Anti-seizure medication exposure and the risk of dementia: A meta-analysis of observational studies

Objective: There is growing evidence of a relationship between anti-seizure medication (ASM) use and the risk of dementia. This study examined this association using a meta-analysis approach. Methods: PubMed, EMBASE, and Cochrane Library were systematically searched for peer-reviewed observational studies published up to February 2023. Study quality was evaluated using the Newcastle-Ottawa Scale, and an overall odds ratio (OR) was pooled using fixed or random-effects models. Results: The analysis included 9 publications with 10 studies. The results showed that overall ASM exposure was associated with an increased risk of dementia [OR: 1.09, 95% confidence interval (CI): 1.03-1.15; P = 0.003] in general population. However, this association disappeared (OR: 1.02, 95% CI: 0.97-1.07; P = 0.361) when the study data adjusted for drug indications were pooled. Subgroup analysis based on individual drugs found only a positive association among those exposed to valproate, carbamazepine, and clonazepam. Furthermore, an increased risk was found in patients with bipolar disorder exposed to ASMs (OR: 1.43, 95% CI: 1.07-1.92; P = 0.015). Conclusions: The statistically significant association between ASM and dementia in general population may be driven by unmeasured confounding or several individual first-generation ASMs. However, a higher risk of dementia was observed among bipolar disorder patients treated with ASMs. Given the few included studies and evidence of high heterogeneity, further larger, prospective studies that control for important confounders are needed to verify our findings.