan. Therefore, for headaches of long duration and with a tendency to recur naratriptan may be the most appropriate treatment. Thus, knowledge of the metabolic, pharmacokinetic and clinical profiles of the TELs facilitates the selection of a triptan which allows optimisation of the clinical benefits for individual patients, minimising the risk of drug interactions and a minimally effective dose to reduce potential adverse events (AEs).",2001.0,0,0
154,11252291,A systematic review of the use of triptans in acute migraine.,M J Gawel; I Worthington; A Maggisano,"A systematic review of the literature was undertaken, to consolidate evidence concerning the efficacy and safety of triptans currently available in Canada (sumatriptan, rizatriptan, naratriptan, zolmitriptan), and to provide guidelines for selection of a triptan. Data from published, randomized, placebo-controlled trials were pooled and a combined number needed to treat (NNT) and number needed to harm (NNH) was generated for each triptan. Direct comparative trials of triptans were also examined. The lowest NNT for headache response/pain-free at one/two hours is observed with subcutaneous sumatriptan. Among the oral formulations, the lowest NNT is observed with rizatriptan and the highest NNT with naratriptan. The lowest NNH is observed with subcutaneous sumatriptan. Triptans are relatively safe and effective medications for acute migraine attacks. However, differences among them are relatively small. Considerations in selecting a triptan include individual patient response/tolerance, characteristics of the attacks, relief of associated symptoms, consistency of response, headache recurrence, delivery systems and patient preference.",2001.0,0,1
155,11264684,"Naratriptan as short-term prophylaxis of menstrually associated migraine: a randomized, double-blind, placebo-controlled study.",L Newman; L K Mannix; S Landy; S Silberstein; R B Lipton; D G Putnam; C Watson; M Jöbsis; A Batenhorst; S O'Quinn,"To determine the efficacy of naratriptan 1-mg and 2.5-mg tablets twice daily compared with placebo as short-term prophylaxis of menstrually associated migraine. Approximately 60% of women with migraine report headaches associated with their menstrual cycles. Results from an open-label study suggest that short-term administration of sumatriptan is useful in the prophylaxis of menstrually associated migraine. A randomized, double-blind, three-arm, parallel-group, placebo-controlled study was conducted in women aged 18 years or older with a history of migraine with or without aura, as defined by the International Headache Society, of at least 6 months. Two dose strengths of naratriptan (1 mg, 2.5 mg) or identical-appearing placebo tablets (1:1:1) were administered twice daily for 5 days starting 2 days prior to the expected onset of menses across four perimenstrual periods. End points included the number of menstrually associated migraines, total migraine days, peak headache severity, lost work/activity time, migraine-related quality of life, and incidence of adverse events. Overall, the intent-to-treat population comprised 206 women (naratriptan 1 mg, n = 70; naratriptan 2.5 mg, n = 70, and placebo, n = 66); 171 women treated four perimenstrual periods. Significantly more perimenstrual periods per subject treated with naratriptan, 1 mg, were headache-free compared with placebo (50% versus 25%, P =.003). Naratriptan, 1 mg, significantly reduced the number of menstrually associated migraines (2.0 versus 4.0, P <.05) and menstrually associated migraine days (4.2 versus 7.0, P <.01) compared with placebo. More patients treated with naratriptan, 1 mg, were headache-free across all treated perimenstrual periods compared with placebo (23% versus 8%). No difference in headache severity was observed in breakthrough headaches. The incidence and severity of adverse events was similar across treatment groups. Naratriptan, 2.5 mg, was not statistically superior to placebo for any measure. Naratriptan, 1 mg, with tolerability similar to placebo, is an effective, short-term, prophylactic treatment for menstrually associated migraine.",2001.0,0,1
156,11264685,Differentiating the efficacy of 5-HT(1B/1D) agonists.,F D Sheftell; A W Fox; R E Weeks; S J Tepper,"To examine, for a set of published clinical trials of serotonin (5-HT(1B/1D)) agonists as acute treatments for migraine, whether transformation of efficacy data into therapeutic gain (TG) or number needed to treat (NNT) is useful. Pivotal clinical trials of 5-HT(1B/1D) agonists in migraine use a primary end point of change in pain score from 3 or 2 to 1 or 0. Placebo response rates among such studies are variable. Meta-analytic comparisons of 5-HT(1B/1D) agonists often employ TG and NNT as efficacy measures. Data from US product labeling or published sources were converted into TG (TG = active response rate [%] - placebo response rate [%]) and NNT (NNT = 1/TG). Pivotal clinical trial data were compared before and after transformation. Therapeutic gain ranged from 17.5% to 51%. The transformation of TG into NNT yielded no clinically significant difference in efficacy estimate for the range of 17.5% to 47% (N = 29 clinical trials). However, NNT and TG had a nonlinear relationship for some secondary end points. When the relationship between the standard primary and secondary end points was compared, the correlation of TG with clinical disability (Pearson coefficient R = 0.93) was stronger than for NNT. Placebo response rates correlated more strongly with NNT (R = 0.66) than active response rates (R = 0.42; N = 29 clinical trials), although both TG and NNT were sensitive to placebo response rate. Transforming efficacy rates into TG or NNT adds no new information to placebo-controlled trials. The variables, TG and NNT, should not be used to compare members of this class of drugs. Migraine therapies can only be compared using well-designed head-to-head studies and not by meta-analysis. Broader measures of efficacy should be used to describe and compare 5-HT(1B/1D) efficacy.",2001.0,0,1
157,11264686,Efficacy and tolerability of rizatriptan 10 mg in migraine: experience with 70 527 patient episodes.,H Göbel; A Heinze; K Heinze-Kuhn; V Lindner,"As patients who suffer from migraine need long-term treatment, the safety and consistent efficacy of such therapy is very important. Concurrent illness and additional medication can interfere with the treatment chosen for the attacks of migraine. The objective of this open-label study was to investigate the efficacy and tolerability of rizatriptan, in the treatment of up to three attacks of migraine, in the clinical setting. From October 1998 to July 1999, 6 174 doctors enrolled 33 147 patients into the study (26 644 women, 650 men). The mean age was 42.7 years. We were able to examine standardized migraine diaries relating to 25 501 patients and 70 537 migrainous episodes. Rizatriptan scored consistently high on efficacy and showed a consistently rapid onset. There was no evidence of tolerance to repeated use. An effect was reported within 1 hour of ingestion in 79% of attacks treated. In 27.8% of attacks, remission of headache was complete at 1 hour. Two hours after ingestion, 74% of attacks had subsided completely. Repeated administration of rizatriptan was well tolerated, and few adverse effects were seen. The most common unwanted effects were dizziness, weakness, fatigue, and nausea. No cardiovascular disturbance was seen. In the clinical setting, rizatriptan, 10 mg, is an effective and well-tolerated agent for the treatment of migraine attacks. Particularly noteworthy is the rapid onset of effect, with swift disappearance of headache. Rizatriptan has a favorable side effect profile, and, provided contraindications are observed, severe adverse cardiovascular complications are extremely unlikely.",2001.0,0,1
158,11264695,Zolmitriptan versus sumatriptan comparison trial.,W J Becker,,2001.0,0,0
159,11279915,Comparison of rizatriptan and sumatriptan: a reply to O'Quinn et al.,P Tfelt-Hansen; J Goldstein; W Malbecq; C Lines,,2001.0,0,0
160,11279918,Headache and cardiovascular risk factors: positive association with hypertension.,M Cirillo; D Stellato; C Lombardi; N G De Santo; V Covelli,"The study analyzes the prevalence of cardiovascular risk factors in 1343 patients with severe headache (399 men and 944 women), aged 15 to 64 years; analyses were controlled for sex, age, and type and frequency of headache. Prevalence of various forms of headache was different between men and women. Age and days per year with headache were significantly different among various forms of headache. For men and women with headache, age directly related to prevalence of hypertension, hypercholesterolemia, and obesity. Due to low prevalence, analyses by age were not done for diabetes mellitus. For cigarette smoking, prevalence was not related to age in men, but was inversely related to age in women. With control for age, prevalence of cardiovascular risk factors was not significantly different among patients with different forms of headache, except for cluster headache. Among men with cluster headache, prevalence was high for cigarette smoking, but low for hypercholesterolemia. With control for age, days per year with headache did not relate to prevalence of cardiovascular risk factors except for cigarette smoking in men. Compared to data for a population sample used as control, patients with headache had higher prevalence of hypertension in both sexes, independent of age (odds ratio 1.51, 95% confidence interval 1.28 to 1.80); the difference between patients with headache and the control population was lower with increasing age. The high prevalence of hypertension among patients with headache was not due to overweight. The data indicate that headache is significantly associated with hypertension, but not with other cardiovascular risk factors.",2001.0,0,0
161,11279939,,,,,0,1
162,11284383,The multinational impact of migraine symptoms on healthcare utilisation and work loss.,W C Gerth; G W Carides; E J Dasbach; W H Visser; N C Santanello,"To compare self-reported healthcare resource utilisation, paid work loss, unpaid work loss and loss of effectiveness at work due to migraine in a clinic-based adult migraine population. The Migraine Background Questionnaire (MBQ) was translated and pilot-tested for use in 25 countries. The questionnaire was then self-administered by patients at a screening visit for 3 phase III clinical trials of rizatriptan [a selective serotonin (5-hydroxytryptamine) 5-HT1B/1D receptor agonist] in 23 US and 78 non-US sites. Persons 18 to 65 years of age with at least a 6-month history of moderate to severe migraines prior to the screening visit were surveyed. A total of 2670 persons (54.7% Europe, 16.5% Latin America, 23.1% North America, 5.5% other countries) completed the MBQ and had responses which could be analysed. On average, each patient reported 2.78 doctor visits, 0.53 emergency room visits and 0.06 hospitalisations related to migraine per year. Patients self-reported being only 46% effective while on the job with migraine symptoms. Extrapolation of patient self-reported work and productivity loss for the last 4 weeks to an annual basis suggested that clinic-based patients with migraine lose 19.5 workday equivalents (8.3 days due to absenteeism, 11.2 days due to reduced workday equivalents) due to migraine per year. In the US, the annual employer cost of this total migraine-related work loss is estimated to be $US3309 (2000 values) per patient with migraine. The levels of self-reported healthcare resources utilised for migraine and work loss were generally consistent across geographic regions. The impact of migraine symptoms on healthcare resource utilisation and work loss was similar across most measures in Europe, Latin America, North America and other countries. Total migraine-related work loss due to absenteeism and reduced workday equivalents accounts for most of the economic burden of migraine, regardless of country, in a clinic-based migraine population.",2001.0,0,0
163,11284462,Crossover comparison of rizatriptan 5 mg and 10 mg versus sumatriptan 25 mg and 50 mg in migraine. Rizatriptan Protocol 046 Study Group.,J Goldstein; R Ryan; K Jiang; A Getson; B Norman; G A Block; C Lines,"Rizatriptan is a selective 5-HT1B/1D receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This double-blind, placebo-controlled, crossover study compared rizatriptan 5 mg versus sumatriptan 25 mg, and rizatriptan 10 mg versus sumatriptan 50 mg. A total of 1329 patients were allocated to one of five groups for treatment of two attacks: rizatriptan 5 mg/sumatriptan 25 mg; sumatriptan 25 mg/rizatriptan 5 mg; rizatriptan 10 mg/sumatriptan 50 mg; sumatriptan 50 mg/rizatriptan 10 mg; placebo/placebo. For each attack, patients rated headache severity, presence of associated symptoms, and functional disability prior to dosing and at intervals through 4 hours thereafter. Patients also rated their satisfaction with medication. Rizatriptan 5 mg and 10 mg provided faster relief of headache pain and greater relief of migraine symptoms than the 25-mg and 50-mg doses of sumatriptan, respectively. The response to rizatriptan was better than sumatriptan on additional measures including functional disability and satisfaction with medication. All active treatments were highly effective compared to placebo and acted as early as 30 minutes after dosing. All active treatments were well-tolerated and showed comparable safety profiles.",2001.0,0,1
164,11284463,Oral rizatriptan versus oral sumatriptan: a direct comparative study in the acute treatment of migraine. Rizatriptan 030 Study Group.,P Tfelt-Hansen; J Teall; F Rodriguez; M Giacovazzo; J Paz; W Malbecq; G A Block; S A Reines; W H Visser,"Rizatriptan is a potent, oral, 5-HT1B/1D agonist with more rapid absorption and higher bioavailability than oral sumatriptan. It was postulated that this would result in more rapid onset of effect. This randomized, double-blind, triple-dummy, parallel-groups study compared rizatriptan 5 mg, rizatriptan 10 mg, sumatriptan 100 mg, and placebo in 1268 outpatients treating a single migraine attack. Headache relief rates after rizatriptan 10 mg were consistently higher than sumatriptan at all time points up to 2 hours, with significance at 1 hour (37% versus 28%, P = 0.010). All active agents were significantly superior to placebo with regard to headache relief and pain freedom at 2 hours (P < or = 0.001). The primary efficacy endpoint of time to pain relief through 2 hours demonstrated that, after adjustment for age imbalance, rizatriptan 10 mg had earlier onset than sumatriptan 100 mg (P = 0.032; hazard ratio 1.21). Rizatriptan 10 mg was also superior to sumatriptan on pain-free response (P = 0.032), reduction in functional disability (P = 0.015), and relief of nausea at 2 hours (P = 0.010). Significantly fewer drug-related clinical adverse events were reported after rizatriptan 10 mg (33%, P = 0.014) compared with sumatriptan 100 mg (41%). We conclude that rizatriptan 10 mg has a rapid onset of action and relieves headache and associated symptoms more effectively than sumatriptan 100 mg.",2001.0,1,1
165,11284464,Efficacy and safety of rizatriptan versus standard care during long-term treatment for migraine. Rizatriptan Multicenter Study Groups.,G A Block; J Goldstein; A Polis; S A Reines; M E Smith,"Rizatriptan is a novel, selective 5-HT1B/1D receptor agonist with a rapid onset of action after oral dosing for the acute treatment of migraine. We conducted a long-term (up to 1 year), multicenter, randomized study in 1831 patients treating more than 46,000 attacks to compare the efficacy and tolerability of rizatriptan 5 mg and 10 mg to standard care medications routinely used for the acute treatment of migraine attacks. Both doses of rizatriptan were highly effective, without evidence of tachyphylaxis. Rizatriptan 10 mg was consistently superior (P < 0.05), both to the 5-mg dose and to standard care, in providing relief in 90% of attacks, with 50% pain-free by 2 hours after dosing. The most common dose-related adverse events were nausea, somnolence, and asthenia/fatigue. Based on this large, multicenter, long-term trial, rizatriptan is an important new oral agent for the acute treatment of migraine.",2001.0,0,1
166,11286039,Efficacy and tolerability of sumatriptan in the treatment of multiple migraine attacks.,G Bussone; G C Manzoni; P Cortelli; M Roncolato; L Fabbri; C Benassuti,"This cross-over, double blind, randomized, multicentre study evaluated the consistency of efficacy and safety of oral sumatriptan in 233 migraneurs. The patients received 50 mg oral sumatriptan or placebo for the treatment of 12 migraine attacks. Within each group of 4 attacks, three were treated with sumatriptan and one with placebo, according to a randomization list. Over all the attacks, the efficacy rate was statistically significant for sumatriptan against placebo at 2 or 4 hours (2 hours: sumatriptan 60%, PLO 38%, p < 0.001; 4 hours sumatriptan 79%, PLO 47%, p < 0.001). Oral sumatriptan was similarly effective at relieving the associated symptoms and at reducing clinical disability in most attacks. The incidence of adverse events did not differ between treatment groups. All the events recorded were mild to moderate as intensity and resolved spontaneously.",2001.0,0,1
167,11286443,Cluster headache: review of the literature.,J M Zakrzewska,"All papers on cluster headaches were reviewed according to preset criteria under the following headings: classification, epidemiology, aetiology, pathophysiology, and clinical features. The management review used the Cochrane systematic review guidelines and so is based on randomized controlled trials wherever possible. A meta-analysis was not done. Other treatments are discussed and their drawbacks are highlighted and guidelines proposed based on the evidence of this review.",2001.0,0,1
168,11292228,Preventive therapy in pediatric migraine.,W W Wasiewski,"Preventive therapy for migraine headache includes identification of migraine precipitants, possible adjustments in lifestyle, appropriate management of acute headache, and, when necessary, the use of pharmacologic agents. There are no well-controlled clinical trials with sufficient patient numbers to support the use of any agent in the prevention of migraine headache in children. Data on the use of amitriptyline and divalproex sodium in open-label studies suggest that these agents may be efficacious. The mechanism of action for these agents is unknown but may be related to the 5-hydroxytyptamine-2 (5-HT2) receptor antagonism or regulation of ion channels. A review of the pertinent literature on migraine prophylaxis in children is presented. Dosing guidelines are presented based on the limited data available and clinical experience.",2001.0,0,0
169,11293557,Effect of encapsulation on absorption of sumatriptan tablets: data from healthy volunteers and patients during a migraine.,E Fuseau; O Petricoul; A Sabin; A Pereira; S O'Quinn; S Thein; M Leibowitz; H Purdon; S McNeal; R Salonen; A Metz; P Coates,"Some comparative trials of selective serotonin 1B/ID-agonists in migraine have reported -15% lower efficacy for sumatriptan tablets than that reported in placebo-controlled trials. This study was designed to test the hypothesis that the encapsulation methods used to mask active drug may delay absorption of sumatriptan from dosing to 2 hours after dosing (the traditional end point in clinical trials of migraine treatment), an effect that may be enhanced by migraine-associated gastric stasis. Two randomized, open-label, 2-way crossover trials were conducted to evaluate the absorption and bioequivalence of conventional 50-mg sumatriptan tablets and encapsulated 50-mg sumatriptan tablets in supine, fasted, healthy volunteers (Glaxo Wellcome protocol SUM40270) and supine patients experiencing a migraine (Glaxo Wellcome protocol SUM40268). Absorption was assessed by calculating the area under the plasma concentration-time curve from dosing to 2 hours after dosing (AUC2) and the times to first measurable plasma concentration, 10 ng/mL, 20 ng/mL, and maximum plasma concentration. Data for the AUC from time zero to infinity and maximum plasma concentration were used to assess standard bioequivalence, which is considered to occur when the 90% CIs for the geometric mean treatment ratios (test/reference) fall between 0.8 and 1.25. Study 1 included 26 healthy subjects (73% men, 27% women; mean age, 39.1 years), and study 2 included 30 patients with migraine (67% women, 33% men; mean age, 42.7 years). Sumatriptan absorption was delayed with the encapsulated tablet compared with the conventional tablet 0 to 2 hours after dosing, particularly during a migraine. AUC2 values with encapsulated sumatriptan compared with the conventional tablet were 21% lower in healthy volunteers (ratio of capsule/tablet, 0.79; 90% CI, 0.588-1.050) and 27% lower in patients experiencing a migraine (ratio of capsule/tablet, 0.73; 90% CI, 0.519-1.023). Standard bioequivalence was demonstrated in both healthy volunteers and patients experiencing a migraine. Encapsulation delayed absorption of sumatriptan 0 to 2 hours after dosing, particularly during a migraine. This delay in absorption of the encapsulated form may account for the lower efficacy of sumatriptan in some comparative studies.",2002.0,0,1
170,11293559,"Efficacy, tolerability, and patient satisfaction with 50- and 100-mg sumatriptan tablets in those initially dissatisfied with the efficacy of 50-mg sumatriptan tablets.",N Savani; V Pfaffenrath; L Rice; D Boswell; L Black; M Jones; Sumatriptan SUMB4007 Study Group,"Both 50- and 100-mg sumatriptan tablets are effective and well tolerated in the acute treatment of migraine. However, given a choice between the 2 doses, many patients in clinical practice and clinical studies prefer the 100-mg dose. This study was designed to assess whether patients initially dissatisfied with the efficacy of 50-mg sumatriptan tablets would be satisfied with 100-mg sumatriptan tablets. In phase 1 of the study, triptan-naive patients with migraine (International Headache Society diagnosis) received open-label treatment of 3 migraine attacks with 50-mg sumatriptan tablets. At the end of phase 1, those who were dissatisfied with the efficacy but satisfied with the tolerability of 50-mg sumatriptan tablets entered phase 2 and were randomized in a double-blind, parallel-group fashion to receive either 50- or 100-mg sumatriptan tablets for the treatment of 3 attacks. Patients who were satisfied with the efficacy or dissatisfied with the tolerability of the 50-mg tablets in phase 1 were given the option of continuing open-label treatment with 50-mg sumatriptan tablets in phase 2. The primary end point was the percentage of patients satisfied with medication at the end of phase 2 double-blind treatment. Patient satisfaction with specific medication attributes was assessed using the Patient Perception of Migraine Questionnaire. Seven hundred twenty-two patients were enrolled in phase 1 of the study (the intent-to-treat population), 609 of whom had evaluable satisfaction data at the end of open-label treatment. Three hundred twenty-six (54%) of these patients were satisfied with 50-mg sumatriptan tablets, whereas 283 (46%) were not satisfied. Among those who were dissatisfied, lack of efficacy was cited as the sole reason for dissatisfaction by 242 (86%). Two hundred thirty-one of those who were dissatisfied with efficacy only and wished to continue the study were randomized to double-blind treatment with either 50-mg sumatriptan tablets (n = 123; 82% female, 18% male; mean age, 37.6 years) or 100-mg sumatriptan tablets (n = 108; 86% female, 14% male; mean age, 36.0 years). The remaining 310 patients elected to continue open-label treatment with 50-mg sumatriptan tablets. At the end of double-blind treatment, 64 of 101 patients (63%) in the 100-mg group indicated that they were satisfied with treatment, compared with 55 of 113 (49%) in the 50-mg group (P = 0.031). Across the 3 attacks treated in the double-blind phase. headache relief 2 hours postdose was reported by 47% to 53% of patients in the 50-mg group and 45% to 60% of patients in the 100-mg group. The overall incidence of patients reporting > or =1 adverse event was 19% (23/123) in the 50-mg group and 22% (24/108) in the 100-mg group. For most patients, 50 mg is the appropriate starting dose of sumatriptan tablets. In patients who experience inadequate relief with 50 mg, increasing the dose to 100 mg is an appropriate therapeutic option.",2002.0,0,1
171,11298658,"Sumatriptan: economic evidence for its use in the treatment of migraine, the Canadian comparative economic analysis.",G Caro; D Getsios; J J Caro; G Raggio; M Burrows; L Black,"The objective of this study was to evaluate economic and health effects of sumatriptan relative to customary therapy in Canada. The relationship between treatment and functionality was established based on analysis of existing data from a multinational study. A Monte Carlo model was developed to simulate 1 year for each of customary therapy and six sumatriptan formulations. Costs are expressed in 1998 Canadian dollars. Sumatriptan is expected to reduce the time spent with migraine symptoms and resulting time lost. Under customary therapy, the annual cost of lost time is estimated at pound908 ($1973). With sumatriptan, these costs ranged from pound406 ($882) with subcutaneous sumatriptan to pound577 ($1254) with nasal sumatriptan 10 mg, saving pound331-502 ($719-1091) in the annual cost of time lost. All these benefits are expected to be obtained at an additional drug cost ranging from pound869 ($1889) for subcutaneous sumatriptan to pound278 ($605) for sumatriptan suppository. The cost of sumatriptan treatment is significantly offset by a substantial reduction of costs associated with time lost due to migraine symptoms.",2001.0,0,0
172,11298665,"Lack of pharmacokinetic interaction between the antimigraine compound, almotriptan, and propranolol in healthy volunteers.",J C Fleishaker; T A Sisson; B J Carel; N E Azie,"This study was designed to assess the pharmacokinetics of almotriptan, a 5-HT1B/1D agonist, when administered in the presence and absence of propranolol. Healthy male (n = 10) and female (n = 2) volunteers received (i) 80 mg propranolol twice daily for 7 days and 12.5 mg almotriptan on day 7, and (ii) 12.5 mg almotriptan on day 7, according to a two-way crossover design. Plasma and urinary almotriptan concentrations were measured by high performance liquid chromatography (HPLC) methods. Treatment effects on pharmacokinetic parameters were assessed by analysis of variance (ANOVA). Statistically significant differences between treatments in area under the curve (AUC), clearance, and half-life were observed (P < 0.03), but these differences were < 7%. Ninety percent confidence interval analysis of log-transformed pharmacokinetic parameters showed that the treatments were equivalent. Adverse events were mild to moderate in intensity, and no treatment effects on vital signs were observed. The results show that propranolol has no effect on the pharmacokinetics of almotriptan. Concomitant administration of the two drugs is well tolerated.",2001.0,0,0
173,11298669,Rizatriptan wafer--sublingual vs. placebo at the onset of acute migraine.,C Allen; J Dayno; C Lines; K McCarroll,,2001.0,0,0
174,11303412,Workplace productivity. A review of the impact of migraine and its treatment.,P Stang; R Cady; A Batenhorst; L Hoffman,"Migraine is a common disorder characterised by recurrent episodes of disability. Despite the high prevalence of migraine, data have been lacking on its impact in a working population. The advent of new therapies has stimulated interest in this area, and evidence is now available that documents the substantial impact of migraine on workplace productivity and the likelihood of untreated migraine leading to unemployment or underemployment for the patient. This paper reviews current findings of both observational and interventional studies about the impact of migraine on productivity and employment. When considered in the light of migraine demographics, the high prevalence of migraine, and its low consultation and treatment rates, this evidence indicates that improved screening and treatment for this common condition could have a substantial impact on worker productivity and on patient well-being.",2001.0,0,0
175,11313163,"Sumatriptan, 5-HT(1D) receptors and obsessive-compulsive disorder.",L M Koran; S Pallanti; L Quercioli,"After considering the effects of 5-HT receptor agonists with different binding profiles on the symptoms of obsessive-compulsive disorder (OCD), Zohar and Kindler hypothesized that the 5-HT(1D) receptor was implicated in this disorder's pathophysiology. We explored the 5-HT(1D) hypothesis in a 5-day, random, double-blind, placebo-controlled trial of oral sumatriptan 100 mg/day in medication-free adults with OCD. We hypothesized that sumatriptan, a 5-HT(1D) agonist, would diminish 5-HT release, thereby worsening OCD symptoms. We further hypothesized that by beginning to desensitize 5-HT(1D) receptors, sumatriptan pretreatment would promote a faster response or an increased likelihood of response to subsequent treatment with a selective serotonin reuptake inhibitor. The five sumatriptan subjects' OCD symptom worsening, as measured by the Yale-Brown scale ( upward arrow 17.6% (S.D. 14.6)), was significant when compared to the slight symptom decrease in the five placebo subjects ( downward arrow 5.2% (S.D. 4.9), P<0.015). The sumatriptan group did not exhibit a faster response or greater likelihood of response to a 90-day, open label trial of paroxetine. Longer term studies of the effects of 5-HT(1D) agonists on OCD symptoms are indicated. Zolmitriptan, a potent 5-HT(1D) receptor agonist with better penetration of the blood-brain barrier, may be a preferred challenge agent.",2001.0,0,0
176,11318884,Sumatriptan nasal spray and cognitive function during migraine: results of an open-label study.,K Farmer; R Cady; J Bleiberg; D Reeves; G Putnam; S O'Quinn; A Batenhorst,"To examine measures of cognitive function during acute migraine, before and after treatment with sumatriptan nasal spray, 20 mg. Migraineurs frequently report symptoms of cognitive impairment during migraine. The efficacy of sumatriptan for treatment of migraine-related cognitive impairment is undocumented. This open-label, single-attack study of 28 subjects used the Headache Care Center-Automated Neuropsychological Assessment Metrics, a computerized neuropsychological assessment battery, to measure cognitive function under three patient conditions: migraine-free, untreated migraine, and following sumatriptan (primary outcome). Headache response and pain-free response, percent effectiveness, and clinical disability were measured. Cognitive function (simple reaction time, sustained attention/concentration, working memory, visual-spatial processing) and alertness/fatigue were adversely affected during migraine compared with migraine-free performance (P<.05), and rapidly restored following sumatriptan nasal spray, 20 mg (P<.05). Headache and pain-free response were 86% and 68%, respectively, at 135 minutes postdose. Changes in migraine pain severity, clinical disability, and percent effectiveness following treatment with sumatriptan nasal spray, 20 mg, were significantly correlated with cognitive function measures across all subtests (P<.001). Sumatriptan nasal spray, 20 mg, restored migraine-related cognitive function and clinical disability.",2001.0,0,1
177,11318886,"Comparative study of a combination of isometheptene mucate, dichloralphenazone with acetaminophen and sumatriptan succinate in the treatment of migraine.",F G Freitag; R Cady; F DiSerio; A Elkind; R M Gallagher; J Goldstein; J A Klapper; A M Rapoport; C Sadowsky; J R Saper; T R Smith,"To compare the safety and efficacy of isometheptene mucate, dichloralphenazone with acetaminophen to sumatriptan succinate for the treatment of mild-to-moderate migraine, with or without aura, when taken at the first sign of an attack. The Food and Drug Administration approved sumatriptan succinate and the combination of isometheptene mucate, dichloralphenazone with acetaminophen for the treatment of migraine. As part of the stratified treatment of migraine, those patients whose headaches are mild or moderate may benefit from nontriptan medications. Additionally, early treatment of acute migraine before the headache has become moderate or severe may improve response to treatment. This was a multicenter, double-blind, randomized, parallel-group study to assess the safety and efficacy of the combination of isometheptene mucate, dichloralphenazone with acetaminophen and sumatriptan succinate in the early stages of a single migraine attack. Patients diagnosed with migraine, with or without aura, as defined by the International Headache Society diagnostic criteria were enrolled. One hundred thirty-seven patients were enrolled in the study. Data for efficacy were available for 126 patients; safety data were available for 128 patients. No statistically significant difference between the two active agents in the patient's response to treatment was demonstrated. Headache recurrence was not significantly different over the 24-hour evaluation period for those patients responding in the first 4 hours. In those with headache recurrence, it was statistically significantly more severe in those patients treated with sumatriptan succinate. Improvement in functional disability was, in general, better among those treated with isometheptene mucate, dichloralphenazone with acetaminophen. Global analysis of efficacy was similar in the two active groups. Patients treated with sumatriptan succinate were somewhat more likely to have adverse effects than the isometheptene mucate, dichloralphenazone with acetaminophen group. Both isometheptene mucate, dichloralphenazone with acetaminophen and sumatriptan succinate are safe and effective when used early in the treatment of an acute migraine. Several parameters suggest that isometheptene mucate, dichloralphenazone with acetaminophen may have a slight advantage compared with sumatriptan succinate in the early treatment of mild-to-moderate migraine.",2001.0,0,1
178,11327198,Pharmacokinetics and pharmacodynamics of the triptan antimigraine agents: a comparative review.,S S Jhee; T Shiovitz; A W Crawford; N R Cutler,"The current approach to antimigraine therapy comprises potent serotonin 5-HT1B/1D receptor agonists collectively termed triptans. Sumatriptan was the first of these compounds to be developed, and offered improved efficacy and tolerability over ergot-derived compounds. The development of sumatriptan was quickly followed by a number of 'second generation' triptan compounds, characterised by improved pharmacokinetic properties and/or tolerability profiles. Triptans are believed to effect migraine relief by binding to serotonin (5-hydroxy-tryptamine) receptors in the brain, where they act to induce vasoconstriction of extracerebral blood vessels and also reduce neurogenic inflammation. Although the pharmacological mechanism of the triptans is similar, their pharmacokinetic properties are distinct. For example, bioavailability of oral formulations ranges between 14% (sumatriptan) and 74% (naratriptan), and their elimination half-life ranges from 2 hours (sumatriptan and rizatriptan) to 25 hours (frovatriptan). Clearly, such diverse pharmacokinetic properties will influence the effectiveness of the compounds and favour the prescription of one over another in different patient populations. This article reviews the pharmacological properties of the triptans (time to peak plasma concentration, half-life, bioavailability and receptor binding) and relates these properties to efficacy and time of onset. It also considers the effects of concomitant medication, food, age and disease on the pharmacokinetics of the compounds. In addition, the relative merits, such as headache recurrence, tolerability and route of administration, are discussed. Finally, the performance of the triptans is considered in the context of direct head-to-head comparative trials that have assessed the efficacy profile of the compounds.",2001.0,0,0
179,11328332,"Zolmitriptan versus sumatriptan for the acute oral treatment of migraine: a randomized, double-blind, international study.",K Gruffyd-Jones; B Kies; A Middleton; L J Mulder; Ø Røsjø; D S Millson,"This randomized, double-blind, parallel-group study compared the efficacy and tolerability of zolmitriptan (2.5 or 5 mg) and sumatriptan (50 mg) in the acute oral treatment of up to six moderate-to-severe migraine attacks. The intention to treat (ITT) population comprised of 1522 patients: 500 treated with zolmitriptan 2.5 mg (2671 attacks), 514 with zolmitriptan 5 mg (2744 attacks) and 508 with sumatriptan 50 mg (2693 attacks). Overall, the 2-h headache response rates in these groups were 62.9, 65.7 and 66.6%, respectively. There were no statistically significant differences between sumatriptan 50 mg and zolmitriptan 2.5 mg (P = 0.12) or 5 mg (P = 0.80). Approximately 40% of patients in each group reported a 2-h headache response in > or = 80% of attacks. There were no statistically significant differences between the groups in the rates of headache response at 1 h (zolmitriptan 2.5 mg 36.9%, zolmitriptan 5 mg 39.5% and sumatriptan 50 mg 38.0%) or 4 h (70.3, 72.9 and 72.2%, respectively) or in the rates of meaningful migraine relief at 1, 2 or 4 h or sustained (24-h) pain relief. All treatments were well tolerated. In conclusion, zolmitriptan (2.5 or 5 mg) proved similarly efficacious compared with sumatriptan (50 mg), both in terms of response rates and consistency across attacks.",2001.0,1,1
180,11371755,Headache and female hormones: what you need to know.,S D Silberstein,"The normal female lifecycle is associated with hormonal milestones, including menarche, pregnancy, contraceptive use, menopause, and the use of replacement sex hormones. Attacks of migraine without aura, but not with aura, are more likely to occur 2 days before onset and on the first 2 days of menses, but they are not more severe than those that occur outside the perimenstrual period. Oral sumatriptan and naratriptan are effective as short-term perimenstrual prophylaxis. Postdural headache can occur during the postpartum period. The International Headache Society Task Force assessed the efficacy of treatment of women who had migraine with combined oral contraceptives and hormone replacement therapy, as well as the risk of ischemic stroke associated with their use. There is no contraindication to the use of oral contraceptives in women with migraine in the absence of migraine aura or other risk factors. There is a potentially increased risk of ischemic stroke in women with migraine who are using combined oral contraceptives and have additional risk factors that cannot easily be controlled, including migraine with aura. There is no compelling evidence that postmenopausal hormone replacement therapy either decreases or increases stroke risk.",2001.0,0,0
181,11371756,Recent development in paediatric headache.,V Guidetti; F Galli,"Headache is one of the most common disorders that occurs during the early, developmental years of life. The present review critically discusses the most recently published reports concerning headache with onset in youngsters, delineating the current status of research in the various fields and outlining areas that require further investigation. Age-related characteristics need to be taken into account with considering the aetiology, diagnosis and treatment of juvenile headache.",2001.0,0,0
182,11371757,Pharmacological opportunities and pitfalls in the therapy of migraine.,A May; P J Goadsby,"The mild vasoconstrictor effects of modern antimigraine drugs, such as serotonin (5-HT; 5-hydroxytryptamine)1B/D agonists, have led to a search for nonvasoconstrictor approaches to therapy. Such approaches have included substance P (neurokinin I) antagonists, endothelin antagonists and highly specific 5HT1D agonists. All of these substances are effective in animal models and have no significant vasoconstrictive effects. However, all of them failed to demonstrate any antimigraine effects. Current clinical and experimental evidence therefore supports the view that isolated peripheral trigeminal nerve inhibition is insufficient to relieve acute migraine.",2001.0,0,0
183,11379275,New generation anti-epileptics for facial pain and headache.,V Delvaux; J Schoenen,"The prophylactic management of recurrent head and facial pains may be challenging because of lack of efficacy and/or bothersome adverse effects of available drug therapies. New generation antiepileptic drugs offer new perspectives in difficult cases. We will review the available published data and present our experience with lamotrigine in various head and facial pains such as migraine, cluster headache, neuropathic trigeminal pain, atypical facial pain, and chronic tension-type headache. Twenty-five patients were enrolled and followed for 18 months. The dose was gradually increased in steps of 25 mg up to the effective dose (mean 250 mg/d). Lamotrigine was most effective in trigeminal neuralgia and dysesthesia, but was of little utility in the other head or facial pains.",2001.0,0,0
184,11380642,Oral almotriptan in the treatment of migraine: safety and tolerability.,D W Dodick,"To summarize safety and tolerability data on orally administered almotriptan from premarketing clinical trials. Almotriptan is a new 5-HT1B/1D receptor agonist similar to sumatriptan in mode of action and therapeutic efficacy. In addition, the safety and tolerability profile of almotriptan has been demonstrated in a number of controlled clinical trials. Sumatriptan is generally safe and well tolerated; however, in controlled clinical trials, it has been associated with chest symptoms (pressure, warmth, and other unpleasant sensations) with an incidence of 3% to 5%. Three phase 1 dose-finding and pharmacokinetic studies in healthy men and women volunteers were reviewed to assess the safety and tolerability of oral almotriptan at single doses ranging from 2 to 200 mg. The objective of one study was to evaluate cardiovascular safety. Two phase 2 trials assessed the safety and tolerability of single doses of 2 to 150 mg in migraine (n=911). Two phase 3 trials assessed the safety and tolerability of a single 12.5-mg oral dose after three attacks (n=910) and repeated doses of 12.5 mg for multiple attacks over the long term (n=747). All studies were conducted in Europe. Data from the United States is currently being analyzed and will be published at a later date. In phase 2 and 3 trials comprising more than 2500 patients with migraine and 15 000 attacks, adverse events were infrequent and mild. The most common events-dizziness, nausea and vomiting, headache, fatigue, paresthesia, and drowsiness-were reported in fewer than 3% of patients. At the recommended therapeutic dose of 12.5 mg, the adverse events profile was not statistically different from placebo. The incidence of chest symptoms was 0.2% in the phase 3 trials. The long-term safety and tolerability profile after treatment of more than 10 000 attacks was similar to that following the single-dose studies. In all clinical trials, almotriptan demonstrated a very favorable adverse event profile, particularly with respect to nonischemic-related chest symptoms. Almotriptan was safe and well tolerated in nearly all adult patients with migraine, with and without aura, enrolled in these studies. The incidence of chest symptoms in preclinical studies was substantially lower than that reported for sumatriptan in premarketing studies, indicating that almotriptan may be better tolerated than sumatriptan at clinically anticipated doses. However, any potential difference in cardiovascular safety between almotriptan and sumatriptan cannot be determined or inferred from this data. Cardiovascular risk profiles for all drugs within this class (triptans) should be considered similar. Only extensive postmarketing data, not currently available, can potentially change this recommendation.",2001.0,0,1
185,11380643,Treatment of migraine in Canada with naratriptan: a cost-effectiveness analysis.,J J Caro; D Getsios; G Raggio; G Caro; L Black,"To evaluate the cost-effectiveness of naratriptan for the treatment of migraine in Canada. The substantial disability brought on by migraine, coupled with the high prevalence of this disorder, leads to substantial costs. Naratriptan is a newly developed triptan shown to be effective in the treatment of migraine. Monte Carlo modeling techniques were used to simulate the experience of Canadian migraineurs over the course of 1 year. Data from a multinational study comparing oral naratriptan 2.5 mg to customary therapies were used in the cost-effectiveness analysis. Naratriptan leads to an annual reduction in symptom duration of 225 hours compared to customary therapy not including other triptans. Reductions in lost productivity yield savings of Can $390 (1998 Canadian dollars) relative to customary therapy, which exceed the increase in drug costs resulting in overall savings of Can $109 per year. The use of naratriptan in the treatment of migraine is an economically attractive option, leading to savings in overall costs. Increases in drug costs seem acceptable in light of reductions in symptom duration.",2001.0,0,0
186,11385257,Tolerability and efficacy of almotriptan in the long-term treatment of migraine.,J Pascual; R Falk; R Docekal; A Prusinski; J Jelencsik; X Cabarrocas; X Segarra; X Luria; P Ferrer,"Almotriptan is a highly specific 5-HT(1B/1D) receptor agonist, which acts selectively on blood vessels of the brain. Short-term studies have demonstrated that almotriptan provides rapid, effective and reliable relief of migraine attacks, while offering excellent tolerability. To assess the long-term tolerability and efficacy of oral almotriptan 12.5 mg administered for every migraine attack over a 1-year period. A total of 762 patients treated 13,751 attacks (1-97 per patient); 61.5% of attacks were treated with one 12.5-mg dose, while for 38.5% of attacks, patients took a second dose within 24 h. Three hundred and ninety-one patients (51.3%) experienced a total of 1,617 adverse events (AEs). The majority (88.6%) of AEs were of mild-to-moderate intensity, and only 28.8% of AEs were considered to be related to the study drug. Only 2 patients experienced serious AEs possibly related to almotriptan, syncope and chest pain; both recovered without any sequelae. Patients reported at least 1 AE in 11% of attacks treated. The incidence of AEs decreased during the study. Only 6 (0.8%) study withdrawals were due to AEs considered to be related to almotriptan. Tolerability was not compromised in patients taking 2 doses of almotriptan or in those using migraine prophylactics. Patient age or sex did not influence the incidence of AEs. There was no evidence of tachyphylaxis in those patients completing the study. Pain relief at 2 h after the initial dose was achieved in 84.2% of moderate/severe attacks. Patients were pain free at 2 h after dose in 58.2% of all attacks. Older patients (> 40 years) tended to respond better than younger ones (< 40 years). Efficacy was not modified by use of migraine prophylactics or hormonal contraceptives. Efficacy measurements were consistent on treating repeated moderate/severe migraine attacks. This large, open study indicates that the new, specific 5-HT(1B/1D) agonist almotriptan, at a dose of 12.5 mg, is a well tolerated and effective treatment for migraine pain when used over a period of up to 1 year.",2001.0,0,1
187,11385269,Comparison of preference for rizatriptan 10-mg wafer versus sumatriptan 50-mg tablet in migraine.,J Pascual; G Bussone; J F Hernandez; C Allen; F Vrijens; K Patel; Rizatriptan-Sumatriptan Preference Study Group,"Rizatriptan (MAXALT, a registered trademark of Merck & Co. Inc.) is a selective 5-HT(1B/1D) receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This randomized, open-label, crossover outpatient study assessed the preference of 481 patients for rizatriptan 10-mg rapidly disintegrating tablets versus sumatriptan (IMIGRAN, a registered trademark of GlaxoWellcome PLC) 50-mg tablets in the treatment of a single migraine attack with each therapy. Almost twice as many patients preferred rizatriptan 10-mg rapidly disintegrating tablet to sumatriptan 50-mg tablet (64.3 vs. 35.7%, p < or = 0.001). Faster relief of headache pain was the most important reason for the preference, cited by 46.9% of patients preferring rizatriptan and 43.4% of patients who preferred sumatriptan. Headache relief at 2 h was 75.9% with rizatriptan and 66.6% with sumatriptan (p < or = 0.001), with rizatriptan being superior to sumatriptan within 30 min of dosing. Fifty-five percent of patients were pain free 2 h after rizatriptan, compared with 42.1% treated with sumatriptan (p < or = 0.001), rizatriptan being superior within 1 h of treatment. Forty-one percent of patients taking rizatriptan were pain free at 2 h and had no recurrence or need for additional medication, compared to 32.3% of patients on sumatriptan. Rizatriptan was also superior to sumatriptan in terms of the proportions of patients with no nausea, phonophobia or photophobia, and patients with normal function 2 h after treatment intake (p < 0.05). More patients were (completely, very or somewhat) satisfied 2 h after treatment with rizatriptan (73.3%) than 2 h after treatment with sumatriptan (59.0%) (p < or = 0.001). Additionally, 2 h after the dose, more patients found rizatriptan to be very convenient, convenient or somewhat convenient (87.2%) than they did sumatriptan (76.3%) (p < or = 0.001). Both active treatments were well tolerated. The most common side effects with rizatriptan and sumatriptan were nausea (6.6 and 6.9% of patients, respectively), dizziness (6.1 and 5.8%) and somnolence (7.4 and 6.7%).",2001.0,0,1
188,11398305,Dihydroergotamine nasal spray in the treatment of acute migraine.,T A Treves; A Kuritzky; R Hering; A D Korczyn,"To evaluate the efficacy and safety of dihydroergotamine (DHE) nasal spray in patients suffering from common or classical migraine. In a double-blind parallel-group study, 52 outpatients with migraine were randomly allocated to DHE nasal spray or to placebo. Two puffs, one in each nostril, was taken as an initial dose (resulting in either 0.5 or 1 mg of DHE), followed by another puff (0.5 mg) after 30 and 60 minutes, if necessary, achieving a maximum dose of 2 mg for patients of the DHE 1-mg group or of 1.5 mg for patients of the 0.5-mg group. Four consecutive attacks were thus treated. The efficacy analysis was done for observed cases. The main outcome measure was reduction of the severity of the attacks. No differences were observed in the migraine characteristics or the number of treatments of the patients from the different groups. Dihydroergotamine 1 mg tended to provide better relief than 0.5 mg, although the effect was not statistically significant. Patients taking DHE used less rescue medications, with a dose-dependent effect. Side effects were reported by four patients receiving DHE but not placebo. The tolerability of the drug was assessed as good by 94% of the patients. These findings suggest that DHE nasal spray is well tolerated and has dose-dependent efficacy in migraine.",2001.0,0,0
189,11398306,Prostaglandin analog mechanisms are not effective in refractory chronic cluster headache.,S Evers; H Masur; P Sörös; R Brilla; I W Husstedt,"Prostaglandin E analogs have been shown to be effective in the treatment of refractory trigeminal neuralgia in patients with multiple sclerosis. Prostaglandin E inhibits the functions of T lymphocytes which are involved in the pathophysiology of cluster headache. Therefore, a double-blind, placebo-controlled, crossover study on the efficacy of misoprostol in chronic refractory cluster headache was performed. Eight patients were treated with 600 micrograms misoprostol and with placebo for a 2-week period. No differences in attack frequency, intensity, global impression, and side effects could be detected, suggesting that prostaglandin E analogs are not effective in the treatment of chronic cluster headache.",2001.0,0,0
190,11405809,"Oral almotriptan vs. oral sumatriptan in the abortive treatment of migraine: a double-blind, randomized, parallel-group, optimum-dose comparison.",E L Spierings; B Gomez-Mancilla; D E Grosz; C R Rowland; F S Whaley; K J Jirgens,"Almotriptan malate is a novel, selective serotonin(1B/D) agonist, or triptan, developed for the abortive treatment of migraine. In double-blind, placebo-controlled studies, it has been shown to be effective, well tolerated, and safe. To compare the efficacy, tolerability, and safety of almotriptan with that of the ""standard triptan,"" sumatriptan succinate. The power calculation of the study was based on 24-hour headache recurrence, an efficacy measure in the abortive treatment of migraine, and on the occurrence of adverse events. Subjects, aged between18 and 65 years, with migraine with or without aura but otherwise healthy, were randomized to take orally either almotriptan malate, 12.5 mg, or sumatriptan succinate, 50 mg. The medications were provided in identical-looking capsules to ensure blinding and were taken for the treatment of moderate or severe headache. Efficacy was determined in terms of (1) headache relief-a decrease in pain intensity to mild or no pain; (2) headache freedom-a decrease to no pain; (3) use of rescue medications, allowed after 2 hours; and (4) headache recurrence-moderate or severe pain returning within 24 hours after headache relief at 2 hours. Adverse events were collected for 96 hours after treatment and for safety evaluation, vital signs, blood tests, and electrocardiograms were performed at the screening and exit visits. Seventy-five investigators enrolled 1255 subjects of whom 1173 were treated (591 with almotriptan and 582 with sumatriptan). At 2 hours, almotriptan treatment provided headache relief in 58.0% of the subjects and sumatriptan treatment in 57.3%; headache freedom was provided by the medications in 17.9% and 24.6%, respectively (P =.005). Rescue medications were taken by 36.7% of the subjects in the almotriptan-treated group and by 33.2% in the sumatriptan-treated group; headaches returned to moderate or severe intensity in 27.4% and 24.0%, respectively. Treatment-emergent adverse events occurred in 15.2% of the subjects in the almotriptan-treated group and in 19.4% in the sumatriptan-treated group (P =.06); treatment-related adverse events occurred in 9.1% and 15.5% of the subjects, respectively (P =.001), including chest pain, which occurred in 0.3% and 2.2%, respectively (P =.004). Almotriptan and sumatriptan are similarly effective in the abortive treatment of moderate or severe migraine headache; they are also similarly well tolerated and safe.",2001.0,0,1
191,11407649,Neuroendocrine effects of subcutaneous sumatriptan in patients with migraine.,I Rainero; W Valfrè; L Savi; S Gentile; L Pinessi; L Gianotti; E Arvat; E Ghigo; P Del Rizzo; P Calvelli; P Limone,"We evaluated the sensitivity of 5-HT1D receptors in patients with migraine using sumatriptan as a pharmacological probe. The drug inhibits the release of ACTH, cortisol and prolactin and this effect may be used to explore the function of serotoninergic systems in vivo. We administered sumatriptan (6 mg sc) and placebo to 15 migraineurs, during the headache-free period, and to 10 healthy controls. Blood samples were collected -15, 0, 15, 30, 45, 60 and 90 min after injections. Sumatriptan induced a significant (p<0.01) decrease of ACTH, cortisol and prolactin concentrations both in patients with migraine and in controls. The neuroendocrine response was not significantly different in the two groups. Our results suggest that 5-HT1D receptor sensitivity is not altered in migraine.",2001.0,0,0
192,11422001,"Effect of MAO-A inhibition on the pharmacokinetics of almotriptan, an antimigraine agent in humans.",J C Fleishaker; K K Ryan; J M Jansat; B J Carel; D J Bell; M T Burke; N E Azie,"To assess the effect of a reversible MAO-A inhibitor, moclobemide, on the single-dose pharmacokinetics of almotriptan and assess the clinical consequences of any interaction. Twelve healthy volunteers received the following treatments in a randomized, open-label, two-way crossover design (with a 1 week washout between treatments): (A) one 150 mg moclobemide tablet every 12 h for 8 days and one 12.5 mg almotriptan tablet on the morning of day 8; and (B) one 12.5 mg almotriptan tablet on day 8. Plasma almotriptan was quantified by h.p.l.c.-MS-MS, while urinary concentrations were measured by h.p.l.c.-u.v. Vital signs, ECGs, and adverse events were evaluated after almotriptan administration. Treatment effects on pharmacokinetics and vital signs were assessed by analysis of variance. Mean almotriptan AUC was higher (483 +/- 99.9 vs 352 +/- 75.4 ng ml-1 h, P = 0.0001) and oral clearance was lower (26.6 +/- 4.00 vs 36.6 +/- 5.89 l h-1, P = 0.0001) when almotriptan was administered with moclobemide. Mean half-life was longer (4.22 +/- 0.78 vs 3.41 +/- 0.45 h, P = 0.0002) after coadministration with moclobemide. Renal clearance of almotriptan was unaffected by moclobemide. No serious adverse events occurred and no clinically significant vital sign changes were observed. Moclobemide increased plasma concentrations of almotriptan on average by 37%, but the combined administration of these two compounds was well tolerated. The degree of interaction was much less than that seen previously for sumatriptan or zolmitriptan given with moclobemide.",2001.0,0,0
193,11422089,Intravenous metamizol (Dipyrone) in acute migraine treatment and in episodic tension-type headache--a placebo-controlled study.,M E Bigal; C A Bordini; J G Speciali,"Acute headache is a very frequent symptom, responsible for significant demand at primary care units and emergency rooms. In such sets in Brazil, metamizol is easily found but, on the other hand, neither ergotics nor triptans are available. The aim of this study is to compare intravenous metamizol with placebo in the acute treatment of migraine with aura, migraine without aura and episodic tension-type headache. Fifty-four migraine with aura patients, 95 migraine without aura patients and 30 tension-type headache patients were treated with metamizol. Ninety patients (30 migraine with aura, 30 migraine without aura and 30 tension-type headache patients) received placebo. Pain intensity, nausea, aura, photo- and phonophobia were investigated at 30 min and 60 min after the administration of the drug. Significant improvement of pain after 30 min and 60 min post-dosage was achieved from metamizol groups compared with placebo groups. Significant improvement of all other symptoms was achieved after 60 min post-dosage. Side-effects were mild and with small incidence. Metamizol is an effective, safe and low price drug. It may be regarded as a good alternative drug for the treatment of common acute primary headaches.",2001.0,0,0
194,11422095,Meta-analysis of rizatriptan efficacy in randomized controlled clinical trials.,M D Ferrari; E Loder; K A McCarroll; C R Lines,"Data from seven randomized, placebo-controlled, double-blind phase III clinical trials were analysed to further evaluate the efficacy of rizatriptan 10 mg (n = 2068) in comparison with placebo (n = 1260) and rizatriptan 5 mg (n = 1486) for the acute treatment of a migraine attack. Migraine was diagnosed according to International Headache Society criteria. Headache severity, associated migraine symptoms and functional disability were measured immediately before dosing and at 0.5, 1, 1.5 and 2 h. Headache recurrence (return of moderate or severe headache after an initial response) was also recorded. In addition to conventional pain relief (reduction of moderate or severe headache to mild or none) and pain free measures, the analysis looked at the elimination of associated migraine symptoms and disability in patients who had symptoms or disability at baseline. Maintenance of pain relief or pain-free status over 24 h was also analysed. At 2 h, rizatriptan 10 mg was significantly more effective than placebo for pain relief (71% vs. 38%, P < 0.001), and for elimination of pain, nausea, photophobia, phonophobia and functional disability. The benefit was maintained over 24 h; 37% of patients on rizatriptan 10 mg had sustained pain relief vs. 18% for placebo (P < 0.001). Rizatriptan 10 mg was also more effective than rizatriptan 5 mg, with a significant superiority at 2 h on all measures except for elimination of nausea. The benefit was maintained over 24 h; 38% of patients on rizatriptan 10 mg had sustained pain relief vs. 32% for rizatriptan 5 mg (P = 0.001).",2001.0,0,1
195,11427330,A comparison of visual analog scale and categorical ratings of headache pain in a randomized controlled clinical trial with migraine patients.,C R Lines; K Vandormael; W Malbecq,"A visual analog scale (VAS) method of assessing headache pain was compared with a standard categorical four-grade scale (4GS) in a randomized, placebo-controlled, double-blind, clinical trial involving 792 treated migraine outpatients who received oral rizatriptan 5 mg, sumatriptan 50 mg, or placebo for a moderate or severe headache. The VAS and 4GS were equally useful in demonstrating that the active drugs were superior to placebo at reducing headache pain, and in showing that the active drugs were similarly effective. For both rizatriptan and sumatriptan, slightly larger effect sizes were observed with the 4GS compared with the VAS. In analyses using data combined across all treatment groups, VAS and 4GS scores were highly correlated. Use of the VAS imposed additional administrative burdens. These findings suggest that the 4GS may be the preferred scale for assessing headache pain in clinical trials involving adult migraineurs.",2001.0,0,1
196,11437887,Headache in the emergency department.,L B Morgenstern; J C Huber; H Luna-Gonzales; K R Saldin; J C Grotta; S G Shaw; L Knudson; R F Frankowski,"To perform an observational study of the demographics, clinical factors, and therapeutic efficacy in patients presenting to the emergency department with a chief complaint of headache. Acute headache presentations to the emergency department are a therapeutic dilemma for physicians. Patients presenting with nontraumatic headache to the emergency department of Hermann Hospital in Houston, Texas, during a 16-month period were prospectively ascertained by active and passive surveillance. The medical record was abstracted. Demographic and clinical information are presented with descriptive statistics. Relative benefit of individual therapies are compared with odds ratios (95% confidence intervals). Of the 38 730 patients who were prospectively screened, 455 presented with a chief complaint of headache. Seventy-six percent were women, and the mean age was 37 years. Non-Hispanic whites were more likely diagnosed with migraine compared with Hispanics or African Americans (P<.001). Three percent had subarachnoid hemorrhage. Neurologist follow-up was ordered in 10%. The median time in the emergency department was 265 minutes. With the initial treatment, 44% resolved, 47% improved, and 9% had no change; none worsened. In comparison with all other therapies used, there was a trend suggesting the superiority of antiemetics (odds ratio, 2.66; 95% confidence interval, 0.81 to 8.61). Acetaminophen was less helpful (odds ratio, 0.27; 95% confidence interval, 0.10 to 0.70). When comparing specific agents to therapies which could be used at home, antiemetics led to headache resolution most often (odds ratio, 3.18; 95% confidence interval, 1.40 to 7.22); ketorolac showed a similar trend (odds ratio, 2.05; 95% confidence interval, 0.86 to 4.89). Headache in the emergency department is a phenomena of young women who spend a long time waiting and receive many tests. A variety of therapies are used. Antiemetics may be especially useful for headache resolution.",2002.0,0,0
197,11448293,Establishing a standard of speed for assessing the efficacy of the serotonin(1B/1D) agonists (triptans).,D A Marcus,"The current International Headache Society guidelines for migraine clinical trials recommend assessment of pain relief at 2 hours as a primary end point. Patients, however, express a clear preference for more rapid pain relief, with most patients defining rapid relief as occurring within 30 minutes after drug administration. Thus, consideration should be given to establishing clinical trial end points that more accurately reflect the preferences of patients with migraine. In this case, assessment of pain relief at 1 hour would be an appropriate primary end point. Using speed of relief as a criterion for migraine drug selection also is appropriate. The migraine-specific serotonin(1B/1D) agonists, or triptans, are able to meet this faster relief end point and are preferred by patients.",2001.0,0,1
198,11452689,Pharmacology and efficacy of eletriptan for the treatment of migraine attacks.,C Allen,,2001.0,0,0
199,11453892,"Influence of beta-adrenoceptor antagonists on the pharmacokinetics of rizatriptan, a 5-HT1B/1D agonist: differential effects of propranolol, nadolol and metoprolol.",M R Goldberg; D Sciberras; M De Smet; R Lowry; L Tomasko; Y Lee; T V Olah; J Zhao; K P Vyas; R Halpin; P H Kari; I James,"Patients with migraine may receive the 5-HT1B/1D agonist, rizatriptan (5 or 10 mg), to control acute attacks. Patients with frequent attacks may also receive propranolol or other beta-adrenoceptor antagonists for migraine prophylaxis. The present studies investigated the potential for pharmacokinetic or pharmacodynamic interaction between beta-adrenoceptor blockers and rizatriptan. Four double-blind, placebo-controlled, randomized crossover investigations were performed in a total of 51 healthy subjects. A single 10 mg dose of rizatriptan was administered after 7 days' administration of propranolol (60 and 120 mg twice daily), nadolol (80 mg twice daily), metoprolol (100 mg twice daily) or placebo. Rizatriptan pharmacokinetics were assessed. In vitro incubations of rizatriptan and sumatriptan with various beta-adrenoceptor blockers were performed in human S9 fraction. Production of the indole-acetic acid-MAO-A metabolite of each triptan was measured. Administration of rizatriptan during propranolol treatment (120 mg twice daily for 7.5 days) increased the AUC(0, infinity) for rizatriptan by approximately 67% and the Cmax by approximately 75%. A reduction in the dose of propranolol (60 mg twice daily) and/or the incorporation of a delay (1 or 2 h) between propranolol and rizatriptan administration did not produce a statistically significant change in the effect of propranolol on rizatriptan pharmacokinetics. Administration of rizatriptan together with nadolol (80 mg twice daily) or metoprolol (100 mg twice daily) for 7 days did not significantly alter the pharmacokinetics of rizatriptan. No untoward adverse experiences attributable to the pharmacokinetic interaction between propranolol and rizatriptan were observed, and no subjects developed serious clinical, laboratory, or other significant adverse experiences during coadministration of rizatriptan with any of the beta-adrenoceptor blockers. In vitro incubations showed that propranolol, but not other beta-adrenoceptor blockers significantly inhibited the production of the indole-acetic acid metabolite of rizatriptan and sumatriptan. These results suggest that propranolol increases plasma concentrations of rizatriptan by inhibiting monoamine oxidase-A. When prescribing rizatriptan to migraine patients receiving propranolol for prophylaxis, the 5 mg dose of rizatriptan is recommended. Administration with other beta-adrenoceptor blockers does not require consideration of a dose adjustment.",2001.0,0,0
200,11472386,Patterns of ergotamine and sumatriptan use in the Netherlands from 1991 to 1997.,H Rahimtoola; A C Egberts; H Buurma; C C Tijssen; H G Leufkens,"The objective of this study was to assess usage patterns of ergotamine and sumatriptan over a period of 6 years, primarily to evaluate the impact that sumatriptan has had on the prescription of ergotamine. This study used ergotamine and sumatriptan prescription data representing inhabitants of eight cities in the Netherlands and covering the period of 1991-1997. The yearly incidence of new users between 1991 and 1997 was estimated for both drugs as well as for the drug of first choice to be prescribed to patients initiating specific abortive migraine treatment with either ergotamine or sumatriptan. Intra-individual ergotamine and sumatriptan usage patterns, characterized by single (incidental), continuous (rate of retention) or switch use, were examined for five patient cohorts, each for a follow-up period of 1 year. During the year of sumatriptan introduction (1991-1992), the overall incidence of new use for both drugs was highest (5.4 per 1000 inhabitants). Hereafter, a substantial reduction of more than 50% was observed. From 1992 to 1996, the yearly incidence of ergotamine first-time use was significantly higher than that of sumatriptan and up to 1996 ergotamine was more than twice as likely than sumatriptan to be prescribed to patients initiating specific abortive treatment. Hereafter, sumatriptan was as likely as ergotamine to be prescribed as the drug of first choice, which coincided with the full reimbursement of sumatriptan tablets. Overall, neurologists were more likely than general practitioners (GPs), to prescribe sumatriptan as the drug of first choice. Approximately half of the total study population were identified as single-time users. This phenomonen occurred more frequently in the ergotamine cohorts. The sumatriptan cohorts displayed a slight yet significant stronger retention rate compared with the ergotamine cohorts. The overall impact of sumatriptan on ergotamine use in The Netherlands was marginal, predominantly due to GP's adherence to migraine treatment guidelines and reimbursement policies concerning sumatriptan tablets. Overall, incidental use was relatively high and may reflect the reported difficulties in diagnosing migraine, lack of patient-doctor consultation, or that anticipated benefits of the drug were not achieved. Further study is required to clarify these issues.",2001.0,0,0
201,11480257,Pediatric headache.,S L Linder; P Winner,"Headaches are frequent in children and adolescents and at times can be extremely disabling. Disability scales, such as the MIDAS scale, have been useful in helping follow adult patients. Modifications of this scale have been helpful in following pediatric and adolescent patients. Greater attention has been paid to epidemiology and classification of headache in children. Studies are being done on serotonin 1B/1D agonist for treating acute migraine, and this agent has been found to be efficacious despite a high placebo response. It is anticipated that FDA approval of sumatriptan nasal spray in adolescents is forthcoming. Despite advancements, there is no wonder drug. There continues to be a need for studying preventive therapies in a double-blind, placebo-controlled environment, and plans are under way for such studies. Many adult patients with chronic daily headaches report that their headaches began in childhood and adolescence. A better understanding of diagnostic criteria, early diagnosis, and more effective treatment may be the key to influencing the prevalence of headaches in adults. Continued research is the only answer to the questions raised by the most recent studies in this population.",2001.0,0,0
202,11513349,A systematic review of the use of triptans in acute migraine.,B Pham,,2002.0,0,1
203,11524030,When should triptans be taken during a migraine attack?,J Schoenen,"The common strategy to treat a migraine attack as soon as it begins, made for classical acute antimigraine treatments such as ergotamine and analgesics, has not been transposed to the triptans. The recommendation to delay triptan intake until headache intensity is at least moderate is merely a habit generated by the protocol used in triptan trials and a nonvalidated attempt to reduce costs. It is also favoured by the few studies suggesting that sumatriptan is less effective when given early in an attack, especially during the aura phase. Recent retrospective analyses of small numbers of 'protocol violators' in controlled trials of sumatriptan suggest that the drug is more efficient when taken while the headache is mild. Pain-free responses and therapeutic gains over aspirin (acetylsalicylic acid)-metoclopramide or ergotamine-caffeine combinations were increased under these conditions. The available circumstantial evidence is reviewed and discussed. Before any conclusion can be drawn and recommendation made, results are awaited from randomised controlled trials specifically addressing whether or not triptans are more efficient in mild headache. Meanwhile, there seems to be no medical reason to withhold treatment of a mild headache with a triptan as long as triptan intake does not exceed 1 or 2 doses per week. Most mild headaches in patients with migraine appear indeed to be mild migraine attacks, even when the headache characteristics are those of tension-type headache.",2001.0,0,0
204,11531899,"The efficacy and safety of sc alniditan vs. sc sumatriptan in the acute treatment of migraine: a randomized, double-blind, placebo-controlled trial.",H C Diener; P Tfelt-Hansen; F de Beukelaar; M D Ferrari; J Olesen; C Dahlöf; N Mathew; Study Group,"This double-blind, placebo-controlled, parallel-group, multicentre, multinational, phase-III trial was designed to assess the efficacy and safety of a single subcutaneous injection of placebo, 2 doses of alniditan (1.4 mg and 1.8 mg) and 6 mg of sumatriptan in subjects with acute migraine. A total of 114 investigators from 13 different countries screened 2021 subjects. In total 924 patients were treated with placebo (157), alniditan 1.4 mg (309), alniditan 1.8 mg (141) and sumatriptan 6 mg (317). The lower number of subjects in the alniditan 1.8 mg group is due to the termination of this trial arm after the incidence of a serious adverse event and a subsequent protocol amendment. The number of subjects who were pain free at 2 h (primary endpoint) was: 22 (14.1%) with placebo, 174 (56.3%) with alniditan 1.4 mg, 87 (61.7%) with alnditan 1.8 mg and 209 (65.9%) with sumatriptan 6 mg. Alniditan 1.4 mg was significantly better (P < 0.001) than placebo and sumatriptan was significantly better (P = 0.015) than alniditan 1.4 mg. The number of responders (reduction of headache severity from moderate or severe headache before treatment to mild or absent at 2 h), was 59 (37.8%) on placebo, 250 (80.9%) on alniditan 1.4 mg, 120 (85.1%) on alniditan 1.8 mg, and 276 (87.1%) on sumatriptan. Response was significantly higher (P < 0.001) with alniditan 1.4 mg than with placebo, and significantly lower (P = 0.036) with alniditan 1.4 mg than with sumatriptan. Recurrence rates were: 22 (37.3%) with placebo, 87 (34.8%) with alniditan 1.4 mg, 35 (29.2%) with alniditan 1.8 mg and 108 (39.1%) with sumatriptan. Adverse events occurred in 577/924 (62.4%) subjects, i.e. in 62/157 (39.5%) with placebo, 214/309 (69.3%) with alniditan 1.4 mg, 91/141 (64.5%) with alniditan 1.8 mg and 210/317 (66.2%) with sumatriptan 6 mg. Sumatriptan was significantly better than alniditan 1.4 mg for pain free at 2 h. The difference, however, was small and clinically not important. For alniditan, a dose-dependent adverse event relationship was seen. The safety profile of alniditan 1.4 mg was similar to that of sumatriptan.",2002.0,0,1
205,11531900,An open preference study with sumatriptan 50 mg and zolmitriptan 2.5 mg in 100 migraine patients.,J Pascual; R Muñoz; R Leira,"Understanding factors influencing patients' preference will improve guidance to make rational choices in expanded symptomatic migraine treatment. The objective of this open-label, cross-over study was to explore patients' preferences for sumatriptan 50 mg vs. zolmitriptan 2.5 mg tablets, focusing on factors influencing this preference. One hundred consecutive migraine patients attending our clinics were asked to treat three attacks with each medication and then fill out a preference questionnaire. Ninety-four migraineurs completed the trial and 42 (44%, 95% CI 34-58%) reported that they preferred zolmitriptan 2.5 mg over sumatriptan 50 mg tablets and 27 (29%, 20-38%) preferred sumatriptan 50 mg. The remaining 25 (27%, 18-36%) did not show any preference. For the initial treatment of the attacks, there were more patients needing just one tablet of zolmitriptan 2.5 mg compared with sumatriptan 50 mg (67 vs. 39%). The reasons for preference among those 69 patients who had shown preference for either of the two triptans were: a faster onset of action (speed of onset) (73%), a longer duration of the effects (39%), fewer adverse events (35%) and lower price (13%). Only one-quarter of the studied migraine population thought that sumatriptan 50 mg and zolmitriptan 2.5 mg were equivalent, which suggests that most migraine patients differentiate between triptans. A faster onset of action (speed of onset) was the most important reason for preference.",2002.0,0,1
206,11554952,Prevalence and burden of migraine in the United States: data from the American Migraine Study II.,R B Lipton; W F Stewart; S Diamond; M L Diamond; M Reed,"To describe the prevalence, sociodemographic profile, and the burden of migraine in the United States in 1999 and to compare results with the original American Migraine Study, a 1989 population-based study employing identical methods. A validated, self-administered questionnaire was mailed to a sample of 20 000 households in the United States. Each household member with severe headache was asked to respond to questions about symptoms, frequency, and severity of headaches and about headache-related disability. Diagnostic criteria for migraine were based on those of the International Headache Society. This report is restricted to individuals 12 years and older. Of the 43 527 age-eligible individuals, 29 727 responded to the questionnaire for a 68.3% response rate. The prevalence of migraine was 18.2% among females and 6.5% among males. Approximately 23% of households contained at least one member suffering from migraine. Migraine prevalence was higher in whites than in blacks and was inversely related to household income. Prevalence increased from aged 12 years to about aged 40 years and declined thereafter in both sexes. Fifty-three percent of respondents reported that their severe headaches caused substantial impairment in activities or required bed rest. Approximately 31% missed at least 1 day of work or school in the previous 3 months because of migraine; 51% reported that work or school productivity was reduced by at least 50%. Two methodologically identical national surveys in the United States conducted 10 years apart show that the prevalence and distribution of migraine have remained stable over the last decade. Migraine-associated disability remains substantial and pervasive. The number of migraineurs has increased from 23.6 million in 1989 to 27.9 million in 1999 commensurate with the growth of the population. Migraine is an important target for public health interventions because it is highly prevalent and disabling.",2001.0,0,0
207,11554957,Effectiveness of nasal sumatriptan in 5- to 12-year-old children.,A D Hershey; S W Powers; S LeCates; A L Bentti,"To assess the tolerability and effectiveness of nasal sumatriptan in the treatment of migraine in 5- to 12-year-old children. Although headaches are a common disorder and occur in up to 10.6% of children, many of the new migraine abortive agents have not been well evaluated in this population. It has recently been reported that nasal sumatriptan is effective in the treatment of migraine in adolescents. In younger children, it is yet to be characterized. In addition, many children have significant amounts of vomiting with their migraines, limiting their use of oral medications. Children with headache were evaluated by a child neurologist, child psychologist, and pediatric nurse practitioner. Clinical and International Headache Society diagnoses were established for each child. Patients with headaches that were either unresponsive to oral medications or had significant vomiting were treated with nasal sumatriptan. Initial administration and tolerability were performed in the Headache Center at Cincinnati's Children's Hospital Medical Center. Patients or their parents were contacted to assess the overall effectiveness of nasal sumatriptan after home administration. Ten patients aged between 5 and 12 years (mean, 9.9 years) received either a 5-mg (n = 2) or 20-mg (n = 8) dose of sumatriptan. All 10 patients had a clinical diagnosis of migraine; 7 met the International Headache Society criteria for migraine. The mean age of headache onset was 6.6 years. A total of 57 headaches were treated; 47 (82.5%) responded to sumatriptan. Of the patients who treated headaches, the mean number of headaches treated was 5.2, while the mean number of responsive headaches was 4.3. One patient had no response, 2 patients had a 50% response, and 6 patients had 100% response to the nasal sumatriptan. Three patients reported persistent ""bad taste."" This report demonstrates that nasal sumatriptan may be effective in aborting migraine in young children (aged 5 to 12 years). It also suggests that there may be subgroups for which it works well. This information suggests that double-blind, placebo-controlled studies are necessary to determine the overall effectiveness of nasal sumatriptan in this age group.",2001.0,0,0
208,11563413,Lack of pharmacokinetic and pharmacodynamic interaction between rizatriptan and paroxetine.,M R Goldberg; R C Lowry; D G Musson; K L Birk; A Fisher; M E De Puy; C R Shadle,"Rizatriptan is a potent, oral 5-HT(1B/1D) agonist with a rapid onset of action being investigated for the acute treatment of migraine. This study examined the clinical and pharmacolinetic interaction between rizatriptan and the selective serotonin reuptake inhibitor, paroxetine. In this two-period crossover study, 12 healthy young subjects (6 males and 6 females) received 1 mg rizatriptan following 14 days of treatment with placebo or paroxetine (20 mg once daily). Plasma was sampled for rizatriptan and N-monodesmethyl rizatriptan, a minor but active metabolite of rizatriptan. Safety evaluations included monitoring for adverse events, vital signs, and visual analog scale assessment of mood. Plasma levels of rizatriptan and N-monodesmethyl rizatriptan were not altered when rizatriptan was administered with paroxetine compared to the placebo. Clinically, coadministration of rizatriptan with paroxetine was well tolerated. Blood pressure, heart rate, and temperature changes during the observation period did not differ to a clinically significant degree when rizatriptan was administered with paroxetine compared to the placebo. No effects on mood occurred following treatment with the combination compared to rizatriptan alone. Adverse events following rizatriptan administration with paroxetine were similar to those reported when rizatriptan was given with the placebo.",2001.0,0,0
209,11575714,Donitriptan (Pierre Fabre).,M Dukat,"Pierre Fabre is developing donitriptan, a piperazide 5-HT1D agonist, as a potential treatment for migraine [175854]. In January 2001, donitriptan had completed phase I trials for migraine and was scheduled to enter phase II development [396027]. This compound has an increased potency and, importantly, markedly higher intrinsic activity in comparison to the well described tryptamine derivatives, naratriptan, zolmitriptan and sumatriptan [295769].",2002.0,0,0
210,11576197,Preference comparison of rizatriptan ODT 10-mg and sumatriptan 50-mg tablet in migraine.,E Loder; J L Brandes; S Silberstein; F Skobieranda; N Bohidar; L Wang; D Boyle; A Kolodny; F Guerra; N Santanello; L Johnson-Pratt; Rizatriptan Protocol 060 Study Group,"To compare the proportion of patients who prefer rizatriptan orally disintegrating tablet (ODT) 10-mg to sumatriptan 50-mg tablet. Migraineurs express treatment preference based on a variety of attributes including the speed of pain relief and medication formulation. Rizatriptan ODT is an orally disintegrating formulation of rizatriptan, a selective 5-HT1B/1D receptor agonist. This study was conducted to determine patient preference between rizatriptan ODT 10-mg and sumatriptan 50-mg tablet for the acute treatment of migraine. This was a multicenter, randomized, open-label, two-period crossover study conducted in the United States with 524 enrolled patients. Patients treated a single moderate or severe headache in each treatment period. Patients treated one migraine with either rizatriptan ODT 10-mg or sumatriptan 50-mg tablet, then treated a second migraine with the alternate therapy. Patients completed diary assessments at baseline, and 30, 45, 60, 90, and 120 minutes postdose and rated headache severity on a 4-point scale (0 = none, 1 = mild, 2 = moderate, and 3 = severe). At the final study visit following treatment of their second migraine, patients expressed preference for one of the two study medications by completing an interviewer-administered Global Preference Question and then responded to a self-administered series of questions to capture their most important reason for preferring one study medication over the other. Safety measurements were recorded through standard adverse experience reporting. Three hundred eighty-six patients treated two migraine attacks. For those patients who expressed a preference for either rizatriptan ODT or sumatriptan (n = 374), the percentage of patients who preferred rizatriptan ODT 10-mg (57%, n = 213) was significantly greater than those who preferred sumatriptan 50-mg tablet (43%, n = 161) (P<.01). For those patients who treated two migraine attacks and had drug severity measures for both attacks (n = 384), a significantly greater percentage of patients reported pain relief after taking rizatriptan ODT than sumatriptan at the 45- and 60-minute time points (38% versus 29% and 58% versus 49%, respectively) (P<.01). In addition, a significantly greater percentage of patients taking rizatriptan ODT reported a pain-free status at the 60- and 120-minute time points (23% versus 17% [P<.05] and 60% versus 52% [P<.01], respectively). Both rizatriptan ODT and sumatriptan were well tolerated. A significantly greater proportion of patients preferred rizatriptan ODT 10-mg to sumatriptan 50-mg tablet for the acute treatment of migraine. Efficacy and safety data are consistent with the preference findings.",2002.0,0,1
211,11576198,Effect of rizatriptan and other triptans on the nausea symptom of migraine: a post hoc analysis.,R B Lipton; J Pascual; P J Goadsby; H Massiou; K A McCarroll; K Vandormael; K Jiang; C R Lines,"To compare the effects of oral rizatriptan, sumatriptan, naratriptan, and zolmitriptan on the relief and emergence of nausea during a migraine attack. Data from five randomized, placebo-controlled, double-blind clinical trials in which oral rizatriptan 10 mg was directly compared with oral sumatriptan 100 mg (N = 772), 50 mg (N = 1168), 25 mg (N = 1180), naratriptan 2.5 mg (N = 406), or zolmitriptan 2.5 mg (N = 571) for the acute treatment of a migraine attack were retrospectively analyzed. Migraine was diagnosed according to International Headache Society criteria. Presence or absence of nausea was recorded at baseline and at 0.5, 1, 1.5, and 2 hours after dosing. The end points analyzed were relief of nausea in those who had it at baseline and emergence of nausea in those who were free of it at baseline. Treatments were compared using odds ratios estimated from logistic regression models at 2 hours, and averaged odds ratios for the first 2 hours posttreatment. Approximately 60% of patients in each treatment group had nausea at baseline. In those patients with nausea at baseline, significantly more patients treated with rizatriptan 10 mg were free of nausea at 2 hours compared with sumatriptan 100 mg (66% versus 58%, P =.043), sumatriptan 50 mg (68% versus 57%, P =.010), sumatriptan 25 mg (68% versus 59%, P =.017), and naratriptan 2.5 mg (59% versus 45%, P =.014). Averaging over the four posttreatment time points in the first 2 hours, significantly more patients treated with rizatriptan 10 mg were free of nausea compared with sumatriptan 100 mg (P =.004), sumatriptan 50 mg (P =.001), and naratriptan 2.5 mg (P =.015). No significant differences in nausea relief were seen between rizatriptan 10 mg and zolmitriptan 2.5 mg, either at 2 hours (65% versus 61%, P =.210) or over the first 2 hours (P =.781). Rates of treatment-emergent nausea at 2 hours ranged from 11% to 18% with placebo, from 5% to 13% with rizatriptan 10 mg, and from 10% to 20% with other comparator triptans. Oral rizatriptan 10 mg was more effective than oral sumatriptan and naratriptan at eliminating nausea within 2 hours in patients who had it at baseline. Rates of emergent nausea in patients who were free of it at baseline were low, and no consistent differences were observed between active treatments.",2002.0,0,1
212,11576203,Effects of medication use on health state in postictal migraineurs.,E J Mulder; J Passchier; W H Linssen; E J de Geus,"We investigated whether headache-free patients with migraine report a lower health state compared with healthy controls, and whether health state is differently affected during the postattack period after using sumatriptan versus habitual nonvasoactive medication. Mood, health state, and personality questionnaires were administered once during an interictal period and twice within 30 hours after different migraine attacks treated with sumatriptan or habitual nonvasoactive medication. Twenty migraineurs without aura, 10 migraineurs with aura, and 30 matched and headache-free controls participated in this study. During an interictal period, patients with migraine reported more problems regarding social activities and pain compared with healthy controls. During the postictal period, mood (fatigue and emotional state) was negatively affected by an attack that was treated with habitual medication, whereas health state (physical pain, social activities, current pain) was similar to the migraine-free period. Sumatriptan treatment had beneficial effects on aspects of health state and mood during the postictal period.",2002.0,0,0
