Association Between Antidepressant Use and Risk of Venous Thromboembolism: A Systematic Review and Meta-Analysis

Objectives: To evaluate the association between antidepressant use and the risk of venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism (PE), through a systematic review and meta-analysis of observational studies. Methods: A comprehensive literature search was conducted in Medline, Embase^®, and Web of Science^® up to December 2024. Eighteen studies (cohort, case-control, and nested case-control designs) meeting inclusion criteria were analyzed. Study quality was assessed using the Newcastle-Ottawa Scale. Pooled relative risks (RR) with 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup analyses were performed based on recency of antidepressant use, VTE onset type (first vs. recurrent), and VTE subtype (PE). Results: Antidepressant use was associated with a significantly increased risk of VTE (RR = 1.22; 95% CI: 1.12-1.32; p < 0.001). Subgroup analyses revealed a stronger association for recent use (within 90 days), first-onset VTE, recurrent VTE, and PE. Heterogeneity was high (I² = 87.92%), but sensitivity analysis confirmed result robustness. No publication bias was detected. Conclusions: This meta-analysis indicates a modest but statistically significant increase in the risk of VTE associated with antidepressant use, particularly among recent users, individuals experiencing either first-time or recurrent VTE, and those with PE-type events. These findings highlight the importance of individualized VTE risk assessment when initiating antidepressant therapy.