Antidepressants and the risk of sudden cardiac death and ventricular arrhythmia: Antidepressants and Sudden Cardiac Death/Ventricular Arrhythmia

Purpose—To examine the association between exposure to antidepressants and emergency department or inpatient admission for sudden cardiac death and ventricular arrhythmia (SD/VA), and to examine the impact of dose and cytochrome P-450 inhibition Methods—A cohort study was conducted within 1999–2003 Medicaid claims data from beneficiaries of five large states, supplemented with Medicare claims for dually-eligible individuals. Exposures were prescription claims for antidepressants of interest or a reference antidepressant. Outcomes were incident first-listed emergency department or principal inpatient diagnoses indicative of SD/VA originating in the outpatient setting, an outcome previously found to have a positive predictive value of 85%. Results—In 1.3 million person-years of antidepressant exposure, we identified 4,222 SD/VA outcomes for a rate of 3.3/1,000 person-years (95% CI, 3.2 – 3.4). Compared to paroxetine (a referent with a putatively favorable cardiovascular risk profile), adjusted hazard ratios (HRs) were 0.80 (0.67 – 0.95) for bupropion, 1.24 (0.93 – 1.65) for doxepin, 0.79 (0.55 – 1.15) for lithium, and 1.26 (1.11 – 1.42) for mirtazapine. HRs for amitriptyline, citalopram, fluoxetine, nefazodone, nortriptyline, sertraline, trazodone, and venlafaxine were near unity. For antidepressants having non-null risks (bupropion and mirtazapine), we observed no relationship with antidepressant dose and some relationships with concomitant cytochrome P-450 inhibition. Conclusions—Of antidepressants studied, only mirtazapine had a statistically significantly greater SD/VA risk versus paroxetine. However, baseline differences between these users suggest that this finding may be attributable to residual confounding. Eleven other antidepressants had SD/ VA risks no greater than that of paroxetine, thereby providing reassurance regarding the comparative cardiovascular safety of antidepressants.