The efficacy and safety of topiramate as adjunctive therapy for Lennox-Gastaut syndrome were studied in an 11-week multicenter, double-blind, placebo-controlled trial involving 98 patients, 1-30 years of age, and reported from the New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ. A greater than 50% reduction in drop attacks and tonic-clonic seizures was obtained in one third, and parental global evaluations indicated a reduction in seizure severity. Adverse events occurring with greater frequency in the topiramate patients than in controls included somnolence, anorexia, nervousness, behavioral problems, fatigue, dizziness, and weight loss, but none caused treatment to be completely withdrawn. [1]

COMMENT. Topiramate may be effective as adjunctive therapy in Lennox-Gastaut syndome.

Topiramate pharmacokinetics and tolerability were studied in 18 children, 4-17 years of age, at the Epilepsy Care Center, Chesterfield, MO, using graded doses from 1 mg/kg/day, increasing weekly to 9 mg/kg/day or 800 mg/day at the 4th week [2]. Oral plasma clearance was independent of dose, and plasma concentrations were proportional to the dose. Topiramate clearance was 50% greater than that in adults, and higher in children receiving enzyme-inducing antiepileptic drugs. Steady-state plasma topiramate concentrations are 33% lower in pediatric than in adult patients, for the same mg/kg dose. Adverse events occurring in 39% to 17% of patients included anorexia, fatigue, nervousness, and attention problems.