Repetitive Versus Deep Transcranial Magnetic Stimulation for Major Depression

Study Overview
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Brief Summary
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The goal of this randomized controlled trial is to he effectiveness of two different TMS techniques in TRD, repetitive TMS (rTMS) and deep TMS (dTMS). The main questions it aims to answer are: type of study: clinical trial participant population/health conditions : Major Depressive Disorder To assess the superiority of dTMS over rTMS in TRD To evaluate the predictive capacity of scalable candidate biomarkers Participants will be randomly allocated to one of the two intervention groups (rTMS or dTMS).

Detailed Description
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The primary aim of this trial is to compare the effectiveness of two different TMS techniques in TRD, repetitive TMS (rTMS) and deep TMS (dTMS). Compared to rTMS, dTMS delivers a broader magnetic field, which in turn reduces coil positioning error and maximizes the probability of optimal cortical stimulation. A past RCT comparing both approaches found a greater depression score decrease and response/remission rates for dTMS, but was short of reaching significance for remission rates (primary outcome). Critical components of this RCT were suboptimal, including too few treatment sessions and insufficient statistical power, both of which could have obscured an actual difference between modalities. Proof of a more effective type of TMS over another would translate into increased odds of improvement for TRD patients who live with a chronic and disabling illness.

Official Title
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Comparative Effectiveness of Repetitive Versus Deep Transcranial Magnetic Stimulation for Major Depression: A Randomized Controlled Trial

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Device: transcranial magnetic stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Major Depressive Disorder, at least moderate intensity, single or recurrent episode HRSD-17 score of at least 18 No improvement to at least two adequate courses of antidepressants (based on the ATHF) or were unable to tolerate at least two separate trials of antidepressants of inadequate dose and duration On a stable antidepressant regimen for the past four weeks before screening Patients with a chronic depressive episode >2 years and who have previously received ECT or ketamine will be eligible to participate Exclusion Criteria: Having previously received TMS; Substance use disorder within the last three months Diagnosis of bipolar or psychosis spectrum disorder Anxiety or personality disorder that is assessed by a study investigator to be the primary cause and causing greater impairment than MDD Concomitant major unstable medical or neurological illness Intracranial implant, cardiac pacemaker or implanted medication pump Significant laboratory abnormality; Active suicidal intent Pregnancy If participating in psychotherapy, must have been in stable treatment for at least three months before entry into the study, with no anticipation of change Currently taking more than the equivalent of 2 mg of lorazepam of a benzodiazepine daily or any dose of an anticonvulsant due to the potential to limit TMS effectiveness

