Newer-generation antiseizure medications improve treatment retention and safety in older adults with epilepsyNewer Antiseizure Medications May Improve Treatment Retention in Seniors

ObjectiveOlder 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.MethodsPubMed, 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.ResultsNine studies involving 2,507 participants were included, comprising randomized, open-label, post-hoc subgroup, and retrospective evidence. Overall seizure freedom did not differ significantly between the two medication categories (RR = 1.18, 95% CI 0.80–1.76; I2 = 93%), and the restricted sensitivity analysis remained non-significant (RR = 1.11, 95% CI 0.94–1.30). No significant difference was observed in seizure-free retention. Newer-generation ASMs were associated with higher treatment retention (RR = 1.34, 95% CI 1.22–1.47), with the inverse outcome of withdrawal for any reason correspondingly lower (RR = 0.71, 95% CI 0.64–0.80); adverse-event-related discontinuation was also lower (RR = 0.54, 95% CI 0.45–0.64). In the exploratory post-stroke analysis based on two randomized studies, the random-effects estimate did not show a significant difference in seizure freedom (RR = 1.30, 95% CI 0.81–2.08; I2 = 77%).ConclusionAcross 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.