Efficacy, treatment retention, and tolerability of newer- versus older-generation antiseizure medications in older adults with epilepsy: a systematic review and meta-analysis.

Objective: Older adults with epilepsy frequently have multiple comorbidities, polypharmacy, and reduced medication tolerance; therefore, ASM selection must consider seizure control, treatment persistence, and tolerability. This study compared the efficacy and safety outcomes of newer-generation and older-generation ASMs in older adults with epilepsy. Methods: PubMed, Embase, Web of Science Core Collection, and the Cochrane Library were searched from inception to April 30, 2026. Comparative clinical studies evaluating newer-generation versus older-generation ASMs in populations defined as older adults by the original studies were eligible. The primary outcome was seizure freedom; secondary outcomes included seizure-free retention, treatment retention, withdrawal for any reason, discontinuation due to adverse events, and adverse reactions. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using fixed- or random-effects models according to statistical and clinical heterogeneity. Results: Nine studies involving 2,507 participants were included, comprising randomized, open-label, Conclusion: Across a small and clinically heterogeneous evidence base, seizure freedom did not clearly differ between newer- and older-generation ASMs, whereas treatment retention and adverse-event-related discontinuation favored newer-generation agents; however, the certainty of evidence was low or very low. These class-level findings should be interpreted cautiously because the medication categories were pharmacologically heterogeneous and the evidence included mixed study designs, variable age definitions, and inconsistent outcome windows.