title: Evaluation of the FDA warning against prescribing citalopram at doses exceeding 40 mg.
abstract: OBJECTIVE
  A recent Food and Drug Administration (FDA) warning cautioned that citalopram dosages exceeding 40 mg/day may cause abnormal heart rhythms, including torsade de pointes. The authors assessed relationships between citalopram use and ventricular arrhythmias and mortality.
  
  
  METHODS
  A cohort study was conducted using Veterans Health Administration data between 2004 and 2009 from depressed patients who received a prescription for citalopram (N=618,450) or for sertraline (N=365,898), a comparison medication with no FDA warning. Cox regression models, adjusted for demographic and clinical characteristics, were used to examine associations of antidepressant dosing with ventricular arrhythmia and cardiac, noncardiac, and all-cause mortality.
  
  
  RESULTS
  Citalopram daily doses >40 mg were associated with lower risks of ventricular arrhythmia (adjusted hazard ratio=0.68, 95% CI=0.61-0.76), all-cause mortality (adjusted hazard ratio=0.94, 95% CI=0.90-0.99), and noncardiac mortality (adjusted hazard ratio=0.90, 95% CI=0.86-0.96) compared with daily doses of 1-20 mg. No increased risks of cardiac mortality were found. Citalopram daily doses of 21-40 mg were associated with lower risks of ventricular arrhythmia (adjusted hazard ratio=0.80, 95% CI=0.74-0.86) compared with dosages of 1-20 mg/day but did not have significantly different risks of any cause of mortality. The sertraline cohort revealed similar findings, except there were no significant associations between daily dose and either all-cause or noncardiac mortality.
  
  
  CONCLUSIONS
  This large study found no elevated risks of ventricular arrhythmia or all-cause, cardiac, or noncardiac mortality associated with citalopram dosages >40 mg/day. Higher dosages were associated with fewer adverse outcomes, and similar findings were observed for a comparison medication, sertraline, not subject to the FDA warning. These results raise questions regarding the continued merit of the FDA warning.
authors: Department of Veterans Affairs, National Serious Mental Illness Treatment Resource and Evaluation Center, Ann Arbor, Michigan, USA. kzivin@umich.edu
authors: Kara
authors: K
authors: Zivin
authors: Paul N
authors: PN
authors: Pfeiffer
authors: Amy S B
authors: AS
authors: Bohnert
authors: Dara
authors: D
authors: Ganoczy
authors: Frederic C
authors: FC
authors: Blow
authors: Brahmajee K
authors: BK
authors: Nallamothu
authors: Helen C
authors: HC
authors: Kales
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D015283:Citalopram / Q000008:administration & dosage / Q000009:adverse effects*; D003866:Depressive Disorder / Q000188:drug therapy; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009026:Mortality; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D020280:Sertraline / Q000008:administration & dosage / Q000009:adverse effects; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D015283:Citalopram; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline