Depression—it’s more than an occasional down-in-the-dumps feeling. It’s a low mood, despair or hopelessness that lasts for weeks, months, or even longer. In fact, most health professionals today consider depression a chronic illness that requires long-term treatment, much like diabetes or high blood pressure. The most common treatments are psychotherapy and antidepressants ,which work to correct the chemical imbalance in the brain thought to cause depression. There are several different classifications of antidepressants, depending on which brain chemical the drug affects. For example, selective serotonin reuptake inhibitors (SSRIs) increase the production of serotonin in the brain; monoamine oxidase inhibitors (MAOIs) block monoamine oxidase, an enzyme that breaks down neurotransmitters. All antidepressants have some side effects, the most common being headache, nausea, constipation, dry mouth, agitation and sexual problems. But most occur in the early weeks of therapy and lessen over time.

However, some side effects can be serious. In October 2004, the U.S. Food and Drug Administration (FDA) directed manufacturers to add a boxed warning, the most serious type of warning used on prescription drugs, to the labeling of all antidepressant medications to alert the public about the increased risk of suicidal thinking or suicide attempts by children and adolescents taking antidepressants. In May 2007, after a more detailed analysis of antidepressant clinical trials, the FDA directed that the warning be extended to include young adults up through age 24.

Earlier this year, a study published in the Journal of the American College of Cardiology concluded that women with no history of cardiac problems but who used antidepressants are at heightened risk for sudden cardiac death (SCD), though the exact reason for the link remains unclear. And most recently, a report published in the December 14 Archives of Internal Medicine shows that postmenopausal women who take antidepressants have an increased risk of stroke and death compared to women of the same age who don’t take the drugs.

For the study, researchers looked at data from 136,293 women who participated in the Women’s Health Initiative (WHI) of the National Institutes of Health, a 15-year study of more than 160,000 U.S. women to examine risk factors for and potential preventative measures against cardiovascular disease, cancer and osteoporosis. At enrollment, none of the participants were taking antidepressants but at their first follow-up visit, either one or three years after study entry, about 5,500 reported currently taking an antidepressant. Six years later, the researchers compared that group’s subsequent history of cardiovascular disease with that of the remaining participants who had not started taking antidepressants.

While there was no difference in the rates of heart attacks, those taking antidepressants were 45 percent more likely to suffer a stroke than the participants not taking the medications. No difference in stroke risk was found between the two major classes of antidepressants, SSRIs or tricyclic antidepressants (TCAs). However, there did appear to be a higher risk of hemorrhagic stroke caused by a bleed in the brain in SSRI users. When overall death rates were examined, those on antidepressants were found to have a 32 percent higher risk of death from all causes than non-users. However, because depression itself is known to be a risk factor for cardiovascular problems, it remains unclear whether taking anti-depressants is solely responsible for the increased risk of stroke.

“Although these results raise concerns about adverse effects of antidepressants, it is important to note that depression itself has been implicated as a risk factor for coronary heart disease, stroke, early death, and other adverse outcomes,” said lead author Dr. Jordan W. Smoller, of the Massachusetts General Hospital Department of Psychiatry. “In addition, inadequately treated depression is associated with substantial disability, impairments in quality of life, and health care costs.”

Joanne Murphy, Research Liaison Officer for The Stroke Association, said that while the study did seem to show a link between antidepressants and stroke, the overall risk is relatively small. “We are already aware of links between depression and the risk of stroke and we are currently funding further studies to look into this,” she said. “Everyone can help reduce their risk of stroke by making lifestyle changes, such as reducing their blood pressure, giving up smoking, reducing alcohol intake, improving their diet and getting plenty of exercise.” Murphy stressed that “anyone who is at all concerned should consult their GP.”