SSRIs reduce rate of ischemia triggered by mental stress

Patients with coronary heart disease (CHD) who received selective serotonin reuptake inhibitors (SSRIs) for six weeks had a lower rate of mental stress-induced myocardial ischemia compared with those who took placebos, according to results of the REMIT trial published May 22 in the Journal of the American Medical Association.

REMIT (Responses of Mental Stress Induced Myocardial Ischemia to Escitalopram Treatment) is a randomized double-blind placebo-controlled trial that compared the SSRI escitalopram with placebo in patients with clinically stable CHD and laboratory-diagnosed mental stress-induced myocardial ischemia (MSIMI).

“Few studies have examined therapeutics that effectively modify MSIMI, perhaps because of the mechanistic complexity underlying this phenomenon, which encompasses a wide range of central and peripheral physiological changes associated with emotions and behaviors,” explained Wei Jiang, MD, of Duke University Medical Center in Durham, N.C., and colleagues. “However, recent evidence suggests that selective serotonin reuptake inhibitors (SSRIs) may reduce mental stress–induced hemodynamic response, metabolic risk factors, and platelet activity.”

The study enrolled 127 patients between 2007 and 2011 and randomized them to receive escitalopram (64 patients, 5 mg a day increasing to 10 mg a day the first week and to 20 mg a day the third through sixth week) or placebo (63 patients). Participants underwent three mental stress tests and one treadmill exercise stress test at baseline and at six weeks.

The main outcome was the occurrence of MSIMI. The researchers defined that as the presence of one or more the following markers compared with rest measurements: development or worsening of regional wall motion; reduction of left ventricular ejection fraction (LVEF) by 8 percent or more; deviation of ST segment in two or more leads lasting for three or more consecutive beats, during one or more of the three mental stress tasks.

They used the same ischemic markers for exercise stress-induced myocardial ischemia and also obtained biophysiological and psychological measures at baseline and at six weeks.  

The escitalopram group was older and the placebo group was more likely to be female and have lower LVEF and higher rates of resting abnormal wall motion. In each group, 56 patients completed the study.

At six weeks, there was an absence of MSIMI in 34.2 percent of the escitalopram group compared with 17.5 percent of the placebo group during mental stress testing, and the odds of not experiencing MSIMI were 2.62 higher in the escitalopram group. Escitalopram treatment improved biophysiological measures and the hemodynamic response to mental stress such as heart rate was lower in the escitalopram group.

The escitalopram group also claimed they felt more in control and calmer during the mental stress testing than did the placebo group. “This finding is notable because positive expectations and attitudes have been shown to be associated with lower rates of mortality in patients with CHD,” Jiang et al wrote.

The rate of exercise stress-induced myocardial ischemia was slightly lower in the escitalopram group but it was not statistically significant. Also, 71.9 percent of the escitalopram group reported adverse effects compared with 44.4 percent of the placebo group; the authors described the effects as relatively mild.

“Our study shows that escitalopram can significantly reduce MSIMI that cannot be modified by conventional antiischemic agents and suggests that enhancing central synaptic availability of serotonin may be an important step in management of CHD,” they wrote.

Jiang et al listed among limitations the relatively small sample size and use of one medical center. Findings may not be generalizable to other patient populations or settings. They called for more multicenter trials to confirm their results.