Comparing Different Patterns of rTMS in Major Depression

Study Overview
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Brief Summary
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This trial will compare the trajectories of improvement for three different patterns of twice-daily rTMS in major depression: two daily sessions of dorsomedial prefrontal rTMS delivered at 0 min vs. 30 min vs. 60 min intervals.

Official Title
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A Randomized Controlled Trial Comparing Different Patterns of Repetitive Transcranial Magnetic Stimulation in the Treatment of Refractory Depression

Conditions
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Depression; Bipolar Disorder

Intervention / Treatment
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* Device: Dorsomedial prefrontal rTMS


Participation Criteria
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Eligibility Criteria
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Participants are eligible for the study if they: 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, or Bipolar Disorder with a current Major Depressive Episode 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 episode OR have been unable to tolerate at least 2 separate trials of antidepressants of inadequate dose and duration (ATHF 1 or 2) have a score ≥18 on the 17-item Hamilton Rating Scale for Depression (HRSD-17) have had no increase or initiation of any psychotropic medication in the 4 weeks prior to screening are able to adhere to the treatment schedule pass the TMS safety-screening questionnaire have normal thyroid functioning and no clinically significant abnormalities on complete blood count (CBC), on pre-study blood work. Participants are ineligible for the study if they: have a history 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 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 have a clinically significant laboratory abnormality, in the opinion of the investigator currently (or in the last 4 weeks prior to the study) have taken more than lorazepam 4 mg daily (or equivalent) or any dose of an anticonvulsant due to the potential to limit rTMS efficacy have a 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 60 min inter-session interval<br>Repetitive transcranial magnetic stimulation (rTMS) to bilateral dorsomedial prefrontal cortex, twice daily, 5 days per week for 4 weeks (Inter-session interval, 60 min). | Device: Dorsomedial prefrontal rTMS<br>* Dorsomedial prefrontal rTMS, bilateral, iTBS, 600 pulses per hemisphere, 120% RMT, 2 sessions at 0, 30, or 60 min inter-session interval<br>|
| Experimental: 30 min inter-session interval<br>Repetitive transcranial magnetic stimulation (rTMS) to bilateral dorsomedial prefrontal cortex, twice daily, 5 days per week for 4 weeks (Inter-session interval, 30 min). | Device: Dorsomedial prefrontal rTMS<br>* Dorsomedial prefrontal rTMS, bilateral, iTBS, 600 pulses per hemisphere, 120% RMT, 2 sessions at 0, 30, or 60 min inter-session interval<br>|
| Experimental: 0 min inter-session interval<br>Repetitive transcranial magnetic stimulation (rTMS) to bilateral dorsomedial prefrontal cortex, twice daily, 5 days per week for 4 weeks (Inter-session interval, 0 min). | Device: Dorsomedial prefrontal rTMS<br>* Dorsomedial prefrontal rTMS, bilateral, iTBS, 600 pulses per hemisphere, 120% RMT, 2 sessions at 0, 30, or 60 min inter-session interval<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 1-week post-treatment. A 50% improvement in the score is considered a response to rTMS. A final score of ≤7 is categorized as remission. | Baseline, after each week of treatment (i.e. after 5 days of treatment), and 1, 4, and 12 weeks post-treatment. Treatment will include 5 daily weekday visits over 4 weeks (20 sessions total). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Beck Depression Inventory-II (BDI-II) | Outcome measured by a change in BDI-II score from baseline to 1-week post-treatment. A 50% improvement in the score is considered a response to rTMS. A final score of ≤12 is categorized as remission. | Daily for 4 weeks, 5 days per week, in addition to three follow-up visits at 1, 4, and 12 weeks post-treatment |