TREAD: Adding Exercise to Antidepressant Medication Treatment for Depression

Sponsor
University of Texas Southwestern Medical Center (Other)
Overall Status
Completed
CT.gov ID
NCT00076258
Collaborator
National Institute of Mental Health (NIMH) (NIH)
126
1
2
52
2.4

Study Details

Study Description

Brief Summary

This study will assess the effectiveness of an exercise program in improving antidepressant medication treatment for individuals with major depressive disorder (MDD).

Condition or Disease Intervention/Treatment Phase
  • Behavioral: SSRI + LD
  • Behavioral: SSRI + PHD
N/A

Detailed Description

Partial response to antidepressant treatment is common in people with MDD and is associated with significant morbidity and reduced quality of life. Pharmacological therapies have been used to augment the effect of antidepressants; however, such therapies are associated with a range of adverse effects. Studies indicate that exercise may be safe and effective in augmenting depression treatment. This study will determine whether exercise can complement selective serotonin reuptake inhibitor (SSRI) therapy in people with MDD who have residual symptoms of depression despite drug treatment.

Participants will be randomly assigned to either high frequency exercise or low frequency exercise for 12 weeks. Depression symptoms will be measured weekly. Quality of life and satisfaction with the study will also be measured. Depression scales and self-reports will be used to assess participants.

Study Design

Study Type:
Interventional
Actual Enrollment :
126 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Treatment With Exercise Augmentation for Depression (TREAD)
Study Start Date :
Apr 1, 2003
Actual Primary Completion Date :
Oct 1, 2006
Actual Study Completion Date :
Aug 1, 2007

Arms and Interventions

Arm Intervention/Treatment
Experimental: SSRI+ LD

A low dose aerobic exercise (LD) augmentation intervention to SSRI

Behavioral: SSRI + LD
Eligible participants who have completed an adequate trial of SSRI monotherapy and all screening visits are randomly assigned to 24 weeks of SSRI augmentation with : a low dose of aerobic exercise (LD) or a public health dose of aerobic exercise (PHD). The acute phase of TREAD consists of the first 12 weeks of exercise augmentation intervention and includes: a) an individualized PHD- or LD aerobic exercise prescription; b) an empiricallybased behavioral intervention, including selfmonitoring tools and an interactive website, designed to maximize exercise adherence and minimize drop-out; and c) exercise instruction and supervised training sessions at The Cooper Institute (CI) as well as self-administered, home-based training sessions.

Experimental: SSRI+ PHD

A public health dose of aerobic exercise (PHD) augmentation intervention to SSRI

Behavioral: SSRI + PHD
Eligible participants who have completed an adequate trial of SSRI monotherapy and all screening visits are randomly assigned to 24 weeks of SSRI augmentation with : a low dose of aerobic exercise (LD) or a public health dose of aerobic exercise (PHD). The acute phase of TREAD consists of the first 12 weeks of exercise augmentation intervention and includes: a) an individualized PHD- or LD aerobic exercise prescription; b) an empiricallybased behavioral intervention, including selfmonitoring tools and an interactive website, designed to maximize exercise adherence and minimize drop-out; and c) exercise instruction and supervised training sessions at The Cooper Institute (CI) as well as self-administered, home-based training sessions.

Outcome Measures

Primary Outcome Measures

  1. Percentage of Participants With Remission (Score of 12 or Less on Inventory for Depressive Symptomatology- Clinician-rated) [12 weeks]

    The primary outcome measure- percentage of participants with remission (score of 12 or less on Inventory for Depressive Symptomatology- Clinician-rated). The change over time in probability of remission (IDS-C30 score ≤ 12) was compared between groups using a generalized linear mixed model (GLMM)41 as implemented in SAS (Proc Glimmix; SAS Institute Inc, Cary, North Carolina).

