R C Sachdeo1, T A Glauser, F Ritter, R Reife, P Lim, G Pledger. 1. Department of Neurology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick 08903-0019, USA.
Abstract
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 frequently 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-week, double-blind treatment phase with either topiramate or placebo. Topiramate was titrated to target doses of approximately 6 mg/kg/d. RESULTS: For drop attacks, the most severe seizures associated with this syndrome, the median percentage reduction from baseline in average monthly seizure rate was 14.8% for the topiramate group and -5.1% (an increase) for the placebo group (p = 0.041). Topiramate-treated patients demonstrated greater improvement in seizure severity than did placebo-treated patients based on parental global evaluations (p = 0.037). The percentage of patients with a > or = 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 adverse events in both groups were CNS related; there were no discontinuations from topiramate therapy due to adverse events. CONCLUSIONS:Topiramate adjunctive therapy was effective in reducing the number of drop attacks and major motor seizures and in improving seizure severity as determined by parental global evaluation.
RCT Entities:
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 frequently 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-week, double-blind treatment phase with either topiramate or placebo. Topiramate was titrated to target doses of approximately 6 mg/kg/d. RESULTS: For drop attacks, the most severe seizures associated with this syndrome, the median percentage reduction from baseline in average monthly seizure rate was 14.8% for the topiramate group and -5.1% (an increase) for the placebo group (p = 0.041). Topiramate-treated patients demonstrated greater improvement in seizure severity than did placebo-treated patients based on parental global evaluations (p = 0.037). The percentage of patients with a > or = 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 adverse events in both groups were CNS related; there were no discontinuations from topiramate therapy due to adverse events. CONCLUSIONS:Topiramate adjunctive therapy was effective in reducing the number of drop attacks and major motor seizures and in improving seizure severity as determined by parental global evaluation.