213,11579012,Pregnancy outcome following gestational exposure to venlafaxine: a multicenter prospective controlled study.,A Einarson; B Fatoye; M Sarkar; S V Lavigne; J Brochu; C Chambers; P Mastroiacovo; A Addis; D Matsui; L Schuler; T R Einarson; G Koren,"Because there are no studies available on the safety of venlafaxine during pregnancy, the authors' goal in this study was to determine whether venlafaxine increases the risk for major malformations. Data on 150 women exposed to venlafaxine during pregnancy in seven pregnancy counseling centers were compared with data from studies of pregnant women who 1) received selective serotonin reuptake inhibitor antidepressants (SSRIs) (N=150) and 2) who received nonteratogenic drugs (N=150). Among the 150 women who were exposed to venlafaxine during pregnancy, 125 had live births, 18 had spontaneous abortions, and seven had therapeutic abortions; two of the babies had major malformations. There were no significant differences between these women and the two comparison groups on any of the measures analyzed. These results suggest that the use of venlafaxine during pregnancy does not increase the rates of major malformations above the baseline rate of 1%-3%.",2001.0,0,0
214,11587494,Modeling and stimulation for clinical trial design involving a categorical response: a phase II case study with naratriptan.,I Nestorov; G Graham; S Duffull; L Aarons; E Fuseau; P Coates,"The overall aim of the present study was to investigate retrospectively the feasibility and utility of model-based clinical trial simulation as applied to the clinical development of naratriptan with effect measured on a categorical scale. A PK-PD model for naratriptan was developed by using information gathered from previous naratriptan and sumatriptan preclinical and clinical trials. The phase IIa naratriptan data were used to check the PK-PD model in its ability to describe future data. A further PK-PD model was developed by using the phase IIa naratriptan data, and a phase IIb trial was designed by simulation with the use of Matlab. The design resulting from clinical trial simulation was compared with that derived by using D-optimal design. The PK-PD model showed reasonable agreement with the data observed in the phase IIa naratriptan clinical trial. Clinical trial simulation resulted in a design with four or five arms at 0 mg, 2.5 and/or 5 mg, 10 mg, and 20 mg, PD measurements to be taken at 0, 2, and 4 or 6 h and at least 150 patients per arm. A sub-D-optimal design resulted in two dosing arms at 0 and 10 mg and PD measurements to be taken at 1 and 2 h. Clinical trial simulation is a useful tool for the quantitative assessment of the influence of the controllable factors and is the only tool for the quantitative assessment of the uncontrollable factors on the power of a clinical trial.",2002.0,0,0
215,11593269,Dexamethasone decreases migraine recurrence observed after treatment with a triptan combined with a nonsteroidal anti-inflammatory drug.,A V Krymchantowski; J S Barbosa,"Triptans are effective drugs for the acute treatment of migraine. However, 30-40% of the patients commonly present recurrence before 24 hours therefore requiring another dose. Nonsteroidal anti-inflammatory drugs (NSAID) such as tolfenamic acid and naproxen sodium combined with sumatriptan have demonstrated efficacy in reducing recurrence observed with the single use of this drug. Steroids also have been suggested to treat refractory migraine and status migranosus. The aim of this study was to evaluate whether patients presenting frequent recurrence with the combination triptan plus NSAID, would decrease it with the association of dexamethasone. Twenty three patients, 17 women and 6 men with migraine according to IHS criteria were prospectively studied. All patients presented frequent recurrence (> or= 60%, mean recurrence rate 74,8%) with the single use of sumatritpan 100 mg or zolmitriptan 2,5 mg or rizatriptan 10mg in at least 5 consecutive attacks, and didn't present a reduction of the recurrence rate superior than 20% with the combination of tolfenamic acid 200 mg or rofecoxib 25 mg in at least 5 other consecutive attacks (mean recurrence rate 60%). The patients had to treat 6 consecutive moderate or severe migraine attacks with their usual combination plus 4 mg of dexamathasone with a maximum of twice a week, and fill out a diary reporting headache parameters. Twenty patients, 16 women and 4 men completed the study. Of those who completed the study, 11 took rizatriptan plus rofecoxib, 4 rizatriptan plus tolfenamic acid, 3 zolmitriptan plus rofecoxib, 1 zolmitriptan plus tolfenamic acid and 1 patient took sumatriptan plus tolfenamic acid, having the 20 patients taken as a third medication, a single tablet of 4 mg of dexamethasone. All patients took oral formulations and none presented vomiting after that. Among all 20 patients, one female and one male patient presented recurrence in 3 out of the 6 attacks (50%) while the remaining 18 patients revealed recurrence in 1 or 2 treated attacks (mean 23,4%) (p<0,001). We concluded that the judicious use of oral dexamethasone might be useful for a limited population of migraine patients still presenting recurrence with the combination of a triptan and a NSAID. Case-control studies and studies with a randomized double-blind design are necessary to confirm these observations.",2002.0,0,0
216,11595003,Drug-resistant cluster headache responding to gabapentin: a pilot study.,M Leandri; M Luzzani; G Cruccu; A Gottlieb,"Prompted by the results of gabaergic drugs, such as valproate and topiramate, we performed this pilot study to assess the effect of gabapentin in cluster headache. Eight patients suffering from episodic cluster headache and four suffering from chronic cluster headache were studied. All of them had failed to respond to traditional prophylactic drugs. The design of the study was an open trial. The main parameter for effectiveness was the number of daily attacks. Gabapentin was given at the daily dosage of 900 mg. All patients were pain free after a maximum of 8 days after starting therapy, with a bout duration thus reduced to 16-40% of the average previous bouts (only applies to episodic cluster patients). We hypothesize that the gabaergic action of gabapentin, perhaps combined with other mechanisms, such as calcium channel blockade, may be responsible for its remarkable effects on cluster headache.",2002.0,0,0
217,11596834,The cost effectiveness of stratified care in the management of migraine.,P Williams; A J Dowson; A M Rapoport; J Sawyer,"To examine the cost effectivess of a stratified-care regimen for patients with migraine--in which patients are stratified by severity of illness, and then prescribed differing treatments according to level of severity--compared with a conventional stepped-care approach. A decision analytic model was constructed to simulate a controlled clinical trial in which patients with migraine receiving primary medical care were randomly assigned to treatment under a stepped-care or a stratified-care regimen. A health service payer perspective was adopted and the time horizon was 1 year. Data inputs were: (i) the frequency and disability of migraine, derived from population-based studies; (ii) disability level-specific treatment response rates for over-the-counter analgesics,aspirin/metoclopramide and zolmitriptan as the representative of high-end therapy obtained from an international consensus opinion enquiry; and (iii) unit costs of healthcare obtained from UK health service sources. The estimated 1-year direct healthcare costs per primary care patient with migraine were pound sterling 156.82 for stepped care and sterling pound 151.57 for stratified care. Estimates of treatment response rates were 40 and 71% for stepped and stratified care, respectively. The cost per successfully treated attack was sterling pound 23.43 for stepped care and sterling pound 12.60 for stratified care. Stratified care remained cost effective when tested in a wide range of one-way sensitivity analyses, and probabilistic sensitivity analysis showed the cost effectiveness of stratified care to be significant at the 3% level. Conditional confidence analysis showed that the level of confidence in the cost effectiveness of stratified care varied positively with the case mix, i.e. in populations where the proportion of moderate and severely disabled patients with migraine was greater than 25%, the cost effectiveness of stratified care remained statistically significant. A stratified-care treatment strategy (including zolmitriptan as the representative of high-end therapy) is a highly cost-effective method of managing migraine in the primary care setting compared with stepped care, delivering improved clinical outcomes at no additional cost.",2001.0,0,0
218,11673575,Comparison of rizatriptan and other triptans on stringent measures of efficacy.,J U Adelman; R B Lipton; M D Ferrari; H C Diener; K A McCarroll; K Vandormael; C R Lines,"To compare the efficacy of oral rizatriptan 10 mg with oral doses of sumatriptan, naratriptan, and zolmitriptan on stringent outcome measures. Retrospective analysis of data from five randomized, placebo-controlled, double-masked clinical trials in which oral rizatriptan was directly compared with oral sumatriptan 100 mg (n = 772), 50 mg (n = 1116), 25 mg (n = 1183), naratriptan 2.5 mg (n = 413), and zolmitriptan 2.5 mg (n = 580) for the acute treatment of a moderate or severe migraine attack. Percentage of patients pain-free at 2 hours, symptom-free at 2 hours (no pain, nausea, photophobia, phonophobia, vomiting, or functional disability), 24-hour sustained pain-free (no headache at 2 hours, no recurrence, and no additional antimigraine medications for 24 hours). More patients taking rizatriptan 10 mg were pain-free at 2 hours than were patients taking sumatriptan 100 mg (40% vs 33%, p = 0.019), sumatriptan 50 mg (40% vs 35%, p = 0.009), sumatriptan 25 mg (38% vs 27%, p < 0.001), naratriptan 2.5 mg (45% vs 21%, p < 0.001), and zolmitriptan 2.5 mg (43% vs 36%, p = 0.041). More patients taking rizatriptan 10 mg were symptom-free at 2 hours than were patients taking sumatriptan 100 mg (31% vs 22%, p = 0.002), sumatriptan 50 mg (33% vs 28%, p = 0.003), sumatriptan 25 mg (33% vs 24%, p < 0.001), naratriptan 2.5 mg (30% vs 11%, p < 0.001), and zolmitriptan 2.5 mg (31% vs 24%, p = 0.042). More patients taking rizatriptan 10 mg had a 24-hour sustained pain-free response than did patients taking sumatriptan 100 mg (27% vs 23%, p = 0.112), sumatriptan 50 mg (30% vs 26%, p = 0.015), sumatriptan 25 mg (27% vs 20%, p = 0.005), naratriptan 2.5 mg (29% vs 17%, p = 0.004), and zolmitriptan 2.5 mg (32% vs 24%, p = 0.013). Oral rizatriptan 10 mg was more effective than oral sumatriptan, naratriptan, and zolmitriptan on stringent outcome measures of pain-free response at 2 hours, symptom-free response at 2 hours, and 24-hour sustained pain-free response.",2002.0,0,1
219,11675061,Selective seratonin 1F (5-HT(1F)) receptor agonist LY334370 for acute migraine: a randomised controlled trial.,D J Goldstein; K I Roon; W W Offen; N M Ramadan; L A Phebus; K W Johnson; J M Schaus; M D Ferrari,"Triptans (5-HT(1B/1D) receptor agonists) are effective drugs for acute migraine, but the side-effect of coronary vasoconstriction restricts their use in patients who are at risk of coronary artery disease. We have studied the efficacy of LY334370, a selective serotonin 1F (5-HT(1F)) receptor agonist with preclinical efficacy and no vasoconstriction, for migraine relief. We gave LY334370 (20, 60, or 200 mg) or placebo to 99 outpatients with moderate or severe migraine headaches in a double blind, parallel group study. We measured efficacy by sustained response, response at 2 h, pain free at 2 h, and sustained pain free. The proportions of patients with defined endpoints for placebo and LY334370 20, 60, and 200 mg, respectively, were: sustained response, two of 26 (8%), three of 22 (14%), 11 of 30 (37%), and 11 of 21 (52%) (dose response p<0.001); response, five of 26 (19%), four of 22 (18%), 15 of 30 (50%), and 15 of 21 (71%) (p<0.001); pain free, one of 26 (4%), none of 22, eight of 30 (27%), and eight of 21 (38%) (p=0.001); sustained pain free, one of 26 (4%), none of 22, seven of 30 (23%), and seven of 21 (33%) (p=0.002); recurrence rates, one of five (20%), none of four, four of 15 (27%), and three of 15 (20%). More patients given LY334370 than placebo reported asthenia, somnolence, and dizziness. Our findings show that LY334370 is effective in treatment of acute migraine through selective trigeminovascular neuronal inhibition.",2001.0,0,1
220,11678812,Sumatriptan by injection.,M D Ferrari,,2002.0,0,0
221,11678813,,,,,0,1
222,11678814,The sumatriptan nasal spray: a review of clinical trials.,A Rapoport,,2002.0,0,0
223,11678815,Sumatriptan in the treatment of cluster headache.,H C Diener,,2002.0,0,0
224,11678816,The sumatriptan difference.,R Salonen,,2002.0,0,0
225,11678817,Sumatriptan in paediatric and adolescent migraine.,M Ueberall,,2002.0,0,0
226,11678820,Building on the sumatriptan experience: the development of naratriptan.,H E Connor,,2002.0,0,0
227,11695077,Patient satisfaction with rizatriptan versus other triptans: direct head-to-head comparisons.,W C Gerth; K A McCarroll; N C Santanello; K Vandormael; Q Zhang; L K Mannix,"This study summarises the impact of treatment with rizatriptan 10 mg versus other 5-HT 1B/1D receptor agonists (triptans) on patient satisfaction with medication. Rizatriptan is a potent, selective 5-HT1B/1D receptor agonist shown to be fast, effective and well tolerated in the acute treatment of migraine. We investigated patients' overall satisfaction with treatment in studies in which direct comparisons with other triptans were made. Data from five double-blind, placebo-controlled trials in which rizatriptan 10 mg was compared with another triptan were included in the analysis. Rizatriptan 10 mg was compared with sumatriptan 100 mg in one parallel study (n = 916), sumatriptan 50 mg in two crossover studies (n = 1599), naratriptan 2.5 mg in one parallel study (n = 502), and zolmitriptan 2.5 mg in one parallel study (n = 701). Satisfaction was reported by patients on a seven-point scale ranging from 'completely satisfied, couldn't be better' to 'completely dissatisfied, couldn't be worse' at 2 hours after dosing. The percent of patients in the top two 'satisfied' categories (completely or very satisfied) were analysed. More patients on rizatriptan 10 mg were completely or very satisfied compared with sumatriptan 100 mg (33% vs 26%, p < 0.05), sumatriptan 50 mg (40% vs 35%, p < 0.05), naratriptan 2.5 mg (33% vs 19%, p < 0.01), and zolmitriptan 2.5 mg (38% vs 30%, p < 0.05). In all five studies more patients treated with rizatriptan 10 mg or other triptans were completely or very satisfied with treatment than patients receiving placebo (p < 0.001, except naratriptan vs placebo p = 0.004). The results, combined with the superior efficacy profile (fast, effective, well tolerated) of rizatriptan 10 mg, should enhance the treatment of migraine headache and lead to improved therapeutic intervention in clinical practice.",2002.0,0,1
228,11700778,Different approaches to valuing the lost productivity of patients with migraine.,J H Lofland; J C Locklear; K D Frick,"To calculate and compare the human capital approach (HCA) and friction cost approach (FCA) methods for estimating the cost of lost productivity of migraineurs after the initiation of sumatriptan from a US societal perspective. Secondary, retrospective analysis to a prospective observational study. A mixed-model managed care organisation in western Pennsylvania, USA. Patients with migraine using sumatriptan therapy. Patient-reported questionnaires collected at baseline, 3 and 6 months after initiation of sumatriptan therapy. The cost of lost productivity estimated with the HCA and FCA methods. Of the 178 patients who completed the study, 51% were full-time employees, 13% were part-time, 18% were not working and 17% changed work status. Twenty-four percent reported a clerical or administrative position. From the HCA, the estimated total cost of lost productivity for 6 months following the initiation of sumatriptan was $US117905 (1996 values). From the FCA, the six-month estimated total cost of lost productivity ranged from $US28329 to $US117905 (1996 values). This was the first study to retrospectively estimate lost productivity of patients with migraine using the FCA methodology. Our results demonstrate that depending on the assumptions and illustrations employed, the FCA can yield lost productivity estimates that vary greatly as a percentage of the HCA estimate. Prospective investigations are needed to better determine the components and the nature of the lost productivity for chronic episodic diseases such as migraine headache.",2002.0,0,0
229,11702897,,,,,0,1
230,11703169,Treatment of migraine with targeted nutrition focused on improved assimilation and elimination.,J Sensenig; M Johnson; T Staverosky,"This study was undertaken to assess the impact of three months of targeted nutritional therapy for migraine on health-related quality of life. The study is also intended to lend support to a theory that migraine is caused by an underlying dysfunction involving assimilation or elimination mechanisms. Forty people were selected from approximately 120 applications. Fourteen participants were selected from among those applicants within the authors' practices and 26 from applicants solicited via the Internet. Participants were required to complete the Medical Outcomes Trust Migraine Specific Quality of Life (MSQ) Questionnaire. Eighty percent of the study participants experienced significant and sustained improvements in quality of life during the 90 days of the study. The study instrument is specifically designed to measure quality of life improvement and thus does not solicit responses relative to number of migraine attacks or duration of each migraine. However, it should be noted that improvement in quality of life is likely due to a reduction in the duration and frequency of migraine attacks.",2002.0,0,0
231,11703472,Mixing sumatriptan: a prospective study of stratified care using multiple formulations.,R G Kaniecki,"To assess the acceptability, utility, and tolerability of a system of stratified care of acute migraine using multiple formulations of sumatriptan. Stratified care matches the treatment of a disease to its level of severity. Sumatriptan, with its multiple formulations, seems a logical option in a stratified care approach. Little data exists on the use of multiple formulations in a single patient population. A prospective, open-label, outpatient study recruited patients from a single center during the period from January 1998 through June 1998. Entry criteria included International Headache Society migraine diagnostic codes 1.1 or 1.2 and an established response to sumatriptan tablets or nasal spray. Patients who enrolled were allowed to use subcutaneous sumatriptan as either primary or rescue therapy for individual migraine attacks. Two hundred eighteen (80%) of 273 patients on tablets and 40 (85%) of 47 patients on nasal spray enrolled. During a period of 6 months, 61% of the patients on tablets and 85% of the patients using the nasal spray used at least one subcutaneous dose of sumatriptan. This system was efficacious and well tolerated. The majority of injections were used as rescue treatments following a failed oral or nasal dose. Two percent withdrew due to lack of efficacy, and 6% withdrew due to adverse events; however, 92% professed satisfaction with subcutaneous sumatriptan as an available tool for migraine management. A system of stratified care using multiple formulations of sumatriptan is efficacious, well tolerated, and preferable to a program involving a single form of the drug.",2002.0,0,1
232,11703474,Efficacy and tolerability of subcutaneous sumatriptan for acute migraine: a comparison between ethnic groups.,P Burke-Ramirez; M Asgharnejad; C Webster; R Davis; A Laurenza,"To evaluate efficacy and tolerability of subcutaneous sumatriptan 6 mg versus placebo for acute migraine between ethnic groups. Patients in previous sumatriptan studies have been predominantly Caucasian and the effects of sumatriptan between different ethnic groups are unknown. This was a multicenter, 3-phase, 12-attack study. Phases I and III (inclinic) were randomized, double-blind, placebo-controlled, crossover designs. Phase II (outpatient) was a single-blind design. Sumatriptan was compared to placebo across 2 groups (non-Caucasian and Caucasian) and individual ethnic subgroups (black, Hispanic, and others). Headache response, pain-free response, associated symptoms, and clinical disability were assessed. Tolerability assessments included the incidence of adverse events, physical examinations, vital signs, electrocardiograms, and clinical laboratory data. Two hundred patients treated at least one migraine attack (150 non-Caucasians: 46 blacks, 68 Hispanics, 36 others). Two hours postdose, significantly more inclinic sumatriptan-treated patients reported headache response (non-Caucasians, 81% versus 37% placebo; Caucasians, 87% versus 19% placebo; P<.001) and mild or no clinical disability, compared with placebo (non-Caucasians, 87% versus 50% placebo; Caucasians, 90% versus 38% placebo; P<.001). Blacks (80%), Hispanics (83%), and others (74%) reported similar patterns of headache response at 2 hours. Similar results were reported during the outpatient phase. The incidence of adverse events following sumatriptan during the inclinic phase was similar between ethnic groups (non-Caucasian, 75%; Caucasian, 79%) and higher than placebo (non-Caucasian, 51%; Caucasian, 31%). Overall, adverse events in the outpatient phase of the study were lower than in the inclinic phase. Sumatriptan injection is effective and well tolerated in non-Caucasians and Caucasians for the treatment of acute migraine attacks. Only minor differences in efficacy or tolerability were observed between blacks, Hispanics, and others.",2002.0,0,1
233,11706113,Clinical features of withdrawal headache following overuse of triptans and other headache drugs.,Z Katsarava; G Fritsche; M Muessig; H C Diener; V Limmroth,"Complete withdrawal from headache medication is the treatment of choice for medication-overuse headache. Discontinuation of the overused headache medication, however, results in the development of withdrawal headache, often associated with nausea, vomiting, and sleep disturbances. In a prospective study of 95 patients, the authors investigated the duration and severity of withdrawal headache after overuse of various headache drugs, including single and combination analgesics, ergots, and triptans. All patients underwent standard inpatient withdrawal therapy for 14 days. The duration of withdrawal headache was shorter in patients overusing triptans (4.1 days) than in patients overusing ergots (6.7 days) or analgesics (9.5 days; p < 0.002). The mean headache intensity on the first day of withdrawal did not differ between the groups (p = 0.821). By day 14, however, it was lower in patients overusing triptans (0.08) than in patients overusing ergots (0.4) or analgesics (0.9; p < 0.005). Rescue medication was requested less by patients undergoing triptan withdrawal (0.25 requests) than by patients undergoing ergot withdrawal (1.25) or analgesic withdrawal (1.85; p < 0.05). Similar to findings in the entire patient population, withdrawal headache was shorter and less severe in migraineurs overusing triptans than in those overusing ergots or analgesics. Because only patients with migraine, but no patient with tension-type headache, overused triptans, withdrawal headache was shorter in the group of patients with migraine alone (6.7 days versus 9.6 days for patients with tension-type headache and 8.5 days for patients with combination headache, p < 0.02). The duration and severity of withdrawal clearly depend on the type of overused headache drug only.",2002.0,0,1
234,11717813,Development of CGRP antagonists for the treatment of migraine.,H Doods,"Migraine is one of the most common neurological disorders, involving periodical attacks of headache and nausea as well as a plethora of other symptoms. Although considerable progress has been made, the pathophysiology of migraine is still not understood. However, several observations point to an involvement of calcitonin gene-related peptide (CGRP). Migraine headache involves the activation of the trigeminal system and dilatation of cranial vessels. CGRP is localized to neurons in the trigeminal ganglia and CGRP levels are increased during a migraine attack, presumably causing the vasodilation observed. Accordingly, it is conceivable that inhibition of CGRP-evoked dilatation of the cranial vessels may provide a novel treatment for migraine headache. The non-peptidic CGRP antagonist BIBN-4096BS (Boehringer Ingelheim) is presently under clinical investigation to assess the importance of CGRP in migraine headache and to answer the question of whether the concept of CGRP antagonists may offer advantages, e.g., higher efficacy, lower recurrence rate or improved side-effect profile, compared to the currently used antimigraine drugs.",2002.0,0,0
235,11718585,Patient treatment preferences and the 5-HT1B/1D agonists.,R E Ryan,"Migraineurs have specific preferences with regard to migraine therapy. In surveys, they consistently cite several attributes they seek in a migraine medication: rapid pain relief, complete pain relief, ability to return to normal functioning, relief of migraine-associated symptoms, reduction in headache recurrence, and minimal adverse effects. When prescribing medication for patients with migraine, physicians should respect patients' treatment preferences and select drugs that most closely meet patients' needs. As a class, the 5-HT(1B/1D) agonists, or triptans, have many of these attributes, including effectively relieving pain and associated symptoms and allowing patients to return fairly quickly to their normal activities. However, differences have emerged in the ability of specific triptans to satisfy patient preferences. Physicians should consider these differences when prescribing triptans for their patients with migraine.",2002.0,0,1
236,11723269,"Dose finding, placebo-controlled study of oral almotriptan in the acute treatment of migraine.",C Dahlöf; P Tfelt-Hansen; H Massiou; A Fazekas; Almotriptan Study Group,"To assess the efficacy and tolerability of oral almotriptan, a selective serotonin receptor (5-HT1B/1D) agonist, when used at different doses in the treatment of acute migraine. This was a placebo controlled, double-blind, parallel-group, dose-finding study. Patients satisfying International Headache Society criteria for acute migraine were randomized to a single dose of placebo or oral almotriptan 2, 6.25, 12.5, or 25 mg at the onset of moderate or severe pain. Patients graded pain intensity on a 4-point verbal scale from 0 (no pain) to 3 (severe pain) and recorded adverse events. The primary efficacy variable was headache response at 2 hours. Data were analyzed on an intent-to-treat basis. Nine hundred and three patients were randomized, and 742 were included in the evaluation of the efficacy and tolerability. Headache response at 2 hours was 32.5% with placebo, and 30%, 56.3%, 58.5%, and 66.5% with almotriptan 2, 6.25, 12.5, and 25 mg doses (p < 0.05 for 6.25, 12.5, and 25 mg vs placebo). A dose-dependent decrease in the incidence of migraine-associated symptoms and the need for escape medication was observed. The incidence of adverse events with the almotriptan 2-mg, 6.25-mg, and 12.5-mg groups was comparable to that with the placebo group. Almotriptan 12.5 mg demonstrated the most favorable ratio between efficacy and tolerability, offering equivalent efficacy and better tolerability compared with the 25 mg dose. The minimum effective dose of almotriptan was 6.25 mg.",2002.0,0,1
237,11725851,Migraine and tension-type headache reduction through pericranial muscular suppression: a preliminary report.,W E Shankland,"Migraine and tension-type headaches have always plagued mankind. In spite of all the research dollars spent trying to determine the etiologies of these headaches, the neurology community still has not established a known cause of migraine and tension type headaches. This paper describes a study that was conducted for the U.S. Food and Drug Administration in which the efficacy of the Nociceptive Trigeminal Inhibition Tension Suppression System was evaluated and proved safe and efficacious in the reduction of medically diagnosed migraine and tension-type headache.",2002.0,0,0
238,11728541,Oral triptans (serotonin 5-HT(1B/1D) agonists) in acute migraine treatment: a meta-analysis of 53 trials.,M D Ferrari; K I Roon; R B Lipton; P J Goadsby,"The triptans, selective serotonin 5-HT(1B/1D) agonists, are very effective acute migraine drugs with a well- developed scientific rationale. Seven different triptans will soon be clinically available, making evidence-based selection guidelines necessary. Triptan trials have similar designs, facilitating meta-analysis; this will provide a foundation for using triptans in clinical practice. We asked pharmaceutical companies and the principal investigators of company-independent trials for raw patient data of all double-blind, randomised, controlled, clinical trials of oral triptans in migraine. We calculated summary estimates across studies for important efficacy and tolerability parameters, and separately summarised direct comparator trials. 53 clinical trials (12 unpublished) involving 24089 patients, met the criteria for inclusion. Mean results for 100 mg sumatriptan were 59% (95% CI 57-60) for 2 h headache response (improvement from moderate or severe to mild or no pain); 29% (27-30) for 2 h pain free (improvement to no pain); 20% (18-21) for sustained pain free (pain free by 2 h and no headache recurrence or use of rescue medication 2-24 h post dose); and 67% (63-70) for consistency (response in at least two of three treated attacks); placebo-subtracted proportions for patients with at least one adverse event (AE) were 13% (8-18), for at least one central nervous system AE 6% (3-9), and for at least one chest AE 1.9% (1.0-2.7). Compared with these data, 10 mg rizatriptan showed better efficacy and consistency, and similar tolerability; 80 mg eletriptan showed better efficacy, similar consistency, but lower tolerability; 12.5 mg almotriptan showed similar efficacy at 2 h but better other results; 2.5 mg naratriptan and 20 mg eletriptan showed lower efficacy and (the first two) better tolerability; 2.5 mg and 5 mg zolmitriptan, 40 mg eletriptan, and 5 mg rizatriptan showed very similar results. The results of the 22 trials that directly compared triptans show the same overall pattern. We received no data on frovatriptan, but publicly available data suggest lower efficacy. At marketed doses, all oral triptans were effective and well tolerated. 10 mg rizatriptan, 80 mg eletriptan, and 12.5 mg almotriptan provide the highest likelihood of consistent success.",2002.0,0,1
239,11731730,Intranasal sumatriptan in post-ECT headache: results of an open-label trial.,J S Markowitz; C H Kellner; C L DeVane; M D Beale; J Folk; C Burns; H L Liston,"Significant headaches occur in up to 45% of patients receiving electroconvulsive therapy (ECT) as a result of treatment. Headaches may at times be severe and affect patient compliance with this treatment modality. The 5-HT(1B/1D) receptor agonist sumatriptan has been reported to be effective for post-ECT headache in several case reports. The aim of the present open-label study was to assess the efficacy and tolerability of intranasal sumatriptan for post-ECT headache. Patients undergoing ECT who experienced moderate-to-severe post-ECT headache were enrolled in the study. Patients were asked to rate their headache severity and describe headache characteristics using a standard headache diary. Headaches rated as severe or moderate were treated with 20 mg of intranasal sumatriptan. Additional headache ratings were recorded at 0.25, 0.5, 1.0, 1.5, and 2 hours after sumatriptan administration and compared with baseline values. Eight female patients (ages 34-45 years old) participated in the trial and experienced a total of 13 post-ECT headaches, which were treated with intranasal sumatriptan. Of the headaches treated, six (46.2%) were described as severe and seven (53.8%) were characterized as moderate in severity. Twelve (92.3%) of the treated headaches responded by the 2 hour posttreatment time point and 11 (84.6%) had responded within 1 hour. Comparisons made at the 1- and 2-hour time point revealed a statistically significant improvement from baseline (p = 0.002). Of the 12 headaches that responded, 6 (50%) were reported as no pain and 5 (38.5%) were reported as only mild pain at 1 hour following treatment. At the 2-hour assessment, an additional headache, which had previously not responded, was rated at mild resulting in six (50%) headaches with complete resolution of pain and six (50%) with a decrease in pain symptoms from moderate or severe to mild. Overall, sumatriptan treatment was well tolerated, and no significant adverse effects or changes in vital signs were recorded. In no case was a second dose of sumatriptan given. The most common complaint was the taste of the medication (n = 4), which was not treatment limiting. No patient withdrew from the study due to an adverse event. Intranasal sumatriptan spray may be an effective, well-tolerated, and prompt treatment for patients experiencing moderate-to-severe post-ECT headache. Preventing post-ECT headache may contribute to patient compliance with the ECT treatment modality. Additionally, the known pharmacologic effects of sumatriptan and the generally positive results found in the present study suggest that ECT-induced headache is vascular in origin. Further placebo-controlled, double-blind studies are needed to confirm our open-label results.",2002.0,0,0
240,11735616,Frovatriptan.,S E Easthope; K L Goa,"black triangle Frovatriptan, a new serotonin receptor agonist developed for the acute treatment of migraine, has high affinity for serotonin 5-HT1B and 5-HT1D receptor subtypes and is a potent stimulator of contraction in human basilar arteries. black triangle A long terminal elimination half-life (approximately 26 hours) is a distinctive pharmacokinetic feature of frovatriptan which appears to be independent of dose, age, gender and renal function. black triangle A single oral dose of frovatriptan 2.5mg was effective in the acute treatment of migraine providing meaningful relief within 2 hours to approximately twice as many recipients as placebo in clinical trials. black triangle Consistent relief of migraine symptoms was achieved in patients who treated a number of consecutive attacks with frovatriptan and the incidence of 24-hour migraine recurrence was reduced. black triangle Frovatriptan was well tolerated in clinical trials, with the overall incidence of adverse events occurring with frovatriptan 2.5mg only slightly higher than that reported with placebo. Mild to moderate fatigue, nausea and paraesthesia were the most commonly reported drug-related adverse events.",2002.0,0,0
241,11737002,Assessing patient preference in migraine treatment.,C Dahlöf,,2002.0,0,0
242,11737014,Tolerability of sumatriptan: clinical trials and postmarketing experience.,C Allen; J Dayno,,2002.0,0,1
243,11762561,Pharmacokinetics and safety of oral eletriptan during different phases of the menstrual cycle in healthy volunteers.,A K Shah; L Laboy-Goral; N Scott; T Morse; G Apseloff,"The purpose of this study was to determine the pharmacokinetics and safety of eletriptan in different phases of the menstrual cycle. Female volunteers (n = 16) with a regular menstrual cycle (28 +/- 4 days) received a single oral dose of 80 mg eletriptan during each of the four cycle phases: phase 1 (menses), days 1 to 4; phase 2 (follicular), days 6 to 10; phase 3 (ovulatory), days 11 to 13; and phase 4 (luteal), days 21 to 24. Eletriptan plasma concentrations were determined from serial plasma samples taken during a 24-hourperiod after dosing. Blood pressure, pulse rate, and ECG measurements were performed at baseline, 1 and 24 hours after dosing. No significant differences between phases were observed for maximum plasma concentration (cmax, range of means = 188-234 ng/ml), time to maximum concentration (tmax, range of means = 1.8-2.5 h), or systemic exposure (area under the curve [AUC], range of means = 1194-1514 ng x h/ml). Although there was a statistically significant difference in the terminal phase elimination rate constant (kel) between phases 1 and2 (0.175/h vs. 0.158/h, p = 0.044), the corresponding difference in terminal phase half-life (t 1/2) (4.0 h vs. 4.4 h) was not considered to be clinicallyrelevant. No clinically relevant differences in blood pressure, pulse rate, or ECG were observed, and the incidence, nature, and severity of adverse events were similar in all phases. The different phases of the menstrual cycle had no clinically significant effect on the pharmacokinetics, safety, or tolerability of oral 80 mg eletriptan in healthy females.",2002.0,0,0
244,11768838,"Efficacy and tolerability of subcutaneous almotriptan for the treatment of acute migraine: a randomized, double-blind, parallel-group, dose-finding study.",X Cabarrocas; Almotriptan Study Group,"The 5-hydroxytryptamine-receptor agonist almotriptan was found to be well tolerated and efficacious when administered orally in clinical trials of migraine treatment. The primary objective of this study was to assess the efficacy and tolerability of 3 different doses of subcutaneous almotriptan in the treatment of acute migraine attacks. This was a Phase II multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-finding study conducted over 7 months at 13 practice-oriented centers and 1 larger research-focused center. Patients experiencing moderate to severe migraine with or without aura, as defined by International Headache Society criteria, were randomly assigned to receive a single subcutaneous dose of almotriptan 2, 6, or 10 mg or placebo. The primary end point, pain relief at 2 hours, was self-assessed on a 4-point scale (severe, moderate, mild, or no pain). Patients indicating mild or no pain were considered responders. The analysis was performed on an intent-to-treat basis. A total of 123 patients were enrolled (23 men, 100 women). Overall, almotriptan 6 and 10 mg were significantly more effective than placebo (P < 0.05, Fisher exact test). Response rates for the 6- and 10-mg doses were 96.5% and 90.3%, respectively, compared with 50.0% for placebo (P < 0.05, Fisher exact test). The proportion of patients with pain relief at 2 hours was not significantly different between almotriptan 2 mg and placebo. The response profile for the secondary end points was also better with almotriptan 6 and 10 mg than with placebo. Administration of almotriptan was well tolerated; the most frequently observed drug-associated adverse event was transient local irritation at the injection site. Almotriptan was well tolerated and significantly more effective than placebo in relieving moderate to severe migraine pain when administered as a single 6- or 10-mg subcutaneous dose.",2002.0,0,1
245,11772240,Migraine and beyond: cardiovascular therapeutic potential for CGRP modulators.,S A Doggrell,"CGRP is a potent vasodilator that has been shown to have a physiological and/or pathological role in neurogenic inflammation, headaches including migraine, thermal injury, circulatory shock, pregnancy and menopause, hypertension and heart failure and is known to be cardioprotective. CGRP is also a positive inotrope and increases heart rate. Clinical trials have shown beneficial effects of the vasodilatory action of CGRP in hypertension, angina, heart failure, Raynaud's disease and venous stasis ulcers. However, the clinical potential of CGRP is limited as it has to be given by infusion and is quickly broken down. Oral long acting CGRP-mimetics may have potential in disorders in which CGRP has been shown to be beneficial. CGRP-mimetics include capsaicin/vanilloid receptor agonists and gene transfer of an adenoviral vector that encodes prepro-CGRP. CGRP inhibitors have therapeutic potential in conditions in which excessive CGRP-mediated vasodilatation is present; neurogenic inflammation, migraine and other headaches, thermal injury, circulatory shock and flushing in menopause. CGRP inhibitors include capsaicin, antagonists at capsaicin/vanilloid receptors, civamide, CGRP receptor antagonists and 5-HT1D-receptor agonists. Drugs that are 5-HT1D-receptor agonists, the 'triptans' are already commonly used in migraine and the first small molecule CGRP antagonist, BIBN4096BS, is under clinical investigation for the treatment of migraine.",2002.0,0,0
246,11772292,Eletriptan.,M J Gawel; N N Grujich,"Eletriptan (Relpax, Pfizer) is one of a group of anti-migraine medications commonly referred to as 'triptans'. It is a potent serotonin agonist at the 5-HT(1B/1D) receptor and is indicated for the acute treatment of migraine headaches. Eletriptan is administered orally. It is rapidly absorbed and has a bioavailability of 50% compared to 14% for sumatriptan. The relatively high lipophilicity of eletriptan compared to sumatriptan may explain its faster oral absorption and shorter time to onset of action. Results from comparative studies between oral eletriptan and sumatriptan indicate that eletriptan 80 mg was superior to sumatriptan 100 mg in onset of action, headache response rate, pain free response rate and relief of associated migraine symptoms at the 1 or 2 h time intervals. Although there was a modest increase in adverse events with eletriptan 80 mg than with sumatriptan 100 mg, eletriptan received a high patient acceptability rating (84%).",2002.0,0,1
247,11772329,Emerging treatments for irritable bowel syndrome.,Joseph Ahn; Eli D Ehrenpreis,"Irritable bowel syndrome (IBS) is a functional GI disorder that is associated with abdominal discomfort and altered bowel habits. It accounts for up to 28% of patients presenting to a gastroenterology practice and poses a significant personal, societal and economic burden internationally. The Manning, Rome I and Rome II criteria were developed to identify appropriate IBS patients for entry into IBS studies in a consistent manner. Refinements in the understanding of the physiology of the enteric nervous system (ENS), which controls motility, secretion and sensation, provided the basis for our comprehension of the pathophysiology of IBS. Visceral hypersensitivity and neurotransmitter imbalance currently receive the most attention as possible mechanisms of IBS. This article outlines conventional treatments and reviews the data on emerging and experimental therapies for IBS. Emerging therapies for IBS using 5-HT mediation include 5-HT(3) antagonists, such as ondasetron, granisetron and alosetron, as well as 5-HT(4) agonists such as tegaserod and prucalopride. In addition to opioid agonists (e.g. fedotozine) several other drugs that act on other ENS receptors are being studied. In spite of significant progress in IBS research, these emerging therapies require more studies before they can be utilised as clinical treatments.",2002.0,0,0
248,11773947,"Gastroparesis: prevalence, clinical significance and treatment.",M Horowitz; Y C Su; C K Rayner; K L Jones,"The application of novel techniques to quantify gastric motor function and gastric emptying has yielded important insights into the prevalence, pathogenesis and clinical sequelae of gastroparesis. Both acute and chronic gastroparesis occur frequently; gastric emptying of solids is delayed in 30% to 50% of patients with diabetes mellitus, functional dyspepsia and gastroesophageal reflux disease. While many patients with gastroparesis experience upper gastrointestinal symptoms that adversely affect quality of life, the concept that symptoms are inevitably the direct outcome of delay in gastric emptying is now recognized to be overly simplistic. In contrast, the potential impact of gastroparesis on oral drug absorption and blood glucose control in patients with diabetes mellitus has probably been underestimated. While the use of prokinetic drugs (cisapride, domperidone, metoclopramide and erythromycin) forms the mainstay of therapy in symptomatic patients with gastroparesis, a number of novel pharmacological therapies are being evaluated, and preliminary studies using gastric pacing show promise.",2002.0,0,0
249,11800504,Sumatriptan challenge in bipolar patients with and without migraine: a neuroendocrine study of 5-HT1D receptor function.,T Mahmood; T Silverstone; R Connor; P Herbison,"An association between bipolar disorder and migraine has been lately recognized and an abnormality of central serotonergic function is suggested as the underlying neurophysiological disturbance. To examine the role of serotonin in bipolar disorder and migraine, we used the neuroendocrine challenge paradigm, and we chose sumatriptan, a 5HT1D agonist, as the pharmacological probe. We studied nine bipolar patients with migraine, nine bipolar patients without it, seven migraine patients, and nine matched normal controls. A post-hoc analysis showed subsensitivity of serotonergic function, reflected in a blunted growth hormone response to sumatriptan challenge in bipolar patients who also suffered from migraine.",2002.0,0,0
250,11807151,Migraine--current understanding and treatment.,Peter J Goadsby; Richard B Lipton; Michel D Ferrari,,2002.0,0,0
251,11811168,The proximal stomach and postprandial symptoms in functional dyspeptics.,G E Boeckxstaens; D P Hirsch; S D Kuiken; S H Heisterkamp; G N J Tytgat,"It remains unclear whether postprandial symptom profiles in patients with visceral hypersensitivity and in those with impaired fundic accommodation differ. Therefore, we evaluated the postprandial symptoms in functional dyspepsia (FD) patients classified according to proximal stomach function. In addition, the effect of gastric relaxation induced by sumatriptan on postprandial symptoms was studied in FD patients with impaired fundic accommodation. Twenty-five healthy volunteers (HVs) and 44 FD patients filled out a disease-specific questionnaire (Nepean Dyspepsia Index) and underwent a gastric barostat study to evaluate visceral sensitivity, meal-induced fundic relaxation, and postprandial symptoms. Postprandial symptoms evoked by a drink test or reported during the barostat study were compared between FD patients subdivided according to the underlying pathophysiological mechanism. Finally, the effect of sumatriptan on postprandial symptoms evoked by a drink test was investigated in HVs and in FD patients with impaired fundic accommodation. There was no clear relationship between any of the 15 Nepean Dyspepsia Index symptoms and proximal stomach function. Postprandial symptoms evoked during the barostat study or after the drink tests were significantly higher in FD patients than in HVs; however, no clear differences in symptom profile could be demonstrated between the different subclasses of FD. Sumatriptan did not affect the maximal ingested volume or the postprandial symptoms in HVs or FD patients after a drink test. No clear relationship could be demonstrated between postprandial symptoms and proximal stomach function.",2002.0,0,0
252,11817980,Almotriptan: a review of its use in migraine.,Susan J Keam; Karen L Goa; David P Figgitt,"Almotriptan is a selective serotonin 5-HT(1B/1D) receptor agonist ('triptan'). Its efficacy and tolerability have been assessed in a number of randomised, controlled trials in over 4800 adults with moderate or severe attacks of migraine. Oral almotriptan has a rapid onset of action (significant headache relief is observed 0.5 hours after administration of a 12.5mg dose) and efficacy is sustained in most patients who respond by 2 hours. The drug is significantly more effective than placebo as measured by a number of parameters including 2-hour headache response and pain-free response rates. Other symptoms of migraine, including nausea, photophobia and phonophobia, are also alleviated by almotriptan. The efficacy of oral almotriptan appears to be maintained over repeated doses for multiple attacks of migraine treated over a long period (up to 1 year). High headache response rates were reported over all attacks without tachyphylaxis. For the relief of single attacks of migraine, oral almotriptan 12.5mg had similar efficacy to oral sumatriptan 50mg. Patients given almotriptan report less concern with adverse effects than patients given sumatriptan. The lower incidence of chest pain following treatment with almotriptan than with sumatriptan may lead to a reduction in direct costs, with fewer patients requiring management of chest pain. Almotriptan is well tolerated. Most adverse events were of mild or moderate intensity, transient, and generally resolved without intervention or the need for treatment withdrawal. The most common adverse events associated with oral almotriptan 12.5mg treatment were dizziness, paraesthesia, nausea, fatigue, headache, somnolence, skeletal pain, vomiting and chest symptoms. The incidence of adverse events did not differ from placebo and decreased in the longer term. Almotriptan can be coadministered with drugs that share a common hepatic metabolic path; in addition, dosage reduction is required only in the presence of severe renal or hepatic impairment. Almotriptan is an effective drug for the acute treatment of moderate or severe attacks of migraine in adults. An oral dose of almotriptan 12.5mg has shown greater efficacy than placebo; current data indicate that efficacy is similar to that of oral sumatriptan 50mg, and is maintained in the long term (<or=1 year). Almotriptan has a good adverse event profile and a generally similar overall tolerability profile to sumatriptan; of note, almotriptan is associated with a significantly lower incidence of chest pain than sumatriptan. However, further clinical experience is required to clearly define the place of almotriptan among the other currently available triptans. Nevertheless, because triptans have an important place in various management regimens, and because the nature of individual patient response to triptans is idiosyncratic, almotriptan is likely to become a useful treatment option in the management of adults with moderate or severe migraine headaches.",2002.0,0,1
253,11824428,Sibutramine: new preparation. Slight weight loss; but also a slight rise in blood pressure ...,,"(1) The reference treatment for achieving weight loss by obese patients is a combination of dietary measures, exercise and behavioural interventions. There is currently no drug treatment with demonstrated efficacy on the morbidity or mortality associated with excess body weight. (2) Sibutramine, a serotonin- and noradrenaline-reuptake inhibitor structurally related to the amphetamines has been granted marketing authorisation in France for the treatment of obesity and excess body weight in patients with associated risk factors. (3) The clinical file on sibutramine contains no trial focusing on morbidity or mortality end points. (4) According to comparative clinical trials, weight loss during a 6-12 month course of sibutramine is, on average, between 3 and 9 kg greater than that on placebo. Patients regain weight after sibutramine cessation. (5) Sibutramine has little or no benefit on blood sugar or lipid parameters. (6) The main known adverse effect of sibutramine is increased blood pressure. Sibutramine also has amphetamine-like side effects. (7) In practice, sibutramine currently has no place in the management of obesity.",2002.0,0,0
254,11826560,Frovatriptan approved as migraine treatment.,Cheryl A Thompson,,2002.0,0,0
255,11844897,"Zolmitriptan versus a combination of acetylsalicylic acid and metoclopramide in the acute oral treatment of migraine: a double-blind, randomised, three-attack study.",G Geraud; A Compagnon; A Rossi; COZAM Study Group,"This multicentre, randomised, double-blind study compared oral zolmitriptan 2.5 mg with a combination of oral acetylsalicylic acid 900 mg and metoclopramide 10 mg as acute anti-migraine therapy for 3 migraine attacks. In total, 666 patients took at least one dose of study medication (326 took zolmitriptan and 340 took acetylsalicylic acid plus metoclopramide). The percentage of patients with a 2-hour headache response after the first dose for all 3 attacks (the primary end point) was 33.4% with zolmitriptan and 32.9% with acetylsalicylic acid plus metoclopramide [odds ratio 1.06, 95% confidence interval (CI) 0.77-1.47; p = 0.7228]. For the majority of secondary end points, the two treatments demonstrated comparable efficacy. However, post hoc analysis showed that significantly more patients receiving zolmitriptan were free of pain 2 h after the first dose in all 3 attacks compared with patients receiving acetylsalicylic acid plus metoclopramide (10.7 vs. 5.3%; odds ratio 2.19, 95% CI 1.23-4.03; p = 0.0095). In addition, post hoc analysis showed that the overall 2-hour pain-free response rate was consistently higher with zolmitriptan (34.6%) than with acetylsalicylic acid plus metoclopramide (27.9%) (odds ratio 1.40, 95% CI 1.09-1.78; p = 0.007). Both treatments reduced migraine-associated nausea, vomiting, phonophobia and photophobia. There were no important inter-group differences with respect to the onset of meaningful migraine relief, the frequency of headache recurrence, the usage or efficacy of a second dose of medication or the use of escape medication. However, at the last attack, the proportion of patients who expressed overall satisfaction with the treatment was significantly higher in the zolmitriptan group, i.e. 83.7%, versus 75.0% with acetylsalicylic acid plus metoclopramide (p = 0.0346). Both agents were well tolerated. Adverse events were reported by 40.8% (133/326) of zolmitriptan-treated patients and 29.1% (99/340) of those treated with acetylsalicylic acid plus metoclopramide. The incidence of withdrawals due to adverse events was very low with both zolmitriptan (0.9%) and the combination regimen (1.5%); the latter percentage included 1 patient who withdrew from the study due to phlebitis, which was classified as a serious adverse event. This study showed that zolmitriptan is effective and well tolerated for the acute treatment of moderate to severe migraine. Zolmitriptan was at least as effective as acetylsalicylic acid plus metoclopramide in achieving a 2-hour headache response, but significantly more effective than the combination therapy for other end points, including the 2-hour pain-free response.",2002.0,0,1
256,11844898,"Efficacy, tolerability and safety of oral eletriptan and ergotamine plus caffeine (Cafergot) in the acute treatment of migraine: a multicentre, randomised, double-blind, placebo-controlled comparison.",Hans-Christoph Diener; Jan-Peter Jansen; Avinoan Reches; Julio Pascual; Daniela Pitei; Timothy J Steiner; Eletriptan and Cafergot Comparative Study Group,"The 5-HT(1B/1D/1F) agonist eletriptan, at an oral dose of 80 mg, has been shown to be more efficacious than sumatriptan 100 mg and placebo in the treatment of migraine attacks with or without aura. Another commonly prescribed oral treatment for migraine attacks is Cafergot (1 mg ergotamine tartrate with 100 mg caffeine per tablet). The efficacy, tolerability and safety of 40- and 80-mg doses of eletriptan and 2 tablets of Cafergot were compared in a double-blind, randomised, placebo-controlled, parallel-group trial involving 733 migraine patients. Patients recorded symptoms at baseline (before treatment) and 1, 2, 4 and 24 h after dosing. Headache intensity was assessed on a 4-point scale (3 = severe pain, 2 = moderate pain, 1 = mild pain, 0 = no pain). Significantly more eletriptan-treated patients (80 mg, 68%; 40 mg, 54%) than Cafergot-treated patients (33%; p < 0.001) reported headache response (improvement from moderate-to-severe to mild or no pain) at 2 h. Substantially more eletriptan recipients reported no pain (80 mg, 38%; 40 mg, 28%; Cafergot, 10%; placebo, 5%; p < 0.001). Eletriptan headache response rates at 1 h were significantly higher (80 mg, 39%; 40 mg, 29%; Cafergot, 13%; placebo, 13%; p < 0.002 for each comparison). Both doses of eletriptan were significantly more effective than Cafergot in reducing nausea (p < 0.0001), photophobia (80 mg, p < 0.0001; 40 mg, p < 0.002), phonophobia (80 mg, p < 0.0001; 40 mg, p < 0.003) and functional impairment (p < or = 0.001) at 2 h. Adverse events were generally mild or moderate and transient. This randomised trial shows that oral eletriptan is more efficacious in the acute treatment of migraine than oral Cafergot and is well tolerated.",2002.0,0,0
257,11858532,Cluster headache: evidence for a disorder of circadian rhythm and hypothalamic function.,Tamara Pringsheim,"This article reviews the literature for evidence of a disorder of circadian rhythm and hypothalamic function in cluster headache. Cluster headache exhibits diurnal and seasonal rhythmicity. While cluster headache has traditionally been thought of as a vascular headache disorder, its periodicity suggests involvement of the suprachiasmatic nucleus of the hypothalamus, the biological clock. Normal circadian function and seasonal changes occurring in the suprachiasmatic nucleus and pineal gland are correlated to the clinical features and abnormalities of circadian rhythm seen in cluster headache. Abnormalities in the secretion of melatonin and cortisol in patients with cluster headache, neuroimaging of cluster headache attacks, and the use of melatonin as preventative therapy in cluster headache are discussed in this review. While the majority of studies exploring the relationship between circadian rhythms and cluster headache are not new, we have entered a new diagnostic and therapeutic era in primary headache disorders. The time has come to use the evidence for a disorder of circadian rhythm in cluster headache to further development of chronobiotics in the treatment of this disorder.",2002.0,0,0
258,11866398,Divalproex sodium in the treatment of migraine and cluster headaches.,R Michael Gallagher; Loretta L Mueller; Frederick G Freitag,"The discovery of a new class of effective migraine-abortive medications, the triptans, has sparked a new interest in the study of vascular headache. Over the past few years, the Food and Drug Administration (FDA) has approved six new abortive pharmacologic therapies, with several others in various stages of clinical trials. Unfortunately, concurrent pharmacologic changes in headache prophylaxis have not kept pace with their abortive counterparts. However, divalproex sodium (Depakote), which is approved by the FDA as a migraine prophylactic agent, is the first in the anticonvulsant class of medication for migraine headache and has expanded the options in headache treatment. The objective of this retrospective multicenter study of 284 patients with migraine or cluster headaches was to examine the clinical efficacy and safety of divalproex sodium as prophylaxis in monotherapy and in polytherapy. Sixty-one percent of migraineurs and 73% of cluster patients noted a decrease in pain with divalproex sodium and continued that therapy for more than 3 months. Reported negative side effects included weight gain, nausea, somnolence, tremor, alopecia, dysequilibrium, and rash. However, only 14% of subjects discontinued therapy due to these side effects. Overall, divalproex sodium was found to be an effective and generally well-tolerated prophylactic treatment option as monotherapy or in polytherapy for migraine and cluster headache.",2002.0,0,0
259,11866674,,,,,0,0
260,11876686,Review article: the complexity of drug development for irritable bowel syndrome.,M A Kamm,"Drug development for functional gastrointestinal disorders is complex. These conditions involve central and peripheral physiological changes, together with psychological factors. Methodological problems have included a poor appreciation of the physiological and psychological correlates of patients' symptoms, a lack of animal models of proven relevance, and safety issues. Government, patient pressure groups and the Internet can also influence a drug's success. Most recent interest has focused on the serotonin (5-HT) modifying drugs. Cisapride has been withdrawn in some countries because of concerns related to QT prolongation and cardiac arrhythmias. The 5-HT3 antagonists, developed to modify visceral sensation, have caused constipation; alosetron, also withdrawn, caused ischaemic colitis. The 5-HT4 agonists induce peristalsis; tegaserod and prucalopride, both delayed in their development due to issues of safety and efficacy, benefit patients with 'constipation-predominant' irritable bowel syndrome or idiopathic constipation. 5-HT1 agonists improve impaired gastric accommodation and symptoms in patients with functional dyspepsia. Antidepressants also affect serotonin metabolism. Previous examples of success in this area involved drugs targeted at peripheral receptors mediating motor function or secretion. Modification of sensory function is a much more challenging objective. The experience with serotonin modifying drugs has been mixed, and some important lessons are there to be learnt.",2002.0,0,0
261,11888029,Diagnosis and treatment of migraine.,Roger Cady; David W Dodick,"Despite recent advances in understanding the pathophysiology and treatment of migraine, considerable uncertainty remains surrounding the diagnosis and treatment of this disorder. This uncertainty is reflected in studies that show both underdiagnosis and undertreatment of migraine. While the diagnosis can be assisted by criteria from the International Headache Society, other approaches may be useful in clinical practice. Treatment of migraine must be based on an individualized patient strategy that integrates education, patient participation, and effective use of pharmacological interventions. Many patients, despite self-treatment with simple analgesics, continue to suffer considerable disability associated with their migraines. Triptans, which are more effective at relieving migraine symptoms and maintaining patient function than are nonspecific therapies, are used in only a minority of patients with migraine. Treatment goals of rapid, complete relief with no recurrence and minimal adverse effects can be achieved when effective therapy is matched to individual patient goals. For prophylaxis, anticonvulsant drugs emerging as effective options are being added to the armamentarium with traditional compounds such as tricyclic antidepressants and beta-blockers.",2002.0,0,0
262,11888339,Assessing the efficacy of drugs for the acute treatment of migraine: issues in clinical trial design.,Nabih M Ramadan,"Clinical trials of therapies for acute migraine attacks have evolved over the years from open-label, small observational studies to highly structured randomised, controlled trials. The International Headache Society Committee on Clinical Trials in Migraine developed a tool to guide in designing scientifically sound trials. The proof of effect is best achieved in a clinical trial with: clearly defined objectives;a well-characterised study population, identified using well-validated diagnostic tools;proper randomisation and blinding;inclusion of a placebo arm, with proper balancing of patients receiving placebo and those receiving active drug;adequate study power; and appropriate statistical methods. Both parallel and crossover studies may be suitable in clinical trials of antimigraine agents, although the latter are a better choice in patient preference and bioequivalence studies. Although various efficacy measures are used to assess treatment effect, the 2-hour pain free rate (total resolution of pain within 2 hours after an initial moderate to severe headache) is preferred because it is clinically relevant and is relatively 'placebo-insensitive'. Various migraine surveys have indicated that a rapid onset of therapeutic effect is a highly desirable attribute of an antimigraine drug. Therefore, accurate measurements of treatment effect before 2 hours are becoming increasingly emphasised. Consistency of effect across multiple attacks adds to the understanding of the therapeutic efficacy of a test drug. Finally, preference and satisfaction studies allow us to assess patients' global impression of a particular treatment, weighing the positive effects on pain and associated symptoms of migraine against potential adverse effects.",2002.0,0,1
263,11888361,Cost-effectiveness analysis of stratified versus stepped care strategies for acute treatment of migraine: The Disability in Strategies for Care (DISC) Study.,Mark Sculpher; David Millson; David Meddis; Lynne Poole,"The Disability in Strategies for Care (DISC) study was the first large randomised controlled trial to compare alternative treatment strategies in the acute treatment of migraine. With 835 patients in its intention-to-treat efficacy analysis, DISC compared a stratified care strategy, where initial therapy was based on clinical need as determined by the Migraine Disability Assessment Scale (MIDAS) and two stepped care strategies (across attacks and within attacks), where first-line therapy with a simple combination analgesic was escalated, if response had been inadequate, to zolmitriptan, a migraine-specific therapy. To report on the cost effectiveness of these three strategies from a societal perspective. A cost-effectiveness analysis was undertaken using data from the DISC study, and including both health service and productivity costs. Data were collected prospectively on drug usage (main therapy and rescue medication); resource use associated with adverse events was estimated by a clinician blinded to treatment strategy. Health service resource use was costed using UK unit costs (1999 to 2000 values). Data were collected using diary cards on the amount of time patients lost from work, and on reduced effectiveness at work, due to a migraine attack. This facilitated an estimate of the productivity costs associated with the treatment strategies. To assess cost effectiveness, the differences in costs between the strategies were related to the two primary outcome measures in the trial: headache response 2 hours after initial therapy and disability-adjusted time during the first 4 hours after initial therapy. Although the mean health service cost was higher in the stratified care group (mean over 6 attacks of pound 28.25 versus pound 11.74 and pound 23.15 in the stepped care across attacks group and within attacks group, respectively), mean productivity costs over 6 attacks were lower in the stratified group (pound 112.22 versus pound 144.70 and pound 127.53). The total mean cost over six attacks was, therefore, lowest in the stratified care group (pound 138.95 compared with pound 157.19 in the stepped care across attacks group and pound 148.53 in the stepped care within attacks group), although these differences did not reach statistical significance. In terms of headache response, stratified care was statistically significantly more effective than both forms of stepped care. Using disability-adjusted time, stratified care was statistically significantly more effective than stepped care across attacks, but not against stepped care within attacks. Given its lower mean costs and higher mean effectiveness, a stratified care strategy, which included zolmitriptan, was the dominant strategy and was unequivocally more cost effective from a societal perspective than either stepped care strategy. When the uncertainty around these means was considered, stratified care had the highest probability of being cost effective.",2002.0,0,1
264,11888547,The medical benefit of 5-HT research.,Brian J Jones; Thomas P Blackburn,"5-HT research is now more than 50 years old, and it has generated a wealth of therapeutic agents, some of which have had a major impact on disease management. The 5-HT reuptake inhibitors (SSRIs) are among the most widely prescribed drugs for treating depression and a variety of other disorders including anxiety, social phobia and premenstrual dysphoria (PMD). The other major success stories of 5-HT research are the discovery of 5-HT1B/D receptor agonists for treating migraine and 5-HT3 receptor antagonists for chemotherapy and radiation-induced emesis. The role of 5-HT in the mechanism of action of antipsychotic agents remains a topic of intense research, which promises better treatments for schizophrenia in the future. Compounds interacting with 5-HT1F, 5-HT2C, 5-HT6 and 5-HT7 receptors are currently under investigation and may prove to have important therapeutic applications in the future.",2002.0,0,0
265,11903292,Evidence-based migraine therapy.,C Lines; C Allen; K McCarroll,,2002.0,0,0
266,11918620,Gastric emptying in diabetes: clinical significance and treatment.,M Horowitz; D O'Donovan; K L Jones; C Feinle; C K Rayner; M Samsom,"The outcome of recent studies has led to redefinition of concepts relating to the prevalence, pathogenesis and clinical significance of disordered gastric emptying in patients with diabetes mellitus. The use of scintigraphic techniques has established that gastric emptying is abnormally slow in approx. 30-50% of outpatients with long-standing Type 1 or Type 2 diabetes, although the magnitude of this delay is modest in many cases. Upper gastrointestinal symptoms occur frequently and affect quality of life adversely in patients with diabetes, although the relationship between symptoms and the rate of gastric emptying is weak. Acute changes in blood glucose concentration affect both gastric motor function and upper gastrointestinal symptoms. Gastric emptying is slower during hyperglycaemia when compared with euglycaemia and accelerated during hypoglycaemia. The blood glucose concentration may influence the response to prokinetic drugs. Conversely, the rate of gastric emptying is a major determinant of post-prandial glycaemic excursions in healthy subjects, as well as in Type 1 and Type 2 patients. A number of therapies currently in development are designed to improve post-prandial glycaemic control by modulating the rate of delivery of nutrients to the small intestine.",2002.0,0,0
267,11926699,Dipyridamole may be used safely in patients with ischaemic heart disease.,D M Humphreys; J Street; H Schumacher; J M Bertrand-Hardy; R Palluk,"It is thought that up to 50% of patients with cerebrovascular disease will have concurrent ischaemic heart disease. Dipyridamole co-formulated with aspirin has been shown to increase the relative reduction in risk of second stroke in patients with prior stroke/transient ischaemic attack beyond that obtaining with aspirin alone. We have sought to resolve the question of whether dipyridamole treatment increases the risk of cardiac adverse events in patients with co-existing ischaemic heart disease. The published literature, periodic safety update reports, the randomised controlled trials of antiplatelet agents in stroke prevention and those including dipyridamole in cardiovascular indications, have been reviewed and analysed. The early reports of serious adverse cardiac effect attributable to dipyridamole occurred in patients with severe coronary artery disease using dipyridamole as a stress test adjunct to cardiac imaging. The randomised controlled trials databases show no evidence of mortality and only isolated cases of significant cardiac morbidity attributable to dipyridamole at recommended oral doses in patients with ischaemic heart disease. We conclude that patients with cerebrovascular and mild to moderate concomitant ischaemic heart disease may be treated safely with dipyridamole for the secondary prevention of stroke.",2002.0,0,0
268,11926869,Emergency department treatment of migraine headaches.,David R Vinson,,2002.0,0,0
269,11954875,Treatment of acute cluster headache with 20 mg sumatriptan nasal spray--an open pilot study.,Sigrid Schuh-Hofer; Uwe Reuter; Stephan Kinze; Karl Max Einhäupl; Guy Arnold,"We investigated the efficacy and tolerability of 20 mg sumatriptan nasal spray in the acute treatment of cluster headache attacks in an open-label study. 10 patients met the criteria of the International Headache Society (IHS) for episodic or chronic cluster headache and were enrolled in our study. The primary efficacy measure was ""pain free"" 30 minutes after treatment. Secondary end-points included ""headache response"" (defined as headache improvement from ""very severe"", ""severe"" or moderate"" pain to ""mild"" or ""no"" pain) 15, 30, 45 and 60 minutes after treatment. We also assessed the participant's overall treatment satisfaction at the end of the study. Sumatriptan nasal spray was applied in 154 ""moderate"" to ""very severe"" cluster headache attacks. 30 minutes after nasal spray application, 50% of attacks were completely aborted and 58% of attacks responded to treatment. The overall efficacy of sumatriptan nasal spray was considered ""excellent"" in two, ""good"" in four, ""reasonable"" in two and ""poor"" in two patients. Eight patients indicated their intention to treat further attacks with intranasal sumatriptan. Seven patients were interviewed after a follow-up period of six months. Four patients continued to treat all cluster headache attacks with the intranasal sumatriptan formula, two patients had switched to subcutaneous sumatriptan and one patient was in remission since the end of the study. We conclude that 20 mg sumatriptan nasal spray might be an alternative therapy for the treatment of cluster headache attacks, but double-blind studies are needed to further evaluate its efficacy.",2002.0,0,0
270,11971092,Acute migraine headache: possible sensitization of neurons in the spinal trigeminal nucleus?,H Kaube; Z Katsarava; S Przywara; J Drepper; J Ellrich; H-C Diener,"To investigate trigeminal sensory processing in patients with migraine using a novel ""nociception-specific"" blink reflex. Seventeen patients with unilateral migraine headache were studied within 6 hours of onset. Blink reflexes were elicited with a standard stimulating electrode (standard blink reflex) and concentric stimulating electrode (nociception-specific blink reflex) during the acute migraine attack, after treatment with IV lysine acetylsalicylate (1,000 mg) or oral zolmitriptan (5 mg) and interictally. After standard stimulation, no differences were detected for the R1 and R2 onset latencies and areas under the curve (AUC) between the different time points and the headache and nonheadache side. Nociception-specific stimulation revealed a shortening of R2 onset latencies (44.3 +/- 5.4 ms for headache side vs 48.9 +/- 5.8 ms for nonheadache side) during the acute migraine attack compared with the headache-free interval (49.8 +/- 5.3 vs 49.8 +/- 4.5 ms). The AUC of the R2 increased on the headache side by 680% and on the nonheadache side by 230% compared with the headache-free interval. Drug treatment parallel to pain relief increased the onset latencies (zolmitriptan: 48.0 +/- 8.2 ms for headache side vs 52.3 +/- 7.6 ms for nonheadache side; lysine acetylsalicylate: 48.0 +/- 5.0 ms for headache side vs 51.2 +/- 5.6 ms for nonheadache side) and reduced the AUC of R2 (zolmitriptan by 45% and lysine acetylsalicylate by 48%). The data suggest temporary sensitization of central trigeminal neurons during acute migraine attacks.",2002.0,0,0
271,11972576,Zolmitriptan orally disintegrating tablet is effective in the acute treatment of migraine.,A J Dowson; E A MacGregor; R A Purdy; W J Becker; J Green; S L Levy,"A new formulation of zolmitriptan has been developed that dissolves on the tongue without the need for additional fluid intake. In this double-blind, parallel study, 471 patients were randomized to receive the zolmitriptan orally disintegrating tablet 2.5 mg (n=231) or matching placebo (n=240) to treat a single moderate or severe migraine. Headache relief following zolmitriptan 2.5 mg (63%) was significantly greater than with placebo (22%) at 2 h post-dose (primary endpoint; P < 0.0001). The zolmitriptan orally disintegrating tablet was also significantly more effective than placebo for 1-, 2- and 4-h pain-free response (8% vs. 3%, P=0.0207, 27% vs. 7%, P < 0.0001, and 37% vs. 11%, P < 0.0001, respectively). Of those patients stating a preference, 70% of patients preferred the orally disintegrating tablet to a conventional tablet. Zolmitriptan orally disintegrating tablets are an effective and convenient alternative to a conventional tablet, allowing migraine attacks to be treated anytime a migraine strikes, which can facilitate earlier treatment.",2002.0,1,1
272,11975819,Intraoral chilling versus oral sumatriptan for acute migraine.,M H Friedman; S J Peterson; C F Behar; Z Zaidi,"Migraine pathophysiology is associated with a dural inflammation. Recent evidence suggests that the primary inflammation occurs in a maxillary nerve segment, accessible intraorally. Local tenderness, related to symptom laterality, has been palpated consistently in asymptomatic migraine patients, and significant migraine relief has been obtained from chilling confined to this area. Thirty-five symptomatic episodic migraine patients were enrolled in this study, comparing 40 minutes of bilateral intraoral chilling, 50 mg of oral sumatriptan, and 40 minutes of sham (tongue) chilling. Hollow metal tubes chilled by circulating ice water were held in the maxillary molar periapical areas by the patient. Pain and nausea were recorded at baseline and 1, 2, 4, and 24 hours after start of treatment, using a numeric symptom-relief scale. Significant mean headache relief was obtained by maxillary chilling and sumatriptan at all four time intervals, with poor relief obtained by placebo. Maxillary chilling was more effective than sumatriptan at all four time intervals. Significant nausea relief was obtained by maxillary chilling and sumatriptan at posttreatment and 2 and 4 hours later. At 24 hours, some headache and nausea recurrence was noted with sumatriptan. The repeated-measures analysis of variance indicated that both treatments, drug (P = 0.024) and maxillary chilling (P = 0.001), reduced the headache, as compared with the control group. Tenderness suggests local inflammation associated with vasodilatation and edema. Because chilling can resolve local edema, these findings raise the possibility that an intraoral inflammation may be a factor in migraine etiology.",2002.0,0,1
273,11978220,Which oral triptans are effective for the treatment of acute migraine?,Linda Chang; Eric Henley,,2002.0,0,0
274,11990648,Chronic tension-type headache: advice for the viselike-headache patient.,Glen D Solomon,"About 3% of people experience daily viselike headaches without other associated symptoms, a condition called chronic tension-type headache. Therapy consists of tricyclic antidepressants, biofeedback, and stress management, although compelling data from randomized controlled trials are lacking.",2002.0,0,0
275,11993610,"Efficacy, safety and tolerability of oral eletriptan in the acute treatment of migraine: results of a phase III, multicentre, placebo-controlled study across three attacks.",R Stark; C Dahlöf; S Haughie; J Hettiarachchi; Eletriptan Steering Committee,"The efficacy, safety and tolerability of the 5-HT1B/D receptor agonist eletriptan (40 mg and 80 mg) in acute treatment of migraine was evaluated in a multinational, randomized, double-blind, parallel-group, placebo-controlled, three-attack study treating 1153 patients. In the initial attack, significantly more eletriptan patients reported headache relief and complete pain relief at 2 h vs. placebo (40 mg 62% and 32%, 80 mg 65% and 34%, placebo 19% and 3%; P < 0.0001). Headache relief occurred faster after eletriptan, with more patients at both doses reporting relief 30 min (P < 0.01) and 1 h (P < 0.0001) after treatment than after placebo. There was a significantly lower recurrence rate with eletriptan 80 mg compared with placebo (P < 0.01). Adverse events for all treatments were generally mild or moderate and self-limiting. Eletriptan 40 mg and eletriptan 80 mg both appear to be effective and well-tolerated acute migraine treatments.",2002.0,1,1
276,12005271,Almotriptan increases sustained pain-free outcomes in acute migraine: results from three controlled clinical trials.,David W Dodick,"Evaluate the effect of almotriptan on sustained pain-free outcome in patients with acute migraine. Three randomized, double-blind, placebo-controlled trials of almotriptan for the treatment of acute migraine were examined. Two trials evaluated almotriptan 6.25 mg and 12.5 mg, and the third evaluated almotriptan 12.5 mg and sumatriptan 100 mg. Patients aged 18 to 65 years were instructed to take 1 dose of study medication at the onset of a moderate-to-severe migraine headache. A second dose was allowed for relapse. Sustained pain-free was defined as a decrease in pain severity from moderate or severe at baseline to no pain at 2 hours postdose and without relapse or the use of escape medication between 2 and 24 hours. A total of 1791 adult migraine sufferers were studied. The proportion of patients achieving a sustained pain-free state was significantly (P<.05) higher in the almotriptan 6.25-mg (21.7% to 22.5%) and 12.5-mg (24.6% to 27.6%) groups than in the placebo group (7.5% to 12.1%). The proportion of patients achieving a sustained pain-free state was comparable between almotriptan 12.5 mg (24.6%) and sumatriptan 100 mg (28.5%) and significantly (P<.05) greater than with placebo (12.1%). Among patients with severe baseline pain, a sustained pain-free state was achieved in significantly more patients (P<.05) with almotriptan 12.5 mg (17.3% to 20.9%) than with placebo (3.1% to 3.2%). Among those with moderate baseline pain, a sustained pain-free state was achieved in significantly more patients (P<.01) with almotriptan 12.5 mg (31.3% to 32.0%) than with placebo (10.2% to 16.1%). Almotriptan 12.5 mg is significantly better than placebo and comparable to sumatriptan 100 mg for achieving a sustained pain-free state.",2002.0,0,1
277,12005272,Within-patient early versus delayed treatment of migraine attacks with almotriptan: the sooner the better.,Julio Pascual; Xavier Cabarrocas,"Migraine sufferers typically have been instructed to delay triptan therapy until headache intensity is at least moderate. Recent data suggest that earlier use of triptans may be more beneficial. To address the potential ""within-patient"" benefit of intervention with almotriptan 12.5 mg for migraine headache of mild intensity. We performed a post hoc analysis of a subgroup of patients from a large, open-label, long-term clinical trial wherein 762 migraineurs used almotriptan 12.5 mg for headache attacks of any severity. Specifically, we evaluated the efficacy and safety of treatment in those patients who had treated at least 3 ""mild"" attacks and 3 ""moderate/severe"" attacks, examining rates of pain-free status, use of rescue medication, early recurrence, and adverse events for the first 3 mild and the first 3 moderate/severe attacks treated. There were 118 migraineurs and 708 attacks available for analysis. At 1 hour following treatment, pain-free status was achieved in 47% of mild attacks versus 14% of moderate/severe attacks (P<.001); incidences at 2 hours were 84% of mild attacks and 53% of moderate/severe attacks (P<.001). The chance of achieving pain-free status at 1 hour in at least 2 of 3 treated attacks was 45% for mild attacks and 9% for moderate/severe attacks; at 2 hours the percentages were 88% for mild attacks and 56% for moderate/severe attacks. Rescue medication was required in 8% of mild attacks and in 13% of moderate/severe attacks (P<.01). The incidence of early recurrence was 28% for mild attacks and 33% for moderate/severe attacks (P<.01). There was no difference in the incidence of adverse events for mild versus moderate/severe attacks (6% versus 7%). These results support early intervention with oral triptan therapy. When used for mild intensity head pain, almotriptan 12.5 mg produced a significantly higher incidence of pain-free status at 1 and 2 hours and lower incidences of early headache recurrence or need for rescue medication.",2002.0,0,1
278,12005274,Frovatriptan for the acute treatment of migraine: a dose-finding study.,Jerome Goldstein; C Keywood; 251/96/14 Study Group,"To determine the optimal dose and tolerability of frovatriptan in the acute treatment of migraine. Frovatriptan has a distinctive pharmacological and pharmacokinetic profile compared with sumatriptan. A previous study has shown that frovatriptan doses of 2.5, 5, 10, 20, and 40 mg are equally effective in relieving headache with no evidence of a dose-response relationship. The incidence of adverse events tended to increase with doses of 10 mg and above. This study was a randomized, double-blind, placebo-controlled, parallel-group multicenter trial. Patients (n=635) took a single oral dose of placebo or frovatriptan, 0.5, 1, 2.5, or 5 mg, at the onset of a moderate or severe migraine headache and recorded headache intensity, functional impairment, and migraine-associated symptoms over 24 hours. Frovatriptan 2.5 mg produced clinically and statistically significant headache relief 2 hours post-dose, whereas the effect of lower doses was not significantly different from that of placebo at that time point. The 2.5-mg dose also produced significant symptom relief and improvement in functional impairment. All doses of frovatriptan were well tolerated, and the majority of adverse events were of mild or moderate severity. It is concluded that the 2.5-mg dose of frovatriptan offers optimal efficacy and tolerability in the treatment of acute migraine. Higher doses do not appear to confer greater efficacy and are associated with an increased incidence of adverse effects.",2002.0,0,1
279,12005275,"Rizatriptan 5 mg for the acute treatment of migraine in adolescents: a randomized, double-blind, placebo-controlled study.",Paul Winner; Donald Lewis; W Hester Visser; Kaihong Jiang; Suzanne Ahrens; Judith K Evans; Rizatriptan Adolescent Study Group,"To investigate the tolerability and efficacy of rizatriptan 5 mg in adolescent migraineurs. Randomized, double-blind, placebo-controlled study. Patients aged 12 to 17 years received rizatriptan 5 mg (n = 149) or placebo (n = 147) for a moderate or severe headache and for up to two recurrences. Headache severity, presence or absence of associated symptoms, and functional disability were assessed over a 4-hour postdose period, and any adverse events were recorded. The primary efficacy measure was pain-free status at 2 hours postdose. Rizatriptan 5 mg was well tolerated. The most commonly reported adverse events (all with incidence of 5% or less) among patients receiving rizatriptan were dry mouth, dizziness, asthenia/fatigue, nausea, and somnolence. The percentage of patients pain-free at 2 hours was 32% for rizatriptan 5 mg versus 28% for placebo (P=.474). The percentage of patients with pain relief (reduction of predose pain intensity to mild or none) at 2 hours was 66% for rizatriptan versus 56% for placebo (P=.079). Placebo response rates were higher than those typically observed in previous studies of rizatriptan in adults. Compared with placebo, rizatriptan significantly improved functional disability at 1.5 and 2 hours, and nausea at 1 and 1.5 hours. Post hoc analysis showed a significant benefit of rizatriptan versus placebo in the percentage of patients who had pain relief when their migraine attacks were treated on weekends (65% versus 36%, P=.046) compared with weekdays (66% versus 61%, P=.365), and the weekend placebo response rate was similar to that seen in adults. Rizatriptan 5 mg was well tolerated and effective on some measures when used in adolescents for the treatment of a migraine attack.",2002.0,0,1
280,12005277,New paradigms in the recognition and acute treatment of migraine.,Fred D Sheftell; Stewart J Tepper,"It would be ideal if clinical decisions regarding acute migraine treatment could be made on the basis of three parameters: a critical appraisal of available scientific evidence, clinical experience (including knowledge of the individual patient and his/her attack characteristics), and, of course, patient preferences. Patients are likely to prefer agents that offer rapid relief, pain-free status within 2 hours, no recurrence or need for rescue medication, extended time to recurrence (if present), consistency of therapeutic effect over multiple attacks, oral administration. good tolerability, safety, and minimal drug interactions. Fortunately, a number of specific therapies now are available which place these objectives within the patient's reach. Ongoing barriers to optimal migraine care include underrecognition, underconsultation, undertreatment, restrictions imposed by insurance companies, and exaggerated concerns regarding the safety of the triptans. Overcoming these barriers is likely to prove a more important contribution to patient care than endeavoring to establish the relative merits of one triptan over another. We have described in detail a number of strategies for improving recognition and treatment of migraine. Many headache specialists now believe that recurrent episodes of disabling headache, with a stable pattern over years, should be viewed as migraine until proven otherwise. In the end, this may represent the most useful paradigm in the primary care setting, where time is of the essence. Studies to validate this approach are needed. Acute treatment intervention that is based on scientific evidence, clinical experience, and patients' needs and desires will provide better outcomes than those presently obtained. Preliminary evidence favors early intervention with oral triptans, and randomized, prospective, double-blind, placebo-controlled studies, ideally employing a crossover design, are required to confirm this. The US Consortium's evidence-based guidelines, the National Headache Foundation's standards of care, and the Canadian guidelines have applied the standards of scientific inquiry to the field of headache management and ""translation"" of these guidelines into practical instruments for clinicians through vehicles such as the Primary Care Network's Patient-Centered Strategies for Effective Management of Migraine should raise the general standard of care for patients with migraine. Last, but far from least, initiatives undertaken by the World Health Organization (WHO) will add credibility to the many layfolk and professionals who have struggled to present headache as a disabling disorder worthy of scientific investigation and aggressive medical management. The WHO states: ""These common complaints impose a significant health burden ... Despite this, both the public and the majority of healthcare professionals tend to perceive headache as a minor or trivial complaint. As a result, the physical, emotional, social and economic burdens of headache are poorly acknowledged in comparison with those of other, less prevalent, neurologic disorders."" Migraine is finally out of the closet.",2002.0,0,0
