According to background information in the article, major depressive disorder occurs in 15 percent to 23 percent of patients with acute coronary syndromes and constitutes an independent risk factor for illness and death. However, no published evidence exists that antidepressant drugs are safe or efficacious in patients with unstable ischemic heart disease.

In the randomized, double-blind, placebo-controlled trial, which was conducted in 40 outpatient cardiology centers and psychiatry clinics in the United States, Europe, Canada, and Australia, a total of 369 patients with major depressive disorder (64 percent male; average age, 57.1 years; MI, 74 percent; unstable angina, 26 percent) were enrolled.

After a two-week single-blind placebo period, patients were randomly assigned to receive sertraline in flexible dosages of 50 to 200 mg daily (n = 186) or placebo (n = 183) for 24 weeks.

The authors wrote, "We found no evidence of harm: Sertraline was indistinguishable from placebo across all surrogate measures of cardiovascular safety. Treatment was not associated with any change in left ventricular ejection fraction, blood pressure, heart rate, arrhythmias ... Furthermore, though not statistically significant, the incidence of severe cardiac events, the 'gold standard' for cardiac safety, was numerically lower among patients receiving sertraline than those receiving placebo."

The authors add that in the group with at least one prior episode of depression, and in the more severe major depressive disorder group, scores measuring depression were significantly better in those assigned to sertraline.

According to the authors, "More than a million individuals in the United States experience acute coronary syndrome each year and approximately 20 percent of these persons will also experience major depression, which imparts a three-fold increase in the risk of morbidity and mortality. Even a modest reduction in risk, given the prevalence of these two conditions, would have significant public health consequences. ... Depression that recurs or persists in acute coronary syndrome should be identified and treated because it is a serious illness that is both painful to patients and impedes their medical care."

In an accompanying editorial, Robert M. Carney, Ph.D., of Washington University School of Medicine, St Louis, and Allan S. Jaffe, M.D., of Mayo Clinic, Rochester, Minn., write that "although not without flaws, the [Glassman et al study] is truly an important trial. It provides the first real evidence that at least one of the [serotonin selective] antidepressants, sertraline, is safe for use soon after an acute myocardial infarction or an episode of unstable angina, and that it is an efficacious treatment, at least for relatively severe, recurrent depression. This is a major step forward in the care of depressed patients with coronary heart disease. There is now an alternative to ignoring a comorbid psychiatric disorder that often has devastating consequences for these patients."

They continue: "Based on what has been learned from [this and other trials], future trials of treatment for depression in the context of acute coronary syndromes should attempt to recruit only patients who have depression that is unlikely to remit without treatment. A careful analysis of these data should provide some information about the characteristics of such patients.

"Whether the risk of cardiac mortality and morbidity can be reduced by treating depression is an open question. However, depression is associated with significant psychological, social, and functional impairment. There is evidence that treating depression improves the quality of life and overall functioning of depressed patients seen in primary care settings. We hope that the results of this important study will encourage physicians to recognize and appropriately treat depression in patients with heart disease."