A double-blind, randomized trial of topiramate in Lennox-Gastaut syndrome

Objective: To evaluate the efficacy and safety of topiramate as adjunctive therapy for Lennox-Gastaut syndrome in a multicenter, double-blind, placebo -controlled trial. Background: Conventional antiepileptic drugs are frequen tly ineffective against multiple-seizure types of Lennox-Gastaut syndrome. Methods: Ninety-eight patients >1 year to <30 years of age, with slow spike -and-wave patterns on EEG, seizure types including drop attacks, and either a history of or active atypical absence seizures, were assigned to an 11-w eek, double-blind treatment phase with either topiramate or placebo. Topira mate was titrated to target doses pf;approximately 6 mg/kg/d. Results: For drop attacks, the most severe seizures associated with this syndrome,the me dian percentage reduction from baseline in average monthly seizure rate was 14.8% for the topiramate group and -5.1% tan increase) for the placebo gro up (p = 0.041). Topiramate-treated patients demonstrated greater improvemen t in seizure severity than did placebo-treated patients based on parental g lobal evaluations (p = 0.037). The percentage of patients with a greater th an or equal to 50% reduction from baseline in major seizures (drop attacks and tonic-clonic seizures) was greater in the topiramate group (15/46 or 33 %) than in the control group (4/50 or 8%; p = 0.002). The most common adver se events in both groups were GNS related; there were no discontinuations f rom topiramate therapy due to adverse events. Conclusions: Topiramate adjun ctive therapy was effective in reducing the number of drop attacks and majo r motor seizures and in improving seizure severity as determined by parenta l global evaluation.