Sertraline Treatment of Major Depression in Patients With Acute MI or Unstable Angina
- Alexander H. Glassman, MD;
- Christopher M. O'Connor, MD;
- Robert M. Califf, MD;
- Karl Swedberg, MD;
- Peter Schwartz, MD;
- J. Thomas Bigger, Jr, MD;
- K. Ranga Rama Krishnan, MD;
- Louis T. van Zyl, MD;
- J. Robert Swenson, MD;
- Mitchell S. Finkel, MD;
- Charles Landau, MD;
- Peter A. Shapiro, MD;
- Carl J. Pepine, MD;
- Jack Mardekian, PhD;
- Wilma M. Harrison, MD;
- for the Sertraline Antidepressant Heart Attack Randomized Trial (SADHART) Group
- Author Affiliations: Department of Clinical Psychopharmacology, New York State Psychiatric Institute, New York (Dr Glassman); Departments of Psychiatry (Drs Glassman and Shapiro) and Medicine (Dr Bigger), Columbia University College of Physicians and Surgeons, New York, NY; Departments of Cardiology (Drs O'Connor and Califf) and Psychiatry (Dr Krishnan), Duke University Medical Center, Durham, NC; Department of Medicine, Goteborg University, Goteborg, Sweden (Dr Swedberg); Department of Cardiology, IRCCS Policlinico San Mateo and University of Pavia, Pavia, Italy (Dr Schwartz); Department of Psychiatry, Queens University, Kingston, Ontario (Dr van Zyl); Ottawa Heart Institute and Department of Psychiatry, University of Ottawa, Ottawa, Ontario (Dr Swenson); Department of Medicine, West Virginia University School of Medicine, Morgantown (Dr Finkel); Cardiac Associates of Southern Connecticut, Bridgeport (Dr Landau); Division of Cardiovascular Medicine, University of Florida, Gainesville (Dr Pepine); and Pfizer Inc, New York, NY (Drs Mardekian and Harrison).
Abstract
Context Major depressive disorder (MDD) occurs in 15% to 23% of patients with acute coronary syndromes and constitutes an independent risk factor for morbidity and mortality. However, no published evidence exists that antidepressant drugs are safe or efficacious in patients with unstable ischemic heart disease.
Objective To evaluate the safety and efficacy of sertraline treatment of MDD in patients hospitalized for acute myocardial infarction (MI) or unstable angina and free of other life-threatening medical conditions.
Design and Setting Randomized, double-blind, placebo-controlled trial conducted in 40 outpatient cardiology centers and psychiatry clinics in the United States, Europe, Canada, and Australia. Enrollment began in April 1997 and follow-up ended in April 2001.
Patients A total of 369 patients with MDD (64% male; mean age, 57.1 years; mean 17-item Hamilton Depression [HAM-D] score, 19.6; MI, 74%; unstable angina, 26%).
Intervention After a 2-week single-blind placebo run-in, patients were randomly assigned to receive sertraline in flexible dosages of 50 to 200 mg/d (n = 186) or placebo (n = 183) for 24 weeks.
Main Outcome Measures The primary (safety) outcome measure was change from baseline in left ventricular ejection fraction (LVEF); secondary measures included surrogate cardiac measures and cardiovascular adverse events, as well as scores on the HAM-D scale and Clinical Global Impression Improvement scale (CGI-I) in the total randomized sample, in a group with any prior history of MDD, and in a more severe MDD subgroup defined a priori by a HAM-D score of at least 18 and history of 2 or more prior episodes of MDD.
Results Sertraline had no significant effect on mean (SD) LVEF (sertraline: baseline, 54% [10%]; week 16, 54% [11%]; placebo: baseline, 52% [13%]; week 16, 53% [13%]), treatment-emergent increase in ventricular premature complex (VPC) runs (sertraline: 13.1%; placebo: 12.9%), QTc interval greater than 450 milliseconds at end point (sertraline: 12%; placebo: 13%), or other cardiac measures. All comparisons were statistically nonsignificant (P≥.05). The incidence of severe cardiovascular adverse events was 14.5% with sertraline and 22.4% with placebo. In the total randomized sample, the CGI-I (P = .049), but not the HAM-D (P = .14), favored sertraline. The CGI-I responder rates for sertraline were significantly higher than for placebo in the total sample (67% vs 53%; P = .01), in the group with at least 1 prior episode of depression (72% vs 51%; P = .003), and in the more severe MDD group (78% vs 45%; P = .001). In the latter 2 groups, both CGI-I and HAM-D measures were significantly better in those assigned to sertraline.
Conclusion Our results suggest that sertraline is a safe and effective treatment for recurrent depression in patients with recent MI or unstable angina and without other life-threatening medical conditions.
