With few studies systematically quantifying depressive symptom changes across antiseizure medications (ASMs), this meta-analysis evaluates pre- to post-treatment differences in Beck Depression Inventory (BDI-II) scores using standardized effect sizes with the aim to clarify the differential psychiatric effects of ASMs and support more holistic, patient-centered prescribing.

 We identified 7 studies (6 with analyzable quantitative data and one descriptive multi-drug cohort) across 436 adults (295 in the quantitative analysis) with epilepsy encompassing 16 therapy groups (with 10 distinct anti-seizure medications) that were published from 1996-2024. We then calculated standardized mean change (Cohen’s d) and standard errors from pre- and post-treatment Beck Depression Inventory (BDI-II) scores using pooled SD and r=0.5 on version 19 of Stata SE. For the multi-drug cohort, we calculated unweighted d values.

Across the 16 therapy groups, standardized mean change in depressive symptoms which varied from -1.37 to +1.99 (mean d=-0.42 ± 0.78) where negative d values indicate reduction in depressive symptoms. Most anti-seizure medications were correlated with symptoms improvement, with the greatest effects observed for  Perampanel (d = –0.77),  Brivaracetam (d = –0.55), Lacosamide (d = –0.46),  and Eslicarbazepine Acetate  (d = –0.41). In fact, cannabidiol was the only therapy cohort that was associated with worse BDI scores (d = +1.99). From the descriptive multi-drug cohorts, a similar trend was found.

Decreases in depressive symptoms appear to be an underrecognized yet clinically meaningful secondary effect of antiseizure medications. These findings highlight specific medications that may provide the greatest benefit in co-morbid neuropsychiatric symptoms and underscore an importance of integrating psychiatric outcomes into epilepsy treatment decisions.