Topiramate add-on therapy for adult patients with refractory epilepsy in Japan

Abstract

Purpose: To evaluate the efficacy and tolerability of topiramate (TPM) as add-on therapy in Japanese adult patients with refractory epilepsy. Methods: We performed a retrospective open-label study on 39 Japanese adult patients with refractory seizures (aged 18-64 years, average 36.4 years). Twenty-nine patients with symptomatic partial epilepsy, seven with symptomatic generalized epilepsy, two with Lennox-Gastaut syndrome, and one with severe myoclonic epilepsy in infancy were included in the study. TPM was started at a dose of 50 mg/day in 33 patients and 100 mg/day in 6 patients and adjusted according to individual clinical response at a slow titration of 50 mg/day or less biweekly. We compared the number of seizures in 4-week durations before and 24 weeks after starting TPM therapy. Results: After a follow-up period of 28 weeks, 12 of 39 (31%) responded to TPM at an average dose of 100 mg/day, and four (10%) became seizure free. Thirty-one percent did not respond to TPM and 38% dropped out. Adverse events occurred in 21 patients (54%), 9 of whom discontinued TPM due to serious adverse events such as severe somnolence, depression, leg edema, excitement, and agranulocytosis. Adverse events developed even at the initial TPM dose of 50 mg/day. Conclusion: TPM add-on therapy is effective even at low-dose in Japanese adult patients with refractory epilepsy. However, dose escalation as slow as 25 mg/day every 2 weeks is recommended to avoid adverse effects of TPM.