Middle-aged women taking antidepressants at increased risk for stroke

Dominika Osmolska Psy.D.'s picture

Depressed middle-aged and older women are at significantly increased risk of stroke according to a new study published today in the journal Stroke: Journal of the American Heart Association. Depressed women who were taking popular antidepressants in the SSRI class of drugs such as Paxil, Zoloft and Prozac were most at risk. Researchers are uncertain about the correlation.

Dr. Kathryn Rexrode, an internist at Brigham and Women's Hospital in Boston cautiously stated that there is something about being depressed that puts one at risk for stroke, but exactly what that is is difficult to determine. That’s because correlation does not mean causation. This means that although depressed women are taking these medications, it may not be the drugs themselves that increase the risk, but perhaps the severity of the depression that is the causative factor. She took pains to say that women taking antidepressants should not interpret the findings as a signal that "stopping SSRIs is going to make your risk of stroke go down. There is no data about that."

"I don't think the medications themselves are the primary cause of the risk," Rexrode said. Instead, she suggested that women who medicate their depression might suffer from more severe symptoms than those who don't ask for the pills.

Regardless of the mechanism, Dr. Rexrode feels strongly that doctors need to be made aware of the relationship between depression and strokes. "We ought to intensify efforts to reduce that risk through the usual risk factors for stroke, and we ought to test and research interventions we can to do help modify that risk."

Stokes are the third leading cause of death in this country, and when they don’t outright kill, they leave sufferers with trouble speaking, thinking and with limited use of their limbs. As a result, strokes are a leading cause of permanent disability.

The findings were drawn from the landmark Nurses' Health Study, which began in 1976 and has followed more than 120,000 women for numerous health conditions. Researchers studying stroke risk followed 80,574 of them, predominantly white, female RNs, with an average age of 66, without any stroke history.


Study participants were evaluated periodically and asked if they were diagnosed with depression and/or were taking antidepressants. At the beginning of the study, 22.3 percent of the women were depressed, meaning that they scored high for symptoms of depression, had taken antidepressants or had a formal diagnosis of depression.

Over a period of a six-year follow-up, researchers documented 1,033 strokes. They calculated that depression increased a woman's risk of stroke by 29 percent, compared with women who never reported being depressed. Among depressed women taking any of the SSRIs, stroke risk was 39 percent higher than among women who never reported being depressed or taking antidepressants.

Rexrode points out that the 10 percent difference between the two groups Is not statistically significant, suggesting further that the medications may not be to blame.

Stroke risk was higher among those who were currently depressed versus those who had reported being depressed in the past. More significantly, depressed women were more likely to be single, younger (the group spans ages 54 to 79) and have such cardiovascular risk factors as being overweight, being a smoker or being sedentary. Depressed women also were more likely to suffer from high blood pressure, diabetes and heart disease, which suggests that depression may be an outcome of an unhealthy lifestyle, rather than its precursor.

On the other hand, depression might interfere with a woman's ability to control such risk factors as diabetes and hypertension through medication, or by making important lifestyle changes. depression also might increase the body’s inflammation mechanisms, which are known to damage blood vessels in the heart and brain. Depression also can alter neurological functions and the body's response to stress, and may make blood more likely to clot.

Dr. Sylvia Wassertheil-Smoller, a professor of epidemiology and public health at Albert Einstein College of Medicine in the Bronx, N.Y., agreed with the current study authors about the need to inform doctors about the risks and to conduct additional research. "Since mild or moderate depression is not usually screened for, or even given much attention by primary care physicians, it is important that they be alerted to this finding," she said. "The interesting question is whether depression is a subclinical manifestation of impending stroke or whether there is some causal pathway."

Her 2009 study also showed that depression is a risk factor for subsequent stroke.