Long-term migraine prevention with topiramate: open-label extension of 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. Only a small number of clinical trials have examined the long-term (> or =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.
Rapoport
Alan
A
The New England Center for Headache, PC, Stamford, CT 06902, USA.
Mauskop
Alexander
A
Diener
Hans-Christoph
HC
Schwalen
Susanne
S
Pfeil
Joop
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use; D002648:Child; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005632:Fructose / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000517:prevention & control*; D009325:Nausea / Q000139:chemically induced; D012852:Sinusitis / Q000139:chemically induced; D013997:Time Factors; D000077236:Topiramate; D016896:Treatment Outcome
D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose