Depression
Conditions
Brief summary
This trial will compare the efficacy of active inhibitory OFC-rTMS to sham OFC-rTMS in major depression. The trial will include structural and functional MRI, EEG, and behavioral measures obtained before, during, and after treatment.
Interventions
Sponsors
Canadian Institutes of Health Research (CIHR)
University Health Network, Toronto
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. are outpatients 2. are voluntary and competent to consent to treatment 3. have a Mini-International Neuropsychiatric Interview (MINI) confirmed diagnosis of major depressive disorder (MDD), single or recurrent 4. are between the ages of 18 and 65 5. have failed to achieve a clinical response to an adequate dose of an antidepressant based on an Antidepressant Treatment History Form (ATHF) score of \> 3 in the current 6. have a score \> 18 on the HAMD-17 7. have had no increase or initiation of any psychotropic medication in the 4 weeks prior to screening 8. able to adhere to the treatment schedule 9. Pass the TMS adult safety-screening (TASS) questionnaire 10. have normal thyroid functioning based on pre-study blood work.
Exclusion criteria
1. have a MINI-International Neuropsychiatric (MINI) confirmed diagnosis of substance dependence or abuse within the last 3 months 2. have a concomitant major unstable medical illness, cardiac pacemaker or implanted medication pump 3. have active suicidal intent 4. are pregnant 5. have a lifetime Mini-International Neuropsychiatric Interview (MINI) diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms 6. have a MINI diagnosis of obsessive compulsive disorder, post-traumatic stress disorder (current or within the last year), anxiety disorder (generalized anxiety disorder, social anxiety disorder, panic disorder), or dysthymia, assessed by a study investigator to be primary and causing greater impairment than MDD 7. have a diagnosis of any personality disorder, and assessed by a study investigator to be primary and causing greater impairment than MDD 8. have failed a course of electroconvulsive therapy (ECT) in the current episode or previous episode 9. have any significant neurological disorder or insult including, but not limited to: any condition likely to be associated with increased intracranial pressure, space occupying brain lesion, any history of seizure except those therapeutically induced by ECT, cerebral aneurysm, Parkinson's disease, Huntington's chorea, multiple sclerosis, significant head trauma with loss of consciousness for greater than or equal to 5 minutes 10. have an intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed 11. if participating in psychotherapy, must have been in stable treatment for at least 3 months prior to entry into the study, with no anticipation of change in the frequency of therapeutic sessions, or the therapeutic focus over the duration of the study 12. clinically significant laboratory abnormality, in the opinion of the study investigator 13. currently (or in the last 4 weeks) take more than lorazepam 2 mg daily (or equivalent) or any dose of an anticonvulsant due to the potential to limit rTMS efficacy 14. non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 17-Item Hamilton Rating Scale for Depression (HAMD-17) | Baseline, after each week of treatment (i.e. after 5 days of treatment) and at 1, 4, and 12 weeks post-treatment. | Outcome measured by a change in HAMD-17 score from baseline to 2 weeks post-treatment. A 50% improvement in the score is considered a response to rTMS. A final score of \<8 is categorized as remission. |
Secondary
| Measure | Time frame |
|---|---|
| Beck Depression Inventory-II (BDI-II) | Daily for 6 weeks |
Other
| Measure | Time frame | Description |
|---|---|---|
| Magnetic Resonance Imaging (MRI) | 1 week pre- and 1 week post-treatment | 10 min resting-state functional MRI (rs-fMRI) at 3 Tesla (3T) |
| Electroencephalography (EEG) | Day 1 (First day of treatment), Day 15, and Day 30 (Final day of treatment)] | 10 min resting-state and task-based (response inhibition, reward sensitivity) acquisitions |
Countries
Canada
Outcome results
None listed