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 70 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Diagnosis of Major Depressive Disorder

  • Score of 14 or higher on the Hamilton Depression Scale (HAM-D)

  • 8 to 12 weeks of SSRI treatment, with at least 6 weeks at adequate doses

  • Sedentary lifestyle

  • Physically capable of exercise

  • Body mass index (BMI) less than 40 kg/m2

  • Willing and able to comply with study requirements

Exclusion Criteria:
  • Significant cardiovascular disease or other medical conditions

  • Uncontrolled hypertension

  • Abnormal exercise stress test

  • Hematologic disorders

  • Comorbid disorders, including depression due to another comorbid condition, psychotic disorder, bipolar disorder, schizophrenia, schizoaffective disorder, eating disorder, or obsessive compulsive disorder (OCD)

  • Alcohol and/or substance abuse in the past 6 months

  • Hospitalization for mental illness within the past year

  • High suicide risk

  • Use of psychopharmacological or psychotherapeutic treatment other than SSRIs

  • Failure to respond to two or more adequate pharmacological treatments during the current depressive episode

  • Significantly elevated blood lipids

  • Pregnancy

Contacts and Locations

Locations

Site City State Country Postal Code
1 University of Texas Southwestern Medical Center at Dallas Dallas Texas United States 75235

Sponsors and Collaborators

  • University of Texas Southwestern Medical Center
  • National Institute of Mental Health (NIMH)

Investigators

  • Principal Investigator: Madhukar Trivedi, MD, UT Southwestern Medical Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

Responsible Party:
Madhukar H. Trivedi, MD, Professor of Psychiatry, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:
NCT00076258
Other Study ID Numbers:
  • STU 092010-032
  • R01MH067692-01
First Posted:
Jan 19, 2004
Last Update Posted:
Sep 23, 2020
Last Verified:
Sep 1, 2020
Keywords provided by Madhukar H. Trivedi, MD, Professor of Psychiatry, University of Texas Southwestern Medical Center
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title SSRI+ LD SSRI+ PHD
Arm/Group Description A low dose aerobic exercise (LD) augmentation intervention to SSRI SSRI + LD: Eligible participants who have completed an adequate trial of SSRI monotherapy and all screening visits are randomly assigned to 24 weeks of SSRI augmentation with : a low dose of aerobic exercise (LD) or a public health dose of aerobic exercise (PHD). The acute phase of TREAD consists of the first 12 weeks of exercise augmentation intervention and includes: a) an individualized PHD- or LD aerobic exercise prescription; b) an empiricallybased behavioral intervention, including selfmonitoring tools and an interactive website, designed to maximize exercise adherence and minimize drop-out; and c) exercise instruction and supervised training sessions at The Cooper Institute (CI) as well as self-administered, home-based training sessions. A public health dose of aerobic exercise (PHD) augmentation intervention to SSRI SSRI + PHD: Eligible participants who have completed an adequate trial of SSRI monotherapy and all screening visits are randomly assigned to 24 weeks of SSRI augmentation with : a low dose of aerobic exercise (LD) or a public health dose of aerobic exercise (PHD). The acute phase of TREAD consists of the first 12 weeks of exercise augmentation intervention and includes: a) an individualized PHD- or LD aerobic exercise prescription; b) an empiricallybased behavioral intervention, including selfmonitoring tools and an interactive website, designed to maximize exercise adherence and minimize drop-out; and c) exercise instruction and supervised training sessions at The Cooper Institute (CI) as well as self-administered, home-based training sessions.
Period Title: Overall Study
STARTED 62 64
COMPLETED 61 61
NOT COMPLETED 1 3

