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Comparative Risk of Ventricular Arrhythmia and Sudden Cardiac Death Across Antidepressants in Patients With Depressive Disorders

Wu, Chi-Shin MD, PhD; Tsai, Yu-Ting MS; Hsiung, Chao A. PhD; Tsai, Hui-Ju MPH, PhD

Journal of Clinical Psychopharmacology: February 2017 - Volume 37 - Issue 1 - p 32–39
doi: 10.1097/JCP.0000000000000631
Original Contributions

Objective We aimed to evaluate the risk of ventricular arrhythmia (VA) and/or sudden cardiac death (SCD) associated with antidepressant use.

Methods A cohort study was conducted using data from Taiwan's National Health Insurance Research Database from 2001 to 2012. A total of 793,460 new antidepressant users with depressive disorders were enrolled in the study. Outcomes were defined as the first principal diagnosis of VA or SCD in the emergency department or hospital discharge records. Cox proportional hazards models with stratification of propensity score deciles were used to evaluate the relative risk of VA/SCD for antidepressants compared with selective serotonin reuptake inhibitors (SSRIs).

Results A total of 245 VA/SCD events occurred. The incidence rate of VA/SCD among antidepressant users was 1.5 per 1000 person-years (95% confidence interval [CI], 1.3–1.7). Compared with SSRIs, the risk of VA/SCD was significantly lower for tricyclic or tetracyclic antidepressant (TCAs) (adjusted hazards ratio [aHR], 0.54; 95% CI, 0.36–0.83), but not other antidepressant classes. However, use of moderate- to high-dose TCAs carried a higher risk than low-dose TCAs (aHR, 4.37; 95% CI, 1.23–15.60). Antidepressant polypharmacy was associated with an increased risk of VA/SCD (aHR, 1.63; 95% CI, 1.07–2.49).

Conclusions There was no difference in VA/SCD risk across antidepressant classes except that TCAs were associated with a lower risk than SSRIs. However, the observed comparative risk of TCAs might be attributable to low-dose TCA use, which is quite common in current clinical practice. It would be of importance to carry out further investigations to scrutinize the influence of antidepressants on VA/SCD.

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From the *Department of Psychiatry, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei; †Department of Psychiatry, Far Eastern Memorial Hospital, New Taipei City; ‡Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Zhunan; §Department of Public Health, China Medical University, Taichung, Taiwan; and ‖Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL.

Received January 21, 2016; accepted after revision September 7, 2016.

Reprints: Hui-Ju Tsai, MPH, PhD, Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, 35, Keyan Rd, Zhunan Town, Miaoli County 350, Taiwan (e-mail:;

Supported by grants from National Health Research Institutes, Taiwan (PI: Tsai, PH-104-PP-14, PH-104-SP-05, PH-104-SP-16, PH-105-SP-05, PH-105-SP-04).

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