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: To evaluate the efficacy and safety of topiramate for migraine prophylaxis in adolescent subjects.

Aims: Migraine headaches are a common and disabling disorder in children. Currently, no drugs are FDA-approved for the prophylactic treatment of migraine in pediatric patients.

Design/Methods: Adolescents (ages 12 to 17) with at least a 6-month history of migraine were randomized to receive 16 weeks of daily treatment with topiramate or placebo. The primary efficacy measure was the percent reduction from prospective baseline to the last 12 weeks of double-blind phase in monthly migraine attack rate. The percent reductions from baseline in monthly rates of migraine days, headache days, migraine attacks (24-hour rule [last 12 weeks] and 48-hour rule [last 4 weeks]), and the 50% responder rate were also evaluated. Safety and tolerability were assessed.

Results: Subjects were randomized to topiramate 50mg/day (n=35), topiramate 100mg/day (n=35), or placebo (n=33). A total of 59 topiramate-treated subjects (84.3%) and 26 placebo-treated subjects (79.0%) completed double-blind treatment. Topiramate 100mg/day, but not 50mg/day, resulted in a statistically significant percent reduction from baseline (adjusted P=0.016) vs. placebo in the monthly migraine attack rate (median 72.2% vs. 44.4%) during the last 12 weeks of double-blind treatment. Topiramate 100mg/day, but not 50mg/day, also resulted in statistically significant percent reductions from baseline vs. placebo in monthly rates of migraine days (P=0.002), headache days (P=0.004), and migraine attacks (24-hour rule [last 12 weeks]: P=0.011; 48-hour rule [last 4 weeks]: P=0.015). The responder rate favored topiramate 100mg/day (83% vs. 45% for placebo [P=0.002]). Upper respiratory tract infection, paresthesia, and dizziness occurred more commonly in the topiramate groups vs. placebo.

Conclusions: Topiramate 100mg/day was an effective, and generally safe and well-tolerated treatment for migraine prophylaxis in adolescent subjects.