Antidepressant use and the risk of atrial fibrillation and ventricular arrhythmia: A systematic review and meta-analysis.
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.
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.
Authors
Amirat Amirat, Almasalma Almasalma, Mohamed Mohamed, Elhosary Elhosary, Abusalah Abusalah, Mohamed Mohamed, Mansour Mansour
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