rTMS for Suicidality in Opioid Use Disorder

Study Overview
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Brief Summary
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This trial is a randomized, double blind, controlled pilot study that will compare bilateral theta burst stimulation (TBS) and sham treatment for patients with opioid use disorder (OUD) and Major Depressive Disorder (MDD) experiencing suicidality.

Detailed Description
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Repetitive transcranial magnetic stimulation (rTMS) to the dorsolateral prefrontal cortex (DLPFC) is used therapeutically in major depressive disorder resistant to standard treatments, and recently also shown to be effective in reducing suicidality with a bilateral approach. Recently, a new form of rTMS has been developed called theta burst stimulation (TBS) which requires a much shorter daily treatment duration and has been found to be non-inferior to standard rTMS. The investigators propose to conduct a randomized controlled clinical trial of a daily, 20 session course of bilateral TBS versus sham stimulation in the treatment of suicidality in patients with OUD and MDD. The investigators will explore whether TBS can have other clinical effects on decreasing symptoms of MDD, craving for opioids, and rates of relapse to opioid use. The investigators will also examine whether rTMS can engage GABA mediated inhibition using combined transcranial magnetic stimulation and electroencephalography (TMS-EEG) will be assessed before and after intervention. Clinical outcomes measured before, during, at end of treatment, and 4-weeks post treatment.

Official Title
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Repetitive Transcranial Magnetic Stimulation for Suicidality in Opioid Use Disorders

Conditions
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Major Depressive Disorder, Opioid-use Disorder

Intervention / Treatment
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* Device: Active TBS
* Device: Sham TBS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Capable of providing informed consent and research procedures according to the brain stimulation attending psychiatrist Between the ages of 18-60 years Mini-International Neuropsychiatric Interview (MINI) confirmed diagnosis of Opioid Dependence and MDD. On a stable treatment regimen without any change in opioid agonist or antidepressant medications or dosages in the last 30 days. Participants will be asked not to change their medication regimen for the duration of the study. Baseline score of >/=4 on the scale for suicidal ideation (SSI). Exclusion Criteria: Currently pregnant or intending to be pregnant during the duration of the study Bipolar disorder, any psychotic disorder or current psychotic symptoms Previous rTMS treatment Known active seizure disorder, significant head injury with an imaging verified lesion Unstable medical illness Presence of cardiac pacemaker, intracranial implant, or metal in the cranium Participants taking > 2 mg lorazepam (or a benzodiazepine at an equivalent dose) or taking any anticonvulsant medication during treatment.

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active TBS<br>Daily, 4-week, 5-days per week treatment sessions, each consisting of: First, intermittent TBS (iTBS) over the L-DLPFC: triplet 50 Hz bursts, repeated at 5 Hz, 2 s on and 8 s off, (600 pulses per session, total duration of 3 min 9 s), then continuous TBS (cTBS) over the R-DLPFC as 40 s uninterrupted bursts (600 pulses). Intensity at 120% resting motor threshold (RMT). | Device: Active TBS<br>* MagPro X100 device equipped with a Cool-B70 A/P coil and Qooler fluid-cooling device (MagVenture, Farum, Denmark)<br>|
| Sham Comparator: Sham TBS<br>Daily, 4-week, 5-days per week treatment sessions. The sham coil will generate auditory and somatosensory (vibratory) stimuli identical to the active stimulation. | Device: Sham TBS<br>* MagPro X100 device equipped with a Cool-B70 A/P coil and Qooler fluid-cooling device (MagVenture, Farum, Denmark)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Scale for Suicidal Ideation Remission | A semi-structured interview for assessing suicidal ideation, min value=0, max value = 38. Higher score = worse outcome. | Change from baseline, to end of TBS treatment course (4 weeks), and at 1 month follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Scale for Suicidal Ideation Change | A semi-structured interview for assessing suicidal ideation, min value=0, max value = 38. Higher score = worse outcome. | Change from baseline, to end of TBS treatment course (4 weeks), and at 1 month follow up | 
| Change in Columbia - Suicide Severity Rating Scale Change | An interviewer-rated suicide risk assessment tool. Min value = 0, Max value = N/A. Higher score = worse outcome | Change from baseline, to end of TBS treatment course (4 weeks), and at 1 month follow up | 
| 17-item Hamilton Rating Scale for Depression (HRSD-17) Change | A rating scale for measuring severity of depressive symptoms. Min value = 0 Max value = 52. Higher score = worse outcome | Baseline, after TBS treatment course (4 weeks), and at 1 month follow up | 
| Visual Analogue Scale for Opioid Cravings Change | A rating scale for subjective cravings to use opioids. Min value = 0 Max value = 100. Higher score = worse outcome. | Baseline, after TBS treatment course (4 weeks), and at 1 month follow up | 
| Timeline Followback Change | Self-reported substance use over a designated period of time. Min value = 0 Max value = N/A. Higher score = worse outcome. | Baseline, after TBS treatment course (4 weeks), and at 1 month follow up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Suicidality, rTMS