A randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of topiramate for migraine prevention in pediatric subjects 12 to 17 years of age

OBJECTIVE. Currently, no drugs are Food and Drug Administration-approved for migraine prophylaxis in pediatric patients. The objective of this study was to evaluate the efficacy and safety of topiramate for migraine prevention in adolescents. METHODS. Adolescents (12-17 years of age) with a >= 6-month history of migraine were assigned randomly to receive 16 weeks of daily treatment with topiramate (50 or 100 mg/day) or placebo. The primary efficacy measure was the percent reduction in monthly migraine attacks, with the use of the 48-hour rule, from the prospective baseline period to the last 12 weeks of the double-blind phase. The 48-hour rule defined a single migraine episode as all recurrences of migraine symptoms within 48 hours after onset. Several secondary efficacy measures were evaluated, including the reduction from baseline in the monthly migraine day rate and the 50% responder rate. Safety and tolerability were also assessed. RESULTS. A total of 29 (83%) of 35 subjects treated with topiramate at 50 mg/day, 30 (86%) of 35 subjects treated with topiramate at 100 mg/day, and 26 (79.0%) of 33 placebo-treated subjects completed double-blind treatment. Topiramate at 100 mg/day, but not 50 mg/day, resulted in a statistically significant reduction in the monthly migraine attack rate from baseline versus placebo (median: 72.2% vs 44.4%) during the last 12 weeks of double-blind treatment. Topiramate at 100 mg/day, but not 50 mg/day, also resulted in a statistically significant reduction in the monthly migraine day rate from baseline versus placebo. The responder rate favored topiramate at 100 mg/day (83% vs 45% for placebo). Upper respiratory tract infection, paresthesia, and dizziness occurred more commonly in the topiramate groups than in the placebo group. CONCLUSIONS. The 100 mg/day topiramate group demonstrated efficacy in the prevention of migraine in pediatric subjects. Overall, topiramate treatment was safe and well tolerated. Pediatrics 2009;123:924-934