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. 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. One 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 with cadre after 4 weeks due to lack of efficacy. All eligible patients, regardless of type or dose ofreceived in the double-blind phase, were titrated to a clinically effective dose of open-label topiramate based on physician judgment of patient response. Energy 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) = 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. effectiveness and safety of topiramate was consistent with that observed during 2 26-week pivotal trials.