Antidepressants–Not Depression Alone–Linked to Thicker Carotids

A study of middle-aged male twins funded by the National Institutes of Health suggests an association between use of antidepressants and increased intima media thickness in the carotid arteries.

Participants in the Vietnam Era Twin Registry taking antidepressants at the time of the study had an average carotid intima media 41 microns thicker than their brothers who were not taking antidepressants, Amit Shah, M.D., a cardiology fellow at Emory University, said at the American College of Cardiology's annual scientific session in New Orleans in April. The findings appeared in the April 5 Journal of the American College of Cardiology.

In addition, patients who took the antidepressants and also reported depressive symptoms had greater intima media thickness than those who took the drugs without reporting symptoms.

Of those taking antidepressants, 9 percent had no depressive symptoms and 47 percent had a Beck Depression Index score of less than 10, Shah told Psychiatric News. About 60 percent had a lifetime history of major depression, and 11 percent had current DSM-IV major depressive disorder. How long the participants had been taking the medications was not known, he said.

Shah and his co-investigator, Viola Vaccarino, M.D., Ph.D., chair of the Department of Epidemiology at Emory's Rollins School of Public Health, found an association between intima media thickness and antidepressant use but not with depression alone. "[That] strengthens the argument that it is more the antidepressants than the actual depression that could be behind the association," Shah said.

The category of antidepressant used (SSRIs or other types) made no difference in the findings, he pointed out.

The study covered 513 middle-aged male twins both of whom served in the U.S. military during the Vietnam War. Shah was careful to point out the findings are preliminary.

"Antidepressants have a clinical benefit that has been established, so nobody taking these medications should stop based only on these results," he said. "This isn't the kind of study where we can know cause and effect, let alone mechanism, and we need to see whether this holds up in other population groups."

The researchers assessed depression and posttraumatic stress disorder with the Structured Clinical Interview for the Diagnosis of Psychiatry Disorders. Depressive symptoms were measured using the Beck Depressive Inventory.

This was one of several strengths of the research, said Lawson Wulsin, M.D., a professor of psychiatry and family medicine at the University of Cincinnati, who was not involved in the study.

"This was not a shot in the dark," said Wulsin, in an interview with Psychiatric News. "Beside good measures of depression, it was done in a large, well-controlled sample of twins, and data were well-collected and linked to well-established biological markers of coronary artery disease."

However, the study's limitations also have to be considered, Wulsin noted. It would need to be replicated, and women as well as men need to be studied.

It would also be important, he added, to provide information about whether the antidepressants effectively treated the participants' depression or about other markers of heart disease and outcomes, like heart attacks or death.

Shah and Vaccarino did not have information on the participants' depression status before starting medication or their responses to the drugs, only the difference in thickness between those who reported symptoms and those who did not, said Shah. "We are in the process of collecting hard outcomes, although these data will take several years."

"One of the strongest and best-studied factors that thickens someone's arteries is age, and that happens at around 10 microns per year," Shah said. "In our study, users of antidepressants see an average 40 micron increase in IMT [intima media thickness], so their carotid arteries are in effect four years older."

He hypothesized that antidepressants might raise levels of serotonin or norepinephrine in the circulatory system, which might cause blood vessels to thicken or constrict.

Wulsin noted that even if these findings eventually hold up, the effect may be clinically significant only in the context of other factors.

"Cardiovascular disease is a complex, chronic condition with multiple risk factors," said Wulsin. "Antidepressant use may raise one minor, well-known risk factor, but might also reduce several others. The net effect is what's important."

Shah and Vaccarino's work adds evidence to a complex picture of the relationship between antidepressant use and coronary disease.

An unrelated study of 93,653 veterans that was published in the April American Journal of Medicine found that patients who received at least 12 weeks of continuous antidepressant therapy had lower rates of incident heart attack and all-cause mortality. The study was by psychiatric epidemiologist Jeffrey Scherrer, Ph.D., an assistant professor of psychiatry at Washington University School of Medicine in St. Louis.

A video interview and press release about Shah's research are posted at <http://shared.web.emory.edu/whsc/news/releases/2011/04/antidepressants-linked-to-thicker-arteries.html>.