Enhancing Recovery in Coronary Heart Disease - ENRICHD


The goal of the Enhancing Recovery in Coronary Heart Disease (ENRICHD) trial was to evaluate whether treatment of depression and low perceived social support (LPSS) with cognitive behavior therapy (CBT), supplemented with a selective serotonin reuptake inhibitor (SSRI) antidepressant, reduces mortality and recurrent infarction in patients with myocardial infarction (MI).


Treatment of depression and low social support early after an acute MI will reduce death and nonfatal recurrent infarctions.

Study Design

Study Design:

Patients Screened: 33,780
Patients Enrolled: 2,481
Mean Follow Up: average 3.4 years
Mean Patient Age: mean age 61 years
Female: 44%
Mean Ejection Fraction: Severe dysfunction: 25% in usual care arm and 26% in treatment arm

Patient Populations:

Men and women recruited within 28 days post-acute MI; initial diagnosis of acute MI: enzyme increases 2 x upper limit of normal (except for creatine kinase-MB, for which any elevation with a rising/falling pattern indicative of acute MI was found) and either symptoms compatible with acute MI or characteristic evolution electrocardiographic ST-T changes or new Q waves; if marker criteria are not met, patients are also eligible if they underwent acute intervention for ST elevation upon presentation; and identification of major or minor depression based on DSM-IV criteria and/or low social support


Acute MI occurring after coronary artery bypass graft surgery or percutaneous transluminal coronary angioplasty; noncardiac condition likely to be fatal within one year; medical condition limiting ability to participate; major psychiatric comorbidity (e.g., schizophrenia); immediate suicide risk; unwilling to provide informed consent; unable to complete screening visits; and inaccessible for intervention and follow-up

Primary Endpoints:

Recurrent MI or death from any cause

Secondary Endpoints:

Recurrent nonfatal MI, death from any cause, cardiac death, revascularization procedures, cardiovascular hospitalizations, and change in Hamilton Rating Score (for depression) or ENRICHD Social Support Instrument scores (for LPSS)

Drug/Procedures Used:

Patients were randomized to usual medical care (n=1,243) or CBT-based psychosocial intervention (n=1,238), focusing on behavioral activation, cognitive restructuring, social skills training, and mobilization of social resources. Trained counselors conducted sessions over a six-month period. Patients began with individual therapy, which could be supplemented by group therapy. Patients who were severely depressed (scored >24 on a severity depression rating scale or did not respond adequately to CBT) were referred and evaluated for pharmacotherapy with an SSRI.

Concomitant Medications:

Sertraline (50 mg/d and adjusted to a maximum of 200 mg/d if deemed necessary by the treating psychiatrist) in severely depressed patients

Principal Findings:

There were no significant differences in the primary endpoint of recurrent MI or all-cause mortality between the groups (24.1% for usual care vs. 24.2% for the intervention arm, hazard ratio 1.01, 95% confidence interval 0.86-1.18), nor was there any difference between the groups when looking only at the low social support or depression cohorts.

At six months and an average of 10 sessions by trained counselors, there was a modest but significant intervention improvement in psychosocial measures. For patients with low social support, the ESSI score was significantly higher in the intervention arm (24.4 vs. 22.6 in the usual care group, p<0.001). Among depressed patients, the Hamilton depression severity score was 7.6 among the intervention group versus 9.4 for usual care (p<0.001). The change in scores from baseline to six months were also modestly but significant improved, with the ESSI scores changing by 5.1 versus 3.4 and the Hamilton scores –10.1 versus –8.4 (p<0.001 for each).

Among demographic subgroups (gender and minority status) for which researchers had preplanned analyses, there were no significant effects, although data trended toward a negative effect among the female patients, and a benefit in the male patients.


Among patients experiencing an acute MI, treatment of depression and LPSS with CBT was not associated with a reduction in the primary endpoint of all-cause mortality or recurrent MI. Epidemiological evidence suggests that the absence of social support is a risk factor for cardiac morbidity and mortality. It is estimated that the prevalence of such low social support is 15% to 25% among MI patients, with the adjusted risk for mortality or cardiovascular morbidity ranging from 2.0 to 4.0. Other studies indicate depression predicts survival as well. The prevalence of major depression is about 20% in coronary heart disease patients, with adjusted risks increasing by 2.2 to 4-fold or more. Thus, both depression and social isolation increase mortality and morbidity by the same order of magnitude as many important clinical prognostic indicators.

While the epidemiological data are strong, the evidence that psychosocial interventions in general can improve prognosis is mixed, with some studies showing significant effect and others showing none. In either case, however, there are no trials to date that have investigated whether treating depression and social support improves survival and decreases cardiac risk in post-MI patients.

The investigators noted that the most likely explanation for the lack of benefit with the intervention therapy seen in the ENRICHD trial is the modest difference in psychosocial measures between the groups after treatment. Response in the treated group was substantial and characteristic of that seen in other trials of depression; however, improvement in measures of social isolation and depression in untreated patients has not previously been reported. While therapy could have included more sessions, been more tailored to specific groups, or included more group sessions, the results suggest that CBT was efficacious. What is unclear is the reason for such improvement in the usual care group, which is in contrast to prior data in an acute MI setting.

Another hypothesis is that involvement in the trial led the usual care group to seek help outside of the trial. By six months, many of the usual care patients were on psychotropic agents, and nearly half indicated they had acquired the skill set normally associated with CBT.

In ENRICHD, 50% of all events occurred within the first six months, two-thirds of which were within the first three months. However, approximately 17 days passed before patients started therapy; if therapy required several weeks to influence psychosocial substrate with yet more time required to induce changes in the brain, the intervention may have taken too long to influence the early hazard of many of the events.


Writing Committee for the ENRICHD Investigators. Effects of Treating Depression and Low Perceived Social Support on Clinical Events After Myocardial Infarction: The Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) Randomized Trial. JAMA 2003;289:3106-16.

Clinical Topics: Heart Failure and Cardiomyopathies

Keywords: Depression, Myocardial Infarction, Depressive Disorder, Serotonin Uptake Inhibitors, Creatine Kinase, Diagnostic and Statistical Manual of Mental Disorders, Social Support, Social Isolation, Counseling, Psychotherapy, Group, Cognitive Therapy

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