Cenobamate in pediatric epilepsy and developmental and epileptic encephalopathies: Efficacy, safety, and...

Cenobamate, a dual-mechanism antiseizure medication with sodium channel and GABA-A receptor activity, has demonstrated superior efficacy in adult focal epilepsy but remains understudied in pediatric populations and developmental and epileptic encephalopathies (DEEs). This comprehensive narrative review synthesized available evidence from 27 studies examining cenobamate use in pediatric epilepsy and DEEs through systematic literature search and narrative synthesis. Eight studies encompassing 624 pediatric patients (aged 16 months-18 years) demonstrated responder rates of 50-84 % and seizure freedom in 3-31 % of patients, with high retention rates (81-100 %). Weight-based dosing proved necessary in younger children (≤6 years: ∼5 mg/kg/day vs. adolescents: ∼2.7 mg/kg/day). Common adverse effects included somnolence (10-42 %), dizziness/ataxia (11-24 %), and behavioral changes, with rare but serious psychiatric symptoms including suicidality (1-2 % of patients). Drug-drug interactions required proactive management, particularly with clobazam and sodium channel blockers. Nineteen studies in DEEs with 339 patients showed syndrome-specific variability. Lennox-Gastaut syndrome (242 patients) achieved good efficacy (35-86 % responders, 10-31 % seizure-free) with acceptable tolerability. SCN8A-related DEE demonstrated exceptional responses (83 % responders). Conversely, Dravet syndrome showed concerning age-dependent outcomes-favorable adult responses contrasted sharply with pediatric seizure worsening and universal discontinuation in one cohort. In conclusion, cenobamate shows promise in select pediatric epilepsy populations, with efficacy comparable to adult studies. However, syndrome-specific considerations are critical, particularly the risk of seizure exacerbation in pediatric Dravet syndrome. Age-appropriate dosing strategies, psychiatric monitoring, and careful syndrome selection are essential for safe use of cenobamate in these populations. Importantly, the benefits of cenobamate may extend beyond seizure control to include improvements in cognition, behavior, and quality of life.