Antidepressant Curbs Mental-Stress Induced Myocardial Ischemia

Posted on: May 21, 2013


Last Updated: 2013-05-21 16:35:20 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Treatment with a selective serotonin reuptake inhibitor (SSRI) protected against mental stress-induced myocardial ischemia in patients with stable coronary heart disease in the randomized controlled REMIT trial.

According to a report in JAMA this week, patients in the study were less apt to experience mental stress-induced myocardial ischemia (MSIMI) while taking the SSRI escitalopram (Lexapro), and they showed greater improvements in hemodynamic responses to mental stress and certain measures of psychological functioning during mental stress.

"This is an interesting paper that notably advances our knowledge of how the brain communicates with the heart," Dr. Joel E. Dimsdale, Distinguished Professor of Psychiatry Emeritus, University of California San Diego, who wasn't involved in the study, told Reuters Health.

"We have known for years that depression and stress are not just emotionally painful but are also toxic to the heart. This study found that an antidepressant seems to block some of those toxic effects. It's an important next step but we need to see many other studies like this before this is part of standard treatment," Dr. Dimsdale said.

MSIMI occurs in up to 70% of patients with clinically stable CHD and increases their risk of death and cardiovascular events, Dr. Wei Jiang from Duke University Medical Center in Durham, North Carolina, who led the REMIT study with Duke colleagues, told Reuters Health.

The study tested the hypothesis that escitalopram would reduce MSIMI to a greater extent than placebo in patients with clinically stable CHD and MSIMI at enrollment. They had subjects undergo mental and exercise stress testing during baseline screening. Those who had evidence of MSIMI were randomly allocated in a double-blind fashion to receive escitalopram or matching placebo for six weeks.

For the study, the presence of MSIMI was defined as development or worsening of regional wall motion abnormality; left ventricular ejection fraction reduction of 8% or more; and/or horizontal or down-sloping ST-segment depression of 1 mm or more in two or more leads, lasting for three or more consecutive beats, during one of three mental stressor tasks.

The study team eventually randomized 64 subjects to escitalopram or 63 to placebo, and 56 in each group completed the assessments.

At the end of six weeks, more patients taking escitalopram than placebo were free of MSIMI during the three mental stressor tasks (34.2% vs 17.5%). A significant difference favoring escitalopram was observed (odds ratio, 2.62), the researchers report.

Rates of exercise-induced ischemia were slightly lower at six weeks in the escitalopram group (45.8% vs 52.5% with placebo) but this difference was not statistically significant (adjusted odds ratio 1.24; p=0.56).

"In summary, six-week pharmacologic enhancement of serotonergic function superimposed on the best evidence-based management of CHD appeared to significantly improve MSIMI occurrence," the researchers say. "These results support and extend previous findings suggesting that modifying central and peripheral serotonergic function could improve CHD symptoms and may have implications for understanding the pathways by which negative emotions affect cardiovascular prognosis."

In a statement from Duke, Dr. Eric Velazquez, who worked on the study, said, "All physicians treating patients with coronary artery disease need to be aware of how emotional stressors may negatively impact their disease management. We should be having conversations with our patients about their lifestyles to gauge their levels of mental stress and whether the coping mechanisms they use are adequate or if more mental health-focused help is needed."

"Personally, I would recommend every patient with coronary heart disease have a mental-stress test," Dr. Jiang told Reuters Health. "We here at Duke hope to start that kind of service for patients who need it."

The REMIT study didn't look at hard outcomes, only biomarkers associated with adverse cardiovascular events. But Dr. Jiang told Reuters Health that in a study published in JAMA in 1996, the Duke team found that patients with CHD and MSIMI had a worse cardiovascular outcome over five years compared with patients with CHD who didn't have MSIMI.

The study was funded by the National Heart Lung and Blood Institute. Escitalopram and matching placebo were provided by Forest Research Institute Inc., Germantown, Maryland. Dr. Jiang is named on a patent application to Duke University related to SSRI treatment for MSIMI. A complete list of author disclosures is listed with the article.


JAMA 2013;309:2139-2149.

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