Abstract
OBJECTIVE: To evaluate the real-world effectiveness and safety of adjunctive zonisamide in children with developmental epileptic encephalopathy/epileptic encephalopathy (DEE/EE), focusing on younger children and highly drug-resistant cases. METHODS: This open-label, nonrandomized, self-controlled, real-world study included 127 children with DEE/EE at a single center from 2020 to 2025. The primary endpoint was the responder rate (≥ 50% seizure reduction) at 3, 6, 9, and 12 months, analyzed using last observation carried forward. Secondary endpoints included seizure freedom, retention, and adverse events (AEs). Multivariable analysis identified predictors of efficacy. RESULTS: Responder rates were 51.2%, 55.3%, 53.7%, and 53.7% at 3, 6, 9, and 12 months, respectively. Seizure-free rates were 23.6%, 26.8%, 24.4%, and 27.6%. Efficacy was consistent across age and etiology. Female gender (OR = 3.00) and fewer prior anti-seizure medications (OR = 0.77) independently predicted 12-month response. Among children failing ≥ 5 prior medications, 44.3% responded, and 20.0% achieved seizure freedom. The 12-month retention rate was 81.9%. AEs occurred in 14.2%, most commonly reduced appetite (7.9%); most were tolerable. CONCLUSION: Adjunctive zonisamide provides sustained efficacy and favorable tolerability in children with DEE/EE, including young children < 6 years and highly drug-resistant cases. Gender and prior treatment history predict long-term efficacy, supporting its reliable risk-benefit profile for refractory epilepsy.