July 5, 2005 STANFORD, Calif. - The use of antidepressants in patients who have suffered a heart attack appears to reduce the risk of recurrent events and cardiac death, according to a large, multi-center study conducted by the National Heart, Lung and Blood Institute. The findings suggest that post-heart attack patients who suffer from depression should talk with their physicians about taking the medication.
"Our study provides much stronger evidence than we've ever had before that antidepressants are safe and may benefit these patients," said C. Barr Taylor, MD, professor of psychiatry and behavioral sciences at the Stanford University School of Medicine and lead author of the paper published in the July issue of Archives of General Psychiatry.
Cardiovascular disease, the leading cause of death, major morbidity and disability in the United States, is often linked with depression: according to past studies, 20 percent of patients with coronary heart disease suffer from major depression and 20 percent from minor depression. Studies have also shown that depression among post-heart attack patients is associated with death and recurrent heart attacks.
Researchers launched the ENRICHD (ENhancing Recovery In Coronary Heart Disease) study to determine whether cognitive behavioral therapy would impact mortality and morbidity in post-heart attack patients with depression. Following publication of their findings that cognitive therapy significantly reduced depression but had little effect on mortality rates, the researchers conducted a secondary analysis on the use of antidepressants among the study participants.
"Our initial results were published in JAMA, and there was some evidence that the participants on antidepressants had decreased morbidity and mortality," said Taylor. "Once we saw the effect we wanted to examine it more thoroughly."
The ENRICHD study, which is the largest psychotherapy trial in coronary patients to date, involved 1,834 depressed or "socially isolated" post-heart attack patients (985 men and 849 women). The participants were enrolled during a three-year period (October 1996-October 1999) and randomized to the therapy group or the control group.
Patients who received therapy participated in a series of individual and group sessions delivered over six to nine months. Those patients who had more severe depression or who didn't respond after five weeks of treatment were also given sertraline hydrochloride (Zoloft). If antidepressants were still needed at the end of the study, patients were referred to physicians for subsequent treatment.
Taylor and his colleagues at eight study sites used patient interviews and records, hospital records and/or participants' physicians to conduct follow-up evaluations six months after randomization and annually after that. By the end of the follow-up, 28 percent of the participants who had received therapy had used antidepressants, and 20 percent of participants in the control group had. The median duration of antidepressant use was 12 months for both groups, and participants were most likely to take selective serotonin reuptake inhibitors, or SSRIs, such as Zoloft instead of tricyclics or other types.
After analyzing the data, the researchers found that 26 percent of study participants who hadn't received antidepressants died or had a recurrent heart attack, while 21 percent of those participants who had taken antidepressants at some point died or had a recurrent event. After adjusting for baseline depression and cardiac risk, SSRI use was associated with 43 percent lower risk of death or recurrent non-fatal heart attack, and 43 percent lower risk of death from all causes.
"The results basically suggest that these medications are very useful for patients who have had heart attacks and are depressed," said Taylor, adding that he would recommend that any post heart-attack patient with depression be evaluated for treatment.
While encouraged by the results, Taylor pointed out that the study does have limitations. Because the study was not designed to evaluate the use of antidepressants, its findings are observational. The researchers also lacked a direct measure of when exactly patients took the antidepressants.
The authors noted that the results of the study show a need for a prospective, randomized trial on the safety and benefit of antidepressants in this population.
Taylor is also now analyzing results of a related study, called IMPROVE (IMProve mood/Reduce risk Of Vascular Events), which examined the relationship between depression and cardiovascular physiology, risk factors and biological variables. The study focused on people who are more depressed than those in the ENRICHD study and who have not had a previous cardiovascular event.
The ENRICHD study was funded by the National Heart, Lung and Blood Institute. Robert F. DeBusk, MD, professor of medicine, served as principal investigator at the Stanford site.
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