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Long‐Term Migraine Prevention With Topiramate: Open‐Label Extension of Pivotal Trials
Author(s) -
Rapoport Alan,
Mauskop Alexander,
Diener HansChristoph,
Schwalen Susanne,
Pfeil Joop
Publication year - 2006
Publication title -
headache: the journal of head and face pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.14
H-Index - 119
eISSN - 1526-4610
pISSN - 0017-8748
DOI - 10.1111/j.1526-4610.2006.00506.x
Subject(s) - topiramate , migraine , placebo , medicine , aura , clinical trial , randomized controlled trial , anesthesia , epilepsy , psychiatry , alternative medicine , pathology
Objective.—To demonstrate that topiramate is an effective and generally well‐tolerated migraine preventive therapy when used for up to 14 months. Background.—Topiramate 100 and 200 mg/d significantly reduced mean monthly migraine frequency during 2 large, 26‐week, randomized, placebo‐controlled trials. Only a small number of clinical trials have examined the long‐term (≥1 year) effectiveness and safety of migraine preventive therapies. Methods.—Five hundred sixty‐seven patients with an established history of migraine with or without aura were enrolled in this 8‐month, open‐label extension of 2 large (49 US and 52 US and Canadian medical centers), randomized, double‐blind, placebo‐controlled, parallel group, 26‐week trials of identical design. To be eligible for the open‐label extension, patients were required to have either completed the double‐blind phase of the 2 pivotal migraine prevention trials or withdrew after 4 weeks due to lack of efficacy. All eligible patients, regardless of type or dose of study medication (topiramate or placebo) received in the double‐blind phase, were titrated to a clinically effective dose of open‐label topiramate based on physician judgment of patient response. Efficacy of topiramate was measured as the change in mean monthly migraine frequency. Results.—The mean topiramate dose during the open‐label extension phase was 124.7 mg/d and 150.3 mg/d for patients on placebo (n = 159) or topiramate (n = 408), respectively, during the double‐blind phase (N = 567, 91% female, mean age 39.4 years). Patients on topiramate for up to 14 months had 2.2 ± 2.4 (mean ± SD) migraines per month after completion of the open‐label extension phase (3.4 ± 2.6 at double‐blind endpoint). Patients on topiramate during the open‐label extension phase only (placebo during the double‐blind phase) had 3.0 ± 2.9 migraines per month at open‐label extension endpoint (4.9 ± 3.0 migraines per month at double‐blind endpoint). Discontinuation rates due to adverse events during the double‐blind phase were 22.2% for patients on topiramate and 11.0% for patients on placebo. Discontinuation rates due to adverse events during the open‐label extension phase were 8.6% for those patients who had already received topiramate during the double‐blind phase and 20.9% for those patients who had previously received placebo. Conclusions.—Patients receiving topiramate experienced a sustained reduction in migraine frequency for up to 14 months. The effectiveness and safety of topiramate was consistent with that observed during 2 26‐week pivotal trials.