title: Outcomes of Citalopram Dosage Risk Mitigation in a Veteran Population.
abstract: A public safety communication issued by the Food and Drug Administration declared that citalopram dosages exceeding 40 mg/day were no longer considered safe because of a newly recognized risk of dosage-dependent QT interval prolongation. The authors compared the incidence of hospitalizations and mortality when higher dosages of citalopram were or were not reduced to ≤40 mg/day.
  
  
  
  National electronic medical records compiled by the Veterans Health Administration were used to conduct a retrospective study of a population filling citalopram prescriptions for more than 40 mg/day when the safety communication was first issued in August 2011. Hospitalizations and mortality after dosages of citalopram were or were not reduced to ≤40 mg/day were compared using multivariable Cox regression.
  
  
  
  The at-risk cohort of 35,848 veterans (mean age, 58 years [SD=11]; 92% male) had citalopram prescriptions for 64 mg/day (SD=8.3), on average. Within 180 days after the safety communication was issued, 60% had filled prescriptions for ≤40 mg/day. All-cause hospitalizations or deaths were found to significantly increase after dosage reductions (adjusted hazard ratio=4.5, 95% CI=4.1-5.0), as were hospitalizations for depression or all-cause death (adjusted hazard ratio=2.2, 95% CI=1.8-2.6). Mortality did not decline (adjusted hazard ratio=1.0, 95% CI=0.8-1.3), and neither did hospitalizations for arrhythmias or all-cause deaths (adjusted hazard ratio=1.3, 95% CI=1.0-1.7).
  
  
  
  Reduction of prescribed citalopram dosages to a new safety limit was associated with a higher rate of hospitalization in a large patient population who had been treated with substantially higher dosages. Stipulating a safety limit for citalopram dosages before the benefits and risks of doing so were firmly established appears to have had unintended clinical consequences.
authors.affiliation: From the Center for Chronic Disease Outcomes Research, the Division of Cardiology, and the Department of Psychiatry, Minneapolis VA Health Care System, and the Department of Medicine, University of Minnesota, Minneapolis; and the VA Center for Medication Safety, Hines, Ill.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Rector
authors.affiliation: From the Center for Chronic Disease Outcomes Research, the Division of Cardiology, and the Department of Psychiatry, Minneapolis VA Health Care System, and the Department of Medicine, University of Minnesota, Minneapolis; and the VA Center for Medication Safety, Hines, Ill.
authors.forename: Selcuk
authors.initials: S
authors.lastname: Adabag
authors.affiliation: From the Center for Chronic Disease Outcomes Research, the Division of Cardiology, and the Department of Psychiatry, Minneapolis VA Health Care System, and the Department of Medicine, University of Minnesota, Minneapolis; and the VA Center for Medication Safety, Hines, Ill.
authors.forename: Francesca
authors.initials: F
authors.lastname: Cunningham
authors.affiliation: From the Center for Chronic Disease Outcomes Research, the Division of Cardiology, and the Department of Psychiatry, Minneapolis VA Health Care System, and the Department of Medicine, University of Minnesota, Minneapolis; and the VA Center for Medication Safety, Hines, Ill.
authors.forename: David
authors.initials: D
authors.lastname: Nelson
authors.affiliation: From the Center for Chronic Disease Outcomes Research, the Division of Cardiology, and the Department of Psychiatry, Minneapolis VA Health Care System, and the Department of Medicine, University of Minnesota, Minneapolis; and the VA Center for Medication Safety, Hines, Ill.
authors.forename: Eric
authors.initials: E
authors.lastname: Dieperink
mesh_terms: D000328:Adult; D000368:Aged; D002423:Cause of Death; D015283:Citalopram / Q000008:administration & dosage* / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D029593:Jervell-Lange Nielsen Syndrome / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012306:Risk; D014728:Veterans
chemical_list: D015283:Citalopram