SSRIs are not associated with greater risk of cardiovascular conditions

Researchers in the United Kingdom have found that selective serotonin reuptake inhibitor (SSRI) antidepressants aren’t associated with greater risk of cardiovascular conditions—including heart attack, arrhythmia, and stroke/transient ischemic attack—in working-age adults with depression, according to a study published March 22, 2016 in The British Medical Journal.

Depression on its own increases the risk of cardiovascular outcomes, the researchers noted. But it’s not clear whether antidepressants, particularly SSRIs, can increase or reduce that risk. Although one large observational study found an increased risk of heart attack in elderly patients with depression, other studies that included patients of different ages found no association or even a reduction in risk.

In this study, the researchers looked for associations between common antidepressants (including tricyclics and related antidepressants, SSRIs, monoamine oxidase inhibitors, and others), and different adverse cardiovascular outcomes. They used a large primary care database to obtain information on 238,963 patients, ages 20 to 64, who were diagnosed with depression between 2000 and 2011. The researchers followed the patients for 5 years.

“We found no evidence that SSRIs were associated with an increased risk of arrhythmia, heart attacks, or stroke in people with depression over the 5-year period,” said Carol Coupland, PhD, Professor of Medical Statistics in Primary Care at the University of Nottingham, in Nottingham, UK. “But there was a significant doubling of risk for arrhythmia during the first 4 weeks of taking tricyclic and related antidepressants.”

The results also indicated that some SSRIs, particularly fluoxetine, were associated with a reduced risk of heart attacks. “Absolute risks of heart attacks were 6 per 10,000 for selective serotonin reuptake inhibitors over 1 year and 4 per 10,000 for fluoxetine, compared with 10 per 10,000 for non-use,” Dr. Coupland said.

Also, citalopram was not significantly associated with an increased risk of arrhythmia, even at higher doses. In 2011, the Food and Drug Administration and the European Medicines Agency each issued safety recommendations against taking high doses of the drug (greater than 40 mg per day) based on findings of QT interval prolongation.

But even though citalopram was the most commonly prescribed antidepressant among patients in this study, only a relatively small proportion of patients were prescribed the drug at high doses. So the researchers couldn’t rule out the possibility of an increased risk of arrhythmia. “We suggest that high doses of citalopram should not be prescribed without a strong indication, particularly in patients with any risk factors for an increased QT interval,” they wrote.

Because this was an observational study, the findings yielded no conclusions between cause and effect, the authors noted. Still, “these findings are reassuring in light of recent safety concerns about selective serotonin reuptake inhibitors,” they wrote.