Zonisamide clinical trials: European experience

Abstract

European clinical trials of zonisamide as adjunctive therapy for refractory partial seizures included a 12-week double-blind, placebo-controlled study and a 15-month open-label extension study. In the double-blind study, patients (n = 144) were randomized to placebo or zonisamide (400 mg QD) after baseline evaluation. Patients completing the double-bind study (n = 115) continued on open-label zonisamide for up to 18 months. Median percent reduction in partial seizures from baseline was significantly greater in zonisamide-treated patients compared to those receiving placebo (31.6% versus 3.3%, respectively; P = 0.008). Additionally, more zonisamide-treated patients achieved > or = 50% reduction in seizure frequency relative to baseline than did placebo patients (30.4% versus 14.7%, respectively; P = 0.03). The extension study showed that zonisamide efficacy was maintained or improved over time. Patient and physician assessments favored zonisamide over placebo in terms of patient improvement with treatment. Median zonisamide maintenance dosage was 400mg/day, and the average therapeutic blood level was 16.9 microg/mL. Both studies showed that zonisamide was well tolerated; adverse events were generally mild to moderate and most frequently included fatigue, dizziness, somnolence, and anorexia. Collectively, these findings corroborate those of US and Asian clinical trials, which also show that zonisamide is safe and effective for adjunctive therapy of partial seizures.