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 70 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
Interventional Model Description: randomized, single-center, two-arm, parallel-group superiority trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: repetitive Transcranial Magnetic Stimulation<br>rTMS on a MagPro X100 research grade stimulator (MagVenture) equipped with a B70 fluid-cooled coil. Participant will receive the MDD FDA-approved iTBS protocol (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, 120% hand motor threshold) | Device: transcranial magnetic stimulation<br>* Participants will receive either rTMS or dTMS<br>* Other names: deep transcranial magnetic stimulation;|
| Experimental: deep Transcranial Magnetic Stimulation<br>dTMS on a research Brainsway system equipped with an H7-Coil. Participants will receive the MDD FDA-cleared 18 Hz stimulation protocol (2 sec ON, 20 sec OFF, 55 trains; 1980 pulses per session; 20 min 10 s duration; 120% hand motor threshold) | Device: transcranial magnetic stimulation<br>* Participants will receive either rTMS or dTMS<br>* Other names: deep transcranial magnetic stimulation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hamilton Rating Scale for Depression-17 (HRSD-17) | score change. Higher score means worse outcome. (Min = 0, Max = 53) | Baseline to Week 6 | 
| Response (yes/no) on Hamilton Rating Scale for Depression-17 | Defined as a score reduction of 50% or more | baseline to Week 6 | 
| Remission (yes/no) on Hamilton Rating Scale for Depression-17 | Defined as a score of 7 or less | Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hamilton Rating Scale for Depression-17 | score change. Higher score means worse outcome. (Min = 0, Max = 53) | Baseline to Week 7 | 
| Hamilton Rating Scale for Depression-17 | score change. Higher score means worse outcome. (Min = 0, Max = 53) | Baseline to Week 10 | 
| Hamilton Rating Scale for Depression-17 | score change. Higher score means worse outcome. (Min = 0, Max = 53) | Baseline to Week 18 | 
| Response (yes/no) on Hamilton Rating Scale for Depression-17 | Defined as a score reduction of 50% or more | Baseline to Week 7 | 
| Response (yes/no) on Hamilton Rating Scale for Depression-17 | Defined as a score reduction of 50% or more | Baseline to Week 10 | 
| Response (yes/no) on Hamilton Rating Scale for Depression-17 | Defined as a score reduction of 50% or more | Baseline to Week 18 | 
| Remission (yes/no) on Hamilton Rating Scale for Depression-17 | Defined as a score of 7 or less | Baseline to Week 7 | 
| Remission (yes/no) on Hamilton Rating Scale for Depression-17 | Defined as a score of 7 or less | Baseline to Week 10 | 
| Remission (yes/no) on Hamilton Rating Scale for Depression-17 | Defined as a score of 7 or less | Baseline to Week 18 | 
| Hamilton Rating Scale for Depression-28 | score change. Higher score means worse outcome. (Min = 0, Max = 90) | Baseline to Week 6, Week 7, Week 10, Week 18 | 
| Hamilton Anxiety Rating Scale (HAM-A) | score change. Higher score means worse outcome. (Min = 0, Max = 56) | Baseline to Week 6, Week 7, Week 10, Week 18 | 
| Quick Inventory of Depressive Symptomatology (self-report) (QIDS-SR 16) | score change. Higher score means worse outcome. (Min = 0, Max = 42) | Baseline to Week 6, Week 7, Week 10, Week 18 | 
| General Anxiety Disorder-7 (GAD-7) | score change. Higher score means worse outcome. (Min = 0, Max = 21) | Baseline to Week 6, Week 7, Week 10, Week 18 | 
| Snaith-Hamilton Pleasure Scale (SHAPS) | score change. Higher score means worse outcome. (Min= 0, Max = 56) | Baseline to Week 6, Week 7, Week 10, Week 18 | 
| Columbia-Suicide Severity Rating Scale (C-SSRS) | score change. Higher score means worse outcome. (Min = 0, Max = 30) | Baseline to Week 6, Week 7, Week 10, Week 18 | 
| Rumination Response Scale (RRS) | score change. Higher score means worse outcome. (Min = 0, Max = 88) | Baseline to Week 6, Week 7, Week 10, Week 18 | 
| Adult AHDH Self-Report Scale | qualitative. | Baseline to Week 18 | 
| McLean Screening Instrument for Borderline Personality Disorder | score. Higher score means worse outcome. (Min = 0, Max = 10) | Baseline | 
| World Health Organization Quality of Life Short Version (WHOQOL-BREF) | Difference score. Lower score means worse outcome. (Min = 26, Max = 130) | Baseline to Week 6, Week 7, Week 10, Week 18 | 
| Cognitive Difficulties Scale (MacNair-R) | Difference score. Higher score means worse outcome. (Min = 0, Max = 156) | Baseline to Week 6, Week 7, Week 10, Week 18 | 
| Memory Complaints Scale (MacNair) | score. Higher score means worse outcome. (Min = 0, Max = 45) | Baseline to Week 6, Week 7, Week 10, Week 18 | 
| Sheehan Disability Scale | score. Higher score means worse outcome. (Min = 0, Max = 30) | Baseline to Week 6, Week 7, Week 10, Week 18 | 
| Visual Pain Scale | Maximum score (during treatment). Higher score means worse outcome. (Min = 0, Max = 10). | Each treatment day | 
| Sex and Gender scale | Descriptive statistics | Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MDD, TMS, deep TMS