281,12005278,Headache recurrence as a criterion for assessing efficacy of triptans: a perspective.,Sheena K Aurora,,2002.0,0,1
282,12005279,Evidence-based assessment of pregnancy outcome after sumatriptan exposure.,Anthony W Fox; Christina D Chambers; Philip O Anderson; Merle L Diamond; Egilius L H Spierings,"Assessment of best available evidence for tolerability of sumatriptan after inadvertent exposure during pregnancy. Migraine's demography suggests that inadvertent exposure to acute therapies is likely during the earliest undiagnosed stages of pregnancy. The tolerability of such therapies under these conditions is not amenable to clinical trial for ethical reasons. In the United States, sumatriptan is currently labeled pregnancy category C (ie, not recommended for use during pregnancy unless the potential benefit justifies the potential risk to the fetus). Three types of adverse events were studied: spontaneous abortion, fetal abnormality, and obstetric complications. Traditional evidence-based criteria were used to assess a search-protocol product of four clinical studies and two case reports. The single positive finding (""preterm delivery"" without low birth weight) was in the smallest study; this study was retrospective and the finding was externally inconsistent with the other three larger studies, all of which were prospective. No study followed children for more than 4 years, which is the period needed to identify the maximum number of congenital anomalies. Rigorous teratological technique was generally not employed. Post hoc power calculations were used to provide parameters of the hazard detectable by these studies in aggregate. Pregnancy categories B and C both seem feasible for sumatriptan. Within the limits of the examined studies, there is no evidence for any specific effect of sumatriptan on pregnancy outcome. Patients inadvertently exposed to sumatriptan during an early stage of pregnancy should be reassured by these data.",2002.0,0,1
283,12005282,Triptans for migraine prodrome.,Randolph W Evans; Lisa K Mannix,,2002.0,0,0
284,12005301,Comparison of triptan tablet consumption per attack: a prospective study of migraineurs in Spain.,Julio Pascual; Benet Fité; Arturo López-Gil,"To compare patient self-reported tablet consumption of rizatriptan 10 mg per attack (24 hours) with that of sumatriptan 50 mg, zolmitriptan 2.5 mg, and naratriptan 2.5 mg on an unselected, prescription-based, Spanish migraine population. One hundred twenty community pharmacies recruited patients with migraine, who used their pharmacies, to fill a triptan prescription. In diaries, patients recorded baseline pain intensity and the number of triptan tablets and additional medication taken per attack. Patients treated a maximum of three attacks. Analysis of variance or the Student t test and chi-square or Fisher exact tests were used for univariate comparisons. Hochberg corrections were used for multiple-group comparisons. A generalized estimating equation method was used to correct for within-subject correlation. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Two hundred thirty-one patients (84% women) treated 589 evaluable migraine attacks (sumatriptan, n = 135; naratriptan, n = 90; zolmitriptan, n = 149; rizatriptan, n = 149). Triptan tablet consumption per attack (mean +/- SD) for rizatriptan (1.24 +/- 0.56) was significantly lower than that of sumatriptan (1.75 +/- 1.2; P< .05), zolmitriptan (1.61 +/- 0.86; P < .05), or naratriptan (1.46 +/- 0.62; P= .05). The average number of triptan tablets taken and additional medication use increased according to baseline pain severity. More attacks were treated with one tablet of rizatriptan (81.2%) than with one tablet of sumatriptan (51.9%), zolmitriptan (55.7%), or naratriptan (60%). The probability of using more than one triptan tablet per attack (24 hours) was more than three times greater for sumatriptan (adjusted OR = 3.71; CI, 2.05 to 6.7; P = .001) and zolmitriptan (adjusted OR = 3.32; CI, 1.82 to 6.17; P = .001), and more than two times greater for naratriptan (adjusted OR = 2.66; CI, 1.36 to 5.21; P =.004) than for rizatriptan. Rizatriptan was associated with significantly lower triptan tablet use and additional medication use per attack than the other triptans. Additional randomized studies are needed to confirm the conclusions of this study.",2002.0,0,0
285,12005302,How does almotriptan compare with other triptans? A review of data from placebo-controlled clinical trials.,Carl G H Dahlöf; David Dodick; Andrew J Dowson; Julio Pascual,"Almotriptan, the new selective 5-HT1B/1D agonist, has a higher oral bioavailability than any other triptan, with more than two thirds of the administered dose absorbed within the first hour both inside and outside of a migraine attack. Gender or the presence of food in the stomach does not affect its pharmacokinetic profile, and the compound has no clinically relevant interactions with other drugs. Among the available triptans, response rates at 2 hours range from 50% to 80%, with 20% to 50% of patients pain-free. Almotriptan 12.5 mg provides similar efficacy, with significant advantage over placebo at 30 minutes and a reliable consistency (75% in two of three attacks). Headache typically recurs in 25% to 45% of patients with most triptans. The recurrence rate with almotriptan 12.5 mg, 18% to 27%, is among the lowest reported. The tolerability of almotriptan 12.5 mg is close to that of placebo with a low incidence of central nervous system side effects and chest symptoms. In conclusion, almotriptan's consistent pharmacokinetics and good efficacy, in combination with excellent tolerability, make it an attractive choice in the acute treatment of migraine attacks.",2002.0,0,1
286,12010399,Mixing sumatriptan.,Richard B Lipton; Roger Cady,,2002.0,0,0
287,12011309,Clinical features of withdrawal headache following overuse of triptans and other headache drugs.,Alexander Mauskop,,2002.0,0,0
288,12017346,The pharmacokinetics and safety of single escalating oral doses of eletriptan.,Ajit K Shah; Stephen C Harris; Catherine Greenhalgh; Joel Morganroth,"The pharmacokinetics, safety, and tolerability of the 5-HT(1B/1D) agonist eletriptan were characterized in a randomized, double-blind, placebo-controlled, dose escalation study. Healthy males received single oral doses of 10 to 120 mg. Following screening and baseline measurements, plasma and saliva eletriptan concentrations were measured at intervals over 48 hours and 24 hours, respectively. Samples were analyzed using high-performance liquid chromatography with ultraviolet detection. Both the maximum plasma concentration and the area under the plasma eletriptan concentration-time curve showed an essentially linear relationship to the administered dose. Eletriptan exhibited a median time to maximum plasma concentration of 1 to 1.25 hours and a mean elimination half-life of 3.6 to 7.0 hours. Mean salivary-plasma ratios for pharmacokinetic parameters generally remained constant across the 30 to 90 mg dose range. Eletriptan was well tolerated, with mostly mild and transient adverse events. In conclusion, oral doses of eletriptan in the therapeutic range were rapidly absorbed and exhibited essentially linear plasma and saliva pharmacokinetics.",2002.0,0,0
289,12017347,"Pharmacokinetics, pharmacodynamics, and safety of the 5-HT(1B/1D) agonist eletriptan following intravenous and oral administration.",K Ashley Milton; Nicholas R Scott; Michael J Allen; Samantha Abel; Vivienne C Jenkins; Gerry C James; David J Rance; Malcolm D Eve,"Four separate studies were conducted to examine the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of eletriptan, a 5-HT(1B/1D) receptor agonist being developed for the treatment of migraines, after oral and intravenous administration. Fifty-five males received oral (1.5-30 mg or 30-120 mg) or intravenous (1.67-50 microg/kg or 50-102 microg/kg) eletriptan in four double- and single-blind, placebo-controlled, ascending-dose crossover studies. The maximum plasma concentration (Cmax) and area under the concentration curve (AUC) appeared linear over all dose ranges, with an apparent terminal half-life of 4 to 5 hours. Clearance and volume of distribution remained constant with dose. The time to first occurrence of Cmax (tmax) for oral eletriptan was approximately 1 hour and was unaffected by dose. Comparison of AUC values suggested an absolute bioavailability of approximately 50%. A linear PK/PD model, fitted to the data, predicted small, transient elevations in diastolic blood pressure following eletriptan doses > or = 60 mg. These effects were considered unlikely to be clinically significant. Eletriptan was well tolerated, and treatment-related adverse events were mild to moderate and transient. These PK properties should result in eletriptan having a rapid onset and sustained duration of action in terms of migraine efficacy.",2002.0,0,1
290,12017397,Use of rescue medication in trials of almotriptan versus placebo in the treatment of acute migraine.,Ninan T Mathew,"Almotriptan malate is a recently marketed triptan for the treatment of acute migraine. Results from controlled clinical trials demonstrate efficacy superior to placebo and an adverse event rate comparable to that with placebo. The goal of this study was to assess the effect of oral almotriptan on the use of rescue medication in the treatment of acute migraine attacks. Three Phase II and III, placebo-controlled, randomized, double-blind studies of almotriptan used as the basis for regulatory approval of the drug were included in the analysis. Two studies (1 single dose, 1 multiple dose) assessed almotriptan 6.25 mg and 12.5 mg and a third compared almotriptan 12.5 mg and sumatriptan 100 mg. Primary results from all 3 trials were previously published. Rescue medication was permitted if migraine pain had not decreased to mild severity or to no pain at 2 hours after study medication. The primary end point of this analysis was use of rescue medication. A total of 1777 patients were included in the analysis. Mean patient age ranged from 39.4 to 44.0 years; approximately 87% were women, and >98% were white. Patients were well matched for demographic characteristics. Overall, use of rescue medication was significantly lower with almotriptan 6.25 mg and 12.5 mg compared with placebo (P < or = 0.05 for each group). No significant difference was noted between the almotriptan 12.5-mg and sumatriptan 100-mg groups. In 2 of the studies, patients with moderate or severe baseline pain used significantly less rescue medication in the almotriptan groups compared with placebo. Oral almotriptan 6.25 mg or 12.5 mg significantly reduced use of rescue medication compared with placebo among patients with acute migraine. Use of rescue medication was comparable with almotriptan 12.5 mg and sumatriptan 100 mg.",2002.0,0,1
291,12017403,The pharmacokinetics of sumatriptan when administered with clarithromycin in healthy volunteers.,Katy H P Moore; Philip T Leese; Scott McNeal; Peter Gray; Stephen O'Quinn; Carole Bye; Mark Sale,"Macrolide antibiotics such as clarithromycin are potent inhibitors of the cytochrome P450 (CYP)3A4 isozyme and have the potential to attenuate the metabolism and increase blood concentrations of drugs metabolized by this pathway. In vitro studies have suggested that sumatriptan is metabolized primarily by the monoamine oxidase-A isozyme and not by CYP3A4. This study sought to determine the effect of coadministration of clarithromycin dosed to steady state on the pharmacokinetics of a single dose of sumatriptan. A secondary objective was to assess the safety and tolerability of combining these agents. This was an open-label, randomized, 2-way crossover study in healthy volunteers. During treatment period 1, subjects received either a single oral dose of sumatriptan 50 mg (sumatriptan alone) or clarithromycin 500 mg orally every 12 hours on days 1 to 3 and a single oral dose of sumatriptan 50 mg plus a single oral dose of clarithromycin 500 mg on the morning of day 4 (combination treatment). During treatment period 2, they received the alternative regimen. Equivalence between sumatriptan alone and combination treatment was concluded if the 90% CI for the ratio of reference to test means of loge-transformed data for area under the plasma concentration-time curve extrapolated to infinity (AUC(infinity)) and maximum plasma concentration (Cmax) fell within the interval from 0.8 to 1.25. In the 24 evaluable subjects (12 men, 12 women) included in the pharmacokinetic analysis, mean sumatriptan AUC(infinity) and Cmax values after administration of combination treatment were 9% and 14% higher, respectively, than the corresponding values after administration of sumatriptan alone. The 90% CI for the ratio of reference to test means for AUC(infinity) was 1.03 to 1.15. The 90% CI for the ratio of reference to test means for Cmax was 1.03 to 1.26, above the traditional bioequivalence criterion. All other pharmacokinetic parameters tested, including nonparametric analysis of the time to Cmax, met the criterion for equivalence between treatments. Both treatments were well tolerated in the 27 subjects (13 men, 14 women) included in the safety analysis. The extent of absorption of sumatriptan was similar after oral administration alone and in combination with clarithromycin dosed to steady state. These data are consistent with previous reports that sumatriptan is unaffected by coadministration with the potent CYP3A4 inhibitor clarithromycin, supporting concomitant administration of these agents without the need for dose adjustment of sumatriptan in the acute treatment of migraine.",2002.0,0,0
292,12018810,Migraine headache.,Luis E Morillo,,2002.0,0,0
293,12027785,Practical approaches to migraine management.,Seymour Diamond; Richard Wenzel,"Migraine is a recurrent clinical syndrome characterised by combinations of neurological, gastrointestinal and autonomic manifestations. The exact pathophysiological disturbances that occur with migraine have yet to be elucidated; however, cervico-trigemino-vascular dysfunctions appear to be the primary cause. Despite advances in the understanding of the pathophysiology of migraine and new effective treatment options, migraine remains an under-diagnosed, under-treated and poorly treated health condition. Most patients will unsuccessfully attempt to treat their headaches with over-the-counter medications. Few well designed, placebo-controlled studies are available to guide physicians in medication selection. Recently published evidence-based guidelines advocate migraine-specific drugs, such as serotonin 5-HT(1B/1D) agonists (the 'triptans') and dihydroergotamine mesylate, for patients experiencing moderate to severe migraine attacks. Additional headache attack therapy options include other ergotamine derivatives, phenothiazines, nonsteroidal anti-inflammatory agents and opioids. Preventative medication therapy is indicated for patients experiencing frequent and/or refractory attacks.",2002.0,0,0
294,12044621,Pharmacological treatments for acute migraine: quantitative systematic review.,Anna D Oldman; Lesley A Smith; Henry J McQuay; R Andrew Moore,"We wanted to compare the analgesic efficacy and adverse effects of pharmacological treatments for acute migraine through a systematic review of randomised controlled trials in patients with acute migraine pain of moderate to severe intensity. Trials were identified from systematic searching of bibliographic databases. For eletriptan information from all trials was supplied by Pfizer Inc. Outcomes sought were headache relief at 1 and 2h, patients pain free at 2h and sustained relief over 24h for treatments compared with placebo. Numbers-needed-to-treat (NNTs) were calculated, together with relative benefit. Information on adverse effects was also collected. Comparisons of relative efficacy used the same definition of headache, the same degree of pain at the start of treatment and the same definitions of outcomes, and always compared with placebo. Forty-eight publications reporting on 54 trials were included in the meta-analyses, with 79 placebo comparisons for the primary outcome of headache relief at 2h. Information on any outcome was available for nine oral medications, two intranasal medications and subcutaneous sumatriptan in 21,022 patients. For headache relief at 2h NNTs ranged from 2.0 for subcutaneous sumatriptan 6mg to 5.4 for naratriptan 2.5mg. For patients pain free at 2h NNTs ranged from 2.1 for subcutaneous sumatriptan 6mg to 8.6 for aspirin 900mg plus metoclopramide 10mg. For sustained relief over 24h NNTs ranged from 2.8 for eletriptan 80mg to 8.3 for rizatriptan 5mg. It was not possible to systematically review adverse effects data. Most interventions are effective. There is considerable information on relative efficacy for a number of outcomes.",2002.0,0,0
295,12054095,Sensitization: its role in primary headache.,Lars Bendtsen,"The pathophysiology of the two most common primary headaches, migraine and tension-type headache, is complex and not yet fully understood. Recent animal and human studies examining these headaches indicate that the nociceptive input to the central nervous system (CNS) may be increased due to activation or sensitization of peripheral sensory afferents. The barrage of nociceptive impulses may result in sensitization of second- and third-order neurons in the CNS. In this way, sensitization may play a role in initiation and maintenance of migraine and tension-type headache. It is likely that the effects of established medication for both disorders may be partly due to a reduction in sensitization. Several interesting drugs that counteract sensitization are under development, and targeting this mode of action seems to be a promising way of improving the treatment for these prevalent disorders.",2002.0,0,0
296,12056924,Spotlight on almotriptan in migraine.,Susan J Keam; Karen L Goa; David P Figgitt,"Almotriptan is a selective serotonin 5-HT(1B/1D) receptor agonist ('triptan'). Its efficacy and tolerability have been assessed in a number of randomised, controlled trials in over 4800 adults with moderate or severe attacks of migraine. Oral almotriptan has a rapid onset of action (significant headache relief is observed 0.5 hours after administration of a 12.5mg dose) and efficacy is sustained in most patients who respond by 2 hours. The drug is significantly more effective than placebo as measured by a number of parameters including 2-hour headache response and pain-free response rates. Other symptoms of migraine, including nausea, photophobia and phonophobia, are also alleviated by almotriptan. The efficacy of oral almotriptan appears to be maintained over repeated doses for multiple attacks of migraine treated over a long period (up to 1 year). High headache response rates were reported over all attacks without tachyphylaxis. For the relief of single attacks of migraine, oral almotriptan 12.5mg had similar efficacy to oral sumatriptan 50mg. Patients given almotriptan report less concern with adverse effects than patients given sumatriptan. The lower incidence of chest pain following treatment with almotriptan than with sumatriptan may lead to a reduction in direct costs, with fewer patients requiring management of chest pain. Almotriptan is well tolerated. Most adverse events were of mild or moderate intensity, transient and generally resolved without intervention or the need for treatment withdrawal. The most common adverse events associated with oral almotriptan 12.5mg treatment were dizziness, paraesthesia, nausea, fatigue, headache, somnolence, skeletal pain, vomiting and chest symptoms. The incidence of adverse events did not differ from placebo and decreased in the longer term. Almotriptan can be coadministered with drugs that share a common hepatic metabolic path; in addition, dosage reduction is required only in the presence of severe renal or hepatic impairment. Almotriptan is an effective drug for the acute treatment of moderate or severe attacks of migraine in adults. An oral dose of almotriptan 12.5mg has shown greater efficacy than placebo; current data indicate that efficacy is similar to that of oral sumatriptan 50mg, and is maintained in the long term (< or = 1 year). Almotriptan has a good adverse event profile and a generally similar overall tolerability profile to sumatriptan; of note, almotriptan is associated with a significantly lower incidence of chest pain than sumatriptan. However, further clinical experience is required to clearly define the place of almotriptan among the other currently available triptans. Nevertheless, because triptans have an important place in various management regimens, and because the nature of individual patient response to triptans is idiosyncratic, almotriptan is likely to become a useful treatment option in the management of adults with moderate or severe migraine headaches.",2002.0,0,1
297,12058095,Efficacy of oral ketoprofen in acute migraine: a double-blind randomized clinical trial.,M Dib; H Massiou; M Weber; P Henry; S Garcia-Acosta; M G Bousser; Bi-Profenid Migraine Study Group,"Certain nonsteroidal anti-inflammatory drugs are effective in the acute treatment of migraine attacks. The authors report a double-blind, placebo-controlled, randomized cross-over trial of a dual-release formulation of oral ketoprofen in the acute treatment of migraine attacks. The authors compared the efficacy of two doses of ketoprofen (75 or 150 mg) with that of placebo (primary analysis) and zolmitriptan 2.5 mg (secondary analysis) on one to four consecutive attacks in 235 intent-to-treat patients (out of 257 randomized patients) with migraine with or without aura. The principal efficacy outcome was headache relief (reduction in headache severity from severe or moderate to mild or absent at 2 hours). Results are based on 838 attacks with a severe or moderate headache that were evaluable at 2 hours. Relief was reported for 62.6% of headaches treated with ketoprofen 75 mg, 61.6% with ketoprofen 150 mg, and 66.8% with zolmitriptan. The difference between the three active treatments and placebo (27.8% relief) was highly significant, both tests of ketoprofen vs placebo being globally controlled at a 5% level for the type I error (primary analysis). Headaches at 2 hours disappeared more frequently for the active treatments than for placebo. The authors also demonstrated efficacy on most other secondary outcomes. The tolerance of ketoprofen was good (similar to that of placebo). Oral ketoprofen (75 mg or 150 mg) in a dual-release formulation is an effective and well-tolerated drug in the acute treatment of migraine attacks.",2002.0,0,0
298,12071780,Signal generation in the New Zealand Intensive Medicines Monitoring Programme: a combined clinical and statistical approach.,David M Coulter,"The New Zealand Intensive Medicines Monitoring Programme (IMMP) undertakes prospective observational cohort studies on selected new drugs in the early postmarketing period using prescription-event monitoring (PEM) methodology with the purpose of identifying signals of previously unrecognised ADRs and establishing risk profiles for each drug. Events are reviewed by a physician and a relationship is established between each event and the drug. The events are then sorted into reactions and incidents. The latter are used to assist signal detection and control for bias. Rates for reports, reactions and incidents are used to assess the adequacy of reporting, signal detection and identification of confounders. Most signals are identified by clinical evaluation of the reports at a stage when statistical analyses are unlikely to have the power to detect them with confidence. The incident group is used for signal detection and controlling for bias. A low reporting rate indicates that certain types of event are unlikely to be reported. A systematic review of the original case reports at the site of collection provides the best opportunity for early signal detection. More resources need to be invested in the training and support of clinical evaluators. Categorising events into reactions and incidents gives added value to the data. Rates of reporting should be quoted with the results of cohort studies to facilitate assessment of their power to detect new signals.",2002.0,0,0
299,12083998,Review of zolmitriptan and its clinical applications in migraine.,Andrew J Dowson; Bruce Charlesworth,"Preclinical studies have shown that zolmitriptan is a selective serotonin 5-HT(1B/1D) receptor agonist (triptan). Randomised, placebo-controlled, double-blind trials in patients with migraine have shown that zolmitriptan has good efficacy measured using 2 h response and pain-free rates. Migraine-associated symptoms, including nausea, photophobia and phonophobia, are also improved with zolmitriptan. Oral zolmitriptan (2.5 and 5 mg) has an onset of action within 45 min and efficacy is sustained in most patients who respond at 2 h. The orally-disintegrating zolmitriptan tablet has the advantage that it may be taken immediately, without the need for additional fluids, any time a migraine headache occurs. Patients may benefit in terms of improved efficacy from the convenience of the disintegrating tablet, since there is evidence that taking triptan therapy as early as possible in an attack is advantageous. For similar reasons, as well as improved efficacy, a nasal spray formulation is in development. Zolmitriptan is effective in the treatment of migraine associated with menses and migraine with aura. There is no tachyphylaxis following repeated doses for multiple attacks of migraine over a prolonged period of time. Compared to placebo, the incidence of persistent migraine headache is reduced by zolmitriptan and recurrent migraine headache occurs less frequently. Zolmitriptan has also shown efficacy in the treatment of persistent and/or recurrent migraine headache. Comparative clinical studies have shown overall that zolmitriptan has similar or superior efficacy to sumatriptan in the treatment of migraine. Specifically, zolmitriptan 2.5 mg was significantly more effective than sumatriptan 25 or 50 mg according to a number of end points, including headache response at 2 h. Oral zolmitriptan is also effective in the acute treatment of cluster headache. Zolmitriptan is generally well tolerated, with most adverse events being mild-to-moderate, transient and resolving without intervention or the need for treatment withdrawal. The consistent efficacy in treating all types of migraine and the choice of available formulations make zolmitriptan acceptable to patients and a suitable first-line therapy for the treatment of migraine.",2002.0,0,1
300,12093318,Rizatriptan: an update of its use in the management of migraine.,Keri Wellington; Greg L Plosker,"Rizatriptan is an orally active serotonin 5-HT(1) receptor agonist that potently and selectively binds to 5-HT(1B/1D) subtypes. Earlier clinical trials demonstrated that rizatriptan 5 or 10mg is more effective than placebo at providing pain relief and a pain-free state, relieving associated symptoms of migraine, normalising functional ability and improving patient quality of life, and showed that rizatriptan provides faster freedom from pain and reduces nausea to a greater extent than oral sumatriptan. More recently, rizatriptan 10mg was shown to be more effective than zolmitriptan 2.5mg or naratriptan 2.5mg at producing a pain-free state 2 hours postdose. Furthermore, compared with naratriptan, significantly more patients who received rizatriptan were pain free or had pain relief from 1 hour onwards. The number of patients with normal functional ability at 2 hours was significantly higher after rizatriptan than after naratriptan or zolmitriptan. Rizatriptan was also generally more effective than zolmitriptan or naratriptan at relieving migraine-associated symptoms. Rizatriptan is generally well tolerated and adverse events are usually mild and transient. The most common adverse events associated with rizatriptan in recent randomised trials were asthenia/fatigue, dizziness, somnolence and nausea. There was a trend towards a lower incidence of adverse events with rizatriptan compared with zolmitriptan (31.2 vs 38.8%). However, rizatriptan was associated with a significantly higher incidence of adverse events than naratriptan (39 vs 29%). The incidence of chest pain was similar after the administration of rizatriptan, zolmitriptan or naratriptan (2 to 4%). Rizatriptan is an effective drug for the acute treatment of moderate or severe migraine. Oral rizatriptan 5 and 10mg have shown greater efficacy than placebo in providing pain relief, an absence of pain, relief from associated symptoms, normal functional ability and an improvement in patient quality of life. Earlier results showed that rizatriptan provides faster freedom from pain and reduces nausea to a greater extent than oral sumatriptan. More recent studies have shown that rizatriptan 10mg provides faster pain relief and a higher percentage of patients with an absence of pain and normal functional ability at 2 hours than naratriptan 2.5mg or zolmitriptan 2.5mg. The efficacy of rizatriptan is retained when used in the long term and the drug is generally well tolerated. Although well designed studies comparing rizatriptan with almotriptan, eletriptan and frovatriptan would further define the position of rizatriptan, current data suggest rizatriptan should be considered as a first-line treatment option in the management of migraine.",2002.0,0,0
301,12100089,CNS effects of sumatriptan and rizatriptan in healthy female volunteers.,J van der Post; M T Schram; R C Schoemaker; M S M Pieters; E Fuseau; A Pereira; S Baggen; A F Cohen; J M A van Gerven,"This study investigates the CNS effects of sumatriptan and rizatriptan, with temazepam as an active comparator, in healthy female volunteers. Sixteen volunteers completed a randomized, double-blind, crossover study and on four separate occasions received either 100 mg sumatriptan, 20 mg rizatriptan or 20 mg temazepam. The main parameters were eye movements, EEG, body sway, visual analogue scales and a cognitive test battery. Rizatriptan and sumatriptan decreased saccadic peak velocity by 18.3 (95% CI: 5.7, 30.8) and 15.0 (2.2, 27.9) degrees/sec, respectively, about half the decrease induced by temazepam (35.0 (22.1, 47.8) degrees/sec). Body sway increased (30% for rizatriptan (16%, 45%) and 14% for sumatriptan (1%, 27%), respectively). Temazepam caused larger, similar effects. In contrast to temazepam, sumatriptan and rizatriptan decreased reaction times of recognition tasks and increased EEG alpha power (significant for sumatriptan, 0.477 (0.02, 0.935). Therapeutic doses of sumatriptan and rizatriptan caused CNS effects indicative of mild sedation. For EEG and recognition reaction times the effects were opposite to temazepam, indicating central stimulation.",2002.0,0,0
302,12100090,A pharmacokinetic interaction study between butorphanol and sumatriptan nasal sprays in healthy subjects: importance of the timing of butorphanol administration.,N N Vachharajani; W-C Shyu; P S Nichola; D W Boulton,"Sumatriptan and butorphanol nasal sprays are commonly used agents for the management of migraine headaches. Under certain circumstances, these two agents may be administered closely in time. However, the possibility of a pharmacokinetic interaction and the safety of this regime have not been examined. In this crossover design study, 24 healthy subjects received the following four treatments, each separated by at least 7 days: 1 mg butorphanol (Stadol NS7); 20 mg sumatriptan (Imitrex Nasal Spray); or both formulations together with butorphanol administered either 1 or 30 min after sumatriptan. Serial plasma samples were collected for 24 h post-dose and analysed for butorphanol and/or sumatriptan by HPLC-MS/MS. Butorphanol plasma concentrations were reduced when it was administered 1 min (mean 28.6% decrease in AUC(0-infinity)), but not 30 min, after sumatriptan. The pharmacokinetics of sumatriptan were not substantially altered by butorphanol. The combination of nasally administered sumatriptan and butorphanol appeared safe. However, if butorphanol nasal spray is administered <30 min after sumatriptan nasal spray, the analgesic effect of butorphanol may be diminished due to reduced nasal absorption resulting from probable transient vasoconstriction of nasal blood vessels by sumatriptan.",2002.0,0,0
303,12100094,Rizatriptan combined with rofecoxib vs. rizatriptan for the acute treatment of migraine: an open label pilot study.,A V Krymchantowski; J S Barbosa,"Rizatriptan is an effective and fast acting drug for the acute treatment of migraine. As with any other acute treatment for migraine, headache recurrence may occur in up to one-third of responders. Combination with non-steroidal anti-inflammatory drugs (NSAIDs) seems to reduce the incidence of headache recurrence in clinical practice. Rofecoxib is a member of a new class of NSAIDs, which selectively inhibits the COX-2 enzyme and therefore is associated with a lower risk of gastrointestinal side-effects; the drug has a long plasma half-life (17 h). This open label study compared rizatriptan with rizatriptan plus rofecoxib in the acute treatment of migraine. Fifty-six triptan naive patients from a tertiary centre (37 women and 19 men, ages 16-55 years, mean 35 years) with International Headache Society migraine were randomized into two groups. They were instructed to treat three consecutive moderate or severe attacks with either 10 mg rizatriptan (group 1: 18 women and 10 men) or with 10 mg rizatriptan plus 25 mg rofecoxib (group 2: 19 women and 9 men). The presence of headache and nausea at 1, 2 and 4 h, and of side-effects, use of rescue medication and recurrence were compared. Fifty-four patients completed the study. Group 1 treated 76 attacks and group 2 treated 81 attacks. Absence of headache at 1 h was seen in 19 attacks (25%) in group 1 and in 34 attacks (42%) in group 2 (P=0.082); at 2 h absence of headache was seen in 60% of group 1 attacks and in 76% of group 2 attacks (P=0.115). At 4 h, 75% of group 1 attacks and 88% of group 2 attacks were pain free (P=0.122). With regard to nausea, of those who had nausea at baseline, 31% and 49% of attacks in groups 1 and 2, respectively, were nausea free at 1 h (P=0.091), 75% and 79% at 2 h (P=0.736) and 82% and 91% (P=0.479) at 4 h. Recurrence, based on all attacks of those patients who achieved pain free at 4 h, was observed in 53% of group 1 and 20% of group 2 attacks (P<0.001). Sustained pain-free rates (for the 4-h time point) were 45.6% of group 1 and 78.9% of group 2 attacks. There were no significant differences with regard to rescue medication consumption after 4 h and side-effects in both groups. There was a non-significant trend for the combination group to have a higher response rate. The group treated with rizatriptan and rofecoxib had a lower recurrence rate than the group treated with rizatriptan. This study demonstrated that combining a fast acting triptan such as rizatriptan with rofecoxib reduced headache recurrence rates, was well tolerated and may be more effective than the use of rizatriptan alone. Double-blind, placebo-controlled studies are necessary to confirm these observations.",2002.0,0,0
304,12100220,Serotonergic modulating drugs for functional gastrointestinal diseases.,Robin Spiller,"After many years of basic research we have now begun to learn how to manipulate the serotonergic mechanisms within the gut. This has lead to a number of significant advances including 5HT3 antagonists for the treatment of functional diarrhoea, 5HT4 agonists for the treatment of constipation and 5HT1 agonists for the treatment of impaired fundal relaxation. Initial enthusiasm has been somewhat dented by the withdrawal of alosetron because of ischaemic colitis, but it remains to be seen whether this adverse event will be seen with other 5HT3 antagonists. Finally it should be recognized that, in a substantial proportion of patients attending clinics complaining of functional symptoms, anxiety is a major component. The drugs so far described are by and large devoid of CNS effects. It remains possible therefore that a drug which combines both peripheral and central effects would likely to be beneficial.",2003.0,0,0
305,12100223,"The effect of rizatriptan, ergotamine, and their combination on human peripheral arteries: a double-blind, placebo-controlled, crossover study in normal subjects.",Peer Tfelt-Hansen; Kaj Seidelin; Michael Stepanavage; Christopher Lines,"To compare the peripheral vasoconstrictor effects of ergotamine, rizatriptan, and their combination, in normal subjects. This was a double-blind, four-way, crossover study. Sixteen young male volunteers, selected as responders to the vasoconstrictor effect of 0.5 mg ergotamine i.v., were administered 10 mg oral rizatriptan, 0.25 mg i.v. ergotamine, 10 mg oral rizatriptan+0.25 mg i.v. ergotamine, and placebo. The vasoconstrictor effect on peripheral arteries was measured with strain gauge plethysmography up to 8 h after dosing. The 8 h assessment period was divided into two 4 h intervals to assess the immediate (0-4 h) vs sustained effect (4-8 h) of treatment. For the 0-4 h interval, the decreases in peripheral systolic blood pressure gradients were: placebo (-1 mmHg [95% CI: -3, 1])<rizatriptan (-5 mmHg [95% CI: -7, -3])<ergotamine (-15 mmHg [95% CI: -16, -13])=rizatriptan+ergotamine (-15 mmHg [95% CI: -17, -13]). For the 4-8 h interval, the decreases were: placebo (-5 mmHg [95% CI: -8, -3])=rizatriptan (-8 mmHg [95% CI: -11, -5])<ergotamine (-26 mmHg [95% CI: -29, -24])=rizatriptan+ergotamine (-28 mmHg [95% CI: -31, -26]). In normal subjects, rizatriptan 10 mg orally had only a small transient vasoconstrictor effect on peripheral arteries compared with the sustained and more pronounced effect of 0.25 mg i.v. ergotamine. Furthermore, rizatriptan exerted no additional effect on ergotamine-induced constriction of peripheral arteries when the two drugs were given in combination.",2003.0,0,0
306,12105300,Neurocognitive sequelae of cancer treatment.,Roger J Packer; Minesh Mehta,,2002.0,0,0
307,12110113,Zolmitriptan is effective and well tolerated in Japanese patients with migraine: a dose-response study.,F Sakai; M Iwata; K Tashiro; Y Itoyama; S Tsuji; Y Fukuuchi; G Sobue; K Nakashima; M Morimatsu,"This phase II study investigated the efficacy, tolerability and dose-response relationship of oral zolmitriptan in the treatment of a single migraine attack in Japanese patients. A bridging analysis then assessed the validity of extrapolating western clinical data to these Japanese patients. In this multicentre, randomized, double-blind, placebo-controlled study, patients received a single dose of placebo or zolmitriptan 1, 2.5 or 5 mg. The primary endpoints were 2-h headache response and the tolerability of zolmitriptan. A statistically significant dose-response relationship was observed for the 2-h headache response (P=0.003). The 2.5 mg group had significantly greater 2-h headache response than the placebo group (P=0.032). The adverse event profile was similar to that reported in western patients, and no adverse events unique to the Japanese population were observed. The bridging analysis report confirmed similar efficacy and tolerability of zolmitriptan in Japanese and western populations. In the Japanese patients, the estimated response rates were 34.3%, 45.2%, 57.7% and 66.2% for placebo, and zolmitriptan 1, 2.5 and 5 mg, respectively, while in the western population the corresponding rates were 39.9%, 49.6%, 61.2% and 71.7%. Zolmitriptan is effective and well tolerated in the acute treatment of migraine in Japanese patients. The optimal dose was 2.5 mg, although the 5 mg dose may provide further benefit for some patients. The bridging analysis supports extrapolation of data from western to Japanese patients.",2003.0,1,1
308,12117355,Mechanisms of action of the 5-HT1B/1D receptor agonists.,Stewart J Tepper; Alan M Rapoport; Fred D Sheftell,"Recent studies of the pathophysiology of migraine provide evidence that the headache phase is associated with multiple physiologic actions. These actions include the release of vasoactive neuropeptides by the trigeminovascular system, vasodilation of intracranial extracerebral vessels, and increased nociceptive neurotransmission within the central trigeminocervical complex. The 5-HT(1B/1D) receptor agonists, collectively known as triptans, are a major advance in the treatment of migraine. The beneficial effects of the triptans in patients with migraine are related to their multiple mechanisms of action at sites implicated in the pathophysiology of migraine. These mechanisms are mediated by 5-HT(1B/1D) receptors and include vasoconstriction of painfully dilated cerebral blood vessels, inhibition of the release of vasoactive neuropeptides by trigeminal nerves, and inhibition of nociceptive neurotransmission. The high affinity of the triptans for 5-HT(1B/1D) receptors and their favorable pharmacologic properties contribute to the beneficial effects of these drugs, including rapid onset of action, effective relief of headache and associated symptoms, and low incidence of adverse effects.",2002.0,0,0
309,12120731,Headache in primary care: how important is diagnosis to management?,Norma O'Flynn; Leone Ridsdale,"Headache is a common presentation in primary care. The classification of headache was overhauled by the International Headache Society (IHS) in 1988, and the past decade has seen rapid growth in the understanding of headache disorders. The IHS places particular importance on precise headache diagnosis. This paper discusses the relevance of such an approach to primary care. A review of the literature revealed a dearth of evidence regarding headache management in primary care settings. The evidence from other settings is considered and gaps in the literature highlighted.",2002.0,0,0
310,12133040,"Efficacy and safety of eletriptan 20 mg, 40 mg and 80 mg in Japanese migraineurs.",Eletriptan Steering Committee in Japan,"This prospective multicentre, double-blind, randomized, parallel-group, placebo-controlled trial evaluated the efficacy and safety of a single dose of eletriptan 20 mg, 40 mg and 80 mg in Japanese migraineurs. A total of 402 adult Japanese migraineurs were diagnosed using International Headache Society (IHS) criteria. At 2 h after a single dose, the headache response rates of eletriptan 20 mg, 40 mg, 80 mg and placebo were 64%, 67%, 76% and 51%, respectively, with all doses significantly superior to placebo (P<0.05). Eletriptan had a statistically significant dose response for headache relief and pain-free response at 2 h post-dose (P=0.0011 and P=0.0291, respectively). Most all-causality adverse events were mild and there were no deaths or discontinuations. Saliva samples were used to assess serum eletriptan levels 2 h post-dose. Pharmacokinetic evaluations showed no clinically significant differences between Japanese and Western subjects. Eletriptan was shown to be efficacious, safe, and well tolerated in Japanese migraineurs.",2003.0,0,0
311,12133045,"Almotriptan is an effective and well-tolerated treatment for migraine pain: results of a randomized, double-blind, placebo-controlled clinical trial.",A J Dowson; H Massiou; J M Laínez; X Cabarrocas,"Almotriptan is a novel and specific serotonin 5-HT1B/1D agonist for the acute treatment of migraine. This randomized, single-dose, double-blind, multicentre, study assessed the efficacy and safety of oral almotriptan (12.5 mg and 25 mg) in patients with migraine, and compared it with the standard treatment (sumatriptan 100 mg) and placebo. A total of 668 patients treated one migraine attack of moderate or severe intensity with study medication. The primary efficacy assessment was migraine pain relief, improvement from severe or moderate pain to mild or no pain, at 2 h after treatment. Response rates, stratified for variation in baseline pain levels, for both almotriptan doses were equivalent to sumatriptan and significantly better than placebo. Other efficacy assessments confirmed the equivalence of the almotriptan groups with the sumatriptan group. Almotriptan 12.5 mg was as well tolerated as placebo (P=0.493) and significantly better tolerated than sumatriptan (P<0.001), in terms of the overall incidence of adverse events. There was no statistically significant difference in the incidence of adverse events between almotriptan 25 mg and sumatriptan 100 mg (P=0.376). The results from this large clinical study indicate that the new, specific 5-HT1B/1D agonist, almotriptan, is an effective and well-tolerated treatment for migraine pain.",2003.0,0,1
312,12136370,The pharmacokinetics of the antimigraine compound zolmitriptan in Japanese and Caucasian subjects.,R A Yates; M Tateno; K Nairn; A Ikegami; A Dane; J Kemp,"Zolmitriptan is a 5HT(1B/1D) receptor agonist effective in the acute treatment of migraine. Clinical trials in the USA and Europe have demonstrated the optimal oral therapeutic dose to be 2.5 mg. The 2.5-mg oral tablet has recently been licensed in Japan. To compare the pharmacokinetics of zolmitriptan and its metabolites in Japanese and Caucasian subjects and evaluate the effect of gender on these pharmacokinetics in Japanese volunteers. In this open, parallel-group study, 30 Japanese and 30 Caucasian volunteers (20-45 years) received a single 2.5-mg zolmitriptan tablet in the fasting state. Blood samples were taken up to 15 h post-dose to determine plasma concentrations of zolmitriptan and its active metabolite, 183C91. Urinary excretion of zolmitriptan, 183C91 and the inactive N-oxide and indole acetic acid metabolites were measured over 24 h. Japanese volunteers were, on average, smaller and lighter than Caucasian volunteers. Plasma-concentration profiles of zolmitriptan and 183C91 were similar in the two groups. Although geometric mean zolmitriptan and 183C91 area under the plasma concentration-time curve (AUC) and maximum plasma concentration (C(max)) were slightly higher in Japanese subjects (up to 20%), these differences were not considered to be of clinical relevance as the 90% confidence interval for the ratio of AUCs fell within pre-specified limits (0.67 to 1.5). Mean zolmitriptan and 183C91 half-lives were around 2.5 h for both populations. Urinary excretion of the four analytes was similar in Japanese and Caucasians. Plasma concentrations of zolmitriptan were higher in Japanese females than males (AUC 40% and C(max) 29% higher), consistent with the results previously obtained in Caucasians. Pharmacokinetic parameters of zolmitriptan were similar between Caucasian and Japanese volunteers.",2003.0,0,0
313,12167141,Intravenous valproate sodium in the treatment of daily headache.,Tamara H Schwartz; Vladimir V Karpitskiy; Richard S Sohn,"Treatment of chronic daily headache/transformed migraine is challenging, especially when it is complicated by overuse of analgesics, triptans, or both. One common approach involves the use of repetitive intravenous dihydroergotamine. We investigated the use of intravenous valproate sodium in the treatment of chronic daily headache/transformed migraine in patients who had contraindications to the use of or had failed treatment with dihydroergotamine. We administered intravenous valproate sodium (Depacon) to patients with chronic daily headache/transformed migraine (loading dose 15 mg/kg, followed by 5 mg/kg every 8 hours). All analgesics and triptans were discontinued prior to treatment with divalproex sodium, and preventative medications for migraine were begun or continued. All patients received instruction in behavioral modification and the proper use of analgesics and triptans. Improvement in headache was reported by 80% of the patients treated, and valproate sodium was tolerated well by most. Intravenous valproate sodium may be of assistance in the initial management of patients with chronic daily headache/transformed migraine and analgesic/triptan overuse, especially when dihydroergotamine is ineffective or contraindicated.",2002.0,0,0
314,12185552,Non-invasive assessment of selective 5-HT(1B/1D)-receptor agonist-induced peripheral vascular effects in humans: comparison of different techniques.,F H Vanmolkot; J N de Hoon; P Barrington; R W Peck; N S Dallow; P M Williams; J McColm,"To compare the sensitivity of three non-invasive techniques for detecting serotonin (5-HT)(1B/1D)-receptor agonist-induced peripheral vascular effects in humans: the measurement of (1) systolic (SBP) and diastolic (DBP) blood pressures, (2) dorsal hand vein (DHV) diameter and (3) toe-arm systolic blood pressure gradient (DeltaSBP(toe-arm)). A double-blind, placebo-controlled, three-way, cross-over study was performed in 12 healthy male volunteers. According to a randomly assigned allocation schedule, subjects were administered sumatriptan 3 mg, sumatriptan 6 mg or placebo subcutaneously. Measurements were performed at baseline, every 5 min for 30 min and at 40 min and 60 min after drug administration. SBP and DBP were recorded using a semi-automated oscillometric device. DHV diameter was measured using a linear variable differential transformer. DeltaSBP(toe-arm) was calculated after measuring toe and arm SBP with a strain-gauge technique. Sensitivity was evaluated with responsiveness statistics. Based on weighted mean and compared with placebo, sumatriptan 3 mg and 6 mg increased SBP by 3.3 mmHg ( P=0.023) and 6.4 mmHg ( P<0.001) and DBP by 5.0 mmHg ( P=0.006) and 7.5 mmHg ( P<0.001), respectively. Sumatriptan 3 mg and 6 mg decreased DHV diameter by 36% ( P=0.015) and 40% ( P=0.005), respectively. DeltaSBP(toe-arm) did not change. Peak changes were observed within 10-15 min after drug administration. The rank order of responsiveness was: BP > DHV diameter > DeltaSBP(toe-arm.) Clinically relevant doses of subcutaneous sumatriptan increased blood pressure and decreased DHV diameter without affecting DeltaSBP(toe-arm). The increase in blood pressure appeared to be dose dependent. Compared with DHV diameter and DeltaSBP(toe-arm), blood pressure measurement appeared to be the most sensitive technique for detecting selective 5-HT(1B/1D)-receptor agonist-induced peripheral vascular effects in humans.",2003.0,0,0
315,12190330,Clinical pharmacokinetics of intranasal sumatriptan.,Eliane Fuseau; Olivier Petricoul; Katy H P Moore; Andrew Barrow; Tim Ibbotson,"A substantial proportion of migraine patients have gastric stasis and suffer severe nausea and/or vomiting during their migraine attack. This may lead to erratic absorption from the gastrointestinal tract and make oral treatment unsatisfactory. For such patients, an intranasal formulation may be advantageous. Sumatriptan is a potent serotonin 5HT(1B/1D) agonist widely used in the treatment of migraine; the effectiveness of the intranasal formulation (20mg) has been well established in several clinical studies. This article reviews the pharmacokinetics of intranasal sumatriptan and includes comparisons with oral and subcutaneous administration. After intranasal administration, sumatriptan is directly and rapidly absorbed, with 60% of the maximum plasma concentration (C(max)) occurring at 30 minutes after administration of a single 20mg dose. Following intranasal administration, approximately 10% more sumatriptan is absorbed probably via the nasal mucosa when compared with oral administration. Mean C(max) after a 20mg intranasal dose is approximately 13.1 to 14.4 ng/mL, with median time to C(max) approximately 1 to 1.75 hours. When given as a single dose, intranasal sumatriptan displays dose proportionality in its extent of absorption and C(max) over the dose range 5 to 10mg, but not between 5 and 20mg for C(max). The elimination phase half-life is approximately 2 hours, consistent with administration by other routes. Sumatriptan is metabolised by monoamine oxidase (MAO; predominantly the A isozyme, MAO-A) to an inactive metabolite. Coadministration with a MAO-A inhibitor, moclobemide, leads to a significant increase in sumatriptan plasma concentrations and is contraindicated. Single-dose pharmacokinetics in paediatric and adolescent patients following intranasal sumatriptan were studied to determine the effect of changes in nasal morphology during growth, and of body size, on pharmacokinetic parameters. The pharmacokinetic profile observed in adults was maintained in the adolescent population; generally, factors such as age, bodyweight or height did not significantly affect the pharmacokinetics. In children below 12 years, C(max) is comparable to that seen in adolescents and adults, but total exposure (area under the concentration-time curve from zero to infinity) was lower in children compared with older patients, especially in younger children treated with 5mg. Clinical experience suggests that intranasal sumatriptan has some advantages over the tablet (more rapid onset of effect and use in patients with gastrointestinal complaints) or subcutaneous (noninvasive and fewer adverse events) formulations.",2002.0,0,0
316,12196035,Global trends in migraine care: results from the MAZE survey.,Jan Lewis Brandes,"Many patients with migraine do not consult a physician, or do not achieve adequate relief after consulting a physician because of undertreatment. The objective of the Migraine and Zomig Evaluation study was to provide insights into the management of migraine in the general population. In phase I, 5553 members of the general public in the UK, France, Germany, Italy, and the US were interviewed by telephone and classified according to International Headache Society criteria. The Migraine Disability Assessment Scale (MIDAS) questionnaire was used to assess the impact of migraine on work, home and social lives. In phase II, 516 patients with clinically diagnosed migraine were interviewed to assess the impact of migraine on daily life, attitudes towards migraine, perceptions of current treatments and aspirations for future treatments. In phase I, the average prevalence of migraine over the five countries was 9%. Migraine posed a significant burden in terms of the impact on patients' daily lives, and attack severity and frequency. However, medical consultation rates were low; reasons for this included patients not recognising that they had migraine or having low expectations about treatment benefits. On average, only 10% of patients who had consulted a physician had been prescribed a triptan. Only 22% of participants in phase II thought that migraine did not markedly affect their lives. In each of the five countries, > or = 50% of patients required bed rest to manage migraine attacks, demonstrating the impact of migraine-related disability on patients' lives. Assessment of MIDAS scores confirmed the debilitating effect of migraine; > 50% of respondents had a MIDAS grade of III or IV, indicating moderate or severe disability. Less than one-third of patients reported that their current medication was consistently effective and only 36% were 'very satisfied' with their current therapy. High efficacy and rapid pain relief were rated as the most important attributes of migraine medications. When asked which formulation they would like to see more of, most patients chose a tablet that dissolves in the mouth without the need to take liquids. These results show that migraine patients worldwide are still not receiving adequate treatment and there remains a significant unmet need in migraine care. The challenge for the future is to diagnose migraine early and offer patients effective migraine-specific therapies. Physicians particularly need to reach patients who do not realise they have migraine and those who have lapsed from care.",2002.0,0,0
317,12199263,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
318,12201791,Prospective study designs in outcomes research: the case of migraine.,Elizabeth A Rothermich; Meryl I Brod; Warren H Schonfeld; Clayton R Rowland; Baltazar Gomez-Mancilla,"Patient-reported outcomes (PROs), including resource utilisation, productivity and quality of life, are important outcomes in the field of migraine. Clinical trials have begun to incorporate PROs; however, not all research questions can be answered fully within the framework of a clinical trial design. Other prospective designs, including effectiveness trials, observational studies, and study hybrids may be used to answer many of the different research questions related to PROs. This paper reviews prospective study designs, their strengths and weaknesses, and examples of their application in migraine health-outcomes research. Guidance is provided for researchers in the selection of prospective research designs and the incorporation of PROs-research objectives.",2002.0,0,0
319,12212757,The comparative clinical and economic benefits of drugs should be established and discussed as part of any formulary decision process.,Mary S Richardson; Brian W Bowers; Jonathan L Petrie,,2002.0,0,0
320,12269863,,,,,0,1
321,12353056,"Almotriptan, a new anti-migraine agent: a review.",Jordi Gras; Jesús Llenas; Josep M Jansat; José Jáuregui; Xavier Cabarrocas; José M Palacios,"Almotriptan is a new anti-migraine agent with nanomolar affinity for human 5-HT(1B), 5-HT(1D), and 5-HT(1F) receptors, weak affinity for 5-HT(1A) and 5-HT(7) receptors and no significant affinity for more than 20 other pharmacological receptors. Almotriptan was effective in animal models predictive of anti-migraine activity in humans and had a good safety profile in animal studies. From the toxicological point of view, almotriptan has a profile similar to that of other marketed triptans. In animal studies, at levels substantially higher than required for therapeutic activity in humans, almotriptan was devoid of any oncogenic, genotoxic or teratogenic effects. Almotriptan is well absorbed orally; its absolute bioavailability in humans is 70%. Its peak plasma levels are reached at 1 to 3 h after its administration; its elimination half-life is 3 to 4 h. Almotriptan is metabolized by monoamine oxidase-mediated oxidative deamination and cytochrome P450-mediated oxidation as the major metabolic route and by flavin monooxygenase as the minor route. No dose adjustment is required for gender or age, and only in the case of severe renal impairment the dose should not exceed 12.5 mg over a 24-h period. There was no significant interaction between a single dose of almotriptan and propranolol, fluoxetine or verapamil, at multiple doses. The efficacy of almotriptan in the treatment of acute migraine was demonstrated in clinical trials on more than 3000 patients with migraine. At two h after oral administration of almotriptan, 12.5 mg, the percentages of patients showing pain relief and a pain-free score were 64 and 36%, respectively. The effects of almotriptan were significantly better than those of placebo. When almotriptan was administered in the early phase of migraine, the percentage of pain-free patients at 2 h rose to 84%. In a phase III, double-blind and placebo-controlled study, the incidence of adverse events with almotriptan was not statistically different from that of placebo. Based on the available data, it appears that almotriptan is the triptan of choice when good efficacy and high tolerability are desired.",2002.0,1,1
322,12370451,Statins as immunomodulators: comparison with interferon-beta 1b in MS.,O Neuhaus; S Strasser-Fuchs; F Fazekas; B C Kieseier; G Niederwieser; H P Hartung; J J Archelos,"Recent data suggest that statins may be potent immunomodulatory agents. In order to evaluate the potential role of statins as immunomodulators in MS, the authors studied their immunologic effects in vitro and compared them to interferon (IFN)beta-1b. Peripheral blood mononuclear cells (PBMC) obtained from untreated or IFN beta-1-treated patients with relapsing-remitting MS or from healthy donors (HD) and T cells were stimulated with concanavalin A, phytohemagglutinin, or antibody to CD3 in the presence of lovastatin, simvastatin, mevastatin, IFN beta-1b, or statins plus IFN beta-1b. The authors analyzed proliferative activity of T cells and B cells, cytokine production and release, activity of matrix metalloproteinases (MMP), and surface expression of activation markers, adhesion molecules, and chemokine receptors on both T and B cells. All three statins inhibited proliferation of stimulated PBMC in a dose-dependent manner, with simvastatin being the most potent, followed by lovastatin and mevastatin. IFN beta-1b showed a similar effect; statins and IFN beta-1b together added their inhibitory potentials. Furthermore, statins reduced the expression of activation-induced adhesion molecules on T cells, modified the T helper 1/T helper 2 cytokine balance, reduced MMP-9, and downregulated chemokine receptors on both B and T cells. Besides strong anti-inflammatory properties, statins also exhibited some proinflammatory effects. Statins are effective immunomodulators in vitro that merit evaluation as treatment for MS.",2002.0,0,0
323,12371307,New drugs with novel therapeutic characteristics. Have they been subject to randomized controlled trials?,Joel Lexchin,"To determine how many randomized controlled trials on the safety or efficacy of new drugs are published when these drugs are first marketed in Canada, and to determine the quality of the information in those trials. A MEDLINE search was conducted on each drug identified as having novel therapeutic characteristics and first marketed between 1990 and 2000. Number of trials dealing with the safety or efficacy of each drug published at the time the drug was marketed. Number of patients taking the study drug, length of the trial, and type of control. The number of trials varied substantially. For some drugs, there were more than 20 studies; for others only a single study. Many trials were small and short-term, and used placebo controls. Too few trials or inadequate trials on the safety and efficacy of new drugs are published when these drugs are first marketed in Canada. The lack of published trials means that physicians do not know whether results are generalizable to their patients, how to position the drug in relation to other treatments, or whether the drugs have long-term safety and efficacy.",2002.0,0,0
324,12373035,Restoring migraine sufferers' ability to function normally: a comparison of rizatriptan and other triptans in randomized trials.,Gennaro Bussone; Domenico D'Amico; Kathleen A McCarroll; William Gerth; Christopher R Lines,"Many migraine patients are unable to function normally during a migraine attack. Assessments of treatment efficacy have tended to focus on migraine symptoms, rather than looking at functional impact. This study compared the efficacy of different oral triptans for restoring normal function in migraine sufferers. Retrospective subgroup analysis of data from five randomized, placebo-controlled, double-blind clinical trials in which oral rizatriptan was directly compared with oral sumatriptan 100 mg (772 attacks), 50 mg (2,227 attacks), and 25 mg (1,182 attacks), naratriptan 2.5 mg (413 attacks), and zolmitriptan 2.5 mg (578 attacks) for the acute treatment of a moderate or severe migraine attack. Functional disability was evaluated by patients on a 4-grade scale ('normal', 'mild impairment', 'severe impairment', 'requires bedrest') at baseline and at 0.5, 1, 1.5, 2, 3 and 4 h after dosing. This analysis looked at the percentage of patients who had normal functional ability at 2 h, the last time point before escape medications were allowed, in the subgroup of patients who had some level of disability at baseline. Most patients in each trial and treatment group had some level of disability at baseline (range = 94-100%). At 2 h, more patients on rizatriptan 10 mg were able to function normally compared with sumatriptan 100 mg (39 vs. 32%, odds ratio = 1.4, p = 0.021), sumatriptan 50 mg (47 vs. 42%, odds ratio = 1.2, p = 0.033), sumatriptan 25 mg (48 vs. 36%, odds ratio = 1.7, p < 0.001), naratriptan 2.5 mg (39 vs. 22%, odds ratio = 2.5, p < 0.001), and zolmitriptan 2.5 mg (45 vs. 36%, odds ratio = 1.6, p = 0.008). In direct head-to-head comparative clinical trials, oral rizatriptan 10 mg enabled more migraine sufferers to function normally at 2 h after dosing than oral sumatriptan, naratriptan, and zolmitriptan.",2002.0,1,1
325,12383060,"Triptans (serotonin, 5-HT1B/1D agonists) in migraine: detailed results and methods of a meta-analysis of 53 trials.",M D Ferrari; P J Goadsby; K I Roon; R B Lipton,"The triptans, selective serotonin 5-HT1B/1D agonists, are very effective acute migraine drugs. Soon, seven different triptans will be clinically available at 13 different oral doses, making evidence-based selection guidelines necessary. Triptan trials have similar designs, facilitating meta-analysis. We wished to provide an evidence-based foundation for using triptans in clinical practice, and to review the methodological issues surrounding triptan trials. We asked pharmaceutical companies and the principal investigators of company-independent trials for the 'raw patient data' of all double-blind, randomized, controlled, clinical trials with oral triptans in migraine. All data were cross-checked with published or presented data. We calculated summary estimates across studies for important efficacy and tolerability parameters, and compared these with those from direct, head-to-head, comparator trials. Out of 76 eligible clinical trials, 53 (12 not yet published) involving 24089 patients met the criteria for inclusion. Mean results (and 95% confidence intervals) for sumatriptan 100 mg, the first available and most widely prescribed oral triptan, are 59% (57-60) for 2 h headache response (improvement from moderate or severe to mild or no pain); 29% (27-30) for 2 h pain free (improvement to no pain); 20% (18-21) for sustained pain free (pain free by 2 h and no headache recurrence or use of rescue medication 2-24 h post-dose), and 67% (63-70) for consistency (response in at least two out of three treated attacks); placebo-subtracted proportions for patients with at least one adverse event (AE) are 13% (8-18), for at least one central nervous system AE 6% (3-9), and for at least one chest AE 1.9% (1.0-2.7). Compared with these data: rizatriptan 10 mg shows better efficacy and consistency, and similar tolerability; eletriptan 80 mg shows better efficacy, similar consistency, but lower tolerability; almotriptan 12.5 mg shows similar efficacy at 2 h but better sustained pain-free response, consistency, and tolerability; sumatriptan 25 mg, naratriptan 2.5 mg and eletriptan 20 mg show lower efficacy and better tolerability; zolmitriptan 2.5 mg and 5 mg, eletriptan 40 mg, and rizatriptan 5 mg show very similar results. The results of the 22 trials that directly compared triptans show the same overall pattern. We received no data on frovatriptan, but publicly available data suggest substantially lower efficacy. The major methodological issues involve the choice of the primary endpoint, consistency over multiple attacks, how to evaluate headache recurrence, use of placebo-subtracted proportions to control for across-study differences, and the difference between tolerability and safety. In addition, there are a number of methodological issues specific for direct comparator trials, including encapsulation and patient selection. At marketed doses, all oral triptans are effective and well tolerated. Differences among them are in general relatively small, but clinically relevant for individual patients. Rizatriptan 10 mg, eletriptan 80 mg and almotriptan 12.5 mg provide the highest likelihood of consistent success. Sumatriptan features the longest clinical experience and the widest range of formulations. All triptans are contra-indicated in the presence of cardiovascular disease.",2003.0,0,0
326,12383062,Sum of Pain Intensity Differences (SPID) in migraine trials. A comment based on four rizatriptan trials.,P Tfelt-Hansen; K McCarroll; C Lines,"Sum of Pain Intensity Difference (SPID) is an outcome measure that summarizes treatment response over a clinically relevant period. SPID is widely reported in clinical trials of analgesics but has been little used in migraine trials. We compared SPID over 2 h with the standard migraine outcome measures of pain-free at 2 h and headache relief at 2 h using data from four published clinical trials of rizatriptan in migraine patients. In assessing treatment response (rizatriptan and sumatriptan versus placebo, rizatriptan versus sumatriptan, within-treatment dose effects), SPID usually yielded similar results to the more easily understood pain-free measure.",2003.0,0,1
327,12383065,Determinants of migraine-specific quality of life.,N C Santanello; G Davies; C Allen; M Kramer; R Lipton,"This paper reports an analysis of two randomized controlled trials of rizatriptan, in which the 24-h Migraine Quality of Life QuestionnaireCopyright was used to assess migraine-specific quality of life in patients receiving acute treatment. The objective of the analysis was to determine which clinical effects of a migraine medication, as measured by traditional clinical trial endpoints, contribute to a better short-term health-related quality of life. The results demonstrate that patients who experience complete pain relief and are able to function at their normal ability within 2 h and experience no headache recurrence have the highest migraine-specific quality of life scores. Patients who were satisfied with medication at 2 h had higher migraine-specific quality of life scores than those who were not satisfied. In conclusion, migraine therapy that provides rapid, complete, and sustained pain relief, with restoration of functional ability, has the most beneficial impact on short-term health-related quality of life for migraineurs.",2003.0,1,1
328,12390618,Triptans versus analgesics.,Lawrence Robbins,"To retrospectively assess patient preferences between triptans and analgesics in treating migraine headache. The study assessed patient preferences for triptans versus commonly used migraine analgesic preparations. Over a 3-month period, 663 patients with migraine between the ages of 17 and 62 years completed an office-based survey. Most patients preferred a treatment regimen that included either a triptan alone (52%) or a triptan with an analgesic medication within 1 hour (18%). Overall, 70% of patients who had been given triptans in the past chose to continue to use them, either alone or with an analgesic. Patients who preferred analgesics alone comprised 21% of the total. Nine percent preferred not to take either triptans or analgesic medications. Among the patients who preferred triptans, 62% stated that increased efficacy was the primary reason for their preference. Thirty percent cited both efficacy and decreased adverse events. The remaining 8% believed that decreased adverse events was the basis for their preference. Despite cost and other limitations of triptans, most patients prefer them over nontriptan medications. Enhanced efficacy was the main reason for choosing triptans over analgesics.",2002.0,0,1
329,12390621,Further evaluation of rizatriptan in menstrual migraine: retrospective analysis of long-term data.,Stephen D Silberstein; Helene Massiou; Kathleen A McCarroll; Christopher R Lines,"To determine the long-term efficacy of oral rizatriptan 10-mg wafers in the treatment of menstrual migraine attacks. Data from an extension study where patients with migraine used rizatriptan 10 mg to treat moderate or severe migraine attacks occurring over periods of up to 6 months were included in a retrospective analysis. Patients used a diary card to record details of each migraine attack and onset of menstruation. Attacks in women were classified as menstrual or nonmenstrual according to 3 time windows relative to onset of menstruation (day 0): -3 to +3 days (7-day window), -2 to + 2 days (5-day window), and 0 to +1 days (2-day window). The analysis looked at the efficacy of rizatriptan 10 mg by menstrual category of attack for each definition on three measures: pain relief at 2 hours (reduction of pain to mild or none), pain free at 2 hours, 24-hours sustained pain free (pain free at 2 hours with no headache recurrence and no use of additional medications from 2 to 24 hours). Ninety-five women used rizatriptan 10 mg to treat a total of 1,839 attacks. The percentage of menstrual attacks was 30% for the -3 to +3 days definition, 23% for the -2 to +2 days definition, and 11% for the 0 to +1 days definition. Rizatriptan 10 mg was equally effective in menstrual and nonmenstrual migraine attacks regardless of the definition used. For example, using the -3 to +3 days definition, 78% of menstrual migraine attacks were relieved at 2 hours after dosing compared with 78% of nonmenstrual attacks. Pain relief rates for the other definitions were as follows: -2 to +2 days, menstrual = 78%, nonmenstrual = 78%; 0 to +1 days, menstrual = 79%, and nonmenstrual = 78%. No differences between menstrual and nonmenstrual attacks were found for the 2-hour pain free and 24-hour sustained pain free measures for any of the three definitions. Rizatriptan 10-mg wafers were equally effective in the treatment of menstrual and nonmenstrual migraine attacks occurring over 6 months, regardless of the precise definition of menstrual association used and even when the outcome criteria were very stringent. These data provide further evidence that triptans are effective treatments for menstrual migraine.",2002.0,0,0
330,12390633,Decreased sensitivity of 5-HT1D receptors in chronic tension-type headache.,I Rainero; W Valfrè; L Savi; M Ferrero; P Del Rizzo; P Limone; G C Isaia; L Gianotti; A Pollo; R Verde; F Benedetti; L Pinessi,"To assess the sensitivity of 5-HT1D receptors in chronic tension-type headache using sumatriptan as a pharmacological probe. Previous studies have suggested involvement of serotonergic systems in chronic tension-type headache (CTTH), but relevant experimental data are limited. Sumatriptan, a 5-HT1B/1D receptor agonist, stimulates the release of growth hormone (GH) and inhibits the release of ACTH, cortisol, and prolactin. These effects may be used to explore the function of serotonergic systems in vivo. We measured GH, ACTH, cortisol and prolactin (PRL) plasma concentrations in 15 patients with chronic tension-type headache and in 18 healthy controls after subcutaneous administration of sumatriptan (6 mg) or placebo. Placebo administration had no effect on hormone concentrations. GH and PRL secretion after sumatriptan administration was significantly (P<0.01 and <0.05) altered in CTTH patients in comparison with controls. Our results suggest that cerebral serotonergic functions mediated by 5-HT1D receptors are altered in CTTH.",2002.0,0,0
331,12390651,Intractable cluster headaches in a migraineur.,John F Rothrock; Ninan T Mathew; Alex O Kaup; Randolph W Evans,Some migraineurs have the additional misfortune of suffering from cluster headaches; this situation can be challenging.,2002.0,0,0
332,12391349,"Eletriptan vs sumatriptan: a double-blind, placebo-controlled, multiple migraine attack study.",G Sandrini; M Färkkilä; G Burgess; E Forster; S Haughie; Eletriptan Steering Committee,"To compare the efficacy of oral eletriptan, 40 mg and 80 mg, and oral sumatriptan, 50 mg and 100 mg, in the acute treatment of migraine. Patients with a history of migraine (n = 1,008) were randomly assigned to receive placebo, 40 mg of eletriptan, 80 mg of eletriptan, 50 mg of sumatriptan, or 100 mg of sumatriptan to treat up to three attacks. Early headache response (at 1 hour) was the primary endpoint, in addition to the standard endpoint, 2-hour headache response. Headache response rates were 12% at 1 hour and 31% at 2 hours for placebo; 24% at 1 hour and 50% at 2 hours for sumatriptan 50 mg; 27% at 1 hour and 53% at 2 hours for sumatriptan 100 mg; 30% at 1 hour and 64% at 2 hours for eletriptan 40 mg; and 37% at 1 hour and 67% at 2 hours for eletriptan 80 mg. More patients receiving eletriptan 80 mg achieved a 1-hour headache response than did patients receiving sumatriptan 50 mg (p < 0.05). All doses of eletriptan were superior to sumatriptan at 2 hours for headache response and complete pain relief (p < 0.05). Significantly more patients on eletriptan 80 mg achieved headache response in all attacks than did patients receiving either sumatriptan dose. Eletriptan 40 mg was superior to both sumatriptan doses in functional improvement (p < 0.005). The superior efficacy of both eletriptan doses was associated with higher rates of patient acceptability than sumatriptan 50 mg (p < 0.05). Eletriptan and sumatriptan were well tolerated. Oral eletriptan (40 mg and 80 mg) is effective, safe, and tolerable in the acute treatment of migraine and yields a consistent response.",2002.0,1,1
333,12392581,St John's wort (Hypericum perforatum): drug interactions and clinical outcomes.,L Henderson; Q Y Yue; C Bergquist; B Gerden; P Arlett,"The aim of this work is to identify the medicines which interact with the herbal remedy St John's wort (SJW), and the mechanisms responsible. A systematic review of all the available evidence, including worldwide published literature and spontaneous case reports provided by healthcare professionals and regulatory authorities within Europe has been undertaken. A number of clinically significant interactions have been identified with prescribed medicines including warfarin, phenprocoumon, cyclosporin, HIV protease inhibitors, theophylline, digoxin and oral contraceptives resulting in a decrease in concentration or effect of the medicines. These interactions are probably due to the induction of cytochrome P450 isoenzymes CYP3A4, CYP2C9, CYP1A2 and the transport protein P-glycoprotein by constituent(s) in SJW. The degree of induction is unpredictable due to factors such as the variable quality and quantity of constituent(s) in SJW preparations. In addition, possible pharmacodynamic interactions with selective serotonin re-uptake inhibitors and serotonin (5-HT(1d)) receptor-agonists such as triptans used to treat migraine were identified. These interactions are associated with an increased risk of adverse reactions. In Sweden and the UK the potential risks to patients were judged to be significant and therefore information about the interactions was provided to health care professionals and patients. The product information of the licensed medicines involved has been amended to reflect these newly identified interactions and SJW preparations have been voluntarily labelled with appropriate warnings.",2003.0,0,0
334,12412822,Preliminary studies of the pharmacokinetics and tolerability of zolmitriptan nasal spray in healthy volunteers.,Roger Yates; Kevin Nairn; Ruth Dixon; Emma Seaber,"Two preliminary studies of the pharmacokinetics and tolerability of zolmitriptan nasal spray were conducted, each involving 12 healthy volunteers. In study 1, an initial double-blind, dose escalation phase (placebo or 2.5, 5.0, or 10 mg zolmitriptan intranasally) was followed by an open crossover phase in which all subjects received 10 mg zolmitriptan as a nasal spray, tablet, and oral solution. In study 2, subjects received, on three separate occasions, zolmitriptan 2.5 mg as an intranasal solution at pH 7.4, at pH 5.0, and as an oral tablet. In study 1, plasma concentrations of zolmitriptan and its active metabolite, 183C91, were broadly dose proportional. Plasma concentrations of zolmitriptan were detected earlier following nasal spray administration than after either tablet or oral solution. Similarly, in study 2, zolmitriptan was absorbed more rapidly following nasal spray administration with detectable plasma concentrations 5 minutes after dosing. Plasma levels were maintained at a plateau between 1 and 6 hours postdose, then decreased with a half-life of approximately 3 hours. There was no statistically significant difference for AUG or C(max) values between the two nasal spray solutions or between nasal spray and oral formulations. Other pharmacokinetic parameters for zolmitriptan were similar between the formulations. Plasma concentrations of 183C91 were higher for the first 2 hours after oral than after nasal spray administration. All formulations of zolmitriptan were well tolerated.",2003.0,0,0
335,12412823,"Pharmacokinetics, dose proportionality, and tolerability of single and repeat doses of a nasal spray formulation of zolmitriptan in healthy volunteers.",Roger Yates; Kevin Nairn; Ruth Dixon; J V Kemp; A L Dane,"The objective of this study was to investigate the pharmacokinetics, dose proportionality, and tolerability of a range of single and multiple doses of a nasal spray formulation of zolmitriptan in a randomized, double-blind, placebo-controlled, balanced, incomplete crossover study. Thirty healthy male or female volunteers received two of five dose levels of zolmitriptan nasal spray: 0 (placebo), 0.5, 1, 2.5, and 5 mg. At each level, treatment comprised a single dose on day 1 and two doses (separated by 2 h) on each of days 2, 3, and 4. Zolmitriptan was well tolerated, and symptoms were generally mild and of short duration. The most commonly reported adverse events were taste disturbance, paresthesia, hyperesthesia, headache, and nasal/throat discomfort. Volunteers generally reported fewer adverse events during the multiple-dose phase than after the single-dose phase. Zolmitriptan was detectable in plasma within 15 minutes, and t(max) was similar for each dose and after single and multiple dosing. Dose proportionality was shown for the C(max) and AUC of both zolmitriptan and its active metabolite, 183C91. Mean t1/2 for zolmitriptan and 183C91 was approximately 3 hours. It was concluded that the pharmacokinetics (C(max) and AUC) for both zolmitriptan and 183C91 was proportional to dose after both single and multiple dosing. Nasal spray zolmitriptan was well tolerated; the frequency and nature of adverse events did not increase after multiple dosing.",2003.0,0,0
336,12418843,"Review: several drugs, especially triptans, are effective for pain relief in acute migraine.",Elizabeth Loder,,2002.0,0,0
337,12421156,Tinted spectacles and visually sensitive migraine.,A J Wilkins; R Patel; P Adjamian; B J W Evans,"A double-masked randomized controlled study with cross-over design compared the effectiveness of precision ophthalmic tints in the prevention of headache in migraine sufferers. Seventeen patients chose the colour of light that optimally reduced perceptual distortion of text and maximized clarity and comfort. They were later given glasses with spectral filters providing optimal colour under conventional white lighting ('optimal' tint) or glasses that provided a slightly different colour ('control' tint). The tints were supplied in random order, each for 6 weeks, separated by an interval of at least 2 weeks with no tints. Headache diaries showed that the frequency of headaches was marginally lower when the 'optimal' tint was worn, compared with the 'control'. The trial extends to adults with migraine, the results of a previous double-masked study demonstrating, in children with reading difficulty, beneficial effects of precision tints in reducing symptom frequency. In the present study, however, the effects are suggestive rather than conclusive.",2003.0,0,0
338,12422253,Impact of migraine symptoms on health care use and work loss in Canada in patients randomly assigned in a phase III clinical trial.,Jean Lambert; George W Carides; Jacques P Meloche; William C Gerth; Michael A Marentette,"Migraine is prevalent and associated with substantial direct and indirect costs that may vary across geographic and national boundaries. The effects of migraine, self-reported by Canadians, on health care resource use as well as paid and unpaid work loss were examined. The Migraine Background Questionnaire (MBQ) was self-administered during the screening visit of a phase III clinical trial of rizatriptan (a potent, selective 5-hydroxytryptamine(1B/1D)-receptor agonist or 'triptan'). Patients suffering from moderate to severe migraine in the previous six months were offered the opportunity to participate. Migraine frequency was determined and costs were estimated and assigned based on known direct costs of health care resource utilization, and indirect costs of paid and unpaid work and productivity loss. One hundred thirty-four patients completed the MBQ. In the previous year, 89% of those patients reported visiting a clinic, 23% reported visiting an emergency room and 5% reported being hospitalized for migraine. Patients reported an average of 6.5 days absent from work, 44 days working with migraine headache and 10.4 reduced workday equivalents due to ineffectiveness at work with migraine. Based on data obtained from the Ontario, the average overall annual cost due to migraine was estimated to be 3,025 dollars/patient; most of this (87%) due to indirect costs. In Canada, patients with moderate to severe migraine, as identified in a phase III clinical trial, reported lost work days and reduced effectiveness while at work, as well as increased health care resource utilization due to migraine. The associated cost was estimated to be substantial.",2003.0,0,0
339,12435222,Pharmacologic management of acute attacks of migraine and prevention of migraine headache.,Vincenza Snow; Kevin Weiss; Eric M Wall; Christel Mottur-Pilson; American Academy of Family Physicians; American College of Physicians-American Society of Internal Medicine,,2002.0,0,1
340,12453029,Cost-effectiveness of antiepileptic drugs in migraine prophylaxis.,James U Adelman; Leon C Adelman; Randal Von Seggern,"To analyze the cost-effectiveness of antiepileptics in migraine prophylaxis. A cost-effectiveness analysis was performed using efficacy data from three recent, double-blind, placebo-controlled, clinical trials of antiepileptic drugs studied for migraine prevention and cost data. Two measures of cost-effectiveness were used: cost per headache prevented and the cost-equivalent number. In the double-blind, placebo-controlled, clinical trials evaluated, three antiepileptic drugs were shown to be effective in migraine prevention. All three antiepileptic drugs had high costs per migraine reduced. Gabapentin was the most costly at dollars 138.00 per migraine prevented, whereas the cost per migraine prevented with topiramate was US dollars 114.80 and with divalproex sodium was US dollars 48.00. For migraine prevention divalproex sodium became cost-effective with 10 migraines per month, whereas gabapentin and topiramate required considerably more migraines per month to be cost-effective. Antiepileptic drugs have proven effectiveness in migraine prophylaxis. However, in patients responsive to their acute care medications, the antiepileptic drugs are only cost-effective for those patients with a high frequency of migraines and those with comorbid diseases. Future studies should be done with antiepileptic drugs in patients exhibiting a migraine frequency of 10 or more headaches per month.",2003.0,0,0
341,12455302,Efficacy and safety of almotriptan malate for migraine.,Ebrahim A Balbisi,"The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of almotriptan are reviewed. Migraine is a common disorder with a serious impact on quality of life. Newer serotonin-receptor agonists have been developed with the aim of improving pharmacokinetic characteristics. Almotriptan, a selective agonist of serotonin receptors 1B and 1D, carries FDA-approved labeling for use in the management of migraine with or without aura in adults. The efficacy and receptor affinity resemble those of sumatriptan, but almotriptan has a more favorable pharmacokinetic profile. It has a rapid onset of action, an oral bioavailability of 70-80%, and a longer half-life than sumatriptan. In clinical trials, almotriptan has been significantly more effective than placebo and as effective as sumatriptan. However, it has been associated with better tolerability and greater patient satisfaction. In clinical trials, the most commonly reported adverse effects were nausea, dry mouth, dizziness, somnolence, fatigue, vomiting, and paresthesia. Almotriptan is contraindicated in patients with known ischemic heart disease, coronary vasospasm, and other significant cardiovascular disorders. Almotriptan has a lower acquisition cost than other triptans and possibly lower overall health care costs because of a lower frequency of cardiovascular adverse effects. The recommended dose of almotriptan is one 6.25- or 12.5-mg tablet given at the onset of symptoms. Almotriptan is effective for the management of migraine and offers the potential for fewer adverse effects than other agents in its class.",2003.0,0,1
342,12463724,"Absolute bioavailability, pharmacokinetics, and urinary excretion of the novel antimigraine agent almotriptan in healthy male volunteers.",Josep M Jansat; Joan Costa; Pau Salvà; Francisco J Fernandez; Antonio Martinez-Tobed,"Absolute bioavailability, pharmacokinetics, and urinary excretion of almotriptan, a novel 5-HT(1B/1D) receptor agonist, were studied in 18 healthy males following single intravenous (i.v.) (3 mg), subcutaneous (s.c.) (6 mg), and oral (25 mg) doses. Volunteers received each dose in a randomized sequence separated by a 7-day washout. Blood and urine samples for pharmacokinetic evaluations were taken for up to 24 hours after dosing. The disposition kinetics of almotriptan after i.v. and s.c. administration showed biphasic decline described by a two-compartment model. The fastest disposition phase was well observed, although estimates of the rate constant showed high variability. After s.c. administration of almotriptan, the bioavailability was 100% with a time to maximum plasma concentration (tmax) of 5 to 15 minutes, whereas after oral administration, the bioavailability was about 70% with a tmax of 1.5 to 3.0 hours. No significant differences were observed between administration routes in the elimination half-life (t(1/2), obtaining mean values ranging from 3.4 to 3.6 hours. The volume of distribution, total clearance, and t(1/2) indicated that almotriptan was extensively distributed and rapidly cleared from the body irrespective of dose or route of administration. The primary route of elimination was renal clearance (approximately 50%-60% of total body clearance). About 65% of the i.v. and s.c. dose and 45% of the oral dose were excreted unchanged in urine in 24 hours, with nearly 90% of this in the first 12 hours. Renal clearance was approximately 2- to 3-fold that of the glomerular filtration rate in man, suggesting that almotriptan is eliminated in part by renal tubular secretion.",2003.0,0,0
