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Exercise and Pharmacotherapy in the Treatment of Major Depressive Disorder

Blumenthal, James A. PhD; Babyak, Michael A. PhD; Doraiswamy, P Murali MD; Watkins, Lana PhD; Hoffman, Benson M. PhD; Barbour, Krista A. PhD; Herman, Steve PhD; Craighead, W Edward PhD; Brosse, Alisha L. PhD; Waugh, Robert MD; Hinderliter, Alan MD; Sherwood, Andrew PhD

doi: 10.1097/PSY.0b013e318148c19a
Original Articles

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.

From the Department of Psychiatry and Behavioral Sciences (J.A.B., M.A.B., P.M.D., L.W., B.H., K.B., S.H., A.L.B., A.S.), Duke University Medical Center, Durham, North Carolina; Department of Psychiatry and Behavioral Sciences (W.E.C.), Emory University, Atlanta, Georgia; Department of Medicine (R.W.), Duke University Medical Center, Durham, North Carolina; and Department of Medicine (A.H.), University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Trial Registration. Clinical Trials Government Identifier: NCT-00331305.

Address correspondence and reprint requests to James Blumenthal, Department of Psychiatry and Behavioral Sciences, Box 3119, Duke University Medical Center, Durham, NC 7710. E-mail:

Received for publication March 16, 2007; revision received May 14, 2007.

This research was supported by Grant MH 49679 (JAB) from the National Institutes of Health and National Institutes of Health Grant MO1-RR-30 from the National Center for Research Resources, Clinical Research Centers Program. Medication and matched placebo pills were provided by a grant from Pfizer Pharmaceuticals, Inc. Dr. Blumenthal previously received an investigator initiated research grant from Pfizer/Eisai for an unrelated study. Dr. Doraiswamy has received research grants and honoraria from several pharmaceutical companies and antidepressant manufacturers, including Pfizer, but does not own stock in these companies. Dr. Craighead owns stock in Novadel.

Copyright © 2007 by American Psychosomatic Society
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