Comparative trial of low- and high-dose zonisamide as monotherapy for childhood epilepsy

PURPOSE: To evaluate the effectiveness of zonisamide (ZNS) as monotherapy in children with newly diagnosed epilepsy. METHODS: This randomized, multicenter trial included a 2-4-week titration and a 24-week maintenance phase after randomization to low-(3-4 mg/kg/day) or high-(6-8 mg/kg/day) dose groups as target maintenance dosages. The primary outcome measure was the seizure-free rate over 6 months, while a secondary measure was the change in cognition and behavior from screening to the end of the maintenance phase. RESULTS: Out of 125 patients enrolled, 90 (49 low-dose and 41 high-dose) completed the study. Forty-one patients (63.1%) in the low-dose group and 34(57.6%) in the high-dose group achieved 6 months' freedom from seizures (p=0.66). After treatment, the picture arrangement subtest improved in the low-dose group (p=0.047) while the vocabulary subtest worsened in the high-dose group (p=0.020). Comparing between the two groups, the vocabulary subtest in the high-dose group was significantly worse than that in the low-dose group (p=0.002). Social competence, somatic complaints, depression/anxiety and delinquent and aggressive behavior in the low-dose group were significantly improved (p<0.05). Moreover, total social competence, somatic complaints, delinquent behavior, externalizing, and total behavior problems were significantly more improved in the low-dose group than the high-dose group (p