343,12464714,Crossover comparison of efficacy and preference for rizatriptan 10 mg versus ergotamine/caffeine in migraine.,Suzanne Christie; Hartmut Göbel; Valentin Mateos; Christopher Allen; France Vrijens; Malathi Shivaprakash; Rizatriptan-Ergotamine/Caffeine Preference Study Group,"Rizatriptan is a selective 5-HT(1B/1D) receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This randomized double- blind crossover outpatient study assessed the preference for 1 rizatriptan 10 mg tablet to 2 ergotamine 1 mg/caffeine 100 mg tablets in 439 patients treating a single migraine attack with each therapy. Of patients expressing a preference (89.1%), more than twice as many preferred rizatriptan to ergotamine/caffeine (69.9 vs. 30.1%, p < or = 0.001). Faster relief of headache was the most important reason for preference, cited by 67.3% of patients preferring rizatriptan and 54.2% of patients who preferred ergotamine/caffeine. The co-primary endpoint of being pain free at 2 h was also in favor of rizatriptan. Forty-nine percent of patients were pain free 2 h after rizatriptan, compared with 24.3% treated with ergotamine/caffeine (p < or = 0.001), rizatriptan being superior within 1 h of treatment. Headache relief at 2 h was 75.9% for rizatriptan and 47.3% for ergotamine/caffeine (p < or = 0.001), with rizatriptan being superior to ergotamine/caffeine within 30 min of dosing. Almost 36% of patients taking rizatriptan were pain free at 2 h and had no recurrence or need for additional medication within 24 h, compared to 20% of patients on ergotamine/caffeine (p < or = 0.001). Rizatriptan was also superior to ergotamine/caffeine in the proportions of patients with no nausea, vomiting, phonophobia or photophobia and for patients with normal function 2 h after drug intake (p < or = 0.001). More patients were (completely, very or somewhat) satisfied 2 h after treatment with rizatriptan (69.8%) than at 2 h after treatment with ergotamine/caffeine (38.6%, p < or = 0.001). Recurrence rates were 31.4% with rizatriptan and 15.3% with ergotamine/caffeine. Both active treatments were well tolerated. The most common adverse events (incidence > or = 5% in one group) after rizatriptan and ergotamine/caffeine, respectively, were dizziness (6.7 and 5.3%), nausea (4.2 and 8.5%) and somnolence (5.5 and 2.3%).",2003.0,1,1
344,12467489,Safety of sumatriptan in pregnancy: a review of the data so far.,Elizabeth Loder,"The high prevalence of migraine in women during their reproductive years means that new drug treatments for migraine, such as the serotonin 5-HT(1B/1D) receptor agonists (the 'triptans'), are likely to be widely used by women of childbearing potential. Scrutiny of these agents in an effort to detect any signal of teratogenicity is thus important. A systematic review of the medical literature was conducted to identify information regarding the safety of sumatriptan during pregnancy. This agent was chosen to be investigated because it has been available for the longest and is the most widely used of the triptan class. Information was obtained regarding the impact of migraine on pregnancy outcome, and data on sumatriptan use in pregnancy were obtained from animal studies, preclinical drug trials, postmarketing surveillance efforts, prospective pregnancy registries, national birth registries and teratogen information services. Synthesis of information from these sources is sufficient to rule out a large increase in birth defects from sumatriptan use during pregnancy and is reassuring for cases where inadvertent exposure to sumatriptan during pregnancy has occurred. However, current information is not sufficient to rule out small increases in the risk for birth defects. For this reason, caution should be exercised in making a positive recommendation for the use of sumatriptan during pregnancy.",2003.0,0,0
345,12469987,Sumatriptan nasal spray for migraine: a review of studies in patients aged 17 years and younger.,M Hämäläinen; M Jones; J Loftus; J Saiers,"This review considers the epidemiology, clinical manifestations and functional consequences of migraine in children and adolescents and surveys the studies establishing the efficacy and tolerability of sumatriptan nasal spray in this patient population. Although therapeutic advances in paediatric and adolescent migraine have lagged behind those in adult migraine, the first systematic studies of migraine medications in young patients have brought about progress in the past five years. These studies show that therapeutic approaches suitable for adult patients are not always applicable to paediatric and adolescent patients. Because of the unique characteristics of paediatric and adolescent migraine, it has been difficult to demonstrate in young patients the efficacy of oral sumatriptan and other triptan tablets, which are the medications of choice for adult migraine. With sumatriptan, this finding has proven to be a consequence of the form in which the drug was administered rather than the inherent properties of the drug. The availability of sumatriptan nasal spray allows the benefits of migraine-specific therapy to be extended to children and adolescents. In both well-controlled, single-episode studies and long-term, multiple-episode studies, sumatriptan nasal spray has been effective and well tolerated for the acute treatment of migraine in children and adolescents. Except for unpleasant taste, which is not significantly distressing to patients, sumatriptan nasal spray has a tolerability profile similar to thatof placebo in young patients.",2003.0,0,0
346,12482222,Triptans for migraine management in adolescents.,Paul Winner,"To review triptan efficacy and tolerability data for adolescent migraine sufferers to assist clinicians in selecting triptans for this age group. Migraine is a common cause of headache among adolescents. To date, no medications, including those with proven headache relief in adults, have been approved for treatment of migraine in adolescents. Recent triptan clinical trials conducted in adolescent migraine sufferers 12 to 17 years of age were reviewed and results were summarized. The success of individual triptan clinical trials conducted in adolescent appears related to time to treatment (1.9 to 6 hours), placebo response (25% to 57%), and day of the week (weekday versus weekend). Overall, triptan tolerability in adolescents is similar to that reported in adults. Study results suggest that the triptan class of antimigraine drugs may effectively alleviate migraine in adolescents. Future research should address placebo response and earlier treatment paradigms.",2003.0,0,0
347,12482223,Comparison of therapeutic gain with therapeutic ratio for the assessment of selective 5HT(1B/1D) agonist efficacy in migraine.,Anthony W Fox; Charlotte Keywood; Fred D Sheftell; Egilius L H Spierings; Paul Winner,"Comparison of use of therapeutic gain (TG) and therapeutic ratio (TR) for relative assessments of selective 5HT(1B/1D) agonist efficacy in the acute treatment of migraine. Comparison of selective 5HT(1B/1D) agonist efficacy in the acute treatment of migraine is complicated by the impracticality of conducting high-quality head-to-head active comparator trials for all permutations of drug, dose, and route of administration; the clinical trials that are available are usually noncontemporaneous, and have fluctuating active and placebo response rates (ARR and PRR, respectively) for the necessarily subjective endpoints. The standard primary endpoint is conversion of headache score 2 (moderate pain) or score 3 (severe pain) into score 0 (no pain) or score 1 (mild pain) at a single timepoint (usually 2 or 4 hours postdose). Two principal methods have been used for comparison of ARR between studies: TG = ARR - PRR and TR = ARR/PRR. Secondary endpoints can be treated in the same way, although the 24-hour remedication rate is the only secondary endpoint that is subject to regulatory authority standardization. Does either TG or TR have an advantage over the other? Efficacy data were collected from published sources and included pain score conversion at 2- and 4-hour, as well as 24-hour remedication rates. TG and TR were calculated for each endpoint, as shown above. The ranges of these variables were found from all observed measures. Correlations between TG and TR were found using least squares methods. The 95% confidence intervals (CI) for TG and TR were then found for all clinical trials, and for the whole range of observed PRR. Values for TR and TG generally were well correlated for pain score conversion at 2 hours postdose (n = 51 clinical trials). Deviations from this correlation were greatest for drugs that were evidently very efficacious. When standardized for the observed ranges of PRR and ARR, the 95% CI for TR were narrower than for TG. A subset of these studies also reported 4-hour data (n = 23 clinical trials), but the correlation between TR and TG was again good, with narrower 95% CI for TR than TG. For the 24-hour remedication data (n = 18 trials), PRR was less variable; TR and TG again correlated well, but there was little difference in their relative 95% CI. For comparison of drugs in noncontemporaneous studies, when PRR fluctuates, relative ranges for TR are narrower than for TG. For assessing single clinical trial results (ie, point estimates of efficacy) TR will generally be relatively nearer to its mean than TG. For both these reasons, TR is a more robust statistic than TG.",2003.0,0,0
348,12484694,,,,,0,0
349,12485208,Naratriptan in the preventive treatment of cluster headache.,L J M M Mulder; E L H Spierings,"We describe the preventive use of naratriptan, mostly as add-on to high-dose verapamil treatment, in nine patients with cluster headache. The addition of the naratriptan further improved the headaches in seven of the nine patients.",2003.0,0,0
350,12498013,Eletriptan Pfizer.,Paul J L M Strijbos; Andrew A Parsons; Anders Fugelli,"Pfizer has developed and launched eletriptan, a 5-HT1B/1D agonist, for the potential treatment of migraine with and without aura. Eletriptan has 6-fold greater affinity for the 5-HT1D receptor than sumatriptan, and a 3-fold greater affinity for the 5-HT1B receptor [249570]. Eletriptan pharmacology has also been evaluated in vitro in comparison with zolmitriptan (AstraZeneca plc) and naratriptan (GlaxoSmithKline plc) [290116].",2003.0,0,0
351,12498015,Frovatriptan Vernalis.,Hermann A M Mucke,"Vanguard (now Vernalis) has developed frovatriptan, a selective 5-HT1B/1D partial agonist licensed from GlaxoSmithKline as a potential treatment for migraine [188478], [194382], [377863].",2003.0,0,0
352,12501881,The pharmacokinetics of sumatriptan when administered with norethindrone 1 mg/ethinyl estradiol 0.035 mg in healthy volunteers.,Katy H P Moore; Scott McNeal; Margaret R Britto; Carole Bye; Mark Sale; Mary S Richardson,"Because the majority of migraineurs are young women in their peak reproductive years, it is important to understand the possible effects on the pharmacokinetics of both medications when sumatriptan is coadministered with an oral contraceptive (OC). The primary objective of this study was to assess the effect of multiple dosing of the OC norethindrone 1 mg/ethinyl estradiol 0.035 mg (NE/EE) on the single-dose pharmacokinetics of sumatriptan in healthy volunteers. Secondary objectives were to determine the effect of a single dose of sumatriptan on the multiple-dose pharmacokinetics of NE and EE, and to assess the safety and tolerability of the combination. This was an open-label, 1-sequence, crossover study in healthy women who had been receiving NE/EE for at least 3 months. Subjects received 1 cycle of NE/EE, consisting of 21 days of OC and 7 days of placebo. They also received a single dose of sumatriptan 50 mg on the last day of the OC or placebo regimen. Blood samples for the determination of plasma sumatriptan concentrations were collected on days 21 and 28, and blood samples for the determination of plasma NE and EE concentrations were collected on days 20 and 21. Treatments were compared by analysis of variance. Equivalence between treatments was to be concluded if the 90% Cl for the ratio of reference to test means for log(e)-transformed parameters (area under the plasma concentration-time curve [AUCI and maximum measured plasma concentration [C(max)]) for each analyte fell within the interval 0.80 to 1.25. Twenty-six women (mean age, 29.8 years; age range, 18-44 years; weight range, 52-82 kg) participated in the study. The 90% CI for the ratio of reference to test means for the AUC extrapolated to infinity (AUC(infinity)) of sumatriptan was 1.11 to 1.22, and the 90% CIs for the AUC over the dosing interval at steady state (AUC(tau)) of NE and EE were 0.96 to 1.00 and 0.91 to 0.97, respectively. The 90% CIs for the ratio of reference to test means for the C(max) of sumatriptan, NE, and EE were a respective 1.05 to 1.30, 0.76 to 0.88, and 0.88 to 1.04. Study treatments were well tolerated. Adverse events were mild or moderate, and there were no clinically significant changes in vital signs or laboratory values. The extent of absorption (AUC) of sumatriptan, NE, and EE was similar after oral administration of sumatriptan and NE/EE, both alone and in combination. Thus, in the opinion of the study investigators, there were no clinically relevant changes in the AUC of any of the medications when sumatriptan and NE/EE were administered concomitantly compared with administration alone. The results of this study suggest that dose adjustment is not necessary when sumatriptan is administered concomitantly with NE/EE in healthy premenopausal women.",2003.0,0,0
353,12503978,Prophylactic treatment of migraine with an angiotensin II receptor blocker: a randomized controlled trial.,Erling Tronvik; Lars J Stovner; Grethe Helde; Trond Sand; Gunnar Bovim,"There is a paucity of effective, well-tolerated drugs available for migraine prophylaxis. To determine whether treatment with the angiotensin II receptor blocker candesartan is effective as a migraine-prophylactic drug. Randomized, double-blind, placebo-controlled crossover study performed in a Norwegian neurological outpatient clinic from January 2001 to February 2002. Sixty patients aged 18 to 65 years with 2 to 6 migraine attacks per month were recruited mainly from newspaper advertisements. A placebo run-in period of 4 weeks was followed by two 12-week treatment periods separated by 4 weeks of placebo washout. Thirty patients were randomly assigned to receive one 16-mg candesartan cilexetil tablet daily in the first treatment period followed by 1 placebo tablet daily in the second period. The remaining 30 received placebo followed by candesartan. The primary end point was number of days with headache; secondary end points included hours with headache, days with migraine, hours with migraine, headache severity index, level of disability, doses of triptans, doses of analgesics, acceptability of treatment, days of sick leave, and quality-of-life variables on the Short Form 36 questionnaire. In a period of 12 weeks, the mean number of days with headache was 18.5 with placebo vs 13.6 with candesartan (P =.001) in the intention-to-treat analysis (n = 57). Some secondary end points also favored candesartan, including hours with headache (139 vs 95; P<.001), days with migraine (12.6 vs 9.0; P<.001), hours with migraine (92.2 vs 59.4; P<.001), headache severity index (293 vs 191; P<.001), level of disability (20.6 vs 14.1; P<.001) and days of sick leave (3.9 vs 1.4; P =.01), although there were no significant differences in health-related quality of life. The number of candesartan responders (reduction of > or =50% compared with placebo) was 18 (31.6%) of 57 for days with headache and 23 (40.4%) of 57 for days with migraine. Adverse events were similar in the 2 periods. In this study, the angiotensin II receptor blocker candesartan provided effective migraine prophylaxis, with a tolerability profile comparable with that of placebo.",2003.0,0,0
354,12525714,Measuring the impact of MS on walking ability: the 12-Item MS Walking Scale (MSWS-12).,J C Hobart; A Riazi; D L Lamping; R Fitzpatrick; A J Thompson,"To develop a patient-based measure of walking ability in MS. Twelve items describing the impact of MS on walking (12-Item MS Walking Scale [MSWS-12]) were generated from 30 patient interviews, expert opinion, and literature review. Preliminary psychometric evaluation (data quality, scaling assumptions, acceptability, reliability, validity) was undertaken in the data generated by 602 people from the MS Society membership database. Further psychometric evaluation (including comprehensive validity assessment, responsiveness, and relative efficiency) was conducted in two hospital-based samples: people with primary progressive MS (PPMS; n = 78) and people with relapses admitted for IV steroid treatment (n = 54). In all samples, missing data were low (< or =3.8%), item test-retest reproducibility was high (> or =0.78), scaling assumptions were satisfied, and reliability was high (> or =0.94). Correlations between the MSWS-12 and other scales were consistent with a priori hypotheses. The MSWS-12 (relative efficiency = 1.0) was more responsive than the Functional Assessment of Multiple Sclerosis mobility scale (0.72), the 36-Item Short Form Health Survey physical functioning scale (0.33), the Expanded Disability Status Scale (0.03), the 25-ft Timed Walk Test (0.44), and Guy's Neurologic Disability Scale lower limb disability item (0.10). The MSWS-12 satisfies standard criteria as a reliable and valid patient-based measure of the impact of MS on walking. In these samples, the MSWS-12 was more responsive than other walking-based scales.",2003.0,0,0
355,12534326,Tolerability of the triptans: clinical implications.,Giuseppe Nappi; Giorgio Sandrini; Grazia Sances,"The triptans represent a relatively new class of compounds effective in the treatment of migraine. The safety and tolerability of these drugs have been extensively investigated since the first triptan (sumatriptan) became commercially available. A report on a very large population of patients tested during clinical trials and in postmarketing studies, confirms that these drugs are safe and well tolerated when correctly used. Adverse events are frequently reported, but are usually mild and only a few patients discontinue therapy because of them. These adverse events include, in particular, the so-called 'triptan symptoms' (tingling, sensation of warmth, etc.). The exact mechanism of chest symptoms reported by 20% of patients with migraine treated with triptans remains unclear, but are exceptionally related to a cardiac mechanism. CNS adverse events (i.e. somnolence) are also reported, but it is a matter of debate whether they are related to the pharmacological properties (i.e. lipophilicity) of the drug or are symptoms of the disease itself. The potential risk for drug overuse must be taken into account when the triptans are given to patients with a high frequency of migraine attacks. Clinical interaction of triptans with other drugs metabolised in the liver may theoretically influence the incidence of adverse events, but there is little evidence to support this assumption. There is no evidence of a teratogenic risk of triptans in pregnant women taking these drugs.",2003.0,1,1
356,12542558,Acupuncture versus placebo versus sumatriptan for early treatment of migraine attacks: a randomized controlled trial.,D Melchart; J Thormaehlen; S Hager; J Liao; K Linde; W Weidenhammer,"To investigate whether acupuncture is superior to placebo and equivalent to sumatriptan for the early treatment of an acute migraine attack. Randomized, partly double-blind (sumatriptan versus placebo) trial. Two hospitals in Germany (one specialized in traditional Chinese medicine and one in the treatment of headache). A total of 179 migraineurs experiencing the first symptoms of a developing migraine attack. Traditional Chinese acupuncture, sumatriptan (6 mg subcutaneously) or placebo injection. Number of patients in whom a full migraine attack (defined as severe migraine headache) within 48 h was prevented. In patients who developed a migraine attack in spite of early treatment, acupuncture and sumatriptan were applied a second time, whilst patients initially randomized to placebo received sumatriptan. A full migraine attack was prevented in 21 of 60 (35%) patients receiving acupuncture, 21 of 58 (36%) patients receiving sumatriptan and 11 of 61 (18%) patients receiving placebo (relative risk of having a full attack 0.79 (95% CI, 0.64-0.99) for acupuncture versus placebo, and 0.78 (95% CI, 0.62-0.98) for sumatriptan versus placebo). Response to the second intervention in patients who developed a full attack was better with sumatriptan (17/31 patients who received sumatriptan twice and 37/46 patients who had had placebo first) than with acupuncture (4/31). The number of patients reporting side-effects was 14 in the acupuncture group, 23 in the sumatriptan group and 10 in the placebo group. In this trial acupuncture and sumatriptan were more effective than a placebo injection in the early treatment of an acute migraine attack. When an attack could not be prevented, sumatriptan was more effective than acupuncture at relieving headache.",2003.0,0,0
357,12547019,Nasal drug delivery: new developments and strategies.,Lisbeth Illum,"The use of the nasal route for the delivery of challenging drugs has created much interest in recent years in the pharmaceutical industry. Consequently, drug delivery companies are actively pursuing the development of novel nasal drug-delivery systems and the exploitation of these for administration of conventional generic drugs and peptides, both in-house and with partners in the pharmaceutical industry. This review sets out to discuss some new developments and strategies in nasal drug delivery. An exiting discovery that drugs can be transported directly from nose to brain via the olfactory pathway is discussed and examples of proof-of-concept in man are given.",2003.0,0,0
358,12558771,"Ergotamine and dihydroergotamine: history, pharmacology, and efficacy.",Stephen D Silberstein; Douglas C McCrory,"Ergotamine and dihydroergotamine share structural similarities with the adrenergic, dopaminergic, and serotonergic neurotransmitters. As a result, they have wide-ranging effects on the physiologic processes that they mediate. Ergotamine and dihydroergotamine are highly potent at the 5-HT1B and 5-HT1D antimigraine receptors and, as a consequence, the plasma concentrations that are necessary to produce the appropriate therapeutic and physiologic effects are very low. The broad spectrum of activity at other monoamine receptors is responsible for their side effect profile (dysphoria, nausea, emesis, unnecessary vascular effects). Both ergotamine and dihydroergotamine have sustained vasoconstrictor actions. In acute migraine treatment, their mechanisms of action involve constricting the pain-producing intracranial extracerebral blood vessels at the 5-HT1B receptors and inhibiting the trigeminal neurotransmission at the peripheral and central 5-HT1D receptors. The scientific evidence for efficacy is stronger for dihydroergotamine than for ergotamine. Their wide use is based on long-term experience.",2003.0,0,0
359,12582449,,,,,0,0
360,12588077,Antidepressants: update on new agents and indications.,Adrienne Z Ables; Otis L Baughman,"A number of antidepressants have emerged in the U.S. market in the past two decades. Selective serotonin reuptake inhibitors have become the drugs of choice in the treatment of depression, and they are also effective in the treatment of obsessive-compulsive disorder, panic disorder, and social phobia. New indications for selective serotonin reuptake inhibitors include post-traumatic stress disorder, premenstrual dysphoric disorder, and generalized anxiety disorder. Extended-release venlafaxine has recently been approved by the U.S. Food and Drug Administration for the treatment of generalized anxiety disorder. Mirtazapine, which is unrelated to the selective serotonin reuptake inhibitors, is unique in its action--stimulating the release of norepinephrine and serotonin. The choice of antidepressant drug depends on the agent's pharmacologic profile, secondary actions, and tolerability. Sexual dysfunction related to the use of antidepressants may be addressed by reducing the dosage, switching to another agent, or adding another drug to overcome the sexual side effects. Augmentation with lithium or triiodothyronine may be useful in patients who are partially or totally resistant to antidepressant treatment. Finally, tapering antidepressant medication may help to avoid discontinuation syndrome or antidepressant withdrawal.",2003.0,0,0
361,12588464,Effect of the 5-HT1 agonist sumatriptan on oesophageal motor pattern in patients with ineffective oesophageal motility.,L Grossi; A F Ciccaglione; L Marzio,"The 5-HT1 agonist sumatriptan (SUM) elicits an increase in amplitude of oesophageal motor waves and of lower oesophageal sphincter (LOS) tone in healthy subjects. The aim of the study was to evaluate whether such an effect occurs also in patients with ineffective oesophageal motility (IOM). 16 patients (nine males and seven females, age range 34-55 years) with chest pain and mild to moderate dysphagia were studied; all had undergone previous cardiologic, radiologic and upper gastrointestinal endoscopic exams that were normal. An oesophageal manometry was performed using an electronic probe to record swallows, oesophageal, LOS and gastric motility. The patients whose motor pattern were compatible with IOM (>30% of motor waves with amplitude <30 mmHg and/or non-transmitted) received SUM or placebo 6 mg s.c., injected in the morning and in the afternoon in a random order. The data analysis was limited to 1 h before and 1 h after the drug injections. Ten out of the 16 patients showed an IOM motor pattern. The administration of SUM caused a significant increase in the number of swallows (SUM 99.5 +/- 15.4 vs 78.6 +/- 16.1 basal, P = 0.03) and of primary oesophageal motor waves (SUM 89.6 +/- 13.4 vs 67.2 +/- 12.9 basal, P = 0.04) with no significant changes in the percentage of swallows associated with propagation. Placebo was not associated with increase in the number of swallows (80.3 +/- 14.6, P = 0.9) or of primary oesophageal motor waves (70.1 +/- 12.3, P = 0.7). The amplitude and the percentage of propagated oesophageal motor waves as well as the mean basal LOS tone were unaltered by SUM. There was no change in the symptoms reported after SUM. Although effective in healthy subjects, SUM 6 mg s.c. improves only the numbers but not the amplitude or propagation of oesophageal motility of patients with IOM. The 5-HT1 pathway and its acute stimulation seem to play only a minor role in the pathogenesis of such a disease.",2003.0,0,0
362,12603635,Migraine preventive medication reduces resource utilization.,Stephen D Silberstein; Paul K Winner; Joseph J Chmiel,"To determine if long-term resource utilization is reduced by adding a preventive medication to a migraine management regimen that already includes acute medication. In 2000, new evidence-based guidelines for the treatment of migraine were released by the US Headache Consortium and the American Academy of Neurology. Although these guidelines emphasize the role of preventive medication in achieving significant clinical improvement, little yet is known concerning the impact of such management on medical and pharmaceutical resources. Methods.-Resource utilization information in a large claims database was analyzed retrospectively. Adding a preventive medication to migraine management reduced the use of other migraine medications, as well as visits to physician offices and emergency departments. In addition, both acute and preventive medications were associated with lower utilization of computed tomography and magnetic resonance imaging scans. Migraine preventive drug therapy is effective in reducing resource consumption when added to therapy consisting only of an acute medication.",2003.0,0,0
363,12603638,"Efficacy, safety, and tolerability of oral eletriptan for treatment of acute migraine: a multicenter, double-blind, placebo-controlled study conducted in the United States.",Fred Sheftell; Robert Ryan; Verne Pitman; Eletriptan Steering Committee,"To investigate the efficacy, consistency, safety, and tolerability of oral eletriptan in the acute treatment of three migraine attacks. Eletriptan is a selective 5-HT1B/1D agonist member of a class of agents known to be effective in the acute treatment of migraine. Thirteen hundred thirty-four patients were randomized to 20 mg, 40 mg, or 80 mg of eletriptan, or placebo and could treat up to three attacks. The primary efficacy endpoint was 2-hour headache response for the first attack. Secondary endpoints included associated symptom relief, and pain-free, sustained pain-free, and consistency of response. Eletriptan 20 mg, 40 mg, and 80 mg achieved significantly (P <.0001) better headache response rates than placebo at 2 hours (47%, 62%, and 59%, respectively, versus 22%) and 4 hours (64%, 76%, and 79%, respectively, versus 25%). Headache response was observed to be rapid, showing improvement at 0.5 hour and 1 hour. Two-hour pain-free response rates for eletriptan 20 mg, 40 mg, and 80 mg were 14%, 27%, and 27%, respectively, compared with 4% for placebo. Sustained pain-free response rates were significantly (P <.001) better for eletriptan 20 mg (10%), 40 mg (20%), and 80 mg (18%) compared with placebo (3%). Eletriptan had a higher consistency of intrapatient response than placebo in two of three (68% to 82%) and three of three attacks (32% to 60%) versus 16% and 8%, respectively. All eletriptan doses yielded significant functional improvement at 2 hours. Adverse events were generally mild or moderate and transient, with eletriptan 20 mg having an adverse event profile comparable to placebo. Eletriptan is efficacious, displaying high consistency of response over multiple attacks, and is well tolerated for the acute treatment of migraine.",2003.0,1,1
364,12603639,Comparative efficacy of eletriptan 40 mg versus sumatriptan 100 mg.,Ninan T Mathew; Jean Schoenen; Paul Winner; Nancy Muirhead; Carolyn R Sikes,"To confirm the efficacy advantage of eletriptan 40 mg over sumatriptan 100 mg. Background.-Eletriptan 80 mg has demonstrated significantly greater efficacy when compared to both sumatriptan 50 mg and 100 mg in two studies. Eletriptan 40 mg demonstrated significantly greater efficacy than sumatriptan 100 mg in one previous trial. Two thousand one hundred thirteen patients with a diagnosis of migraine according to International Headache Society criteria were randomized using a double-blind, double-dummy, parallel-group design, and treated for a single migraine attack with either eletriptan 40 mg, sumatriptan 100 mg, or placebo. The primary endpoint was 2-hour headache response. Secondary endpoints included headache response rates at 1 hour, pain-free rates, absence of associated symptoms, functional response at 1 and 2 hours, and sustained headache response. Headache response rates at 2 hours postdose were significantly higher for eletriptan 40 mg (67%) than for sumatriptan 100 mg (59%; P <.001) and placebo (26%; P <.0001). Eletriptan 40 mg consistently showed significant (P <.01) efficacy over sumatriptan 100 mg across secondary clinical outcomes, including 1-hour headache response; 2-hour pain-free response; absence of nausea, photophobia, and phonophobia; functional improvement; use of rescue medication; treatment acceptability; and sustained headache response (P <.05). Overall, treatment-related adverse events were low, nausea being the only adverse event with an incidence of 2% or higher (4.9% with eletriptan, 4.2% sumatriptan, 2.8% placebo). This trial confirmed that eletriptan 40 mg offers superior efficacy in treating migraine pain and associated symptoms and in restoring patient functioning when compared with sumatriptan 100 mg.",2003.0,1,1
365,12603640,Real-world experiences in migraine therapy with rizatriptan.,Dara Jamieson; F Michael Cutrer; Jerome Goldstein; Jeffrey Dayno; X Henry Hu; USMAP Investigators,"To evaluate the effectiveness of rizatriptan for acute migraine treatment and patient satisfaction with the drug in usual clinical practice settings. Although rizatriptan has been shown to effectively relieve migraine symptoms in clinical trials, we wished to assess its utility in typical patient care settings. Design.-Multicenter, open-label design involving the patients of practicing clinicians. Adult migraineurs treated two migraine attacks with either rizatriptan 10-mg standard tablets or rizatriptan 10-mg orally disintegrating tablets in a crossover manner. Participants had not taken rizatriptan previously and chose which formulation to take first. Patients reported their treatment experiences via an interactive voice response system approximately 24 hours after treatment. Prior migraine treatment experiences were reported by patients on a baseline questionnaire completed at participating clinics. We used conditional logistic regression analysis adjusted for treatment sequences to test the statistical significance of comparisons with results recorded on the baseline questionnaire. Of the 5388 patients enrolled, 3953 (73%) completed at least one follow-up and 3183 (59%) completed two follow-up reports. Patients reported the following outcomes for attacks treated with the rizatriptan tablet and orally disintegrating tablet formulations, respectively, compared with their prior responses to oral usual care medications (P <.05 in all comparisons with baseline data): onset of pain relief within 30 minutes postdose: 18% and 23% versus 16%; no or mild headache 2 hours postdose: 66% and 67% versus 37%; largely symptom-free within 2 hours postdose: 52% and 54% versus 35%; return to usual activities within 2 hours postdose: 50% and 51% versus 31%; and very or somewhat satisfied with treatment: 72% and 74% versus 53%. In this ""real-world"" setting involving a patient population selected by clinicians, rizatriptan appeared to offer better treatment outcomes than those from prior treatments with other oral migraine medications.",2003.0,0,0
366,12603644,Effect of autogenic training on drug consumption in patients with primary headache: an 8-month follow-up study.,Terezia Zsombok; Gabriella Juhasz; Agota Budavari; Jozsef Vitrai; Gyorgy Bagdy,"To examine the effects of Schultz-type autogenic training on headache-related drug consumption and headache frequency in patients with migraine, tension-type, or mixed (migraine plus tension-type) headache over an 8-month period. Behavioral treatments often are used alone or adjunctively for different types of headache. There are, however, only a few studies that have compared the efficacy and durability of the same treatment in different types of primary headache, and the effects of treatment on headache-related drug consumption rarely have been assessed even in these studies. Twenty-five women with primary headache (11 with mixed headache, 8 with migraine, and 6 with tension-type headache) were evaluated via an open-label, self-controlled, 8-month, follow-up study design. After an initial 4 months of observation, patients began learning Schultz-type autogenic training as modified for patients with headache. They practiced autogenic training on a regular basis for 4 months. Based on data from headache diaries and daily medication records, headache frequencies and the amounts of analgesics, ""migraine-specific"" drugs (ergots and triptans), and anxiolytics taken by the patients were compared in the three subgroups over the 8-month period. Results.-From the first month of implementation of autogenic training, headache frequencies were significantly reduced in patients with tension-type and mixed headache. Significant reduction in frequency was achieved in patients with migraine only from the third month of autogenic training. Decreases in headache frequencies were accompanied by decreases in consumption of migraine drugs and analgesics resulting in significant correlations among these parameters. Reduction in consumption of anxiolytic drugs was more rapid and robust in patients with tension-type headache compared to patients with migraine, and this outcome failed to show any correlation with change in headache frequency. Schultz-type autogenic training is an effective therapeutic approach that may lead to a reduction in both headache frequency and the use of headache medication.",2003.0,0,0
367,12631424,Transient minor improvement of high altitude headache by sumatriptan.,Dominik Utiger; Urs Eichenberger; Dirke Bernasch; Ralf W Baumgartner; Peter Bärtsch,"High-altitude headache often fulfills the criteria of migraine. Therefore, we hypothesized that sumatriptan, a 5-HT1 receptor agonist specifically effective for treatment of migraine, would also alleviate high altitude headache. A randomized, placebo-controlled double-blind trial was performed on 29 mountaineers with at least moderate headache on the day of arrival at 4559 m. Fourteen subjects received 100 mg sumatriptan orally and 15 subjects received placebo. Before treatment there were no significant differences between groups regarding rate of ascent, duration and severity of headache, and acute mountain sickness score. All 6 female subjects were randomly assigned to placebo. Absolute values and the reduction of headache scores 1, 3, and 12 h after the administration of sumatriptan did not differ between treatment groups, but headache scores tended to be lower with sumatriptan after 1 or 3 h when compared with placebo. Considering only male mountaineers, there was a significant decrease of headache scores after 1 and 3 h. Because there was only a minor transient amelioration of high altitude headache with sumatriptan, we conclude that 5-HT1 receptors do not play a major role in the pathophysiology of high altitude headache.",2003.0,0,0
368,12636467,Headache assessment and management.,Robert Kaniecki,,2003.0,0,0
369,12637123,An open-label study to assess changes in efficacy and satisfaction with migraine care when patients have access to multiple sumatriptan succinate formulations.,Eric Weidmann; Jeffrey Unger; Stephen Blair; Christopher Friesen; Carolyn Hart; Roger Cady,"Because a patient's migraines often differ in duration, intensity, and accompanying symptoms, as well as the conditions and circumstances at the time of the headache, the mode for treatment also may change. The goal of this study was to determine whether migraine management is improved by providing 3 formulations of sumatriptan succinate to patients, together with education to assist them in selecting the most appropriate formulation for specific attacks. This was an open-label study conducted in 3 family practice settings. Patients were recruited who had at least a 1-year history of migraine meeting International Headache Society criteria and experienced 2 to 6 attacks per month within the previous 3 months. Patients received instructions on oral, intranasal, and subcutaneous (SC) sumatriptan and were provided with all 3 formulations to treat 6 headaches. Migraine features, formulation used, reason for selecting specific formulation, migraine symptom relief, and use of follow-up doses were recorded in diaries. At follow-up, patients completed a questionnaire assessing satisfaction with access to multiple formulations. Of the 33 enrolled patients (26 women, 7 men; mean age, 38.5 years [range, 23-54 years]), 25 (75.8%) completed all visits. Of 149 headaches treated, 39 (26.2%) were mild at onset, 70 (47.0%) were moderate, and 40 (26.8%) were severe. Eighty (53.7%) headaches were treated with tablets, 35 (23.5%) with nasal spray, and 34 (22.8%) with SC injection. Primary reasons for selecting specific formulations included ""fewer side effects"" for tablets, ""convenience"" for nasal spray, and ""quick onset of action"" for SC injection. Twenty-one (84.0%) patients reported being either very satisfied or satisfied with their ability to manage their headaches. Physicians reported that 18 of 24 (75.0%) patients had an improved attitude toward managing their headaches. All formulations were well tolerated. Eight (32.0%) patients reported adverse events, the 2 most common being chest pressure and fatigue. The patients in this study reported greater satisfaction with migraine management when given access to multiple sumatriptan formulations and education regarding their appropriate use.",2003.0,0,0
370,12655411,Post-dural puncture headaches in children. A literature review.,Elke Janssens; Peter Aerssens; Phillipe Alliët; Phillipe Gillis; Marc Raes,"Post-dural puncture headache (PDPH) is a well recognised complication of spinal and epidural anaesthesia. It can also occur after diagnostic or therapeutic lumbar puncture. Few cases have been reported in children. We reviewed the literature regarding definition, aetiology, incidence, risk factors, prevention and treatment, in order to provide some recommendations. Significant factors include age, gender, needle diameter, needle tip design, orientation of the tip during puncture, previous PDPH, history of migraine and repeated attempts to achieve puncture. There is no evidence for the use of increased fluids or bed rest to prevent PDPH. Once the diagnosis is made, conservative therapy is recommended for 48 h. Persistent PDPH can be treated in several ways; an epidural blood patch is one of the most effective methods. occurrence of post-dural puncture headache after lumbar puncture in children is rare. There are conflicting data about risk factors, prevention and treatment.",2003.0,0,0
371,12656709,"Migraine headache recurrence: relationship to clinical, pharmacological, and pharmacokinetic properties of triptans.",Gilles Géraud; Charlotte Keywood; Jean Michel Senard,"Triptan use is associated with headache recurrence, and this has been cited as an important reason for patient dissatisfaction with the treatment. The mechanism by which recurrence occurs is not clear, and the incidence of recurrence varies with the triptan used. In order to explore the pharmacological and physiological interaction of triptans and migraine headache recurrence further, some specific clinical, pharmacological, and pharmacokinetic factors that might influence migraine recurrence were evaluated in a review of the major efficacy data for the drugs in the triptan class. These factors were 5-HT1B and 5-HT1D receptor activities, the pharmacokinetic elimination half-life of each triptan, and the clinical efficacy of each compound, determined by the proportion of patients with headache relief and the therapeutic gain over placebo. Clinical data were derived from 31 triptan, placebo-controlled, major efficacy studies used in a previous meta-analysis. The mean recurrence rate, mean headache response, and therapeutic gain were calculated using the results from the individual clinical studies. Mean headache response and therapeutic gain were calculated at the time point used to define recurrence in each study. Data for binding affinity and potency were taken from a direct-comparison in vitro pharmacology study, and the elimination half-life quoted in the data sheet for each triptan was used. Rank correlation with recurrence rate was performed for each of the test parameters. Mean headache recurrence rates ranged from 17% for frovatriptan 2.5 mg to 40% for rizatriptan. Elimination half-life and recurrence were inversely correlated (r = -1.0, P =.0016). There was also a significant inverse correlation between 5-HT1B receptor potency and recurrence (r = -0.68, P =.034), but 5-HT1D receptor potency was not correlated with recurrence (r = -0.20, P =.54). In addition, the binding affinities for the 5-HT1B and 5-HT1D receptors were not correlated to headache recurrence. Importantly, it also was demonstrated that initial clinical efficacy was not correlated to headache recurrence. The correlation coefficient for headache response was 0.18 (P =.53) and for therapeutic gain, -0.11 (P =.71). The incidence of migraine headache recurrence varies between drugs in the triptan class. Migraine recurrence does not appear to be related to initial clinical efficacy, but is influenced by the pharmacological and pharmacokinetic properties of the individual triptans. The triptans with longer half-lives and greater 5-HT1B receptor potency had the lowest rates of headache recurrence.",2003.0,1,1
372,12656711,Efficacy of sumatriptan nasal spray in recurrent migrainous headache: an open prospective study.,J A Carpay; W H J P Linssen; P J J Koehler; L R Arends; H G M Tiedink,"To evaluate the effectiveness of sumatriptan 20 mg via nasal spray and 100-mg tablets in treating migrainous headache in patients without a concomitant migraine diagnosis. We prospectively investigated the efficacy of sumatriptan 20 mg via nasal spray and 100-mg tablets in patients with a history of at least 5 moderate to severe headache attacks lasting 2 to 72 hours that consistently did not meet the International Headache Society (IHS) criteria for migraine or episodic tension-type headache. Nineteen headache attacks classifiable as migrainous disorder without aura (IHS 1.7) were evaluated in 13 patients using 20-mg sumatriptan nasal spray within a 10-week period. A 2-point decrease in headache severity on a four-point scale was achieved in 74% (95% confidence interval [CI], 50% to 89%) of the attacks within 2 hours. The pain-free incidence (a reduction in headache severity from moderate or severe to none) was 37% (95% CI, 17% to 63%) after 2 hours. Ten patients completed the second part of the study, taking oral sumatriptan for 14 migrainous attacks: a 2-point decrease in headache severity was achieved in 38% (95% CI, 13% to 71%) of the attacks within 2 hours and in 77% (95% CI, 48% to 92%) within 4 hours. This is the first prospective study to show that intranasal or oral sumatriptan may be effective in patients experiencing moderate to severe headache attacks which consistently do not fulfill the IHS criteria for migraine or episodic tension-type headache.",2003.0,0,0
373,12656712,Sumatriptan in migraine with unilateral cranial autonomic symptoms: an open study.,Piero Barbanti; Giovanni Fabbrini; Nicola Vanacore; Marina Pesare; Maria Gabriella Buzzi,"To investigate the response to sumatriptan in migraineurs with unilateral cranial autonomic symptoms such as lacrimation, eye redness, eyelid edema, nasal congestion, and rhinorrhea. Given the potential large-scale recruitment of peripheral neurovascular 5-HT1B/1D receptors consequent to the activation of the trigeminal autonomic reflex in such patients, the presence of unilateral cranial autonomic symptoms may predict a positive response to sumatriptan. Seventy-two consecutive migraineurs with unilateral cranial autonomic symptoms were given sumatriptan 50-mg tablets to treat 1 migraine attack and were asked to record their clinical response to the drug at different time points. End points were pain-relief and pain-free response at 1 and 2 hours. Pain relief was reported by 47 patients (65.3%) at 1 hour and by 59 (81.9%) at 2 hours. Pain-free response was reported by 22 patients (30.6%) at 1 hour and by 44 (61.1%) at 2 hours. Responsiveness to sumatriptan did not correlate with the type or number of unilateral cranial autonomic symptoms, demographic characteristics, prophylactic treatments, use of contraceptives, or concomitant tension-type headache. Migraineurs with unilateral cranial autonomic symptoms seem to respond to sumatriptan better than other migraineurs. The presence of unilateral cranial autonomic symptoms may predict a positive response to the triptans.",2003.0,1,1
374,12665402,Opinion and evidence in neurology and psychiatry.,,,2003.0,0,0
375,12674472,AAFP/ACP-ASIM release guidelines on the management and prevention of migraines.,Barrett M Schroeder; AAFP; ACP-ASIM,,2003.0,0,0
376,12675262,A comparison of familial and sporadic migraine in a headache clinic population.,Innocenzo Rainero; Walter Valfrè; Salvatore Gentile; Rossana Lo Giudice; Margherita Ferrero; Lidia Savi; Lorenzo Pinessi,"We compared the clinical, psychological and pharmacological characteristics of patients with familial migraine and patients with sporadic migraine. Five hundred and thirty consecutive new patients attending our Headache Center over a two-year period were involved in the study. The patients were divided into two groups: A. Familial migraine (famM)--at least one first-degree relative affected; B. Sporadic migraine (spoM)--no first-degree relative affected. Four hundred and twenty-four patients (80%) fulfilled the criteria for famM and 106 (20%) for spoM. The patients with famM showed a significantly (p<0.01) earlier age at onset of the disease. No significant difference in all the remaining features examined was found. Our data suggest that famM and spoM represent a single disease entity.",2003.0,0,0
377,12680880,"Quality, efficacy and safety of complementary medicines: fashions, facts and the future. Part II: Efficacy and safety.",Joanne Barnes,"This is the second of two papers which review issues concerning complementary medicines. The first reviewed the extent of use of complementary medicines, and issues related to the regulation and pharmaceutical quality of these products; the second considers evidence for the efficacy of several well-known complementary medicines, and discusses complementary-medicines pharmacovigilance. The term complementary medicines describes a range of pharmaceutical-type preparations, including herbal medicines, homoeopathic remedies, essential oils and dietary supplements, which mainly sit outside conventional medicine. The use of complementary medicines is a popular healthcare approach in the UK, and there are signs that the use of such products is continuing to increase. Patients and the public use complementary medicines for health maintenance, for the treatment or prevention of minor ailments, and also for serious, chronic illnesses. There is a growing body of evidence from randomized controlled trials and systematic reviews to support the efficacy of certain herbal extracts and dietary supplements in particular conditions. However, many other preparations remain untested. Strictly speaking, evidence of efficacy (and safety) for herbal medicines should be considered to be extract specific. Pharmacovigilance for complementary medicines is in its infancy. Data are lacking in several areas relevant to safety. Standard pharmacovigilance tools have additional limitations when applied to investigating safety concerns with complementary medicines.",2003.0,0,0
378,12682669,The year's new drugs.,Ann I Graul,"The United States was the most active market for new product launches (22 products, 62.5%) in a year that saw 35 new chemical entities and biological drugs and two diagnostic agents reach their first markets. The most active therapeutic groups were anti-infective, oncolytic and metabolic drugs with five launches for each.",2003.0,0,0
379,12684590,Update on the role of drug therapy in non-ulcer dyspepsia.,Nicholas J Talley,"Non-ulcer dyspepsia is common and is often confused with other diagnoses. It remains a condition identified by exclusion, and continues to be a challenge to manage. Currently, only a limited number of pharmacological options are available. Antacids are no more effective than placebo in treating nonulcer dyspepsia. H2-receptor antagonists appear to be superior to placebo in efficacy, but many of the studies suggesting this finding have had a suboptimal study design. Proton pump inhibitors have been shown to be superior to placebo, although questions remain as to whether the only subgroup that responds is comprised of patients with unrecognized gastroesophageal reflux disease. Studies have found that prokinetic agents are superior to placebo, but currently only a very limited number of agents within this class can be prescribed in the United States. Sparse data support the role of metoclopramide and its side effects limit its use even further. The eradication of Helicobacter pylori has a small but positive therapeutic benefit in non-ulcer dyspepsia, and can be considered in those confirmed to be infected. Sucralfate is unlikely to be effective, and misoprostol is ineffective. Bismuth alone is probably not efficacious. Tricyclic antidepressants may have a therapeutic role, but this is not firmly established and this class of medication should be reserved for resistant cases. Emerging therapies include drugs that relax the gastric fundus, such as buspirone or sumatriptan, and the new prokinetic tegaserod. Psychological therapies may play a role but studies of these therapies are limited. Therapy for non-ulcer dyspepsia remains challenging and is usually empiric; it will remain so until the mechanisms that induce symptoms of dyspepsia are better understood.",2003.0,0,0
380,12697002,The triptan formulations : how to match patients and products.,Alan M Rapoport; Stewart J Tepper; Marcelo E Bigal; Fred D Sheftell,"The 5-HT(1B/1D) receptor agonists (the 'triptans') are migraine-specific agents that have revolutionised the treatment of migraine. They are usually the drugs of choice to treat a migraine attack in progress. Different triptans are available in various strengths and formulations, including oral tablets, orally disintegrating tablets, nasal sprays and subcutaneous injections. In Europe, sumatriptan is also available as a suppository. Specific differences among the triptans exist, as evidenced by different pharmacological profiles including half-life, time to peak plasma concentrations, peak plasma concentrations, area under the concentration-time curve, metabolism and drug-drug interaction profiles. How or whether these differences translate to clinical efficacy and tolerability advantages for one agent over another is not well differentiated. However, delivery systems may play an important role in onset of action. Given that the clinical distinctions among these agents are subtle, identification of the most appropriate triptan for an individual patient requires consideration of the specific characteristics of the patient and knowledge of patient preference, an accurate history of the efficacy of previous acute-care medications and individual features of the drug being considered. The selection of an acute antimigraine drug also depends upon the stratification of the patient's migraine attack by peak intensity, time to peak intensity, level of associated symptoms such as nausea and vomiting, time to associated symptoms, comorbid diseases and concomitant treatments that might cause drug-drug interactions. Individual patient response to the triptans seems to be idiosyncratic and possibly genetically determined. Therefore, a set of specific questions can be used to determine whether a currently used triptan is optimally effective, whether the dose needs to be increased or whether another triptan should be tried. The clinician has in his/her armamentarium an ever-expanding variety of triptans, available in multiple formulations and dosages, which have good safety and tolerability profiles. Continued clinical use will yield familiarity with the various triptans, and it should become possible for the interested physician to match individual patient needs with the specific characteristics of a triptan to optimise therapeutic benefit. Use of the methods outlined in this review in choosing a triptan for an individual patient is probably more likely to lead to migraine relief than making an educated guess as to which triptan is most appropriate.",2003.0,0,0
381,12698833,"Backache, headache, and neurologic deficit after regional anesthesia.",Uma Munnur; Maya S Suresh,"Back pain, chemical backache, PDPH, and neurologic deficit all may be reported after regional anesthesia for childbirth. Back pain is common during pregnancy, but epidural analgesia during labor does not increase the incidence of long-term back pain. Chemical backache caused by 2-chloroprocaine is probably a result of hypocalcemic tetany of paraspinous muscles. The mechanism is presumed to be chelation of calcium by sodium bisulfite, an antioxidant present in nesacaine-MPF. PDPH after dural puncture is caused by leakage of CSF, which causes cerebral hypotension. Cerebral hypotension leads to traction on pain-sensitive intracranial structures and cerebral vasodilation. Initial therapy includes hydration, caffeine, and sumatriptan. EBP is the most effective treatment in severe PDPH. If the first EBP fails, a second blood patch can be performed. Neurologic deficits after regional anesthesia are rare. Meticulous technique and vigilance are the keystones in avoiding major neurologic complications of regional anesthesia. Rapid diagnosis and appropriate treatment are essential to optimize a successful outcome if complications do develop.",2003.0,0,0
382,12721393,Hypersensitivity reactions to non-beta-lactam antibiotics.,Stephen A Tilles; Christopher G Slatore,"As alternatives to beta lactam antibiotics continue to be developed, an increasing number of patients are experiencing hypersensitivity reactions to these agents. Unfortunately, unlike penicillin, there are no validated skin testing reagents to aid in confirming the presence of specific IgE antibodies to these drugs. This review summarizes what is known about hypersensitivity reactions to non-beta lactam antibiotics, and includes practical approaches to readministering these drugs in selected situations. Sulfonamides, vancomycin, macrolides, tetracyclines, fluoroquinolones, and anti-virals are included in the discussion.",2003.0,0,0
383,12723463,Interaction between ketoconazole and almotriptan in healthy volunteers.,Joseph C Fleishaker; Beth D Herman; Barbara J Carel; Nkechi E Azie,"The interaction between almotriptan, a 5-HT1B/1D agonist, and the potent CYP3A4 inhibitor ketoconazole was examined in 16 healthy volunteers. Subjects received (A) 12.5 mg almotriptan orally on Day 2 of a 3-day regimen of 400 mg ketoconazole once daily and (B) 12.5 mg almotriptan in a crossover design. Plasma and urine concentrations of almotriptan were measured by HPLC. Treatment effects on almotriptan pharmacokinetics were assessed by analysis of variance. Ketoconazole coadministration increased mean almotriptan AUC and Cmax from 312 to 490 ng h/mL and 52.6 to 84.5 ng/mL, respectively. Mean oral clearance was decreased from 40.7 to 26.2 L/h by ketoconazole, with an accompanying increase in the fraction of almotriptan excreted unchanged in the urine (40.6% to 53.3%) and a decrease in renal clearance (16.4 to 13.8 L/h). These effects were statistically significant. The effects of ketoconazole on almotriptan clearance were consistent with inhibition of the CYP3A4-mediated metabolism and a slight effect on the active tubular secretion of almotriptan.",2003.0,0,0
384,12724434,Serotonin syndrome after single doses of co-amoxiclav during treatment with venlafaxine.,Henry Connor,,2003.0,0,0
385,12739315,Acute and prophylactic management of migraine.,D W Dodick,"Although considerable advances have been made in the understanding and treatment of migraine, uncertainty about the management of this disorder remains. Once a diagnosis is established, an effective treatment plan should be developed that includes education for the patient about migraine and reassurance that the headaches are not caused by structural pathology, stress, or psychopathology. Rapidly effective acute treatment, nonpharmacologic treatment such as behavioral and lifestyle changes, preventive measures, and patient follow-up are other essential elements of migraine management.",2003.0,0,0
386,12739316,Comparative aspects of triptans in treating migraine.,J U Adelman; E J Lewit,"Triptans, beginning with sumatriptan, have revolutionized the treatment of migraine. New triptans in several formulations will soon become available in the United States. Although the similarities of these 5-hydroxytryptamine (5-HT) 1B/1D receptor agonists outweigh their differences, important differences in pharmacokinetics and clinical responses do exist. Subcutaneous sumatriptan has the most rapid onset of action and greatest efficacy but the most adverse effects. Intranasal sumatriptan also has rapid onset of action, but at 2 hours its efficacy is comparable to that of oral zolmitriptan. Of the oral triptans, rizatriptan seems to have the greatest early efficacy. Both rizatriptan and zolmitriptan are now available as rapidly dissolving wafers. Almotriptan, the newest of the triptans, has a response rate similar to that of oral sumatriptan and may produce fewer adverse effects. Naratriptan and frovatriptan, with their slow onset, high tolerability, and long half-lives, may have a role in aborting prolonged migraine attacks and in headache prevention. Eletriptan at higher doses (80 mg) has a response rate approaching that of rizatriptan but may be limited by potential side effects. The many triptans available offer the opportunity to individualize migraine treatment, depending on the patient's attack characteristics, tolerance, and preferences.",2003.0,0,0
387,12749502,A review of the effects of almotriptan and other triptans on clinical trial outcomes that are meaningful to patients with migraine.,Brian E Mondell,"Traditional end points in clinical trials of migraine therapy, such as 2-hour pain response, may not fully address the outcomes patients consider most important: rapid and sustained freedom from pain over 24 hours, and a low, placebo-like incidence of adverse events. A composite efficacy measure such as the sustained pain-free rate (no pain by 2 hours after dosing, no recurrence, no use of rescue medication from 2 to 24 hours after dosing) may be more appropriate. Clinically relevant differences between almotriptan and other triptans were reviewed in the context of the attributes of acute migraine treatment that patients consider most important. This review was based on published reports of open-label and placebo-controlled clinical trials of almotriptan, results of a survey concerning the attributes patients consider most important in a migraine medication, and a published meta-analysis of 53 placebo-controlled clinical trials of triptans involving >24,000 patients. Almotriptan was effective and well tolerated in the placebo-controlled clinical trials; results of the 6- and 12-month open-label studies supported its good tolerability profile. A respective 87% and 86% of respondents to the patient survey indicated that they considered complete freedom from pain and no recurrence among the most important attributes of migraine treatment, both of which are included in the sustained pain-free rate. In the meta-analysis, almotriptan had a favorable efficacy and tolerability profile compared with other triptans, particularly with respect to sustained pain-free rate, which was significantly higher with almotriptan 12.5 mg compared with sumatriptan 100 mg (25.9% vs 20.0%, respectively; P < 0.05). In addition, the placebo-subtracted rate of adverse events was significantly lower with almotriptan compared with sumatriptan (1.8% vs 4.4%, respectively; P < 0.05). Results of a head-to-head placebo-controlled trial of almotriptan 12.5 mg and sumatriptan 100 mg supported the balance of efficacy and tolerability observed for almotriptan in the meta-analysis. Data from clinical trials suggest that almotriptan is effective and well tolerated in the treatment of acute migraine pain. Based on a sustained pain-free rate that is among the highest and an adverse-event rate that is among the lowest for the triptans, almotriptan represents a therapeutic option for the initial treatment of acute migraine with or without aura.",2003.0,1,1
388,12752749,Demographic and migraine characteristics of adolescents with migraine: Glaxo Wellcome clinical trials' database.,P Winner; A D Rothner; D G Putnam; M Asgharnejad,"To describe the demographics and migraine characteristics of patients in the Glaxo Wellcome adolescent clinical trials' database. Data from 8 sumatriptan (tablet and nasal spray) and naratriptan (tablet) trials (6 placebo controlled and 2 open label) were reviewed. Adolescents aged 12 to 17 years who had participated in migraine clinical trials and used at least 1 dose of study medication were summarized using descriptive statistics. Patient demographic (gender, age, race, height, and weight) and migraine (diagnosis, pain location and intensity, time and day of migraine onset and treatment, and associated symptoms) characteristics were examined. One thousand nine hundred thirty-two adolescents with migraine were identified; mean age was 14.1 years (standard deviation, 1.64; range, 11 to 18) and 54% of patients were female. More males were represented in the 12- to 14-year-old group (646 [73%] of 885) than in the 15- to 17-year-old group (234 [26%] of 885). Most patients reported migraine without aura (67%, 1121 of 1672), unilateral migraine pain (58%, 458 of 787), and pulsating pain (74%, 582 of 790). Migraine was aggravated by physical activity in most of the adolescents (88%, 526 of 598). Most migraine attacks (73%, 1363 of 1858) began between 6 am and 6 pm, and proportionately more attacks occurred Monday through Wednesday. Pretreatment vomiting was experienced by 5% (97 of 1830) of patients, nausea by 53% (983 of 1849), and photophobia or phonophobia (or both) by 88% (1628 of 1858) of patients. The incidence of associated symptoms was directly related to pretreatment headache severity. In this large clinical trials' database, adolescents had migraine without aura characterized by unilateral and pulsating pain and aggravated by activity. The incidence of associated symptoms was directly related to pretreatment pain intensity. More migraines occurred Monday through Wednesday during typical school hours. These data may facilitate clinicians' efforts to tailor migraine therapy to the needs of this patient population.",2003.0,0,0
389,12764120,"Conscious expectation and unconscious conditioning in analgesic, motor, and hormonal placebo/nocebo responses.",Fabrizio Benedetti; Antonella Pollo; Leonardo Lopiano; Michele Lanotte; Sergio Vighetti; Innocenzo Rainero,"The placebo and nocebo effect is believed to be mediated by both cognitive and conditioning mechanisms, although little is known about their role in different circumstances. In this study, we first analyzed the effects of opposing verbal suggestions on experimental ischemic arm pain in healthy volunteers and on motor performance in Parkinsonian patients and found that verbally induced expectations of analgesia/hyperalgesia and motor improvement/worsening antagonized completely the effects of a conditioning procedure. We also measured the effects of opposing verbal suggestions on hormonal secretion and found that verbally induced expectations of increase/decrease of growth hormone (GH) and cortisol did not have any effect on the secretion of these hormones. However, if a preconditioning was performed with sumatriptan, a 5-HT(1B/1D) agonist that stimulates GH and inhibits cortisol secretion, a significant increase of GH and decrease of cortisol plasma concentrations were found after placebo administration, although opposite verbal suggestions were given. These findings indicate that verbally induced expectations have no effect on hormonal secretion, whereas they affect pain and motor performance. This suggests that placebo responses are mediated by conditioning when unconscious physiological functions such as hormonal secretion are involved, whereas they are mediated by expectation when conscious physiological processes such as pain and motor performance come into play, even though a conditioning procedure is performed.",2003.0,0,0
390,12783603,Current and potential pharmacological treatments for obsessive-compulsive disorder.,Joyce Davidson; Throstur Bjorgvinsson,"In the past 20 years, several effective treatments have been developed for obsessive-compulsive disorder. Despite this, it is a disorder that is often inadequately treated by available therapies. Recent advances in neuroimaging and neurophysiology have provided some clues to possible treatments that may be more effective in treating this disorder. Serotonin agents remain the cornerstone of pharmacological treatment for obsessive-compulsive disorder. The development of agents that target specific serotonin receptor subtypes may improve the effectiveness of drug treatment. Other possible future treatment approaches are also discussed.",2003.0,0,0
391,12786937,The truth about frovatriptan.,Peer Tfelt-Hansen; Timothy Steiner,,2003.0,0,0
392,12796836,Short latency trigemino-sternocleidomastoid response in patients with migraine.,Raffaele Nardone; Frediano Tezzon,"To investigate the central trigeminal circuits in migraine patients. Short latency responses can be recorded in sternocleidomastoid (SCM) muscles after stimulation of the trigeminal nerve (trigemino-cervical reflex). This brainstem reflex was investigated in 20 healthy subjects, in 20 patients suffering from migraine with aura (MWA) and in 20 patients suffering from migraine without aura (MWOA) during and between the attacks. The trigemino-cervical responses were bilaterally abnormal in 17 patients with MWA and 15 patients with MWOA during the headache attacks, in 11 patients with MWA and in 10 patients with MWOA during the interictal period. In the patients with normal trigemino-cervical responses during the pain-free phase the triptan was significantly more effective at relieving headache. Our findings further support and emphasise the role of the trigeminal system in the pathogenesis of migraine. The bilateral location of the abnormalities suggests a centrally located dysfunction. Therefore, the trigemino-cervical reflex is sensitive in disclosing a disturbed brainstem activity and may be an index of neuronal activity in the human brainstem; moreover their assessment may help as valuable prognostic tool for predicting the efficacy of triptans therapy.",2003.0,0,0
393,12806521,The triptan formulations: a critical evaluation.,Marcelo E Bigal; Carlos A Bordini; Ana L Antoniazzi; José G Speciali,"The migraine-specific triptans have revolutionized the treatment of migraine and are usually the drugs of choice to treat a migraine attack in progress. Different triptans are available in different strengths and formulations including oral tablets, orally disintegrating tablets, nasal sprays and subcutaneous injections. In Europe, sumatriptan is also available as a suppository. Specific differences among the triptans exist as evidenced by different pharmacological profiles including T1/2, Tmax, Cmax, AUC, metabolism, drug-drug interaction profiles, amongst other parameters. How or whether these differences translate to clinical efficacy and tolerability differences is not well differentiated. Clinical distinctions among these agents are subtle and proper choice of triptan requires attention to the specific characteristics of each individual patient, knowledge of patient preference, accurate history of the efficacy of previous acute care medications as well as individual features of the drug being considered. Delivery systems may play an important role in the onset of action of triptans. The selection of an acute antimigraine drug for a patient depends upon the stratification of the patient's migraine attack by peak intensity, time to peak intensity, level of associated symptoms such as nausea and vomiting, time to associated symptoms, comorbid diseases, and concomitant treatments that might cause drug-drug interactions. The clinician has in his armamentarium an ever-expanding variety of medications, available in multiple formulations and dosages, with good safety and tolerability profiles. Continued clinical use will yield familiarity with the various triptans, and it should become possible for the interested physician to match individual patient needs with the specific characteristics of a triptan to optimize therapeutic benefit.",2003.0,0,0
394,12811706,A prospective double-blind study of nasal sumatriptan versus IV ketorolac in migraine.,John T Meredith; Scott Wait; Kori L Brewer,"We conducted a study to compare the efficacy in migraine headache of nasal sumatriptan and intravenous ketorolac. The study was a prospective, double-blind study done with a convenience sample of 29 patients presenting to the emergency department (ED) with acute migraine. Patients received either 20 mg of nasal sumatriptan or 30 mg of intravenous ketorolac. Patients scored the severity of their headache on a 100-mm visual analog scale (VAS) of pain prior to medication, and again 1 hour after medication. Differences between initial and 1-hour scores were analyzed. Before treatment, no difference existed between the groups in the intensity of headache. One hour after medication, the sumatriptan group had a decrease in pain score of 22.937 mm and the ketorolac group a decrease of 71.462 mm on the VAS. The decrease in pain score with ketorolac was significantly greater than that with sumatriptan (P < 0.001). The study therefore showed that both sumatriptan and ketorolac effectively reduced the pain associated with acute migraine headache, but that intravenous ketorolac produced a greater reduction in pain than did nasal sumatriptan.",2003.0,0,0
395,12828501,"Speed of onset and efficacy of zolmitriptan nasal spray in the acute treatment of migraine: a randomised, double-blind, placebo-controlled, dose-ranging study versus zolmitriptan tablet.",Bruce R Charlesworth; Andrew J Dowson; Allan Purdy; Werner J Becker; Steen Boes-Hansen; Markus Färkkilä,"Zolmitriptan oral tablet is highly effective and well tolerated in the acute treatment of migraine with and without aura in adults. A nasal spray formulation has now been developed. The objective of this study was to compare the efficacy and tolerability of fixed doses of zolmitriptan administered via a nasal spray with placebo and zolmitriptan oral tablet in the acute treatment of migraine. This was a randomised, double-blind, double-dummy, placebo-controlled, parallel-group, multicentre, dose-ranging study. 1547 patients aged 18-65 years with an established diagnosis of migraine with or without aura (as defined by International Headache Society criteria) who had at least a 1-year history of migraine and an age of onset <50 years were included. Patients were able to distinguish typical migraine from nonmigraine headaches and had experienced an average of one to six migraine headaches per month during the 2 months preceding the study. Patients were randomised to zolmitriptan (Zomig) The use of tradenames is for product identification purposes only and does not imply endorsement.) nasal spray (5.0, 2.5, 1.0 or 0.5 mg), zolmitriptan oral tablet (2.5mg) or placebo for the treatment of three moderate or severe migraine attacks. The primary outcome measure was headache response at 2 hours following treatment, defined as reduced intensity of migraine pain (using a scale of none, mild, moderate or severe) from severe or moderate at baseline to mild or no pain at 2 hours after treatment. Secondary outcome measures included early headache response at 15, 30 and 45 minutes and headache response at 1 and 4 hours postdose, as well as pain-free rates at 15, 30 and 45 minutes and 1, 2 and 4 hours postdose. Laboratory assessments, vital signs, 12-lead ECGs and nose and throat examinations were performed at screening and follow-up visits. Adverse events were recorded throughout the study using Coding Symbols for Thesaurus of Adverse Reaction Terms (COSTART) terminology. Each dose of zolmitriptan nasal spray produced a greater 2-hour headache response rate than placebo (70.3%, 58.6%, 54.8% and 41.5% for zolmitriptan nasal spray 5.0, 2.5, 1.0 and 0.5mg, compared with 30.6% for placebo [all p < 0.001 vs placebo]). The 2-hour headache response rate for zolmitriptan nasal spray 5.0mg was significantly higher than that of the zolmitriptan 2.5mg oral tablet (61.3%; p < 0.05), while comparisons of nasal spray 0.5, 1.0 and 2.5mg with zolmitriptan 2.5mg oral tablet were not statistically significant. The nasal spray 5.0 and 2.5mg showed a rapid onset of action, with a significant difference in headache response compared with placebo from 15 minutes through 4 hours after administration and a significant difference between the nasal spray 5.0mg and 2.5mg oral tablet from 15 minutes through to 2 hours (the other nasal spray doses were not statistically significant compared with 2.5mg oral tablet). Zolmitriptan nasal spray resulted in pain-free rates that were dose dependent. While all doses from 1.0 mg upwards produced significant pain-free outcomes from 30 minutes versus placebo, only the 5.0mg dose produced pain-free rates significantly superior to both placebo and the 2.5mg oral tablet. Zolmitriptan nasal spray was well tolerated, with the most common adverse events being unusual taste and paresthesia. The majority of adverse events were of short duration and mild or moderate intensity. Only ten patients were withdrawn from the trial because of adverse events. Serious adverse events were reported by nine patients after taking study medication, but none was considered to be causally related to study medication. Zolmitriptan was not associated with any clinically significant changes in laboratory test values or vital signs. All doses of zolmitriptan nasal spray produced significant 2-hour headache response rates compared with placebo. The 5.0 and 2.5mg doses were also significantly more effective than placebo for the majority of secondary efficacy measures. Zolmitriptan nasal spray 5.0mg provided a headache response statistically superior to both placebo and the 2.5mg tablet as early as 15 minutes after administration, while demonstrating pain-free outcomes significantly superior to placebo and the 2.5mg tablet as early as 30 minutes after administration. All doses of zolmitriptan nasal spray were well tolerated, resulting in an optimal therapeutic index and clinical recommendation for the 5.0mg dose.",2003.0,0,0
396,12831340,A review of the clinical efficacy and tolerability of almotriptan in acute migraine.,David W Dodick,"Almotriptan is a serotonin (5-hydroxytryptamine, 5HT)(1B/1D)-receptor agonist approved for the acute treatment of migraine. In 3500 acute migraine patients enrolled in short-term trials and 1500 patients in long-term open-label trials, almotriptan 12.5 mg was effective and well-tolerated. Almotriptan maintains a consistency of response across three attacks and patients continue to respond to almotriptan for up to 1 year. Results from two comparative studies and a meta-analysis of 53 randomised, placebo-controlled studies of oral triptans in > 24,000 patients, confirm that almotriptan 12.5 mg demonstrates comparable efficacy with sumatriptan 50 and 100 mg. The incidence of treatment-related adverse events with almotriptan is comparable to that of placebo and significantly lower than that with sumatriptan. Drug-drug interaction studies indicate that almotriptan may be coadministered with other commonly prescribed drugs without dose modification. Almotriptan can be recommended as first-line treatment for acute migraine.",2003.0,0,0
397,12849329,Sumatriptan versus eletriptan: which is best?,David W Dodick,,2003.0,0,1
398,12856385,Pharmacokinetics of sumatriptan nasal spray in adolescents.,Michael L Christensen; Robin K Mottern; J T Jabbour; Eliane Fuseau,"Sumatriptan is a potent and selective vascular 5-HT1 receptor agonist effective for the treatment of migraine. In adults, intranasal sumatriptan is well absorbed and tolerated. The authors evaluated the pharmacokinetics and tolerability of a single dose of 20 mg intranasal sumatriptan in healthy adolescent migraineurs ages 12 to 17 years, administered outside of migraine attack. Serum sumatriptan levels were measured by high-performance liquid chromatography (HPLC) with electrochemical detection in serial samples collected over 8 hours. Physical exam, vital signs, clinical laboratory tests, and electrocardiogram measurements were monitored to assess safety and tolerability. A total of 16 subjects (10 males and 6 females) had pharmacokinetic data that could be analyzed, 2 withdrew from the study 30 and 60 minutes after dosing following the loss of venous access for blood sampling, and a bioanalysis failure resulted in loss of data from 3 subjects. Noncompartmental pharmacokinetic parameters (geometric mean and 95% confidence interval) for the remaining 16 subjects were as follows: Cmax was 13.9 (11.0, 17.6) ng/mL, AUC infinity was 57.3 (47.6, 69.0) ng/mL.h, and t1/2 was 2.0 (1.8, 2.3) hours. Population pharmacokinetic analysis for all subjects (n = 21) showed that clearance and volume of distribution increase slightly with age and body size, but the changes were minimal and would not warrant dose adjustment: CL/F was 316 L (coefficient of variance [CV] = 25%) and Vd/F was 1070 L (CV = 46%). Sumatriptan was well tolerated with only minor adverse events reported, which all resolved spontaneously. The pharmacokinetic parameters in these adolescent subjects were similar to those previously reported in adults, suggesting that adolescents should be dosed similar to adults.",2003.0,0,0
399,12858070,Update on cluster headache.,Arne May; Massimo Leone,"Although cluster headache has traditionally been thought of as a vascular headache disorder, its periodicity suggests an involvement of central areas such as the hypothalamus. This review covers the past 3 years, which have seen remarkable progress in understanding the pathophysiology of circadian headache syndromes and have brought exciting news. As more cluster headache patients are seen by headache specialists, new forms of this well-defined primary headache syndrome are being identified. In addition, we discuss recent findings with regard to abnormalities in the secretion of hormones, genetic influences, neuroimaging of cluster headache attacks, and the use of newer substances as preventive therapy in cluster headache. We have entered a new diagnostic and therapeutic era in primary headache disorders. In recent reports, the use of deep brain stimulation of the hypothalamus has enabled intractable chronic cluster headache patients to be successfully operated upon. Further research in this field is urgently needed and the recent possibility of combining deep brain stimulation with positron emission tomography will certainly help to unravel the brain circuitry implicated in stimulation-produced analgesia. The time has come to use the evidence for a disorder of circadian rhythm in cluster headache to further the development of chronobiotics in the treatment of this disorder.",2003.0,0,0
400,12858071,The evolving management of migraine.,Avi Ashkenazi; Stephen D Silberstein,"To review recent advances in acute and preventive migraine treatment. The number of migraine drugs continues to expand, allowing for more flexible and tolerable treatment plans. Two new triptans, frovatriptan and eletriptan, and a nasal formulation of zolmitriptan have been recently developed. Eletriptan is effective for acute migraine treatment and may have some pharmacologic and clinical advantages. Frovatriptan has a longer half-life and lower headache recurrence rates compared with other triptans. It may be useful for patients who have prolonged attacks and high headache recurrence rate. Zolmitriptan nasal spray has a rapid onset of action and high efficacy. It should be considered when patients have rapid-onset attacks, especially when associated with severe nausea or vomiting. The butyrophenone neuroleptic droperidol is very effective in aborting acute migraine attacks. Central nervous system side effects are common, however, and the ECG should be monitored. Botulinum toxin type A shows promise as a safe, tolerable and effective drug for migraine prevention, with the unique advantages of almost no systemic adverse events and a long interval between treatments. The anticonvulsant topiramate is effective for migraine prevention. Cognitive side effects are of less concern with the lower doses needed for migraine. The angiotensin converting enzyme receptor blocker candesartan appears to be effective and highly tolerable in the prevention of migraine, but needs to be further evaluated. New drugs expand the spectrum of migraine treatment both for the acute attack and for prevention.",2003.0,0,1
401,12859585,A cost-effectiveness analysis of eletriptan 40 and 80 mg versus sumatriptan 50 and 100 mg in the acute treatment of migraine.,Nicholas Wells; Jayasena Hettiarachchi; Michael Drummond; Mcom DPhil; David Carter; Tamiza Parpia; Francis Pang,"This article explores the application of cost-effectiveness analysis in a comparison of eletriptan and sumatriptan in the acute treatment of migraine. The study employs data from a randomized, double-blind, placebo-controlled clinical trial comparison of oral eletriptan (40 and 80 mg) and oral sumatriptan (50 and 100 mg). Analyses were undertaken using two composite measures of treatment outcome constructed to reflect the requirements of patients more comprehensively than the conventional efficacy indicator of headache response at 2 hours. On the cost side of the equation, reflecting the health-care system perspective of the analysis, drug costs for initial dosing, second dosing for nonresponse, and recurrence and rescue medication were taken into account. The analysis found that eletriptan treatment resulted in lower costs per successfully treated attack than those of sumatriptan under both outcome criteria. Further refinement of outcomes measurement in migraine would be valuable and eletriptan has a potentially important role to play in the cost-effective management of the disorder.",2003.0,0,0
402,12864754,Migraine prevalence and treatment patterns: the global Migraine and Zolmitriptan Evaluation survey.,E Anne MacGregor; Jan Brandes; Astrid Eikermann,"The objectives of the Migraine And Zolmitriptan Evaluation (MAZE) survey were to assess the prevalence of migraine in the general population across 5 different countries, to understand migraineurs' experience of migraine and its management on a global level, and to assess patient perceptions and preferences of current and future treatment formulations. A two-phase, international survey was performed in France, Germany, Italy, the UK, and the USA, and involved a total of 5553 adults. In Phase I, >/=1000 adults from the general population in each country were interviewed by telephone using a routine consumer survey. The proportion of subjects meeting International Headache Society (IHS) criteria for migraine was assessed using an adapted Kiel headache questionnaire, whereas the impact of migraine on daily life was assessed using the Migraine Disability Assessment Scale (MIDAS) questionnaire. In Phase II, >/=100 clinically diagnosed migraineurs per country were recruited through their general practitioners and migraine clinics. Semi-structured interviews based on written questionnaires assessed the impact of, and attitudes toward, migraine and its treatments. Respondents also completed the MIDAS questionnaire. Patients also sampled a demonstrator version of the new orange-flavored orally disintegrating tablet of zolmitriptan. Phase I: An estimated 5% to 12% of the population in the different countries were classified as suffering from migraine, with most attacks categorized as fairly severe to very severe. Between 23% and 42% of migraineurs reported>24 attacks in the previous 12 months. Approximately one-half of all migraineurs did not seek medical advice. Of those who did consult a physician, only 3% to 19% were prescribed triptans. In all countries, the most commonly used current treatment was simple analgesics (22% to 54%). Phase II: Current migraine therapy was consistently effective in only 19% to 31% of patients, and only 21% to 50% of patients were satisfied with their current treatment. Many sufferers supplemented their prescription therapy with alternative management strategies, including herbal and homeopathic remedies, stress management, relaxation therapy, avoidance of trigger factors, and bed rest. Patients indicated that the most important attributes of migraine therapies are high efficacy and rapid pain relief. When asked to identify delivery options that they would like to see more of in the future, most patients (73%) specified ""a dissolve-in-the-mouth tablet."" Ninety percent of patients who sampled the demonstrator version of the zolmitriptan orally disintegrating tablet considered it to be ""very easy"" to use, and 99% stated it was suitable for use ""anytime/anywhere."" In the general population samples we surveyed, there was a 5% to 12% prevalence of migraine across 5 different countries. As reported from previous epidemiologic studies, we found that many migraineurs still do not consult a physician. Despite high levels of disability, as assessed by MIDAS scores and evidenced by the need for bed rest during attacks, many migraineurs continue to treat their headaches with simple analgesics, which, if ineffective, leads to dissatisfaction with treatment. Patients desire a medication with high efficacy and a rapid onset of action, and an orally disintegrating tablet such as that used for the new zolmitriptan formulation, is a favored formulation and route of administration.",2003.0,0,0
403,12864757,"Coprescription of triptans with potentially interacting medications: a cohort study involving 240,268 patients.",Stewart Tepper; Christopher Allen; David Sanders; Alison Greene; Stephen Boccuzzi,"Little information exists about the actual prescription of triptans within large, geographically diverse populations, in terms of demographic characteristics and co-prescriptions with other medications with potential interactions. To investigate the demographic characteristics associated with triptan use, and examine the rate of co-prescription of triptans with specified pharmacologic agents with the potential for drug interactions. This study examined the rate of co-prescription of triptans available in the US up to May 2001 (sumatriptan, naratriptan, rizatriptan, and zolmitriptan) with specified agents with potential for drug interactions. A cohort of 240,268 patients receiving pharmacy benefits from Merck-Medco (N = 65 + M) was followed over a one-year period. This analysis included patients who received at least two triptan prescriptions during the study (6/00-5/01). Ninety-one percent of the cohort remained on the same triptan during the study period. 'Co-prescription' was defined as any fill for a medication that was contraindicated or could potentially adversely interact with a triptan, obtained between and during the first and last triptan fills throughout the study period. Mean patient age was 43 (SD +/- 11.6) and 82% were female. Twenty-one percent were co-prescribed selective serotonin reuptake inhibitors, reflecting the considerable co-morbidity of migraine and depression. Patients taking triptans were almost never co-prescribed monoamine oxidase inhibitors (0.02%), and co-prescription of ergots was also low (1.45%). Less than one percent (0.45%) received cimetidine while taking zolmitriptan, while 2.7% of patients taking rizatriptan 10 mg also took propranolol. While agents unavailable in the U.S. were not evaluated in this cohort, six percent of patients were treated with potent CYP 3A4 inhibitors, which would not be expected to cause any problems with the triptans in the survey. However, such agents are specifically contraindicated for use with one triptan (eletriptan), recently launched in the EU, suggesting that continued vigilance will be necessary to avoid coprescription of medicines with the potential for producing adverse side effects. Triptan use mirrors migraine demographics. The frequency of co-prescription of triptans with SSRIs is about 20%. Continued vigilance will be necessary to avoid co-prescription of medicines with the potential for producing adverse drug events.",2003.0,0,0
404,12864931,Management of menstrual migraine.,Lisa K Mannix,"Migraine is more prevalent in women than men. Hormonal changes can influence the occurrence of migraine, particularly related to the menstrual cycle. Menstrual migraine may require both acute and preventive treatment. Gender differences in migraine may be a result of variations in the central nervous system of men and women as well as the effects of estrogen. Migraine attacks occurring in the perimenstrual period respond well to acute treatment with triptans. Hormonal manipulation may reduce migraine occurrence, especially when related to hormonal fluctuations in the perimenstrual period. Effective migraine management requires an understanding of the unique epidemiologic and pathophysiological factors affecting women. An understanding of associated hormonal influences facilitates development of individualized treatment plans.",2003.0,0,0
405,12890127,Sumatriptan plus metoclopramide in triptan-nonresponsive migraineurs.,Elliott A Schulman; Kathleen F Dermott,"We evaluated the effectiveness of combination treatment using sumatriptan plus metoclopramide versus sumatriptan alone for the treatment of acute migraine. The patients who were treated had failed to respond to triptans in the past despite adequate doses on at least 2 separate trials of the same triptan or 2 trials involving different triptans. There is limited evidence that dopaminergic antagonists may benefit the migraineur by relieving migraine pain and associated symptoms. The exact mechanism of action in migraine is unknown. The postulated action is the inhibition of dopaminergic overactivity. A dopaminergic antagonist, metoclopramide, may improve the efficacy of a 5-HT1B/1D agonist, sumatriptan. In this double-blind, randomized, crossover study, 16 adult migraineurs fulfilling International Headache Society (IHS) criteria for migraine with or without aura who had failed to receive adequate relief from triptans treated one migraine with each treatment: sumatriptan 50 mg plus metoclopramide 10 mg or sumatriptan 50 mg plus placebo to match metoclopramide. Patients treated their migraines when they were moderate or severe in intensity and recorded pain severity and symptoms prior to treatment and 30, 60, 90, and 120 minutes and 24 hours after treatment. Thirteen women and 3 men (mean age, 40 years) completed the study; ie, treated 2 migraines (a total of 32 migraines), one attack with each treatment. Meaningful relief was attained in 10 (63%) of 16 migraines treated with the combination of sumatriptan 50 mg plus metoclopramide 10 mg compared with 5 (31%) of 16 migraines treated with sumatriptan 50 mg plus placebo. Headache response (moderate or severe to mild or no pain at 2 hours) was achieved in 7 (44%) of 16 migraines with the combination of sumatriptan 50 mg plus metoclopramide 10 mg compared with 5 (31%) of 16 migraines treated with sumatriptan 50 mg plus placebo. There did not appear to be a difference between treatment groups with respect to associated symptoms. The combination of sumatriptan 50 mg plus metoclopramide 10 mg was well tolerated. Combining sumatriptan with metoclopramide provided relief in some migraineurs who failed to achieve adequate relief with a triptan alone. It remains unknown whether initiating therapy when pain was mild or using a higher dose of sumatriptan (ie, 100 mg) would have provided additional benefit. Further studies are indicated.",2003.0,0,0
406,12890128,Almotriptan versus rizatriptan in patients with migraine in Spain.,Rogelio Leira; Elena Dualde; Horacio del Barrio; Manuel Machuca; Arturo López-Gil; Spanish Group for the Study of Triptan Consumption in Community Pharmacies,"To compare patient-reported use of rizatriptan 10 mg with that of almotriptan 12.5 mg per migraine attack (24 hours) in a Spanish population. One hundred twenty Spanish community pharmacies recruited patients with migraine to whom they had dispensed almotriptan and rizatriptan. No other selection criteria were used. Patients kept diaries for baseline pain intensity, the number of triptan tablets used, additional medication taken per attack, and their degree of satisfaction with the medication 2 hours after the initial dose. Patients recorded details for a maximum of 3 attacks. Analysis of variance or the Student t test and chi-squared or Fisher exact tests were used for univariate comparisons. A generalized estimating equation method was used to correct for within-subject variability. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. One hundred twenty-six patients (85% women) recorded data for 318 migraine attacks. Rizatriptan was used to treat 122 attacks, almotriptan was used to treat 110 attacks, and a nontriptan medication was used in the initial treatment of 86 attacks. Triptan use (adjusted mean, 95% CI) per attack in this study was lower for rizatriptan (1.19 tablets; 95% CI, 1.06 to 1.32) than for almotriptan (1.43 tablets; 95% CI, 1.30 to 1.56; P=.003). The use of a triptan and additional medication per attack increased with baseline pain severity. Rizatriptan was used to treat more attacks with only one tablet (78%) than almotriptan (58%). Treatment of attacks with almotriptan was more than twice as likely to involve the use of more than one tablet per attack (24 hours) than those treated with rizatriptan (adjusted OR, 2.42; 95% CI, 1.37 to 4.30; P=.003). Patient satisfaction with treatment response at 2 hours was more than 2-fold greater for rizatriptan (85%) than for almotriptan (68%) (adjusted OR, 2.55; 95% CI, 1.11 to 5.87; P=.03). In this prescription-selected Spanish population, a significantly lower number of rizatriptan tablets were required to treat migraine attacks compared with almotriptan. Further, patients were more than twice as likely to use more than one tablet or additional medication (or both) for attacks treated with almotriptan than for those treated with rizatriptan. Although these data suggest that rizatriptan may be a more effective treatment for migraine than almotriptan, further randomized studies are required to confirm this conclusion.",2003.0,0,0
407,12890142,Droperidol and other neuroleptics/antiemetics for the management of migraine.,Randolph W Evans; William B Young,,2003.0,0,0
408,12890143,Therapeutic gain or therapeutic ratio?,Peter J Goadsby; Michel D Ferrari; Richard B Lipton,,2003.0,0,0
409,12906016,"Pain therapeutics-SMi Conference. 11-12 June, 2003, London, UK.",Sarah De la Rue,,2003.0,0,0
410,12912857,Assessment of meal induced gastric accommodation by a satiety drinking test in health and in severe functional dyspepsia.,J Tack; P Caenepeel; H Piessevaux; R Cuomo; J Janssens,"Impaired gastric accommodation is a major pathophysiological mechanism in functional dyspepsia. The aim of the present work was to assess a satiety drinking test in the evaluation of accommodation in health and dyspepsia. Twenty five controls and 37 severely dyspeptic patients seen at a tertiary care centre completed a dyspepsia questionnaire, and gastric emptying and gastric barostat studies. The amount of liquid meal ingested at maximum satiety during a slow satiety drinking test was determined. In controls, we studied the influence of caloric density and of pharmacological agents that influence accommodation. In patients, satiety scores were higher and maximum satiety occurred at lower calories (542 (50) v 1508 (53) kcal; p<0.0001). Six patients had required nutritional support, but excluding these did not alter the correlations. With increasing severity of early satiety, less calories were ingested at maximum satiety. In multivariate analysis, the amount of calories was significantly correlated to accommodation but not to gastric emptying or sensitivity. Sensitivity and specificity of the satiety test in predicting impaired accommodation reached 92% and 86%, respectively. At different caloric densities, ingested volume rather than caloric load determined maximum satiety. Pharmacological agents (sumatriptan, cisapride, erythromycin) affected the satiety test according to their effect on accommodation. A slow caloric drinking test can be used to evaluate accommodation and early satiety. It provides a non-invasive method of predicting impaired accommodation and quantifying pharmacological influences on accommodation.",2003.0,0,0
411,12918889,Establishing principles for migraine management in primary care.,A J Dowson; J Sender; S Lipscombe; R K Cady; S J Tepper; R Smith; T R Smith; F R Taylor; G P Boudreau; N P van Duijn; A C Poole; V Baos; C Wöber,"Published guidelines for the management of migraine in primary care were evaluated by an international advisory board of headache specialists, to establish evidence-based principles of migraine management that could be recommended for international use. Twelve principles of migraine management were identified, covering screening, diagnosis, management and treatments: Almost all headaches are benign/primary and can be managed by all practising clinicians. Use questions/a questionnaire to assess the impact on daily living and everyday activities, for diagnostic screening and to aid management decisions. Share migraine management between the clinician and the patient. Provide individualised care for migraine and encourage patients to manage their migraine. Follow up patients, preferably with migraine calendars or diaries. Regularly re-evaluate the success of therapy using specific outcome measures and monitor the use of acute and prophylactic medications regularly. Adapt migraine management to changes that occur in the illness and its presentation over the years. Provide acute medication to all migraine patients and recommend it is taken at the appropriate time, during the attack. Provide rescue medication/symptomatic treatment for when the initial therapy fails. Offer to prescribe prophylactic medications, as well as lifestyle changes, to patients who have four or more migraine attacks per month or who are resistant to acute medications. Consider concurrent co-morbidities in the choice of appropriate prophylactic medication. Work with the patient to achieve comfort with mutually agreed upon treatment and ensure that it is practical for their lifestyle and headache presentation. Using these principles, practising clinicians can screen and diagnose their headache patients effectively and manage their migraine patients over the long-term natural history of the migraine process. In this way, the majority of migraine patients can be well treated in primary care, ensuring a structured and individualised approach to headache management, and conserving valuable healthcare resources.",2003.0,0,0
412,12921494,Tolerability and consistency of effect of zolmitriptan nasal spray in a long-term migraine treatment trial.,Andrew J Dowson; Bruce R Charlesworth; Allan Purdy; Werner J Becker; Steen Boes-Hansen; Markus Färkkilä,"To primarily assess the tolerability of zolmitriptan (Zomig) nasal spray 5mg in the long-term treatment of migraine, as well as determine efficacy and consistency of effect over time (up to 1 year). This randomised, double-blind-to-dose, parallel-group, multicentre study was designed as a two-phase, crossover trial with a total duration of 1 year. In the pre-crossover phase, 1,093 patients aged 18-65 years with an established diagnosis of migraine with or without aura received intranasal zolmitriptan 5, 2.5, 1 or 0.5mg for the treatment of mild, moderate or severe migraine attacks. When a headache persisted or recurred, a second dose of zolmitriptan nasal spray (or other approved escape medication) was permitted 2 hours post-administration but no later than 24 hours after the first dose. In the post-crossover phase, once a placebo-controlled, dose-finding study had established 5mg as the dose with the optimal clinical utility, all patients were crossed over under blinded conditions to receive this dose. As this was primarily a safety study, the primary endpoints for the study were the incidence and nature of all serious adverse events (at any time before or after administration) and nonserious adverse events (within 24 hours of administration), as well as the incidence of clinically significant abnormalities in either ECG or haematology and clinical chemistry parameters. Nose and throat examinations were performed before and after the study at 30 predetermined trial centres. Other endpoint measures included headache response rate, pain-free assessments, reduction in headache intensity, time to resumption of normal activities and consistency of headache response. Efficacy rates were measured in 90-day intervals up to a period of 360 days. Zolmitriptan nasal spray 5mg was well tolerated, with only 1.9% of patients withdrawing from the 12-month long-term trial because of adverse events. Adverse events occurred in 22.1% of attacks treated with zolmitriptan nasal spray 5mg, and the majority were of short duration and mild or moderate intensity. Serious adverse events occurred in 0.2% of attacks treated with zolmitriptan nasal spray 5mg. There was no evidence of increased incidence of adverse events with increasing duration of treatment. Nasopharyngeal adverse events were reported in 5.5% of attacks treated with zolmitriptan nasal spray 5mg. Again, events were generally transient and of mild intensity. For the 1,093 patients who treated 13,806 attacks during the pre-crossover phase, headache response rates at 2 hours over all attacks were 73.2%, 70.5%, 49.9% and 41.5% for zolmitriptan nasal spray 5, 2.5, 1 and 0.5mg, respectively. Pain-free rates at 2 hours over all attacks were 51.5%, 48.1%, 24.7% and 21.8%, respectively. For the 783 patients receiving the 5mg dose in either the pre- or post-crossover phases, the 2-hour headache response rates were 72.9%, 74.4%, 74.6% and 74.1% for the four 90-day periods between day 0 and day 360. Normal activities were resumed within 2 hours in 60.4% of attacks. Long-term usage of zolmitriptan nasal spray 5mg was also associated with a consistently effective response, with 57.8% of patients experiencing a 2-hour headache response in over 75% of attacks. The majority of patients (70.3%) rated their overall satisfaction with zolmitriptan nasal spray 5mg as good or excellent. Zolmitriptan nasal spray 5mg provides good tolerability and efficacy in long-term use in a clinical setting, with consistently high 2-hour headache and pain-free rates. This combination of benefits translates to high patient satisfaction with this formulation of zolmitriptan.",2003.0,0,0
413,12945540,Eletriptan issues.,Jayasena Hettiarachchi; Carolyn Sikes,,2003.0,0,1
414,12946550,Migraine treatment patterns and patient satisfaction with prior therapy: a substudy of a multicenter trial of rizatriptan effectiveness.,Maria Angeles Ceballos Hernansanz; Rafael Sanchez Roy; Antonio Cano Orgaz; Arturo López-Gil; START 10 Study Group,"Migraine is a common, chronic, often disabling neurologic condition that is underdiagnosed and undertreated. We undertook this questionnaire-based study as a substudy of a multicenter trial of rizatriptan effectiveness. Our goal was to assess the history of acute migraine medication use and the relationship between different migraine medication regimens and patient satisfaction with prior therapy. This study was conducted at 85 neurology clinics throughout Spain from March Lo December 2001. It was planned prospectively as part of the screening visit for a multicenter trial of the effectiveness of rizatriptan therapy for migraine. Male and female patients >/=18 years of age were eligible for the primary trial, and hence for this study, if they had a history of migraine attacks and did not have a contraindication for triptan use. At the screening visit for the primary trial, a questionnaire was used by clinicians to record past and current use, and duration and order of use, of analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), ergot derivatives, and triptans; satisfaction with treatment was scored on a 5-point scale ranging from ""very dissatisfied"" to ""very satisfied."" Of 712 patients completing the questionnaire (mean [SD] age, 34 [10] years; range, 18-69 years), 75% were women and 94% experienced moderate or severe functional disability during migraine attacks. Analgesics were used by the majority of patients (81%) and for the longest mean [SD] duration (8.8 [7.6] years) but were associated with the least satisfaction (10% of patients ""very satisfied"" or ""somewhat satisfied""). Triptans were used by the fewest patients (32%) and for the shortest mean duration (18 [1.6] years) but were associated with the highest rate of satisfaction (66%) compared with NSAIDs (27%) and ergot derivatives (31%). Regardless of duration or order of drug use, or sex or age of the patient, the likelihood of satisfaction with triptans was significantly greater (P < 0.001) than with nontriptan regimens, with an adjusted odds ratio (95% CI) of 16.8 (11.4-24.9) versus analgesics, 5.1 (3.6-7.1) versus NSAIDs, and 4.1 (2.8-6.0) versus ergot derivatives. Our results showed that analgesics, NSAIDs, and ergot derivatives were used for long durations but provided low satisfaction among patients. Triptans were rarely used as a first treatment choice; however, patients reported the highest treatment satisfaction scores after triptan therapy compared with ergot derivatives, NSAIDs, or analgesics.",2003.0,0,0
415,12971707,The effects of exercise and exercise-related changes in blood nitric oxide level on migraine headache.,S Osün Narin; L Pinar; D Erbas; V Oztürk; F Idiman,"To observe the effects of moderate aerobic exercise on migraine headache, to assess exercise-related changes in blood nitric oxide (NO) levels, and to examine the impact of such changes on migraine attacks. Controlled clinical trial. School of Physical Therapy and Rehabilitation. Forty women with general migraine attending the Neurology Department of the Faculty of Medicine Faculty of Dokuz Eylül University. Patients were assigned alternately into two groups: exercise group undertaking 1 hour aerobic exercise three times weekly, and a control group. Patients were assessed before and after treatment using three clinical scales--visual analogue scale for headache, Pain Disability Index and Quality of Life Scale--and chemiluminescence analysis for plasma nitric oxide. After the eight-week therapy period, patient complaints concerning the intensity, frequency and duration of pain had decreased significantly in both groups; however, visual analogue scale scoring showed better pain relief in the exercised group than in the controls (from 8.8 +/- 1.7 to 4.0 +/- 1.4 and from 8.5 +/- 0.8 to 7.0 +/- 0.9 respectively). Quality of life measures also revealed better migraine relief in the exercised women than in those who received medical treatment only. Blood NO rose significantly from pre- to post-therapy in the exercised group, but the change was not significant in the control group. The study showed that regular long-term aerobic exercise reduced migraine pain severity, frequency and duration possibly due to increased nitric oxide production.",2003.0,0,0
416,14521481,Central nervous system abnormalities in migraine.,Dawn A Marcus,"Migraine is associated with structural and functional CNS changes, for example, ictal hyperalgesia and allodynia and interictal neural excitation. Structural abnormalities, most notably white matter changes, occur in greater prevalence in migraineurs (16 - 40%). Several studies have examined the neuropsychological correlates of migraine and/or white matter abnormalities. These studies suggest mild, interictal dysfunction in migraineurs. More research is needed to correlate migraine severity, frequency and/or treatment with neuropsychological testing. Additional studies should: identify interictal cognitive changes; clarify the contribution to long-term cognitive changes from migraine genotype, sequelae of repeated pain episodes or their treatment and the consequences of co-morbid vascular disease; and include cognitive measures as secondary end points in clinical trials.",2003.0,0,0
417,14529055,Patients with migraine prefer zolmitriptan orally disintegrating tablet to sumatriptan conventional oral tablet.,A J Dowson; B R Charlesworth,"The Zolmitriptan Evaluation versus Sumatriptan Trial (ZEST) assessed patient preference for 2.5 mg zolmitriptan orally disintegrating tablet (ODT) or 50 mg sumatriptan conventional tablet in 218 patients with significant migraine disability. Significantly more patients preferred zolmitriptan ODT to sumatriptan conventional tablet (60.1% vs 39.9%; p = 0.0130). In terms of efficacy, significantly more patients considered zolmitriptan ODT to be an effective migraine treatment than sumatriptan conventional tablet (77% vs 63%; p = 0.0063). When asked about specific formulation attributes, significantly more patients selected zolmitriptan ODT as the least disruptive therapy (83.6% vs 16.4%), the easiest to take (85.5% vs 14.5%), the most convenient to take (86.1% vs 13.9%), and the one which enabled them to maintain an active lifestyle (65.5% vs 34.5%), compared with the sumatriptan conventional tablet (all comparisons p < 0.001). Zolmitriptan ODT is a convenient and beneficial alternative to conventional tablets and is preferred to sumatriptan conventional tablets by migraineurs.",2003.0,0,1
418,14530242,Acute migraine treatment guideline.,Catherine Marino,,2003.0,0,0
419,14531480,"Pain-free results with sumatriptan taken at the first sign of migraine pain: 2 randomized, double-blind, placebo-controlled studies.",Paul Winner; Lisa K Mannix; D Gayla Putnam; Scott McNeal; Jackie Kwong; Stephen O'Quinn; Mary S Richardson,"To evaluate the efficacy and tolerability of sumatriptan, 50-mg and 100-mg tablets, compared with placebo for treatment of migraine at the first sign of pain. Two identical multicenter randomized, double-blind, placebo-controlled, single-attack studies were conducted from May through November 2000 in adults (aged 18-65 years). Patients treated migraine at the first sign of pain, while pain was mild, but not more than 2 hours after onset with oral sumatriptan, 50 mg or 100 mg, or matching placebo. The primary end point was pain-free relief at 2 hours after treatment with 50 mg of sumatriptan compared with placebo. There were 354 patients in study 1 and 337 patients in study 2. Significantly more patients treated with sumatriptan, 50 mg and 100 mg, were completely free from pain 2 and 4 hours after treatment vs patients treated with placebo (at 2 hours, 50% and 57% vs 29%; at 4 hours, 61% and 68% vs 30%; for both, P < .001). Also, significantly more patients treated with sumatriptan, 50 mg and 100 mg, were migraine-free (no pain or associated symptoms) vs those treated with placebo at 2 and 4 hours after treatment (at 2 hours, 43% and 49% vs 24%; at 4 hours, 54% and 63% vs 28%; for both, P < .001). The incidence of overall adverse events was low with the 50- and 100-mg dose of sumatriptan (placebo, 7%; sumatriptan at 50 mg, 14%; sumatriptan at 100 mg, 16%). Treatment of migraine at the first sign of pain with sumatriptan, 50-mg and 100-mg tablets, provides superior pain-free relief at 2 and 4 hours after treatment compared with placebo. Results of these studies suggest that sumatriptan at 100 mg may be more efficacious than at 50 mg when used in the early treatment paradigm. Because these studies were not powered to detect statistical differences between active doses, studies to investigate this finding are warranted.",2003.0,0,0
420,14551015,Pain-free efficacy after treatment with sumatriptan in the mild pain phase of menstrually associated migraine.,Robert Nett; Steve Landy; Steve Shackelford; Mary S Richardson; Michael Ames; Michelle Lener,"To estimate the efficacy of sumatriptan 50-mg and 100-mg tablets in menstrually associated migraine when treatment is administered during the mild pain phase. A randomized, double-blind, placebo-controlled, single-attack study was conducted. Menstrually associated migraine was defined as any migraine beginning on or between day -2 and day 4, with day 1 = first day of flow. Patients had at least a 1-year history of migraine as defined by International Headache Society criteria and reported regularly occurring menstrually associated migraines typically having a mild pain phase. Patients treated attacks within 1 hour of the onset of pain but only if the pain was mild at onset and while the pain was still mild. In the 349 women with menstrually associated migraine, sumatriptan was significantly more effective than placebo: 61% and 51% of patients who used sumatriptan 100 mg and 50 mg, respectively, were pain-free 2 hours after treatment compared with 29% of patients who used placebo (P <.001 for both comparisons). At 2 hours, 51% and 45% of patients who used sumatriptan 100 mg and 50 mg were free of pain and associated symptoms (photophobia, phonophobia, nausea, vomiting) compared with 25% of placebo patients (P <.001 for both comparisons). Adverse events were low for sumatriptan 100 and 50 mg, and both doses were generally well tolerated. Sumatriptan 50-mg and 100-mg tablets are generally well tolerated and effective in providing pain-free relief and relief of the associated symptoms of menstrually associated migraine when administered in the mild pain phase.",2003.0,0,0
421,14562585,Cyclic vomiting syndrome: a brain-gut disorder.,B U Li; Larry Misiewicz,"Despite the ""black box"" surrounding CVS, the authors' understanding of this clinical entity has advanced substantially in the last decade as a result of an international interdisciplinary clinical and research effort. Although CVS is now recognized as a unique clinical entity, patients still undergo innumerable hospitalizations and diagnostic tests. Although controlled therapeutic studies are lacking, reasonably effective empiric approaches have been developed by trial and error using anti-migraine, anti-emetic, and anti-epileptic regimens. The ongoing investigations of migraine mechanisms through NMR spectroscopy, mitochondrial DNA mutations and cellular energetics, corticotropin-releasing factor and gastric motility, and brainstem regulation of autonomic function may lead to breakthroughs in the understanding of and new therapies for CVS in the next decade.",2003.0,0,0
422,14613361,Meta-analysis of oral triptan therapy for migraine: number needed to treat and relative cost to achieve relief within 2 hours.,James U Adelman; Jonathan Belsey,"To determine the cost-effectiveness of the 5-HT1B/1D agonists, or triptans, in the acute treatment of migraine. To determine the cost-effectiveness of the triptans, a meta-analysis was conducted of the efficacy data from 27 oral triptan trials, using the endpoint of ""pain-free"" status within 2 hours after initial dosing as the indicator of efficacy. Efficacy data were used to determine the number needed to treat (NNT) to achieve pain-free status in 1 patient within 2 hours postdose and then applied the per-dose costs for each triptan to the NNT values. Rizatriptan 10 mg and almotriptan 12.5 mg were the most cost-effective of the triptans, costing $48.34 and $48.57 US dollars, respectively, to achieve pain-free status in 1 patient within 2 hours postdose. Frovatriptan 2.5 mg was the most costly, with a cost-effective ratio of $162.49 US dollars. All other triptans fell between these extremes: zolmitriptan 5 mg ($65.18 US dollars), sumatriptan 100 mg ($70.83 US dollars), sumatriptan 50 mg ($75.67 US dollars), zolmitriptan 2.5 mg ($78.74 US dollars), and naratriptan 2.5 mg ($141.43 US dollars), in decreasing order of cost-effectiveness. Using an NNT analysis, the least-costly drugs to achieve migraine cure within 2 hours are rizatriptan 10 mg and almotriptan 12.5 mg. From a population health perspective, the lower acquisition cost of almotriptan 12.5 mg allows for effective treatment of more patients than rizatriptan 10 mg for no additional medication cost.",2003.0,0,0
423,14613452,Evaluation of a monthly coverage maximum (drug-specific quantity limit) on the 5-HT1 agonists (triptans) and dihydroergotamine nasal spray.,Lauren Hoffman; George Mayzell; Alex Pedan; Maureen Farrell; Thomas Gilbert,"Ensuring the appropriate use of migraine therapies is an important consideration for care providers, patients, employers, and managed care organizations (MCOs) because of the high cost of treatment for this fairly prevalent disabling disease. A review of utilization of serotonin 5-HT1 receptor agonists (triptans) in an MCO determined that about 24% of the patients who received triptan therapy exceeded the manufacturers. recommendations regarding the maximum daily dose and safe treatment guidelines in a 30-day period. An initiative was designed to manage the coverage of migraine abortive therapies with the anticipated outcome of decreasing potential misuse or overuse of the medications. The objective of this retrospective, observational study was to determine the impact of a monthly drug-specific milligram coverage maximum (quantity limit) on serotonin 5-HT1 receptor agonists (triptans) and dihydroergotamine (DHE) nasal spray on the utilization and costs of migraine care in an MCO with approximately 600000 covered members. A longitudinal, retrospective cohort analysis was conducted. All migraine-related services were analyzed, including outpatient medical visits, emergency department utilization, inpatient hospitalizations, and outpatient prescription drug use. The analysis was conducted using medical and pharmacy administrative claims. Analysis of data was performed for the period 12 months prior (October 1999 to September 2000) and 18 months postimplementation of the monthly drug-specific milligram coverage maximum (October 2000 through March 2002). Imposition of a monthly coverage maximum for migraine-abortive therapies was associated with a 26.1% reduction in overall per- patient-per-month (PPPM) medical costs for migraine care, from US dollars 55.52 PPPM to US dollars 41.02 PPPM (P<0.01). Utilization of serotonin 5-HT1 receptor agonists and DHE nasal spray declined by 16.7%, from 0.18 prescriptions PPPM to 0.15 prescriptions PPPM (P=0.039), and direct drug costs declined by 28.8%, from US dollars 29.18 PPPM to US dollars 20.78 PPPM (P<0.001). Utilization and costs of outpatient and inpatient migraine-related medical services declined by 40% from US dollars 16.58 PPPM in the preperiod to US dollars 9.94 PPPM in the postperiod (P<0.001). A monthly drug-specific milligram coverage maximum was associated with significant reduction in drug costs and utilization of serotonin 5-HT1 receptor agonists (triptans) and DHE nasal spray. Utilization and costs of migraine-related medical services also declined after implementation of the coverage maximum for triptans and DHE nasal spray. The monthly drug-specific milligram coverage maximum appeared to have been successful in managing utilization of triptans and DHE nasal spray, including reduction of overall costs of migraine-related medical services and direct drug costs.",2003.0,0,0
424,14616928,Comparative efficacy of eletriptan vs. naratriptan in the acute treatment of migraine.,G Garcia-Ramos; E A MacGregor; B Hilliard; C A Bordini; J Leston; J Hettiarachchi,"This was a randomized, double-blind study designed to evaluate the comparative efficacy and tolerability of the 40-mg dose of eletriptan and the 2.5-mg dose of naratriptan. Patients (n = 548) meeting International Headache Society (IHS) criteria for migraine were randomized to treat a single migraine attack with either eletriptan 40 mg, naratriptan 2.5 mg, or placebo. Headache response rates at 2 h and 4 h, respectively, were 56% and 80% for eletriptan, 42% and 67% for naratriptan (P < 0.01 for both time-points vs. eletriptan), and 31% and 44% for placebo (P < 0.0001 vs. both active drugs at both time-points). Eletriptan also showed a significantly greater pain-free response at 2 h (35% vs. 18%; P < 0.001) as well as lower use of rescue medication (15% vs. 27%; P < 0.01) and higher sustained headache response at 24 h (38%) compared with naratriptan (27%; P < 0.05) and placebo (19%; P < 0.01). Both eletriptan and naratriptan were well tolerated. The results confirm previous meta-analyses that have suggested the superiority of eletriptan vs. naratriptan in the acute treatment of migraine.",2003.0,1,1
425,7501338,The efficacy and safety of subcutaneous sumatriptan in the acute treatment of menstrual migraine. The Sumatriptan Menstrual Migraine Study Group.,F Facchinetti; G Bonellie; P Kangasniemi; J Pascual; A Shuaib,"To compare the efficacy and safety of subcutaneous sumatriptan with placebo in the treatment of menstrual migraine. A double-blind, placebo-controlled, parallel group study was conducted to assess the efficacy and safety of subcutaneous sumatriptan in the treatment of menstrual migraine over two attacks. A total of 179 subjects received sumatriptan or placebo to treat at least one menstrual migraine attack. The efficacy results were consistent for attacks one and two. Two hours after treatment in attacks one and two, 53 (73%) and 51 (81%) of the sumatriptan-treated subjects, respectively, reported headache relief (reduction of a severe or moderately severe headache to a mild or no headache), compared with 27 (31%) and 18 (29%) of the placebo-treated subjects (P < .001). Within 24 hours of treatment in attack one, 28 (53%) and 14 (52%) of the initial responders to sumatriptan and placebo, respectively, experienced headache recurrence. The incidence and nature of adverse events in this study were similar to that seen in previous studies. Subcutaneous sumatriptan is an effective and well-tolerated acute treatment for menstrual migraine.",1995.0,0,1
426,7515328,Function of the peripheral serotoninergic pathways in migraine: a proposal for an experimental model.,P Martelletti; G Stirparo; C Rinaldi; B M Fusco,We propose a model for assessing the function of 5HT receptors in migraine by evaluating their expression on monocytes by means of double-labeling fluorocytometry (CD14-positive cells FITC-labeled). This model demonstrates that during headache induced in migraine without aura sufferers given isosorbide dinitrate followed by sumatriptan treatment 5HT expression on monocytes progressively increases. This increase may be due to the activation of 5HT turnover and to the increased availability of 5HT displaced by sumatriptan from cerebrovascular receptors during head pain.,1994.0,0,0
427,7516861,Sumatriptan. A reappraisal of its pharmacology and therapeutic efficacy in the acute treatment of migraine and cluster headache.,G L Plosker; D McTavish,"Sumatriptan is a potent and selective agonist at a vascular serotonin1 (5-hydroxytryptamine1; 5-HT1) receptor subtype (similar to 5-HT1D) and is used in acute treatment of migraine and cluster headache. Following administration of sumatriptan 100mg orally, relief of migraine headache (at 2 hours) was achieved in 50 to 67% of patients compared with 10 to 31% with placebo in controlled clinical trials. In a comparative study, oral administration of sumatriptan 100mg consistently achieved significantly greater response rates than a fixed combination of ergotamine 2mg plus caffeine 200mg during 3 consecutive migraine attacks (66 vs 48% for first attack). Oral sumatriptan 100mg was also more effective than aspirin 900mg plus metoclopramide 10mg orally in a similar study. In the majority of controlled clinical trials, headache relief (at 1 hour after administration) was achieved in 70 to 80% of patients with migraine receiving sumatriptan 6mg subcutaneously compared with 18 to 26% of placebo recipients. Approximately 40% of patients who initially responded to oral or subcutaneous sumatriptan experienced recurrence of their headache, usually within 24 hours, but the majority of these patients responded well to a further dose of sumatriptan. Patients with cluster headache were treated for acute attacks with sumatriptan 6mg subcutaneously or placebo in 2 crossover trials. Headache relief was achieved within 15 minutes in 74 and 75% of patients receiving sumatriptan in these studies compared with 26 and 35%, respectively, with placebo. Patients receiving sumatriptan 12mg had a similar response rate as those receiving 6mg, but the higher dose was associated with an increased incidence of adverse events. Based on extensive safety data pooled from controlled clinical trials, sumatriptan is generally well tolerated and most adverse events are transient. The most frequently reported adverse events following oral administration include nausea, vomiting, malaise, fatigue and dizziness. Injection site reactions (minor pain and redness of brief duration) occur in approximately 40% of patients receiving subcutaneous sumatriptan, although the incidence appears to be markedly reduced when patients self-administer the drug with an auto-injector. Chest symptoms (mainly tightness and pressure) occur in 3 to 5% of sumatriptan recipients, but have not been associated with myocardial ischaemia except in a few isolated cases. Sumatriptan is contraindicated in patients with ischaemic heart disease, angina pectoris including Prinzmetal (variant) angina, previous myocardial infarction and uncontrolled hypertension, but is not contraindicated in patients with migraine and asthma. Data from long term studies in acute treatment of migraine and cluster headache suggest that sumatriptan remains effective and well tolerated over several months.(ABSTRACT TRUNCATED AT 400 WORDS)",1994.0,0,0
428,7518321,Human in vivo evidence for trigeminovascular activation in cluster headache. Neuropeptide changes and effects of acute attacks therapies.,P J Goadsby; L Edvinsson,"Cluster headache is a rare very severe disorder that is clinically well characterized with a relatively poorly understood pathophysiology. In this study patients with episodic cluster headache fulfilling the criteria of the International Headache Society were examined during an acute spontaneous attack of headache to determine the local cranial release of neuropeptides. Blood was sampled from the external jugular vein ipsilateral to the pain before and after treatment of the attack. Samples were assayed for calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), substance P and neuropeptide Y. Attacks were treated with either oxygen inhalation, sumatriptan or an opiate. Thirteen patients were studied of whom 10 were male and three female. All had well-established typical attacks of cluster headache when blood was sampled. During the attacks external jugular vein blood levels of CGRP and VIP were raised while there was no change in neuropeptide Y or substance P. Calcitonin gene-related peptide levels rose to 110 +/- 7 pmol/l (normal: < 40) while VIP levels rose to 20 +/- 3 pmol/l (normal: < 7). Treatment with both oxygen and subcutaneous sumatriptan reduced the CGRP level to normal, while opiate administration did not alter the peptide levels. These data demonstrate for the first time in vivo human evidence for activation of the trigeminovascular system and the cranial parasympathetic nervous system in an acute attack of cluster headache. Furthermore, it is shown that both oxygen and sumatriptan abort the attacks and terminate activity in the trigeminovascular system.",1994.0,0,0
429,7540279,Increase in plasma calcitonin gene-related peptide from the extracerebral circulation during nitroglycerin-induced cluster headache attack.,M Fanciullacci; M Alessandri; M Figini; P Geppetti; S Michelacci,"In this study, changes in plasma levels of calcitonin gene-related peptide (CGRP) and substance P (SP) during a spontaneous-like cluster headache attack provoked by nitroglycerin were evaluated. Peptide variations after spontaneous or sumatriptan-induced remission were also assessed. Blood was collected from the external jugular vein homolateral to the pain side of 30 male cluster headache patients; 18 men were in an active and 12 in a remission one. Plasma levels of CGRP and SP were determined using sensitive radioimmunoassays for each peptide. CGRP-like immunoreactivity (CGRP-LI) was found to be augmented in patients in an active period and became elevated further at the peak of the provoked attack. A complete reversal occurred both after spontaneous and sumatriptan-induced remission. On the contrary, nitroglycerin neither provoked a cluster headache attack nor altered CGRP-LI in the patients in a remission period. The augmented levels of CGRP-LI measured before and after nitroglycerin administration, when the provoked attack reached the maximum intensity, suggest an activation of the trigeminovascular system during the active period of cluster headache. Moreover, the clinical and biochemical actions showed by sumatriptan stress the involvement of serotonin in cluster headache mechanisms.",1995.0,0,0
430,7553802,Long-term subcutaneous sumatriptan in cluster headache.,N T Mathew,,1995.0,0,0
431,7553814,Cluster headache attacks treated for up to three months with subcutaneous sumatriptan (6 mg). Sumatriptan Cluster Headache Long-term Study Group.,K Ekbom; A Krabbe; G Micieli; A Prusinski; J A Cole; A J Pilgrim; D Noronha; G ] Micelli G [corrected to Micieli,"In the first three months of a 24-month open study to assess the safety and efficacy of subcutaneous sumatriptan 6 mg in the long-term acute treatment of cluster headache, 138 patients treated a maximum of two attacks daily each with a single 6 mg injection. A total of 6353 attacks were treated. Adverse events, reported in 28% of sumatriptan-treated attacks, were qualitatively similar to those seen in migraine long-term trials. Their incidence did not increase with frequent use of sumatriptan. There were no clinically significant treatment effects on vital signs, ECG recordings or laboratory parameters. Headache relief (a reduction from very severe, severe or moderate pain to mild or no pain) at 15 min was obtained for a median of 96% of attacks treated. There was no indication of tachyphylaxis, decrease in the speed of response, or increased frequency of attacks with long-term treatment. This study demonstrated that, in long-term use, subcutaneous sumatriptan 6 mg is a well-tolerated and effective acute treatment for cluster headache.",1995.0,0,1
432,7564725,The effectiveness of combined oral lysine acetylsalicylate and metoclopramide compared with oral sumatriptan for migraine.,P Tfelt-Hansen; P Henry; L J Mulder; R G Scheldewaert; J Schoenen; G Chazot,"Aspirin is commonly used to treat migraine attacks, although sumatriptan, a much more expensive treatment, is also effective. We compared a combination of lysine acetylsalicylate (equivalent to 900 mg aspirin) and 10 mg metoclopramide (LAS+MTC) with oral sumatriptan (100 mg) and placebo in 421 patients with migraine. LAS+MTC was as effective as sumatriptan with a decrease of headache from severe or moderate to mild or none of 57% and 53%, respectively, for the first migraine attack treated. Both treatments were better than placebo (success rate 24%, p < 0.0001). LAS+MTC was significantly more effective in the treatment of nausea than sumatriptan (p < 0.0001) and was better tolerated (adverse events in 18% and 28%, respectively, p < 0.05). LAS+MTC is as effective as sumatriptan in the treatment of migraine attacks. It is also much cheaper.",1995.0,0,1
433,7579128,Histamine induces migraine via the H1-receptor. Support for the NO hypothesis of migraine.,L H Lassen; L L Thomsen; J Olesen,"In primates, histamine activates cerebral endothelial H1-receptors leading to formation of nitric oxide (NO). Twenty migraine patients received pretreatment with placebo or the histamine-H1-receptor antagonist, mepyramine, in a randomized, double blind fashion, followed in both groups by i.v. histamine (0.5 microgram kg-1 min-1 for 20 min). Headache characteristics were subsequently observed for 12 h. In patients given placebo histamine caused immediate headache during the infusion followed by a delayed migraine attack fulfilling IHS criteria for migraine without aura. The temporal profile of induced headache was exactly the same as after glyceryl trinitrate. Mepyramine pretreatment abolished both immediate headache and delayed migraine attacks. Our results suggest that a migraine attack can be caused by NO formation in the endothelium of cerebral arteries.",1995.0,0,0
434,7583516,"The 21st Meeting of the British Inflammation Research Society, ""Inflammatory pain"", King's College, London, 19th December, 1994.",H Cambridge,,1995.0,0,0
435,7585147,,,,,0,0
436,7585924,Experimental headache in humans.,H K Iversen,"The need for valid human experimental models of headache is obvious. Several compounds have been proposed as headache-inducing agents, but only the nitroglycerin (NTG) model has been validated. In healthy subjects, intravenous infusions of the nitric oxide (NO) donor NTG induce a dose-dependent headache and dilatation of the temporal, radial and middle cerebral artery. NTG-induced headache, although less intense, resembles migraine in pain characteristics, but the accompanying symptoms are rarely present. Cephalic large arteries are dilated during migraine headache as well as during NTG headache. N-acetylcysteine enhances the formation of NO and potentiates NTG-induced headache, whereas mepyramine, a H1-antagonist capable of blocking histamine-induced headache, has no effect. Thus, the headache is dependent on NO or other steps in the NO cascade. The model is useful for pharmacological interventions and sumatriptan reduced the NTG-induced headache. The NTG model may be a valuable tool in the development of future migraine drugs.",1995.0,0,0
437,7585925,Assessment of peripheral vascular effects of antimigraine drugs in humans.,N M van Es; T A Bruning; J Camps; P C Chang; G J Blauw; M D Ferrari; P R Saxena; P A van Zwieten,"The vascular beds of the forearm and finger can be used to study the peripheral effects of antimigraine drugs under normal and pathologic circumstances. We have investigated the novel antimigraine drug sumatriptan, a selective agonist for 5HT1 receptors. Its antimigraine effect may be attributed, at least in part, to constriction of cranial arteriovenous anastomoses (AVAs). In assessing the peripheral vascular effects of sumatriptan we used a forearm and finger blood flow model. Forearm blood flow (FBF) is mainly determined by resistance vessels, whereas finger blood flow (FiBF) mainly involves skin vessels, which contain many AVAs. Changes in FBF and FiBF can be assessed using venous occlusion plethysmography. Changes in AVA flow are determined by measuring the patency of the vascular beds of the forearm and hand to well-defined radiolabelled microspheres, which are injected into the brachial artery. We report the effects of sumatriptan on FBF, FiBF and AVA flow when administered into the brachial artery of healthy volunteers, and discuss the peripheral vascular effects of therapeutic doses of sumatriptan when given subcutaneously in migraine patients during and between attacks.",1995.0,0,0
438,7588137,Efficacy and tolerability of oral sumatriptan in the treatment of acute migraine.,T O Kwasa; J O Jowi; E O Amayo,"An open prospective study of the efficacy and tolerability of oral sumatriptan in the treatment of acute migraine attacks at the Kenyatta National Hospital, Nairobi, Kenya, is presented. Thirty two patients were initially recruited and 24 completed the trial giving a drop-out rate of 25%. The age range was 17 to 55 years with a mean of 35 years. Sumatriptan was found to be effective in 22 (92%) out of 24 patients. Side effects occurred in 38% (9/24) patients. These were mild and transient and included nausea, vomiting, numbness of limbs, fever and a feeling of heat in the head. It is concluded that oral sumatriptan is an effective drug in the treatment of acute migraine headaches. It has few side effects and is well tolerated by majority of patients.",1995.0,0,0
439,7591735,Health-related quality of life in headache research.,R B Lipton; W F Stewart,,1995.0,0,1
440,7601299,High efficacy and low frequency of headache recurrence after oral sumatriptan. The Oral Sumatriptan Italian Study Group.,L A Pini; E Sternieri; L Fabbri; O Zerbini; F Bamfi,"This multicentre, double-blind study compared (100 mg) sumatriptan administered orally with placebo in treating an acute attack of migraine; 238 patients were studied over a 48-h period. Four hours after treatment, 92 of the 142 evaluable sumatriptan patients (65%) showed significant reductions (P < 0.001) in headache severity, clinical disability and accompanying symptoms compared with 32 of the 80 evaluable placebo-treated patients (40%). The duration of attack prior to taking medication and the history of persistent migraine do not influence the observed difference between the two treatment regimens (sumatriptan and placebo), which remained statistically significant (P < 0.001) in both cases. The incidence of headache recurrence in patients who experienced relief 4 h after initial treatment was low, occurring in 16 (17%) and 4 (13%) of the sumatriptan- and placebo-treated patients, respectively. Only patients with a history of migraine attacks lasting longer than 24 h suffered headache recurrences, and these recurrences were not consistent with the International Headache Society definition of migraine. Treatment with sumatriptan was well tolerated.",1995.0,0,1
441,7614531,"Comparison of the economic, clinical, and humanistic attributes of dihydroergotamine and sumatriptan.",C M Kozma; C E Reeder,,1995.0,0,0
442,7635718,Validation of a new quality of life questionnaire for acute migraine headache.,N C Santanello; S L Hartmaier; R S Epstein; S D Silberstein,"A brief migraine-specific quality of life questionnaire was developed to assess the quality of life decrement associated with an acute migraine attack in the 24-hour period following headache onset. The migraine quality of life questionnaire has 15 questions across five domains (work functioning, social functioning, energy, concerns, and symptoms). A prospective, observational study was conducted to evaluate the characteristics of internal consistency, construct and discriminant validity, and responsiveness of the migraine quality of life questionnaire. One hundred thirty-eight subjects with migraine were recruited. One hundred seven subjects completed a baseline and a 24-hour postmigraine quality of life questionnaire, along with a migraine diary for recording headache severity, activity limitation, associated symptoms, duration of headache, and use of migraine medication. All five migraine quality of life questionnaire domains showed good internal consistency (Cronbach's alpha, 0.74-0.95). The strongest correlations were seen between activity limitation and associated symptoms and the migraine quality of life questionnaire work, social, and energy domains. Significant differences in mean questionnaire scores between subjects were found with frequency of medication use, global change in symptoms, headache duration, and severity. All five domains showed significant responses within subjects from a migraine-free period to an acute migraine period (P < 0.0001). In summary, the migraine quality of life questionnaire showed good internal consistency, construct and discriminant validity, and responsiveness to acute migraine attacks.",1995.0,0,0
443,7636454,Patient preferences for migraine therapy: subcutaneous sumatriptan compared with other medications.,R J Luciani; J T Osterhaus; D L Gutterman,"This study was conducted to identify, from the patient's perspective, the important attributes of a migraine therapy and to assess the performance of subcutaneous sumatriptan, aspirin, acetaminophen, and patients' usual therapies with respect to these attributes. Six hundred forty-eight patients who had received subcutaneous sumatriptan (one or two doses, 6 mg per dose, for a single migraine episode) or placebo in a clinical trial completed questionnaires. According to patients, the four most important attributes of a migraine therapy are ""how well it works,"" ""how safe it is,"" ""how fast it works,"" and ""side effects."" The least important attribute is ""cost of drug."" Subcutaneous sumatriptan received significantly more favorable scores than did aspirin, acetaminophen, or patients' usual therapies with respect to the attributes of how well it works, how fast it works, and number of doses needed to relieve pain. Subcutaneous sumatriptan was also rated more favorably than either aspirin or patients' usual therapies with respect to side effects. Acetaminophen and aspirin were rated significantly more favorably than subcutaneous sumatriptan on the attributes ""easy to take"" and ""easy to buy."" Asked which drug they would use again for migraine, more patients selected subcutaneous sumatriptan than any other single medication. More patients also ranked subcutaneous sumatriptan as the best overall performer compared with other migraine medications taken in the last 12 months. These data indicate that according to patients' preferences, subcutaneous sumatriptan possesses many of the attributes of an ideal migraine therapy.",1995.0,0,1
444,7640145,"The effects of oral sumatriptan, a 5-HT1 receptor agonist, on circulating ACTH and cortisol concentrations in man.",S J Entwisle; P A Fowler; M Thomas; D J Eckland; S Lettis; M York; P S Freedman,"1. The effects of oral sumatriptan (50, 100 and 200 mg), a 5-HT1 receptor agonist, and placebo, on circulating adrenocorticotrophic hormone (ACTH) and cortisol concentrations were determined over 24 h after dosing, in 26 healthy male subjects. ACTH was measured by immunoradiometric assay and cortisol by radioimmunoassay. 2. After sumatriptan all subjects displayed a normal diurnal rhythm for circulating ACTH and cortisol compared with placebo. 3. There was a reduction in the trough circulating ACTH concentration over 0-4 h which was 18% with 100 mg (P = 0.002), and 25% with 200 mg (P < 0.001). The 5 h, post-prandial, peak ACTH concentration was reduced by 21% with 100 mg (P = 0.018) and by 20% with 200 mg (P = 0.024). The weighted mean ACTH over 24 h was reduced by 8% with 100 mg (P = 0.029) and by 8% with 200 mg (P = 0.018). The nadir concentration of ACTH over the 24 h and the ACTH concentration 24 h after sumatriptan were not, however, significantly reduced. All results are compared with placebo. 4. There was a reduction in the trough circulating cortisol concentration over 0-4 h which was 15% with 50 mg (P = 0.015), 14% with 100 mg (P = 0.022) and 24% with 200 mg (P < 0.001). The 5 h, post-prandial, peak cortisol concentration was reduced by 16% with 100 mg (P = 0.012) and by 15% with 200 mg (P = 0.017).(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
445,7644049,Oral sumatriptan in preventing headache recurrence after treatment of migraine attacks with subcutaneous sumatriptan.,A M Rapoport; W H Visser; N R Cutler; C J Alderton; L A Paulsgrove; R L Davis; M D Ferrari,"Headache recurrence (HR) may occur within 24 hours in approximately 40% of migraine attacks initially treated successfully with 6 mg subcutaneous (SC) sumatriptan. This may be due to the short plasma half-life of sumatriptan. We studied whether an additional dose of 100 mg oral sumatriptan 4 hours after treatment of a migraine attack with 6 mg SC sumatriptan could prevent HR. Patients (n = 667) treated up to three migraine attacks in a randomized, double-blind, placebo-controlled, parallel-group, multicenter clinical trial. For each attack, they initially took open-label 6 mg SC sumatriptan by autoinjector. Four hours later all patients took either 100 mg oral sumatriptan or matched placebo. Patients could take an additional optional oral dose of 100 mg sumatriptan to treat HR. The primary efficacy end point was the number of successfully treated patients without HR within 24 hours after the initial SC injection for the first study attack. Two hundred twenty-five patients were not assessable for HR, mainly because of protocol violations. Of 442 assessable patients, 82/212 in the sumatriptan-treated group (39%) and 89/230 in the placebo-treated group (39%) reported HR in attack 1. Median times to recurrence were 15.6 hours after sumatriptan and 10.3 hours after placebo (p = 0.006). One hundred mg oral sumatriptan taken 4 hours after 6 mg SC sumatriptan does not prevent HR but significantly delays time to recurrence.",1995.0,0,1
446,7650235,Lack of pharmacokinetic interaction between butorphanol tartrate nasal spray and sumatriptan succinate.,N R Srinivas; W C Shyu; D Upmalis; J S Lee; R H Barbhaiya,"The pharmacokinetics of butorphanol tartrate given in a nasal spray with and without the co-administration of sumatriptan succinate were studied in 24 healthy men and women. In this crossover design study, all subjects received 2 treatments: a single 1-mg dose of butorphanol nasal spray and a 1-mg dose of butorphanol nasal spray plus a single 6-mg subcutaneous (SC) dose of sumatriptan. There was a two-week washout period between sessions. Serial blood samples were collected and plasma samples analyzed using validated radioimmunoassay and high-performance liquid chromatography/electrochemical procedures to determine the concentrations of unchanged butorphanol and sumatriptan, respectively. There were no statistically significant differences for butorphanol between the 2 treatments on any of the following pharmacokinetic parameters: Cmax, tmax, AUC, t1/2, CL/f, and Vz/f. Similarly, the pharmacokinetic parameters obtained for sumatriptan (given with butorphanol nasal spray) were comparable with the literature values obtained for a single 6-mg SC dose of sumatriptan. These data show a lack of pharmacokinetic interaction between butorphanol nasal spray and sumatriptan. Butorphanol nasal spray and sumatriptan were well tolerated. The adverse experience profiles of butorphanol nasal spray were comparable between the treatments, with and without sumatriptan. It can be concluded that regimens of butorphanol nasal spray and sumatriptan need not be changed for either pharmacokinetic or safety considerations when the two compounds are co-administered in treating acute migraine attacks.",1995.0,0,0
447,7652970,"[Sumatriptan treatment of migraine in general practice. A randomized, double-blind, placebo-controlled cross-over study].",M B Russell; O E Holm-Thomsen; M R Nielsen; A Cleal; A J Pilgrim; J Olesen,"Two hundred and thirty migraineurs diagnosed by their general practitioners in accordance with their usual practice were included. The patients treated two migraine attacks at home by subcutaneous injection of sumatriptan or placebo and the alternative medication for the second attack (cross-over). When sumatriptan was compared to placebo, significantly more of the 209 evaluable patients reported headache relief at one hour (56% v 8%, p < 0.001) and two hours (62% v 15%, p < 0.001) after the first injection. Resolution of nausea, photophobia and phonophobia was significantly more common in patients on sumatriptan than on placebo (p < 0.001 for all comparisons). The adverse events were usually transient and of mild or moderate severity, although, three patients withdrew due to adverse events. Ninety-five percent of patients evaluated by a neurological research fellow met the International Headache Society's criteria for migraine. In general practice, sumatriptan taken subcutaneously using an autoinjector at home was an effective and well tolerated acute treatment for migraine.",1995.0,0,0
448,7672873,Upregulated expression of peripheral serotonergic receptors in migraine and cluster headache by sumatriptan.,P Martelletti; G Stirparo; C Rinaldi; M Giacovazzo,"The double-label flow cytometric analysis of peripheral serotonergic pathways of migraine and cluster headache on a monocyte model has been used to evaluate the activity of drugs with a selective activity on central vascular 5-HT1D receptors, such as sumatriptan, ergotamine and ondansetron. The results indicated that sumatriptan and ergotamine progressively increase the peripheral expression of 5-HT (5-hydroxytryptamine, serotonin). The increase obtained in migraine after ergotamine is more evident than that obtained in cases of cluster headache. Ondansetron produced a moderate increase in serotonergic expression only in cluster headache. The events that occur at intracranic neural and vascular level may cause the described changes of 5-HT expression on the monocyte model as an indirect, reflective, peripheral registration of central serotonergic variations during headache attack as well as during the drug-sustained recovery phase.",1994.0,0,0
449,7697683,"A literature review comparing the economic, clinical, and humanistic attributes of dihydroergotamine and sumatriptan.",C M Kozma; R P Mauch; C E Reeder; B J Lawrence,"The value of different pharmaceuticals in treating migraine is frequently based on clinical efficacy only. This article assumes a broader perspective and compares the clinical, economic, and humanistic attributes of two antimigraine medications, dihydroergotamine (DHE) and sumatriptan, based on a literature review. DHE is an established product with over 40 years of use in the treatment of migraine. Sumatriptan is a new product with a higher acquisition cost than DHE. Because sumatriptan costs more than DHE, the question must be asked. ""Does sumatriptan provide advantages that offset this price differential?"" This question reflects the growing concern among payers and patients over the cost and effectiveness of therapies. However, it is not easily answered. Direct comparative data are not available, and data sources are different for the two products. Moreover, the products are currently marketed in different dosage forms--intramuscular for DHE and subcutaneous for sumatriptan. The literature reviewed indicates that the clinical attributes of the two products are similar, with each having slightly different advantages and disadvantages. However, the DHE literature is generally limited to uncontrolled studies, whereas the sumatriptan literature reports the results of rigorously designed, randomized, double-blind, placebo-controlled clinical trials. Published data on the products' economic and humanistic attributes are limited. We concluded that the literature does provide important, albeit limited, data on the economic, clinical, and humanistic attributes of DHE and sumatriptan that permit restricted comparisons. The limitations of the data highlight the need for comparative studies of these products' multidimensional attributes both in controlled clinical trials and under actual practice conditions.",1994.0,0,0
450,7710149,Subcutaneous sumatriptan for treatment of acute migraine in patients admitted to the emergency department: a multicenter study.,B E Akpunonu; A B Mutgi; D J Federman; F G Volinsky; K Brickman; R L Davis; C Gilbert; M Asgharnejad,"To assess the efficacy of SC sumatriptan injection versus placebo in the treatment of acute migraine in ED patients and that of open-label 100 mg sumatriptan PO tablets for recurrent migraine. Randomized, double-blind, placebo-controlled, multi-center trial. Twelve EDs in the United States. Adult patients presenting to the ED from September 1992 through April 1993 with a diagnosis of migraine as determined by International Headache Society criteria. Patients were randomized to receive 6 mg sumatriptan SC or placebo. Patients were monitored for improvement in headache severity using a four-point scale and for time to meaningful relief using a stopwatch. The time to discharge from the ED was recorded. An open-label 100 mg sumatriptan PO tablet was given to all patients on discharge from the ED for use at home if the headache recurred within 24 hours. One hundred thirty-six patients were enrolled. Seventy-five percent of patients treated with sumatriptan achieved meaningful relief compared with 35% treated with placebo (P < .001). The median time to meaningful relief was 34 minutes in the group that received sumatriptan. Seventy percent of patients in the sumatriptan group versus 35% in the placebo group reported mild or no pain at discharge (P < .001). Migraine-associated symptoms such as nausea, photophobia, and phonophobia were significantly reduced in the sumatriptan group (P < .005). The median time to discharge from the ED was shorter for the sumatriptan group than for the placebo group (60 versus 96 minutes, respectively; P = .001). At baseline, 15% of patients in the sumatriptan group and 19% of patients in the placebo group reported mild or no clinical disability. At the time of discharge, patients with mild or no disability increased to 75% in the sumatriptan group compared with 44% in the placebo group (P = .001). Fifty-seven of 92 patients (62%) with mild or no pain at discharge took open-label oral sumatriptan for headache recurrence, and 37 (65%) experienced meaningful relief within 2 hours. Median time to meaningful relief after oral sumatriptan was 65 minutes. Sumatriptan (6 mg SC) is effective in treating acute migraine in the ED. Oral sumatriptan (100 mg) is effective in treating headache recurrence within 24 hours.",1995.0,0,1
451,7710163,Sumatriptan: a clinical standard?,S J Stratton,,1995.0,0,0
452,7712661,Pharmacokinetic considerations in gastrointestinal motor disorders.,G S Hebbard; W M Sun; F Bochner; M Horowitz,"Although it has been recognised that alterations in gastrointestinal motility, whether induced by physiological or pathological processes, have significant effects on the pharmacokinetics of orally administered drugs, this subject has received inappropriately little attention. Studies relating to this topic have focused on healthy volunteers and animals and have largely been confined to the effects of single drug doses. There is limited information about the effects of disease on pharmacokinetics under steady-state conditions. Changes in gastrointestinal motility may affect the pharmacokinetics of orally administered drugs by altering the rate of delivery, bioavailability or mucosal absorption of the drug. In general the rate of absorption and time taken to achieve maximal plasma concentrations for well absorbed drugs may be modified by changes in gastrointestinal motility, but overall bioavailability is not usually affected. In these cases the therapeutic and clinical effects of the alteration in pharmacokinetics will, therefore, depend on which parameters are important for the action of the drug. For poorly absorbed drugs both the rate of absorption and bioavailability are likely to be altered by changes in gastrointestinal motility. However, the complex effects of food and disease, as well as the properties and formulation of any drug (solubility, ease of dispersion, delayed release formulation) often make the prediction of the magnitude, or even the direction, of any effect difficult to predict. Drugs with direct effects on gastrointestinal motility may influence their own patterns of absorption. In patients with gastrointestinal motility disorders, drugs administered in a controlled release formulation, or those with poor bioavailability, are most likely to have a poorly predictable therapeutic effect. Care should be taken to ensure that the formulation of the drug, its timing of administration in relation to meals and the use of coadministered drugs optimise, or at least ensure consistent absorption.",1995.0,0,0
453,7721573,SUNCT syndrome: trials of drugs and anesthetic blockades.,J A Pareja; P Kruszewski; O Sjaastad,"Nine patients with the SUNCT syndrome (Spanish and Norwegian patients) have, over many years, been given several drugs effective in the cluster headache syndrome, trigeminal neuralgia, and other headaches, as well as drugs not previously used in headache. Various cranial nerves were also anesthetized in an endeavor to ameliorate the suffering of those patients. Although a partial effect was obtained with carbamazepine and corticosteroids in some patients, none of the drugs or anesthetic blockades had consistent, lasting, complete effect on headache paroxysms in SUNCT. The essentially negative outcome of this study aids in further characterizing SUNCT as a separate disorder, and, above all, in distinguishing it from trigeminal neuralgia and the cluster headache syndrome.",1995.0,0,0
454,7726901,In the pipeline: a wave of valuable medical technology.,W B Schwartz,"Technologic change has proceeded at a rapid pace during the past twenty years, and advances that are even more remarkable are in sight over the next decade. These changes will be driven largely by advances in molecular and cell biology, imaging techniques, and tissue engineering. Therapies directed toward causes rather than consequences of disease could conceivably produce inexpensive cures and thus slow the rise in medical costs. A more likely scenario envisions a continued rise in costs as advances in technology produce many expensive interventions that extend life but are not curative.",1994.0,0,0
455,7737866,Intranasal lidocaine for cluster headache.,L Robbins,"Thirty male patients with cluster headache were given 4% lidocaine solution to use intranasally as an abortive therapy. Four sprays of lidocaine were used ipsilateral to the pain, and two more were used, if necessary. Twenty-seven percent of the men reported moderate relief, 27% obtained mild relief, and 46% stated that they had no relief from the lidocaine, Side effects were minimal. In this study, intranasal lidocaine was only a marginally helpful therapy for cluster headache. However, because of the ease of administration and lack of side effects, lidocaine may remain worthwhile as an adjunctive medication.",1995.0,0,0
456,7768259,Single dose pharmacokinetics of sumatriptan in healthy volunteers.,L F Lacey; E K Hussey; P A Fowler,"Sumatriptan is classified as a vascular 5HT1 receptor agonist and is effective in the acute treatment of migraine and cluster headache. Sumatriptan is available as an injection for subcutaneous administration and as a tablet for oral administration. The pharmacokinetics of sumatriptan differ depending on the route of administration. The mean subcutaneous bioavailability is 96% compared to 14% for the oral tablet. The lower bioavailability following oral administration is due mainly to presystemic metabolism. The inter-subject variability in plasma sumatriptan concentrations is greater following oral administration and a faster rate of absorption of drug into the systemic circulation is achieved following subcutaneous dosing. The pharmacokinetics of sumatriptan are linear up to a subcutaneous dose of 16 mg. Following oral dosing up to 400 mg, the pharmacokinetics are also linear, with the exception of rate of absorption, as indicated by a dose dependent increase in time to peak concentration. Sumatriptan is a highly cleared compound that is eliminated from the body primarily by metabolism to the pharmacologically inactive indoleacetic acid analogue. Both sumatriptan and its metabolite are excreted in the urine. Although the renal clearance of sumatriptan is only 20% of the total clearance, it exceeds the glomerular filtration rate, indicating that sumatriptan undergoes active renal tubular secretion. Sumatriptan has a large apparent volume of distribution (170 l) and an elimination half-life of 2 h. Oral doses of sumatriptan were administered as a solution of dispersible tablets and subcutaneous dosing was by injection into the arm. In clinical practice, sumatriptan is administered as a film coated tablet or by subcutaneous injection into the thigh.",1995.0,0,0
457,7782393,Case in point. Systemic amyloidosis.,H L Fred,,1995.0,0,0
458,7783861,The use of sumatriptan in patients on monoamine oxidase inhibitors.,S Diamond,,1995.0,0,0
459,7828188,Neuropeptides in migraine and cluster headache.,L Edvinsson; P J Goadsby,"The cerebral circulation is invested by a rich network of neuropeptide Y (NPY) and noradrenaline containing sympathetic nerve fibers in arteries, arterioles and veins. However, the nerve supply of vasoactive intestinal peptide (VIP), substance P (SP) and calcitonin gene-related peptide (CGRP) containing fibers is sparse. While noradrenaline and NPY cause vasoconstriction, VIP, SP and CGRP are potent vasodilators. Stimulation of the trigeminal ganglion in cat and man elicits release of SP and CGRP. Subjects with spontaneous attacks of migraine show release of CGRP in parallel with headache. Cluster headache patients have release of CGRP and VIP during bouts. Treatment with sumatriptan aborts headache in migraine and cluster headache as well as the concomitant peptide release.",1994.0,0,0
460,7828190,"Oral sumatriptan: effect of a second dose, and incidence and treatment of headache recurrences.",M D Ferrari; M H James; D Bates; A Pilgrim; E Ashford; B A Anderson; G Nappi,"Oral sumatriptan in a dose of 100 mg aborts about 60% of migraine attacks within 2 h, but the headache may recur within 24 h. We investigated: (i) the incidence of headache recurrence after oral sumatriptan (ii) whether a second tablet of sumatriptan at 2 h increases initial efficacy and/or (iii) prevents headache recurrence and (iv) whether a further tablet of sumatriptan treats headache recurrence. In a randomized parallel-group clinical trial, 1246 patients treated one to three migraine attacks (with or without aura), with 100 mg oral sumatriptan. Two hours later they all took a double-blind randomized second table of sumatriptan (group I) or placebo (group II). Patients who initially improved, but then experienced headache recurrence took a further double-blind randomized tablet of sumatriptan or placebo. Proportions of patients who improved from moderate/severe headache to mild/none were similar in groups I and III at 2 h (55 vs 56%) and 4 h (80 vs 77%). Incidences of headache recurrence (moderate/severe-any grade of headache) and median times to headache recurrence were also similar: 22-32% at 16 h in group I and 25-33% at 16.5 h in group II. Sumatriptan was superior to placebo in treating headache recurrence: 74 vs 49% (p = 0.017) in group I and 70 vs 30% (p = 0.0001) in group II. Thus, one-fourth of patients experience headache recurrence at about 16 h after successful treatment of a migraine attack with 100 mg oral sumatriptan. A second tablet of sumatriptan at 2 h does not increase initial efficacy and neither prevents nor delays headache recurrence.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,1
461,7828198,Ergotamine-induced headache can be sustained by sumatriptan daily intake.,T Catarci; F Fiacco; C Argentino; G Sette; R Cerbo,We describe the case report of a migraine sufferer who developed ergotamine-induced headache and subsequently replaced ergotamine with daily sumatriptan (100 mg p.o.). The features of the headache were unchanged except for the presence of superimposed migraine-like headaches that occurred every 24 h.,1994.0,0,0
462,7835380,The clinical profile of sumatriptan: efficacy in migraine.,A J Pilgrim,"The efficacy of the 5-HT1 receptor agonist sumatriptan in the acute treatment of migraine has been investigated in an extensive programme of controlled clinical trials. Sumatriptan provided rapid relief from migraine headache with onset of relief occurring within 10 min of a 6 mg subcutaneous injection and within 30 min of a 100 mg oral dose. Maximum benefit was observed by 2 h after the injection and 4 h after the oral dose. Sumatriptan also significantly decreased the incidence of associated migraine symptoms (nausea, photophobia, phonophobia) and the need for rescue medication. Sumatriptan was an effective treatment for migraine with and without aura and when used at any time during the attack. Oral sumatriptan 100 mg provided significantly greater pain relief and had a more rapid onset of action than two commonly used acute treatments for migraine. Efficacy is maintained in long-term use, with no evidence of tachyphylaxis or dependence. Sumatriptan, whether given subcutaneously or orally, is an effective long-term acute treatment for migraine.",1994.0,0,1
463,7835381,The clinical profile of sumatriptan: cluster headache.,P J Goadsby,"Cluster headache is a rare form of severe idiopathic headache characterized by unilateral short-lasting episodes of excruciating pain in association with autonomic disturbances. Subcutaneous sumatriptan has been investigated as an acute treatment for cluster headache in two randomized, double-blind, placebo-controlled, crossover trials. About 75% of patients given subcutaneous sumatriptan 6 mg reported headache relief within 15 min, in comparison with 26-35% given placebo (p < 0.001 in both studies). The need for rescue medication (100% oxygen by inhalation) at 15 min was significantly lower after sumatriptan treatment as were the severity of functional disability and incidence of non-headache symptoms. Results of a long-term study indicate that the tolerability and efficacy of sumatriptan 6 mg is maintained in long-term use, and that there is no evidence of tachyphylaxis.",1994.0,0,1
464,7843948,Sumatriptan in acute migraine using a novel cartridge system self-injector. United Kingdom Study Group.,M L Gross; J Kay; A M Turner; K Hallett; A L Cleal; H Hassani,"This double-blind, randomized, placebo-controlled, parallel-group, multicenter study assessed the efficacy, acceptability, safety, and tolerability of subcutaneous sumatriptan 6 mg administered using a novel cartridge system self-injector for the acute treatment of migraine. Eighty-six patients treated one migraine attack at home with sumatriptan or placebo. A second identical injection was available after 1 hour for inadequate relief or if the headache recurred. Rescue medication was available 1 hour later. The primary end point was headache relief (improvement in headache from moderate or severe to mild or no pain) within 60 minutes of the first injection. Secondary end points included the acceptability of the self-injector, requirement for and efficacy of a second dose, relief of nonheadache symptoms, use of rescue medication, and adverse events. Significantly more patients taking sumatriptan than placebo reported headache relief 1 hour after the first injection (88% vs 11%, P < 0.001). The device was well accepted by patients; about 90% found it easy to use and wanted to take further medication using it. Significantly fewer patients taking sumatriptan than placebo required a second injection (33% vs 92%, P < 0.001) or rescue medication after the second injection (35% vs 67% P < 0.05). Significantly more patients taking sumatriptan than placebo reported headache relief after the second injection (83% vs 32%, P < 0.01), and resolution of nonheadache migraine symptoms (54% vs 23%, P < 0.01). Sumatriptan was generally well tolerated. Subcutaneous sumatriptan 6 mg self-administered using the novel self-injector is an effective, well accepted, and well tolerated acute treatment of migraine.",1994.0,0,1
465,7843952,Treatment of juvenile migraine with subcutaneous sumatriptan.,J T MacDonald,"An open, prospective study was undertaken to assess the efficacy and safety of subcutaneous sumatriptan in 17 children, ages 6 to 16 years, with severe, recurrent migraine. A 6-mg dose was used in 15 patients and relieved headache within 1 hour in six and by 2 hours in five others. Two smaller children received a 3-mg dose and both were headache-free within 2 hours. Most also reported marked improvement in associated symptoms such as nausea and photophobia. Four subjects had no clinical improvement after a 6-mg dose. Side effects, such as neck pressure, were brief and mild. These findings suggest that subcutaneous sumatriptan can be both effective and safe as an abortive agent in juvenile migraine, but the appropriate dose in smaller children will need further investigation.",1994.0,0,0
466,7843955,Alleviation of migraines with therapeutic vitamin D and calcium.,S Thys-Jacobs,Two postmenopausal migraineurs who developed frequent and excruciating migraine headaches (one following estrogen replacement therapy and the other following a stroke) were treated with combination vitamin D and calcium. Therapeutic replacement with vitamin D and calcium resulted in a dramatic reduction in the frequency and duration of their migraine headaches.,1994.0,0,0
467,7848120,Cerebral blood flow during migraine attacks without aura and effect of sumatriptan.,M D Ferrari; J Haan; J A Blokland; J W Arndt; P Minnee; A H Zwinderman; E K Pauwels; P R Saxena,"To study regional cerebral blood flow (rCBF) during migraine attacks without aura and after treatment with sumatriptan. We performed three technetium Tc99m hexemethyl-propyleneamineoxime single photon emission computed tomography scanning procedures in patients with migraine who participated in a double-blind, placebo-controlled, randomized clinical trial (1) outside an attack, (2) during an attack, and (3) after treatment of the attack with 6 mg of subcutaneous sumatriptan. University hospital. We studied 20 patients with migraine without aura, 15 of whom were evaluated under all three conditions and five of whom were evaluated under only two conditions. The single photon emission computed tomographic images were evaluated semiquantitatively with regard to (1) the degree of asymmetry of the rCBF between the headache side and the nonheadache side and (2) the ratio of the rCBF in regions of interest to the rCBF in two reference areas (cerebellum or frontal cortex). We found no significant rCBF asymmetries outside or during the attack or after treatment with sumatriptan, and there were no significant changes of the rCBF ratios during the attack (compared with outside the attack) or after treatment of the attack (compared with during the attack). Migraine attacks without aura and treatment of the attacks with 6 mg of subcutaneous sumatriptan are not associated with detectable focal changes of the rCBF.",1995.0,0,0
468,7851052,Sumatriptan clinical pharmacokinetics.,A K Scott,"Sumatriptan is a novel serotonin 1 (5-hydroxytryptamine 1; 5-HT1)-like agonist which has been shown to be effective in the treatment of acute migraine. Single-dose pharmacokinetic studies reflect the way that sumatriptan will be used in routine practice, but relatively few studies have been published. Bioavailability is high (96%) following subcutaneous injection, but low (14%) following oral administration because of first-pass metabolism. Absorption is rapid after subcutaneous injection, with peak concentration reached in 10 minutes. After oral administration, multiple peak concentrations are observed, but a concentration that is 75% of the final peak concentration is usually reached within 45 minutes. Less than 20% of the drug is protein bound. The volume of distribution is greater than total body water at 170L. Total plasma clearance is rapid, with an elimination half-life of around 2 hours. There is one major metabolite (an indole acetic acid analogue) which is excreted in the urine as the free acid and its ester glucuronide conjugate. The pharmacokinetic profile of sumatriptan is not significantly affected by an acute migraine attack (absorption phase), old age or gender. Pharmacokinetic studies in individuals with hepatic and renal disease have not been published; however, care should be taken when sumatriptan is administered to patients with liver disease until such information is available. No significant interaction was found between sumatriptan and propranolol, flunarizine, pizotifen or alcohol (ethanol).",1994.0,0,0
469,7862876,Neuroendocrine effects of sumatriptan.,J R Herdman; N J Delva; R E Hockney; G M Campling; P J Cowen,"The neuroendocrine effects of the 5-HT receptor agonist, sumatriptan (6 mg subcutaneously), were studied in 11 healthy male subjects using a placebo-controlled, cross-over design. Compared to placebo, sumatriptan significantly lowered levels of plasma prolactin but increased those of plasma growth hormone. There was no effect on plasma cortisol concentrations. The neuroendocrine effects of sumatriptan differ from those of previously described 5-HT-receptor agonists, and may be a consequence of selective activation of 5-HT1D or 5-HT1B receptors. However, the present data cannot exclude the possibility that the neuroendocrine changes reflect nonspecific stress responses or changes in pituitary blood flow.",1994.0,0,0
470,7884208,Emergency pain management: a Canadian Association of Emergency Physicians (CAEP) consensus document.,J Ducharme,"Pain is the most common presenting complaint heard in Emergency Medicine, yet it is poorly controlled. Evaluation of this pain should be with use of objective pain scales completed by the patient, not relying on physician impression. Treatment modalities available in the Emergency Department, a review of medications and their dosing as well as specifics to pediatric pain management are presented. The final section reviews situation or diagnosis specific pain control: headaches, renal colic, polytrauma victims, abdominal pain, soft tissue injury and acute arthritis. These recommendations are based on a Canadian Association of Emergency Physicians (CAEP) consensus conference held in April 1993. The literature was reviewed extensively and used as the basis for the consensus workshops and discussion. At the writing of the consensus paper, however, no specific ideas were borrowed from any one article. The appended bibliography is suggested reading, selected from the larger literature review. There are to date few controlled multi centre trials in overall pain management that would allow guidelines to be produced.",1994.0,0,0
471,7928312,Measuring the functional status and well-being of patients with migraine headache.,J T Osterhaus; R J Townsend; B Gandek; J E Ware,"Compare adult migraineurs' health related quality of life to adults in the general U.S. population reporting no chronic conditions, and to samples of patients with other chronic conditions. Subjects (n = 845) were surveyed 2-6 months after participation in a placebo-controlled clinical trial and asked to complete a questionnaire including the SF-36 Health Survey, a migraine severity measurement scale and demographics. Results were adjusted for severity of illness and comorbidities. Scores were compared with responses to the same survey by the U.S. sample and by patients with other chronic conditions. Response rate was 67%. After adjustment for comorbid conditions, SF-36 scale scores were significantly (P 0.001) lower in migraineurs, relative to age and sex-adjusted norms for the U.S. sample with no chronic conditions. Some health dimensions were more affected by migraine than other chronic conditions, while other dimensions were less affected by migraine. Measures of bodily pain, role disability due to physical health and social functioning discriminated best between migraineurs, the U.S. sample, and patients with other chronic conditions. Patients reporting moderate, severe and very severe migraines scored significantly (P < or = 0.001) lower on five of the eight SF-36 scales than the U.S. sample. Migraine has a unique, significant quality of life burden.",2001.0,0,0
472,7928317,Abortive migraine therapy in the office with dexamethasone and prochlorperazine.,H A Saadah,"Corticosteroids are commonly used in the abortive therapy of status migrainosus. However, this practice is based more on clinical experience than on published data. At my office, over a period of two years, 108 patients (156 migraine episodes) were treated with intravenous dexamethasone. Most of these patients had prolonged migraines that had resisted other forms of abortive therapy. The first 22 patients (32 migraine episodes) were given 10 mg of dexamethasone over 5 minutes, the next 39 patients (55 migraine episodes) were given 20 mg over 10 minutes, and the last 47 patients (69 migraine episodes) were given 3.5 mg of prochlorperazine over 5 minutes followed by 20 mg of dexamethasone over 10 minutes. Adverse effects were minor and patients with episodic migraines responded more favorably than those with intractable migraines. In the episodic migraine groups, response rates ranged from 80-89%, relapse rates from 29-35%, and remission rates from 57-83%. After the intravenous injections, repetitive oral abortive therapy was often required to treat relapses and secure remission. Adding 3.5 mg of prochlorperazine to 20 mg of intravenous dexamethasone significantly shortened the response time.",1994.0,0,0
473,7928323,Joint 1994 Wolff Award Presentation. Peripheral and central trigeminovascular activation in cat is blocked by the serotonin (5HT)-1D receptor agonist 311C90.,P J Goadsby; L Edvinsson,"Migraine headache involves the activation of trigeminal afferents that are predominantly found in the first or ophthalmic division of the nerve. The headache is often pounding and the connections of the trigeminal nerve, the trigeminovascular system, have therefore been implicated in the pathophysiology of migraine and studied extensively. Considerable attention has been given to the peripheral ramifications of the system as a possible locus of action for anti-migraine drugs while little attention has been focused upon possible central sites of action. It has been shown that certain peptides can act as markers for the trigeminal system, in particular calcitonin gene-related peptide (CGRP), and that CGRP is elevated in migraine. We have employed an animal model for activation of the trigeminovascular system to evaluate a new antimigraine compound, 311C90, that may have central and as well as peripheral trigeminal actions. Cats were anesthetized by halothane induction and alpha-chloralose maintenance (60 mg/kg, intraperitoneal), intubated, paralyzed and ventilated. Biparietal craniotomies were carried out to measure cerebral blood flow using laser Doppler flowmetry (CBFLDF). The external jugular vein was cannulated and blood drawn, centrifuged and frozen until processing. Stimulation of the trigeminal ganglion resulted in a mean maximum increase in CBFLDF of 39 +/- 5% at 20/s. The 5HT1 agonist 311C90 was administered intravenously in two doses (30 and 100 micrograms/kg) to cover the range of doses likely to be effective clinically. At each dose the CBFLDF effect of trigeminal ganglion stimulation was inhibited.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
