Risk of hostility and aggression with perampanel monotherapy versus combination therapy in pediatric epilepsy: A Japanese post‐marketing database study using a nested case–control design

OBJECTIVE: To compare the incidence of hostility- and aggression-related adverse events in children with focal-onset seizures (FOS), with or without focal to bilateral tonic-clonic seizures (FBTCS), receiving perampanel as monotherapy or in combination with other antiseizure medications (ASMs). METHODS: This analysis used a real-world Japanese database integrating claims data, electronic medical records, and Diagnosis Procedure Combination data, alongside study-specific physician-reported outcomes. Children aged 4-11 years treated with perampanel for FOS with or without FBTCS were included. Using a nested case-control design, analyses adjusted for baseline covariates were conducted to compare the incidence of hostility- and aggression-related adverse events in children treated with perampanel as monotherapy vs. combination therapy with other ASMs. RESULTS: Among 158 prospectively collected patients included in the primary analysis set, 10 (6.3%) experienced 14 hostility- and aggression-related adverse events, including irritability (n = 5), aggression (n = 5), anger (n = 2), anxiety (n = 1), and hallucinations (n = 1). There were no significant differences in the risk of hostility or aggression between patients receiving perampanel as monotherapy or in combination with other ASMs. Secondary and sensitivity analyses confirmed the robustness of these findings. SIGNIFICANCE: The safety profile of perampanel in routine pediatric practice was consistent with prior clinical trial data. The potential for hostility- and aggression-related adverse events warrants caution, but rates did not differ between perampanel as monotherapy vs. in combination with other ASMs. This study also demonstrated the feasibility of integrating physician-reported outcomes into post-marketing surveillance using a real-world database, providing detailed insights beyond standard medical information.