title: Exercise as an augmentation treatment for nonremitted major depressive disorder: a randomized, parallel dose comparison.
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.
  
  
  METHODS
  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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00076258.
authors.affiliation: Division on Mood Disorders, Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9119, USA. madhukar.trivedi@utsouthwestern.edu
authors.forename: Madhukar H
authors.initials: MH
authors.lastname: Trivedi
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Greer
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Church
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Carmody
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Grannemann
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Galper
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Dunn
authors.forename: Conrad P
authors.initials: CP
authors.lastname: Earnest
authors.forename: Prabha
authors.initials: P
authors.lastname: Sunderajan
authors.forename: Steven S
authors.initials: SS
authors.lastname: Henley
authors.forename: Steven N
authors.initials: SN
authors.lastname: Blair
mesh_terms: D003131:Combined Modality Therapy; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000628:therapy*; D005081:Exercise Therapy / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D011569:Psychiatric Status Rating Scales; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D017367:Selective Serotonin Reuptake Inhibitors