TOPIRAMATE PLACEBO-CONTROLLED DOSE-RANGING TRIAL IN REFRACTORY PARTIAL EPILEPSY USING 600-MG, 800-MG, AND 1,000-MG DAILY DOSAGES

We conducted a multicenter, double-blind, randomized, parallel, placeb o-controlled trial in 190 patients to evaluate the safety and efficacy of three dosages of topiramate (600, 800, and 1,000 mg/day) as adjunc tive therapy for patients with refractory partial epilepsy. During an 18-week double-blind treatment period, median percent reductions from baseline in average monthly seizure rates were 1% for placebo, 41%, fo r topiramate 600 mg/day and topiramate 800 mg/day, and 38% for topiram ate 1,000 mg/day. There was a 50% or greater reduction from baseline i n seizure frequency in 9% of patients in the placebo group and in 44% for topiramate 600 mg/day. 40% for topiramate 800 mg/day, and 38% for topiramate 1,000 mg/day. No placebo patients were improved by 75 to 10 0% in seizure frequency, whereas 20% of the topiramate patients were i mproved to this degree. All intent-to-treat drug-placebo comparisons i ncluding seizure reduction, percent responders, and investigator and p atient global evaluations significantly (p less than or equal to 0.02) favored topiramate. Treatment-emergent adverse Events consisted mainl y of neurologic symptoms commonly observed during antiepileptic drug ( AED) therapy. Sixteen percent of patients on topiramate discontinued t herapy due to adverse events. Results of this study indicate that topi ramate is a highly efficacious and generally well tolerated well AED. When 1 are compared, incremental efficacy in the add-on setting is not observed at topiramate dosages above 600 mg/day; however, higher dose s may prove beneficial to individual patients who tolerate them.