Do aerobic exercise and escitalopram reduce anxiety and improve coronary heart disease biomarkers more than a placebo?
In this randomized clinical trial including 128 patients with coronary heart disease and anxiety, escitalopram, but not exercise, resulted in reduced levels of anxiety and depression compared with a placebo control.
For patients in this study with coronary heart disease and high anxiety, escitalopram was an effective treatment for reducing anxiety, although the extent to which this benefit may improve clinical outcomes remains uncertain.
Anxiety is common among patients with coronary heart disease (CHD) and is associated with worse health outcomes; however, effective treatment for anxiety in patients with CHD is uncertain.
To determine whether exercise and escitalopram are better than placebo in reducing symptoms of anxiety as measured by the Hospital Anxiety and Depression-Anxiety Subscale (HADS-A) and in improving CHD risk biomarkers.
Design, Setting, and Participants
This randomized clinical trial was conducted between January 2016 and May 2020 in a tertiary care teaching hospital in the US and included 128 outpatients with stable CHD and a diagnosed anxiety disorder or a HADS-A score of 8 or higher who were older than 40 years, sedentary, and not currently receiving mental health treatment.
Twelve weeks of aerobic exercise 3 times per week at an intensity of 70% to 85% heart rate reserve, escitalopram (up to 20 mg per day), or placebo pill equivalent.
Main Outcomes and Measures
The primary outcome was HADS-A score. CHD biomarkers included heart rate variability, baroreflex sensitivity, and flow-mediated dilation, along with 24-hour urinary catecholamines.
The study included 128 participants. The mean (SD) age was 64.6 (9.6) years, and 37 participants (29%) were women. Participants randomized to the exercise group and escitalopram group reported greater reductions in HADS-A (exercise, −4.0; 95% CI, −4.7 to −3.2; escitalopram, −5.7; 95% CI, −6.4 to −5.0) compared with those randomized to placebo (−3.5; 95% CI, −4.5 to −2.4; P = .03); participants randomized to escitalopram reported less anxiety compared with those randomized to exercise (−1.67; 95% CI, −2.68 to −0.66; P = .002). Significant postintervention group differences in 24-hour urinary catecholamines were found (exercise z score = 0.05; 95% CI, −0.2 to 0.3; escitalopram z score = −0.24; 95% CI, −0.4 to 0; placebo z score = 0.36; 95% CI, 0 to 0.7), with greater reductions 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). All groups achieved comparable but small changes in CHD biomarkers, with no differences between treatment groups.
Conclusions and Relevance
Treatment of anxiety with escitalopram was safe and effective for reducing anxiety in patients with CHD. 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.
ClinicalTrials.gov Identifier: NCT02516332
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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
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