Low dose and slow titration of topiramate as adjunctive therapy in refractory partial epilepsies: a multicentre open clinical trial

Abstract

Purpose: A multicentre open clinical trial was conducted to evaluate the clinical usefulness of a slower titration of topiramate (TPM) to 300 mg /day as adjunctive therapy for medically intractable partial epilepsies. Methods: Ninteen centres participated in the trial. Study patients had to have had two or more seizures per 4 weeks whilst taking maximum tolerated doses of one but not more than two anti-epileptic drugs. The starting dose of TPM was 25 mg /day and the dose was increased weekly by 25 mg /day until 100 mg /day was reached. Thereafter TPM was increased by 50 mg /day weekly up to the target dose of 300 mg /day, which was followed by an 8 week maintence phase. Seizure outcomes were measured by intention-to-treat analysis (ITTA) Results: Two hundred and thirteen patients entered the study. Median seizure frequency reduction rate was 44.8%, responder rate was 47.6%, and seizure free rate was 9.0%. These results were comparable to that of TPM 600 mg /day in our previous controlled trial. In subgroup analysis, seizure free rate was higher in those patients with a lower baseline seizure frequency rate. Seventeen patients (8.0%) were prematurely withdrawn from the study due to adverse events (AE) or lack of effect. One or more AEs were reported in 22% of patients, with dizziness being the most frequent AE. Other AEs occurred in less than 5% of patients. Conclusion: TPM 300 mg /day was effective and in conjunction with a slower dose-titration, markedly reduced the incidence of AEs, compared with previous study.