Exercise and Pharmacotherapy in the Treatment of Major Depressive Disorder

TLDR

The study aimed to determine whether aerobic exercise, performed at home or in a supervised group, yields depression reductions comparable to sertraline and superior to placebo. In a prospective, randomized controlled trial (SMILE study) conducted from 2000 to 2005, 202 adults with major depression were randomly assigned to supervised exercise, home exercise, sertraline, or placebo for 16 weeks, with outcomes assessed via structured interview and the Hamilton Depression Rating Scale. After four months, remission rates were 45% for supervised exercise, 40% for home exercise, 47% for sertraline, and 31% for placebo, with no significant HAM‑D score differences among active treatments versus placebo, indicating exercise is similarly effective to medication and better than placebo. Abbreviations used include BDI, CI, HAM‑D, ITT, MDD, SD, SSRIs, and TSH.

Abstract

Objective: To assess whether patients receiving aerobic exercise training performed either at home or in a supervised group setting achieve reductions in depression comparable to standard antidepressant medication (sertraline) and greater reductions in depression compared to placebo controls. Methods: Between October 2000 and November 2005, we performed a prospective, randomized controlled trial (SMILE study) with allocation concealment and blinded outcome assessment in a tertiary care teaching hospital. A total of 202 adults (153 women; 49 men) diagnosed with major depression were assigned randomly to one of four conditions: supervised exercise in a group setting; home-based exercise; antidepressant medication (sertraline, 50–200 mg daily); or placebo pill for 16 weeks. Patients underwent the structured clinical interview for depression and completed the Hamilton Depression Rating Scale (HAM-D). Results: After 4 months of treatment, 41% of the participants achieved remission, defined as no longer meeting the criteria for major depressive disorder (MDD) and a HAM-D score of <8. Patients receiving active treatments tended to have higher remission rates than the placebo controls: supervised exercise = 45%; home-based exercise = 40%; medication = 47%; placebo = 31% (p = .057). All treatment groups had lower HAM-D scores after treatment; scores for the active treatment groups were not significantly different from the placebo group (p = .23). Conclusions: The efficacy of exercise in patients seems generally comparable with patients receiving antidepressant medication and both tend to be better than the placebo in patients with MDD. Placebo response rates were high, suggesting that a considerable portion of the therapeutic response is determined by patient expectations, ongoing symptom monitoring, attention, and other nonspecific factors. BDI = Beck Depression Inventory; CI = confidence interval; HAM-D = Hamilton Depression Rating Scale; ITT = intention-to-treat; MDD = major depressive disorder; SD = standard deviation; SSRIs = selective serotonin reuptake inhibitors; TSH = thyroid stimulating hormone.