NEW ORLEANS - Carotid intima-media thickness was found to be increased in middle-aged men taking antidepressants in a study reported at the annual scientific sessions of the American College of Cardiology.
"There is a clear association between increased intima-media thickness [IMT] and taking an antidepressant of any kind, and this trend is even stronger when we look at people who are on these medications and are more depressed," said Dr. Amit Shah, a cardiology fellow at Emory University, Atlanta.
Dr. Janet Wright senior vice president of science and quality for the ACC, commented that the study should be viewed as "directional. ... It only tees things up for the next range of studies." Dr. Wright, a cardiologist in Chico, Calif., added that "it does suggest that perhaps a person who is depressed and on an antidepressant may need monitoring."
Carotid IMT and brachial flow-mediated dilation was assessed using B-mode ultrasound in 513 middle-aged male twins from the Vietnam Era Twin Registry. Traditional risk factors for ischemic heart disease were measured. Depression and posttraumatic stress disorder (PTSD) were assessed with the Structured Clinical Interview for the Diagnosis of Psychiatric Disorders, and depressive symptoms were measured via the Beck Depression Inventory. Medication regimens were verified by a clinician. Mixed effects regression models were used to analyze the overall association and to examine differences within twin pairs discordant for antidepressant intake.
Participants were a mean age of 55 years; 95% were white and 16% were taking antidepressants, mainly selective serotonin reuptake inhibitors (60%). In an analysis of the association by type of antidepressant, an increase in IMT was noted regardless of the class of antidepressants.
Antidepressant use was associated with an IMT increase of 37 microns, which represents about a 5% increase from the mean IMT value of 762 microns seen in the population, a significant difference compared with men not taking antidepressants.
The findings emerged from an adjusted analysis that controlled for conventional cardiovascular risk factors and for depressive symptoms, history of major depression and heart disease, alcohol and coffee consumption, statin use, physical activity, education, and employment status.
In an analysis of 59 twin pairs where one brother was taking an antidepressant and the other was not, the antidepressant user had an IMT that was 41 microns thicker (P = .01), he reported.
Each additional year of life is associated with a 10-micron increase in IMT, therefore, the brother on the antidepressant could be considered to be 4 years "older" in terms of atherosclerosis. In previous studies, each 10-micron increase in IMT has been linked to a 1.8% increase in risk, Dr. Shah noted.
Previous studies have linked the presence of depression with an increased risk of cardiovascular disease. In this study, neither depression nor posttraumatic stress disorder significantly predicted an increase in IMT. However, the study did show that subjects taking antidepressants who also reported clinical symptoms of depression had higher IMTs than those taking antidepressants who had fewer symptoms of depression.
"Because we didn’t see an association between depression itself and a thickening of the carotid artery, it strengthens the argument that this is more likely the antidepressants than the actual depression that is behind the association," Dr. Shah said.
History of a previous myocardial infarction, which was noted for 12% of the cohort, was not independently associated with increased IMT, nor was there a differential effect for identical and fraternal twins.
Speculating on the possible mechanism for the association, the investigators suggested that antidepressants may increase IMT through augmented release of vasoconstrictive neuropeptides. "The antidepressants may act synergistically with depressive symptoms to increase vascular disease," he said. "There is a potential interaction between the depressive symptoms, the neurohormonal effects of the depression itself, and the medication."
The findings suggest that the risk/benefit ratio of antidepressants should be considered, especially in patients with pre-existing cardiovascular disease, Dr. Shah said. "While not showing causality, it is important to take studies such as this into account in patient care, especially when the patient may not be deriving much benefit from the antidepressant."
Dr. Shah and Dr. Wright reported no relevant conflicts of interest.