SSRI use associated with increased risk for heart patients

In a surprising finding, patients with coronary artery disease who take commonly used antidepressant drugs may be at significantly higher risk of death, Duke University Medical Center researchers have found.

Even after controlling for such factors as age, degree of heart disease and severity of depression, the researchers found that heart patients taking antidepressant medications had a 55 percent higher risk of dying. Previously, Duke researchers reported that the presence of depression is an important risk factor for heart patients. This new finding of the risk from anti-depressants raises issues about the optimal way to treat depression in cardiac patients, the researchers said.

According to Duke team leader Lana Watkins, Ph.D., the researchers believe their findings add further support for the potential role oft non-pharmocological approaches to treating depression, such as exercise, in reducing the risk of death in depressed heart patients. She said that physicians caring for heart patients who are taking antidepressants should monitor patients closely.

Watkins added that the design of the study prevents definitive conclusions regarding the effects of antidepressant drugs. In the current observational study, patients were not randomized to receive an antidepressant or a placebo drug, therefore characteristics of the patients, such as more likelihood for their depression or their medical condition to worsen, may be responsible for the effects, she said.

Randomized placebo-controlled trials are needed to not only replicate the Duke findings, but to better understand whether antidepressant use is identifying patients likely to have more severe or worsening depression or worsening medical disease during the follow-up period, Watkins added.

"This finding that antidepressant use was an independent risk factor for mortality in patients with coronary artery disease was quite unexpected," said Watkins, who presented the results of the Duke study March 4, 2006, at the annual meeting of the American Psychosomatic Society in Denver. The research was supported by the National Heart, Lung, and Blood Institute.

"We were surprised since antidepressants, particularly the newer class of antidepressants known as selective serotonin reuptake inhibitors (SSRI), have been generally considered safe," Watkins said. "However, even after taking into account many patient variables, as well as the type of antidepressant, the risk still remained. So there is something important going on here that we don't fully understand."

During the past decade, cardiologists and physicians have gained a greater appreciation that depression should be considered as an important risk factor for patients with coronary artery disease, said the researchers. For this reason, they have increasingly prescribed antidepressants for these patients; however, this increase in use has not been accompanied by conclusive scientific data on the effects of antidepressants - especially SSRIs - on mortality.

For her study, Watkins prospectively analyzed the clinical data of 921 Duke University Hospital patients receiving a cardiac angiography procedure to determine the extent of blockage in their coronary arteries. Of the total number of patients, just under one in five (19.4 percent) were taking an antidepressant; with SSRIs being taken by 66 percent of those patients.

During their hospitalization, patients were given the Beck Depression Inventory (BDI), a commonly used depression screening test. In general, patients with a BDI score of 10 or higher are considered depressed. In the Duke study, those patients who were not taking antidepressants had an average BDI score of 7, while those on antidepressants had an average score of 11, a statistically significant difference.

The patients were followed over an average of three years, and during that time 21.4 percent of the patients who were taking antidepressants had died, compared to 12.5 percent for those not on antidepressants.

After adjusting for such factors as age, gender, heart pumping strength, smoking history, degree of other illnesses, heart procedures, BDI score and education, the researchers found that patients taking antidepressants had a 55 percent higher risk of dying. The difference between SSRI and non-SSRI use - 61 percent vs. 49 percent - was not statistically significant.

Watkins said the future studies are needed to uncover the reasons responsible for depression's negative effect on mortality. Also, she said, researchers do not fully understand the physiological effects of SSRIs on patients with coronary artery disease.

While physicians do not know why there appears to be a link between depression and increased risk of mortality, there are a number of theories, said Watkins. Depression has been linked to supression of the immune system, as well as alteration of the aggregation properties of blood platelets. It has also been linked to other such cardiovascular risk factors as insulin resistance, hypertension, obesity, increased cigarette smoking, alcohol abuse and physical inactivity, she noted.

In April, Duke investigators will begin enrolling depressed patients in a randomized trial testing the abilities of exercise and SSRIs to impact such physiological markers of coronary artery disease as platelet aggregation, heart rate variability and baroreflex sensitivity, or the ability of blood vessel walls to respond appropriately to changes in blood pressure.

Other Duke colleagues on the study included James Blumenthal, Ph.D., Jonathan Davidson, M.D., Charles McCants, Christopher O'Connor, M.D. and Michael Sketch, M.D.