Women participating in the Women's Health Initiative study who reported taking an antidepressant drug had a small but statistically significant increase in the risk of stroke and of death compared with participants not taking antidepressants. The authors of a report in the December 14 Archives of Internal Medicine note that their findings are not conclusive but may signify a need for additional attention to patients' cardiovascular risk factors.
"Depression is a serious illness with its own health risks, and we know that antidepressants can be life-saving for some patients. No one should stop taking their prescribed medication based on this one study, but women who have concerns should discuss them with their physicians," says Jordan W. Smoller, MD, ScD, of the Massachusetts General Hospital (MGH) Department of Psychiatry, the study's lead author. "Older women taking antidepressants can talk with their physicians about their cardiovascular risk, work on modifying other risk factors, and discuss the risks and benefits of various treatment options. We need to study this association more to determine exactly what it signifies."
Depression is a known risk factor for cardiovascular disease and premature death, and one of the reasons that tricyclic antidepressants are used less frequently is their potential for negative effects on heart function. Selective serotonin reuptake inhibitor (SSRI) antidepressants have fewer side effects in general and are known to have aspirin-like effects on bleeding, which could protect against clot-related cardiovascular disorders. Since the use of antidepressants has increased greatly in recent years and since older women are also at risk for cardiovascular disease, a team of researchers from several academic medical centers examined the link between antidepressant use and cardiovascular disease in such patients.
The Women's Health Initiative (WHI) of the National Institutes of Health followed more than 160,000 postmenopausal U.S. women for up to 15 years, examining risk factors for and potential preventive measures against cardiovascular disease, cancer and osteoporosis. For the current study, the research team began with data from more than 136,000 WHI participants who were not taking antidepressant drugs when they entered the study. At their first follow-up visit, either one or three years after study entry, about 5,500 of those women reported currently taking an antidepressant. The research team compared that group's subsequent history of cardiovascular disease with that of participants who had not started taking antidepressants.
While the study did not find any relationship between antidepressant use and heart disease, during a follow-up period averaging nearly six years, participants taking antidepressants did have an increased risk of death from any cause and of hemorrhagic stroke among those taking SSRIs. The overall risks were small - remaining less than 2 percent annually for all groups - but the increase was statistically significant. "There are a lot of things this study couldn't tell us, such as whether this risk truly is attributable to the drugs and not to depression itself and whether participants were being treated for depression or for anxiety, which also has cardiovascular risks," Smoller says. "We also don't know whether there is any similar association in younger women or in men, since they were not part of this study."
"Previous studies have shown that depression itself has risks as high as those seen with medication in this study," he adds. "There are other effective forms of therapy for patients at high cardiovascular risk who also have depression, so concerned women can explore these options with their physicians. But for most patients with significant depression, the benefits of antidepressants will outweigh the risks." Smoller is an associate professor of Psychiatry at Harvard Medical School.
Senior author Sylvia Wassertheil-Smoller, PhD, of Albert Einstein College of Medicine is also a principal investigator in the Women's Health Initiative. Additional co-authors are Matthew Allison, MD, MPH, University of California, San Diego; Barbara Cochrane, PhD, RN, University of Washington; David Curb, MD, MPH, University of Hawaii; Roy Perlis, MD, MSc, MGH; Jennifer Robinson, MD, MPH, University of Iowa; Milagros Rosal, PhD, University of Massachusetts Medical Center; and Nanette Wenger, MD, Emory University. Both the Women's Health Initiative and the current study were supported by grants from the National Institutes of Health.
Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $600 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, systems biology, transplantation biology and photomedicine.