Psychiatrists should know that antidepressants, especially selective serotonin reuptake inhibitors, decrease the risk for recurrent myocardial infarction and death in depressed patients who have had a myocardial infarction, according to an article in the July issue of Archives of General Psychiatry.
Major depression is found in approximately 20 percent of patients with a recent myocardial infarction, with minor depression found in another 20 percent. Depression is a risk factor for recurrent non-fatal infarction as well as cardiac death in patients who have an acute myocardial infarction, independent of cardiac disease severity. Despite their effectiveness in treating depression, the use of antidepressants in this patient population remains controversial.

C. Barr Taylor, M.D., from Stanford Medical Center, Stanford, Calif., and colleagues conducted a secondary analysis of data from the Enhancing Recovery in Coronary Heart Disease (ENRICHD) clinical trial to determine the effects of antidepressants on post-infarction patients. The ENRICHD trial randomized 2,481 depressed and/or socially isolated patients from October 1, 1996 to October 31, 1999.

The analysis in the current report is based on 1834 patients (985 men and 849 women) who had depression, with or without low social support. Of these, 446 patients took antidepressants during the study, including 301 who were prescribed a selective serotonin reuptake inhibitor and 145 patients who were prescribed other types of antidepressants.

During an average follow-up of 29 months, 457 fatal and non-fatal cardiovascular events occurred. Twenty-six percent (361/1388) of the patients who did not receive antidepressants died or had a recurrent myocardial infarction compared with 21.5 percent (96/446) of patients who took antidepressants.

After adjusting for baseline depression and cardiac risk, use of a selective serotonin reuptake inhibitor (SSRI) was associated with a 43-percent lower risk of death or recurrent non-fatal infarction and 43-percent lower risk of death from all causes compared with patients who did not use an antidepressant in this class. Risk of death or recurrent infarction, all-cause death, or recurrent myocardial infarction was 28 percent, 36 percent, and 27 percent lower, respectively, in patients taking non-SSRI antidepressants compared with non-antidepressant users.

"The main finding of this study is that antidepressant use post-acute myocardial infarction by depressed patients in the ENRICHD clinical trial was associated with significantly lower rates of the study primary end points, death and reinfarction," the authors wrote.

In an editorial accompanying this study, Alexander H. Glassman, MD, of the New York State Psychiatric Institute, wrote that in the ENRICHD trial "only the most depressed patients, those known to be at higher risk for cardiac events, were offered antidepressants. In addition, there was no control over when the drug was started or stopped, and even the reported start and stop times were only estimates. However, the sample was large, the number of events reasonable, and the magnitude of the effect is hard to ignore.

Had the ENRICHD study observed an uncontrolled 40 percent increase in mortality with antidepressant drug treatment, public advocates would be clamoring for review by the Food and Drug Administration, label changes, or even 'black box' warnings. Yet this observation of a 40 percent decrease in life-threatening outcomes has been in the literature for almost three years with no systematic follow-up and minimal medical or psychiatric awareness."

"There are multiple mechanisms by which depression could increase vascular disease," Dr. Glassman writes. "It increases platelet activation and inflammatory markers, reduces heart variability, and leads to multiple adverse health behaviors; all are associated with increased cardiovascular risk and death. Whatever links depression and heart disease, it is more likely to involve all of the above rather than any single pathway."

"Acknowledging the implications of major depressive disorder for cardiac morbidity and mortality would validate depression as a systemic disease with implications for the entire body, and reduce the stigma of this diagnosis for medical professionals, the public, and the patients themselves," Dr. Glassman concluded. "The ENRICHD investigators have made a significant step in that direction."