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

Abstract

Objectives: The aim of this study was to assess the efficacy of exercise and antidepressant medication in reducing depressive symptoms and improving cardiovascular biomarkers in depressed patients with coronary heart disease.

Background: Although there is good evidence that clinical depression is associated with poor prognosis, optimal therapeutic strategies are currently not well defined.

Methods: One hundred one outpatients with coronary heart disease and elevated depressive symptoms underwent assessment of depression, including a psychiatric interview and the Hamilton Rating Scale for Depression. Participants were randomized to 4 months of aerobic exercise (3 times/week), sertraline (50-200 mg/day), or placebo. Additional assessments of cardiovascular biomarkers included measures of heart rate variability, endothelial function, baroreflex sensitivity, inflammation, and platelet function.

Results: After 16 weeks, all groups showed improvement on Hamilton Rating Scale for Depression scores. Participants in both the aerobic exercise (mean -7.5; 95% confidence interval: -9.8 to -5.0) and sertraline (mean -6.1; 95% confidence interval: -8.4 to -3.9) groups achieved larger reductions in depressive symptoms compared with those receiving placebo (mean -4.5; 95% confidence interval: -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 improvements in heart rate variability compared with placebo (p = 0.052); exercise tended to result in greater improvements in heart rate variability compared with sertraline (p = 0.093).

Conclusions: Both exercise and sertraline resulted in greater reductions in depressive symptoms compared to placebo in patients with coronary heart disease. 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. (Exercise to Treat Depression in Individuals With Coronary Heart Disease; NCT00302068).

Figure 1

Participant Flow in the UPBEAT Randomized Clinical Trial

Figure 2. Aerobic capacity (Panel A) and treadmill time (Panel B) at 16 weeks, adjusted for age, gender, ethnicity, and baseline scores of the outcome

Contrasts were planned and non-orthogonal: Exercise vs. Sertraline and Exercise vs. Placebo, with Bonferroni correction. Thicker horizontal line represents median; thinner, wider line represents mean. Box represents 25^th and 75^th percentiles. Following treatment, Exercise was associated with higher levels of aerobic capacity and longer treadmill time compared to either Sertraline or Placebo (P’s < .001).

Figure 3. HAM-D scores adjusted for age, gender, ethnicity, and baseline scores of the outcome

Thicker horizontal line represents median; thinner, wider line represents mean. Box represents 25^th and 75^th percentiles. HAM-D scores were lower for the active treatments (Exercise and Sertraline) compared to Placebo, P = .034, but were not different from each other P = .607.