By definition, medical researchers test their hypotheses because they are uncertain whether a procedure or medication will actually help patients combat illness. So when a promising technique fails to meet expectations, doctors then know that a particular treatment may not deliver, and that it is time to test other methods. But when an eight-year, multicenter study that cost nearly $30 million failed to show that cognitive-behavioral therapy (CBT) and enhanced social support following a heart attack had an effect on survival or the likelihood of recurrent cardiac events, it left investigators puzzling over what went wrong and what to do next.
Even the study's acronym, ENRICHD, which stands for Enhancing Recovery in Coronary Heart Disease patients, evoked the confidence teams of researchers brought to a project that ultimately enrolled nearly 2,500 subjects within 28 days of a heart attack. Those patients, recruited from 1996 to 1999, came from 73 hospitals affiliated with eight clinical centers across the country. Once evaluated with depression, low social support or both, patients were randomized to either receive usual care or a CBT-based psychosocial intervention. The researchers hypothesized that members of the treatment group would live longer and suffer fewer future cardiac events.
They didn't. In June, researchers published the results of the ENRICHD randomized trial in JAMA (289:3106-3116), concluding that the therapy-based intervention had no effect on mortality and did not reduce cardiac events during an average 29-month follow-up period. That result, however, was tempered by a finding that those patients who took a selective serotonin reuptake inhibitor antidepressant did have a lower risk of dying or non-fatal myocardial infarction. The antidepressant use, which was not randomized and was provided to patients who needed them in both groups, has now raised new questions about the way heart attack victims should be treated in a system that already shortchanges their mental health care needs.
In the aftermath of the study's negative results, researchers are shrugging off their disappointment and attempting to understand why patients who received treatment for depression failed to respond with longer lives or fewer heart attacks. With prior studies establishing a link between depression and low perceived social support (LPSS) and cardiac mortality and morbidity, it seemed likely that providing a mental health intervention would yield improvement. The treatment did help alleviate the group's depression and lack of social supports, raising the question of whether quality-of-life enhancement should have been the appropriate endpoint of the study.
"The questions of survival and cardiac events are still important questions," said Susan Czajkowski, Ph.D., ENRICHD's project officer and a research psychologist with the National Heart, Lung and Blood Institute (NHLBI), the agency that funded the study. She told Psychiatric Times, "One way of looking at ENRICHD is that it was a specific type of intervention for a specific group patients and a very specific time point in the course of disease, which was immediately after the myocardial infarction ... Therefore, what we are doing right now is taking a look and thinking about the parameters of that and whether there might be better or longer interventions at different time points in cardiovascular disease, and whether there might be different kinds of patients that might benefit."
That scientific soul-searching could be important because of the data that indicated treatment with an SSRI antidepressant could generate the survival and anti-recurrence effect sought by investigators. For the time being, the finding has raised more questions about what care heart attack patients should receive, since the use of antidepressants may have been a confounding factor that yielded the negative results in the ENRICHD study.
The antidepressant medication became a confounding factor by possibly masking the benefits of therapy, said Ranga Krishnan, M.D., chair of psychiatry at Duke University School of Medicine, one of the clinical centers involved in the study. Meanwhile, because administration of antidepressants was not randomized, the findings relating to the benefits of SSRI use could not be confirmed with a high degree of confidence.
"It is fair to conclude that [talk therapy] will treat depression but not the problem," Krishnan told PT. "At this point in time, probably the most positive way of putting is to say you can't tell one way or another whether it will affect survival and there's no data to support that it will affect survival." Since the CBT-based intervention helped treat the depression, however, it should not be rejected as a possible therapeutic intervention, particularly because there are individuals who will not take medication, he added.