Context Small open-label and controlled trials suggest that the antiepileptic
drug topiramate is effective for migraine prevention.
Objective To assess the efficacy and safety of topiramate for migraine prevention
in a large controlled trial.
Design, Setting, and Patients A 26-week, randomized, double-blind, placebo-controlled study was conducted
during outpatient treatment at 52 North American clinical centers. Patients
were aged 12 to 65 years and had a 6-month history of migraine (International
Headache Society criteria) and 3 to 12 migraines a month but no more than
15 headache days a month during a 28-day prospective baseline phase.
Interventions After a washout period, patients meeting entry criteria were randomized
to topiramate (50, 100, or 200 mg/d) or placebo. Topiramate was titrated by
25 mg/wk for 8 weeks to the assigned or maximum tolerated dose, whichever
was less. Patients continued receiving that dose for 18 weeks.
Main Outcome Measures The primary efficacy measure was change from baseline in mean monthly
migraine frequency. Secondary efficacy measures included responder rate (proportion
of patients with ≥50% reduction in monthly migraine frequency), reductions
in mean number of monthly migraine days, severity, duration, and days a month
requiring rescue medication, and adverse events. The month of onset of preventive
treatment action was assessed.
Results Of 483 patients randomized, 468 provided at least 1 postbaseline efficacy
assessment and comprised the intent-to-treat population. Mean monthly migraine
frequency decreased significantly for patients receiving topiramate at 100
mg/d (−2.1, P = .008) and topiramate at 200
mg/d (−2.4, P<.001) vs placebo (−1.1).
Statistically significant reductions (P<.05) occurred
within the first month with topiramate at 100 and 200 mg/d. The responder
rate was significantly greater with topiramate at 50 mg/d (39%, P = .01), 100 mg/d (49%, P<.001), and 200
mg/d (47%, P<.001) vs placebo (23%). Reductions
in migraine days were significant for the 100-mg/d (P =
.003) and 200-mg/d (P<.001) topiramate groups.
Rescue medication use was reduced in the 100-mg/d (P =
.01) and 200-mg/d (P = .005) topiramate groups. Adverse
events resulting in discontinuation in the topiramate groups included paresthesia,
fatigue, and nausea.
Conclusion Topiramate showed significant efficacy in migraine prevention within
the first month of treatment, an effect maintained for the duration of the