The aim of this study was to evaluate the efficacy and tolerability of topiramate for the prevention of chronic migraine in a randomized, double-blind, placebo-controlled trial. Chronic migraine is a common form of disabling headache presenting in headache subspecialty practice. Preventive treatments are essential for chronic migraine management, although there are few or no controlled empirical trial data on their use in this patient population. Topiramate is approved for the prophylaxis of migraine headache in adults. Patients (18-65 years) who experienced chronic migraine (defined as > or =15 monthly migraine days) for > or =3 months prior to trial entry and had > or =12 migraine days during the 4-week (28-day) baseline phase were randomized to topiramate or placebo for a 16-week, double-blind trial. Topiramate was titrated (25 mg weekly) to a target dose of 100 mg/day, allowing dosing flexibility from 50 to 200 mg/day, according to patient need. Existing migraine preventive treatments, except for antiepileptic drugs, were continued throughout the trial. The primary efficacy measure was the change in number of migraine days from the 28-day baseline phase to the last 28 days of the double-blind phase in the intent-to-treat population, which consisted of all patients who received at least one dose of study medication and had one outcome assessment during the double-blind phase. Health-related quality of life was evaluated with the Migraine Specific Quality of Life Questionnaire (MSQ, Version 2.1), the Headache Impact Test (HIT-6) and the Migraine Disability Assessment (MIDAS) questionnaires, and tolerability was assessed by adverse event (AE) reports and early trial discontinuations. Eighty-two patients were screened. Thirty-two patients in the intent-to-treat population (mean age 46 years; 75% female) received topiramate (mean modal dose +/- SD = 100 +/- 17 mg/day) and 27 patients received placebo. Mean (+/-SD) baseline number of migraine days per 4 weeks was 15.5 +/- 4.6 in the topiramate group and 16.4 +/- 4.4 in the placebo group. Most patients (78%) met the definition for acute medication overuse at baseline. The mean duration of treatment was 100 and 92 days for topiramate- and placebo-treated patients, respectively. Study completion rates for topiramate- and placebo-treated patients were 75% and 52%, respectively. Topiramate significantly reduced the mean number of monthly migraine days (+/-SD) by 3.5 +/- 6.3, compared with placebo (-0.2 +/- 4.7, P < 0.05). No significant intergroup differences were found for MSQ and HIT-6. MIDAS showed improvement with the topiramate treatment group (P = 0.042 vs. placebo). Treatment emergent adverse events were reported by 75% of topiramate-treated patients (37%, placebo). The most common AEs, paraesthesia, nausea, dizziness, dyspepsia, fatigue, anorexia and disturbance in attention, were reported by 53%, 9%, 6%, 6%, 6%, 6% and 6% of topiramate-treated patients, respectively, vs. 7%, 0%, 0%, 0%, 0%, 4% and 4% of placebo-treated patients. This randomized, double-blind, p...

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Topiramate has been shown to be effective as a preventive treatment for migraine in three large placebo-controlled, dose-ranging trials. Because the protocols were similar in design using the same primary and secondary endpoints, data from these studies were pooled to evaluate the consistency of efficacy, efficacy by gender and tolerability of topiramate 100 mg/day (n = 386) versus placebo (n = 372). Topiramate was superior to placebo as measured by the reduction in mean monthly migraine frequency, monthly migraine days and monthly migraine duration. The responder rates, defined as at least 50% reduction for the respective parameters, were significantly in favour of topiramate (p < 0.001), for example 46.3% of patients on topiramate achieved at least 50% reduction in monthly migraine period frequency compared with 22.8% on placebo (p < 0.001). Use of medication to treat the acute migraine attack was significantly reduced by topiramate compared with placebo (p < 0.001). The therapeutic effect was consistent throughout the different studies and independent of gender. The most common adverse effect was paraesthesia, mostly of mild-to-moderate severity. The findings confirm that, at a dose of 100 mg/day, topiramate is an effective and well-tolerated drug for migraine prevention.

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Clinical experience shows that neuropsychological side effects due to opioid therapy usually decrease during the first weeks of therapy. However, the effect of long-term treatment with transdermal fentanyl on complex activities, such as driving, is not yet clear. In a prospective trial, patients with continuous noncancer pain, who had received stable doses of transdermal fentanyl for at least 2 weeks, completed a series of computerized tests to measure attention, reaction, visual orientation, motor coordination and vigilance. Data from 90 healthy volunteers were matched to 30 patients; 9 patients were excluded from the per-protocol analysis because they took additional drugs in violation of the protocol. None of the performance measures for the 21 remaining fentanyl patients was significantly inferior to the controls. We conclude that stable doses of transdermal fentanyl for the treatment of chronic non-cancer pain are not associated with significant impairments in psychomotor and cognitive performance. The threshold for fitness to drive as defined by German law did not differ significantly between the groups.