Abstracts

Rationale: To evaluate the efficacy and tolerability of zonisamide (ZNS) as monotherapy in children less than 16 years of age, using a dose-controlled study design. Methods: We conducted a multicenter, randomized, comparative trial in children with newly diagnosed epilepsy that was not being treated when randomized to low(3-4 mg/kg/day) or high(6-8 mg/kg/day) ZNS as target maintenance dosages. Patients had to have over two episodes of unprovoked partial or generalized-onset seizures in the 6-month retrospective baseline. The primary efficacy end point was the seizure-free rate at 6 months; a secondary efficacy measure was the change from screening to the end of the maintenance phase in a combined analysis of standardized measures of cognition, behavior and quality of life. Results: Out of 123 patients enrolled, 89 patients (49 low dosage, 40 high dosage) completed the study. Thirty-five (54.7%) patients on low dose group and 31 (52.5%) subjects on high dose group achieved 6 months of seizure freedom (p=0.665). Neuropsychological data were available for 58 patients (28 patients for low dose and 30 patients for high dose). Perceptual Organization of the cognitive variables, Somatizaiton, Anxiety/Depression and Aggression scores of the behavioral variables were significantly improved for both groups after treatment (p<0.05). On comparing low with high dose, vocabulary subtest of the cognitive variables, Total Competence, Delinquent behavior, Externalizing and Total Behavior problem on low dose showed significant improvements comparing with high dose (p<0.05). Conclusions: Low dose and high dose ZNS monotherapy demonstrate similar efficacy for treatment of newly diagnosed childhood epilepsy. As shown in this subset analysis, ZNS is effective and well tolerated as monotherapy in children. And, low dose ZNS monotherapy has similar efficacy in seizure control and more beneficial neurocognitive effects than high dose.