474,7934431,Is chest pain after sumatriptan oesophageal in origin?,L A Houghton; J M Foster; P J Whorwell; J Morris; P Fowler,"3-5% of patients taking the 5HT1D agonist sumatriptan for migraine have chest discomfort, suggesting a cardiac origin. We have investigated an alternative explanation of an oesophageal cause in 24 volunteers after the subcutaneous administration of a supratherapeutic dose of sumatriptan (16 mg) or placebo in a randomised, double-blind crossover study. Sumatriptan did not alter the electrocardiogram but increased the amplitude (p < 0.001) and duration (p < 0.001) of oesophageal contractions without affecting velocity of propagation. Clinically abnormal motility was also increased (p = 0.001), and was more common in the 5 subjects with chest pain after sumatriptan. The effect of sumatriptan on oesophageal function provides an alternative explanation for the chest symptoms.",1994.0,0,0
475,7936279,Subcutaneous sumatriptan during the migraine aura. Sumatriptan Aura Study Group.,D Bates; E Ashford; R Dawson; F B Ensink; N E Gilhus; J Olesen; A J Pilgrim; P Shevlin,"This double-blind, placebo-controlled, multicenter, parallel-group study assessed whether subcutaneous sumatriptan administered during the migraine aura would prolong or modify the aura and prevent or delay development of the headache. One hundred seventy-one patients (88 receiving 6 mg sumatriptan, 83 receiving placebo) treated a single attack of migraine with typical aura at home, by self-injection. The median duration of aura following the first injection was 25 minutes for the sumatriptan group and 30 minutes for the placebo group (NS). The aura symptom profile was similar for the two treatment groups. The proportion of patients who developed a moderate or severe headache within 6 hours after dose administration was similar in the two groups--68% among those receiving sumatriptan and 75% among those receiving placebo (NS). Sumatriptan given during the aura did not prolong or alter the nature of the migraine aura and did not prevent or significantly delay headache development.",1994.0,0,1
476,7938165,International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin).,D Hoyer; D E Clarke; J R Fozard; P R Hartig; G R Martin; E J Mylecharane; P R Saxena; P P Humphrey,"It is evident that in the last decade or so, a vast amount of new information has become available concerning the various 5-HT receptor types and their characteristics. This derives from two main research approaches, operational pharmacology, using selective ligands (both agonists and antagonists), and, more recently, molecular biology. Although the scientific community continues to deliberate about the hierarchy of criteria for neurotransmitter receptor characterisation, there seems good agreement between the two approaches regarding 5-HT receptor classification. In addition, the information regarding transduction mechanisms and second messengers is also entirely consistent. Thus, on the basis of these essential criteria for receptor characterisation and classification, there are at least three main groups or classes of 5-HT receptor: 5-HT1, 5-HT2, and 5-HT3. Each group is not only operationally but also structurally distinct, with each receptor group having its own distinct transducing system. The more recently identified 5-HT4 receptor almost undoubtedly represents a fourth 5-HT receptor class on the basis of operational and transductional data, but this will only be definitively shown when the cDNA for the receptor has been cloned and the amino acid sequence of the protein is known. Although those 5-HT receptors that have been fully characterised and classified to date (and, hence, named with confidence) would seem to mediate the majority of the actions of 5-HT throughout the mammalian body, not all receptors for 5-HT are fully encompassed within our scheme of classification. These apparent anomalies must be recognised and need further study. They may or may not represent new groups of 5-HT receptor or subtypes of already known groups of 5-HT receptor. Even though the cDNAs for the 5-ht1E, 5-ht1F, 5-ht5, 5-ht6, and 5-ht7 receptors have been cloned and their amino acid sequence defined, more data are necessary concerning their operational and transductional characteristics before one can be confident of the suitability of their appellations. Therefore, it is important to rationalise in concert all of the available data from studies involving both operational approaches of the classical pharmacological type and those from molecular and cellular biology.(ABSTRACT TRUNCATED AT 400 WORDS)",1994.0,0,0
477,7954759,A randomized double-blind placebo-controlled crossover study of subcutaneous sumatriptan in general practice.,M B Russell; O E Holm-Thomsen; M Rishøj Nielsen; A Cleal; A J Pilgrim; J Olesen,"To evaluate the therapeutic response to sumatriptan in the acute migraine attack, Two hundred and thirty migraineurs diagnosed by their general practitioners in accordance with their usual practice were included in the study. The patients treated two migraine attacks at home by subcutaneous injection of sumatriptan or placebo for the first attack and the alternative medication, i.e. placebo or sumatriptan, for the second attack (crossover). Following treatment, a neurology resident interviewed and examined the patients. When sumatriptan was compared to placebo, significantly more of the 209 evaluable patients reported headache relief at 1 h (56% vs 8%, p < 0.001) and 2 h (62% vs 15%, p < 0.001) after the first injection. Resolution of nausea, photophobia, and phonophobia was significantly more common in patients on sumatriptan than in those on placebo (p < 0.001 for all comparisons). The adverse events were usually transient and of mild or moderate severity; however, three patients withdrew due to adverse events. Ninety-five percent of patients evaluated by a neurology resident met the IHS criteria for migraine. In general practice, sumatriptan taken subcutaneously using an autoinjector at home was an effective and well tolerated acute treatment for migraine.",1994.0,0,1
478,7954760,Combined oral lysine acetylsalicylate and metoclopramide in the acute treatment of migraine: a multicentre double-blind placebo-controlled study.,H Chabriat; J E Joire; J Danchot; P Grippon; M G Bousser,"This multicentre, double-blind, randomized, placebo-controlled, parallel study was designed to evaluate the efficacy of combined oral lysine acetylsalicylate and metoclopramide (LAS-MCP) in the acute treatment of migraine attacks. A total of 266 patients, 18-65 years old, with two to six attacks of migraine with or without aura (IHS criteria) per month were included. The patients had to treat two migraine attacks with LAS-MCP (1620 mg lysine acetylsalicylate--the equivalent of 900 mg aspirin--combined with 10 mg metoclopramide) or placebo. The main outcome measure was headache relief (reduction in headache severity from grade 3 or 2--severe or moderate--to grade 1 or 0--mild or none) 2 h after treatment. LAS-MCP was superior to placebo for headache relief (56% vs 28%) and for the following secondary outcome measures: complete headache relief (18% vs 7%; p < 0.001), nausea (28% vs 44%; p < 0.001), vomiting (3% vs 11%; p = 0.001), use of rescue medication (47% vs 68%; p < 0.001), global efficacy judged as good or excellent (32% vs 14%; p < 0.001). The tolerability was considered as good in 94% of treated attacks in both groups. Combined oral lysine acetylsalicylate and metoclopramide is an effective and well-tolerated acute treatment of migraine attacks.",1994.0,0,0
479,7958382,An open study of self-administration of subcutaneous sumatriptan to treat successive attacks of acute migraine. Portuguese Sumatriptan Auto-injector Study Group.,,"The efficacy and safety of single doses of 6 mg sumatriptan, self-administered subcutaneously by patients using an auto-injector, for the acute treatment of up to three successive attacks of migraine was investigated in a multicentre, open, uncontrolled study in which 178 patients were enrolled. At attack 1, there was an improvement in headache (from severe or moderate to mild or no headache) in 74% of patients at 1 h, and in 82% at 2 h. The incidence of symptoms associated with migraine was decreased after sumatriptan injection. Nausea, vomiting and photo/phonophobia were reported by 72, 54, and 85% of patients, respectively, before the injection to treat attack 1, but by only 22, 12 and 27%, respectively, 2 h after the injection. Migraine recurred within 24 h in 27% of patients, but in 89% of patients was effectively treated with a further dose of 6 mg sumatriptan. Results for attacks 2 and 3 were similar. About 40% of patients experienced at least one adverse event; most of these were mild or moderate in intensity and were transient. It is concluded that 6 mg sumatriptan, self-administered using an auto-injector, is an effective and well tolerated treatment for migraine. Sumatriptan was as effective at attack 3 as at attack 1, and there was no evidence of a change in the incidence or the nature of adverse events with successive uses of the drug.",1994.0,0,1
480,7964913,Intranasal sumatriptan for the acute treatment of migraine. International Intranasal Sumatriptan Study Group.,R Salonen; E Ashford; C Dahlöf; R Dawson; N E Gilhus; V Lüben; D Noronha; J M Warter,"Two double-blind, placebo-controlled, randomised, multicentre, multinational, parallel-group studies were carried out to identify the optimum dose of intranasal sumatriptan for the acute treatment of migraine. Study medication was taken as a single dose through one nostril in the first study, and as a divided dose through two nostrils in the second study. Totals of 245 and 210 patients with a history of migraine were recruited into the one- and two-nostril studies, respectively. In both studies, headache severity had significantly improved at 120 min after doses of 10-40 mg sumatriptan compared to placebo (P < 0.05) and the greatest efficacy rates were obtained with 20 mg sumatriptan. With 20 mg sumatriptan 78% and 74% of patients experienced headache relief in one- and two-nostril studies respectively. Sumatriptan was generally well tolerated, the most frequently reported event being taste disturbance. The results of the two studies are similar and indicate that administering sumatriptan as a divided dose via two nostrils confers no significant advantage over single-nostril administration.",1994.0,0,1
481,7978566,"Intravenous versus rectal prochlorperazine in the treatment of benign vascular or tension headache: a randomized, prospective, double-blind trial.",S H Thomas; C K Stone; V G Ray; T W Whitley,"To compare the effectiveness of i.v. and PR prochlorperazine for treatment of acute benign vascular or tension headache. Prospective, randomized, double-blind trial. University emergency department with 50,000 annual census. Forty-five adult patients enrolled on 46 visits. Patients received 10 mg prochlorperazine i.v. and placebo suppository or 25 mg prochlorperazine PR and placebo injection. Pain assessment was made using a 10-cm visual-analog scale; scores were analyzed using Wilcoxon/Kruskal-Wallis rank-sum tests (alpha of .01). Mean 60-minute pain scores for i.v. and PR groups were 0.6 and 3.5, respectively (P = .0002). Two patients (8.7%) in the i.v. group and six patients (26.1%) in the PR group required rescue analgesia (P = .12). i.v. prochlorperazine appears to provide more effective relief than PR prochlorperazine for benign vascular or tension headaches.",1994.0,0,0
482,7986182,Clinical experiences from Sweden on the use of subcutaneously administered sumatriptan in migraine and cluster headache.,C Dahlöf; K Ekbom; L Persson,"This article reviews, from the practitioner's point of view, more than 1 year of clinical experience of the use of subcutaneously administered sumatriptan succinate in the short-term treatment of migraine and cluster headache with regard to advantages and disadvantages of the drug. In accordance with the results of clinical trials, subcutaneous sumatriptan, also in the practitioner's hands, was found to relieve migraine headaches and all other symptoms associated with migraine in most patients and within a reasonable period. Adverse events, however, are common and were perceived by about 70% of the patients. The most common adverse events were pressure/stiffness in the neck and throat (32%), general tiredness (22%), pressure/tightness over the chest (21%), injection site reactions (16%), and tingling sensations in the head and arms (14%). Headache recurrence within 24 hours is a clinical problem not only for the patient but also for the prescribing physician. About every second (53%) migraineur using subcutaneous sumatriptan reports headache recurrence. Headache recurrence appears to be effectively treated by a second injection. Pending valid information about effects, adverse events, headache recurrence, and how to handle the autoinjector, the compliance and tolerability of subcutaneous sumatriptan appear to be most satisfactory among eligible patients with migraine.",1994.0,0,1
483,7987510,Oral sumatriptan in the treatment of recurrent headache.,R K Cady; J Rubino; D Crummett; T W Littlejohn,"Sumatriptan is effective for the treatment of acute migraine. However, headache may recur in about 30% of patients within 24 hours of successful treatment. To evaluate the efficacy of oral sumatriptan, 100 mg, in the treatment of headache recurring within 24 hours of achieving headache resolution with subcutaneous sumatriptan, 6 mg. Subcutaneous sumatriptan was administered for up to 12 migraine attacks in a randomized, double-blind, parallel-group study. Patients whose headache was completely resolved 90 minutes after subcutaneous dosing received either oral sumatriptan or placebo at the onset of recurrent headache. Patients whose headache was not completely resolved were offered rescue medication, including sumatriptan. Patients rated headache severity for 24 hours. Fifteen US outpatient clinics. Percentage of patients with relief of recurrent headache and adverse events. Approximately 90% of patients achieved relief of headache (severe or moderate headache reduced to mild or no headache) by 90 minutes after unblinded subcutaneous administration of sumatriptan. Efficacy rates were at least 80% regardless of whether the headache fulfilled the International Headache Society criteria for migraine. About 64% of patients achieved complete relief. Oral sumatriptan, 100 mg, relieved moderate or severe recurrent headache within 4 hours in up to 81% of patients. Oral sumatriptan administered as rescue medication to patients not headache-free did not relieve persistent headache. The incidence, pattern, and severity of adverse events after combined subcutaneous and oral administration of sumatriptan were similar to those after subcutaneous administration alone. Oral sumatriptan was consistently effective in the treatment of headache recurrence.",2001.0,0,1
484,7998046,[Sumatriptan in the treatment of migraine in general practice].,E Midelfart; M Winnem,"Approximately 5% of the adult Norwegian population suffer from migraine. Sumatriptan is a new anti-migraine drug which has been shown in clinical studies to be efficacious in up to 80% of attacks treated. These early clinical studies have all been carried out at specialist centres and the present study was planned to see if migraine patients treated by general practitioners would also benefit from this new therapy. This placebo controlled, randomized, double blind study was carried out by 50 general practitioners and two neurologists, and included 294 patients. A total of 1,485 migraine attacks were treated. The results show that Sumatriptan is equally efficacious and well tolerated when used to treat patients in general practice as at specialist clinics. Sumatriptan was efficacious in relieving pain and other migraine symptoms in 76% of the migraine attacks treated, while placebo had the desired effect in 29% of attacks.",1994.0,0,1
485,8035909,The effects of sumatriptan on pituitary secretion in man.,R Franceschini; A Cataldi; A Garibaldi; P Cianciosi; A Scordamaglia; T Barreca; E Rolandi,"Sumatriptan, a new antimigraine drug with high affinity and selectivity for certain 5-hydroxytryptamine (5-HT1D) receptor subtypes, was administered to 12 normal subjects, in order to investigate the effects of 5-HT receptor activation on anterior pituitary secretion. Sumatriptan increased plasma growth hormone (GH) levels from 2.5 +/- 0.5 mIU/l in basal conditions to 17.3 +/- 2.6 mIU/l 30 min after administration of the drug. After pre-treatment with cyproheptadine, an anti-serotoninergic drug known to inhibit GH secretion, the mean integrated sumatriptan-induced GH response decreased from 14.8 +/- 3.9 muI/l*hr to 3.7 +/- 1.7 mIU/l*hr. Sumatriptan administration did not have any effect on the secretion of the other anterior pituitary hormones. It is concluded that sumatriptan selectively increases GH secretion in man, but the exact nature of the receptors involved is not yet known.",1994.0,0,0
486,8062353,Exteroceptive suppression of temporalis muscle activity during migraine attack and migraine interval before and after treatment with sumatriptan.,H Göbel; S Krapat; M Dworschak; D Heuss; F B Ensink; D Soyka,"We compared the early (ES1) and late (ES2) exteroceptive suppression (ES) periods of temporalis muscle activity in 18 migraine patients during both the migraine interval and migraine attack and investigated the effect of sumatriptan and placebo on ES parameters. The measurements were performed in a balanced sequence at four different times on each patient, twice during the migraine interval and once in each of two migraine attacks. First ES1 and ES2 were measured (stimulus intensity 20 mA, stimulus duration 0.2 ms, stimulation frequency 2 Hz, averaging of 10 responses), then the medication was given on a double-blind basis with an autoinjector using either 6 mg sumatriptan or a placebo solution. Thirty minutes after application the measurements were repeated. No significant differences were found in early and late exteroceptive suppression latencies and durations between baseline measurements. Treatment did not affect the latencies of ES1 and ES2. While sumatriptan caused a significant increase in ES1 duration (p < or = 0.05) both during the migraine interval and during the migraine attack, placebo showed no significant effect on ES1 duration. Treatment with sumatriptan during the migraine attack was accompanied by a significant increase in the duration of ES2 (p < or = 0.05), but no significant changes in the durations of the late suppression periods were observed under any other conditions. The results do not support the assumption that under the experimental conditions chosen migraine attacks are accompanied by a paroxysmal change in the brain-stem mechanisms involved in the modulation of the ES parameters.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
487,8069007,Healthcare resource use and costs associated with migraine in a managed healthcare setting.,J C Clouse; J T Osterhaus,"To compare healthcare use and associated costs in patients with migraine and patients without migraine headache. Retrospective review of a managed care organization's medical and pharmacy claims databases for claims filed between January 1, 1989 and June 30, 1990. Patients between 18 and 64 years old with a 12-month minimum enrollment in the health plan, including enrollment for the prescription drug benefit. Migraine group (n = 1336) inclusion required a medical claim with the diagnosis of migraine headache and a pharmacy claim for a medication potentially used for migraine treatment. Comparison group (n = 1336) inclusion required at least one medical claim with no diagnosis of migraine; a pharmacy claim was not required. Comparison group patients were matched to migraine group patients by age, gender, enrollment status, and subscriber or dependent enrollment status. Total health services use, diagnosis-specific use of services, diagnostic procedures performed, comorbid conditions, medication use, and associated costs were tallied. Migraineurs generated nearly twice as many medical claims as comparison group patients, and nearly 2.5 times as many pharmacy claims. Number of claims generated and numbers of patients who generated claims within each of 19 diagnostic categories indicated greater comorbidity in the migraine group. Migraineurs used emergency services more than did patients in the comparison group. Total medical and pharmacy claims costs were $3.4 million for the migraine group and $2.1 million for the comparison group. The average amount paid per member-month of enrollment was significantly greater in the migraine group than in the comparison group. Comorbid conditions were responsible for a significant portion of costs in the migraine group. The migraine group incurred $83,537 for diagnostic procedures compared with $13,140 incurred by the comparison group. Patients with migraine had greater morbidity in general and incurred 64 percent greater costs in healthcare resource use compared with patients without migraine.",1994.0,0,0
488,8081520,Treatment of the migraine attack.,S D Silberstein,"Migraine is an episodic headache disorder that occurs with or without aura and is often accompanied by other symptoms. Treatment must address these associated symptoms as well as the headache, and it can involve either acute or preventive therapy alone or a combination of both. Acute therapy treats the individual attack; preventive therapy aims to reduce the frequency and severity of attacks. Drug choice requires careful consideration and depends on the character of the migraine attack. Acute drug therapy using sumatriptan, MK-462, 311C90, dihydroergotamine, nonsteroidal anti-inflammatory drugs, butorphanol, metoclopramide, and domperidone is discussed. Prophylactic drug therapy using valproate and fluoxetine is also discussed.",1994.0,0,0
489,8137520,"The neuroendocrine effects of sumatriptan, a specific ligand for 5-HT1-like receptors.",F Facchinetti; R E Nappi; G Sances; L Fioroni; G Nappi; A R Genazzani,"A relationship between the serotoninergic and the opiatergic system in the pathogenesis of head pain is supported by several data. This study was carried out to investigate the neuroendocrine effects of sumatriptan, a specific serotonin agonist used in the treatment of migraine, on hypothalamic-pituitary-adrenal axis (PHA) hormones. Two consecutive studies were performed. In study A, eight subjects received a subcutaneous (s.c.) injection of sumatriptan (6 mg). In study B, a further six subjects were randomized to receive either sumatriptan or placebo. Healthy volunteers recruited within the staff (eight males and six females) were studied. In study A, plasma cortisol and PRL were measured by direct RIA and beta-endorphin after extraction and chromatography. Samples were collected from 60 minutes before to 120 minutes after the administration of the drug, at 15-minute intervals. According to the data of the first study, in study B, in addition to cortisol and beta-endorphin, ACTH was also measured. Significant increases in the mean beta-endorphin and cortisol concentrations were found in every subject receiving sumatriptan, while no significant changes were observed in prolactin plasma levels. Study B confirmed the activation of the pituitary-adrenal axis, additionally demonstrating the release of ACTH, and indicated that placebo has no effects. Acute s.c. stimulation with sumatriptan activates the pituitary-adrenal axis.",1994.0,0,0
490,8150324,Guidelines and recommendations for the treatment of migraine. Italian Society for the Study of Headache (SISC).,,,1993.0,0,0
491,8163368,Subcutaneous sumatriptan in a clinical setting: the first 100 consecutive patients with acute migraine in a tertiary care center.,F D Sheftell; R E Weeks; A M Rapoport; S Siegel; S Baskin; F Arrowsmith,"The first 100 consecutive patients at our center receiving subcutaneous sumatriptan (6 mg) were evaluated over a total of 455 migraine attacks. Parameters included overall efficacy, average time to relief, recurrence rate, average time to recurrence, adverse events, comparison to previous abortive agents, and subjective global ratings. Overall efficacy (defined as headache severity reduction from severe or moderate to mild or none) was 84%. Average time to relief was 40 minutes. Nine percent failed to respond at all. Recurrence rate was 46.5% with 36% of patients having no recurrence. Fourteen percent of patients reported 100% recurrence (minimum 3 attacks; average 5.4 attacks). Time to recurrence varied widely, but averaged 9.1 hours. Eighty-one percent rated the drug better or much better than previous abortive medications in terms of sumatriptan's ability to abort the attack. Seventy-seven percent reported some adverse event (generally mild and transient) with 23% reporting no adverse events. Sixty-nine percent reported a global rating of Good to Excellent and 31% rated Poor or Fair. The rate of recurrence and average time to recurrence were the most significant factors affecting the global ratings. These parameters were further evaluated with respect to a variety of subgroups: 1) migraine alone 2) migraine with co-existent tension-type headache 3) drug-induced headache (analgesic rebound headache) 4) posttraumatic headache 5) preventive versus no preventive medication 6) presence or absence of adverse events 7) presence or absence of recurrence and 8) average duration of migraine with no medication.",1994.0,0,0
492,8164015,Oral sumatriptan compared with placebo in the acute treatment of migraine.,G Nappi; F Sicuteri; M Byrne; M Roncolato; O Zerbini,"This multicentre, double-blind, parallel-group study compared the efficacy, safety and tolerability of oral sumatriptan, given as a new film-coated tablet, with placebo in the acute treatment of migraine. Patients were randomised unequally (1:2) to receive placebo or sumatriptan. Eighty-eight patients received placebo (plus an optional dose 2 h later if the headache persisted plus a further optional dose for recurrence within 24 h) and 162 patients received sumatriptan 100 mg (plus an optional 100 mg dose at 2 h and an optional 100 mg dose within 24 h). Sumatriptan was significantly more effective than placebo at relieving headache (defined as reduction in severity from severe or moderate pain to mild or no pain) at 2 h (51% versus 31%, P = 0.003) and 4 h (71% versus 35%, P < 0.001). Fewer sumatriptan-treated patients required a second dose compared with placebo-treated patients (49% versus 74%, P < 0.001). More sumatriptan-treated patients were completely pain free compared with placebo-treated patients at both 2 h (24% versus 12%) and 4 h (48% versus 18). Patients receiving sumatriptan reported earlier onset of headache relief than patients receiving placebo. Headache relief in sumatriptan-treated patients was similar, irrespective of the type of migraine (with or without aura) or the time of treatment < or = 4 h or > 4 h after onset of migraine). Sumatriptan was more effective than placebo at relieving nausea, vomiting and photophobia/phonophobia. Few patients were evaluable for treatment of headache recurrence, and statistical analysis was not possible.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,1
493,8200027,"Self-treatment of acute migraine with subcutaneous sumatriptan using an auto-injector device: comparison with customary treatment in an open, longitudinal study.",J Schoenen; J Bulcke; J Caekebeke; I Dehaene; J De Keyser; G Hildebrand; A Joffroy; P Laloux; P Louis; G Monseu,"In a multicenter open longitudinal clinical trial where 479 patients suffering from migraine with or without aura were recruited, patients treated at home one to three migraine attacks with their customary treatment, and subsequently, over a 3-month period, one to three migraine attacks with 6 mg sumatriptan sc using an autoinjector. The headache response to customary treatment was 19% at 1 h and 30.5% at 2 h, and was not significantly different when only attacks treated ""adequately"" according to accepted treatment recommendations were considered: 16% at 1 h and 35% at 2 h. In contrast, 69% and 82% of patients treated with 6 mg sumatriptan sc had mild headache or no headache at 1 and 2 h respectively, regardless of migraine type or duration of symptoms prior to treatment. Other migraine symptoms (nausea, vomiting, photo- and phonophobia) were effectively treated with sumatriptan. Recurrence of migraine was observed in 31% of patients and was well controlled by a second injection of sumatriptan. It is concluded that 6 mg sumatriptan sc, self-administered using an autoinjector, is well tolerated and more effective than most currently used acute treatments for migraine in a population of severely affected patients consulting a neurologist.",1994.0,0,1
494,8260340,The use of sumatriptan in the treatment of migraine.,M Gross,"Sumatriptan is a selective agonist of 5-hydroxytryptamine receptors, recommended for the acute treatment of migraine. The 5-HT1 receptor subtype is found in the cranial vasculature of many species including humans, and causes vasoconstriction of these vessels. Sumatriptan as a highly potent 5-HT1 agonist selectively constricts large intracranial blood vessels and also blocks neurogenic inflammation. Those treating patients with severe or inconveniently timed attacks will find sumatriptan the drug of choice.",1993.0,0,0
495,8262783,Subcutaneous sumatriptan in the acute treatment of migraine in patients using dihydroergotamine as prophylaxis. French Migraine Network Bordeaux-Lyon-Grenoble.,P Henry; H d'Allens,"The efficacy of sumatriptan, a 5-HT1 receptor agonist, in patients with migraine attacks occurring despite prophylactic treatment with oral dihydroergotamine, was assessed in a double-blind placebo-controlled study involving 76 patients. Thirty-seven patients were treated with a subcutaneous injection of 6 mg sumatriptan self-administered with an auto-injector and 39 with placebo given by the same route. Patients having inadequate relief were allowed to use a second injection of test medication 1 hour later and rescue treatment between 2 hours and 24 hours after the first dose. Headache relief was achieved within 2 hours after sumatriptan in 26 patients (70%) compared to 8 patients (21%) in the placebo group (P < 0.0001). Of these patients, 19 (51%) and 3 (8%) were, respectively, pain free at this time. A second injection of sumatriptan was used by 8 (22%) patients compared to 30 (77%) patients in the placebo group (P < 0.0001), whereas rescue medication was used respectively by 13 (35%) and 22 (58%) patients (P < 0.024). The adverse event profile of sumatriptan was not affected by the concomitant use of dihydroergotamine and side-effects were all minor and transient. Patient satisfaction was significantly higher in the sumatriptan group (75%) compared to patient satisfaction with placebo (16%). These results show that the high efficacy rate of subcutaneous sumatriptan and its safety profile remain unchanged in migraine patients receiving oral dihydroergotamine as prophylaxis.",1993.0,0,1
496,8294198,Comparison of contingent negative variation between migraine interval and migraine attack before and after treatment with sumatriptan.,H Göbel; S Krapat; F B Ensink; D Soyka,"We compared in a placebo controlled, double blind, crossover within-subject design, the amplitude and area integral of contingent negative variation (CNV) using a 2 second interstimulus interval in migraine patients between attack and interval before and after treatment. The study was conducted on 14 female subjects suffering from migraine without aura. The measurements were performed in a balanced sequence at four different times on each patient, twice during the migraine interval and once in each of two migraine attacks. The CNV in the patients was measured first (baseline), then medication was administered on a double-blind basis with an autoinjector, using either 6 mg sumatriptan or a placebo solution. Thirty minutes after administration the CNV parameters were measured again and the changes between pre- and post-treatment were taken as dependent variables. CNV amplitude baseline readings did not differ significantly between the four conditions. Neither administration of placebo nor sumatriptan led to a significant change in CNV parameters independent of whether significant clinical improvement of migraine headache occurred or not. According to our findings CNV-mechanisms between attack and interval are not subject to short-term changes, even though a small, not significant tendency towards a decrease in CNV amplitude during migraine attacks appears to exist. Therefore, it can be assumed that changes in the systems which are depicted by CNV readings are not involved in initiating and terminating acute migraine attacks.",1993.0,0,0
497,8313451,Amplifying effect of sumatriptan on noradrenaline venoconstriction in migraine patients.,A Panconesi; G Franchi; B Anselmi; C Curradi; B Tarquini,"The venoconstrictive activity of sumatriptan and its interaction with noradrenaline (NA)- and 5-hydroxytryptamine (5HT) venoconstriction was studied in vivo in the hand vein of migraineurs. Sumatriptan, injected at increasing doses into the vein, caused local venoconstriction after a 500 microgram dose, comparable to that induced by 0.5-1 micrograms of 5HT. This venoconstriction was completely inhibited by low doses of ketanserin (5 micrograms). Subcutaneous sumatriptan (6 mg) provoked a minor increase in vein tone, lasting less than 30 min. Non-venoconstrictive doses of sumatriptan (10-100 micrograms), injected in the hand vein, produced an amplification of NA-venoconstriction but not of 5HT-induced venoconstriction. A similar increased effect was displayed by subcutaneous sumatriptan (6 mg) for at least 1 h. Sumatriptan appears to cause peripheral venoconstriction only at high doses locally applied (in the hand vein), by acting on 5HT2 receptors. Clinical subcutaneous doses (6 mg) do not show significant venoconstrictive effects. The amplifying effect on NA venoconstriction, also caused by 5HT, ergotamine and dihydroergotamine in human cranial arteries, may be important in explaining the therapeutic action of sumatriptan in migraine attacks.",1993.0,0,0
498,8313696,Sumatriptan: a novel therapy for the management of acute migraine.,M Klepser,,1993.0,0,0
499,8527845,What's in a gene: using genetic information for the design of clinical trials.,J Lichter; D McNamara,,1995.0,0,0
500,8531896,Sumatriptan does not stimulate PRL and GH secretion in acromegaly.,C M Cuttica; P Sessarego; S Valenti; M R Falivene; M Giusti; G Giordano,"Serotoninergic receptors are involved in the regulation of PRL and GH secretion. We studied the effects of sumatriptan, a new 5-HT1D receptor agonist, on PRL and GH secretion in active acromegaly. After their informed consent, all subjects were submitted to sumatriptan or placebo administration in single blind and in a random order. The time interval between the tests was of 7 days. We examined all patients in the morning, after 12 hours of fasting. All subjects were in recumbent position during the tests. Pulse rate and blood pressure were monitored during the test. Eight acromegalics (42-65 years) and 10 age-matched (33-63 years) normal subjects. Blood samples were taken after needle insertion kept patent by slow saline solution infusion. PRL and GH secretion were evaluated after sumatriptan (6 mg sc) and placebo. Blood samples were taken before (45, 15 and 0 minutes) and every 15 minutes for 2 hours after sumatriptan or placebo administration. No significant changes in PRL secretion were observed after sumatriptan in both groups of subjects. A significant increase in GH levels after sumatriptan was observed in controls but not in acromegalics. An age-related negative trend in GH response to sumatriptan was observed in controls. Our study indicated that 5-HT1D receptors are not involved in PRL and GH secretion in middle-aged acromegalics.",1995.0,0,0
501,8536293,Migraine and cluster headache--their management with sumatriptan: a critical review of the current clinical experience.,M Wilkinson; V Pfaffenrath; J Schoenen; H C Diener; T J Steiner,"Sumatriptan is a potent and selective agonist at the vascular 5HT1 receptor which mediates constriction of certain large cranial blood vessels and/or inhibits the release of vasoactive neuropeptides from perivascular trigeminal axons in the dura mater following activation of the trigeminovascular system. The mode of action of this drug in migraine and cluster headache is discussed. On the basis of a detailed review of all published trials and available data from post-marketing studies, the efficacy, safety, tolerability and the place of oral and subcutaneous sumatriptan in the treatment of both conditions are assessed. A number of double-blind clinical trials have demonstrated that sumatriptan 100 mg administered orally is clearly superior to placebo in the acute treatment of migraine headache and achieves significantly greater response rates than ergotamine or aspirin. In other studies, 70 to 80% of patients receiving sumatriptan 6 mg sc experienced relief of migraine headaches by 1 or 2 h after administration, and patients consistently required less rescue medication for unresolved symptoms. Sumatriptan was also effective in relieving associated migraine symptoms like nausea and vomiting. Sumatriptan was equally effective regardless of migraine type or duration of migraine symptoms. Overall, approximately 40% of patients who initially responded to oral or subcutaneous sumatriptan experienced recurrence of their headache usually within 24 h, effectively treated by a further dose of this drug. In 75% of patients with cluster headache treated with sumatriptan 6 mg sc, relief was achieved within 15 min. Based on pooled study data, sumatriptan is generally well tolerated and most adverse events are transient. Adverse events following oral administration include nausea, vomiting, malaise, fatigue and dizziness. With the subcutaneous injection, injection site reactions occur in approximately 30%. Chest syumptoms are reported in 3 to 5% but have been associated with myocardial ischaemia only in rare isolated cases. The recommended dosage of sumatriptan at the onset of migraine symptoms is 100 mg orally or 6 mg subcutaneously. The recommended dosage for cluster headache is 6 mg sumatriptan sc. Sumatriptan must not be given together with vasoconstrictive substances, e.g., ergotamines, or with migraine prophylactics with similar properties, e.g., methysergide. Sumatriptan should not be given during the migraine aura. It is contraindicated in patients with ischaemic heart disease, previous myocardial infarction, Prinzmetal (variant) angina and uncontrolled hypertension.",1995.0,0,1
502,8536303,Health-related quality of life under six months' treatment of migraine--an open clinic-based longitudinal study.,C G Dahlöf,"Health-related quality of life (HQL) assessment in the clinical setting have distinguished subjective perceptions (e.g., well-being), signs/symptoms of the disease and functional capacity as three major components. The impact of short-term treatment for migraine attacks on these variables was evaluated in an open prospective 6-month study at the Gothenburg Migraine Clinic. Socio-economic factors, subjective symptoms, and general well-being/quality of life were evaluated by self-administered questionnaires in 99 patients with migraine with or without aura in accordance with the classification of the International Headache Society. Short-term treatment comprising conventional therapy or subcutaneous sumatriptan reduced number of days per month with migraine and absenteeism from work, migraine-associated symptoms, but did not significantly improve general well-being between attacks. Future assessment of the patients' HQL in accordance with this approach would enable us to consider all the advantages and disadvantages of current therapies of particular interest in the field of migraine.",1995.0,0,1
503,8536304,Introduction of a novel self-injector for sumatriptan. A controlled clinical trial in general practice.,K Jensen; P Tfelt-Hansen; E W Hansen; E H Krøis; O S Pedersen,"A novel self-injector for the administration of subcutaneous sumatriptan in the treatment of migraine attacks was tested in 138 patients recruited by family physicians in Denmark: 108 patients completed the initial double-blind, crossover part of the study. Sumatriptan 6 mg s.c. was significantly better than placebo at 30, 60, 90 and 120 min after injection in relieving moderate or severe headache to mild or none as well as relieving any headache to none. At 60 min after injection, the treatment response rate was 61% for sumatriptan and 6% for placebo. During the following open-phase trial of four attacks treated with sumatriptan, treatment response rates were 68-74%. During the total of 538 attacks treated, 12 attempts at using the self-injector failed. In the double-blind and open phases, 81% and 90% of patients respectively found the device easy or very easy to use. Adverse effects were benign and short-lasting, but led seven patients to discontinue the study. In conclusion, subcutaneous sumatriptan administered with a novel self-injector is an effective treatment for migraine compared to placebo in patients treated by their family physician.",1995.0,0,1
504,8537803,Improvements in health-related quality of life with sumatriptan treatment for migraine.,P Jhingran; R K Cady; J Rubino; D Miller; R B Grice; D L Gutterman,"The debilitating effects of migraine might be reduced in patients using an effective migraine medication. The serotonin (5HT1) receptor agonist sumatriptan has been shown in clinical trials to alleviate headache and associated symptoms in the majority of patients treated. Three hundred forty-four (344) patients with migraine were allowed to treat an unlimited number of migraine attacks for up to 24 months with subcutaneous sumatriptan (6 mg). Open-label oral sumatriptan (100 mg) could be used between 1 hour and 24 hours after the initial injection for treatment of recurrent or persistent headache. On four occasions during the treatment period, patients completed the Medical Outcomes Study Short Form-36 Health Survey, a general health status instrument; the Migraine-Specific Quality of Life Questionnaire, a disease-specific instrument; and a series of questions designed to measure the impact of migraine on productivity and disability. Treatment with sumatriptan was associated with significant (P < .05) improvements relative to baseline in three of the Short Form-36 Health Survey quality-of-life dimensions (Bodily Pain, General Health Perceptions, and Social Functioning) and three of the Migraine-Specific Quality of Life Questionnaire dimensions (Role Function-Restrictive, Role Function-Preventive, and Emotional Function). Significant (P < .05) improvements in patient-rated productivity and reductions in patient-rated disability also occurred during the trial. Patients using sumatriptan to treat migraines for up to 24 months experienced improvements in disability and productivity as well as in health-related quality of life as measured either by a general health status instrument or a disease-specific instrument.",1996.0,0,1
505,8542914,Comparison of subcutaneous sumatriptan with usual acute treatments for migraine. French Sumatriptan Study Group.,F Boureau; G Chazot; J Emile; L Bertin; H d'Allens,"246 migraine patients (International Headache Society definition, 1-6 severe attacks per month) were randomised into a multicentre, cross-over study comparing subcutaneous (s.c.) sumatriptan 6 mg administered by an auto-injector (Glaxo device) with usual acute migraine treatments. Patients were treated for 2 months or up to 12 attacks, and then crossed over to the alternative treatment for the same duration. Usual treatments were: analgesics (including combinations), 49%; ergotamine, 24%; NSAIDs 19%; DHE, 7%. Rescue medication was allowed 2 h after the first dose. Headache was assessed on a 4-point self-rating scale (0: none, 1: mild, 2: moderate, 3: severe). Other migraine symptoms were assessed as present or absent. Quality of life was assessed before the study and at the end of each treatment period. Two hundred and seventeen patients were eligible for the cross-over analysis. At 2 h post-dosing, an average of 78% of attacks per patient were successfully relieved (grade 3 or 2 to 1 or 0) by s.c. sumatriptan, compared with 34% for the usual treatments (p < 0.001) and 63% of attacks per patient were completely relieved (grade 0) by s.c. sumatriptan compared with 15% for the usual treatments (p < 0.001). Sumatriptan-treated patients used rescue medication for 19% of their attacks, compared to 59% for comparator drugs (p = 0.001). Results for patient preference were: s.c. sumatriptan, 85%; usual treatments, 10%; no preference, 5% (p < 0.001). Sumatriptan was significantly superior to comparator drugs for all other efficacy end-points (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,1
506,8545150,,,,,0,0
507,8550361,Long-term efficacy of subcutaneous sumatriptan using a novel self-injector.,M L Gross; J Kay; A M Turner; J Jewsbury; A L Cleal,"An open, multicenter study investigated the long-term efficacy, tolerability, and acceptability to patients of subcutaneous sumatriptan 6 mg, administered using a novel cartridge system self-injector, for the acute treatment of migraine. Eighty patients treated all migraine attacks for 6 months at home with a subcutaneous injection of sumatriptan 6 mg. A second injection could be taken after 1 to 24 hours if relief was inadequate, or if the headache recurred, and rescue medication could be taken 1 hour after the second injection. The primary end point was the percentage of attacks in which headache improved from severe or moderate before treatment to mild or absent at 1 hour after the first injection. A total of 1566 attacks were treated by the 80 patients and 69 patients completed 6 months of treatment. Headache relief was reported 1 hour after the first injection in a mean of 78% of attacks (83% in the first 3 months and 76% in the second 3 months). A second injection was required in a mean of 40% of attacks, and headache was mild or absent 1 hour after the second injection in a mean of 77% of attacks. Rescue medication was required after the second injection in a mean of 14% of attacks. At the end of the study, 87% of patients said that they would take the medication again, and at each clinic visit over 80% said that they found the injector easy to use. Adverse events were similar to those reported previously with sumatriptan and were mostly mild to moderate in intensity, short-lived, and resolved spontaneously. Subcutaneous sumatriptan 6 mg is an effective, well tolerated, and well accepted, long-term, acute treatment for migraine when self-injected by patients using the novel self-injector.",1995.0,0,1
508,8550362,Preemptive oral treatment with sumatriptan during a cluster period.,I Monstad; A Krabbe; G Micieli; A Prusinski; J Cole; A Pilgrim; P Shevlin,"This multinational, multicenter, randomized, double-blind, placebo-controlled study in 169 patients investigated the effect of a 7-day period of preemptive treatment with oral sumatriptan (100 mg tid) on the frequency and severity of cluster headache attacks occurring during an established cluster headache period. Safety and tolerability were also assessed. Cluster headache patients who were not taking prophylactic medication and had experienced seven or more attacks in the preceding observation week, treated a cluster headache attack at home with subcutaneous sumatriptan 6 mg using an autoinjector device. Patients were then randomized to take sumatriptan 100 mg or placebo at 8-hourly intervals for a 7-day period. Cluster headaches occurring during this period could be treated 5 minutes after onset with rescue medication (100% oxygen or simple analgesics). Diary cards were used to record details of the cluster headache pattern during the observation and study treatment weeks. Preemptive oral treatment with sumatriptan 100 mg tid for 7 days did not produce a significant reduction in the number or severity of cluster headache attacks occurring during an established cluster headache period. Oral treatment with sumatriptan 100 mg tid over a 7-day period was not associated with an increased or altered adverse event profile from that previously reported.",1995.0,0,1
509,8614525,"311C90, a new central and peripherally acting 5-HT1D receptor agonist in the acute oral treatment of migraine: a double-blind, placebo-controlled, dose-range finding study.",W H Visser; K B Klein; R C Cox; D Jones; M D Ferrari,"311C90 is a novel, centrally and peripherally, acting 5-hydroxytryptamine1D receptor agonist. We investigated the efficacy and safety of 1, 5, and 25 mg of oral 311C90 in the acute treatment of migraine in a randomized, double-blind, placebo-controlled, parallel-group clinical trial involving 84 patients. The proportion of patients in whom the headache improved within 2 hours from moderate or severe to mild or no pain (primary efficacy measure) was 15% for placebo-treated patients and 27% (1 mg), 62% (5 mg), and 81% (25 mg) for patients treated with 311C90. Treatment differences compared with placebo were 12% (95% CI - 12, 37; p = 0.460) for 1 mg 311C90, 47% (CI 21, 73; p < 0.005) for 5 mg 311C90, and 66% (CI 43,89; p < 0.001) for 25 mg 311C90. Photophobia and nausea also showed improvement after 311C90. Adverse events were generally mild and transient in all treatment groups. There were no clinically significant changes in ECG recordings, blood pressure, or laboratory tests. Oral 311C90 (5 and 25 mg) is highly effective and well tolerated in the acute treatment of migraine. The response rates and treatment differences compared with placebo in this study suggest possible superiority over existing antimigraine therapies. This needs to be confirmed in formal comparative trials.",1996.0,0,1
510,8623724,Management of depression in patients with coexisting medical illness.,R E Nesse; R E Finlayson,"Depressive illness is common in the general population, with a prevalence of 5 percent. However, 10 to 15 percent of any general medical population has clinically significant depression; in patients with selected chronic illnesses, prevalence rates between 25 to 50 percent are noted. In patients with coexisting medical illness, the diagnosis of depression requires differentiating symptoms of the medical illness from symptoms of the comorbid depression. The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) can be helpful in this endeavor. An understanding of the effect of particular medications on neurotransmitters is required and can guide the clinician in selecting therapeutic agents that have a low incidence of side effects and toxicity.",1996.0,0,0
511,8639069,A double-blind study of subcutaneous dihydroergotamine vs subcutaneous sumatriptan in the treatment of acute migraine.,P Winner; O Ricalde; B Le Force; J Saper; B Margul,"To assess the efficacy and tolerability of subcutaneous dihydroergotamine mesylate (DHE-45) vs subcutaneous sumatriptan succinate (Imitrex) for the treatment of acute migraine with or without aura. Double-blind, randomized trial with parallel treatment arms. Clinics and private neurology practices. Patients of either sex, with migraine with or without aura, between the ages of 18 and 65 years. Patients with moderate or severe head pain were randomized to receive either 1 mg of subcutaneous dihydroergotamine mesylate or 6 mg of subcutaneous sumatriptan succinate. Patients rated head pain, functional ability, nausea, and vomiting at baseline and at 0.5, 1, 2, 4, and 24 hours after the injection. Presence or absence of headache at 3 hours was calculated from collected data. If pain persisted after 2 hours, a second injection of the same study medication was allowed, and self-ratings were repeated 30 and 60 minutes later. Follow-up data were collected at 24 hours. Relief of head pain and recurrence of successfully treated headache. There were 295 evaluable patients. At 2 hours, 73.1% of the patients treated with dihydroergotamine and 85.3% of those treated with sumatriptan had relief (P = .002). There was no statistical difference in headache relief between the groups at 3 or 4 hours. Headache relief was achieved by 85.5% of those treated with dihydroergotamine and by 83.3% of those treated with sumatriptan by 4 hours. By 24 hours 89.7% of dihydroergotamine-treated patients and 76.7% of sumatriptan-treated patients had relief (P = .004). Headache recurred within 24 hours after treatment in 45% of the sumatriptan-treated patients and in 17.7% of the dihydroergotamine-treated patients (P < or = .001). Both sumatriptan and dihydroergotamine were effective in aborting migraine headaches. Headache recurrence was two and a half time as likely with sumatriptan as with dihydroergotamine.",1996.0,0,1
512,8665577,Pilot study of MK-462 in migraine.,N R Cutler; J Claghorn; J J Sramek; G Block; D Panebianco; H Cheng; T V Olah; S A Reines,"MK-462 is a potent, selective 5HT1D receptor agonist which may be useful in treating acute migraine. We conducted a double-blind placebo-controlled inpatient study to assess the preliminary efficacy and safety of oral doses of MK-462 20 mg (n = 8) and 40 mg (n = 36) vs placebo (n = 21), administered to 65 male and post-menopausal female migraine patients aged 22-51 with moderate or severe migraine headache. Headache severity and functional disability were measured at 0.5, 1, 1.5, and 2 h post-dose. The 20 mg dose was well tolerated and 4/8 patients obtained relief in headache severity at the 2 h time point. The 40 mg dose was well tolerated and was significantly (p < 0.05) superior to placebo at the 1.5 and 2 h time points (with 27/36 or 75% obtaining relief at 2 h compared to 7/21 or 33% for placebo). Adverse events occurred in 50% of patients on 20 mg MK-462, 72% of those on 40 mg MK-462, and in 52% of placebo-treated subjects. The most common adverse events associated with MK-462 were drowsiness (20 mg 12%; 40 mg 44%; placebo 24%), dry mouth (40 mg 36%; placebo 19%), and lightheadedness/dizziness (40 mg 17%; placebo 10%). Based on these preliminary results, MK-462 appears worthy of continued study for the treatment of acute migraine.",1996.0,0,1
513,8675426,Effect of hyperbaric oxygen on the immunoreactivity to substance P in the nasal mucosa of cluster headache patients.,F Di Sabato; M Giacovazzo; G Cristalli; M Rocco; B M Fusco,"Exposure to hyperbaric oxygen has been shown to be effective in cluster headache, but the mechanism of the action is still not clear. Primary nociceptive neurons, containing neuropeptides such as substance P and particularly those innervating the nasal mucosa, could be involved in the pathogenesis of cluster headache. The present study evaluated the effect of an exposure to hyperbaric oxygen on the content of substance P in the nasal mucosa of patients affected by cluster headache. The results were compared with those observed in another group of cluster headache patients who underwent a placebo procedure. The samples of nasal mucosa were analyzed by immunocytochemical methods. A qualitative analysis of the slides was carried out by an operator under ""blinded conditions"". A marked decrease in the content of immunoreactivity for substance P was found in the patients exposed to hyperbaric oxygen. The decrease was statistically significant when compared with the findings of the placebo procedure. The results of the present study indicate that an influence on the content of peripheral neuropeptides could be involved in the mechanism of action of the beneficial effect of hyperbaric oxygen in cluster headache.",1996.0,0,0
514,8694672,,,,,0,0
515,8695049,Influence of age on the GH response to sumatriptan administration in man.,V Coiro; R Volpi; C Davoli; G Caffarri; P Chiodera,"The present study was undertaken in order to assess the influence of aging on the serotonergic control of GH secretion in humans. For this purpose, 6 mg 5-HT1D-serotonergic receptor agonist sumatriptan (or placebo during control tests) was injected subcutaneously in a group of 9 young (26-40 yr old) and a group of 9 elderly male subjects (64-80 yr old). Sumatriptan-induced plasma GH rise was recorded during the next 2 hours. Plasma ACTH levels were also measured. The administration of the placebo was without effects in all subjects. Sumatriptan induced a striking increase in plasma GH levels in the younger group, whereas it slightly increased GH secretion in the older group (f = 9.59, p < 0.02). Plasma ACTH levels showed a similar physiological decline in all subjects during tests, regardless of sumatriptan treatment. These data show impaired serotonergic stimulatory regulation of GH secretion in elderly subjects.",1995.0,0,0
516,8706117,Response measures in the acute treatment of migraine.,E Skovlund; O Flaten,"Pain ratings from 268 migraine patients have been used to compare the visual analogue scale (VAS) and a four-point verbal rating scale. All patients completed pain ratings on both scales at the beginning of a migraine attack and 4 h after starting treatment with sumatriptan or placebo. The VAS scores showed large variability within each category on the verbal rating scale. A common way of analysing pain in migraine studies is to classify patient response as a success or failure based on the score on the four-point verbal rating scale. In this study, the statistical power of analysing response either as ""success or failure"" or by means of the VAS score has been investigated by stochastic simulation. The simulations showed that the two response measures resulted in approximately equal power.",1995.0,0,0
517,8714755,5-Hydroxytryptamine in the central nervous system.,E Chojnacka-Wójcik,"The review summarizes the results of studies into the role of 5-HT as a neurotransmitter in the central nervous system. The biosynthesis, release, metabolism and distribution of 5-HT; classification and localization of 5-HT receptors; electrophysiological effects of 5-HT and its influence on second messengers; autoregulation of 5-HT release; effects of 5-HT on the release of other neurotransmitters and pituary hormones; behavioral effects induced by 5-HT receptor agonists and the functional interaction between different receptor subtypes have been described. Additionally, some data on functional changes in the 5-HT system in psychiatric disorders have been cited, and a possibility of clinical utilization of 5-HT-active related drugs in neuropsychiatric and other diseases has been reviewed.",1995.0,0,0
518,8720348,[Evaluation of the efficacy of oral sumatriptan in the management of migraine attacks. Clinical results].,V Centonze; M B Polito; M Di Bari; L Fabbri; M A Cassiano; A Bassi; O Albano,"This italian multicentre, double blind, parallel groups study compared the efficacy, safety and tolerability of oral sumatriptan, given as new film-coated tablet, with placebo in the acute treatment of migraine. 88 Patients received placebo and 162 patients received sumatriptan 100 mg (plus an optional dose 2 h later if the headache persisted plus a further optional dose for recurrence within 24 h). Sumatriptan was significantly more effective than placebo at releiving headache at 2 h (51% versus 31%, P = 0.003) and 4 h (71% versus 35%, P < 0.001). Fewer sumatriptan-treated patients required a second dose compared with placebo-treated patients (49% versus 74%, P < 0.001). Sumatriptan was more effective than placebo at relieving nausea, vomiting and photophobia/phonophobia. Few patients were evaluable for treatment of headache recurrence, and statistical analysis was not possible. More sumatriptan-treated patients than placebo-treated patients reported adverse events (29% versus 16%) but the difference was not statistically significant. More of these events were mild to moderate in severity, of short duration and resolved without treatment. Sumatriptan had no clinically significant effect on blood pressure, heart rate, electrocardiogram or laboratory test results. It is concluded that oral sumatriptan 100 mg, given as a film-coated, tablet, provides an effective and well-tolerated acute treatment for migraine.",1995.0,0,1
519,8720549,Moral crisis.,L L Long,,1996.0,0,0
520,8720550,Treatment of acute migraine with sumatriptan--response in 40 consecutive patients.,H J Blumenthal; M A Weisz; S Burk,"Forty consecutive headache patients self-administered sumatriptan for migraine, diagnosed by the criteria of the International Headache Society (IHS). Eighty percent reported excellent response. Thirty-three percent had recurrence of headache within four to twelve hours, while 67% had no recurrence. Fifty-five percent of the patients reported mild side effects, but only 8% stopped therapy because of adverse reactions. No serious cardiovascular events occurred. Recommendations for safe use of sumatriptan are suggested.",1996.0,0,0
521,8721797,Assessing the quality of reports of randomized clinical trials: is blinding necessary?,A R Jadad; R A Moore; D Carroll; C Jenkinson; D J Reynolds; D J Gavaghan; H J McQuay,"It has been suggested that the quality of clinical trials should be assessed by blinded raters to limit the risk of introducing bias into meta-analyses and systematic reviews, and into the peer-review process. There is very little evidence in the literature to substantiate this. This study describes the development of an instrument to assess the quality of reports of randomized clinical trials (RCTs) in pain research and its use to determine the effect of rater blinding on the assessments of quality. A multidisciplinary panel of six judges produced an initial version of the instrument. Fourteen raters from three different backgrounds assessed the quality of 36 research reports in pain research, selected from three different samples. Seven were allocated randomly to perform the assessments under blind conditions. The final version of the instrument included three items. These items were scored consistently by all the raters regardless of background and could discriminate between reports from the different samples. Blind assessments produced significantly lower and more consistent scores than open assessments. The implications of this finding for systematic reviews, meta-analytic research and the peer-review process are discussed.",1996.0,0,0
522,8730971,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
523,8733984,,,,,0,0
524,8739554,Paroxetine treatment and the prolactin response to sumatriptan.,Y K Wing; E M Clifford; B D Sheehan; G M Campling; R A Hockney; P J Cowen,"We studied the effect of the selective serotonin re-uptake inhibitor (SSRI), paroxetine (20 mg daily for 16 days) on the neuroendocrine, cardiovascular, thermic and subjective responses to the 5-HT1D receptor agonist, sumatriptan (6 mg, SC). Compared to placebo injection, sumatriptan lowered plasma prolactin and oral temperature and increased diastolic blood pressure. While paroxetine increased baseline prolactin concentration, it had no effect on any of the responses to sumatriptan. In addition, paroxetine did not alter concentrations of sumatriptan in plasma. No adverse reactions resulted from the combination of sumatriptan and paroxetine. Our findings suggest that combined treatment with sumatriptan and paroxetine in the doses used in this study is not necessarily contra-indicated. In addition, short-term SSRI treatment may not desensitise 5-HT1D autoreceptors in humans.",1996.0,0,0
525,8741230,The clinical potential of endothelin receptor antagonists in cardiovascular medicine.,C J Ferro; D J Webb,"The endothelin family of peptides are extremely potent endogenous vasoconstrictor and pressor agents. Of the 3 isoforms, endothelin-1 is the major isoform produced by the vascular endothelium and is, therefore, likely to be of most importance for regulation of vascular function. Two endothelin receptor subtypes have so far been cloned in mammalian species; ET A, and ET B. Both receptor subtypes are found on smooth muscle cells and mediate the vasoconstrictor and pressor actions of endothelin. The ET B receptor is also found on vascular endothelial cells and mediates endothelin-dependent vasodilatation through release of nitric oxide and prostacyclin. Since their discovery in 1988, the endothelins have been the subject of intense research on their physiological function and potential pathophysiological role in cardiovascular disease. There is now good evidence that endothelin regulates vascular tone and blood pressure, and studies to support the development of endothelin receptor antagonists in conditions associated with chronic vasoconstriction, such as hypertension and heart failure, as well as in vasospastic disorders, such as subarachnoid haemorrhage and Raynaud's disease. There are now a number of selective ET A and combined ET A/B receptor antagonists available for preclinical studies. However, it is still not clear which of these will prove to be of most therapeutic value. Some of these agents are currently being assessed in early phase clinical trials. Endothelin receptor antagonists represent a novel therapeutic approach to a fundamental and newly discovered endogenous vasoconstrictor mechanism. The results of the current clinical trials are awaited with considerable interest.",1996.0,0,0
526,8749241,Analgesics and NSAIDs in the treatment of the acute migraine attack.,V Pfaffenrath; S Scherzer,"In the treatment of migraine attacks, an antiemetic in combination with an analgesic or ergot alkaloid is widely recommended. Medication should be introduced as early as possible, but only when there is no doubt that the headache is due to migraine. The antiemetic provides relief from the nausea and vomiting and also enhances the resorption of analgesics or ergot preparations. Domperidone 20 mg orally and 20 mg metoclopramide as suppository or 10-20 mg orally are mostly used as antiemetics. Analgesics such as 1000 mg acetylsalicylic acid as effervescent tablets, or 1000 mg paracetamol as effervescent tablets or suppositories should be given 15-20 min later. If this treatment fails, NSAIDs can be tried. In some studies naproxen in doses between 500 and 1000 mg and ibuprofen in doses between 400 and 800 mg have been shown to be effective, as well as NSAIDs like diclofenac, mefenamic acid, ketoprofen, tolfenamic acid and pirprofen. NSAIDs have been found to be superior to placebo and to standard reference drugs in the majority of the reviewed double-blind trials. Nevertheless, these effects are marginal in some studies or even without clinical relevance. Accordingly, there is still a need for further comparative studies.",1995.0,0,0
527,8749242,How does sumatriptan perform in clinical practice?,C G Dahlöf,"The patient's opinion on sumatriptan treatment has been obtained from 351 migraineurs (299F and 52M) by means of a telephone survey. The results are based on the patient's cumulative experience of more than 20,000 subcutaneous injections and more than 2,000 tablet doses. The average period during which subcutaneous sumatriptan (12 mg/ml, 0.5 ml) was used was 19.1 +/- 0.4 months and 84% of the patients had used more than 10 injections. The average number of migraine attacks per month was 3.0 +/- 0.1, injections per attack 1.7 +/- 0.1, and number of tablets (100 mg) per attack 1.8 +/- 0.2. Attack duration was decreased from on average 38.4 +/- 2.1 h to 2.3 +/- 0.5 h by subcutaneous sumatriptan and to 3.4 +/- 1.0 by orally administered sumatriptan. The average degree of efficiency at work with migraine was 76.3 +/- 1.9% on sumatriptan compared with 26.6% on other treatment options; 85% said that sumatriptan was much better than previous conventional therapies tested. During their experience with sumatriptan, 89% of the migraineurs reported altogether 1,058 adverse events (average 3.6 +/- 01, range 1 to 12) in connection with subcutaneous sumatriptan treatment. The three most frequent were drowsiness/sedation (49%), chest symptoms (40%) and injection site symptoms (37%). Among the table users, 87% reported altogether 122 adverse events (average 2.6 +/- 0.3, range 1 to 11). Seventy-eight percent of the responders responded to subcutaneous sumatriptan sometimes (22% always, 15% every second attack, 40% seldom) experienced a recurrence of their headache within 24 h. The average number of recurrences was 1.7 +/- 0.1 and the average time to recurrence 13.0 +/- 0.6 h (range 1.5-24 h). It is concluded that the selected group of migraineurs found sumatriptan to be very effective in reducing the symptoms of their migraine attacks, but also to cause several adverse events, in many cases, with short-lasting effect.",1995.0,0,1
528,8749244,"Treatment of cluster headache: clinical trials, design and results.",K Ekbom,"The spontaneous capricious course of cluster headache may give rise to some problems when treatment is being evaluated. This is one of several explanations for there being so few well-designed, randomized, double-blind clinical trials in cluster headache. The standard treatment of acute attacks of cluster headache is inhalation of 100% oxygen. In the prophylaxis of episodic cluster headache, ergotamine, verapamil, lithium, serotonin, inhibitors and steroids are used. In chronic cluster, lithium is the drug of choice, but verapamil may also be tried. Recently, hyperbaric oxygen has been shown to immediately abort acute attacks, and it seems that it may also be useful in the prophylactic treatment. The introduction of the novel 5HT1 agonist sumatriptan as a symptomatic relief of cluster attacks represents further significant progress. Two randomized, double-blind, placebo-controlled, cross-over trials have shown sumatriptan 6 mg sc to be a rapid, effective and well-tolerated acute treatment for cluster headache attacks. Within 15 min of treatment, 74% of attacks on sumatriptan responded compared to 26% of placebo-treated attacks. Functional disability was also significantly improved. Increasing the dose to 12 mg did not offer significantly greater relief compared to sumatriptan 6 mg, but was associated with an increased incidence of adverse events. Interim analysis of 3 months of data from a recent multinational open trial comprising, 138 patients having treated 6353 attacks with subcutaneous sumatriptan 6 mg revealed a headache relief in 96% of attacks treated. There was no evidence of an increased incidence of adverse events with frequent use of sumatriptan. No tachyphylaxis was seen over the 3 months, suggesting that sumatriptan is effective and well tolerated also in long-term acute treatment for cluster headache.",1995.0,0,1
529,8757005,A comparison of subcutaneous sumatriptan and dihydroergotamine nasal spray in the acute treatment of migraine.,J Touchon; L Bertin; A J Pilgrim; E Ashford; A Bès,"We compared the efficacy and safety of subcutaneous (SC) sumatriptan (6 mg) with that of dihydroergotamine (DHE) nasal spray (1 mg plus optional 1 mg) in the acute treatment of migraine. Two hundred sixty-six adult migraineurs (International Headache Society criteria) completed a multicenter, double-blind, double-dummy, cross-over study. Patients took SC sumatriptan for one attack and DHE nasal spray for the other in random order. Data from both treatment periods show that at all time points from 15 minutes, SC sumatriptan was significantly better than DHE nasal spray at providing both headache relief (moderate/severe headache improving to mild/none) and resolution of headache. Similarly, SC sumatriptan was superior to DHE nasal spray for the other efficacy end points assessed in the study. Patients reported that both treatments were well tolerated. Adverse events were reported by 43% of patients taking SC sumatriptan and 22% of patients taking DHE nasal spray. These were usually mild and transient. We conclude that subcutaneous sumatriptan has a faster onset of action than DHE nasal spray and provides greater relief of acute migraine symptoms.",1996.0,0,1
530,8771561,Different effects of the serotonergic agonists buspirone and sumatriptan on the posterior pituitary hormonal responses to hypoglycemia in humans.,P Chiodera; R Volpi; L Capretti; G Caffarri; M G Magotti; V Coiro,"The responses of serum oxytocin (OT) and vasopressin (AVP) to the serotonergic HT1A agonist buspirone (15 mg p.o.) or the HTD1 agonist sumatriptan (6 mg injected subcutaneously) were evaluated in 7 normal men either in basal conditions or during an insulin (0.15 iu/kg as an i.v. bolus) tolerance test (ITT). Neither buspirone nor sumatriptan administration modified the basal secretion of AVP and OT. Stimulation of 5HT-1D receptors with sumatriptan was unable to change neither AVP nor OT response to insulin-induced hypoglycemia. On the other hand, the pretreatment with the 5HT1A agonist buspirone significantly enhanced the OT response during hypoglycemia, without modifying the AVP rise. The results of this study suggest that serotonergic 5HT1A receptors may interact with hypoglycemia in the stimulation of OT, but not AVP secretion.",1996.0,0,0
531,8783473,Subcutaneous sumatriptan in the clinical setting: the first 50 consecutive patients with acute migraine in a pediatric neurology office practice.,S L Linder,"An open prospective study was undertaken to assess the efficacy and safety of subcutaneous sumatriptan in 50 consecutive children ages 6 to 18 years with severe migraine. There were 28 females and 22 males. The dose of sumatriptan was 0.06 mg/kg. Parameters included overall efficacy, time to relief, recurrence rate, adverse events, and objective global rating. Overall efficacy, defined by headache reduction from severe or moderate to mild or none, was 78%. Twenty-six percent responded within 30 minutes, 46% responded in 60 minutes, and 6% responded between 1 to 2 hours. Twenty-two percent had no response or a suboptimal response. Recurrence rate was only 6%. There was a difference in efficacy between male and female, as 91% of the males responded, while only 68% of the females responded. The males had more migraine alone while the females had migraine often with a coexistent tension-type headache. Eighty percent of all the patients had some adverse event which was usually mild and transient; however, one patient developed a transitory confusional state which resolved in 2 hours. Eighty-four percent reported a global rating of good to excellent, while 16% rated the treatment only fair to poor. These findings suggest that subcutaneous sumatriptan can be both effective and safe in childhood migraine, especially in dealing with migraine alone.",1996.0,0,0
532,8783475,Alternatives in drug treatment of chronic paroxysmal hemicrania.,S Evers; I W Husstedt,"Indomethacin is the drug of first choice in chronic paroxysmal hemicrania with clear relief of pain as a diagnostic criterion. In a few cases, indomethacin is not tolerated because of side effects. Therefore, the efficacy of carbamazepine, verapamil, sumatriptan, acetylsalicylic acid, and oxygen as drugs in the prophylactic or acute treatment of chronic paroxysmal hemicrania was studied in a prospective open trial with 10 patients suffering from chronic paroxysmal hemicrania. The trial results, in accordance with a review of the literature, suggest that acetylsalicylic acid (and probably naproxen and diclofenac) and verapamil are the most effective drugs of second choice in chronic paroxysmal hemicrania. The efficacy of sumatriptan in this condition needs still to be clarified, although there is evidence for partial efficacy. Carbamazepine and oxygen did not show any significant influence on chronic paroxysmal hemicrania.",1996.0,0,0
533,8791025,The clinical effectiveness of 311C90 in the acute treatment of migraine.,M D Ferrari,"Efficacy with currently marketed antimigraine compounds is less than optimal. 311C90 is a novel and selective 5-HT1D receptor agonist in development for the acute treatment of migraine. It shows evidence of both central and peripheral activity within the trigemino-vascular system and it is rapidly absorbed following oral administration. In clinical studies in migraine patients, a headache response at 2 hours has been observed in 65-81% of patients at doses above 1 mg. Favourable response rates are reported as early as 1 hour post-dose and efficacy rates continue to improve up to 4 hours. Headache recurrence is reported by 25-35% of patients and 311C90 is also effective in relieving the non-headache symptoms of migraine.",1996.0,0,0
534,8791030,"Can oral 311C90, a novel 5-HT1D agonist, prevent migraine headache when taken during an aura?",A Dowson,"The purpose of this pilot study was to determine whether 20 mg oral 311C90 can prevent the development of migraine headache when taken during the aura phase of a migraine attack. The study also aimed to provide an initial safety profile for 311C90 when taken during the aura. Forty patients (31 females, 9 males) were entered into this outpatient, double-blind, placebo-controlled, 2-period crossover trial. They all almost invariably experienced a migraine headache after the aura phase. Patients treated two migraine attacks during the aura phase in a random order, one with 311C90 20 mg and the other with placebo. Efficacy assessments were recorded on standard diary cards completed by each patient. A primary response was defined as the complete absence of headache pain in the 24 hour period following administration of the first dose of study medication. Safety assessments included ECGs, laboratory tests and the recording of adverse experiences. Twenty patients completed the study by treating 2 attacks, 16 of these were fully adherent to the study protocol. Three of the 16 patients responded to 311C90 whereas all patients developed a migraine headache after taking placebo. Two patients who did not respond to 311C90 described the developing headache as being ""non-migraine'. Adverse experiences reported were similar to those experienced by patients in previous studies when 311C90 was taken during a migraine headache. There were no reports of 311C90-related adverse effects on the aura. These preliminary results suggest that oral 311C90 may be of value in preventing a migraine headache and is safe when taken during the aura phase. This intriguing possibility therefore warrants further investigation possibly utilising formulations that would deliver meaningful plasma levels of drug more rapidly.",1996.0,0,1
535,8791240,Changes in cerebral blood flow velocity after treatment with sumatriptan or placebo and implications for the pathophysiology of migraine.,V Limmroth; A May; P Auerbach; G Wosnitza; T Eppe; H C Diener,"Whether the primary mechanisms of migraine are vascular or neurogenic is, as yet, unresolved. In humans it is still unclear whether sumatriptan acts via constriction of dilated arteries or through other mechanisms. Doppler sonography is a non-invasive method for measuring blood flow velocities (BFV), an indirect marker of vessel diameter. This double-blind crossover placebo-controlled trial investigated changes in BFV in extra- and intracranial arteries in 132 migraine attacks (66 patients) before and after treatment with either 6 mg sumatriptan s.c. or placebo. Significant increases in BFV were observed only in the middle cerebral artery (MCA) and the basilar artery (BA) after administration of sumatriptan. However, the majority of the patients showed no change in BFV following sumatriptan. No difference in BFV could be detected between headache and non-headache side or between migraine and headache free periods. Despite a slight increase in BFV in intracerebral arteries, this study does not support the concept that vasoconstriction is sumatriptan's principal mechanism in pain relief.",1996.0,0,0
536,8792038,"Prophylaxis of migraine with oral magnesium: results from a prospective, multi-center, placebo-controlled and double-blind randomized study.",A Peikert; C Wilimzig; R Köhne-Volland,"In order to evaluate the prophylactic effect of oral magnesium, 81 patients aged 18-65 years with migraine according to the International Headache Society (IHS) criteria (mean attack frequency 3.6 per month) were examined. After a prospective baseline period of 4 weeks they received oral 600 mg (24 mmol) magnesium (trimagnesium dicitrate) daily for 12 weeks or placebo. In weeks 9-12 the attack frequency was reduced by 41.6% in the magnesium group and by 15.8% in the placebo group compared to the baseline (p < 0.05). The number of days with migraine and the drug consumption for symptomatic treatment per patient also decreased significantly in the magnesium group. Duration and intensity of the attacks and the drug consumption per attack also tended to decrease compared to placebo but failed to be significant. Adverse events were diarrhea (18.6%) and gastric irritation (4.7%). High-dose oral magnesium appears to be effective in migraine prophylaxis.",1996.0,0,0
537,8792040,"311C90 (Zolmitriptan), a novel centrally and peripheral acting oral 5-hydroxytryptamine-1D agonist: a comparison of its absorption during a migraine attack and in a migraine-free period.",L L Thomsen; R Dixon; L H Lassen; M Gibbens; M Langemark; L Bendtsen; D Daugaard; J Olesen,"The oral absorption of a 10-mg oral dose of the novel 5-hydroxytryptamine (5HT1D) agonist, 311C90, was compared during a moderate or severe migraine headache and in a migraine-free period in an open, two-period study. The safety and efficacy of 311C90 in acute migraine were also assessed. Twenty patients attended the clinics during a moderate or severe migraine attack and 18 patients returned for a second dose in a migraine-free period. 311C90 was less rapidly absorbed during a migraine attack compared to the migraine-free period, consistent with gastric stasis during a migraine attach. The median area under the curve (AUC) was 15.7 ng/mlh lower during a migraine (median AUC: 18.4 ng/ml.h, range: 0-60.8 ng/ml.h) compared to the migraine-free period (median AUC: 33.4 ng/ml.h, range 9.4-79.5 ng/ml.h) (95% confidence interval: 6.9, 25.3) and the time to reach maximum plasma concentration was delayed (n = 18). Eleven out of 20 patients experienced a significant improvement in migraine headache intensity at 2 h post-dose. Plasma 311C90 concentrations were generally higher in those patients who responded to treatment with 311C90 in the plasma, but there was one patient with no quantifiable 311C90 in the plasma whose headache improved. Minor adverse experiences were reported in 11 out of 20 patients during a migraine attack and in 11 out of 18 patients outside an attack. They occurred shortly following drug administration and were of short duration, but their occurrence did not appear to be related to plasma 311C90 concentration. There were no clinically significant changes in blood pressure or 12-lead ECG during the assessment period.",1996.0,0,0
538,8824009,High-dose versus low-dose valproic acid as a prophylactic medication.,K Taylor; J Goldstein,"Valproic acid has been shown to be effective in migraine prophylaxis. Its method of action is believed to be the inhibition of gamma-aminobutyric acid transaminase. The therapeutic dose needed to prevent migraine headaches has been examined in several studies, yet the optimum dose has not been found. In this case report, valproic acid was given to a 24-year-old woman with chronic headaches at 1000 mg per day. Her headaches resolved for 2 months. She tapered herself off of the medication, and her headaches returned. She was restarted at 500 mg per day of valproic acid and again, her headaches resolved. She preferred being on the lower dose which she found as effective as the higher dose. Her case makes two interesting points. The first is that lower dosages of valproic acid may be as effective as higher ones in headache prophylaxis. The second is that more studies looking at dose ranges are needed to correlate effectiveness with daily requirements.",1996.0,0,0
539,8826568,Pharmacologic management of postdural puncture headache.,A Choi; C E Laurito; F E Cunningham,"To discuss the pathogenesis, incidence, and clinical presentation of postdural puncture headaches (PDPHs) and to provide a comprehensive evaluation on the pharmacologic management of PDPH. A MEDLINE search was used to identify pertinent literature published in English including review articles, case reports, letters, and abstracts. Information was also extracted from textbooks for background purposes. All clinical studies, case reports, abstracts, and letters were included because of the limited amount of literature available on the pharmacologic therapy for PDPH. Related research articles and review articles were also used to provide background information on PDPH. Methodology and results from clinical trials and abstracts were described and evaluated. Case reports and letters were summarized and critically reviewed for the feasibility of the different treatment modalities. Information on the pathophysiology, incidence and severity, and clinical presentation of PDPH was extracted from related research articles, review articles, and textbooks. The epidural blood patch (EBP) is one of the most effective treatments for PDPH. Pharmacologic management of PDPH offers a less invasive treatment modality than the EBP. Numerous drug therapies have been presented in the literature, though few merit clinical application. Caffeine therapy, both oral and parenteral, is the most commonly used pharmacologic treatment modality. Theophylline and sumatriptan are potentially promising agents for the treatment of PDPH. Epidural administration of fluids and drugs is also effective in the treatment of PDPH. Epidural adrenocorticotropic hormone and epidural morphine also demonstrate some potential in the treatment of PDPH. Individual patient characteristics (i.e., HIV, sepsis) need to be considered when deciding on a treatment. More reports, especially clinical studies, are necessary before a definitive statement can be made regarding any one treatment. In the meantime, therapy will be guided by clinical judgement based on the literature reviewed in this article. Intravenous and oral caffeine are effective and noninvasive treatments for PDPH. Epidural NaCl 0.9% or dextran are alternatives when the EBP is unsuccessful or contraindicated. Several methods of pharmacologic management have been cited in the literature, but all require further evaluation.",1996.0,0,0
540,8838441,The tolerability and pharmacokinetics of the novel antimigraine compound 311C90 in healthy male volunteers.,E Seaber; N On; S Phillips; R Churchus; J Posner; P Rolan,"1. 311C90 is a novel and selective agonist at 5-HT1D receptors, with central and peripheral actions, currently in development for the acute oral treatment of migraine. 2. The pharmacokinetic and tolerability profiles of single oral doses from 1-50 mg 311C90 were investigated in 12 healthy male volunteers in a double-blind, placebo-controlled, dose-escalating study. 3. 311C90 was well tolerated with most adverse experiences of mild and transient nature. 4. Absorption was rapid with dose-independent kinetics. Median tmax was 2-4 h although 50-85% of eventual Cmax was attained within 1 h. The t1/2 was 2.5-3 h with a high apparent plasma clearance (CL/F > 2000 ml min-1) and apparent volume of distribution (Vz/F) of 400-500 l. 5. Three metabolites were detected in plasma and urine, one of which, the N-desmethyl metabolite, has 5-HT1D agonist activity. 6. 311C90 showed no clinically significant effects on blood pressure, heart rate, ECG or laboratory variables at any dose and demonstrated a tolerability and pharmacokinetic profile compatible with an acute oral migraine treatment.",1996.0,0,0
541,8839613,Drug treatment of migraine: acute treatment and migraine prophylaxis.,P Tfelt-Hansen,"Most current randomised controlled trials concern the acute treatment of migraine. Sumatriptan, a serotonin receptor agonist, was evaluated in 8 randomised controlled trials. Using a novel cartridge self-injector system subcutaneous sumatriptan was found superior to placebo, and oral sumatriptan in doses from 25 mg to 100 mg was found superior to placebo with no difference among doses. An oral dose of 100 mg sumatriptan was not superior to a combination of lysine acetylsalicylate plus metoclopramide, and 100 mg sumatriptan given 4 hrs after subcutaneous sumatriptan could not prevent recurrence of headache. Nasal dihydroergotamine was found to have some efficacy in acute migraine treatment, whereas nasal butorphanol, although effective in repeated doses, was hampered by many side effects. The prophylactic effect of valproate was confirmed in one randomised controlled trial.",1996.0,0,0
542,8879897,Efficacy and tolerability of subcutaneous sumatriptan administered using the IMITREX STATdose System.,G R Mushet; R K Cady; C C Baker; B Clements; D L Gutterman; R Davis,"The efficacy and tolerability of subcutaneous (SC) sumatriptan administered with the IMITREX (sumatriptan succinate) STATdose System, which circumvents the need for patients or health care professionals to handle a syringe, were evaluated in two randomized, double-masked, parallel-group, placebo-controlled, multicenter studies. In the clinic, 158 adults with migraine diagnosed according to International Headache Society criteria received SC sumatriptan (6 mg) or placebo delivered with the IMITREX STATdose System for treatment of a migraine attack. By 120 minutes after SC dosing, 73% and 79% of sumatriptan-treated patients, compared with 28% and 37% of placebo-treated patients in studies 1 and 2, respectively, experienced headache relief (a statistically significant difference). Clinical disability scores 120 minutes after dosing showed that 75% and 85% of sumatriptan-treated patients, compared with 30% and 42% of placebo-treated patients, were normal or only mildly impaired (a statistically significant difference). Similar efficacy rates were observed for nausea, phonophobia, and photophobia. No serious or unusual adverse events occurred, and no clinically relevant abnormalities in laboratory test values were reported. Based on these results, we concluded that SC sumatriptan (6 mg) administered using the IMITREX STATdose System is effective for the treatment of migraine. The efficacy and tolerability profiles of SC sumatriptan administered with this device are similar to those reported for SC sumatriptan administered with a conventional syringe.",1996.0,0,1
