Double-Blind, Randomized, Comparative Clinical Trial of Zonisamide and Carbamazepine as Initial Monotherapy in Newly Diagnosed Epilepsy

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Abstract

PURPOSE AND BACKGROUND: Zonisamide(ZNS) is a broad-spectrum antiepileptic drug (AED) effective as an adjunctive therapy for medically ingractable epilepsies. Past clinical experiences of ZNS in Korea have indicated that ZNS was a safe and dffective 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 300mg/day or CBZ 600mg/day. If seizures recurred at the initial target does, the study drugs were increased by 1 tab at 4-week seizure remission
RESULTS
Among 171 patients recruited to the study, 16 patients were sxcluded due to non-drug related causes and remaining 155 patients entered the dose-escalation 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 was40.9-31.7 days in ZNS group (n=13)and 47.8-30.8 days 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-1 discomfort being most common in ZNS group compared with dizziness, comnolence, and skin rash in CBZ group. Also AEs were more frequent during follow-up phase in ZNS group thna CBZ-group(p=0.006).
CONCLUSION
ZNS and CBZ monotherapies were equally effective and safe. However, the profiles of AE were quite different between the drugs and AEs precipitated by ZNS seemed lasting longer than that of CBZ.