Baseline Characteristics

Arm/Group Title SSRI+ LD SSRI+ PHD Total
Arm/Group Description A low dose aerobic exercise (LD) augmentation intervention to SSRI SSRI + LD: Eligible participants who have completed an adequate trial of SSRI monotherapy and all screening visits are randomly assigned to 24 weeks of SSRI augmentation with : a low dose of aerobic exercise (LD) or a public health dose of aerobic exercise (PHD). The acute phase of TREAD consists of the first 12 weeks of exercise augmentation intervention and includes: a) an individualized PHD- or LD aerobic exercise prescription; b) an empiricallybased behavioral intervention, including selfmonitoring tools and an interactive website, designed to maximize exercise adherence and minimize drop-out; and c) exercise instruction and supervised training sessions at The Cooper Institute (CI) as well as self-administered, home-based training sessions. A public health dose of aerobic exercise (PHD) augmentation intervention to SSRI SSRI + PHD: Eligible participants who have completed an adequate trial of SSRI monotherapy and all screening visits are randomly assigned to 24 weeks of SSRI augmentation with : a low dose of aerobic exercise (LD) or a public health dose of aerobic exercise (PHD). The acute phase of TREAD consists of the first 12 weeks of exercise augmentation intervention and includes: a) an individualized PHD- or LD aerobic exercise prescription; b) an empiricallybased behavioral intervention, including selfmonitoring tools and an interactive website, designed to maximize exercise adherence and minimize drop-out; and c) exercise instruction and supervised training sessions at The Cooper Institute (CI) as well as self-administered, home-based training sessions. Total of all reporting groups
Overall Participants 61 61 122
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
48.5
(9.4)
45.6
(10.4)
47.05
(9.9)
Sex: Female, Male (Count of Participants)
Female
48
78.7%
52
85.2%
100
82%
Male
13
21.3%
9
14.8%
22
18%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
1
1.6%
0
0%
1
0.8%
Not Hispanic or Latino
60
98.4%
61
100%
121
99.2%
Unknown or Not Reported
0
0%
0
0%
0
0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
0
0%
0
0%
Asian
0
0%
0
0%
0
0%
Native Hawaiian or Other Pacific Islander
1
1.6%
1
1.6%
2
1.6%
Black or African American
5
8.2%
9
14.8%
14
11.5%
White
54
88.5%
51
83.6%
105
86.1%
More than one race
1
1.6%
0
0%
1
0.8%
Unknown or Not Reported
0
0%
0
0%
0
0%
Hamilton Depression Rating Scale (17 item) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]
18.1
(3.8)
17.8
(3.8)
17.9
(3.8)

Outcome Measures

1. Primary Outcome
Title Percentage of Participants With Remission (Score of 12 or Less on Inventory for Depressive Symptomatology- Clinician-rated)
Description The primary outcome measure- percentage of participants with remission (score of 12 or less on Inventory for Depressive Symptomatology- Clinician-rated). The change over time in probability of remission (IDS-C30 score ≤ 12) was compared between groups using a generalized linear mixed model (GLMM)41 as implemented in SAS (Proc Glimmix; SAS Institute Inc, Cary, North Carolina).
Time Frame 12 weeks

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title SSRI+ LD SSRI+ PHD
Arm/Group Description A low dose aerobic exercise (LD) augmentation intervention to SSRI SSRI + LD: Eligible participants who have completed an adequate trial of SSRI monotherapy and all screening visits are randomly assigned to 24 weeks of SSRI augmentation with : a low dose of aerobic exercise (LD) or a public health dose of aerobic exercise (PHD). The acute phase of TREAD consists of the first 12 weeks of exercise augmentation intervention and includes: a) an individualized PHD- or LD aerobic exercise prescription; b) an empiricallybased behavioral intervention, including selfmonitoring tools and an interactive website, designed to maximize exercise adherence and minimize drop-out; and c) exercise instruction and supervised training sessions at The Cooper Institute (CI) as well as self-administered, home-based training sessions. A public health dose of aerobic exercise (PHD) augmentation intervention to SSRI SSRI + PHD: Eligible participants who have completed an adequate trial of SSRI monotherapy and all screening visits are randomly assigned to 24 weeks of SSRI augmentation with : a low dose of aerobic exercise (LD) or a public health dose of aerobic exercise (PHD). The acute phase of TREAD consists of the first 12 weeks of exercise augmentation intervention and includes: a) an individualized PHD- or LD aerobic exercise prescription; b) an empiricallybased behavioral intervention, including selfmonitoring tools and an interactive website, designed to maximize exercise adherence and minimize drop-out; and c) exercise instruction and supervised training sessions at The Cooper Institute (CI) as well as self-administered, home-based training sessions.
Measure Participants 61 61
Number [percentage of participants in remission]
18
29.5%
18
29.5%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SSRI+ LD, SSRI+ PHD
Comments
Type of Statistical Test Superiority or Other (legacy)
Comments
Statistical Test of Hypothesis p-Value <0.05
Comments
Method Generalized Linear Mixed Model
Comments Both unadjusted and adjusted rates (for significant covariates) were reported
Method of Estimation Estimation Parameter Remission rate
Estimated Value 29.5
Confidence Interval (2-Sided) %
to
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection SSRI+ LD, SSRI+ PHD
Comments For the covariate adjusted GLMM the remission rates were 15.5 for the LD and 28.3 for the PHD with a p < 0.06 and the NNT of 7.8 for the PHD versus the LD.
Type of Statistical Test Superiority or Other (legacy)
Comments
Statistical Test of Hypothesis p-Value <0.05
Comments
Method Generalized Linear Mixed Model
Comments
Method of Estimation Estimation Parameter Remission Rate
Estimated Value 28.3
Confidence Interval (2-Sided) %
to
Parameter Dispersion Type:
Value:
Estimation Comments

