Perampanel, Lacosamide, Eslicarbazepine Acetate, and Brivaracetam in Adults Aged ≥65 Years with Epilepsy: A Narrative Review of Real‐World Evidence and Practical Prescribing Considerations

Epilepsy prevalence sharply increases after age 65 years, but elderly adults are chronically underrepresented in key trials that form the licensing evidence base for antiseizure medications (ASMs), leaving clinicians to extrapolate from the experiences of younger cohorts. This narrative review aims to consolidate real-world evidence regarding the efficacy, safety, and tolerability of 4 commonly prescribed newer ASMs, perampanel (PER), lacosamide (LCM), eslicarbazepine acetate (ESL), and brivaracetam (BRV) among adults ≥65 years, provide pragmatic prescribing recommendations based on this evidence, and define key gaps where further study should be prioritized. Collating data from our structured search of observational cohorts, interventional trials and extensions, pooled and post hoc analyses, pharmacovigilance databases, and case series and reports, we found that reported effectiveness outcomes in older adults were generally comparable to those observed in broader adult populations, although heterogeneity across studies limits direct comparisons. ESL monotherapy produced 1-year retention rates of 72.7% and 6- and 12-month seizure freedom rates of 72.2% and 67.3% among patients ≥65 years; adjunctive LCM demonstrated superior seizure freedom rates among older versus younger patients (56.7% vs. 43.1%); and dedicated ≥65-year-old studies of ESL and BRV reaffirmed efficacy observed in overall populations, frequently at lower doses and slower titration schedules. Key safety signals were drug-specific: hyponatremia (more common and symptomatic in older adults) for ESL; dose-dependent PR interval prolongation and rare high-grade atrioventricular block/ventricular tachycardia, Brugada morphology, and sinus node dysfunction for LCM; and psychiatric or behavioral events, dose-dependent falls for PER. Evidence supported a class-wide relationship between chronic ASM exposure and falls and fractures, while a FAERS analysis found no significant drug reaction with eosinophilia and systemic symptoms (DRESS) signal for BRV and analysis-dependent findings for LCM. In conclusion, newer ASMs are efficacious and generally well tolerated among older adults. However, optimized safe prescribing in this population requires ASM selection tailored to comorbidities, lower starting doses with slower titration, and drug-specific follow-up (e.g., serum sodium monitoring for ESL, cardiac conduction assessment for LCM, and behavior and fall risk assessment for PER). Evidence remains lacking in adults ≥65 years of age, particularly for brivaracetam.