Depression—A Cardiac Risk Factor in Search of a Treatment
Authors: Nancy Frasure-Smith
Journal: JAMA (2003)

THE ENHANCING RECOVERY IN CORONARY HEART DISease Patients (ENRICHD) trial published in this issue of THE JOURNAL is the largest controlled trial of psychotherapy ever completed. In this study, the first multisite behavioral trial funded by the National Heart, Lung, and Blood Institute (NHLBI), the ENRICHD investigators enrolled 2481 post–myocardial infarction (MI) patients from 73 hospitals in 8 US cities in a 6-month course of weekly cognitive behavior therapy (CBT) vs usual care. Three quarters of the study patients had depression, with the remainder included because of low perceived social support (LPSS). The goal was to determine whether treating depression and LPSS would reduce mortality and recurrent infarction. The intervention produced small, statistically significant decreases in depression symptoms and small, significant increases in perceived support. These differences did not translate into any benefit in event-free survival during a mean follow-up of 29 months, so the study is a negative trial. However, much was learned over the course of the ENRICHD trial, and more will be learned as the investigators and others try to understand why results were not as expected. The study also demonstrates that psychologists, psychiatrists, and cardiologists can successfully collaborate to test complicated intervention protocols with large numbers of patients from multiple sites. For these reasons, the ENRICHD trial will remain a standard of comparison for many years. Based on the investigators’ previous publications, as well as the current study, the key assumptions behind the ENRICHD trial were as follows: (1) depression and LPSS are causally related to cardiac mortality and MI recurrence in post-MI patients; (2) these relationships are strong enough to suggest that, with sufficient improvements in depression andLPSS,combinedevent ratesover36monthscanbereduced by at least 30%; (3) these relationships are true regardless of sex, ethnicity, or socioeconomic status; (4) the impact of depression and LPSS is apparent soon after hospital discharge, so intervention needs to be instituted early; (5) it is possible to screen for depression and LPSS during hospitalization, enroll most individuals at apparent risk, and ensure their compliancewithweekly therapysessionsbeginningsoon after discharge; (6) 6 months of individual CBT and group sessions (supplemented by antidepressant treatment for those not responding by 5 weeks) can have a large enough, sustained impact on depression symptoms and LPSS to result in the hypothesized 30% decrease in cardiac events over 36 months; and (7) attending physicians will recognize and treat depression in only a small minority of the usual care group. Because of the disappointing results of this trial, it is important to reconsider these assumptions. In 1994, when the ENRICHD trial was designed, the number of studies suggesting a link between social support and post-MI prognosis was similar to the number implicating depression. However, the studies of social support differed widely in the ways in which support was conceptualized. Was the important variable marital status, living alone, lack of a confidant, poor perceived support, or a small number of close friends? The fact that the ENRICHD investigators had to develop a new measure to screen for LPSS and to develop a new, untested form of CBT to try to treat it, suggests that it was premature to include LPSS. This is not to refute the importance of social factors in post-MI recovery, but to emphasize that the understanding of their role in cardiac prognosis was, and remains, insufficient to target them in an intervention trial. When the ENRICHD trial was designed, the reported relative risks associated with post-MI depression were high, the confidence intervals were wide, and the follow-up periods did not exceed 18 months. Since then, several studies have confirmed the prognostic importance of depression in patients with established coronary artery disease (CAD). A recent review also concluded that depression is a risk factor for incident CAD in previously healthy patients. However, not all studies have been positive, suggesting that the long-term risk associated with depression may be lower than originally