Long-Term Follow-Up of Levetiracetam Monotherapy Versus Add-On Therapy in Pediatric Epilepsy.

Background/Objectives: Epilepsy treatment often continues long-term from childhood. However, evidence comparing long-term treatment persistence and adverse events (AEs) between levetiracetam (LEV) monotherapy and LEV-containing combination therapy in pediatric patients is limited. This study compared the retention rate and the rate of AEs, including irritability and insomnia, between these treatment strategies. Methods: A retrospective cohort study was conducted using data from the Pediatric Medical Information Collection System database. Patients aged ≥0 to <15 years who were diagnosed with epilepsy and prescribed with LEV, based on records registered between 1 April 2016 and 30 September 2025, were included in the study. Results: In total, 3576 patients were analyzed. Among them, 2936 were classified under the monotherapy group and 640 under the combination therapy group. The monotherapy group had a significantly higher retention rate than the combination therapy group. The two groups did not significantly differ in terms of the rates of irritability or insomnia. Conclusions: In pediatric patients with epilepsy, the retention rate of LEV monotherapy was higher than that of LEV-containing combination therapy. Meanwhile, the rates of irritability or insomnia did not substantially differ between the two groups. Based on these findings, adding LEV to other anti-seizure medications was not associated with an evident increase in the rate of irritability or insomnia. Although anti-seizure medication polytherapy has traditionally been considered to increase the risk of psychiatric and behavioral symptoms, the current study showed a different trend.