title: Antidepressants and the risk of sudden cardiac death and ventricular arrhythmia.
abstract: OBJECTIVE
  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 using 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 4222 SD/VA outcomes for a rate of 3.3/1000 person-years (95%CI, 3.2-3.4). Compared with 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 nonnull 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.
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, and Center for Education and Research on Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6021, USA. celeonar@mail.med.upenn.edu
authors.forename: Charles E
authors.initials: CE
authors.lastname: Leonard
authors.forename: Warren B
authors.initials: WB
authors.lastname: Bilker
authors.forename: Craig
authors.initials: C
authors.lastname: Newcomb
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Kimmel
authors.forename: Sean
authors.initials: S
authors.lastname: Hennessy
mesh_terms: D000928:Antidepressive Agents / Q000009:adverse effects*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000453:epidemiology; D015331:Cohort Studies; D016757:Death, Sudden, Cardiac / Q000453:epidemiology / Q000209:etiology*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D012189:Retrospective Studies; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
chemical_list: D000928:Antidepressive Agents