Depression
Conditions
Keywords
Major Depression, Major Depressive Disorder, TMS, rTMS
Brief summary
The purpose of this research is to learn more about how rTMS works to reduce the symptoms of depression. This information can be used to improve the effectiveness of the treatment. The study will use functional magnetic resonance imaging (fMRI) to examine changes in brain function after treatment with rTMS. fMRI is a safe and painless technique that allows investigators to observe the brain at work. The investigators will use fMRI to see what regions of the brain become active when you perform a concentration task and how that activation is changed after rTMS.
Interventions
DEVICErepetitive Transcranial Magnetic Stimulation (rTMS)
20 active sessions, within a 4 week period, where subjects receive the same repetitive Transcranial Magnetic Stimulation (rTMS) treatment parameters as the sham arm.
Sponsors
National Institute of Mental Health (NIMH)
Neuronetics
University of Michigan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
22 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Primary diagnosis of major depressive disorder * Male and female subjects, ages 22-65 * Have failed at least 1 antidepressant medication at adequate dose and duration * On stable antidepressant medication regimen for at least 4 weeks prior to TMS therapy
Exclusion criteria
* Diagnosed with a psychotic, bipolar, obsessive-compulsive or post-traumatic stress disorder * Active substance abuse, including alcohol * Medical and/or neurological condition that could affect your brain function or risk of seizure, including a stroke, epilepsy, or a closed head injury; * No presence of an implanted device like a pacemaker/neurostimulator or metal in the head or body; * Pregnant or trying to get pregnant * Failed to respond to an adequate course of electroconvulsive therapy (ECT) * Previous treatment with TMS * Current depressive episode longer than 5 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Depressive Symptoms at 4 Weeks | 4 weeks after baseline | MADRS: Montgomery Asberg Depression Rating Scale Range: 0 - 60 0 to 6 - normal/symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression \>34 - severe depression |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Depression Symptoms at 4 Weeks- Secondary | 4 weeks after baseline | Depressive symptoms as measured by the 17-item Hamilton Depression Rating Scale (HRSD17) Range: 0-53 Normal: 0-7 Mild: 8 - 13 Moderate 14 - 18 Severe: 19-22 Very severe \> 22 |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited between October 2013 and October 2015. Subjects exhibited moderate levels of treatment resistance
Pre-assignment details
44 patients were screened in person and 40 consented for the study.
Participants by arm
| Arm | Count |
|---|---|
| Active rTMS 20 active sessions | 16 |
| Sham rTMS 20 sham sessions | 16 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 3 |
Baseline characteristics
| Characteristic | Active rTMS | Sham rTMS | Total |
|---|---|---|---|
| Age, Continuous | 46.9 years STANDARD_DEVIATION 10.7 | 44.1 years STANDARD_DEVIATION 11.1 | 45.5 years STANDARD_DEVIATION 10.9 |
| Antidepressant Treatment History Form (ATHF-current) | 2.56 units on a scale STANDARD_DEVIATION 1.75 | 2.94 units on a scale STANDARD_DEVIATION 1.77 | 2.75 units on a scale STANDARD_DEVIATION 1.74 |
| Global assessment of Function (GAF) | 52.6 units on a scale STANDARD_DEVIATION 4.7 | 55.6 units on a scale STANDARD_DEVIATION 4.3 | 54.1 units on a scale STANDARD_DEVIATION 4.6 |
| HRSD-17 | 16 units on a scale STANDARD_DEVIATION 3.9 | 13.1 units on a scale STANDARD_DEVIATION 2.3 | 14.2 units on a scale STANDARD_DEVIATION 4.4 |
| MADRS | 25.4 units on a scale STANDARD_DEVIATION 5.7 | 21.9 units on a scale STANDARD_DEVIATION 3.1 | 23.5 units on a scale STANDARD_DEVIATION 5.1 |
| Sex: Female, Male Female | 11 Participants | 10 Participants | 21 Participants |
| Sex: Female, Male Male | 5 Participants | 6 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 17 | 5 / 17 |
| serious Total, serious adverse events | 0 / 17 | 0 / 17 |
Outcome results
Primary
Depressive Symptoms at 4 Weeks
MADRS: Montgomery Asberg Depression Rating Scale Range: 0 - 60 0 to 6 - normal/symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression \>34 - severe depression
Time frame: 4 weeks after baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active rTMS | Depressive Symptoms at 4 Weeks | 15.6 units on a scale | Standard Deviation 8.3 |
| Sham rTMS | Depressive Symptoms at 4 Weeks | 15.6 units on a scale | Standard Deviation 8.3 |
Comparison: Repeated measures ANCOVA at 4 weeks with baseline MADRS as co-variatep-value: 0.16ANCOVA
Secondary
Depression Symptoms at 4 Weeks- Secondary
Depressive symptoms as measured by the 17-item Hamilton Depression Rating Scale (HRSD17) Range: 0-53 Normal: 0-7 Mild: 8 - 13 Moderate 14 - 18 Severe: 19-22 Very severe \> 22
Time frame: 4 weeks after baseline
Population: Sample analyzed included all participants who entered the study and received MRI scans at baseline and after 4 weeks of treatment. Repeated measures ANCOVA with screening MADRS score as co-variate
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active rTMS | Depression Symptoms at 4 Weeks- Secondary | 9.1 units on a scale | Standard Deviation 4.8 |
| Sham rTMS | Depression Symptoms at 4 Weeks- Secondary | 10.1 units on a scale | Standard Deviation 5.2 |
Comparison: Repeated measures ANCOVA with baseline MADRS as co-variatep-value: 0.04ANCOVA