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 (PՆ.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.

INCE THE EARLY 1990S, STUDIES have reported prevalences of major depression between 17% and 27% in hospitalized patients with coronary artery disease (CAD). 1 Most have also demonstrated that depression has a negative cardiac prognostic impact. 2,3 Only 1 large randomized trial, the Enhancing Recovery in Coronary Heart Disease (ENRICHD) study, 4 has tried to determine whether treating depression could improve cardiac prognosis in CAD patients. Although ENRICHD demonstrated that a combination of short-term individual cognitive behavior therapy (CBT) and a selective serotonin reuptake inhibitor (SSRI), when needed, was significantly better than usual care at reducing depressive symptoms over 6 months in depressed or socially iso-For editorial comment see p 411.

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Objective: To examine whether selective serotonin reuptake inhibitor (SSRI) antidepressants were associated with an increased or decreased risk of cardiovascular adverse events (AEs). Methods:We conducted a systematic review of randomized controlled trials published between 1967 and May 2005 that treated patients with cardiac disease, diabetes mellitus, stroke, geriatric age, nicotine dependence, alcoholism, HIV infection, and obesity. We defined serious AEs as death due to a cardiovascular cause, heart failure, stroke, transient ischemic attack, and myocardial infarction. Nonserious AEs were defined as palpitations, chest pain, angina, arrhythmia, hypertension, hypotension-syncope, and unspecified cardiovascular or neurologic events. Adverse event rates were calculated in 4 groups: SSRIs, tricyclic antidepressants (TCAs), other active therapies, and placebo.Results: Stroke and cardiac patients were the highest-risk groups for cardiovascular AEs. We were unable to detect differences in odds between SSRI and placebo for both serious (odds ratio [OR] 0.69; 95% confidence interval [CI], 0.39 to 1.21) and nonserious (OR 1.18; 95%CI, 0.90 to 1.57) cardiovascular AEs. There was a significant decrease in the odds of nonserious cardiovascular AEs (OR 0.46; 95%CI, 0.24 to 0.86, P = 0.02) for patients receiving SSRIs, compared with TCAs. Over one-half of the selected trials did not report the presence or absence of cardiovascular events. Conclusions:This systematic review of antidepressant trials in high-risk patients did not determine whether SSRIs are associated with a greater or lesser risk of cardiovascular AEs. Reasons for this conclusion include the rarity of serious AEs, the lack of large trials in these patients, and a lack of adequate reporting of AEs in published trials. Further trials assessing the risk of cardiovascular AEs and better trial reporting are needed. Limitations· This review could not determine whether SSRIs are associated with an increased or decreased risk of cardiovascular AEs in patients at risk because of inadequate reporting in clinical trials. · There is a lack of large trials involving patients at risk for cardiovascular AEs who are taking SSRIs.