Abstract / Summary
Antidepressants (ADs) have been associated with adverse cardiovascular effects, including cardiac arrhythmias. Evidence on the association between AD use and the risk of atrial fibrillation (AF) and ventricular arrhythmia/sudden cardiac death (VA/SCD) remains inconsistent. This systematic review and meta-analysis aimed to evaluate the relationship between AD use and the risk of AF and VA/SCD. A detailed search was conducted in PubMed, Scopus, and Web of Science till June 2026. Cohort and case-control studies comparing AD users with non-users and reporting AF, VA, or SCD as outcomes were included. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Twelve studies with 9,619,278 participants were included. AD use was associated with a significantly increased risk of VA/SCD (9 studies, 6,373,522 participants, OR = 1.34, 95% CI: 1.15-1.55; I² = 90.5%). The association remained significant for both SSRIs and TCAs. For AF, no overall significant association emerged (3 Studies, 3,245,756 participants, OR = 1.75, 95% CI: 0.84-3.62; I² = 98.1%). However, sensitivity analysis excluding one influential study showed a significant association with AF (2 Studies, 18,109 participants, OR = 1.27, 95% CI: 1.07-1.50) and eliminated heterogeneity (I² = 0%). This meta-analysis suggests an association between AD use and an increased risk of VA/SCD, while evidence for AF remains uncertain because the results were influenced by a single study. Future large observational studies that better address confounding by indication and adequately adjust for depression are needed to provide more robust evidence.