Topiramate in medically intractable partial epilepsies: Double-blind placebo-controlled randomized parallel group trial

Purpose: To evaluate the efficacy and safety of topiramate (TPM) as add-on therapy in medically intractable partial epilepsies. Methods: We used a multicenter double-blind placebo-controlled randomized p arallel-group trial consisting of 12 weeks of baseline phase, 10 weeks of t itration phase, and 8 weeks of stabilization phase. The primary efficacy va riable was the median seizure frequency reduction rate (MSFRR), and the oth er efficacy variables included responder rate, seizure-free rate, and globa l evaluations by the patient and the physician. The patient should have par tial epilepsies refractory to the maximally tolerable doses of one to two a ntiepileptic drugs (AEDs) and should have two or more episodes of clinical seizures every 4 weeks during the baseline phase. The target dose of study drugs was 600 mg/day. The study drugs were started at the initial dose of 5 0 mg/day and gradually increased to the target dose over a 10-week period. Results: A total of 177 patients was randomized into the TPM group (n = 91) and the placebo (PLC) group (n = 86). Baseline median seizure frequencies were 5.6 episodes/4 weeks in the TPM and the PLC groups. Among those who we re randomized, 174 patients (TPM, 89 patients; PLC, 85 patients) were avail able for the efficacy measurement by intention-to-treat analysis. The MSFRR was 51.3% for TPM and 9.1% for PLC, which was highly in favor of TPM (p = 0.0001). The responder rate was 50.6% for TPM and 12.9% for PLC (p = 0.001) . Seven (7.9%) of 89 patients taking TPM became seizure free compared with one (1.2%) of 85 patients taking PLC (p = 0.004). The global evaluation gre atly favored TPM (p = 0.001). The incidence of adverse events (AEs) was hig her in the TPM (81.3%) than in the PLC (48.9%) group, with central nervous system (CNS)-related AEs being the most frequent. Among individual AEs, ano rexia (20.9%) and abdominal pain or discomfort (20.9%) were the most common AEs in the TPM group. AEs precipitated early drop-out in seven (7.6%) pati ents taking TPM and three (3.5%) patients taking PLC. No serious systemic A Es were observed. Conclusions: TPM was highly effective and safe as add-on therapy in medical ly intractable partial epilepsies. Slower titration; of TPM might be respon sible for the lesser drop-out rate than previous trials, but the incidence of AEs was still high. The AE profile of TPM in Koreans was different from that in whites.