Topiramate for migraine prevention: a randomized controlled trial

JAMA. 2004 Feb 25;291(8):965-73. doi: 10.1001/jama.291.8.965.


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 > or =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 double-blind phase.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anticonvulsants / adverse effects
  • Anticonvulsants / therapeutic use*
  • Child
  • Double-Blind Method
  • Female
  • Fructose / adverse effects
  • Fructose / analogs & derivatives*
  • Fructose / therapeutic use*
  • Humans
  • Linear Models
  • Male
  • Middle Aged
  • Migraine Disorders / prevention & control*
  • Topiramate
  • Weight Loss / drug effects


  • Anticonvulsants
  • Topiramate
  • Fructose