Escitalopram Lowers Anxiety and Depression in Patients With Coronary Heart Disease

Heart, rhythm, echocardiogram
Heart, rhythm, echocardiogram
Researchers conducted the first randomized clinical trial comparing the effect of selective serotonin reuptake inhibitor treatment vs aerobic exercise on anxiety in patients with coronary heart disease.

Escitalopram was found to be more effective at lowering symptoms of anxiety and depression compared with placebo among patients with coronary heart disease (CHD), but it did not improve CHD biomarkers of risk, according to researchers who published the results of their randomized clinical trial in JAMA Psychiatry.

The Understanding the Benefits of Exercise and Escitalopram in Anxious Patients With CHD (UNWIND) trial ( Identifier: NCT02516332) evaluated the effects of escitalopram, aerobic exercise, and placebo on anxiety and CHD risk biomarkers in patients aged 40 years and older. This is the first study to assess the impact of treatment for anxiety on CHD biomarkers of risk and the first randomized clinical trial to evaluate the efficacy of a selective serotonin reuptake inhibitor or aerobic exercise in the treatment of patients with CHD and increased levels of anxiety.

Study participants had stable CHD and severity of anxiety symptoms graded at least 8 on the Hospital Anxiety and Depression-Anxiety Subscale (HADS-A) or a primary diagnosis of an anxiety disorder according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5).  The researchers excluded individuals who were currently receiving mental health treatment and those who exercised at least 1 day per week.

The researchers measured heart rate variability, baroreflex sensitivity, endothelial function, and urinary catecholamines before and after the 12-week interventions.

The researchers randomly assigned participants to aerobic exercise of moderate to high intensity (n=52), escitalopram (n=53), or placebo (n=23) for 12 weeks. The exercise condition involved exercising 3 times per week with 10 minutes of warm-up exercises; 35 minutes of walking, biking, or jogging at 70% to 85% of heart rate reserve; and 5 minutes of cool-down exercises. In the escitalopram condition, participants took escitalopram 5 mg/d, with the dosage increased to 10 mg/d at week 2, 15 mg/d at week 3, and 20 mg/d at week 4 if there were no significant improvement in anxiety.

Participants in the exercise group and the escitalopram group reported greater mean reductions in HADS-A scores (exercise, -4.0; escitalopram, -5.7) compared with those who received placebo (-3.5; P =.03). HADS-A scores for the escitalopram group were lower compared with the exercise group (-1.67; P =.002).

Significant postintervention group differences in 24-hour urinary catecholamines were found (exercise z score = 0.05; escitalopram z score = -0.24; placebo z score = 0.36), with greater reductions reported in the exercise group and escitalopram group compared with the placebo group (F1,127 = 4.93; P =.01) and greater reductions in the escitalopram group compared with the exercise group (F1,127 = 4.37; P =.04).

Post-treatment differences in 24-hour heart rate variability, baroreflex sensitivity, and flow-mediated dilation were inconsistent across treatment groups.

“Treatment of anxiety with escitalopram was safe and effective for reducing anxiety in patients with CHD,” the researchers said. “However, the beneficial effects of exercise on anxiety symptoms were less consistent. Exercise and escitalopram did not improve CHD biomarkers of risk, which should prompt further investigation of these interventions on clinical outcomes in patients with anxiety and CHD.”

The researchers said that modifying the exercise prescription may have improved the outcome for the patients in that group.


Blumenthal JA, Smith PJ, Jiang W, et al. Effect of exercise, escitalopram, or placebo on anxiety in patients with coronary heart disease. JAMA Psychiatry. Published online August 18, 2021. doi:10.1001/jamapsychiatry.2021.2236