새로이 진단된 간질환자에서 조니사마이드(Zonisamide)와 카바마제핀(Carbamazepine)단독약물요법의 비교 : 이중맹검 다기관 임상연구

Abstract

Purpose and background：Zonisamide (ZNS) is a broad-spectrum antiepileptic drug (AED) effective as an adjunctive therapy for medically intractable epilepsies. Past clinical experiences of ZNS in Korea have indicated that ZNS was a safe and effective antiepileptic drug, which raised a possibility of its clinical usefulness as initial montherapy. Korean Zonisamide Study Group was organized to conduct a double-blind multicenter comparative clinical trial of ZNS and carbamazepine (CBZ) monotherapy in newly diagnosed epileptic patients. Methods : Newly diagnosed epileptic patients fulfilling the inclusion criteria were randomized into ZNS and CBZ groups. The protocol consisted of 4 weeks of dose-escalation phase and follow-up phase of variable periods. The drugs were administered by double-dummy method. The initial target dose was either ZNS 300 mg/day or CBZ 600 mg/day. If seizures recurred at the initial target dose, the study drugs were increased by 1 tab at 4-week interval up to the maximum dose of 6 tabs/day or until clinically tolerable. The study end point was 24-week seizure remission. Results : Among 171 patients recruited to the study, 16 patients were excluded due to non-drug related causes and remaining 155 patients entered the doseescalation phase (ZNS＝73, CBZ＝82). The 24-week terminal remission rate was 69.9% in ZNS group compared with 75.6% in CBZ group (p＝0.9). The time interval to the first seizure recurrence was 40.9±31.7 days in ZNS group (n＝13) and 47.8±30.8 days in CBZ group (p＝0.75). The incidence of adverse events (AEs) was 67.1% in ZNS group and 53.7% in CBZ group (p＝0.088). AEs precipitated early drug withdrawal in 11 patients of each groups. The profiles of AE were quite different between the two drugs with anorexia, dizziness, and G-I discomfort being most common in ZNS group compared with dizziness, somnolence, and skin rash in CBZ group. Also AEs were more frequent during follow-up phase in ZNS group than CBZgroup (p＝0.006). Conclusion :ZNS and CBZ monotherapies were equally effective and safe. However, the profiles of AE were quite different between the two drugs and AEs precipitated by ZNS seemed lasting longer than that of CBZ.