Dec. 14, 2009 — Older women who take antidepressants may have a slightly higher risk for stroke and death.

In a new finding from the large study known as the Women’s Health Initiative (WHI), postmenopausal women who took tricyclic or selective serotonin reuptake inhibitor (SSRI) antidepressants had a small increased risk of dying from all causes, compared to women who did not take antidepressants.

SSRI users also had a greater risk for strokes, especially strokes caused by bleeding, but their overall risk was still quite small.

It was not clear if the increase was caused by the medications or by the depression itself.

“Depression is an often serious and debilitating illness, with its own heart risks including heart disease and death,” study researcher Jordan W. Smoller, MD, of Massachusetts General Hospital tells WebMD. “It is difficult to confidently tease apart the contribution of depression and the drugs used to treat it.”

The Women’s Health Initiative (WHI), which began in 1991, followed more than 160,000 postmenopausal women in the U.S. for up to 15 years. The newly published analysis included more than 136,000 WHI participants who were not taking antidepressants at enrollment.

Antidepressants and Stroke

At their first follow-up visit, either one or three years after enrolling in the study, 5,500 women reported taking either tricyclic or SSRI antidepressants.

Compared to women who did not take antidepressants, women who did had no greater risk for heart disease around six years later. But SSRI use was associated with a 32% greater risk of dying from all causes in one analysis and a 45% increased risk for stroke.

Smoller points out that the overall increase in stroke risk among SSRI users was small — less than 2% per year.

“The vast majority of women taking antidepressants did not have one of these bad outcomes,” he says.

He adds that more research is needed to fully understand the impact, if any, of different classes of antidepressants on cardiovascular risk.

It is also not clear if a similar association would be seen in men and younger women.

The researchers note that tricyclic antidepressants have potential to be toxic to the heart. Studies examining SSRIs and the heart have been mixed, with some finding the drugs to be protective against clot-related strokes and others finding them to increase the risk for bleeding.

SSRIs include the drugs Prozac, Paxil, Zoloft, Lexapro, and Celexa.

Some widely prescribed newer antidepressants, including the serotonin norepinephrine reuptake inhibitors (SNRIs) Cymbalta, Pristiq, and Effexor and the unique antidepressant Wellbutrin, entered the market after the study was completed.

Huntsville, Ala., neurologist and American Heart Association spokesman Jeff Harris, MD, says even if antidepressant use is associated with a slight increase in stroke risk, the risks associated with untreated depression are much greater.

“No one should stop taking a needed antidepressant based on the results of this study,” he tells WebMD. “We know that depression is a risk factor for stroke and heart attack, just like high blood pressure and diabetes. And just like these risk factors, it is treatable.”

Harris warns that certain combinations of antidepressants, such as SSRIs and SNRIs, should never be taken together.

“It is important that patients tell all their doctors about the medications they are taking for depression to avoid interactions,” he says. “But I wouldn’t worry about the risk associated with an individual SSRI or tricyclic antidepressant.”

WebMD contacted manufacturers of antidepressants for comment but did not receive replies in time for publication.