Antidepressants and Risk of Sudden Cardiac Death: A Network Meta-Analysis and Systematic Review

Background: Antidepressants are one of the most prescribed medications, particularly for patients with mental disorders. Nevertheless, there are still limited data regarding the risk of ventricular arrhythmia (VA) and sudden cardiac death (SCD) associated with these medications. Thus, we performed systemic review and meta-analysis to characterize the risks of VA and SCD among patients who used common antidepressants. Methods: A literature search for studies that reported risk of ventricular arrhythmias and sudden cardiac death in antidepressant use from MEDLINE, EMBASE, and Cochrane Database from inception through September 2020. A random-effects model network meta-analysis model was used to analyze the relation between antidepressants and VA/SCD. Surface Under Cumulative Ranking Curve (SUCRA) was used to rank the treatment for each outcome. Results: The mean study sample size was 355,158 subjects. Tricyclic antidepressant (TCA) patients were the least likely to develop ventricular arrhythmia events/sudden cardiac deaths at OR 0.24, 0.028-1.2, OR 0.32 (95% CI 0.038-1.6) for serotonin and norepinephrine reuptake inhibitors (SNRI), and OR 0.36 (95% CI 0.043, 1.8) for selective serotonin reuptake inhibitors (SSRI), respectively. According to SUCRA analysis, TCA was on a higher rank compared to SNRI and SSRI considering the risk of VA/SCD. Conclusion: Our network meta-analysis demonstrated the low risk of VA/SCD among patients using antidepressants for SNRI, SSRI and especially, TCA. Despite the relatively lowest VA/SCD in TCA, drug efficacy and other adverse effects should be taken into account in patients with mental disorders.