Exercise and Pharmacological Treatment of Depressive Symptoms in Patients With Coronary Heart Disease: Results From the UPBEAT (Understanding the Prognostic Benefits of Exercise and Antidepressant Therapy) Study

Study Questions:

What is the comparative efficacy of exercise and antidepressant medication in reducing depressive symptoms and improving cardiovascular biomarkers in depressed patients with coronary heart disease (CHD)?


One hundred and one outpatients with CHD and elevated depressive symptoms underwent assessment of depression, including a psychiatric interview and the Hamilton Rating Scale for Depression (HAM-D). Participants were randomized (2:2:1 ratio) to 4 months of aerobic exercise (3x/week), sertraline (titrated by a psychiatrist from 50 to 200 mg/day), or placebo. Additional assessments included measures of heart rate variability, endothelial function, baroreflex sensitivity, inflammation, and platelet function. The primary endpoint was the HAM-D score at the end of 4 months. Secondary endpoints included remission of depression, defined as no major depressive disorder (MDD), a HAM-D score <8, and change in cardiovascular biomarkers.


Mean age was 63.9 years, 73% were white, 68% were male, and the majority had undergone revascularization. Mean baseline HAM-D score was about 14 in each group (mild clinical depression), 47% met criteria for MDD (46% in the exercise group, 50% in the sertraline group, and 42% in the placebo group). After 16 weeks, all groups showed improvement on HAM-D scores. Participants in both the aerobic exercise (mean -7.5; 95% confidence interval [CI], -9.8 to -5.0) and sertraline (mean -6.1; 95% CI, -8.4 to -3.9) groups achieved larger reductions in depressive symptoms compared with those receiving placebo (mean -4.5; 95% CI, -7.6 to -1.5; p = 0.034); exercise and sertraline were equally effective at reducing depressive symptoms (p = 0.607). Exercise and medication tended to result in greater reductions in heart rate variability compared with placebo (p = 0.052); exercise tended to result in greater reductions in heart rate variability compared with sertraline (p = 0.093). Exercise was more effective in reducing clinical depression in the subset of patients who were diagnosed with MDD; 40% were remitted at the end of 16 weeks of exercise, compared with 10% treated with sertraline, and none who received placebo (p = 0.02).


Both exercise and sertraline resulted in greater reductions in depressive symptoms compared to placebo in patients with CHD. Evidence that active treatments may also improve cardiovascular biomarkers suggests that they may have a beneficial effect on clinical outcomes as well as on quality of life.


This study provides further support for routine screening in patients with CHD using the Patient Health Questionnaire-2 or similar tools. Considering the evidence that depression in CHD is associated with a worse outcome, and less compliance with medication and lifestyle change, a large randomized outcome trial comparing exercise and selective serotonin reuptake inhibitors (SSRIs) to usual care is clearly warranted.

Clinical Topics: Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Prevention, Heart Failure and Cardiac Biomarkers, Exercise

Keywords: Depression, Inflammation, Prognosis, Coronary Artery Disease, Biological Markers, Outpatients, Exercise, Baroreflex, Questionnaires, Heart Rate

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