Topiramate in migraine prevention: a double-blind, placebo-controlled study

Headache. Nov-Dec 2001;41(10):968-75. doi: 10.1046/j.1526-4610.2001.01190.x.


Objective: To evaluate the efficacy of topiramate in the preventative treatment of episodic migraine.

Background: Topiramate is a broad-spectrum antiepileptic drug effective for treatment of multiple seizure types in adults and children. Antiepileptic agents have demonstrated efficacy in migraine prevention, and open-label experience from our clinic has suggested that topiramate might be effective for this use. We consequently conducted a single-center, double-blind, placebo-controlled trial to evaluate the efficacy and safety of topiramate for the preventative treatment of migraine.

Methods: Forty patients, aged 19 to 62 years (mean, 38.2 years), were randomly assigned in a 1:1 ratio to receive topiramate (n = 19; all women) or placebo (n = 21; 20 women, 1 man). Following a prospective baseline phase of 4 weeks, the study drug dose was titrated weekly in 25-mg increments over 8 weeks to 200 mg per day or to the maximum tolerated dose. The titration phase was followed by an 8-week maintenance phase.

Results: During the entire double-blind phase, topiramate-treated patients experienced a significantly lower 28-day migraine frequency (3.31 +/- 1.7 versus 3.83 +/- 2.1; P =.002) compared to placebo, irrespective of use of concomitant migraine prevention medications. The mean 28-day migraine frequency was reduced by 36% in patients receiving topiramate as compared with 14% in patients receiving placebo (P =.004). Twenty-six percent of the patients on topiramate and 9.5% of the patients on placebo achieved a 50% reduction in migraine frequency (P >.05). The mean dose of topiramate was 125 mg per day (range, 25 to 200 mg per day). Topiramate was well tolerated; 2 of 19 topiramate-treated patients discontinued treatment due to adverse events. Adverse effects that occurred more frequently in topiramate-treated patients included paresthesia, weight loss, altered taste, anorexia, and memory impairment.

Conclusions: Preventative therapy with topiramate significantly reduced migraine frequency. Larger multicenter clinical studies may further delineate the role of topiramate in migraine prevention.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Analgesics / administration & dosage
  • Anorexia / chemically induced
  • Anticonvulsants / adverse effects
  • Anticonvulsants / pharmacology
  • Anticonvulsants / therapeutic use*
  • Body Weight / drug effects
  • Double-Blind Method
  • Drug Combinations
  • Dysgeusia / chemically induced
  • Female
  • Fructose / adverse effects
  • Fructose / analogs & derivatives
  • Fructose / pharmacology
  • Fructose / therapeutic use*
  • Humans
  • Male
  • Memory Disorders / chemically induced
  • Middle Aged
  • Migraine Disorders / prevention & control*
  • Paresthesia / chemically induced
  • Topiramate
  • Treatment Outcome
  • Weight Loss / drug effects


  • Analgesics
  • Anticonvulsants
  • Drug Combinations
  • Topiramate
  • Fructose