Examining the Efficacy of Orbitofrontal Cortex rTMS for Depression

Study Overview
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Brief Summary
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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.

Official Title
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Efficacy of Orbital Frontal Cortex Repetitive Transcranial Magnetic Stimulation Magnetic Stimulation in the Treatment of Refractory Depression

Conditions
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Depression

Intervention / Treatment
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* Device: Continuous theta-burst stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: are outpatients are voluntary and competent to consent to treatment have a Mini-International Neuropsychiatric Interview (MINI) confirmed diagnosis of major depressive disorder (MDD), single or recurrent are between the ages of 18 and 65 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 have a score > 18 on the HAMD-17 have had no increase or initiation of any psychotropic medication in the 4 weeks prior to screening able to adhere to the treatment schedule Pass the TMS adult safety-screening (TASS) questionnaire have normal thyroid functioning based on pre-study blood work. Exclusion Criteria: have a MINI-International Neuropsychiatric (MINI) confirmed diagnosis of substance dependence or abuse within the last 3 months have a concomitant major unstable medical illness, cardiac pacemaker or implanted medication pump have active suicidal intent are pregnant 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 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 have a diagnosis of any personality disorder, and assessed by a study investigator to be primary and causing greater impairment than MDD have failed a course of electroconvulsive therapy (ECT) in the current episode or previous episode 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 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 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 clinically significant laboratory abnormality, in the opinion of the study investigator 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 non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sham then Active Stimulation<br>Sham repetitive transcranial magnetic stimulation (rTMS) to right orbitofrontal cortex, twice daily, 5 days per week for 3 weeks, then active rTMS to right orbitofrontal cortex, twice daily, 5 days per week for 3 weeks | Device: Continuous theta-burst stimulation<br> <br> |
| Experimental: Active then Sham Stimulation<br>Active repetitive transcranial magnetic stimulation (rTMS) to right orbitofrontal cortex, twice daily, 5 days per week for 3 weeks, then sham rTMS to right orbitofrontal cortex, twice daily, 5 days per week for 3 weeks | Device: Continuous theta-burst stimulation<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 17-Item Hamilton Rating Scale for Depression (HAMD-17) | 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. | Baseline, after each week of treatment (i.e. after 5 days of treatment) and at 1, 4, and 12 weeks post-treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Beck Depression Inventory-II (BDI-II) |  | Daily for 6 weeks |