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Original Research

Exercise as an Augmentation Treatment for Nonremitted Major Depressive Disorder: A Randomized, Parallel Dose Comparison

Madhukar H. Trivedi, MD; Tracy L. Greer, PhD; Timothy S. Church, MD, PhD, MPH; Thomas J. Carmody, PhD; Bruce D. Grannemann, MA; Daniel I. Galper, PhD; Andrea L. Dunn, PhD; Conrad P. Earnest, PhD; Prabha Sunderajan, MD; Steven S. Henley, MS; and Steven N. Blair, PED

Published: May 15, 2011

Article Abstract

Objective: Most patients with major depressive disorder (MDD) require second-step treatments to achieve remission. The TReatment with Exercise Augmentation for Depression (TREAD) study was designed to test the efficacy of aerobic exercise as an augmentation treatment for MDD patients who had not remitted with antidepressant treatment.

Method: Eligible participants in this randomized controlled trial were sedentary individuals (men and women aged 18-70 years) diagnosed with DSM-IV nonpsychotic MDD who had not remitted with selective serotonin reuptake inhibitor (SSRI) treatment. Participants were recruited through physician referrals and advertisements. A total of 126 participants were randomized to augmentation treatment with either 16 kcal per kg per week (KKW) or 4 KKW of exercise expenditure for 12 weeks while SSRI treatment was held constant. Supervised sessions were conducted at The Cooper Institute, Dallas, Texas, with additional home-based sessions as needed to fulfill the weekly exercise prescription. The primary outcome was remission (as determined by a score ≤ 12 on the Inventory of Depressive Symptomatology, Clinician-Rated). The study took place between August 2003 and August 2007.

Results: There were significant improvements over time for both groups combined (F1,121 = 39.9, P < .0001), without differential group effect (group effect: F1,134 = 3.2, P = .07; group-by-time effect: F1,119 = 3.8, P = .06). Adjusted remission rates at week 12 were 28.3% versus 15.5% for the 16-KKW and 4-KKW groups, respectively, leading to a number needed to treat (NNT) of 7.8 for 16 KKW versus 4 KKW. Men, regardless of family history of mental illness, and women without a family history of mental illness had higher remission rates by week 12 with higher-dose (women, 39.0%; men, 85.4%) than with lower-dose exercise (women, 5.6%; men, 0.1%) (women: t95 = 2.1, P = .04; men: t88 = 5.4, P < .0001) (NNT: women, 3.0; men, 1.2).

Conclusions: There was a trend for higher remission rates in the higher-dose exercise group (P < .06), with a clinically meaningful NNT of 7.8 in favor of the high exercise dose. Significant differences between groups were found when the moderating effects of gender and family history of mental illness were taken into account and suggest that higher-dose exercise may be better for all men and for women without a family history of mental illness.

Trial Registration: Identifier: NCT00076258

J Clin Psychiatry 2011;72(5):677-684

Submitted: November 24, 2010; accepted February 23, 2011 (doi:10.4088/JCP.10m06743).

Corresponding author: Madhukar H. Trivedi, MD, Division on Mood Disorders, Department of Psychiatry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9119 (

Volume: 72

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