OBJECTIVE: To assess the effects of supervised and home-based aerobic exercise training, and antidepressant pharmacotherapy (sertraline) on coronary heart disease (CHD) risk factors in a sample of participants with major depressive disorder (MDD). METHODS: The Standard Medical Intervention versus Long-term Exercise (SMILE)-II study randomized 202 adults (153 women, 49 men) diagnosed as having MDD to one of four interventions, each of 4-month duration: supervised exercise, home-based exercise, antidepressant medication (sertraline, 50 to 200 mg daily), or placebo pill. Patients underwent a structured clinical interview for depression and completed the Hamilton Depression Rating Scale. CHD risk factors included brachial artery flow-mediated dilation, carotid intima-media thickness, serum lipids, and 10-year atherosclerotic cardiovascular disease (ASCVD) risk. RESULTS: Compared with placebo, active treatment of depression (supervised exercise, home-based exercise, sertraline therapy) was associated with an improvement in CHD risk factors (improved flow-mediated dilation (p = 0.032), reduced progression of intima-media thickness (p = 0.037), and a reduction in 10-year ASCVD (p = 0.049)). The active treatments did not differ from each other in their effects on the CHD risk outcomes. CONCLUSIONS: Both exercise and antidepressant medication improved CHD risk factors and lowered ASCVD risk in patients with MDD. Because MDD is associated with increased risk for CHD events, treatment of depression with exercise or sertraline may reduce the risk of developing CHD in patients with MDD. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00331305.

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