Exercise of Limited Benefit for Anxiety in Patients With Heart Disease

Investigators report findings from UNWIND that assessed the effects of escitalopram and exercise on anxiety symptoms in patients with heart disease.

Although exercise does have numerous health benefits, its impact on anxiety in patients with heart disease is inconsistent. Escitalopram, however, has been shown to be safe and effective for symptoms of anxiety in these patients, according to the results of a study published in JAMA Psychiatry.

As anxiety disorders are common among people with heart disease, the researchers wanted to examine the effects of escitalopram and aerobic exercise compared with placebo on coronary heart disease (CHD) biomarkers of risk. They conducted the UNWIND study (ClinicalTrials.gov Identifier:  NCT02516332), a single-site, parallel-group, randomized clinical trial that used change in scores on the Hospital Anxiety and Depression-Anxiety Subscale (HADS-A) as the primary outcome.

Enrollment took place between January 2016 and February 2020. Men and women aged 40 and over with documented CHD and an anxiety symptom severity score of 8 or higher on the HADS-A and/or diagnosis of an anxiety disorder as per the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) participated in the study.

A total of 128 participants exercised for 50 minutes 3 times per week at a cardiac rehabilitation facility. Treatment was initiated with escitalopram 5 mg/d or placebo and increased to 10 mg/d at week 2 and 15 mg/d at week 3 if there was no change or only minimal improvement in anxiety symptoms, with a maximum dosage of 20 mg/d at week 4 if no change, only minimal improvement, and no side effects. Participants were randomly assigned to exercise, escitalopram, or placebo in a 2:2:1 ratio. The groups shared similar demographic and clinical characteristics.

All groups were found to experience reduced anxiety levels with mean reductions of -4.0 (95% CI, -4.7 to -3.2) in the exercise group, -5.7 (95% CI, -6.4 to -5.0) in the escitalopram group, and -3.5 (95% CI, -4.5 to -2.4) in the placebo group. HADS-A scores were lowest in the escitalopram group. At 12 weeks, both the escitalopram group and the exercise group had comparable levels of state anxiety. The escitalopram group experienced more rapid improvements early in the study while the exercise group showed improvements in the latter 6 weeks.

Overall, “the effects of exercise in reducing trait anxiety were no better than placebo controls and also provided no advantage compared with placebo in reducing symptoms of depression,” the researchers concluded. However, the study was limited to a single site with a short treatment duration and small sample size. The 12-week treatment period may have been insufficient to measure heart disease biomarkers. The researchers also did not factor diagnoses of major depressive disorder. As the exercise group participated in a program typical in cardiac rehabilitation, adjusting intensity or duration of exercise could have affected the results.


Blumenthal JA, Smith PJ, Jiang W, et al. Effect of exercise, escitalopram, or placebo on anxiety in patients with coronary heart disease: the understanding the benefits of exercise and escitalopram in anxious patients with coronary heart disease (UNWIND) randomized clinical trial. JAMA Psychiatry. 2021;78(11):1270-1278. doi:10.1001/jamapsychiatry.2021.2236