Objective To investigate the efficacy and safety of brivaracetam (BRV) as a substitute therapy for children with drug-resistant epilepsy (DRE) who have exhibited a suboptimal response to levetiracetam (LEV). MethodsTwenty-four children aged 3 to 13 years with drug-resistant epilepsy and poor response to LEV were retrospectively included. LEV was replaced with BRV within 3 days at a dose ratio of 10∶1. The maximum maintenance dose of BRV was ≤5 mg·kg?1·d?1. Patients were followed up for 6 months. Changes in seizure frequency before treatment and at 1, 3, and 6 months of treatment were observed and analyzed. Treatment-related adverse events and laboratory indicators were also recorded. ResultsThrough self-controlled analysis, after 6 months of treatment, the mean frequency of epileptic seizures in pediatric patients decreased from a baseline of 27.2±42.5 times/28 days to 8.9±14.6 times/28 days. The median frequency of seizures decreased from a baseline of 2 times/28 days to 1 time/28 days. The difference compared to baseline was statistically significant (P=0.002). The clinical response rate was 45.8%, and the complete seizure-free rate was 41.7%, with efficacy showing an increasing trend over the treatment duration. Only 3 cases (12.5%) experienced mild to moderate adverse reactions (1 case each of dizziness, nausea/vomiting, and abdominal pain). Only 1 case discontinued medication due to adverse reactions. Hematology, urinalysis, liver and kidney function, etc., showed no abnormalities, and there were no serious adverse events. ConclusionsSubstituting LEV with BRV demonstrates significant efficacy in children with DRE who have a suboptimal response to LEV. The regimen is associated with few adverse events and good tolerability, suggesting it is a viable and effective alternative clinical strategy.