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Original Investigation
July 24/31, 2018

Effect of Escitalopram vs Placebo Treatment for Depression on Long-term Cardiac Outcomes in Patients With Acute Coronary SyndromeA Randomized Clinical Trial

Author Affiliations
  • 1Department of Psychiatry, Chonnam National University Medical School, Republic of Korea
  • 2King’s College London, Institute of Psychiatry, Psychology and Neuroscience, London, England
  • 3South London and Maudsley NHS Foundation Trust, London, England
  • 4Department of Cardiology, Chonnam National University Medical School, Republic of Korea
JAMA. 2018;320(4):350-358. doi:10.1001/jama.2018.9422
Key Points

Question  Does antidepressant treatment of depression shortly after acute coronary syndrome improve long-term cardiac outcomes?

Findings  In this randomized clinical trial that included 300 patients with recent acute coronary syndrome and depression, 24-week treatment with escitalopram compared with placebo resulted in an occurrence of major adverse cardiac outcomes of 40.9% vs 53.6% after a median follow-up of 8.1 years, a difference that was statistically significant.

Meaning  Treatment with escitalopram for depression following recent acute coronary syndrome may improve long-term cardiac outcomes.


Importance  Depression has been associated with poorer medical outcomes in acute coronary syndrome (ACS), but there are few data on the effects of antidepressant treatment on long-term prognosis.

Objective  To investigate the effect on long-term major adverse cardiac events (MACE) of escitalopram treatment of depression in patients with recent ACS.

Design, Setting, and Participants  Randomized, double-blind, placebo-controlled trial conducted among 300 patients with recent ACS and depression enrolled from May 2007 to March 2013, with follow-up completed in June 2017, at Chonnam National University Hospital, Gwangju, South Korea.

Interventions  Patients were randomly assigned to receive either escitalopram in flexible dosages of 5, 10, 15, or 20 mg/d (n = 149) or matched placebo (n = 151) for 24 weeks.

Main Outcomes and Measures  The primary outcome was MACE, a composite of all-cause mortality, myocardial infarction (MI), and percutaneous coronary intervention (PCI). Four secondary outcomes were the individual MACE components of all-cause mortality, cardiac death, MI, and PCI. Cox proportional hazards models were used to compare the escitalopram and placebo groups by time to first MACE.

Results  Among 300 randomized patients (mean age, 60 years; 119 women [39.3%]), 100% completed a median of 8.1 (interquartile range, 7.5-9.0) years of follow-up. MACE occurred in 61 patients (40.9%) receiving escitalopram and in 81 (53.6%) receiving placebo (hazard ratio [HR], 0.69; 95% CI, 0.49-0.96; P = .03). Comparing individual MACE outcomes between the escitalopram and placebo groups, respectively, incidences for all-cause mortality were 20.8% vs 24.5% (HR, 0.82; 95% CI, 0.51-1.33; P = .43), for cardiac death, 10.7% vs 13.2% (HR, 0.79; 95% CI, 0.41-1.52; P = .48); for MI, 8.7% vs 15.2% (HR, 0.54; 95% CI, 0.27-0.96; P = .04), and for PCI, 12.8% vs 19.9% (HR, 0.58; 95% CI, 0.33-1.04; P = .07).

Conclusions and Relevance  Among patients with depression following recent acute coronary syndrome, 24-week treatment with escitalopram compared with placebo resulted in a lower risk of major adverse cardiac events after a median of 8.1 years. Further research is needed to assess the generalizability of these findings.

Trial Registration  ClinicalTrials.gov Identifier: NCT00419471