TREAD: Adding Exercise to Antidepressant Medication Treatment for Depression
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 |
---|---|---|
|
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
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
- 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
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
- Crismon ML, Trivedi M, Pigott TA, Rush AJ, Hirschfeld RM, Kahn DA, DeBattista C, Nelson JC, Nierenberg AA, Sackeim HA, Thase ME. The Texas Medication Algorithm Project: report of the Texas Consensus Conference Panel on Medication Treatment of Major Depressive Disorder. J Clin Psychiatry. 1999 Mar;60(3):142-56. Review.
- Dunn AL, Trivedi MH, Kampert JB, Clark CG, Chambliss HO. The DOSE study: a clinical trial to examine efficacy and dose response of exercise as treatment for depression. Control Clin Trials. 2002 Oct;23(5):584-603.
- Dunn AL, Trivedi MH, O'Neal HA. Physical activity dose-response effects on outcomes of depression and anxiety. Med Sci Sports Exerc. 2001 Jun;33(6 Suppl):S587-97; discussion 609-10. Review.
- Galper DI, Trivedi MH, Barlow CE, Dunn AL, Kampert JB. Inverse association between physical inactivity and mental health in men and women. Med Sci Sports Exerc. 2006 Jan;38(1):173-8.
- Trivedi MH, Greer TL, Grannemann BD, Chambliss HO, Jordan AN. Exercise as an augmentation strategy for treatment of major depression. J Psychiatr Pract. 2006 Jul;12(4):205-13.
- STU 092010-032
- R01MH067692-01
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
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
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 |
madhukar.trivedi@utsouthwestern.edu |
- STU 092010-032
- R01MH067692-01