V. Biton et al., A randomized, placebo-controlled study of topiramate in primary generalized tonic-clonic seizures, NEUROLOGY, 52(7), 1999, pp. 1330-1337
Background and Objective: Topiramate is effective as adjunctive treatment o
f partial-onset seizures in adults. The efficacy and safety of topiramate a
s adjunctive therapy for the treatment of primary generalized tonic-clonic
(PGTC) seizures were investigated in a randomized, double-blind, placebo-co
ntrolled study. Methods: Eighty patients, 3 to 59 years old, who experience
d three or more PGTC seizures during an 8-week baseline phase were randomly
assigned to treatment with either topiramate (n = 39) or placebo (n = 41).
Topiramate was titrated to target doses of approximately 6 mg/kg/day over
8 weeks and maintained for another 12 weeks. Results: The median percentage
reduction from baseline in PGTC seizure rate was 56.7% for topiramate pati
ents and 9.0% for placebo patients (p = 0.019). The proportion of patients
with 50% or higher reduction in PGTC seizure rate was 22/39 (56%) and 8/40
(20%) for the topiramate and placebo groups, respectively (p = 0.001). The
median percentage reduction in the rate of all generalized seizures was 42.
1% for topiramate patients and 0.9% for placebo patients (p = 0.003). The p
roportions of patients with 50% or higher reductions in generalized seizure
rate were 18/39 (46%) and 7/41.(17%) for the topiramate and placebo groups
, respectively (p = 0.003). The most common adverse events were somnolence,
fatigue, weight loss, difficulty with memory, and nervousness. Treatment-L
imiting adverse events occurred in one patient in the topiramate group (ano
rexia and weight loss) and one in the placebo group (granulocytopenia and t
hrombocytopenia). Conclusion: Topiramate is well-tolerated and effective fo
r the adjunctive treatment of PGTC seizures.