title: High-Dose Citalopram and Escitalopram and the Risk of Out-of-Hospital Death.
abstract: OBJECTIVE
  Studies demonstrating that higher doses of citalopram (> 40 mg) and escitalopram (> 20 mg) prolong the corrected QT interval prompted regulatory agency warnings, which are controversial, given the absence of confirmatory clinical outcome studies. We compared the risk of potential arrhythmia-related deaths for high doses of these selective serotonin reuptake inhibitors (SSRIs) to that for equivalent doses of fluoxetine, paroxetine, and sertraline.
  
  
  METHODS
  The Tennessee Medicaid retrospective cohort study included 54,220 persons 30-74 years of age without cancer or other life-threatening illness who were prescribed high-dose SSRIs from 1998 through 2011. The mean age was 47 years, and 76% were female. Demographic characteristics and comorbidity for individual SSRIs were comparable. Because arrhythmia-related deaths are typically sudden and occur outside the hospital, we analyzed out-of-hospital sudden unexpected death as well as sudden cardiac deaths, a more specific indicator of proarrhythmic effects.
  
  
  RESULTS
  The adjusted risk of sudden unexpected death for citalopram did not differ significantly from that for the other SSRIs. The respective hazard ratios (HRs) for citalopram versus escitalopram, fluoxetine, paroxetine, and sertraline were 0.84 (95% CI, 0.40-1.75), 1.24 (95% CI, 0.75-2.05), 0.75 (95% CI, 0.45-1.24), and 1.53 (95% CI, 0.91-2.55). There were no significant differences for sudden cardiac death or all study deaths, nor were there significant differences among high-risk patients (≥ 60 years of age, upper quartile baseline cardiovascular risk). Escitalopram users had no significantly increased risk for any study end point.
  
  
  CONCLUSIONS
  We found no evidence that risk of sudden unexpected death, sudden cardiac death, or total mortality for high-dose citalopram and escitalopram differed significantly from that for comparable doses of fluoxetine, paroxetine, and sertraline.
authors.affiliation: Department of Health Policy, Village at Vanderbilt, Ste 2600, 1501 21st Ave S, Nashville, TN 37212. wayne.ray@vanderbilt.edu.|Department of Health Policy, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Ray
authors.affiliation: Department of Medicine and Pharmacology, Division of Rheumatology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Cecilia P
authors.initials: CP
authors.lastname: Chung
authors.affiliation: Department of Medicine and Pharmacology, Division of Cardiology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.|Department of Medicine and Pharmacology, Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Katherine T
authors.initials: KT
authors.lastname: Murray
authors.affiliation: Department of Health Policy, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Kathi
authors.initials: K
authors.lastname: Hall
authors.affiliation: Department of Medicine and Pharmacology, Division of Rheumatology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.|Department of Medicine and Pharmacology, Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: C Michael
authors.initials: CM
authors.lastname: Stein
mesh_terms: D000328:Adult; D000368:Aged; D000553:Ambulatory Care; D015283:Citalopram / Q000009:adverse effects* / Q000627:therapeutic use; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000401:mortality*; D008297:Male; D001523:Mental Disorders / Q000188:drug therapy* / Q000401:mortality*; D008875:Middle Aged; D058687:Out-of-Hospital Cardiac Arrest / Q000401:mortality*; D012189:Retrospective Studies; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D013714:Tennessee
chemical_list: D015283:Citalopram; D017367:Selective Serotonin Reuptake Inhibitors