Adverse Events

Time Frame 24 months
Adverse Event Reporting Description
Arm/Group Title SSRI+ LD SSRI+ PHD
Arm/Group Description A low dose aerobic exercise (LD) augmentation intervention to SSRI SSRI + LD: Eligible participants who have completed an adequate trial of SSRI monotherapy and all screening visits are randomly assigned to 24 weeks of SSRI augmentation with : a low dose of aerobic exercise (LD) or a public health dose of aerobic exercise (PHD). The acute phase of TREAD consists of the first 12 weeks of exercise augmentation intervention and includes: a) an individualized PHD- or LD aerobic exercise prescription; b) an empiricallybased behavioral intervention, including selfmonitoring tools and an interactive website, designed to maximize exercise adherence and minimize drop-out; and c) exercise instruction and supervised training sessions at The Cooper Institute (CI) as well as self-administered, home-based training sessions. A public health dose of aerobic exercise (PHD) augmentation intervention to SSRI SSRI + PHD: Eligible participants who have completed an adequate trial of SSRI monotherapy and all screening visits are randomly assigned to 24 weeks of SSRI augmentation with : a low dose of aerobic exercise (LD) or a public health dose of aerobic exercise (PHD). The acute phase of TREAD consists of the first 12 weeks of exercise augmentation intervention and includes: a) an individualized PHD- or LD aerobic exercise prescription; b) an empiricallybased behavioral intervention, including selfmonitoring tools and an interactive website, designed to maximize exercise adherence and minimize drop-out; and c) exercise instruction and supervised training sessions at The Cooper Institute (CI) as well as self-administered, home-based training sessions.
All Cause Mortality
SSRI+ LD SSRI+ PHD
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total / (NaN) / (NaN)
Serious Adverse Events
SSRI+ LD SSRI+ PHD
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/62 (0%) 0/64 (0%)
Other (Not Including Serious) Adverse Events
SSRI+ LD SSRI+ PHD
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 62/62 (100%) 64/64 (100%)
Cardiac disorders
Palpitation, dizzy and chest pain 29/62 (46.8%) 188 33/64 (51.6%) 143
Eye disorders
Blurred vision /ears ringing 36/62 (58.1%) 207 25/64 (39.1%) 288
Gastrointestinal disorders
Diarrhea, constipation, dry mouth and Nausea 52/62 (83.9%) 594 55/64 (85.9%) 598
Nervous system disorders
Headache, tremors, coordination and dizzy 56/62 (90.3%) 604 56/64 (87.5%) 515
Psychiatric disorders
Difficulty sleeping, sleeps too much 58/62 (93.5%) 621 61/64 (95.3%) 532
Renal and urinary disorders
Difficult urination, painful urination,frequent urination and irregular menstruation 28/62 (45.2%) 186 28/64 (43.8%) 125
Reproductive system and breast disorders
loss of desire, trouble orgasm and trouble erections 50/62 (80.6%) 521 40/64 (62.5%) 377
Skin and subcutaneous tissue disorders
Rash, perspiration, itching and dry skin 51/62 (82.3%) 600 49/64 (76.6%) 620

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title Madhukar H Trivedi
Organization UT Southwestern Medical Center
Phone 214-648-0188
Email madhukar.trivedi@utsouthwestern.edu
Responsible Party:
Madhukar H. Trivedi, MD, Professor of Psychiatry, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:
NCT00076258
Other Study ID Numbers:
  • STU 092010-032
  • R01MH067692-01
First Posted:
Jan 19, 2004
Last Update Posted:
Sep 23, 2020
Last Verified:
Sep 1, 2020