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Of the 1 million Americans hospitalized each year for a heart attack, about 20 percent will also suffer from depression that puts them at triple the risk of dying. Yet most of these patients are not treated with antidepressants because older antidepressants were known to be cardiotoxic and the effects of the new antidepressants were unknown.

In the first study of an SSRI (selective serotonin reuptake inhibitor) antidepressant in 369 depressed patients recently hospitalized for heart attack, the drug sertraline (Zoloft) has been found to be safe and effective. In this limited-size trial, researchers also noted less life- threatening cardiac events in patients taking Zoloft compared with those on placebo, but the difference was not statistically significant.

The findings of the study, which took place at 40 medical centers throughout the world, were published in the Aug. 14 issue of the Journal of the American Medical Association. The landmark trial paves the way for a larger trial to determine if sertraline treatment reduces death and recurrent heart attack.

"Doctors have been afraid to prescribe antidepressants to heart patients," says Dr. Alexander Glassman, professor of clinical psychiatry at P&S, staff member at the New York State Psychiatric Institute, and the paper's lead author and co-principal investigator. "But our results are very reassuring about the safety of sertraline. It's OK to go ahead and prescribe the drug to treat the depression." Dr. Christopher O'Connor, associate professor of cardiology at Duke University Medical Center, was also co-principal investigator.

Although depressed patients are three times more likely to die after their first hospitalization for a heart attack than patients who are not depressed, doctors do not prescribe antidepressants to people with heart conditions. The older tricyclic drugs are dangerous for heart patients and, until now, no studies using SSRIs, a newer class of antidepressants, had been performed in a population of patients who recently experienced a heart attack. Studies with SSRIs in depressed patients a year after hospitalization for a heart attack showed SSRIs were safe, but the heart is unstable right after an injury like a heart attack and many drugs are dangerous to use.

In the new research, 369 patients who had been hospitalized for heart attack or impending attack and suffered from depression were given sertraline or a placebo. After six months, researchers saw no difference between the two groups with respect to their heart condition, indicating the drug was safe.

The results also showed the drug was effective in treating depression if the patient had a history of the disorder. In patients with a history of two prior episodes of depression, sertraline improved symptoms in 78 percent of patients while only 45 percent improved on placebo. Almost no difference was seen between the drug and the placebo in patients who had never experienced a bout of depression before their hospitalization.

"The primary goal of the research was to make sure the drug is safe and effective and it is extraordinarily safe," Dr. Glassman says. "The real surprise was there was a 23 percent reduction in life-threatening cardiovascular events in people taking the drug."

Dr. Glassman cautions that the 23 percent figure is not statistically significant, but is supported by epidemiological studies that show people taking SSRIs for depression are less likely to develop heart attacks.

"We need to follow our lead and determine whether sertraline reduces life- threatening events by conducting a much larger clinical trial now that we know it is safe to do so," Dr. Glassman says. "In the meantime, it's important for doctors with depressed heart patients to know that they can safely treat the depression."

Pfizer Inc., which manufactures Zoloft, was the major sponsor of the study, which was initiated by the investigators and not by the company. The National Institutes of Health and the New York State Department of Mental Hygiene also contributed.


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