Background
Repetitive transcranial magnetic stimulation (rTMS) in the treatment of major depression
Importance of efficacious anti-depressant treatment in Veteran populations
Methods/design
Population
Inclusion criteria | Exclusion criteria |
---|---|
Between 18 and 80 years of age. | Pregnant or lactating woman (this is an FDA-required exclusion. In the future, if rTMS becomes a proven treatment for major depression, its safety in the context of pregnancy should be studied separately) |
Using the Structured Clinical Interview for DSM Disorders (SCID) for DSM-IV-TR patients will be diagnosed MDD | Unable to be safely withdrawn, at least 2 weeks prior to treatment commencement, from medications that substantially increase the risk of having seizures |
Have a HRSD24 ≥ 20 no more than 7 days prior to randomization | Have a cardiac pacemaker |
Exhibit moderate level of resistance to antidepressant treatment defined, using the ATHF, as failure of at least two adequate medication trials | Have an implanted device or metal in the brain |
Duration of current episode of MDD ≤ 10 years | Have a cochlear implant |
Ability to obtain a motor threshold (MT) (should be determined at the end of the screening process) | Have a mass lesion, cerebral infarct, increased intracranial pressure, or other active central nervous system (CNS) disease, including a seizure disorder |
Currently under the care of a VA psychiatrist | Known current psychosis as determined by DSM-IV or SCID (axis I, psychotic disorder, schizophrenia) or history of a non-mood psychotic disorder |
If on a psychotropic medication regimen, that regimen will be stable for at least 4 weeks prior to randomization in the study and patient will be willing to remain on a stable regimen during the acute treatment phase | Known current bipolar I disorder as determined by SCID or a history of bipolar I disorder |
Has an adequately stable condition and environment to enable attendance at scheduled clinic visits | Current amnestic disorders, dementia, Blessed Orientation-Memory-Concentration score > 10, delirium, or other cognitive disorders |
For female participants, agrees to use one of the following acceptable methods of birth control | Current substance abuse (not including caffeine or nicotine) as determined by positive toxicology screen, or by history via SCID, within 3 months prior to screening |
Able to read, verbalize understanding and voluntarily sign the Informed Consent Form prior to performance of any study-specific procedures or assessments | Patients with an elevated risk of seizure due to TBI |
Participation in another concurrent clinical trial | |
Patients with prior exposure to rTMS | |
Active current suicidal intent or plan as evidenced by a score of 4 or 5 on the suicidal ideation portion of the Columbia Suicide Severity Rating Scale (CSSRS) or the endorsement of an actual attempt, interrupted attempt, or an aborted attempt in the past 6 months | |
Unstable cardiac disease or recent (<3 months previous) myocardial infarction | |
Patient refuses to sign consent for participation in the study |
Randomization to treatment
Blinding
Safety and adverse events
Suicidality monitoring protocol
Substance use monitoring protocol
Study management
Data Coordinating Center
Executive Committee
Data Monitoring Committee
Site Monitoring, Auditing and Resource Team (SMART)
Central Institutional Review Board (CIRB)
Intervention
Treatment stimulus
Treatment control
Stimulation site: the 6 cm rule
Assessment and analysis
Outcomes
Outcomes | Metric scale | Schedule | |
---|---|---|---|
Primary outcome | Hamilton Rating Scale for Depression (HRSD) | 24-Item instrument with overall score range of 0–76 | Measured at screening phase as baseline, end of each acute treatment week, and end of every 4 weeks during the follow-up phase |
Secondary outcomes | Montgomery-Asberg Depression Rating Scale (MADRS) | 10-Item instrument with overall score range of 0–60 | Measured at screening phase as baseline, end of each acute treatment week, and end of every 4 weeks during the follow-up phase |
Beck Depression Inventory (BDI) | 21-Item self-report test with overall score range of 0–63 | Measured at screening phase as baseline, end of each acute treatment week, and end of every 4 weeks during the follow-up phase | |
Beck Scale for Suicide Ideation (BSS) | 21-Item self-report test with overall score range of 0–38 with last 2 items not counted in scoring | Measured at screening phase as baseline, end of each acute treatment week, end of each taper week and week 4, and end of every 4 weeks during the follow-up phase | |
Veterans RAND 36-Item Health Survey (VR-36) | A self-administered survey consisting of two parts, i.e. Physical Component Summary (PCS, standardized score range of 0–100) and Mental Component Summary (MCS, standardized score range of 0–100) | Measured at screening phase as baseline, end of the acute treatment phase, and end of the follow-up phase | |
Neuropsychological Battery | A cognitive function test including measures of executive function, attention, memory, visuospatial ability, processing speed, psychomotor function, and premorbid intelligence | Measured at screening phase as baseline, end of the acute treatment phase, and end of the follow-up phase |
Assessment (domain) and specific measurement | Weeks 2–4 | Acute treatment phase | Follow-up phase | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
4–11 weeks | 24 weeks | |||||||||||||||
End of session numbera
| Taper | Follow up | ||||||||||||||
5 | 10 | 15 | 20 | [25] | [30] | 1 | 2 | 3 | 4 | 8 | 12 | 16 | 20 | 24 | ||
Consent | S* | |||||||||||||||
Screening | S | |||||||||||||||
Randomization | B* | |||||||||||||||
Baseline | S | |||||||||||||||
Medical history | S | |||||||||||||||
Physical exam | S | x | ||||||||||||||
Laboratory measurements | S | |||||||||||||||
SCID-I | S | |||||||||||||||
Current/past ATHF | S | |||||||||||||||
Lifetime drinking history | B | |||||||||||||||
CAPS | B | x | x | |||||||||||||
THQ | B | |||||||||||||||
LSC-R | B | |||||||||||||||
BOMC | S | |||||||||||||||
Medication use | S | x | x | x | x | x | x | x | x | x | x | x | x | x | x | x |
rTMS treatment log | x | x | x | x | x | x | ||||||||||
rTMS taper log | x | x | x | |||||||||||||
HRSD and MADRS | Sb
| x | x | x | x | x | x | x | x | x | x | x | x | |||
BDI | B | x | x | x | x | x | x | x | x | x | x | x | x | |||
QIDS-C16 | B | x | x | x | x | x | x | x | x | x | x | x | x | |||
C-SSRS | S | |||||||||||||||
C-SSRS follow up | x | x | x | x | x | x | x | x | x | x | x | x | x | x | x | |
BSS | S | x | x | x | x | x | x | x | x | x | x | x | x | x | x | x |
BHS | S | x | x | x | x | x | x | x | x | x | x | x | x | x | x | x |
VR-36 | B | x | x | |||||||||||||
Neuropsychological battery | B | x | x | |||||||||||||
DAST | S | x | x | |||||||||||||
PCL | B | x | x | |||||||||||||
MAST | S | x | x | |||||||||||||
STAXI-2 | S | x | x | x | x | x | x | x | x | x | x | x | x | x | x | x |
Urine toxicology screen and alcohol test | S | x | x | X | x | x | x | x | ||||||||
Protocol deviation | As required | |||||||||||||||
AE/SAE/UADE | As required |