Efficacy of Topiramate Using Lower Dose and Slower Dose-Titration in Refractory Partial Epilepsies: A Multicenter Open Clinical Trial

Lee, Byung In

Abstract

PURPOSE AND BACKGROUND: Korean Topiramate Study Group (KTSG) was organized to evaluate the efficacy and safety of lower dose (300 mg/day) and slower dose-titration of topiramate as add-on therapy in medically intractable partial epilepsies.
METHODS
This study was a multicenter open clinical trial consisting of each 8 weeks of baseline phase, titration phase, and maintence phase. The patient should have partial epilepsies refractory to the maximally tolerable doses of one to two antiepileptic drugs and should have at least two or more episodes of clinical seizures every 4 weeks during the baseline phase. The target dose of topiramate (TPM) was 300 mg/day. TPM was started at the initial dose of 25 mg/day and increased by 25 mg/day every week until 100 mg/day was reached. Thereafter, the dose was increased by 50 mg/day every week.
RESULTS
A total of 213 patients entered to the titration phase, 198 patients entered to the maintenance phase, and 182 patients finished the trial as planned. Median baseline seizure frequency was 3.7 episodes/4 weeks which was decreased to 2.1 episodes/4 weeks after the introduction of TPM. Median seizure frequency reduction rate (MSFRR) was 44.8%, responder rate was 47.6% and seizure free rate (SFR) was 9%. Adverse events (AE) occurred in 22% of patients with dizziness being the most common (10.0%). Premature withdrawl from the study due to AE occurred in 13 patients (6.1%).
CONCLUSION
TPM 300 mg/day was as effective as TPM 600 mg/day and safety was markedly improved by a slower dose titration. We did not find any dose-response relationship of TPM in this study.