Exercise and pharmacotherapy in the treatment of major depressive disorder

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.

Trial registration: ClinicalTrials.gov NCT00331305.

Figure 1

Flowchart of participant recruitment and retainment throughout the study. MDD = major depressive disorder; ITT = intention-to-treat.

Figure 2

Mean aerobic capacity and exercise tolerance after 16 weeks of treatment, adjusting for pretreatment levels of outcome variable, age, gender, race, and past major depressive disorder. Participants in the exercise conditions showed greater aerobic capacity (left panel) and exercise tolerance (right panel) compared with patients in the medication or placebo conditions. Error bars represent 95% confidence limits. Planned contrasts for aerobic capacity were as follows: all exercise versus placebo, p = .0001; medication versus placebo, p = .420; all exercise versus medication, p = .0001. For exercise tolerance, the contrast results were: all exercise versus placebo, p = .0001; medication versus placebo, p = .410; all exercise versus medication, p = .0001. VO2 = oxygen consumption; Sup = supervised exercise; Med = medication; Plac = placebo.

Figure 3

Predicted probability of remission, defined as no major depressive disorder diagnosis and Hamilton Depression Rating Scale (HAM-D) score of <8 after treatment, using intention-to-treat (left panel) and limited to patients who did not exhibit an early response (n = 183) (right panel). Early responders are defined as patients with >50% reduction from baseline in Beck Depression Inventory scores after the first week of treatment. Probability estimates are for a patient with the most typical profile in the study: age 52 years, female, Caucasian, one prior major depressive episode, and a baseline HAM-D score of 17. Error bars represent 95% confidence limits. Planned contrasts using intention-to-treat yielded the following test results: all active treatment versus placebo, p = .057; all exercise versus medication, p = .636; supervised exercise versus home exercise, p = .666. After removing early responders, the contrast results were: all active treatment versus placebo, p = .022; all exercise versus medication, p = .879; supervised exercise versus home exercise, p = .519. Sup = supervised exercise; Med = medication; Plac = placebo.

Figure 4

Hamilton Depression Rating Scale (HAM-D) scores after 16 weeks of treatment using intention-to-treat analysis (left panel) and limited to patients who did not exhibit an early response (n = 183) (right panel). Probability estimates are for a patient with the most typical profile in the study: age 52 years, female, Caucasian, one prior major depressive episode, and a baseline HAM-D score of 17. Error bars represent 95% confidence limits. Planned contrasts for the HAM-D using intention-to-treat analysis yielded the following test results: all active treatment versus placebo, p = .231; all exercise versus medication, p = .574; supervised exercise versus home exercise, p = .624. After removing early responders, the contrast results were: all active treatment versus placebo, p = .123; all exercise versus medication, p = .514; supervised exercise versus home exercise, p = .510. Sup = supervised exercise; Med = medication; Plac = placebo.