Postmenopausal women who take antidepressants face a small but statistically significant increased risk for stroke and death compared with those who don't take the drugs, new study findings indicate.

The findings are from the federally-funded, multi-institution, Women's Health Initiative Study sponsored by the National Institutes of Health, and the results were published last month in an online edition of Archives of Internal Medicine.

The study examined data from more than 136,000 study participants, age 50 to 79, who weren't taking antidepressants when they enrolled in the study, and who were followed for an average of six years. Data from about 5,500 women who were taking antidepressants at their first follow-up visit were compared with data from 130,800 not taking antidepressants then. The researchers compared the two groups with respect to the incidence of fatal or nonfatal stroke, fatal or nonfatal heart attack and death due to all causes.

The researchers found no difference in coronary heart disease, which was defined in this case as fatal and nonfatal heart attacks. They did observe, though, a significant difference in stroke rates. Antidepressant users were 45 percent more likely to experience strokes than women who weren't taking antidepressants. The study also found that when overall death rates were compared between the two groups, those on antidepressants had a 32 percent higher risk of death from all causes compared with non-users.

The study's senior author, Dr. Sylvia Wassertheil-Smoller, notes that the overall risk for women taking antidepressants is relatively small—a 0.43 percent risk of stroke annually versus a 0.3 percent annual risk of stroke for women not taking antidepressants. However, because antidepressants are among the most widely prescribed drugs in the U.S.—especially among postmenopausal women—small risk increases can have significant implications for large patient populations.

Wassertheil-Smoller, who is head of epidemiology and a professor of epidemiology and population health at the Albert Einstein College of Medicine, at Yeshiva University, in New York City, cautioned that it remains unclear from the data whether antidepressants are solely responsible for the greater mortality rate among users. The link observed in this study between antidepressant use and increased stroke risk for older women might be due partially to the underlying depression, since several studies have found that depression itself is a risk factor for cardiovascular problems.

In their analysis, the researchers tried to control for depression's effects, but they couldn't rule out the possibility that underlying depression in the antidepressant group might be contributing to their increased stroke risk. The study found no difference in stroke risk between the two major classes of antidepressants, selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs). However, the SSRIs did appear to convey a higher risk of hemorrhagic stroke caused by bleeding in the brain.

Antidepressants are valuable drugs for treating a condition that can be debilitating or even fatal. Wassertheil-Smoller advises women who might be concerned about taking their antidepressants based on this study to discuss the matter with their physicians.

"You have to weigh the benefits that you get from these antidepressants against the small increase in risk that we found in this study," she says.

One of the other authors, Dr. Jordan W. Smoller, who is based at the Massachusetts General Hospital, in Boston, says, "While this study did find an association between antidepressants and cardiovascular events, additional research needs to be done to determine exactly what it signifies. Older women taking antidepressants, like everyone else, should also work on modifying their other risk factors for cardiovascular disease, such as maintaining a healthy weight and controlling cholesterol levels and blood pressure."

The researchers also pointed out other limitations to their findings. This was an observational study, so the findings aren't as conclusive in regard to causality as would be the case for a randomized controlled trial, they said, and since the study was comprised primarily of older white women, the findings might not extend to other groups.

Albert Einstein College of Medicine touts itself as one of the nation's premier centers for research, medical education, and clinical investigation. It is home to nearly 2,800 faculty members, 625 M.D. students, 225 Ph.D. students, 125 students in the combined M.D./Ph.D. program, and 380 postdoctoral research fellows. In 2008, Einstein received more than $130 million in support from the National Institutes of Health for funding of research at Einstein in areas such as diabetes, cancer, liver disease, and AIDS.

In addition to researchers from Einstein and Massachusetts General Hospital, the study included researchers from the University of Washington, the University of California San Diego, the University of Hawaii, the University of Iowa, the University of Massachusetts Medical School, and Emory University School of Medicine.