Frontiers in neurology · 2026
Efficacy, treatment retention, and tolerability of newer- versus older-generation antiseizure medications in older adults with epilepsy: a systematic review and meta-analysis.
СтатьяСистематический обзорМетаанализНазвание и аннотация: Перевод пока не подготовлен
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Fan Changyan, Li Chaosheng, Sui Chenyan, Han Likun, Gu Xin, Liu Yong
Аннотация
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, 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; I 2 = 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; I 2 = 77%).
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.
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, 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; I 2 = 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; I 2 = 77%).
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.