Double-blind, placebo-controlled study of topiramate in patients with refractory partial epilepsy

Epilepsy Res. 1996 Nov;25(3):217-24. doi: 10.1016/s0920-1211(96)00029-0.


The efficacy and safety of topiramate 400 mg/day as adjunctive therapy to traditional antieleptic drugs for partial onset seizures with or without secondary generalization were assessed in a double-blind, parallel-group, placebo-controlled trial. Forty-seven patients with at least one seizure per week during an 8 week baseline were randomly assigned to topiramate (N = 23) or placebo (N = 24) double-blind treatment for a 3 week titration and an 8 week stabilization period. Median percent reduction from baseline in monthly seizure frequency during the double-blind phase was not significantly greater in the topiramate group than in the placebo group (41% vs. 1%; P = 0.065). Nevertheless, other efficacy variables evidenced statistically significant differences in favor of topiramate: a greater number of treatment responders (> or = 50% reduction in seizures; 35% vs. 8%; P = 0.033); better investigator (P = 0.002) and patient (P = 0.021) global assessments; and greater reductions in secondarily generalized seizures compared to placebo (P = 0.002). The most commonly reported topiramate treatment-emergent adverse events were somnolence, fatigue, abnormal vision, weight decrease, and anxiety. Most adverse events were mild or moderate in severity. Among 7 withdrawals due to limiting adverse events, 6 were CNS-related (in 5 topiramate-treated patients). Results of this trial strongly suggest that topiramate 400 mg/day is effective and well tolerated in the treatment of refractory partial epilepsy.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Analysis of Variance
  • Anticonvulsants / adverse effects
  • Anticonvulsants / therapeutic use*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Epilepsies, Partial / drug therapy*
  • Europe
  • Female
  • Fructose / adverse effects
  • Fructose / analogs & derivatives*
  • Fructose / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Placebos
  • Topiramate


  • Anticonvulsants
  • Placebos
  • Topiramate
  • Fructose