543,8884400,"A double-blind, placebo-controlled, crossover, study to evaluate the efficacy of subcutaneous sumatriptan in the treatment of atypical facial pain.",S al Balawi; M Tariq; C Feinmann,"A double-blind, placebo-controlled crossover study was undertaken to assess the efficacy and tolerability of sumatriptan in patients with atypical facial pain. Patients were aged 18-65 years and had at least a 6 months history of atypical facial pain. A total of 19 patients were recruited and assessed for pain scores (total, sensory and affective) by using a short form McGill pain questionnaire preinjection and and at 60 and 120 minutes after subcutaneous injection of sumatriptan (6 mg) or placebo. Safety and tolerability was assessed by recording adverse events during and after the injection. One patient received only one treatment since her pain symptoms resolved after the first treatment. Rest of the patients returned to the clinic 3-6 weeks later and received alternate treatment for atypical facial pain in the same fashion as on the first occasion. Treatment of patients with sumatriptan produced significant relief in sensory, affective and total pain at 120 minutes postinjection (P < .05). Sumatriptan failed to produce a significant reduction in sensory and total pain scores at 60 minutes following treatment, however the result was statistically significant for the affective pain score (P < .05). No death or other serious adverse events were reported. No patient was withdrawn from the study due to an adverse event. However, all the patients treated with sumatriptan experienced one or more adverse events. The most common reported adverse symptoms during the sumatriptan treatment period were injection site reactions, headache, feeling of heaviness, warm or hot sensation and disorders of mouth or tongue. However, most of these side effects were mild and transient. In conclusion, this study points towards some beneficial effect of a single subcutaneous injection of sumatriptan in the treatment of atypical facial pain. However, this data is not sufficient to suggest the clinical utility of subcutaneous sumatriptan (6 mg) for the management of atypical facial pain. Further studies are necessary to test the effects of prolonged subcutaneous and oral multiple dose administration of sumatriptan for the treatment of atypical facial pain.",1996.0,0,0
544,8895256,Sumatriptan and episodic pain syndromes other than migraine.,I Roberts-Thomson; J Argyrides; P Pannall; D Frewin,,1996.0,0,0
545,8900548,"Subcutaneous sumatriptan for the treatment of migraine: humanistic, economic, and clinical consequences.",J A Cohen; D G Beall; D W Miller; A Beck; G Pait; B D Clements,"This study examined the humanistic, economic, and clinical consequences of using subcutaneous sumatriptan for 6 months for the acute treatment of migraine in 126 patients enrolled in a group-model health maintenance organization. Patients received open-label sumatriptan (6 mg) for the treatment of migraines that occurred during a 6-month period. For each migraine, patients recorded migraine pain severity (none, mild, moderate, or severe) before treatment and 2 hours posttreatment and the time until onset of patient-defined meaningful relief. Patients also completed both the Short Form-36 Health Survey and Migraine-specific Quality of Life (QOL) Questionnaire at screening (to cover the period prior to initiation of treatment) and after 3 and 6 months of treatment. Patients' medical records were reviewed to obtain information on the frequency of migraine-related pharmacy use, general outpatient services, and urgent care services during the treatment period and the 12 months prior to initiation of treatment. By 2 hours after the dose, 71% of patients had moderate or severe pain reduced to mild or none, and 86% of patients achieved meaningful relief. At 3 months and 6 months, sumatriptan was associated with improvements relative to pre-sumatriptan baselines in Short Form-36 Health Survey and Migraine-specific QOL Questionnaire scores (P < .002). Sumatriptan was also associated with significant reductions in the average number of migraine-related general outpatient and urgent care services (P < .001). The use of sumatriptan for 6 months was associated with improvements in health-related quality of life, reductions in health care resource use, and a high percentage of treatment successes.",1996.0,0,1
546,8902249,Headache induced by a nitric oxide donor (nitroglycerin) responds to sumatriptan. A human model for development of migraine drugs.,H K Iversen; J Olesen,"Experimental ""vascular"" headache in humans may be used in characterizing new migraine drugs. The effects of sumatriptan on nitroglycerin-(NTG)-induced headache and arterial responses were therefore studied. Following a double-blind randomized crossover design, 10 healthy volunteers received sumatriptan 6 mg s.c. or placebo succeeded by 20 min NTG (0.12 microgram/kg/min) infusion. Headache was rated on a 10 points scale. Temporal and radial artery diameters and velocity in the middle cerebral artery (MCA) were measured with ultrasound. Sumatriptan reduced the NTG-induced headache, median score 1.5 versus 4 after placebo (p < 0.01) and decreased temporal and radial artery diameters 75 +/- 3 and 86 +/- 3% of baseline respectively (p < 0.05). Blood velocity in the MCA was unaffected. The NTG model may prove to be a valuable tool in the development of future migraine drugs. The results suggest that NTG headache in non-migraineurs may share mechanisms with migraine headache.",1996.0,0,0
547,8912486,"Rizatriptan vs sumatriptan in the acute treatment of migraine. A placebo-controlled, dose-ranging study. Dutch/US Rizatriptan Study Group.",W H Visser; G M Terwindt; S A Reines; K Jiang; C R Lines; M D Ferrari,"Rizatriptan (MK-462) is a new 5-hydroxytryptamine1D (serotonin1D; 5-HT1D) receptor agonist for the acute treatment of migraine that has improved pharmacokinetic properties compared with sumatriptan succinate. To assess the efficacy and tolerability of 10-, 20-, and 40-mg doses of oral rizatriptan vs a 100-mg dose of oral sumatriptan succinate and placebo for the acute treatment of migraine. Randomized, double-blind, parallel-group, placebo-controlled, outpatient trial. Ten US and 4 Dutch investigator centers. Patients who had migraine with or without aura (N = 449). The proportion of patients whose conditions improved from severe or moderate headache immediately before dosing to mild or no headache at 2 hours after drug administration (ie, headache relief). The proportion of patients with headache relief was 18% for placebo; 46% for sumatriptan; and 52% for 10-mg, 56% for 20-mg, and 67% for 40-mg rizatriptan. All differences with placebo were statistically significant (P < .001), and 40-mg rizatriptan was superior to sumatriptan (P = .01). The proportion of patients who became free of pain at 2 hours was 3% for the placebo-treated group; 22% for the sumatriptan-treated group; and 26%, 35%, and 47% for the group of patients who took the 10-, 20-, and 40-mg doses of rizatriptan, respectively (all differences with placebo, P < .005; 40-mg rizatripan vs sumatriptan, P = .001). The recurrence of headache within 24 hours was found to be equal across all treatment groups-approximately 40%. Adverse events (most commonly short-lasting mild or moderate dizziness and drowsiness) occurred more frequently after a 40-mg dose of rizatriptan was given than after the other treatments. The antimigraine effect of 10- and 20-mg rizatriptan was superior to placebo, and comparable with that of 100-mg sumatriptan succinate; the efficacy of 40-mg rizatriptan was superior to that of both placebo and 100-mg sumatriptan succinate, although it was associated with a high frequency of adverse events.",1996.0,0,1
548,8913410,"Current developments in neurology, Part I: Advances in the pharmacotherapy of headache, epilepsy, and multiple sclerosis.",B E Gidal; M L Wagner; M D Privitera; C Dalmady-Israel; M L Crismon; S C Fagan; N M Graves,"When caring for patients with disorders of the central nervous system such as migraine headaches, epilepsy, or MS, clinicians are faced with increasingly complex pharmacotherapeutic options. Pharmacotherapeutic strategies directed toward prevention, reversal, or cure of these diseases are hampered by an incomplete understanding of the underlying pathophysiology. In this decade of the brain, basic science research combined with difficult but necessary clinical trials may answer some seemingly overwhelming questions for these devastating illnesses.",1996.0,0,0
549,8916559,Treatment of migraine with BMS180048: response at 2 hours. North American BMS180048 Study Group.,J R Couch; J Saper; J P Meloche,"BMS180048 is a 5HT agonist that was well-tolerated in early phase II trials. This study utilized a double-blind, parallel-group dose ranging format, comparing BMS180048 in doses of 25, 50, or 75 mg to placebo in effectiveness of treatment of a single migraine headache. To assess tolerability of BMS180048, patients received a test dose of the medication they would receive for a headache in the clinic under observation. If no significant side effects occurred, patients were allowed to treat a headache. Headaches were moderate or severe in intensity before treatment, and response at 2 hours was tabulated. Reduction to mild or no headache was the criteria for successful response. Response rates at 2 hours were as follows: placebo--19 of 53 subjects (35.8%); 25 mg--21 of 53 subjects (40.3%); 50 mg--34 of 53 subjects (64.2%); 75 mg--35 of 55 subjects (63.6%) The improvement for subjects treated with 50 or 75 mg of BMS180048 when compared to placebo was highly significant (P < .01). Nausea, photophobia, and phonophobia improved 35% to 50% for BMS180048-treated subjects and 20% to 24% in the placebo group. The improvement in these symptoms in comparison to placebo was statistically significant only for nausea in those treated with 75 mg of BMS180048 (P = .02). Side effects were mild for the most part, and no serious adverse events occurred. The study suggests BMS180048 is effective in acute symptomatic therapy of migraine.",2001.0,0,1
550,8916562,Prescribing practices for the management of headache in Newfoundland and Labrador.,S Furlong; W Pryse-Phillips; M Crowley; C J Turner,"To assess the impact of sumatriptan in clinical practice, we undertook a retrospective analysis of the government of Newfoundland and Labrador's prescription drug program data base for 35 consecutive patients prescribed sumatriptan. The number of doses of all drugs prescribed ranged from 121 to 18,874 on from 4 to 357 prescriptions per patient over 1 to 19 months. The mean number of doses of analgesic drugs prescribed before sumatriptan therapy was 56 per month and after initiation of sumatriptan was 46 per month. The prescribing of multiple analgesics was common; 79% received three or more different analgesics. Twenty-two (63%) patients were prescribed medications indicated for the prophylaxis of migraine concomitantly with drugs indicated for symptomatic treatment. Twenty-four (69%) patients were prescribed medication capable of inducing migraine. We conclude that sumatriptan did not have a major impact on the outcomes of these patients judged by their use of analgesics. The simplest explanation is that many of the patients were suffering from analgesic-induced headache rather than migraine. In addition, we conclude that there were deficiencies in prescribing practices including numbers, quantities, and choice of analgesics; the use of analgesics concomitantly with drugs indicated for migraine prophylaxis; and the use of drugs capable of inducing migraine. Further research is required to validate these findings.",1996.0,0,0
551,8933994,Melatonin versus placebo in the prophylaxis of cluster headache: a double-blind pilot study with parallel groups.,M Leone; D D'Amico; F Moschiano; F Fraschini; G Bussone,"A fall in nocturnal plasma melatonin occurs in patients with cluster headache, suggesting that melatonin may play a role in the promotion of attacks. During a cluster period, we administered melatonin to 20 cluster headache patients (2 primary chronic, 18 episodic) in a double-blind placebo-controlled study of oral melatonin 10 mg (n = 10) or placebo (n = 10) for 14 days taken in a single evening dose. Headache frequency was significantly reduced (ANOVA, p < 0.03) and there were strong trends towards reduced analgesic consumption (ANOVA, p < 0.06) in the treatment group. Five of the 10 treated patients were responders whose attack frequency declined 3-5 days after treatment, and they experienced no further attacks until melatonin was discontinued. The chronic cluster patients did not respond. No patient in the placebo group responded. There were no side effects in either group. Although the response rate is low, melatonin may be suitable for cluster headache prophylaxis in some patients, particularly those who cannot tolerate other drugs.",1996.0,0,0
552,8933995,Alniditan in the acute treatment of migraine attacks: a subcutaneous dose-finding study. Subcutaneous Alniditan Study Group.,J Goldstein; C G Dahlöf; H C Diener; J Olesen; R Schellens; J M Senard; D Simard; T J Steiner,"Alniditan is a new 5HT1D receptor agonist, belonging to a different chemical class from sumatriptan and other indole derivatives used or being developed for the treatment of acute migraine. In a multinational double-blind randomized parallel-groups dose-finding trial, alniditan was given subcutaneously in hospital to patients with migraine headache of moderate or severe intensity at doses of 0.8 mg (n = 44), 1.0 mg (n = 42), 1.2 mg (n = 46) and 1.4 mg (n = 39). Efficacy, tolerability and safety of each dose were compared with those of placebo (n = 41). At 2 h after injection, headache was absent or mild in 83% and 82% of patients receiving alniditan 1.2 and 1.4 mg respectively compared with 39% for placebo (p < or = 0.002). Complete relief from headache was achieved in 72% (1.4 mg). Time to onset of relief decreased with increasing alniditan dose, and there was a dose-dependent reduction in headache recurrence rate: 25% of patients receiving 1.4 mg had responded by 15 min and headache recurred within 24 h in only 16% of the patients who initially responded to alniditan 1.4 mg, significantly less than for placebo (p = 0.018). Alniditan was superior to placebo in reducing the associated symptoms of nausea, phonophobia and photophobia, and in increasing patients' functional ability. The use of rescue medication was reduced when compared with placebo, and up to 87% of patients said that they would use the drug again if available. No clinically relevant cardiovascular effects were seen, nor consistent changes in clinical laboratory findings. Adverse effects, mainly head pressure, paraesthesia, and hot flushes, were reported by 34% of placebo-treated patients and up to 70% of patients receiving alniditan, but all doses were very well tolerated and no clear relationship with dose was established. Comparison with published findings suggests that alniditan 1.4 mg sc may have advantages over sumatriptan 6 mg sc in providing complete relief from acute migraine headache, and may be associated with fewer headache recurrences within 24 h. Both of these suggestions warrant further and larger trials of alniditan in acute migraine.",1996.0,0,0
553,8935482,Oral sumatriptan in the acute treatment of migraine and migraine recurrence in general practice.,R J Scott; W R Aitchison; P R Barker; G I McLaren,"We investigated the efficacy, safety and tolerability compared with placebo of a second dose of oral sumatriptan 100 mg in 1349 general practice patients who had already treated a moderate or severe migraine headache with 100 mg sumatriptan 4 h earlier. Headache was relieved by the first sumatriptan dose in about 70% of patients, but the second dose did not produce significantly more relief than placebo, either in non-responders or in the group as a whole, nor did it reduce other symptoms (photophobia, nausea, vomiting, etc.) at 8 h, or influence the incidence of headache recurrence. The drug was well-tolerated, and a further single dose was effective in treating recurrence after initial relief. A single 100 mg dose of sumatriptan is an effective acute treatment for migraine. A second dose should be reserved for treating headache recurrence.",1996.0,0,1
554,8970446,Subcutaneous dihydroergotamine vs subcutaneous sumatriptan.,T Catarci; R Cerbo,,1996.0,0,1
555,8984084,"Impact of sumatriptan on workplace productivity, nonwork activities, and health-related quality of life among hospital employees with migraine.",G R Mushet; D Miller; B Clements; G Pait; D L Gutterman,"This prospective, open-label study evaluated the effects of subcutaneous sumatriptan versus usual therapy on workplace productivity, activity time outside of work, and health-related quality of life in 43 men or women who were hospital employees diagnosed with migraine according to international Headache Society criteria. Patients treated migraines with their usual therapy for 12 to 18 weeks followed by subcutaneous sumatriptan for 6 months. Health-related quality of life measurements obtained at baseline, after usual therapy, and after sumatriptan therapy included the Short Form-36 Health Survey and the Migraine-Specific Quality of Life Questionnaire. Patient daily diaries were used to capture data on migraine symptoms and on Lost Workplace Productivity and Non-workplace Activity Time. Traditional clinical efficacy measures were obtained to support the pharmacoeconomic data. Clinical data showed that the percentage of treated migraine days per patient on which the patient experienced relief (moderate or severe pain reduced to mild or none) was 75% with sumatriptan and 25% with usual therapy. The mean time to meaningful relief was 1.1 hours during the sumatriptan phase and 4.2 hours during the usual therapy phase. Lost Workplace Productivity and Nonworkplace Activity Time was 35% lower with sumatriptan therapy (1.5 hours) compared with usual therapy (2.3 hours). Time missed from work due to symptoms, time worked with symptoms, and time normal activities were carried on with symptoms were each lower during sumatriptan therapy compared with usual therapy. Scores on each of the three Migraine-Specific Quality of Life Questionnaire dimensions and on the Role-Emotional dimension of the Short Form-36 were significantly more favorable after sumatriptan than after usual therapy (P < 0.05). These data demonstrate that treatment of migraines with sumatriptan for 6 months following usual therapy for 12 to 18 weeks was associated with improvement in clinical efficacy, reduction in lost workplace productivity and nonworkplace activity time, and enhancement of key dimensions of health-related quality of life among employees of a large university hospital.",1996.0,0,1
556,8991488,Pharmacokinetics and food interaction of MK-462 in healthy males.,H Cheng; W J Polvino; D Sciberras; L Yogendran; K A Cerchio; K Christie; T V Olah; D McLoughlin; I James; J D Rogers,"A study was conducted to assess the safety, tolerability, and pharmacokinetics of single intravenous (IV) doses of 5-90 micrograms kg-1 of MK-462, and the effect of food on the pharmacokinetics of MK-462 administered orally to healthy males. Results of this study indicate that IV doses of MK-462 from 5 to 90 micrograms kg-1 are well tolerated. The disposition kinetics of MK-462 were linear for IV doses up to and including 60 micrograms kg-1. The values of the plasma clearance (CL), steady-state volume of distribution (Vss), plasma terminal half-life (t1/2), and mean residence time in the body (MRT) of MK-462 averaged 1376 mL min-1, 140 L, 1.8 h, and 1.7 h, respectively, and remained essentially constant over the dosage range of 10-60 micrograms kg-1 of IV MK-462. However, as the dose increased from 60 to 90 micrograms kg-1, the mean value of the apparent CL decreased from 1376 to 807 mL min-1. Thus, elimination of MK-462 was dose dependent in this dosage range. Based on the disposition decomposition analysis (DDA), it was shown that the Vss value of MK-462 remained essentially constant over the dosage range of 10-90 micrograms kg-1 of IV MK-462. The following values of two dose-independent parameters were also calculated by using DDA: distribution clearance (CLd) = 2028 mL min-1, and mean transit time in the peripheral tissues (MTTT) = 0.74 h. The mean values of AUC, Cmax, tmax, and apparent t1/2 of MK-462 in 12 subjects each receiving a 40 mg tablet of MK-462 without breakfast were 330 ng.h mL-1, 77 ng mL-1, 1.6 h, and 1.8 h, respectively. Although administration of a standard breakfast prior to dosing increased the AUC value (by approximately 20%) of MK-462 and delayed its absorption, there were no significant effects of the meal on the values of Cmax and apparent t1/2 of MK-462.",2000.0,0,0
557,8992678,"[The combination of oral lysine-acetylsalicylate and metoclopramide compared with oral sumatriptan in the treatment of migraine attacks. A randomized, double-blind, placebo-controlled clinical trial].",P Tfelt-Hansen; P Henry; L J Mulder; R G Scheldewaert; J Schoenen; G Chazot,"A combination of lysine acetylsalicylate (equivalent to 900 mg aspirin) and 10 mg metoclopramide (LAS + MTC) was compared with oral sumatriptan (100 mg) and placebo in 421 patients with migraine in a randomized, double-blind, clinical trial. LAS + MTC was as effective as sumatriptan with a decrease in headache from severe or moderate to mild or none in 57% and 53%, respectively, for the first migraine attack treated, the primary efficacy parameter. Both treatments were better than placebo (success rate 24%, p < 0.001). LAS + MTC was better tolerated than sumatriptan (adverse events in 18% and 28%, respectively, p < 0.05).",1996.0,0,0
558,9001842,Sumatriptan and lost productivity time: a time series analysis of diary data.,D W Miller; B C Martin; C M Loo,"Two previously conducted clinical studies assessed lost nonworkplace activity time and lost workplace productivity time due to migraine symptoms in subjects using sumatriptan for 6 months to treat their migraines after a 12- to 18-week period of using their usual therapy without sumatriptan. Although statistically significant differences in lost nonworkplace activity time and lost workplace productivity time between the usual therapy and sumatriptan treatment periods were detected using the Wilcoxon signed-rank test, this test could not determine whether differences were attributable to inherent trends in the data. This current study employed time series analysis, which detects and controls for preexisting trends in data, to further explore the possibility that the observed reductions in lost time in the two clinical studies were related to management of the subjects with sumatriptan. The intercepts and slopes of the computed linear models suggest that the initiation of sumatriptan therapy produced savings of 0.8 hours of nonworkplace activity time and 0.5 hours of workplace productivity time per patient per week. These savings were sustained throughout the sumatriptan treatment period. Preexisting trends in the data were not detected in the models. Thus the productivity gains are not associated with either time effects or the statistical phenomenon of regression to the mean, but variables that are extreme in initial measurements will tend to be closer to the center of the distribution in subsequent measurements. This strengthens the hypothesis that management of migraine with sumatriptan is associated with reductions in lost productivity time.",1996.0,0,1
559,9040124,Sumatriptan decreases food intake and increases plasma growth hormone in healthy women.,S Boeles; C Williams; G M Campling; E M Goodall; P J Cowen,"We studied the effect of the 5-HT1B/ID receptor agonist sumatriptan (6 mg s.c.) on plasma growth hormone and prolactin and food intake in 15 healthy female subjects using a double-blind, placebo-controlled, cross-over design. Sumatriptan significantly elevated plasma growth hormone but did not alter plasma prolactin. Sumatriptan also significantly lowered total food intake in a buffet meal, particularly decreasing the intake of fat. Our results indicate that 5-HT1B/ID receptors may be involved in the regulation of food intake in humans. In addition, while activation of 5-HT1B/ID receptors stimulates growth hormone release in both men and women, sumatriptan lowers plasma prolactin only in men, suggesting sex differences in the 5-HT regulation of prolactin release.",1997.0,0,0
560,9051333,A within-patient comparison of subcutaneous and oral sumatriptan in the acute treatment of migraine in general practice.,K Gruffydd-Jones; C A Hood; D B Price,"This study compared, for the first time in the United Kingdom, the efficacy and safety of oral 100 mg and subcutaneous 6 mg sumatriptan within a patient for the acute treatment of migraine. The patient's preference for the two formulations of sumatriptan were also recorded. The study was a multicentre, randomized, open, crossover design with an optional open parallel group extension. Individual attacks were treated with one formulation only. Over 70% of patients who treated attack 1 in both treatment periods of the crossover phase reported headache relief with each formulation at 4 h. Only 3% of patients failed to respond to at least one of the formulations at this time point. At the end of the crossover phase patient preference for the injection more than doubled from the pretreatment level in those patients who were previously naive to sumatriptan. During the optional phase of the study, 38% of patients chose to treat some attacks with oral and some with subcutaneous sumatriptan. The main reason for choosing injection was speed of relief, whilst convenience was the major reason for the use of the tablet.",1997.0,0,1
561,9056052,Initial human experience with MK-462 (rizatriptan): a novel 5-HT1D agonist.,D G Sciberras; W J Polvino; B J Gertz; H Cheng; M Stepanavage; J Wittreich; T Olah; M Edwards; T Mant,"We evaluated the pharmacokinetics and pharmacodynamics of oral MK-462 in comparison with oral sumatriptan in healthy male volunteers. Sixteen healthy male volunteers were studied in a rising, single dose, alternating panel design with eight subjects per panel. Matching placebo was administered to two of eight study subjects at each dose level of MK-462 in a randomized, double-blind fashion. MK-462 was rapidly absorbed with a median tmax of 1.3 h (range 1-3 h) vs a tmax for sumatriptan of 2.5 h (range 1-4 h, P < 0.001). Administration of either MK-462 or sumatriptan produced maximal mean elevations of 5-10 mmHg in systolic and diastolic blood pressures without effect on heart rate; the changes occurred sooner following MK-462, consistent with more rapid absorption. Both MK-462 and sumatriptan provoked mild increases in serum growth hormone without any effect on serum prolactin concentrations. The most commonly reported symptom following MK-462 was drowsiness. These results indicate that the novel 5-HT1D agonist, MK-462, is rapidly absorbed following oral administration and warrants further investigation of its utility in the treatment of acute migraine.",1997.0,0,0
562,9056596,,,,,0,0
563,9058397,Serotonin 1D (5-HT1D) agonists and other agents in acute migraine.,N T Mathew,"This article discusses the use of serotonin1D agonists in the treatment of acute migraine. Specifically, the author reviews the efficacy and safety of this class of drugs with sumatriptan as the main focus. Agents under clinical trial are also discussed. Recurrence of migraine, long-term usage, and side effects of serotonin1D agonists are included in the review. The article also discusses alternative medications, such as intranasal lidocraine, intravenous chlorpromazine, and intravenous prochlorperazine, for acute treatment of migraine. The limited role of narcotics and sedatives is also mentioned.",1997.0,0,0
564,9073037,Comparison of utilization of Sinemet and Parkinson's disease mortality as surrogate indicators of Parkinson's disease in the United States.,D J Lanska,"To compare two surrogate indicators of population disease burden for Parkinson's disease: utilization of Sinemet and Parkinson's disease mortality. National Center for Health Statistics data were used to tabulate Parkinson's disease mortality in the United States by state for 1987-1989. Sinemet sales data by state were obtained from Merck & Co., Inc. for 1988. Least squares regression analyses were used to assess the relationship between Sinemet utilization and Parkinson's disease mortality. United States. Regression analyses showed extraordinarily strong associations between state-level Parkinson's disease mortality and Sinemet utilization (underlying-cause model r2 = 0.969, p = 0.0001; multiple-cause model r2 = 0.980, p = 0.0001). Sinemet utilization very closely parallels Parkinson's disease mortality, suggesting that Sinemet utilization and Parkinson's disease mortality are both useful indices of the population burden of Parkinson's disease for large-scale epidemiological studies.",1997.0,0,0
565,9085306,Deriving dichotomous outcome measures from continuous data in randomised controlled trials of analgesics: use of pain intensity and visual analogue scales.,A Moore; O Moore; H McQuay; D Gavaghan,"The aim of this study was to examine whether mean data from categorical pain intensity and visual analogue scales for both pain intensity and relief could be used reliably to derive dichotomous outcome measures for meta-analysis. Individual patient data from randomised controlled trials of single-dose analgesics in acute postoperative pain were used. The methods used were as follows: data from 132 treatments with over 4700 patients were used to calculate mean %maxSPID (categorical pain intensity), %maxVAS-SPID (visual analogue pain intensity) and %maxVAS-TOTPAR (visual analogue pain relief); these were used to derive relationships with the number of patients who achieved at least 50% pain relief (%maxTOTPAR). Good agreement was obtained between the actual number of patients with > 50%maxTOTPAR and the number calculated for all three measures. For SPID, verification included independent data sets. For calculations involving each measure, summing the positive and negative differences between actual and calculated numbers of patients with > 50%maxTOTPAR gave an average difference of less than 0.25 patients per treatment arm. Reports of randomised trials of analgesics frequently describe results of studies in the form of mean derived indices, rather than using discontinuous events, such as number of proportion of patients obtaining at least 50% pain relief. Because mean data inadequately describe information with a non-normal distribution, combining such mean data in systematic reviews may compromise the results. Showing that dichotomous data can reliably be derived from mean SPID, VAS-SPID and VAS-TOTPAR as well as TOTPAR data in previously published acute pain studies makes much more information accessible for meta-analysis.",1997.0,0,0
566,9088582,The pharmacokinetics and effects on blood pressure of multiple doses of the novel anti-migraine drug zolmitriptan (311C90) in healthy volunteers.,R Dixon; C Gillotin; M Gibbens; J Posner; R W Peck,"Zolmitriptan (311C90), a novel, selective, centrally and peripherally acting 5-HT1D-receptor agonist is under development as an acute treatment for migraine. The tolerability, pharmacokinetics and effects on blood pressure and heart rate of multiple doses of 5 or 10 mg (5 doses administered over 24 h) were compared, in healthy adult volunteers, with those after placebo and single doses of zolmitriptan. Twelve subjects participated in a randomized, balanced, crossover comparison. Plasma and urine concentrations of zolmitriptan and its metabolites, pulse rate and blood pressure were measured at intervals after drug. Ten volunteers completed the study. Zolmitriptan was well tolerated after single and multiple doses throughout the study. There was no evidence of significant changes in the pharmacokinetic parameters of zomitriptan or its metabolites after the last dose compared to the first, except for an expected rise in peak concentrations and a small, apparent increase in the amount of drug excreted in urine and hence in CLR. After the last 10 mg dose, mean dosing interval zolmitriptan AUC was 80.3 ng ml-1 h compared with 86.5 ng ml-1 h after the single 10 mg dose (95% CI for ratio 0.76-1.13). There was no evidence of changes in the pharmacokinetic parameters of zolmitriptan and its metabolites after 10 mg compared with 5 mg, except a small increase in zolmitriptan CLR. There were no statistically significant increases in peak systolic or diastolic blood pressure after the last doses of zolmitriptan compared to placebo or in peak blood pressure after the last dose compared to the first. There were no significant differences between blood pressure immediately before the first and last doses of each multiple dose regimen. Peak erect systolic blood pressure after the last 10 mg dose (137 mmHg) was significantly lower than that after placebo (147 mmHg, 95% CI for difference -18, -2) and that after the last 5 mg dose (148 mmHg, 95% CI -19, -3). Repeated doses of 5 or 10 mg zolmitriptan are well tolerated despite higher plasma concentrations than expected from single doses.",1997.0,0,0
567,9109909,Sumatriptan for migraine attacks in children: a randomized placebo-controlled study. Do children with migraine respond to oral sumatriptan differently from adults?,M L Hämäläinen; K Hoppu; P Santavuori,"Oral sumatriptan is an effective acute treatment for migraine in adults, but its efficacy in children is still undetermined. Twenty-three children, aged 8.3 to 16.4 years, took both sumatriptan and placebo in a randomized, double-blind, placebo-controlled, crossover trial. The primary endpoint was a > or = 50% decrease in pain intensity on a 100-mm visual analogue scale at 2 hours. Other endpoints of efficacy were pain intensity difference (PID), showing pain relief at each time point; summed pain intensity differences (SPIDs), estimating overall pain relief; and preference. Two hours after sumatriptan, 7 of 23 reached the primary endpoint, and after placebo, 5 of 23 (difference 9%, 95% CI for difference, -21 to 38%; p = ns). Within 2 hours, the headache disappeared completely in 5 of 23 children after sumatriptan and in 2 of 23 children after placebo (p = ns). Median PIDs were slightly better for sumatriptan between 0.5 and 4 hours (p = ns). Median SPIDs increased almost identically up to 2 hours. Thereafter, median SPIDs for placebo remained practically constant, whereas for sumatriptan, the improvement continued. At 4 hours, the median SPID for sumatriptan was 2.4 times as high as for placebo. However, the maximum differences between median SPIDs at 4 hours (38.5, 95% CI, -75.8 to 57.5; Wilcoxon signed rank test, p = 0.4) or at any other point were not statistically significant. Of the 23 children, 13 preferred sumatriptan and 2 placebo (sign test, p = 0.004). The failure of this and previous controlled studies suggests that the response of children to sumatriptan may be different from adults.",1997.0,0,0
568,9117375,Responsiveness of the trigeminovascular system to nitroglycerine in cluster headache patients.,M Fanciullacci; M Alessandri; R Sicuteri; S Marabini,"Nitroglycerine is known to induce a headache attack in cluster headache patients, which is indistinguishable from a spontaneous attack. It has recently been suggested that a release of calcitonin gene-related peptide (CGRP) from peripheral terminals of trigeminal nociceptive neurons, which supply cephalic blood vessels, underlies symptoms of cluster headache. The aim of this study was to investigate whether the provocative action of nitroglycerine in cluster headache is due, at least in part, to activation of the trigeminovascular system. Nineteen subjects suffering from episodic cluster headache participated in the study. Eleven of them were in an active period, whilst the others were in remission at the time of the study. CGRP-like immunoreactivity (CGRP-LI) was measured in blood samples from the extracerebral circulation before and after the sublingual administration of nitroglycerine. Baseline CGRP-LI plasma levels were higher (P < 0.05) in the patients who were in an active period. Only in these patients did nitroglycerine induce an attack, which was preceded by a latent period with a mean duration of 27 +/- 3 min. When compared with the baseline, a significant (P < 0.01) increase in plasma CGRP-LI was detected at the peak of the provoked attack; no such increase was detected during the latent period, or at the onset of the attack. The results of this study suggests that the provocative action of nitroglycerine in cluster headache is due, at least in part, to activation of the trigeminovascular system. This mechanism seems to be slow and unrelated to the well-known rapidly occurring vasodilator effects of the drug. Finally, activation of the trigeminovascular system only occurs in those patients already in an active cluster headache period who also have high basal CGRP-LI plasma levels. This suggests that a hyperactivity of trigeminal nociceptive fibres could make the trigeminovascular system of these patients sensitive to the triggering action of nitroglycerine.",1997.0,0,0
569,9119924,"Sharp, sticking chest pain in a man with a pacemaker.",E W Hancock,,1996.0,0,0
570,9127118,Comparison of the vasoconstrictor properties of the 5-HT1D-receptor agonists rizatriptan (MK-462) and sumatriptan in human isolated coronary artery: outcome of two independent studies using different experimental protocols.,J Longmore; R J Hargreaves; C M Boulanger; M J Brown; B Desta; A Ferro; W N Schofield; A A Taylor; R G Hill,"Rizatriptan (MK-462) is a novel 5-HT1D-receptor agonist and is effective in the treatment of migraine headache. As angiographic studies have shown that the prototypic 5-HT1D/1B-receptor agonist sumatriptan can cause coronary artery constriction in patients with mild coronary artery disease, we have compared the contractile effects of rizatriptan on human isolated coronary artery with those of sumatriptan and 5-HT. Two different experimental protocols were used. In Study 1 (to avoid agonist desensitisation and interaction effects), arterial segments were exposed to a single agonist (either 5-HT, sumatriptan or rizatriptan) and in Study 2 each arterial segment was exposed to all three agonists with randomised first exposure to sumatriptan or rizatriptan. In both these studies the maximum contractions evoked by sumatriptan and rizatriptan were found to be smaller than those evoked by 5-HT, and the maximum contraction evoked by rizatriptan was significantly smaller than that for sumatriptan.",1997.0,0,0
571,9137840,Preventive treatment of migraine: an overview.,S D Silberstein,"The pharmacologic treatment of migraine may be acute (abortive, symptomatic) or preventive (prophylactic). Most migraine preventive medications were designed to treat other disorders (e.g., propranolol for hypertension, valproate for epilepsy, etc.). Preventive medication is usually given daily for months or years; however, treatment can be episodic, subacute, or chronic. The medications can be divided into two major categories: (i) Alternatives of high efficacy, which include beta-blockers, tricyclic antidepressants, and divalproex, and of lower efficacy, which include selective serotonin reuptake inhibitors, calcium channel antagonists, and non-steroidal antiinflammatory drugs, and (ii) second-line choices of high efficacy, which include methysergide and monoamine oxidase inhibitors. The choice of preventive treatment depends on the individual drug's efficacy and side effects, the patient's wants, needs, and response to prior treatment, and the presence of any comorbid or coexistent disease.",1997.0,0,0
572,9137851,Prophylactic treatment of migraine with gamma-linolenic and alpha-linolenic acids.,W Wagner; U Nootbaar-Wagner,"Polyunsaturated fatty acids (PUFA) were administered to 168 patients over a period of 6 months in an open-label uncontrolled study. In 129 patients available for study, 86% experienced reduction in severity, frequency and duration of migraine attacks, 22% became free of migraine and more than 90% had reduced nausea and vomiting. Self-medication changed to simple analgesics in the majority except in 14% of patients without improvement.",1997.0,0,0
573,9146856,,,,,0,0
574,9169294,Atypical facial pain: a double-blind placebo-controlled crossover pilot study of subcutaneous sumatriptan.,S D Harrison; S A Balawi; C Feinmann; M Harris,"A double-blind placebo-controlled crossover pilot study involving 19 patients was undertaken to evaluate the efficacy of subcutaneous sumatriptan, a selective 5-hydroxytryptamine (5-HT)-like receptor agonist, in the treatment of atypical facial pain (AFP). A reduction in total pain was found 120 min post injection in the sumatriptan group. Most patients, however, described the medication as ineffective overall, despite significant pain score reduction. The temporary improvement of pain scores with the active drug was thought to be too small to be of any clinical benefit, but suggests that vascular or neurogenic mechanisms may be involved in the aetiology of AFP. Sumatriptan is not an appropriate therapeutic option for patients with AFP, but could prove a valuable drug in experimental clinical pharmacology.",1997.0,0,0
575,9169967,Selective serotonin reuptake inhibitor-induced serotonin syndrome: review.,R Lane; D Baldwin,"The selective pharmacology of the selective serotonin reuptake inhibitors (SSRIs) results in a lower potential for pharmacodynamic drug interactions relative to other antidepressants such as the tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs). However, the SSRIs have been implicated in the development of the serotonin syndrome--a potentially life-threatening complication of treatment with psychotropic drugs. The syndrome is produced most often by the concurrent use of two or more drugs that enhance central nervous system serotonin activity and often goes unrecognized because of the varied and nonspecific nature of its clinical features. The serotonin syndrome is characterized by alterations in cognition (disorientation, confusion), behavior (agitation, restlessness), autonomic nervous system function (fever, shivering, diaphoresis, diarrhea), and neuromuscular (ataxia, hyperreflexia, myoclonus) activity. The difference between this syndrome and the occurrence of adverse effects caused by serotonin reuptake inhibitors alone is the clustering of the signs and symptoms, their severity, and their duration. There are important pharmacokinetic interactions between SSRIs and other serotonergic drugs due principally to their effects on the cytochrome P450(CYP) isoenzymes, the potential for which varies widely amongst the SSRI group, which may increase the likelihood of a pharmacodynamic interaction. The exceptionally long washout period required after fluoxetine discontinuation may cause additional problems and/or inconvenience. Patients with serotonin syndrome usually respond to discontinuation of drug therapy and supportive care alone, but they may also require treatment with antiserotonergic agent such as cyproheptadine, methysergide, and/or propranolol. To reduce the occurrence, morbidity, and mortality of the serotonin syndrome, it must be both prevented by prudent pharmacotherapy and given prompt recognition when it is present.",1997.0,0,0
576,9171470,Hyperbaric oxygen in chronic cluster headaches: influence on serotonergic pathways.,F Di Sabato; M Rocco; P Martelletti; M Giacovazzo,"A controlled study was done with the aim of assessing the efficacy of hyperbaric oxygen (HBO2) in cluster headache and of studying the possible influence of this therapeutic approach on serotonergic pathways. Fourteen patients, aged between 26 and 56 yr, suffering from the chronic form of cluster headache were treated with HBO2 (n = 10) or environmental air (placebo) ( n = 4) during the 15 sessions of exposure (lasting 30 min each) in the hyperbaric chamber. The influence of this procedure on serotonergic pathways of pain was monitored by means of study of serotonin binding to mononuclear cells before and after the treatment for both subgroups. All of the treated 14 chronic cluster headache patients completed the study. In the subgroup treated with the placebo, no particular modifications on the number of attacks and of analgesic consumption as well as no change in the specific binding curve of serotonin to mononuclear cells were observed, whereas in the subgroup treated with HBO2 the clinical effectiveness and the appearance of plateau in the binding curves indicated that the oxygen therapy could act through serotonergic pathways.",1997.0,0,0
577,9191764,A study of the effects of sumatriptan on myocardial perfusion in healthy female migraineurs using 13NH3 positron emission tomography.,P J Lewis; S F Barrington; P K Marsden; M N Maisey; L D Lewis,"Sumatriptan, a 5-HT1D receptor agonist, is believed to alleviate migraine attacks by extracerebral vasoconstriction. Chest pain associated with myocardial ischemia may occur after sumatriptan administration. We investigated the effect of a single 6-mg subcutaneous dose of sumatriptan on myocardial perfusion (MP) as measured by 13NH3 positron emission tomography (PET) in a randomized, double-blind, placebo-controlled, crossover trial at the Clinical PET Centre, Guy's and St. Thomas' Hospitals, London. Nineteen volunteer female migraineurs, age range 33 to 62 years, at low risk for ischemic heart disease were included. All bad undergone previous treatment with oral or intravenous sumatriptan. Patients were recruited by advertisement and referral from local neurology specialists. Each volunteer underwent two scanning sessions. On each occasion, a baseline dynamic 13NH3 PET scan was acquired followed by a 13NH3 PET scan 10 minutes after subcutaneous injection of placebo or 6 mg of sumatriptan. Regional MP was measured in five myocardial regions using the Patlak system of image analysis. The mean % change from baseline (+/-SD) in global MP after placebo was +9.5% +/- 18.0 and after sumatriptan was +6.6% +/- 18.8 (repeated measures ANOVA for treatment effect p = 0.56). There were no significant differences in MP changes from baseline observed in any of the five myocardial regions (treatment p = 0.32 to 0.84). These data suggest that in healthy female migraineurs, a single 6-mg subcutaneous dose of sumatriptan does not cause a significant change in regional or global myocardial perfusion.",1997.0,0,0
578,9192257,The efficacy of selective serotonin reuptake inhibitors for the management of chronic pain.,A C Jung; T Staiger; M Sullivan,"To assess the effectiveness of selective serotonin reuptake inhibitors (SSRIs) in the management of chronic pain. Randomized, controlled trials of SSRIs in the management of chronic pain were identified by searching MEDLINE from 1966 to 1997 and by contacting the manufacturers of SSRIs available in the United States. Nineteen studies were identified, including 10 on the treatment of headache, 3 on diabetic neuropathy, 3 on fibromyalgia, and 3 on mixed-chronic pain. SSRIs were consistently helpful for mixed-chronic pain. Results were conflicting for migraine headache, tension headache, diabetic neuropathy, and fibromyalgia. SSRIs appear to be beneficial for mixed-chronic pain. It is unclear, from the available evidence, whether SSRIs are beneficial for migraine headaches, tension headaches, diabetic neuropathy, or fibromyalgia. For those patients it may be reasonable to reserve SSRIs for those who fall to respond to other medications or who are intolerant of their side effects.",1997.0,0,0
579,9200177,Inhibition of the blink reflex R2 component after supraorbital and index finger stimulations is reduced in cluster headache: an indication for both segmental and suprasegmental dysfunction?,A Lozza; J Schoenen; P J Delwaide,"Peripheral as well as central mechanisms are thought to play a role in cluster headache pathogenesis. We have studied recovery curves of the R2 component of the blink reflex after conditioning by supraorbital or index finger stimuli in 10 episodic cluster headache (CH) patients during a cluster period and in 10 healthy controls. There was no significant change of R2 threshold, latency or area in CH patients. After paired supraorbital stimuli, R2 recovered more rapidly in patients on the symptomatic side. After index stimulations, R2 recovery was more rapid on both symptomatic and non-symptomatic sides in patients compared to controls. Naloxone (0.4 mg) i.v. in two subjects partially reversed the R2 suppression induced by index finger stimuli. The unilateral decrease of R2 inhibition after a segmental supraorbital stimulus most likely reflects sensitisation in the spinal trigeminal nucleus. Whether the latter is due to irritation of the ophthalmic nerve within the cavernous sinus region, which is thought to be pivotal in CH pathogenesis, remains to be proven. In addition, we propose that the bilateral deficit of R2 inhibition after an extrasegmental exteroceptive stimulus might reflect hypoactivity of reticular nuclei, possibly because of reduced central opioid activity.",1997.0,0,0
580,9205817,,,,,0,0
581,9209769,Symptoms and diseases and smoking habits in female episodic cluster headache and migraine patients.,J Hannerz,"Twenty-seven episodic female cluster headache patients were compared to 27 age-matched female migraine patients with regard to occurrence of symptoms and diseases other than headache, and also with regard to tobacco consumption. Some symptoms and diseases were found to occur significantly or almost significantly more often in the cluster headache patients than in the migraine patients; Chronic fatigue (p < 0.01), vertigo (p < 0.05), arthralgia (p < 0.05), back pain (p = 0.05), spontaneous ecchymoses (p = 0.05) and constipation and/or periodic diarrhea (p = 0.09). There were significantly fewer persons who had never smoked in the cluster headache group than in the migraine group (p < 0.01). The extent of smoking was significantly greater in the cluster headache group than in the migraine group, both as to the number of cigarettes smoked per day (p < 0.001) and as to smoking years (p < 0.001).",1997.0,0,0
582,9209775,"Safety, tolerability, and pharmacokinetics of sumatriptan suppositories following single and multiple doses in healthy volunteers.",R L Kunka; E K Hussey; S Shaw; P Warner; B Aubert; I Richard; P A Fowler; G E Pakes,"A suppository formulation of the 5HT1 agonist sumatriptan could prove an important therapeutic option in migraine patients who dislike or poorly tolerate injectable therapy and where oral tablet administration is unsuitable because of severe migraine-related vomiting. Two independent double-blind, randomized clinical studies were conducted to evaluate the safety, tolerability and pharmacokinetics of sumatriptan suppositories following ascending single doses (four different dose levels) and multiple doses. In the four-period, crossover, single-dose study, 24 healthy male subjects were randomized to receive a suppository containing 12.5, 25, 50, or 100 mg on separate occasions 3-14 days apart. The suppositories were generally well tolerated; transient asthenia, drowsiness, and headache were the most frequently reported adverse events, and these were not dose-related. Peak plasma concentrations (Cmax) of sumatriptan were proportional to dose from 25 to 100 mg; area under the plasma concentration-time curve (AUC infinity) values were proportional to dose except at the highest doses, when they were greater than those predicted from lower doses. For all doses, the tmax of sumatriptan occurred within 2.5 h, and the t1/2 was approximately 2 h. In the two-period, placebo-controlled, crossover, repeat-dose study, 12 healthy adult male subjects were randomized to receive either a 50-mg sumatriptan suppository or placebo suppository, administered rectally twice a day, for 11 doses (5 1/2 days). Adverse events were no more frequent with sumatriptan than with placebo, and stool guaiac, rectal examinations, and physical examinations remained normal. No significant differences were noted between Day 1 and Day 6 values in the AUC, Cmax, time of peak serum concentration (tmax), elimination half-life (t 1/2), fraction of the dose excreted in the urine (fe), or renal clearance (Clr) of sumatriptan or its pharmacologically inactive indole acetic acid metabolite. Serum metabolite concentrations were two to three-fold higher than corresponding sumatriptan concentrations. No clinically significant accumulation of sumatriptan or its metabolite occurred. Overall, these studies show that sumatriptan administration via a suppository formulation is well tolerated, allows rapid absorption of sumatriptan, results in sumatriptan Cmax values that are proportional to dose from 25 to 100 mg, and is not associated with accumulation of sumatriptan or its metabolite.",1997.0,0,0
583,9209776,"Safety, tolerability, and pharmacokinetics of sumatriptan in healthy subjects following ascending single intranasal doses and multiple intranasal doses.",K H Moore; E K Hussey; S Shaw; E Fuseau; C Duquesnoy; G E Pakes,"The delivery of sumatriptan doses intranasally could add greater flexibility in the treatment of migraine than is possible with the currently available subcutaneous and oral sumatriptan preparations. Two independent double-blind, randomized, placebo-controlled clinical studies were conducted to evaluate the safety, tolerability and pharmacokinetics of intranasally administered sumatriptan following ascending single doses (three different dose levels) and multiple doses. In the four-way, crossover, ascending-dose study, 20 healthy female subjects were randomized to receive on separate occasions single intranasal spray doses of 5, 10, or 20 mg sumatriptan (as the hemisulphate salt) or placebo into one nostril. Adverse events were mild and consisted mainly of bitter taste at the back of the throat and events typical of sumatriptan administered by other routes (headache, lightheadedness and tingling). Area under the plasma sumatriptan concentration versus time curve (AUC infinity) and peak plasma concentration (Cmax) increased with the dose. Dose proportionality was demonstrated between 5 and 10 mg but not across the dose range 5-20 mg. Time to maximum plasma concentration (tmax) was variable due to multiple peaking. The elimination half-life (t1/2), approximately 2 h, was unaffected by the magnitude of dose. In the two-period, multiple-dose, crossover study, 12 healthy adult male and female subjects were randomized to receive either sumatriptan hemisulphate 20 mg or placebo, administered intranasally as a spray three times a day for 4 days. The two dosing periods were separated by 3 to 14 days. Multiple doses of sumatriptan were well tolerated, with no serious adverse events occurring or withdrawals due to adverse events. All patients reported a mild to moderate drug-related disturbance of taste. Nasal examinations remained normal, and olfactory function was unaffected. The AUC over the first 8 h following dosing (AUC8) and fraction of the dose excreted in the urine (fe; 6.2% vs 3.6%) were similar on Days 1 and 4. Day 4 values were significantly higher (p < or = 0.05) for Cmax (16.9 ng/ml vs 13.1 ng/ml), renal clearance (Clr; 19.0 l/h vs 14.2 l/h), and t1/2 (2.18 h vs 1.93 h), and shorter for tmax (0.88 h vs 1.75 h). Some accumulation (22%) occurred over the 4 days of dosing. Serum concentrations of the pharmacologically inactive indole acetic acid metabolite of sumatriptan were fourfold to fivefold higher than corresponding sumatriptan concentrations. Overall, these studies show that the sumatriptan intranasal spray formulation is well tolerated, allows rapid absorption of sumatriptan, and results in only a clinically insignificant degree of sumatriptan accumulation upon repeated dosing.",1997.0,0,0
584,9209777,Transdermal clonidine in the prophylaxis of episodic cluster headache.,M Leone; A Attanasio; L Grazzi; G Libro; D D'Amico; F Moschiano; G Bussone,,1997.0,0,0
585,9220056,Intranasal lidocaine for migraine and cluster headaches.,T M Mills; J A Scoggin,"While lidocaine may not be effective for the relief of all cluster or migraine headaches and the pain may recur in some patients, this therapy may offer an important therapeutic alternative for certain migraine patients. Further research may provide more information, such as which headache types best respond to lidocaine, if higher concentrations of lidocaine are more effective, if lidocaine solution is more effective than lidocaine nose spray, and if other local anesthetics are as effective.",1997.0,0,0
586,9233053,Effects of sumatriptan on growth hormone releasing hormone-stimulated growth hormone secretion in acromegaly.,C M Cuttica; P Sessarego; P Ponzani; M R Falivene; S Valenti; D De Martini; M Giusti,"Sumatriptan (SU), a specific 5-HT1D receptor agonist, was recently shown to be able to increase growth hormone (GH) levels in normals, but not in acromegalics, while no effect was seen on prolactine (PRL). SU is also able to produce an increase in GH response to growth hormone releasing hormone (GHRH) in prepubertal children. In this study we investigated whether SU administration influences GHRH-induced GH secretion in 8 acromegalics, and 6 age-matched normal volunteers, as a control group. We evaluated the effects of SU (6 mg s.c.) or placebo (PL) administration on GHRH (1 microgram/kg bw i.v.)-induced GH and PRL secretion. After SU priming the GH response to GHRH did not changed in acromegalics, but significantly decreased in controls, in comparison with that observed after PL plus GHRH. In acromegalics, no difference in GH peak was seen after SU plus GHRH and PL plus GHRH, nor was any difference seen in AUC between tests. In controls, no difference was seen in GH peaks, while SU priming significantly (P < 0.03) decreased the AUC 90-120 min of GH after GHRH administration. In acromegalics, SU did not change the slight GHRH-induced increase in PRL levels. Our study documents that 5-HT1 D receptors do not interfere with GHRH-stimulated GH secretion in acromegalic subjects. In normals, SU is able to decrease GH response to GHRH, thus confirming that 5-HT1D receptors are able to modulate GH secretion in normals.",1997.0,0,0
587,9248904,Intravenous chlorpromazine versus intramuscular sumatriptan for acute migraine.,A M Kelly; M Ardagh; C Curry; J D'Antonio; S Zebic,"To establish whether there is any difference in the efficacy of a chlorpromazine regimen and a sumatriptan regimen for the management of the pain of acute severe migraine. Two urban teaching hospital emergency departments. Prospective, randomised, unblinded, crossover trial. All patients received intravenous metoclopramide 10 mg and 1000 ml of normal saline over 1 h; 20 were then randomised to receive intramuscular sumatriptan 6 mg and 23 to receive intravenous chlorpromazine, 12.5 mg increments to a maximum of 37.5 mg. Response to treatment was measured using visual analogue pain scales. No difference in efficacy between the sumatriptan regimen and the chlorpromazine regimen was found. Adverse effects were mild and equally distributed between the groups. The chlorpromazine and sumatriptan regimens studied are both very effective for the relief of the headache of severe migraine.",1997.0,0,0
588,9251869,Responsiveness of non-IHS migraine and tension-type headache to sumatriptan.,J Olesen,,1997.0,0,0
589,9251874,Responsiveness of non-IHS migraine and tension-type headache to sumatriptan.,R K Cady; D Gutterman; J A Saiers; M E Beach,"In a long-term efficacy and safety study, 424 patients were treated with sumatriptan (6 mg sc) for 1,904 migraine attacks. The patients were diagnosed with migraine based on IHS criteria but individual migraine attacks treated in the study were physician diagnosed; not necessarily required to meet IHS criteria. A re-analysis of the treatment response to open label sumatriptan (6 mg sc) indicated that 43 patients had treated at least one migraine that fulfilled IHS criteria for tension-type headache. Analysis of this population revealed they treated 232 headaches. Of these headaches, 114 were classified per IHS criteria as migraine; 76 as tension-type; and 42 as non-IHS migraine (not classifiable as IHS migraine or IHS tension-type headache). Of the 114 migraines, a positive response to sumatriptan occurred in 109 (96%) cases; of the 76 tension-types, 73 responded to sumatriptan (97%); of the 42 non-IHS migraine, 40 (95%) responded to sumatriptan. An equivalent response to sumatriptan among three diagnostic groups of headache supports the concept of a common biologic mechanism involving 5HT1 receptors that spans a range of clinical presentations.",1997.0,0,1
590,9251875,Oral and subcutaneous sumatriptan in the acute treatment of migraine: an open randomized cross-over study.,H A Carpay; P Matthijsse; M Steinbuch; P G Mulder,"In an open, randomized cross-over study in 124 patients, we compared the efficacy, safety and patient preference of oral and subcutaneous sumatriptan in the acute treatment of migraine. Patients were treated for 3 attacks or 3 months and then crossed over. Primary clinical efficacy was defined as a reduction in headache severity on a four-point self-rating scale from severe (3) or moderate (2) to mild (1) or none (0), or mild (1) to none (0). Efficacy was evaluated 2 h after the administration of subcutaneous and 4 h after the administration of oral sumatriptan. Subcutaneous sumatriptan was significantly more effective than oral sumatriptan in relieving headache (over all three attacks 78% vs 61% improvement), improving clinical disability (55% vs 41% improvement) and relieving nausea (69% vs 53%), vomiting (72% vs 32%) and phono- or photophobia (67% vs 49%). Median time to recurrence was shorter after subcutaneous (12.5 h) than after oral sumatriptan (18 h); the number of patients experiencing a recurrence was similar. Patients reported more adverse events after subcutaneous sumatriptan (1.32 per attack) than after the oral form (0.85 per attack), but all adverse events were mild to moderate in intensity and of short duration. Patient opinion was more often positive after subcutaneous sumatriptan. These results may be useful in counselling patients to choose between the available marketed formulations of sumatriptan.",1997.0,0,0
591,9252796,,,,,0,0
592,9270292,Serum beta-endorphin increase after intravenous histamine treatment of chronic daily headache.,B Anselmi; R Tarquini; A Panconesi; V de Leonardis; F Perfetto; A Piluso; E Naldi; B Tarquini,"Histamine is able to induce spontaneous-like headache attacks in migraine and cluster headache subjects. Therefore, it has been considered as a possible agent in the pathogenesis of headache. Histamine desensitization is used for the treatment of cluster and other chronic headaches like migrains with interparoxysmal headache. However, it is unknown whether desensitization plays a role in headache improvement. Since a disfunction of the opioid system has been considered responsible for idiopathic headache and since low beta-endorphin levels have been demonstrated in some idiopathic headaches, particularly in migraine with interparoxysmal headache, we planned this study to verify if histamine therapy is able to modify serum beta-endorphin concentrations. For this purpose, we studied 24 healthy control subjects and 36 patients suffering from migraine with interparoxysmal headache refractory to conventional therapies. Patients showed baseline serum beta-endorphin levels significantly lower than healthy control subjects and treatment with histamine for 15 days increased their beta-endorphin concentrations. We believe that histamine treatment can activate the opioid endogenous system. However, the therapeutic effect of histamine remains to be verified by evaluating the correlation between beta-endorphin levels and headache improvement.",1997.0,0,0
593,9270596,The thigh may not be suitable as an injection site for patients self-injecting sumatriptan.,A Frid; J E Hardebo,"The objective of our study was to evaluate the differences between injection sites in the midthigh and the upper lateral quadrant of the gluteal area regarding the effect, depth of subcutaneous tissue, side effects, and patient preference in patients with cluster headache who self-inject 6 mg (0.5 ml) of sumatriptan. Our open, prospective clinical study was performed at the outpatient department of a Swedish university clinic. There were 19 male and one female subjects, 34 to 68 years old, suffering from cluster headache. We measured the subcutaneous tissue depth by ultrasound. Subjects performed four self-injections of sumatriptan, two in the thigh and two in the gluteal area. We evaluated the subcutaneous tissue depth from the skin surface to the muscle fascia, the effect on headache, side effects, and patient preference regarding the injection site. Subcutaneous tissue depth laterally in the thigh was 2 to 12 mm (median, 4 mm) and in the gluteal area was 34 to 68 mm (median, 45 mm). The needle of the self-injector protrudes 5 to 6 mm. Forty thigh and 39 gluteal injections were recorded. The effect on headache was equal. Following injection in thigh the patients experienced more bleeding (p < 0.001, chi 2); local pain (p < 0.05, chi 2); and a feeling of oppression in the head, neck, and chest area (p < 0.05, chi 2); compared with injections in the gluteal area. Fifteen patients preferred the gluteal area as the injection site after the study, two patients had no preference, and three preferred the thigh. When using the self-injector in the lateral aspect of the thigh, intramuscular injection is liable to occur frequently in male patients. This may explain the differences in local and general side effects observed in this study. The upper lateral quadrant of the gluteal area is a more suitable injection site for male, and some female, patients when using the sumatriptan self-injector.",1997.0,0,0
594,9277024,Sumatriptan in the acute treatment of migraine without aura: efficacy of 50-mg dose.,F Moschiano; D D'Amico; L Grazzi; M Leone; G Bussone,"We conducted an open study on the efficacy of 50 mg of sumatriptan as an acute treatment for migraine without aura. We recruited 200 consecutive patients, with an established history of migraine without aura, presenting at a headache center. The patients were instructed to take half a 100-mg sumatriptan tablet for their next migraine attack, and to record details of their headache in a diary. The primary outcome of the study was headache relief from one migraine attack. Attacks were moderately intense (46%), moderate to severe (7%), or severe (47%). Total or partial benefit at 2 hours from the 50-mg dose was reported by 140 of 200 patients (70%). Thirty-six patients received no benefit from half a tablet, and 24 did not take sumatriptan, preferring their habitual medication. Side effects were few, mild, and short lasting. We conclude that the 50-mg oral dose is generally effective for migraine without aura attacks of both moderate and severe intensity and recommend this dose for all such patients. If, however, sumatriptan is ineffective at that dose it can be increased to a maximum of 100 mg.",1997.0,0,0
595,9326750,"Sumatriptan-induced growth hormone release in patients with major depression, mania, and normal controls.",L N Yatham; A P Zis; R W Lam; E Tam; I S Shiah,"The purpose of this study was to assess serotonergic function in patients with major depression or mania using sumatriptan, a novel 5-HT1D receptor agonist, as a pharmacological probe in a neuroendocrine challenge paradigm. We studied 18 drug free patients (10 with acute unipolar major depression and 8 with acute mania) who met DSM-IV criteria, and healthy controls. Subjects presented for testing after an overnight fast. After obtaining a blood sample for baseline growth hormone (GH) levels, sumatriptan (6 mg) was given subcutaneously, and further blood samples were collected at half hour intervals for 2 hours. The results showed that GH responses to sumatriptan were blunted in depressed patients but not in manics, compared to healthy controls. There were no differences in basal GH levels between the 3 groups. The results of this study provide further support for the role of serotonergic system in pathophysiology of major depression, but not in mania.",1997.0,0,0
596,9350383,"Peripheral vascular effects and pharmacokinetics of the antimigraine compound, zolmitriptan, in combination with oral ergotamine in healthy volunteers.",R M Dixon; H B Meire; D H Evans; H Watt; N On; J Posner; P E Rolan,"Members of the new class of antimigraine compounds, 5HT1B/1D agonists, as well as ergotamine, may cause vasoconstriction through stimulation of 5HT receptors on peripheral vessels. The cardiovascular effects of 20 mg oral zolmitriptan (Zomig, formerly 311C90), 2 mg oral ergotamine and the combination were assessed in a randomized double-blind, placebo-controlled crossover study in 12 healthy subjects. Pharmacodynamic measures included oscillometric blood pressure, systolic blood pressure at the toe and arm using a strain gauge technique, stroke volume and cardiac output using bioimpedance cardiography, high-resolution ultrasound to measure brachial arterial diameter and a novel Doppler method to measure blood flow velocity. Both drugs produced small degrees of peripheral vasoconstriction, including increases in diastolic blood pressure and blood flow velocity and decreases in arterial diameter and toe-arm systolic pressure gradient. These effects were generally additive with the combination but of no clinical importance. There were no significant changes in cardiac output, stroke volume heart rate or ECG. Zolmitriptan, at eight times the likely therapeutic dose, was generally well tolerated both alone and in combination with ergotamine. Ergotamine had no clinically important effects on zolmitriptan pharmacokinetics.",1997.0,0,0
597,9350384,"Double-blind, placebo-controlled, dose-finding study of rizatriptan (MK-462) in the acute treatment of migraine.",H Gijsman; M S Kramer; J Sargent; M Tuchman; D Matzura-Wolfe; A Polis; J Teall; G Block; M D Ferrari,"Rizatriptan (MK-462) is a potent 5HTID receptor agonist. This multicenter, double-blind, placebo-controlled, outpatient study investigated the clinical efficacy, safety, and tolerability of rizatriptan (2.5, 5, and 10 mg) as a function of dose for acute migraine. Patients with moderate or severe migraine (n = 417) were treated with placebo (n = 67), rizatriptan 2.5 mg (n = 75), 5 mg (n = 130), or rizatriptan 10 mg (n = 145). Headache severity, functional disability, and migraine symptoms were measured immediately before dosing (0) and at 0.5, 1, 1.5, 2, 3, and 4 h post-dose. Patients were permitted to take a second dose of test drug at 2 h if their headache pain was moderate or severe (i.e., placebo initially-->rizatriptan 10 mg as optional second dose; rizatriptan 2.5 mg, 5 mg, or 10 mg initially-->placebo as optional second dose). An upward dose-response relationship was observed among placebo, rizatriptan 2.5 mg, 5 mg, and 10 mg in the primary efficacy measure of proportion of patients reporting pain relief, i.e., a change in headache severity to ""no pain or mild pain"" at 2 h post-dose. The relationship was evident even at the first recorded timepoint, 30 min, and was statistically significant at 1.5 h and beyond. At the primary timepoint of 2 h after the initial dose, the proportion of patients reporting pain relief was 47.6% for rizatriptan 10 mg; 45.4% for rizatriptan 5 mg; 21.3% for rizatriptan 2.5 mg; and 17.9% for placebo. Seventy percent of patients on rizatriptan 10 mg reported pain relief at 4 h. Patients who took rizatriptan 5 mg and 10 mg were significantly less functionally disabled than those who took placebo at 1.5 and 2 h post-dose. Rizatriptan 10 mg was consistently more effective than 5 mg, although the differences were not statistically significant. The most frequent clinical adverse events were dizziness, somnolence, and asthenia/fatigue. No patients were discontinued for any adverse experiences and there were no serious adverse experiences.",1997.0,0,1
598,9350389,Double-blind placebo-controlled trial of lithium in episodic cluster headache.,T J Steiner; R Hering; E G Couturier; P T Davies; T E Whitmarsh,"Lithium is widely used in the prophylaxis of episodic cluster headache without formal evidence of efficacy. Placebo-controlled clinical trials are not easy in conditions characterized by frequent severe pain. In this study, it was assumed that lithium would work quickly if at all, and placebo response would be zero. Strict diagnostic criteria excluded uncertain or atypical cases. Patients were male in so-far untreated episodes expected to last for at least 3 weeks more. In a double-blind, placebo-controlled comparison of matched parallel groups, treatment was either slow-release lithium carbonate, 800 mg/day, or placebo. After 7 days, compliance was estimated by tablet count, blood was taken for lithium assay, efficacy was assessed (attacks stopped or substantially improved) and adverse reactions were recorded. The study was stopped after planned sequential analysis of the 27th patient (13 on lithium, 14 on placebo). Estimated compliance was usually but not always good. Plasma lithium levels were mostly in the range 0.5-0.6 mmol/l on lithium, zero on placebo. Cessation of attacks within 1 week occurred in two patients in each group, substantial improvement in 6/14 (43%) on placebo, 8/13 (62%; NS) on lithium. Only minor adverse events were reported. Lithium treatment was therefore associated with a useful subjective improvement rate but the assumptions made at outset had proved wrong. The trial was stopped because superiority over placebo could not be demonstrated. There were lessons for future trials.",1997.0,0,0
599,9362987,,,,,0,1
600,9371890,Attacking migraine headache from beginning to end.,M A Moskowitz; F M Cutrer,,1997.0,0,0
601,9371896,"Optimizing the dose of zolmitriptan (Zomig, 311C90) for the acute treatment of migraine. A multicenter, double-blind, placebo-controlled, dose range-finding study. The 017 Clinical Trial Study Group.",A M Rapoport; N M Ramadan; J U Adelman; N T Mathew; A H Elkind; D B Kudrow; N L Earl,"This study investigated the efficacy of zolmitriptan (Zomig, formerly 311C90) in acute migraine therapy. Patients with a history of migraine were randomized in a double-blind, multicenter, placebo-controlled, dose range-finding study of oral zolmitriptan 1, 2.5, 5, or 10 mg versus placebo for the treatment of a severe or moderate migraine headache. Patients with persistent or recurrent headache 4 to 24 hours after the initial dose, who did not take escape medication, were eligible to receive a second blinded dose of either zolmitriptan or placebo. Of 1,144 patients treated, 999 evaluable patients completed the study. The headache response rates with zolmitriptan doses > or = 2.5 mg were 44 to 51% at 1 hour, 65 to 67% at 2 hours, and 75 to 78% at 4 hours (all significantly superior to placebo). Also, zolmitriptan effectively relieved migraine-associated symptoms such as nausea, photophobia and phonophobia, and reduced activity impairment. Rates of headache recurrence, headache persistence, and use of escape medication were lower with zolmitriptan doses > or = 2.5 mg than with placebo. In patients with persistent or recurrent headache, a second zolmitriptan dose effectively treated both headache and nonheadache symptoms. Zolmitriptan was well tolerated, with a lower incidence of adverse events being reported with doses < or = 2.5 mg than with those > or = 5 mg. Zolmitriptan is a well tolerated and effective acute migraine therapy providing rapid relief of migraine headache within 1 hour. A clear dose-response relationship between efficacy and tolerability suggests that 2.5 mg is the optimal initial dose for the acute treatment of a migraine attack.",1997.0,0,1
602,9371897,Clinical efficacy and tolerability of 2.5 mg zolmitriptan for the acute treatment of migraine. The 042 Clinical Trial Study Group.,G D Solomon; R K Cady; J A Klapper; N L Earl; J R Saper; N M Ramadan,"Previous studies demonstrated that zolmitriptan at doses of 1 to 25 mg was highly effective in treating acute migraine attacks. The 2.5-mg dose had a favorable therapeutic effect with high efficacy and good tolerability. The objective of this study was to further evaluate the efficacy of a single 2.5-mg dose of zolmitriptan (Zomig, formerly known as 311C90) for acute treatment of a single moderate or severe migraine attack. The study was a randomized, double-blind, placebo-controlled clinical trial. Female and male patients, 12 to 65 years old, with migraine (with or without aura) for > or = 1 year, one to six migraines per month, and age at onset < 50 years were included; 327 patients were screened and randomized to receive either zolmitriptan (n = 219) or placebo (n = 108). Patients treated a single moderate or severe migraine headache with 2.5 mg zolmitriptan or placebo and recorded clinical efficacy and adverse events on a diary form. Headache response at 2 hours was 62% for zolmitriptan compared with 36% for placebo (p < 0.001); at 4 hours, headache response was 70% with zolmitriptan and 37% with placebo (p < 0.001). Headache recurrence in patients treated with 2.5 mg zolmitriptan was 22% (versus placebo 30%). The headache response at 4 hours, pain-free rate, and response rate of nonheadache symptoms favored zolmitriptan over placebo. No serious adverse events were associated with zolmitriptan treatment. A 2.5-mg dose of zolmitriptan is clinically effective and well tolerated for the acute treatment of migraine.",1997.0,0,1
603,9371898,Sumatriptan nasal spray for the acute treatment of migraine. Results of two clinical studies.,R Ryan; A Elkind; C C Baker; W Mullican; S DeBussey; M Asgharnejad,"Sumatriptan nasal spray may be particularly useful for patients whose nausea and vomiting preclude them from using oral migraine medication or for patients who prefer not to use an injectable migraine medication. The objective of this study was to evaluate in two clinical studies the efficacy and tolerability of the intranasal form of sumatriptan in the acute treatment of a single migraine attack. International Headache Society-diagnosed adult migraineurs in two randomized, double-blind, parallel-group, multicenter studies (n = 409 and 436) used sumatriptan nasal spray 20 mg, 10 mg, or placebo (2:1:1) for the acute treatment of a single migraine attack at home. Predose and at predetermined postdose intervals, patients recorded headache severity (none, mild, moderate, severe); time to meaningful relief; clinical disability (none, mildly impaired, severely impaired, bed rest required); presence/absence of nausea, photophobia, and phonophobia; and the occurrence of adverse events. Two hours postdose in the two studies, moderate or severe baseline pain was reduced to mild or none in 62 to 63% of patients treated with sumatriptan 20 mg, 43 to 54% of patients treated with sumatriptan 10 mg, and 29 to 35% of placebo-treated patients (p < 0.05 20 mg versus placebo for both studies and 10 mg versus placebo for study 1). Onset of relief relative to placebo began as early as 15 minutes postdose (sumatriptan 20 mg, study 2). Clinical disability at 2 hours postdose was reported as mildly impaired or normal in 72 to 74% of patients treated with sumatriptan 20 mg, 56 to 68% of patients treated with sumatriptan 10 mg, and 47 to 58% of placebo-treated patients (p < 0.05 20 mg versus placebo for both studies). Similar efficacy rates were observed for nausea, photophobia, and phonophobia. The most common adverse event in the active treatment groups was disturbance of taste (bad, bitter, or unpleasant taste). Aside from this event, the pattern and incidence of adverse events did not differ among treatment groups. From these results we determined that sumatriptan nasal spray is a rapidly effective, well-tolerated migraine treatment. The 20-mg dose was effective in treating the entire migraine symptom complex, and the 10-mg dose was less consistently effective.",1997.0,0,1
604,9377591,Sumatriptan does not affect vasopressin secretion in humans.,T Barreca; R Franceschini; A Cataldi; A Garibaldi; P Cianciosi; E Rolandi,"The aim of the study was to investigate the effects of a new serotoninergic drug, sumatriptan, on arginine vasopressin secretion in humans. Plasma vasopressin concentrations were determined in eight healthy volunteers, before and after administration of 6 mg of sumatriptan, or placebo. No changes in hormone levels were found after sumatriptan or placebo administration. The results suggest that in humans serotoninergic mechanisms, which modulate vasopressin secretion, do not involve the serotonin receptor activated by sumatriptan.",1997.0,0,0
605,9385753,Transdermal clonidine in the prophylaxis of episodic cluster headache: an open study.,M Leone; A Attanasio; L Grazzi; G Libro; D D'Amico; F Moschiano; G Bussone,"Transdermal clonidine has recently been reported to be efficacious in the prophylaxis of cluster headache. A 2-week course of transdermal clonidine (5 mg the first week, 7.5 mg the second week) preceded by a 5-day run-in period, was administered to 16 patients with episodic cluster headache in an active cluster period. In 5 patients, the painful attacks disappeared after the seventh day of treatment. For the group as a whole, no significant variations in headache frequency, pain intensity, or attack duration were observed between the run-in period and the first and second weeks of treatment (ANOVA). Further studies are necessary to clarify the effectiveness of transdermal clonidine in the prophylaxis of episodic cluster headache.",1997.0,0,0
606,9399012,"Pre-clinical pharmacology of zolmitriptan (Zomig; formerly 311C90), a centrally and peripherally acting 5HT1B/1D agonist for migraine.",G R Martin,"Zolmitriptan (Zomig; formerly 311C90) is a novel 5-hydroxytryptamine (5HT)1B/1D receptor agonist with proven efficacy in the acute treatment of migraine with or without preceding aura. The drug differs from presently available members of this drug class in that it combines 5HT1B/1D receptor partial agonist activity with robust oral pharmacokinetics and an ability to inhibit trigeminovascular activation centrally as well as peripherally in preclinical studies. Consistent with its selectivity for 5HT1B/1D receptors, zolmitriptan produces constriction of various isolated blood vessels, most notably cranial arteries. In anaesthetized animals, these vascular effects manifest as a selective constriction of cranial arterio-venous anastomoses resulting in a redistribution of carotid arterial blood flow. This effect is produced without significant effects on heart rate, blood pressure or blood flow to the brain, heart or lungs. Zolmitriptan also inhibits trigeminal-evoked increases in cerebral blood flow in anaesthetized cats and blocks trigeminal-evoked plasma protein extravasation in the dura of guinea-pigs. These actions are consistent with a pre-junctional inhibition of neuropeptide release from perivascular afferents of the trigeminal nerve, as confirmed by independent studies showing that zolmitriptan blocks elevations of calcitonin-gene-related peptide in jugular venous blood during electrical stimulation of the trigeminal ganglion. In all of these effects, zolmitriptan is three to four times more potent than sumatriptan, but produces the same maximum response. Zolmitriptan crosses the intact blood-brain barrier to inhibit trigeminovascular activation in the brainstem. This was shown initially by the ability of the drug to block a brainstem reflex provoking vasoactive intestinal peptide release from the VIIth cranial (facial) nerve during trigeminal stimulation. Subsequent ex vivo autoradiography confirmed that intravenously injected [3H]zolmitriptan labels a discrete population of cells in the trigeminal nucleus caudalis (TNC) and nucleus tractus solitarius. Direct evidence for a central neuromodulatory effect of zolmitriptan was provided by electrophysiological experiments which clearly demonstrated that the drug inhibits the excitability of cells in the TNC after systemic administration. This novel pre-clinical profile not only distinguishes zolmitriptan from sumatriptan, but raises intriguing questions about the clinical relevance of a dual action. Studies to date show that zolmitriptan indeed modulates cranial sensory processing in humans, yet central side-effects are no different from sumatriptan. This property may account for the remarkable consistency in clinical efficacy observed in clinical trials.",1997.0,0,0
607,9399015,"Zolmitriptan (Zomig, 311C90), a novel dual central and peripheral 5HT1B/1D agonist: an overview of efficacy.",J Schoenen; J Sawyer,"The efficacy of zolmitriptan (Zomig, 311C90), a 5-hydroxytryptamine (5HT)1B/1D receptor agonist, in the acute oral treatment of migraine was evaluated in an extensive clinical trial program. Four randomized, placebo-controlled studies (total 2480 patients) were performed; data from two of these trials established that a 2.5 mg dose was on the shoulder of the dose-response curve (2-h headache response rate 64%), showing similar efficacy to the 5 mg dose (67%). In this program, the efficacy of zolmitriptan was not influenced by the pretreatment headache duration; the presence of aura preceding the headache, migraine associated with menses or migraine upon awakening; or by concomitant use of oral contraceptives or antidepressants. In addition, zolmitriptan 5 mg proved consistently effective in the treatment of multiple migraine attacks for up to 1 year. Zolmitriptan reduced the incidence of nausea, photophobia and phonophobia, reduced impairment of normal activity and demonstrated positive effects on patients' quality of life. Thus, zolmitriptan is a highly effective acute oral antimigraine therapy, with 2.5 mg providing the optimal balance between efficacy and tolerability.",1997.0,0,1
608,9399016,"Tolerability profile of zolmitriptan (Zomig; 311C90), a novel dual central and peripherally acting 5HT1B/1D agonist. International clinical experience based on > 3000 subjects treated with zolmitriptan.",J G Edmeads; D S Millson,"Zolmitriptan (Zomig, formerly 311C90) at doses of 0.5-50 mg was administered to 316 unique volunteers in clinical pharmacology studies and 2,750 unique patients in eight clinical studies of acute migraine treatment. Overall, subjects received almost 50,000 doses; 97% of exposures were at doses > or = 2.5 mg. In the clinical pharmacology studies, the overall incidence of subject exposures experiencing at least one adverse event was 52% with zolmitriptan 2.5 mg (28% with placebo). In placebo-controlled studies, the overall incidence of patients with at least one adverse event was dose-dependent for zolmitriptan over the 1-15 mg dose range, e.g. 42% and 46% with 1 and 2.5 mg, respectively and 58% with 5 mg (29% with placebo). Only four serious adverse events attributable to zolmitriptan were reported. In a long-term study, during which 2,058 outpatients treated a total of 31,579 migraine attacks with either one or two zolmitriptan 5 mg doses over a period of up to 1 year, the number of attacks associated with at least one adverse event was similar after one (26%) and two (24%) doses. The majority (59%) of the adverse events reported in this study (59%) occurred within 2 h of dosing, were predominantly mild (59%) or moderate (35%) in intensity, of < or = 4 h duration (58%), required no further action (94%). In placebo-controlled studies, the percentage of patients who reported severe adverse events was similar with zolmitriptan 2.5 mg (4%) and placebo (5%). The most frequently reported adverse events with zolmitriptan in the placebo-controlled clinical studies were asthenia, heaviness (other than chest or neck), dry mouth, nausea, dizziness, somnolence, paresthesia and warm sensations. The type and severity of the adverse events was not influenced by gender (although the frequency of reported adverse events was higher in females, as was the case in the placebo group), age, presence of aura prior to the attack, association of migraine with menstruation, concurrent medication, or by the addition of a second zolmitriptan dose. Zolmitriptan showed a similar tolerability profile in the long-term study, in which a low withdrawal rate due to adverse events of 8% was observed. Zolmitriptan was not associated with an increased frequency of central nervous system-related adverse events in a comparative study of sumatriptan, despite pre-clinical and neurophysiological evidence of a dual peripheral and central action of zolmitriptan. Moreover, zolmitriptan doses of 5-20 mg produced no statistically significant effects on objective assessments of psychometric function. Zolmitriptan had no clinically significant effects on blood pressure (even in patients with controlled mild to moderate hypertension or impaired renal function), ECGs (e.g. there was no evidence of ischemic events) or clinical chemistry, hematological or urinalysis measurements. In summary, zolmitriptan is well tolerated, particularly at the recommended dose of 2.5 mg. Zolmitriptan has a well-defined dose-response with 2.5 mg proving highly effective and optimizing the benefit/risk ratio of treatment. Thus, zolmitriptan is well suited as an acute oral treatment for migraine in the outpatient setting.",1997.0,0,1
609,9399017,"Clinical applications of zolmitriptan (Zomig, 311C90).",R B Lipton; W F Stewart,"Zolmitriptan (Zomig, formerly 311C90) is a novel, oral antimigraine drug that is consistently effective and well tolerated in the acute treatment of migraine headache and its associated symptoms. The purpose of this article is to review data available from pharmacological and clinical trials with zolmitriptan and to summarize the clinically relevant features that distinguish this agent. We will review the attributes desirable in a migraine drug and use this as a template for assessing zolmitriptan. Zolmitriptan provides a new oral treatment option for physicians which should help improve patient outcomes.",1997.0,0,0
610,9403280,Drug-induced chest pain and myocardial infarction. Reports to a national centre and review of the literature.,J P Ottervanger; J H Wilson; B H Stricker,"To analyse reports of drug-induced myocardial infarction and chest pain sent to a national reporting centre. To review which drugs were suspected of exhibiting these adverse events and what mechanisms were involved. During the 20-year period 1975 through 1994, a total of 19,141 reports on adverse reactions to drugs were received by the Netherlands Centre for Monitoring of Adverse Reactions to Drugs. Of these 19,141 reports, 220 (1.1%) were concerned with drug-induced chest pain or myocardial infarction. After excluding reports in which the causal relationship was unlikely, poorly documented reports and reports on cases of overdosage, 183 reports (84%) were analysed. There were 130 reports (71%) of drug-induced chest pain and 53 reports (29%) of drug-induced myocardial infarction. A total of 104 reports concerned females (57%). The most frequently reported suspected drugs were the antimigraine drug sumatriptan (33 reports, 4 concerning myocardial infarction), the calcium antagonist nifedipin (9 reports, 2 of myocardial infarction) and nicotine [9 reports (8 patches, 1 chewing gum), 5 concerning myocardial infarction]. There were 18 reports of a fatal outcome. Several drugs can produce chest pain or myocardial ischaemia. It is important to recognise drugs as a potential cause, especially in patients with normal coronary arteries.",1997.0,0,1
