From The New England Center for Headache, PC, Stamford, CT (Dr. Rapoport); New York Headache Center, New York, NY (Dr. Mauskop); Department of Neurology, Universität Essen, Essen, Germany (Dr. Diener); Janssen-Cilag EMEA, Tilburg, The Netherlands (Dr. Schwalen); and Estimate Medical Statistics BV, Doesburg, The Netherlands (Mr. Pfeil).
Long-Term Migraine Prevention With Topiramate: Open-Label Extension of Pivotal Trials
Version of Record online: 6 JUL 2006
Headache: The Journal of Head and Face Pain
Volume 46, Issue 7, pages 1151–1160, July/August 2006
How to Cite
Rapoport, A., Mauskop, A., Diener, H.-C., Schwalen, S. and Pfeil, J. (2006), Long-Term Migraine Prevention With Topiramate: Open-Label Extension of Pivotal Trials. Headache: The Journal of Head and Face Pain, 46: 1151–1160. doi: 10.1111/j.1526-4610.2006.00506.x
- Issue online: 6 JUL 2006
- Version of Record online: 6 JUL 2006
- Accepted for publication April 20, 2006.
- migraine prevention;
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.