Topiramate for migraine prevention in children: a randomized, double-blind, placebo-controlled trial.

Objective: To assess the efficacy and safety of topiramate for the prevention of pediatric migraine with or without aura in a double-blind, randomized, placebo-controlled trial.

Background: Treatment options for pediatric migraine are currently limited, and no migraine preventive agents are approved for use in children in the United States. Topiramate is an effective migraine preventive therapy in adults, as demonstrated in several large, randomized, placebo-controlled trials.

Methods: One hundred and sixty-two children with migraine (age, 6 to 15 years) were randomized in a 2:1 ratio to receive topiramate (n = 112) or placebo (n = 50). This study was designed to ensure that 150 participants were randomized to study medication. An additional 12 qualified patients were randomized because they had successfully completed the screening phase. The double-blind phase of the trial consisted of a titration period and a maintenance period. Topiramate was initiated at 15 mg/day and titrated over 8 weeks to 2 to 3 mg/kg per day, or maximum tolerated dose, whichever was less (maximum allowed dose was 200 mg/day). The target dose was maintained for 12 weeks. The primary efficacy variable was the change in mean number of migraine days per month (28 days) during the double-blind phase relative to the 4-week prospective baseline phase for each treatment group.

Results: Topiramate treatment was associated with a mean reduction over the entire double-blind phase of 2.6 migraine days per month, compared with a mean reduction of 2.0 migraine days per month for placebo (P = .061 topiramate vs. placebo). A significantly greater percentage of topiramate patients (32%) experienced a > or = 75% reduction in mean monthly migraine days compared with placebo (14%, P = .02). Discontinuation rates due to adverse events were low: 6.5% for the topiramate group and 4.0% for the placebo group. The adverse events that occurred most commonly in the topiramate group at an incidence rate greater than in the placebo group were: upper respiratory tract infection, anorexia, weight decrease, gastroenteritis, paresthesia, and somnolence. The mean average daily dose of topiramate during the maintenance period was 2.0 mg/kg per day.

Conclusions: This pilot study suggests that topiramate may be an effective migraine preventive therapy in children. Topiramate was well tolerated in this population. Further randomized studies would be required to definitively establish the efficacy of topiramate for pediatric migraine prevention.