611,9403359,The way to serotonergic use and abuse in migraine.,M Nicolodi; P L Del Bianco; F Sicuteri,"5-HT is currently indicated to play a role in migraine (M). Previously evidenced 5-HT supersensitivity which characterizes M is insufficient to compensate for a possible deficit in 5-HT bioavailability. Inducing a further up-regulation of 5-HT receptor can yield improvement of M syndrome. Chronic treatments of methysergide and propranolol, drugs exerting antagonist action at 5-HT receptors, induced a significant amelioration in 256M sufferers. On the contrary, chronic treatments of ergotamine and sumatriptan, both provided with a 5-HT1 agonist activity, induced a worsening of M in 134 M sufferers. The M worsening was paralleled by an increase in consumption of analgesic drugs. Discussion concerns the effects of the chronically given 5-HT agonists and antagonists as well as the possible receptor mechanism underlying ""craving for serotonin"" in severe M. The increase of 5-HT supersensitivity evidenced at the end of M attacks is also discussed and its role in determining the interruption of the attack is here suggested.",1997.0,0,0
612,9409334,"Naratriptan is effective and well tolerated in the acute treatment of migraine. Results of a double-blind, placebo-controlled, crossover study. The Naratriptan S2WA3003 Study Group.",N T Mathew; M Asgharnejad; M Peykamian; A Laurenza,"The efficacy and tolerability of naratriptan tablets (2.5 mg, 1 mg, and 0.25 mg) compared with placebo in the acute treatment of migraine were evaluated in a randomized, double-blind, four-period crossover study. Five hundred eighty-six assessable patients received naratriptan 2.5 mg, 595 received 1 mg, 591 received 0.25 mg, 602 received placebo. Headache relief (moderate or severe pain reduced to mild or none) 4 hours postdose was reported in 68% of patients after treatment with naratriptan 2.5 mg compared with 57% after 1 mg, 39% after 0.25 mg, and 33% after placebo (p < 0.001 naratriptan 2.5 mg and 1 mg versus placebo and 1 mg and 2.5 mg versus 0.25 mg). Headache relief was maintained 8, 12, and 24 hours postdose with no use of rescue medication or a second dose of study medication by significantly (p < 0.001) greater percentages of patients after treatment with naratriptan 2.5 mg or 1 mg compared with naratriptan 0.25 mg or placebo. Naratriptan was also more effective than placebo in reducing clinical disability and the incidences of nausea, photophobia, and phonophobia. The overall incidence of adverse events and the incidences of specific adverse events did not differ in the naratriptan groups compared with placebo. No clinically relevant changes in ECG, blood pressure, or laboratory findings were reported. These data demonstrate that naratriptan is effective and well tolerated for the acute treatment of migraine. The 2.5-mg dose was associated with superior efficacy, whereas its adverse event profile was similar to that of placebo.",1997.0,0,1
613,9431839,The interaction between propranolol and the novel antimigraine agent zolmitriptan (311C90).,R W Peck; E J Seaber; R Dixon; C G Gillotin; B C Weatherley; G Layton; J Posner,"Zolmitriptan (Zomig, formerly known as 311C90), a selective 5HT1B/1D agonist is under development as an acute oral treatment for migraine. Despite the use of prophylactic medication, such as propranolol, breakthrough attacks often occur in patients. Consequently we investigated the effects of propranolol on the pharmacokinetics of, and cardiovascular responses to, zolmitriptan. A double-blind, randomized, crossover study of the effects of pre-treatment with propranolol 160 mg daily for 7 days or placebo on the pharmacokinetics and effects on blood pressure of a single 10 mg dose of zolmitriptan in 12 healthy volunteers. Propranolol increased mean zolmitriptan Cmax and AUC by 56% and 37% respectively; mean t1/2 was prolonged from 3.1 to 4.0 h. Mean Cmax and AUC of the pharmacologically active N-desmethyl metabolite were reduced by 24% and 11% respectively and the metabolite:parent AUC ratio (AUCm/AUCp) fell from 0.46 to 0.26. Mean Cmax and AUC for the inactive indole acetic acid metabolite were both reduced by 13% and AUCm/AUCp from 1.04 to 0.59. A small pressor effect of short duration was observed following zolmitriptan with mean peak rises of 13 and 11 mmHg in systolic and diastolic pressures respectively; propranolol had no effect on the pressor response. The results suggest that propranolol inhibits biotransformation of zolmitriptan but with no change in the small pressor response to zolmitriptan. It is therefore unlikely that the pharmacokinetic changes will lead to clinically important changes in pharmacological effects and dosage adjustment of zolmitriptan is not required in patients taking propranolol for migraine prophylaxis.",1998.0,0,0
614,9439085,"Naratriptan is effective and well tolerated in the acute treatment of migraine. Results of a double-blind, placebo-controlled, parallel-group study. Naratriptan S2WA3001 Study Group.",A Klassen; A Elkind; M Asgharnejad; C Webster; A Laurenza,"To evaluate the efficacy and tolerability of naratriptan, a novel 5-HT1 agonist, in the acute treatment of migraine. Six hundred thirteen migraineurs, diagnosed according to International Headache Society criteria, treated a single migraine attack with naratriptan tablets (2.5 mg, 1 mg, 0.25 mg, or 0.1 mg) or placebo in a randomized, double-blind, placebo-controlled, parallel-group study conducted at 54 United States centers. At dosing and at predetermined intervals beginning 30 minutes postdose, patients recorded migraine pain severity, clinical disability, and presence of associated migraine symptoms. Safety measures included adverse events, physical examinations, vital signs, ECGs, and clinical laboratory tests. Headache relief (moderate or severe pain at dosing reduced to mild or no pain) 4 hours postdose was reported in 60% of patients receiving naratriptan 2.5 mg compared with 50%, 35%, 32%, and 34% of patients receiving naratriptan 1 mg, 0.25 mg, 0.1 mg, and placebo, respectively (P < 0.05 naratriptan 2.5 mg and 1 mg versus placebo, 1 mg versus 0.1 mg, and 2.5 mg versus 0.1 mg and 0.25 mg). Clinical disability 4 hours postdose was reported as mild or none for 70% of patients receiving naratriptan 2.5 mg compared with 63%, 47%, 48%, and 48% of patients receiving naratriptan 1 mg, 0.25 mg, 0.1 mg, or placebo, respectively (P < 0.05 naratriptan 2.5 mg and 1 mg versus placebo, 1 mg versus 0.1 mg, and 2.5 mg versus 0.1 mg and 0.25 mg). Four-hour efficacy for absence of nausea, photophobia, and phonophobia was similar to efficacy for headache relief at each dose. The adverse event profile of each dose of naratriptan was similar to that of placebo. No clinically relevant change in any safety measure was reported. Naratriptan is effective and well tolerated for the acute treatment of migraine. The 2.5-mg dose appears to offer the optimum ratio of efficacy to tolerability.",1998.0,0,1
615,9453273,"Intensity dependence of the cortical auditory evoked potentials as a surrogate marker of central nervous system serotonin transmission in man: demonstration of a central effect for the 5HT1B/1D agonist zolmitriptan (311C90, Zomig).",A Proietti-Cecchini; J Afra; J Schoenen,"As shown in animal studies, 5HT1B/D agonists can inhibit activity in the trigeminal nucleus caudalis, which may be advantageous for their antimigraine effect. To demonstrate a possible central nervous system (CNS) action of these compounds in man we studied their effect on the intensity dependence of the cortical auditory evoked potentials (IDAPs), thought to be inversely related to central serotonergic transmission. An amplitude/stimulus intensity function (ASF) slope was computed in healthy volunteers and migraine patients between attacks before and 2 h after oral 311C90 (zolmitriptan ""Zomig"") 10 mg (n=14), 311C90 5 mg (n=7), sumatriptan 100 mg (n=14), dexfenfluramine 15 mg (n=4), lorazepam 1.25 mg (n=4) and placebo (n=14). 311C90 10 mg and, to a lesser degree, 5 mg significantly increased the mean ASF slope (p=0.007 and 0.05 vs placebo). There was a significant positive correlation between plasma levels of 311C90 and ASF slope changes. Sumatriptan and lorazepam had little effect, but dexfenfluramine produced a significant ASF slope decrease. 311C90 is able to modify a CNS activity that is modulated by serotonin, i.e. the IDAP. This effect is probably the consequence of its superior lipophilicity compared to sumatriptan and of activation of prejunctional 5HT1B/D autoreceptors, which lowers central serotonin release and thus the preactivation level of sensory cortices.",1998.0,0,0
616,9453276,Improvement in migraine-specific quality of life in a clinical trial of rizatriptan.,N C Santanello; A B Polis; S L Hartmaier; M S Kramer; G A Block; S D Silberstein,"A validated migraine-specific questionnaire (24-h Migraine Quality of Life Questionnaire: 24-h MQoLQ) was used to assess the impact of migraine and migraine therapy on health-related quality of life during an acute migraine attack. Male and female migraineurs aged 18-55 years were randomized to placebo (n=41), rizatriptan 2.5 mg (n=47), 5 mg (n=74), or 10 mg (n=85) in a triple-blind, placebo-controlled clinical trial. Rizatriptan 5 mg and 10 mg were significantly more efficacious than placebo on pain relief and functional disability. After accounting for multiple comparisons to placebo, rizatriptan 10 mg showed significantly better responses compared to placebo on three of five domains of 24-h MQoLQ (social functioning, migraine symptoms, and feelings/concerns). The O'Brien's Rank Sum Test statistic showed a statistically significant overall difference on the 24-h MQoLQ between the 10 mg rizatriptan and placebo groups (p=0.005) and for the overall dose trend (p< or =0.001).",1998.0,0,1
617,9474711,Cluster headache.,N T Mathew,"Cluster headache is characterized by regular periodicity, high frequency during a cluster period, relative brevity, and extreme intensity. Lancinations, as in trigeminal neuralgia, are rare. An important behavioral difference between migraine and cluster headache is that the patient is usually hyperactive during a cluster headache, whereas the migraineur retreats to a dark, quiet room. Cluster headache is more common in middle-aged men; migraine is more common in young women. Intermediate or overlap syndromes occur. Many of the same prophylactic and abortive treatments are effective in both, although in cluster headache there is a premium on rapid action.",1998.0,0,0
618,9475817,Sumatriptan contraindications and the serotonin syndrome.,D M Gardner; L D Lynd,"To determine the risk for serotonin syndrome associated with the concomitant use of sumatriptan and the currently contraindicated therapies, that is, the monoamine oxidase inhibitors (MAOIs), serotonin selective-reuptake inhibitors (SSRIs), and lithium. A comprehensive search for reports of serotonin syndrome associated with sumatriptan use was conducted by using tertiary drug interaction literature, MEDLINE, EmBASE, Biological Abstracts, Current Contents, Reactions, ClinAlert, and the International Pharmaceutical Abstracts. In addition, related reports from the proprietary manufacturers, the Health Protection Branch of Health Canada, and the World Health Organization Collaborative Centre for International Drug Monitoring were also solicited. The concurrent use of sumatriptan with an SSRI or lithium has been reported to cause symptoms suggestive of serotonin syndrome in 16 and 2 cases, respectively. There were no reports involving MAOIs. In general, the reports indicated a mild-to-moderate, self-limited course with some features consistent with the serotonin syndrome. We found published reports of sumatriptan use without adverse events involving 148 patients receiving SSRIs, 31 patients taking MAOIs, and a small number using lithium. Clinical evidence supporting the strict contraindication of MAOIs, SSRIs and lithium was not identified. The balance of documented clinical experience pertaining to the use of sumatriptan concurrently with SSRIs or lithium suggests that most patients tolerate this combination without incident. Because there is little reliable experience with sumatriptan in combination with MAOIs, we suggest that sumatriptan should continue to be avoided in patients taking these agents until further data demonstrating safety become available.",1998.0,0,1
619,9476036,The novel anti-migraine compound zolmitriptan (Zomig 311C90) has no clinically significant interactions with paracetamol or metoclopramide.,E J Seaber; G Ridout; G Layton; J Posner; R W Peck,"This study investigated potential pharmacokinetic or pharmacodynamic interactions between the novel anti-migraine compound zolmitriptan (Zomig, formerly 311C90) and paracetamol and/or metoclopramide. In an open-label, randomised, crossover study, 15 healthy volunteers received single oral doses of 10 mg zolmitriptan alone, 1 g paracetamol alone, 10 mg zolmitriptan + 1 g paracetamol, 10 mg zolmitriptan + 10 mg metoclopramide or 10 mg zolmitriptan + 1 g paracetamol + 10 mg metoclopramide on five separate occasions. Metoclopramide had no significant effects on the pharmacokinetics of zolmitriptan or the active zolmitriptan metabolite 183C91, nor did it affect interactions between zolmitriptan and paracetamol. Paracetamol marginally increased the maximum plasma concentration (Cmax) (11%) and the area under the curve (AUC) (11%) and reduced the renal clearance of zolmitriptan (9%); similar small effects were seen on 183C91. The AUC, Cmax and half-life of paracetamol were reduced by concomitant zolmitriptan (by 11%, 31% and 8%, respectively), whilst the mean residence time showed a small increase (+0.7 h). There was a trend towards a transient increase in blood pressure following all regimens containing zolmitriptan; this effect was small, was consistent between all zolmitriptan regimens as well as with previous studies, and was considered to be clinically insignificant. Zolmitriptan was well tolerated after all treatment regimens. Concomitant administration of zolmitriptan and paracetamol resulted in a slight increase in bioavailability of zolmitriptan and a reduced rate and extent of paracetamol absorption. These findings are considered to be of no clinical significance and there is no reason to avoid concomitant administration of paracetamol and/or metoclopramide with zolmitriptan.",1998.0,0,0
620,9484515,[Treatment of acute attack of migraine with sumatriptan].,L E González-Espinosa; N Gómez-Viera; I Olivera-Leal; R Reyes-Lorente,"In the Hospital Clínico Quirúrgico Hermanos Almeijeiras a randomized double blind clinical trial was carried out involving 52 patients who presented with painful migraine crises with or without prodromes. A group of 27 patients were given 6 mg of sumatriptan subcutaneously. Another group of 25 patients were given 1 mg of dihydroergotamine intramuscularly. It was seen that both drugs relieved the migrainous pain. However, sumatriptan did so in a greater percentage of patients. There was earlier, and also more complete, relief of pain in those patients receiving sumatriptan. With regard to side-effects of sumatriptan were pain at the back of the site of injection, sensation of pressure at the back of the neck, facial flushing and asthenia.",1998.0,0,0
621,9505001,Monitoring of acute migraine attacks: placebo response and safety data.,S S Jhee; D E Salazar; N F Ford; I E Fulmor; J J Sramek; N R Cutler,"In the course of evaluating the safety and efficacy of an investigational compound for acute migraine headaches, a large number of patients received placebo at a single site, offering the opportunity to characterize subjective and clinical physiologic responses of migraine patients to placebo in a controlled environment. In a single-site, double-blind, placebo-controlled study, 67 patients reported to the clinic while suffering a moderate to severe acute migraine headache and received oral placebo. For 6 hours after treatment, a continuous electrocardiogram (ECG) was performed, and headache severity, adverse events, and vital signs were recorded. Patients returned and repeated the procedure when free from pain. A headache was considered to be improved if its severity dropped to ""mild"" or ""none."" Twenty-five patients (37%; 95% CI: 26% to 50%) experienced headache improvement within 2 hours of receiving placebo, and 32 patients (48%: 36% to 60%) improved within 4 hours. There were no clinically important ECG changes during the migraine visit, and there were no clinically relevant differences in vital signs between the migraine and pain-free visits. Thus, a substantial placebo response occurs in migraine headache. Hemodynamic and ECG parameters are unchanged between migraine and pain-free states.",1998.0,0,1
622,9505883,Actions of the 5-hydroxytryptamine 1 receptor agonist sumatriptan on interdigestive gastrointestinal motility in man.,J Tack; B Coulie; A Wilmer; T Peeters; J Janssens,"Pharmacological studies of the enteric nervous system have shown the presence of several subtypes of 5-hydroxytryptamine (5HT) receptor, which might be involved in control of the migrating motor complex. To study the effect of sumatriptan, an agonist of enteric neuronal 5HT1p receptors, on interdigestive motility in man. In 12 healthy subjects, interdigestive motility was recorded manometrically in the upper gastrointestinal tract. In seven subjects blood samples were drawn every 15 minutes for radioimmunoassay of motilin and somatostatin. After two phase 3s of the migrating motor complex, 6 mg of sumatriptan was administered subcutaneously. Recording continued until two more phase 3s had occurred. Sumatriptan induced a premature phase 3 in the jejunum after a median of 10 (8) minutes. The duration of the migrating motor complex cycle was shortened at the expense of phase 2. After sumatriptan, plasma somatostatin concentrations were reduced and gastric phase 3s were suppressed, although median motilin concentrations and the occurrence of plasma motilin peaks were not affected. Phase 3s of the migrating motor complex preceding sumatriptan were associated with motilin peaks, while phase 3s after sumatriptan were not. Furthermore, pretreatment with sumatriptan prevented the induction of a gastric phase 3 by the motilin agonist erythromycin. Administration of the 5HT1P receptor agonist sumatriptan induces a premature intestinal phase 3, suppresses gastric phase 3s, prevents induction of a gastric phase 3 by erythromycin, and reduces plasma somatostatin concentrations.",1998.0,0,0
623,9514561,Experimental cranial pain elicited by capsaicin: a PET study.,A May; H Kaube; C Büchel; C Eichten; M Rijntjes; M Jüptner; C Weiller; H C Diener,"Using a positron emission tomography (PET) study it was shown recently that in migraine without aura certain areas in the brain stem were activated during the headache state, but not in the headache free interval. It was suggested that this brain stem activation is inherent to the migraine attack itself and represents the so called 'migraine generator'. To test this hypothesis we performed an experimental pain study in seven healthy volunteers, using the same positioning in the PET scanner as in the migraine patients. A small amount of capsaicin was administered subcutaneously in the right forehead to evoke a burning painful sensation in the first division of the trigeminal nerve. Increases of regional cerebral blood flow (rCBF) were found bilaterally in the insula, in the anterior cingulate cortex, the cavernous sinus and the cerebellum. Using the same stereotactic space limits as in the above mentioned migraine study no brain stem activation was found in the acute pain state compared to the pain free state. The increase of activation in the region of the cavernous sinus however, suggests that this structure is more likely to be involved in trigeminal transmitted pain as such, rather than in a specific type of headache as was suggested for cluster headache.",1998.0,0,0
624,9533603,Trigeminal neuralgia with lacrimation or SUNCT syndrome?,R Benoliel; Y Sharav,"An intimate relationship between trigeminal neuralgia (TN) and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) syndrome, based on similar clinical signs and symptoms and on cases demonstrating possible ""transformation"" from one entity to the other, has been widely accepted. We evaluated the presence of lacrimation in 22 consecutive cases that had been diagnosed as TN. Ipsilateral lacrimation was reported by 6 such cases (5M, 1F). These cases responded to antineuralgic therapy with concomitant resolution of lacrimation and were clinically very similar to TN. The differential diagnosis and the possibility of lacrimation in TN are discussed.",1998.0,0,0
625,9536565,,,,,0,1
626,9559030,Ramsay Hunt syndrome: a challenging herpes zoster virus infection.,A R Rahimi,,1998.0,0,1
627,9563207,"The long-term tolerability and efficacy of oral zolmitriptan (Zomig, 311C90) in the acute treatment of migraine. An international study. The International 311C90 Long-term Study Group.",,"This international open-label study evaluated the tolerability and efficacy of zolmitriptan (Zomig, 311C90), a selective 5-HT1B/1D receptor agonist, in the long-term treatment of multiple migraine attacks. Patients who had previously participated in placebo-controlled zolmitriptan studies were recruited. A total of 2058 patients treated 31,579 migraine attacks (average 15 per patient), for up to 1 year. Twenty-six percent of attacks treated with a single zolmitriptan 5-mg dose were associated with at least one adverse event (24% treated with two doses). The most frequent adverse events included asthenia (14% of patients), nausea (12%), somnolence (10%), dizziness (11%), and paresthesia (11%). The rank order of the most common adverse events was not influenced by sex, age, or number of zolmitriptan doses taken and was similar between attacks 1 and 45. The majority of adverse events (59%) occurred within 2 hours of dosing, were of either mild (59%) or moderate (35%) intensity, of 4 hours' duration or less (67%), and required no further action (94%). Following an initial 5-mg dose of zolmitriptan, the 2-hour headache response rate (reduction in headache pain from moderate or severe before treatment to mild or no pain at 2 hours posttreatment) was 81% in patients treating moderate and severe attacks (19,639 of 24,161). Patients were pain-free at 2 hours in 55% of all attacks (16,510 of 29,808). The efficacy of zolmitriptan was not influenced by age, sex, weight, use of prophylactic antimigraine medication, or association of attacks with menstruation. Analysis of the overall population and a subgroup who treated 30 or more migraine attacks showed that zolmitriptan was consistently effective across attacks. Overall, 67% of patients who treated five or more attacks reported zolmitriptan to be effective in 80% to 100% of attacks. Zolmitriptan produced meaningful migraine relief and improvement in normal activity impairment in 73% and 78% of moderate and severe attacks, respectively. Patients treated recurrence of moderate or severe headache with a second zolmitriptan dose in 32% of attacks which responded to the first dose within 2 hours. Where required, a second zolmitriptan 5-mg dose for treatment of recurrence produced a headache response rate of 90% at 2 hours postdose. Thus, zolmitriptan 5 mg (plus an optional second 5-mg dose for treatment of recurrence) is well tolerated and effective in the acute treatment of multiple migraine attacks over periods up to 1 year.",1998.0,0,1
628,9563208,"Efficacy and safety of sumatriptan tablets (25 mg, 50 mg, and 100 mg) in the acute treatment of migraine: defining the optimum doses of oral sumatriptan.",V Pfaffenrath; G Cunin; G Sjonell; S Prendergast,"That sumatriptan tablets are effective and well tolerated in the acute treatment of migraine has been established, but the relationship between dose and efficacy has not been adequately defined to date in clinical trials. This multinational double-blind trial (N = 1003) in which patients treated up to three migraine attacks with sumatriptan 25 mg, 50 mg, 100 mg, or placebo, with a second independently randomized dose for headache recurrence, evaluated the efficacy and tolerability of three doses of sumatriptan. The results demonstrate that all doses of sumatriptan were superior (P < 0.05) to placebo in reducing moderate or severe predose headache to mild or no headache 4 hours postdose for each of the three treated attacks; sumatriptan 50 mg and 100 mg were each superior (P < 0.05) to sumatriptan 25 mg 4 hours postdose for two of three attacks. Sumatriptan (all doses) was similarly effective at relieving nausea and photophobia or phonophobia or both and at reducing clinical disability. Headache recurrence was experienced by similar proportions of patients across treatment groups (35% to 48% after placebo; 26% to 39% after sumatriptan). Relief of recurrent headache 2 hours after the second dose of study medication occurred in greater percentages of patients using any dose of sumatriptan compared with patients using placebo to treat recurrence. The incidence of adverse events with 25-mg and 50-mg sumatriptan tablets was similar to the incidence with placebo and lower than the incidence with 100-mg sumatriptan tablets. These data provide the first demonstration from a large well-controlled clinical trial that both the 50- and 100-mg doses are more effective than the 25-mg dose and that the 50-mg dose is associated with a lower incidence of adverse events than the 100-mg dose.",1998.0,0,1
629,9563210,,,,,0,0
630,9563211,"Tolfenamic acid rapid release versus sumatriptan in the acute treatment of migraine: comparable effect in a double-blind, randomized, controlled, parallel-group study.",V V Myllylä; H Havanka; L Herrala; P Kangasniemi; I Rautakorpi; J Turkka; H Vapaatalo; O Eskerod,"The efficacy and safety of tolfenamic acid and oral sumatriptan in the acute treatment of migraine was studied at five neurological centers in Finland. One hundred forty-one patients experiencing 289 migraine attacks, fulfilling the diagnostic criteria for migraine with or without aura as defined by the International Headache Society, were randomized. For first attacks, 77% of patients receiving tolfenamic acid experienced a reduction of the initial severe or moderate headache to mild or no headache after 2 hours, as compared to 79% in the sumatriptan group and 29% in the placebo group. No significant difference was found between active treatments (P = 0.85, 95% CI [-22%, 18%]), however, both active treatments were significantly better than placebo; P = 0.001, 95% CI (26%, 69%) for tolfenamic acid and P = 0.001, 95% CI (28%, 71%) for sumatriptan. For second attacks, results were similar with 70% of patients receiving tolfenamic acid experiencing relief, as compared to 64% in the sumatriptan group and 39% in the placebo group. No significant differences were observed in accompanying symptoms. Both drugs were well tolerated with the frequency of adverse events; 30% for tolfenamic acid and 41% for sumatriptan, a nonsignificant difference. In this study, tolfenamic acid and oral sumatriptan are comparably effective in the acute treatment of migraine. When comparably effective, factors like individual effect, tolerance, and cost of treatment should be considered when prescribing migraine medication.",1998.0,0,1
631,9588435,"Sumatriptan injection reduces productivity loss during a migraine attack: results of a double-blind, placebo-controlled trial.",R C Cady; R Ryan; P Jhingran; S O'Quinn; D G Pait,"To evaluate the impact of sumatriptan succinate injection compared with placebo on productivity loss during a migraine attack in the workplace. Randomized, double-blind, placebo-controlled, parallel-group clinical trial. Fifteen clinical centers in the United States. One hundred thirty-five patients 18 years and older diagnosed as having migraine according to International Headache Society criteria. Patients self-administered sumatriptan injection (6 mg) or matching placebo to treat a moderate or severe migraine occurring within the first 4 hours of a minimum 8-hour work shift. Mean productivity loss 2 hours after dosing and across the work shift; percentages of patients returning to normal work performance within 2 hours after dosing and across the work shift; percentages of patients experiencing headache relief (reduction of moderate or severe predose pain to mild or no pain) 1 and 2 hours after dosing. Mean productivity loss was significantly (P< or =.002) lower in the sumatriptan group compared with the placebo group both during the 2-hour postdose period (sumatriptan, 39 minutes; placebo, 54 minutes) and across the work shift (sumatriptan, 86 minutes; placebo, 168 minutes). Significantly (P<.001) greater percentages of patients in the sumatriptan group compared with the placebo group returned to normal work performance by 2 hours after dosing (sumatriptan, 52%; placebo, 9%) and across the work shift (sumatriptan, 66%; placebo, 18%). Significantly (P< or =.001) greater percentages of patients in the sumatriptan group compared with the placebo group experienced headache relief 1 hour after dosing (sumatriptan, 69%; placebo, 18%) and 2 hours after dosing (sumatriptan, 79%; placebo, 32%). Sumatriptan reduced migraine-associated productivity loss during a minimum 8-hour work shift by approximately 50% compared with placebo and alleviated headache in more than three fourths of patients.",1998.0,0,1
632,9595865,Practicability and acceptance of subcutaneous self-administration of the selective serotonin agonist sumatriptan.,H Göbel; H Baar; H D Beiküfner; K Böhme; A Beckmann-Reinhold,"To cater to the special situation of much reduced oral bioavailability which occurs in severe migraine attacks with pronounced nausea and vomiting, sumatriptan can also be used in a subcutaneous form that can be self-administered. The aim of this study was to analyze the practicability and acceptance of a method of self-administration (""Glaxo-Pen"") for treatment of severe migraine attacks by subcutaneous injection of sumatriptan. The Glaxo-Pen was compared with the conventional autoinjector for subcutaneous administration of sumatriptan. The multicenter study was conducted under practical conditions by 150 office-based physicians in Germany. Patients who commonly suffered from severe migraine attacks were given a careful explanation of how to use the device (""Glaxo-Pen"") for self-administration of subcutaneous sumatriptan and were able to practice using it under guidance. They were given a Glaxo-Pen with two sumatriptan refills to take with them for treating their own migraine attacks. The patients used a headache diary to document administration outside the practice session. A total of 376 patients were included in the study. The major findings were that 80% of the patients rated the Glaxo-Pen ""very easy"" or ""easy"" to use, and only 6.4% rated it ""difficult"" or ""very difficult."" Compared with the conventional autoinjector, the Glaxo-Pen was rated ""much better"" or ""better"" by 77.9% of patients. Only 8.5% considered the Glaxo-Pen ""worse"" or ""much worse"" than the conventional autoinjector. The figures show that the great majority of patients found it easy to use sumatriptan for treating severe migraine attacks by self-administration under practical conditions. Thus, especially for patients who suffer from severe nausea, vomiting, or diarrhea during migraine attacks, this method of delivery is an easily used means of arresting migraine attacks.",1998.0,0,0
633,9595867,"Rizatriptan (MAXALT) for the acute treatment of migraine and migraine recurrence. A placebo-controlled, outpatient study. Rizatriptan 022 Study Group.",J Teall; M Tuchman; N Cutler; M Gross; E Willoughby; B Smith; K Jiang; S Reines; G Block,"Rizatriptan is a novel 5-HT1B/1D agonist which is rapidly absorbed after oral administration. The efficacy and tolerability of oral rizatriptan (5 mg and 10 mg) were examined in this multicenter, double-blind, outpatient study of 1473 migraineurs which featured randomized, placebo-controlled treatment of migraine recurrences. On experiencing moderate or severe migraine headaches, patients rated headache severity prior to dosing and at 30-minute intervals for 2 hours after dosing. Onset of effect was seen as early as 30 minutes after dosing with rizatriptan 10 mg. At 2 hours postdose, the percentage of patients with pain relief was significantly higher after rizatriptan 5 mg (62%) or 10 mg (71%) compared with placebo (35%). Complete relief was also significantly higher after rizatriptan 5 mg (33%) and 10 mg (42%) compared with placebo (10%). In patients experiencing headache recurrence after initial benefit, further relief was obtained in 71% with rizatriptan 5 mg (placebo 54%) and in 82% with rizatriptan 10 mg (placebo 44%). Complete relief of recurrent headache was obtained in 36% with rizatriptan 5 mg, 49% with rizatriptan 10 mg, and 15% with placebo (P < 0.05). The most common drug-related adverse experiences were dizziness, somnolence, asthenia/fatigue, and nausea (the incidences of which were low and dose related). There was no increase in the incidence of adverse experiences after use of up to three doses of rizatriptan within 24 hours. We conclude that both doses of rizatriptan are effective and well tolerated in the acute treatment of migraine and migraine recurrence, with the 10-mg dose preferred as it is more effective with a faster onset of action.",1998.0,0,1
634,9595871,Melatonin-responsive headache in delayed sleep phase syndrome: preliminary observations.,J E Nagtegaal; M G Smits; A C Swart; G A Kerkhof; Y G van der Meer,"The occurrence of headache and its change after treatment with melatonin 5 mg were studied in 30 patients with delayed sleep phase syndrome. The medication was taken 5 hours before the endogenous nocturnal plasma melatonin concentration had reached 10 pg/mL. Three women (aged 14, 14, and 23 years) suffered from chronic tension-type headache. Their headache disappeared within 2 weeks after the start of treatment with melatonin. One 54-year-old man suffered from disabling migraine attacks without aura, twice a week. After starting melatonin treatment, only three migraine attacks were reported in 12 months. Ever since his 40s, a 60-year-old man complained of cluster headache episodes lasting about 2 months, twice a year. In the year since starting melatonin treatment, only one 5-day cluster episode occurred. Nocturnal melatonin secretion in the patients with delayed sleep phase syndrome and headache did not differ significantly from that in the patients with the sleep disorder but without headache. Melatonin may be helpful in patients with headache who are suffering from delayed sleep phase syndrome. Its effectiveness may be due to modification of vascular and nociceptive systems or to its chronobiological action which adjusts the patient's biological clock to his/her life-style.",1998.0,0,0
635,9596457,Multiple-attack efficacy and tolerability of sumatriptan nasal spray in the treatment of migraine.,S Diamond; A Elkind; R T Jackson; R Ryan; S DeBussey; M Asgharnejad,"Sumatriptan hemisulfate nasal spray may provide a useful therapeutic option for patients with migraine who find injectable medications inconvenient or uncomfortable and for patients whose migraine-associated nausea and vomiting preclude the use of oral medication. This study was the first US trial to evaluate the effects of sumatriptan nasal spray administered for multiple migraine attacks. Sumatriptan nasal spray (5, 10, or 20 mg) was administered via a 1-shot nasal applicator into either nostril for up to 3 migraine attacks occurring over 6 months in a randomized, double-blind, parallel-group, placebo-controlled study. Fifty-six outpatient clinical centers in the United States. A total of 1086 men and women diagnosed with migraine with or without aura per International Headache Society criteria. Percentage of patients with headache relief (moderate or severe predose pain reduced to mild or none); percentage of patients with no or mild (vs moderate or severe) clinical disability; percentage of patients with nausea, vomiting, photophobia, or phonophobia; adverse events; clinical laboratory test results. Across attacks, headache relief in the 20-, 10-, and 5-mg drug and placebo groups was experienced 120 minutes postdose by 60%, 54%, 44%, and 32% of patients, respectively (P<.05 for each sumatriptan nasal spray group vs placebo, for the 10-mg vs 5-mg drug group, and for the 20-mg vs 5-mg drug group). Two thirds of the 20-mg patients treating 3 attacks experienced relief at 2 hours postdose for at least 2 of 3 attacks. Clinical disability scores at 120 minutes in the 20-, 10-, and 5-mg drug and placebo groups reflected no or mild impairment in 70%, 67%, 57%, and 50% of patients, respectively (P<.05 for the 10- or 20-mg drug group vs placebo group, and for the 20-mg vs 5- mg drug group). Similar efficacy rates were observed for nausea, photophobia, and phonophobia. For all parameters, individual-attack efficacy rates did not differ from across-attack rates. The incidence of adverse events was not dose related. The most frequently reported adverse event in the active treatment groups was taste disturbance (bad, bitter, or unpleasant). Sumatriptan hemisulfate nasal spray (5, 10, or 20 mg) is effective and well tolerated in the treatment of multiple migraine attacks. The 20-mg dose was associated with the highest efficacy rates across the greatest number of parameters.",1998.0,0,1
636,9601621,Nitric oxide synthase inhibition: a new principle in the treatment of migraine attacks.,L H Lassen; M Ashina; I Christiansen; V Ulrich; R Grover; J Donaldson; J Olesen,"Glyceryl trinitrate, an exogenous nitric oxide (NO) donor, and histamine, which causes NO formation in vascular endothelium, have been shown to trigger migraine attacks. However, it remains uncertain whether NO is involved in the subsequent phase of migraine attacks. To answer this question we studied the effect of L-NGmethylarginine hydrochloride (546C88), a NO-synthase inhibitor, on spontaneous migraine attacks. In a double-blind study design, 18 patients with migraine without aura randomly received 546C88 (6 mg/kg) or placebo (5% dextrose) i.v. given over 15 min for a single migraine attack (546C88:placebo, 15:3). Furthermore, 11 placebo-treated patients from previous double-blind trials with almost identical design were added to the placebo group in the statistical evaluation. Two hours after the infusion, 10 of 15 L-NGmethylarginine hydrochloride-treated patients experienced headache relief compared to 2 of 14 placebo-treated patients (p = 0.01). Symptoms such as phono- and photophobia were also significantly improved. A similar trend for nausea was not significant. We conclude that NO may be involved in the pain mechanisms throughout the course of spontaneous migraine attacks.",1998.0,0,0
637,9604136,Episodic cluster headache in a community: clinical features and treatment.,C M Riess; W J Becker; M Robertson,"To study the clinical features and treatment given to episodic cluster headache patients in the Calgary region. Fifty-one (51) patients who responded to a media campaign, had previously been diagnosed by their family physicians, and who met International Headache Society (IHS) criteria for episodic cluster headache, formed the population for this study. The media campaign consisted of newspaper advertisements and radio publicity including physician interviews and talk shows. Patients were required to complete by 200-item questionnaire detailing clinical features and treatment of their cluster headache syndrome. Each patient was also interviewed by our research nurse for clarification and proper completion of questionnaire. Fifty-one percent (51%) of our patients had short headache attacks lasting one hour or less. Almost one-half (45%) had three or four attacks per 24 hour period. Eighty-six percent (86%) had been referred to a neurologist. Sixty-nine percent (69%) had never used oxygen, but of those who had, one-half were still using it. Sumatriptan by injection had been tried by 26% of patients and of these, 93% considered it effective. Subcutaneous dihydroergotamine had been tried by 8%. For prophylaxis, 41% had tried methysergide, 31% prednisone, and 4% verapamil. Many patients had been prescribed migraine prophylactic drugs which are ineffective for cluster headache, and some had also undergone dental procedures or nasal and sinus surgeries. Many cluster headache patients had not, to their knowledge, been prescribed or used the best symptomatic and prophylactic treatments for cluster headache. This should be addressed through educational programs and through making up-to-date information on the treatment of cluster headache readily available to physicians and patients.",1998.0,0,0
638,9617601,Sumatriptan. An updated review of its use in migraine.,C M Perry; A Markham,"Sumatriptan is a selective agonist at serotonin 5-HT1-like receptors, including 5-HT1B/1D subtypes. It is an effective treatment for acute migraine attacks and the injectable form has also shown efficacy in the treatment of cluster headaches. In placebo-controlled clinical trials, sumatriptan, administered subcutaneously, orally, intranasally or rectally was significantly more effective than placebo in relieving migraine headache and in producing resolution or reduction of other symptoms associated with migraine, including nausea, photophobia and phonophobia. Improvements in clinical disability were also significantly greater after sumatriptan than after placebo. Headache recurred in 21 to 57% of patients who received oral or subcutaneous sumatriptan, but most patients responded to a second dose of the drug. Results of comparative trials showed that subcutaneous sumatriptan 6 mg was significantly more effective than either patients' usual antimigraine treatments or intranasal dihydroergotamine mesylate 1 mg in relieving migraine headache. Subcutaneous sumatriptan 6 mg and subcutaneous dihydroergotamine mesylate 1 mg provided similarly effective migraine relief, but the headache recurrence rate was significantly higher after sumatriptan than after this formulation of dihydroergotamine mesylate. Response rates achieved after oral sumatriptan were similar to those reported after treatment with oral naratriptan, rizatriptan or lysine acetylsalicylate plus metoclopramide. Treatment of acute migraine attacks with oral or subcutaneous sumatriptan leads to less loss of workplace productivity than other antimigraine therapies. Several pharmacoeconomic analyses showed that gains in workplace productivity in sumatriptan recipients ranged from 12.1 to 89.8 hours per patient per year. Significant improvements from baseline in overall health-related quality-of-life scores were also experienced by sumatriptan recipients. Sumatriptan is generally well tolerated. Nausea, vomiting, malaise and fatigue are the most common adverse events with oral sumatriptan. Injection site reactions occur in 10 to 40% of patients receiving the drug subcutaneously. A bitter taste at the back of the mouth occurs frequently after intranasal administration. Serious adverse events occur in about 0.14% of patients with migraine treated with sumatriptan. As the drug is associated with the rare development of cardiovascular effects, it is contraindicated in patients with a history of cardiovascular disease. Despite its relatively high acquisition cost, reductions in lost workplace productivity experienced by patients treated with sumatriptan may result in savings in the overall cost of migraine to society. Thus, sumatriptan is a useful first- or second-line treatment option for patients with moderate or severe migraine.",1998.0,0,1
639,9630008,Sumatriptan lowers plasma prolactin in healthy female volunteers.,R Whale; P J Cowen,,1998.0,0,0
640,9630786,Dosing of oral sumatriptan: a review of our first 104 patients.,G D Solomon; K Frizelis; J Becker; R S Kunkel,"The introduction of oral sumatriptan in the United States at doses of 25 and 50 mg, compared with 100-mg tablets worldwide, has created the need to develop a protocol for appropriate dosing. We evaluated the first 104 patients in our practice to treat two migraine attacks with oral sumatriptan. For their first treatment with oral sumatriptan, patients were evaluated on their response to 25-mg tablets and the total number of tablets taken. For their second treatment, patients were evaluated on their response to sumatriptan, number of 25-mg tablets taken, and dosage prescribed for future migraines. [table see text] After the second treatment, 41 patients (40%) continued therapy with 25-mg tablets, 54 (53%) were prescribed 50-mg tablets, 2 patients (2%) were prescribed two 50-mg tablets, and 5 patients (5%) were prescribed injectable sumatriptan. Seventy patients had previously used injectable sumatriptan, while 34 had not previously used sumatriptan. There were no significant differences in their response to oral sumatriptan. Oral sumatriptan was effective in clinical practice at doses of 25 and 50 mg. The majority of patients required more than one 25-mg tablet for a migraine attack, reflecting both inadequacy of dosing for some migraines and recurrence of headache, yet 40% of patients continued on treatment with 25-mg tablets. There were no significant differences in response to therapy in patients being switched from injectable to oral sumatriptan compared with those initiating therapy with oral sumatriptan. Both tablet strengths of oral sumatriptan are useful in clinical practice.",1998.0,0,0
641,9673801,NK-mediated links for migraine.,P Martelletti,,1998.0,0,0
642,9673807,Consistency of response to sumatriptan nasal spray across patient subgroups and migraine types.,E Ashford; R Salonen; J Saiers; M Woessner,"With an onset of headache relief as early as 15 min postdose compared with placebo, sumatriptan nasal spray is an important treatment option for patients who seek rapid headache relief and/or a convenient dosing form, whose migraine-associated nausea and vomiting render the use of an oral medication impractical, and those who prefer not to use an injectable form of migraine medication. Although the efficacy and tolerability of sumatriptan nasal spray are documented, the consistency of response to sumatriptan nasal spray across patient subgroups and migraine subtypes of importance to the prescribing clinician have not been described. To provide this information, data from four randomized, double-blind, parallel-group, placebo-controlled, multicenter studies (Glaxo Wellcome protocol numbers S2B-340, S2B-341, S2B-342, and S2B-T50), conducted between January 1993 and December 1994, were pooled and retrospectively analyzed to determine whether the efficacy and tolerability of sumatriptan nasal spray vary with gender, ethnic origin, age, weight, migraine type, concomitant or prior medication use, or pretreatment headache duration. Two-thousand-three-hundred-and-ninety-five (2395) patients treated a moderate or severe migraine with study medication in the four studies. The results demonstrate that sumatriptan nasal spray 20 mg and 10 mg were effective and well tolerated in the acute treatment of migraine consistently across a variety of patient and migraine subgroups. No clinically significant differences in headache relief or adverse event rates were observed for any of the subgroups examined. Approximately two-thirds of patients treated with sumatriptan nasal spray 20 mg compared with approximately one-third of placebo-treated patients reported headache relief 2 h postdose regardless of patient or migraine subgroup. The relationship between active treatment and placebo with respect to the overall incidence of adverse events also did not differ between patient or migraine subgroups. There is no evidence based on this analysis that sumatriptan nasal spray dosage should be adjusted in any of the subgroups examined.",1998.0,0,1
643,9674831,A pilot study of oral sumatriptan as intermittent prophylaxis of menstruation-related migraine.,L C Newman; R B Lipton; C L Lay; S Solomon,"Headaches associated with menstruation are often resistant to abortive and preventative medications. We performed an open-label study in 20 female migraineurs, employing oral sumatriptan perimenstrually as short-term prophylaxis of menstrual migraine. In 126 sumatriptan-treated cycles, headache was absent in 52.4% and reduced in severity by 50% or greater in 42%. Breakthrough headaches were rare and significantly reduced in severity compared with baseline headaches.",1998.0,0,0
644,9710039,Pregnancy outcome following first trimester exposure to sumatriptan.,S Shuhaiber; A Pastuszak; B Schick; D Matsui; G Spivey; J Brochu; G Koren,"We prospectively compared pregnancy outcome after exposure to sumatriptan with that of disease-matched controls and nonteratogen controls. There were no differences in the rates of live births, spontaneous abortions, therapeutic abortions, or major birth defects among the three groups. This first prospective report suggests that the use of sumatriptan during organogenesis is not associated with an apparent increased risk of major birth defects.",1998.0,0,0
645,9725543,"Pharmacokinetics and pharmacodynamics of zolmitriptan in patients with mild to moderate hypertension: a double-blind, placebo-controlled study.",D A Smith; E W Cleary; S Watkins; C S Huffman; S C Dilzer; K C Lasseter,"Zolmitriptan is a potent selective 5HT1B/1D receptor agonist for acute migraine therapy. Zolmitriptan has vasoconstrictor activity in cerebral vessels and may cause slight elevations of blood pressure in subjects without hypertension. Therefore, the pharmacokinetics and pharmacodynamics of zolmitriptan (5, 10, and 20 mg) were evaluated in 16 patients with mild to moderate hypertension (controlled by hydrochlorothiazide 50 mg once daily) and 17 healthy age- and sex-matched control subjects in a randomized, placebo-controlled, double-blind, four-period crossover study. The pharmacokinetics of zolmitriptan and its metabolites were dose proportional. Although area under the concentration-time curve (AUC0-infinity) and maximum concentration (Cmax) were slightly higher in patients with hypertension at all doses, this was only statistically significant for AUC at the 20-mg dose. Differences between subjects with and without hypertension were not clinically significant. Zolmitriptan produced a small increase in blood pressure, but this was similar in subjects with and without hypertension and was of no clinical significance. Zolmitriptan was well tolerated in both groups. Zolmitriptan plasma concentrations were higher in women than in men, with higher values of AUC and Cmax and lower total clearance in women. These results indicate that zolmitriptan can be administered for treatment of migraine in patients with controlled hypertension without dose adjustment.",1998.0,0,0
646,9725544,Effect of hepatic impairment on the pharmacokinetics of zolmitriptan.,R Dixon; S French; J Kemp; M Sellers; V Leclerc; M Delvaux; J Rautureau,"Zolmitriptan, an oral 5HT1D agonist for the acute treatment of migraine, is cleared from the systemic circulation mainly by hepatic metabolism. Consequently, changes in hepatic function may result in changes in the pharmacokinetics of zolmitriptan. This open, parallel-group study was conducted to compare the pharmacokinetics and tolerability of a single 10-mg dose of zolmitriptan in healthy subjects and patients with hepatic impairment. A total of 37 participants entered and completed the study, including 10 healthy volunteers, 11 patients with moderate hepatic impairment, 10 patients with severe hepatic impairment without ascites, and 6 patients with severe hepatic impairment with ascites. The metabolism of zolmitriptan was reduced in patients with severe hepatic impairment compared with healthy subjects, resulting in higher peak plasma concentrations (47%), increased exposure (226%), and prolonged half-life (157%). The changes were similar in the presence and absence of ascites. Smaller changes were observed in patients with moderate hepatic impairment. Plasma concentrations of the three major metabolites of zolmitriptan were reduced in the patients with hepatic impairment. Patients with moderate hepatic impairment require no dosage adjustment, but the recommended daily intake of zolmitriptan may need to be reduced in patients with severe hepatic impairment.",1998.0,0,0
647,9731928,Differences in perceived and presented adverse drug reactions in general practice.,J P Ottervanger; H A Valkenburg; D E Grobbee; B H Stricker,"Postmarketing surveillance (PMS) studies are frequently based on data from general practitioners (GPs). Patients, however, do not always report to their GP suspected adverse drug reactions. A postmarketing cohort study on adverse reactions to sumatriptan, performed with assistance of drug dispensing GPs in The Netherlands. Questionnaires were sent to all drug-dispensing GPs in The Netherlands, as well as to their patients on sumatriptan. To avoid bias, no specific adverse reactions were mentioned in the questionnaires. Of the GPs, 589 (86%) responded; of the patients, 1202 (70%) responded. The most frequently reported suspected adverse reactions to sumatriptan reported by the GPs were dizziness (1.7%), nausea or vomiting (1.5%), drowsiness or sedation (1.4%), and chest pain (1.3%). The most frequently reported suspected adverse reactions by the patients were paraesthesia (11.7%), dizziness (8.1%), feeling of heaviness (8.0%), and chest pain (7.9%). Neither the GPs nor the patients reported serious adverse reactions. First, patients experience significantly more suspected adverse reactions than are registered by their GP. In view of this higher frequency of reporting of suspected adverse reactions, postmarketing studies with data from GPs only, may underestimate the cumulative incidence of adverse reactions. Second, we conclude that it is possible to obtain useful additional information about adverse drug reactions from patients by sending them questionnaires via their GP.",1998.0,0,1
648,9748025,A placebo-controlled crossover study of rizatriptan in the treatment of multiple migraine attacks. Rizatriptan Multiple Attack Study Group.,M S Kramer; D Matzura-Wolfe; A Polis; A Getson; P G Amaraneni; M P Solbach; W McHugh; J Feighner; S Silberstein; S A Reines,"To examine the safety and efficacy of rizatriptan 10 mg PO in the treatment of multiple migraine attacks. Rizatriptan is a potent and rapidly absorbed 5-HT1B/1D receptor agonist. Efficacy and general safety have been examined in controlled trials treating single migraine attacks. In the current placebo-controlled study, we report constancy of safety and efficacy of rizatriptan for patients treating four discrete migraine attacks. Patients with moderate or severe migraine (n = 473) were randomized to one of five sequence groups, in which each patient was to treat four migraine attacks. Patients in four groups received rizatriptan 10 mg for three of four attacks and placebo for the remaining attack. Patients in the fifth group received rizatriptan 10 mg for four attacks. Headache severity, functional disability, and migraine symptoms were measured immediately before dosing and at 0.5, 1, 1.5, 2, 3, and 4 hours postdose. After the first attack, response rates were 77% for rizatriptan and 37% for placebo (p < 0.001). Similar efficacy of rizatriptan, ranging from a 75 to 80% response, was observed in each of the subsequent attacks with no evidence of tolerance to therapeutic effects. Most patients (93%) responded to rizatriptan 10 mg during the first or second attack. Adverse experiences were generally mild and transient, the most common being dizziness and somnolence. Incidence of adverse experiences per attack decreased after the first attack. Rizatriptan 10 mg PO is efficacious and generally well tolerated in acute migraine. Its efficacy is maintained throughout the treatment of multiple, discrete migraine attacks.",1998.0,0,1
649,9748059,Acute therapy for cluster headache with sumatriptan: findings of a one-year long-term study.,H Göbel; V Lindner; A Heinze; M Ribbat; G Deuschl,"The efficacy, safety, and tolerability of subcutaneous sumatriptan in the acute treatment of cluster headache were investigated in a multicenter study over a period of up to 1 year. A total of 2,031 attacks were evaluated in 52 patients. Therapy was successful in 88% of all attacks. Freedom from pain within 15 minutes in more than 90% of all attacks treated was reported by 42% of the patients, and no decline in efficacy occurred during the course of the study. Adverse events were reported by 62% of the patients.",1998.0,0,1
650,9754503,Emergency management of migraine: is the headache really over?,J Ducharme; R C Beveridge; J S Lee; S Beaulieu,"To observe headache frequency after release for acute migraine sufferers treated in an ED; to observe the impact after-release headaches and associated symptoms have on quality of life; and to document the variability in migraine management in an emergency setting. Prospective observational study, including 24- and 72-hour telephone follow-up. Over a 4-month period, 143 patients with headaches (149 visits) were observed in the ED. Of 108 patients successfully contacted, the incidence of headache in the first 24 hours after release was 49.1%. Forty-two patients left the ED without pain; 13 of these subsequently had return of headache. Sixty-six left with some degree of pain, with 40 having headache persistence at 24 hours. The difference in 24-hour headache rate between the 2 groups is significant (p=0.008). Five patients still had headaches at 72 hours after release, but 54 of 70 contacted had taken medication for their symptoms between 24 and 72 hours after release. Forty-five percent were not back to normal function at 24 hours, while 21 of 70 were still not sleeping well at 72 hours. Finally, 8 different classes of medications were used in the ED for migraine headaches, with 20 patients receiving at least 3 types of medication. Treatment for acute migraine headache in this emergency setting was variable. Patients not obtaining complete relief in the ED had a higher rate of headache after release than did those who left with no pain. Migraine sufferers may have normal daily function affected for up to 72 hours or longer after ED treatment.",1998.0,1,1
651,9755356,Serotonergic synergism: the risks and benefits of combining the selective serotonin reuptake inhibitors with other serotonergic drugs.,C DeBattista; M Sofuoglu; A F Schatzberg,"It has become common clinical practice to combine the selective serotonin reuptake inhibitors with other serotonergic agents for augmentation or adjunctive purposes. The empirical basis for using these combinations remains limited, but is growing. Also growing is a literature that suggests that even the most apparently benign combinations of serotonergic drugs carry at least some risk of serious pharmacokinetic or pharmacodynamic drug interactions, such as a serotonin syndrome.",1998.0,0,0
652,9793699,Effects of the antimigraine compound zolmitriptan ('Zomig') on psychomotor performance alone and in combination with diazepam in healthy volunteers.,R Dixon; A M Hughes; K Nairn; M Sellers; J V Kemp; R A Yates,"Zolmitriptan (Zomig) is a 5HT1B/1D agonist which has the ability to cross the intact blood-brain barrier to access central as well as peripheral receptors. Because of the potential for central nervous system side effects, this randomized, double-blind, placebo-controlled, 6-period crossover study evaluated the effects of 2.5 and 5 mg doses of zolmitriptan on psychomotor performance and investigated any pharmacodynamic or pharmacokinetic interaction with diazepam. Twelve healthy volunteers received the following ""treatments"" as single doses: zolmitriptan 2.5 mg, zolmitriptan 5 mg, diazepam 10 mg, zolmitriptan 2.5 mg + diazepam 10 mg, zolmitriptan 5 mg + diazepam 10 mg and placebo. Pre-dose and at 1, 4, 8, and 24 h post-dose, the following validated battery of psychomotor tests was performed: Bond-Lader visual analogue scales (calmness, contentedness, and alertness factors), critical flicker fusion test, choice reaction time (recognition, motor, and total reaction times), finger-tapping test, number cancellation test and digit symbol substitution test. Plasma concentrations of zolmitriptan, its active metabolite, and diazepam and its active metabolites were measured at the same timepoints. Zolmitriptan 2.5 and 5 mg had no effect on psychomotor function when given alone. In contrast, diazepam 10 mg had profound effects, consistent with its sedative properties, but there was no synergism on concomitant administration of either dose of zolmitriptan. Plasma concentrations of zolmitriptan, diazepam, and their respective active metabolites were similar when the two drugs were given alone or in combination.",1998.0,0,0
653,9793700,Effect of subcutaneous naratriptan on forearm blood flow.,L Yogendran; D Boswell; P Nacci; P Winter,"This randomized, double-blind, placebo-controlled, four-way crossover study was conducted on an in-clinic basis to assess forearm perfusion after subcutaneous (s.c.) naratriptan and placebo by reserve volume (hyperemic/baseline) and basal forearm blood flow (FBF) measured by strain gauge plethysmography. Nineteen male and female volunteer migraine subjects (International Headache Society criteria) received s.c. naratriptan 1 mg, 5 mg, 10 mg, and placebo on four separate study days outside a migraine attack. FBF was recorded at baseline, at 7-min intervals post-dose up to 1 h (basal) and once after sublingual glyceryl trinitrate administered at 1 h (hyperemic). Vital signs and electrocardiograms were recorded at baseline and 15, 30, 45, and 60 min post-dose. There were no statistically significant differences in reserve volume (hyperemic/baseline) between any dose of s.c. naratriptan and placebo. The naratriptan to placebo ratio was 102% (95% CI: 87-120%; p = 0.789) for 1 mg; 97% (95% CI: 83-114%, p = 0.737) for 5 mg; and 92% (95% CI: 79-108%; p = 0.325) for 10 mg. There were no statistically significant differences in basal FBF for any dose compared to placebo. The naratriptan to placebo ratio was 95% (95% CI: 87-104%; p = 0.263) for 1 mg; 94% (95% CI: 86-102%; p = 0.142) for 5 mg; and 94% (95% CI: 86-103%; p = 0.157) for 10 mg. The percentage of patients reporting adverse events was 53% with placebo, 53% with s.c. naratriptan 1 mg, 89% with 5 mg and 89% with 10 mg. In conclusion, these results suggest that s.c. naratriptan doses similar to and above the oral therapeutic dose equivalent (single oral dose 2.5 mg) have no significant effect on peripheral blood flow as measured by FBF. S.c. naratriptan doses 1 mg, 5 mg, and 10 mg were well tolerated.",1998.0,0,0
654,9793701,Effect of operationalized computer diagnosis on the therapeutic results of sumatriptan in general practice.,H Göbel; A Heinze; K Kuhn; D Heuss; V Lindner,"A multicenter test was conducted to investigate the effectiveness of the selective serotonin agonist sumatriptan in patients with the computerized headache diagnosis of migraine. A computer program was used for diagnostic evaluation of patients attending a general practice because of headache. The results of the analysis were taken as a direct decision on therapy. If the patients satisfied the criteria for migraine, they were given subcutaneous sumatriptan for treating three migraine attacks. The patients were able to use the study medication under outpatient conditions. The therapeutic efficacy of the medicine was recorded in a headache diary. A total of 91 patients were included in the study at 22 practices in Germany. An average of four patients per practice were recruited. In the first migraine attack treated, headache improvement was experienced by 77.7% of the patients treated. In the second and third attacks an improvement was experienced by 93.5% and 89.8%, respectively. The results show that by optimizing diagnostic reliability with the aid of the computer program a high response rate can be achieved under practice conditions using the selective serotonin agonist sumatriptan. Since the computer program described permits a specific diagnosis, it improves the prospects of effective headache therapy in the individual patient. Thus treatment based on this approach can reduce inputs of time and money in migraine therapy.",1998.0,0,0
655,9793702,Sumatriptan nasal spray (20 mg/dose) in the acute treatment of cluster headache.,J E Hardebo; C Dahlöf,"Subcutaneous injection of sumatriptan is an effective treatment for attacks of cluster headache with a short onset of action. This open, randomized study evaluates whether sumatriptan nasal spray at its highest commercially available dose (20 mg/dose) is equally effective. In 26 patients, four consecutive attacks were treated alternately with nasal spray and subcutaneous injection. Treatment was given within 5 min of onset of pain, and the time interval for the start and completeness of pain relief, provided these occurred within 15 min of administration, were recorded by the patient. After completion of the study, the patients were also asked to indicate which treatment they preferred, based on efficacy, side effects, and handling of the preparation. Forty-nine of the 52 treatments with injection resulted in complete relief of pain within 15 min, with a mean of 9.6 min. The remaining three attacks were reduced by a mean of 86.7% at 15 min. Only 7 of the 52 treatments with nasal spray in the nostril ipsilateral to pain resulted in complete relief within this time period, with a mean of 13.0 min. In 18 of these treatments pain was reduced by a mean of 42.2% at 15 min, whereas no effect on pain was obtained at this time in the remaining 27 treatments. The effect was almost identical when the nasal spray was administered in the nostril on the non-painful side. As an overall judgement, only 2 of the 26 patients preferred nasal spray to injection. We conclude that sumatriptan nasal spray 20 mg/dose is less effective than subcutaneous injection in relieving pain in the great majority of cluster headache sufferers.",1998.0,0,1
656,9795022,"Comparative clinical pharmacokinetics of single doses of sumatriptan following subcutaneous, oral, rectal and intranasal administration.",C Duquesnoy; J P Mamet; D Sumner; E Fuseau,"Sumatriptan, a 5-HT1 receptor agonist active for the acute treatment of migraine, is currently available as subcutaneous injection and oral tablets. Rectal or intranasal formulations may offer advantages over those marketed. This study compared the pharmacokinetics of sumatriptan via all four routes. Usual absorption parameters were described and the rate of absorption was assessed using deconvolution technics. There were no statistical differences between the non-parenteral routes for tmax or Cmax/AUCinfinity. However, Cmax and AUCtmax were statistically greater with the suppository than with the tablet, but there was no difference between intranasal and oral routes. The highest rate of absorption occurred earlier with the intranasal than with the oral route. Relative to the subcutaneous route, the bioavailability for the suppository was greater than for intranasal spray and oral tablet. The amount of sumatriptan excreted in the urine unchanged was similar for all routes. Sumatriptan in this study was well tolerated.",1998.0,0,0
657,9812772,Clinical study of epidural analgesia with clonidine and sumatriptan in posthysterectomy.,Z Liu; Y Tian; C Zhang; S Jin,"A clinical study was conducted to compare the analgesic effect of clonidine with those of sumatriptan and their mixture and their effects on hemodynamics. 40 patients undergoing elective total hysterectomy were randomly divided into 4 groups in terms of the epidurally administered drugs with 10 patients in each group (group C1: clonidine 150 micrograms, group C2: clonidine 75 micrograms, group S: sumatriptan 6 mg and group S + C: clonidine 75 micrograms + sumatriptan 3 mg). MAP, HR, SpO2, VT VAS, VRS and ePDT were measured in the initial 4 h. The demographic data and the doses of intraoperative local anesthetics among the 4 groups were not statistically different. It was found that no significant difference in the pre- and postadministration values of HR, SpO2 and VT. A obvious reduction of MAP appeared in the groups of C1 and C2, but in the other groups the hemodynamical parameters were stable. The groups of C1, C2 and S + C showed significant increase in VAS and VRS, along with increase of ePDT when compared with the pre-drug level. There was no obvious alteration in group S after the drug administration. It was concluded that (1) single use of sumatriptan is ineffective in the dose given in this study; (2) small dose (150 micrograms and 75 micrograms) of clonidine has epidurally analgesic effects; (3) combined use of sumatriptan and clonidine is an acceptable way in epidural analgesia, in terms of its analgesic effect and hemodynamic changes.",1998.0,0,0
658,9827245,Cardiovascular safety of 5HT1B/1D agonists--is there a cause for concern?,C G Dahlöf; N Mathew,,1998.0,0,0
659,9827246,"Safety trial with the 5HT1B/1D agonist avitriptan (BMS-180048) in patients with migraine who have experienced pressure, tightness, and/or pain in the chest, neck, and/or throat following sumatriptan.",C G Dahlöf; L Falk; M Risenfors; C P Lewis,"We investigate whether symptoms of pressure, tightness, and/or pain in the chest, neck, and/or throat after administration of the 5HT1B/1D agonist avitriptan were associated with objective impairment of the myocardial function on 12-lead electrocardiogram (ECG), continuous ECG (Holter) monitoring, and echocardiography. Migraine sufferers who in two-thirds of all attacks treated with sumatriptan had experienced chest/throat/neck symptoms were chosen for study. Baseline measures included vital signs, a 12-lead ECG and an echocardiogram. Patients (n = 51) who had no clinically significant abnormality at baseline received a high dose (150 mg) of avitriptan orally outside of a migraine attack. If pressure, tightness, and/or pain in the chest, neck, and/or throat occurred, an ECG was obtained, and a repeat echocardiogram was done while the symptoms were present in order to monitor for impairment of myocardial function. If symptoms of these types did not occur within 60 min after administration of the study drug, a second echocardiogram was obtained. Forty-five patients (88%) reported at least one adverse event and 23 (45%) experienced pressure, tightness, and/or pain in the chest, neck, and/or throat after administration of avitriptan. No clinically significant myocardial abnormalities were observed in any patients, even in those who had experienced the targeted symptoms. No other serious adverse event occurred. We concluded that the typical 5HT1B/1D agonist-induced chest/throat/neck symptoms are most unlikely to be of cardiovascular origin.",1998.0,0,1
660,9833595,The absolute bioavailability and effect of food on the pharmacokinetics of zolmitriptan in healthy volunteers.,E J Seaber; R W Peck; D A Smith; J Allanson; N R Hefting; J J van Lier; F A Sollie; J Wemer; J H Jonkman,"Zolmitriptan (Zomig (formerly 311C90)) is a novel 5-HT1B/1D receptor agonist developed for the acute oral treatment of migraine. A highly sensitive LCMS-MS assay has been developed which allows quantification of plasma concentrations of zolmitriptan and its active metabolite, 183C91, after therapeutic doses. Two studies using this assay method were conducted to investigate the pharmacokinetics, including absolute bioavailability, of 2.5 and 5 mg oral doses of zolmitriptan in men and women, the dose-proportionality of 2.5, 5 and 10 mg doses and the effect of food on the pharmacokinetics of a 5 mg oral dose. Two randomized, balanced, open-label, 4-period crossover studies were conducted in a total of 32 healthy volunteers. The first study determined the absolute bioavailability of 2.5 and 5 mg doses of zolmitriptan and compared the pharmacokinetics in men and women. The second study examined the dose-proportionality in pharmacokinetics after fasting doses of 2.5, 5 and 10 mg, and the effect of food on a 5 mg dose. Blood pressure, heart rate, ECG, clinical chemistry, haematology and adverse events were also monitored. The mean (s.d.) absolute oral bioavailability was 0.41 (0.14 and 0.40) 0.09 after 2.5 mg and 0.48+/-0.14 and 0.36+/-0.07 after 5 mg in women and men, respectively. Without adjustment for bodyweight, plasma concentrations of zolmitriptan, but not 183C91, were higher in women than men. Mean (+/-s.d.) AUC was 32.7+/-10.1 and 60.2+/-26.8 ng ml(-1) h after 5 mg in men and women, respectively (95% CI for ratio 0.43-0.77). After 2.5 mg mean (+/-s.d.) AUC was 18.4+/-5.4 and 23.1+/-9.9 ng ml(-1) h in men and women, respectively (95% CI for ratio 0.61-1.09). However, these differences were of no clinical significance. Cmax and AUC of oral zolmitriptan were dose-proportional and there was a 13 and 16% fall in mean zolmitriptan Cmax and AUC, respectively, when administered after food. Adverse effects were minor, predominantly mild and transient, and there were no clinically significant effects on ECG, blood pressure, or laboratory parameters. At therapeutic doses zolmitriptan has good oral bioavailability in healthy volunteers and has dose-proportional pharmacokinetics that are not affected by food to any clinically relevant extent.",1998.0,0,0
661,9863486,Involvement of two different pathways in the motor effects of erythromycin on the gastric antrum in humans.,B Coulie; J Tack; T Peeters; J Janssens,"During the interdigestive state in humans, erythromycin 40 mg induces a premature activity front that starts in the stomach, while erythromycin 200 mg induces a prolonged period of enhanced antral contractile activity. To study the involvement of a cholinergic pathway in the motor effects of erythromycin using the muscarinic antagonist atropine and the neural 5-HT1 receptor agonist sumatriptan. In 30 healthy volunteers, fasted antroduodenojejunal motor activity was studied by stationary manometry. Placebo (n = 10), atropine (15 micrograms/kg intravenous bolus plus 15 micrograms/kg/h over 30 minutes; n = 10), or sumatriptan (6 mg subcutaneously; n = 10) was administered, followed by infusion of erythromycin 40 mg or 200 mg. After placebo, erythromycin 40 mg induced a premature activity front with gastric onset after 19.1 (1.7) minutes in all volunteers. After atropine, erythromycin 40 mg failed to induce a premature activity front during a 60 minute period in all volunteers (p < 0.001), while sumatriptan prevented the induction of a premature activity front during a 60 minute period in all but one volunteer (p < 0.005). The number of antral contractions and their mean amplitude in the 60 minutes after erythromycin 200 mg did not differ significantly after atropine or sumatriptan versus placebo. The antral motor effects of erythromycin in humans are mediated via different pathways. The induction of a premature activity front is mediated through activation of an intrinsic cholinergic pathway, while the induction of enhanced antral contractile activity may be mediated via a pathway potentially involving activation of a muscular receptor.",1998.0,0,0
662,9867730,Update in neurology.,M A Samuels,,1998.0,0,0
663,9872339,Pharmacokinetics and tolerability of intravenous rizatriptan in healthy females.,Y Lee; S J Ermlich; A T Sterrett; M R Goldberg; R A Blum; M J Brucker; D A McLoughlin; T V Olah; J Zhao; J D Rogers,"The pharmacokinetics and tolerability of intravenous (i.v.) rizatriptan (MK-0462), a novel 5-HT1D/1B receptor agonist for the acute oral treatment of migraine, were examined in an open, single-dose, four-period, randomized crossover study in healthy females. Results of this study indicated that i.v. rizatriptan (0.5-5 mg) was well tolerated. The disposition kinetics of rizatriptan were linear for i.v. doses up to and including 2.5 mg. Relative to the 0.5 mg dose, geometric mean dose-adjusted AUC ratios were 1.04, 1.09, and 1.18 for 1, 2.5, and 5 mg doses, respectively. Apparent plasma clearance (Cl) ranged between 859 and 941 mL min(-1) from 0.5 to 2.5 mg, but dropped to slightly below 800 mL min(-1) for the 5 mg dose. Therefore, the elimination of rizatriptan appears somewhat dose dependent at the high end of this dose range. Mean plasma half-life (t1/2) was 1.5-2.2 h across all doses while mean residence time in the body (MRT) and steady state volume of distribution (Vss) of rizatriptan remained relatively invariant across doses. Urinary excretion of rizatriptan (Ue) ranged from 14.5 to 34.6% of dose.",2000.0,0,0
664,9877016,Sumatriptan (5-HT1D receptor agonist) does not exacerbate symptoms in obsessive compulsive disorder.,K L Pian; H G Westenberg; H J van Megen; J A den Boer,"The non-selective serotonin (5-HT) receptor agonist meta-chlorophenylpiperazine (mCPP) has been reported to elicit symptoms in patients with obsessive compulsive disorder (OCD). MK-212, another non-selective 5-HT receptor agonist, does not seem to induce obsessive compulsive symptoms in OCD patients. The major pharmacological difference between mCPP and MK-212 is their affinity for the 5-HT(ID) receptor. The aim of this study was to explore the role of the 5-HT(ID) receptor in the pathophysiology of OCD, by using a challenge paradigm with the selective 5-HT(ID) receptor agonist sumatriptan (Imigran). A randomized, double-blind, placebo-controlled crossover challenge with sumatriptan (100 mg PO) was performed in 15 OCD patients. Neither the obsessive compulsive symptoms nor mood or anxiety symptoms changed significantly following sumatriptan administration as compared to placebo. Sumatriptan did induce a significant increase in plasma growth hormone (GH) levels. In the present study, no indication were found for the role of the 5-HT(ID) receptor in the pathophysiology of OCD. It should be noted, however, that sumatriptan does not readily pass the blood-brain barrier. Selective 5-HT(ID) receptors with better brain penetrating properties may shed more light on the role of this 5-HT receptor subtype in OCD.",1999.0,0,0
665,9883001,Exercise testing in patients with chest pain to sumatriptan.,J P Ottervanger; J C Hoorntje; H A Valkenburg; D E Grobbee; B H Stricker,"In order to assess whether chest pain attributed to sumatriptan is associated with abnormalities on cardiac exercise testing, we performed a case-control study. Cases were selected as consumers of sumatriptan who reported sumatriptan associated chest pain. A reference group was selected randomly from consumers of sumatriptan with the same GP as the case, who reported no chest pain after use of sumatriptan. If possible, controls were matched for age (within 5-year groups) and gender. In a total of 74 cases and 55 controls symptom-limited exercise tests were performed. Besides a small difference in age, there were no differences in basic characteristics between cases and controls. Three cases had ST-depression on ECG during exercise. However, none of the variables measured during exercise testing differed significantly between cases and controls. The prevalence of abnormal exercise tests in patients with sumatriptan-induced chest pain is low, and not statistically different from patients without chest pain after intake of sumatriptan. Routine performance of exercise testing in patients with sumatriptan-associated chest pain is not recommended.",1999.0,0,0
666,9885327,Comparative efficacy and safety of calcium carbasalate plus metoclopramide versus ergotamine tartrate plus caffeine in the treatment of acute migraine attacks.,C Le Jeunne; J P Gómez; A Pradalier; F Titus i Albareda; A Joffroy; H Liaño; P Henry; J M Lainez; G Geraud,"This randomized, double-blind, double-dummy, multicenter, parallel-group study aimed at comparing the efficacy and safety of calcium carbasalate (equivalent to 900 mg aspirin) plus metoclopramide 10 mg (CM) with ergotamine tartrate 1 mg plus caffeine 100 mg (EC) administered in the treatment of 2 acute migraine attacks. A total of 296 patients fulfilling the International Headache Society diagnostic criteria for migraine were enrolled. In total, one or two migraine attacks were treated in 268 and 235 patients, respectively. The primary endpoint for the first treated attack was headache relief, with intensity decreasing from moderate or severe to mild or absent 2 h after drug intake. Usual secondary efficacy endpoints were assessed. A superiority of CM over EC was observed for both treated attacks for the main endpoint: success in 54 versus 36%, p = 0.003 for the first attack and 60 versus 44%, p = 0.02 for the second attack. CM was also significantly superior to EC during the first attack for complete headache relief (20 vs. 8%, p = 0.006), nausea (42 vs. 63%, p = 0. 007) and willingness to take the drug again (90 vs. 80%, p = 0.043). The global efficacy evaluation, rated by the investigators, was significantly more favorable to CM for both attacks (p = 0.001 for the first attack and p = 0.02 for the second). The patients' evaluation was significant for the first attack (p = 0.002). The global incidence of adverse events was 45% higher with EC, though not significant (32 vs. 22%, p = 0.075). They were most often unspecific and mild to moderate in intensity. Gastrointestinal side effects were significantly less frequent with CM than EC (7 vs. 21%, p = 0.001). Thus, CM is more effective and has a better gastrointestinal safety than EC in the acute treatment of migraine attacks.",2000.0,0,0
667,9888613,"Lack of an effect of zolmitriptan (Zomig, 311C90) on psychometric task performance: results of a placebo-controlled study in healthy volunteers.",A J Mercer; R J Lamb; P E Rolan; M Gibbens; J Posner,"The novel selective 5-hydroxytryptamine (5-HT)1B/1D agonist, zolmitriptan (Zomig, formerly known as 311C90), has shown good efficacy in the acute oral treatment of migraine. Zolmitriptan acts both centrally and peripherally, therefore it is important to assess central nervous system effects. At single doses of 25-50 mg (up to 8 times the likely therapeutic dose), zolmitriptan can cause sedation; therefore, a study was designed to examine the dose-response. A double-blind, randomized, placebo-controlled, six-limb crossover study in 13 healthy volunteers compared the effects of single oral doses of zolmitriptan (5, 10, 15 or 20 mg) and lorazepam (2 mg) on various psychometric tests. Zolmitriptan doses less than 20 mg had no statistically significant effects on choice reaction time, the Stroop test, visual analog scale (VAS) assessments of physical sedation, tranquilization and other types of feelings, the logical reasoning test or the adaptive tracking test. There was a mild transient increase in the subjective assessment on VAS of mental sedation which was dose related and occurred mainly with the highest zolmitriptan dose and were not reflected in objective measures of drug effects. In contrast, lorazepam (used as a positive control) was associated with statistically significant impairment in all tests (except tranquilization) for up to 10 h after dosing. The results demonstrate that therapeutic doses of zolmitriptan are unlikely to cause clinically significant impairment in psychometric performance.",1999.0,0,0
668,9922821,Subcutaneous sumatriptan compared with usual acute treatments for migraine: clinical and pharmacoeconomic evaluation.,P Laloux; A Vakaet; G Monseu; J Jacquy; P Bourgeois; C van der Linden,"Cost-effectiveness and cost per successful treatment has been evaluated in 186 outpatients randomised to treat moderate to severe migraine attacks either with subcutaneous sumatriptan 6 mg (n = 97) or with their current therapy (n = 89) during an open, multicentre study of 3 months. Within 2 hours, headache severity decreased to none/mild in 86% of all attacks in the sumatriptan group (STG) compared to 25% in the customary group (CTG). Migraine was alleviated earlier in the STG than in the CTG (median 3.78 vs. 13.39 hours, p < 0.0001). The direct and total cost of treatment was 133 and 2012 BF, respectively, in the CTG and 1400 and 2522 BF, respectively, in the STG. Measuring the effectiveness of earlier pain relief with sumatriptan, the incremental cost-effective ratios for direct and total cost were 132 and 53 BF per hour of relieved pain, respectively. For this price, significantly more sumatriptan patients improved their quality of life by more than 20% (61.6 vs. 20.6% patients, p < 0.001) and less sumatriptan patient consulted a medical professional (11.3 vs. 29.2% patients, p < 0.01), used less medication for adverse events (6.2 vs. 22.5%, p < 0.001) and suffered less from associated migraine symptoms. The median number of hours of diminished work-efficiency (3 vs. 7 hours, p < 0.01) or of suspension of non-professional activity (10 vs. 24 hours, p < 0.001) was also significantly lower in the STG. The total cost per successfully treated patient was lower in the STG. Sumatriptan is more effective, provides a better quality of life, reduces health care resource utilisation, and improves work productivity as compared to the CTG, thereby resulting in a favourable cost-effectiveness ratio.",1999.0,0,1
669,9934574,Radiofrequency cervical zygapophyseal joint neurotomy for cervicogenic headache: a prospective study of 15 patients.,H A van Suijlekom; M van Kleef; G A Barendse; M E Sluijter; O Sjaastad; W E Weber,"The present study assessed the clinical efficacy of radiofrequency cervical zygapophyseal joint neurotomy in patients with cervicogenic headache. Fifteen consecutive patients with cervicogenic headache were treated and then assessed one week prior to treatment and, at short-term (8 weeks), intermediate (mean 8.8 months) and long-term (mean 16.8 months) follow-ups. The following were taken as outcome parameters: Visual Analogue Scale (VAS), 7-point Verbal Rating Scale (VRS), number of headache days per week and analgesic intake per week. The results of this study showed that radiofrequency neurotomy of the cervical zygapophyseal joints significantly reduced headache severity in 12 (80%) patients, both at short-term and long-term follow-up assessed by 7-point VRS. Mean VAS decrease was 31.4 mm (p < 0.001) and 53.5 mm (p < 0.0001) respectively in this period. The average mean number of headache days per week decreased from 5.8 days to 2.8 days (p = 0.001) and the average analgesic intake per week showed a reduction from a mean of 17.5 tablets to a mean of 3.4 tablets (p = 0.003). A definitive conclusion about the clinical efficacy of this treatment can only be drawn from a randomized controlled trial.",1999.0,0,0
670,9972386,Medication-induced headache: overview and systematic review of therapeutic approaches.,P J Zed; P S Loewen; G Robinson,"To review medication-induced headache (MIH) through a systematic evaluation of the literature regarding the pharmacologic management of this condition. To identify and evaluate all pharmacologic interventions for MIH, we conducted a qualitative systematic review of the English-language literature from 1966 to June 1998 using MEDLINE. The following search terms were used: chronic daily headache, transformed migraine, analgesic withdrawal headache, analgesic rebound headache, drug-associated headache, medication-induced headache, detoxification, and dihydroergotamine. In addition, a review of the references from relevant literature was also conducted to collect reports not identified in the MEDLINE search. Numerous therapies for acute management of MIH have been evaluated, although no rigorously conducted clinical trials were identified. Therapies evaluated include abrupt withdrawal of analgesics, initiation of dihydroergotamine, nonsteroidal antiinflammatory agents, methylergonovine, dihydroergotamine, sumatriptan, amitriptyline, dexamethasone, piracetam, prothipendyl, and valproate. Epidemiology, diagnosis, clinical features, pathophysiology, and long-term prognosis of therapy are discussed and therapeutic guidelines are offered. MIH is an underrecognized and difficult condition affecting headache-prone patients. The published literature concerning treatment of patients with MIH is scant and of poor quality, making it difficult for clinicians to decide on appropriate therapy. Recognition and treatment of MIH may lead to a long-term improvement in headache relief for many patients. It appears that complete withdrawal of the medications being overused is required for favorable long-term results.",1999.0,0,0
671,9987697,The pharmacodynamics of sumatriptan in nitroglycerin-induced headache.,T Fullerton; D Komorowski-Swiatek; A Forrest; F M Gengo,"Migraine is a common disorder that causes significant morbidity in those afflicted. Many novel antimigraine compounds are in clinical development, yet full characterization of each one's pharmacodynamic behavior is a formidable task due to the difficulty in studying a migraineur during an attack. Nitroglycerin (NTG) administration commonly causes a headache with some features similar to those of a migraine. As such, NTG has been used as a model of vascular headaches, including migraine. The pharmacodynamic effects of nitroglycerin and sumatriptan on middle cerebral artery blood flow velocity (MCAv) and headache scores were studied in 10 healthy male volunteers. An intravenous infusion of NTG titrated to 0.5 mcg/kg/min over 30 minutes resulted in a median reduction from baseline in MCAv of 27% (range: 16.4%-37.3%). Nine of the subjects developed a headache with a median verbal score of 3.5 of 10 (range: 0-5). Subjects received sumatriptan either 2 mg intravenously or 6 mg subcutaneously, which abated clinical headache in 9 of the 10 subjects (p = 0.030). A median sumatriptan-induced increase in MCAv of 21% (p = 0.054) suggested a constricting effect on the NTG-induced dilated MCA. A two-compartment pharmacokinetic/indirect-effects pharmacodynamic model was fit to the sumatriptan concentration and MCAv data using iterative two-stage analysis. This model was unbiased and fit the concentration (r2 = 0.98) and the MCAv (r2 = 0.79) data well. These results suggest that NTG-induced headache and the development of pharmacokinetic/pharmacodynamic models could serve as a useful method for exploring the mechanisms of abortive migraine drugs.",1999.0,0,0