Background and objectivesLacosamide (LCM) is a third-generation concomitant antiseizure medication (ASM) that is widely used in epilepsy treatment. Reported data on the predictors of efficacy of LCM in children with epilepsy are scarce. This study aimed to explore the predictors of LCM efficacy in pediatric patients with epilepsy.MethodsThis single-center retrospective cohort study was conducted in China, consecutively enrolled pediatric epilepsy patients receiving lacosamide treatment; the study period for data collection was September 2021 to April 2025. Demographic data, LCM daily dose, serum concentration, concentration-to-dose ratio (CDR), ASMs, and seizure frequency before and after treatment were collected. Patients were categorized into effective (≥50% seizure reduction) and ineffective groups. Univariate analysis and ridge regression were used to assess the impact of the factors on the efficacy of LCM. The receiver operating characteristic (ROC) curve was used to evaluate the predictive performance of the ridge regression model.ResultsA total of 71 children with epilepsy were enrolled in this study (boys: 35, 49.3%; girls: 36, 50.7%). The overall effectiveness rate was 81.69%. Univariate analysis showed a significantly higher CDR in the effective group compared to the ineffective group (0.768 vs. 0.58, P = 0.031). In this exploratory pilot analysis, ridge regression implied that CDR has a positive effect on the efficacy of LCM. The AUC of the predictive performance of the ridge regression model was 0.767 (95% CI: 0.651–0.875).DiscussionCDR, reflecting weight- and dose-adjusted LCM exposure, is a predictor of LCM efficacy in pediatric epilepsy. These findings support the use of CDR for guiding individualized LCM therapy. Further multicenter studies with larger samples are warranted to validate these results and establish an optimal CDR range.