Accelerated Theta Burst in Treatment-Resistant Depression: A Dose Finding and Biomarker Study

Study Overview
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Brief Summary
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This study evaluates the effectiveness of re-treatment using accelerated schedule of intermittent theta-burst stimulation for treatment-resistant depression. This is an open label study.

Detailed Description
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Repetitive transcranial magnetic stimulation (rTMS) is an established technology as therapy for treatment-resistant depression. The approved method for treatment is 10Hz stimulation for 40 min over the left dorsolateral prefrontal cortex (L-DLPFC). This methodology has been very successful. The limitations of this approach include the duration of the treatment (approximately 40 minutes per treatment session). Recently, researchers have aggressively pursued modifying the treatment parameters to reduce treatment times with some preliminary success. This study will investigate the efficacy of a further modified protocol, creating a more rapid form of the treatment and look at the change in neuroimaging biomarkers. In particular, this study will determine the efficacy of re-treatment in individuals who have already experienced benefit of the accelerated protocol to ensure results can be repeated.

Official Title
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Accelerated Theta Burst in Treatment-Resistant Depression: A Dose Finding and Biomarker Study

Conditions
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Treatment Resistant Depression

Intervention / Treatment
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* Device: Intermittent theta-burst stimulation (iTBS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 18 to 75 years of age. Able to provide informed consent. Diagnosed with Major Depressive Disorder (MDD) or bipolar affective disorder 2 and currently experiencing a Major Depressive Episode (MDE). prior exposure to rTMS Participants must qualify as moderate or severe treatment refractory using the Maudsley staging method. Participants may continue antidepressant regimen, but must be stable for 6 weeks prior to enrollment in the study. They must maintain that same antidepressant regimen throughout the study duration. Participants are required to have a stable psychiatrist for the duration of study enrollment. Exclusion Criteria: History of MI, CABG, CHF, or other cardiac history Any neurological conditions History of epilepsy OCD Independent sleep disorder Autism Spectrum Disorder

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Accelerated theta burst treatment<br>All participants will receive theta-burst TMS. | Device: Intermittent theta-burst stimulation (iTBS)<br>* Participants will receive iTBS to the left DLPFC or bilateral DLPFC, to the right and left DLPFC. The DLPFC will be targeted utilizing either Localite's neuronavigation system or Nexstim's eField neuronavigation system. Stimulation intensity will be standardized at 90% of RMT and adjusted to the skull to cortical surface distance (see Nahas 2004). Stimulation will be delivered to the L-DLPFC or bilateral DLPFC using either a MagVenture MagPro X100 or a Nexstim TMS device.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change in Hamilton Depression Rating Scale 21-Item score | A 21 item clinical assessment tool used to rate a patient's level of depression - total scores range from 0-63 with higher scores indicating worse depression | Difference between baseline and one month after aiTBS treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hamilton Rating Scale for Depression (HAMD-17) | A provider administered questionnaire used to rate a patient's level of depression - total scores range from 0-52 with higher scores indicating worse depression | Pretreatment, immediately posttreatment, 2 weeks posttreatment, 4 weeks posttreatment | 
| Change in The Scale for Suicide Ideation | A rating scale that measures the current intensity of specific attitudes, behaviors, and plans to commit suicide - total scores range from 0-38 with higher scores indicating greater suicidality | Pretreatment, immediately posttreatment, 2 weeks posttreatment, 4 weeks posttreatment | 
| Change in Hamilton Rating Scale for Depression (HAMD-6) | rate a patient's level of depression - total scores range from 0-22 with higher scores indicating worse depression | Every day of stimulation, follow-up every 2 weeks after treatment for 6 months by telephone] | 
| Change from baseline functional connectivity | We will assess functional connectivity as seen on resting state fMRI, between the subcallosal cingulate to the default mode network and within the default mode network. | Pretreatment, immediately post-treatment, 4 weeks post-treatment | 
| Change in Beck Depression Inventory (BDI) | Self-report measure of depressive symptoms - total scores range from 0-63 with higher scores indicating worse depression | Pretreatment, immediately post-treatment, 4 weeks post-treatment | 
| Change in Montgomery-Åsberg Depression Rating Scale (MADRS) | A 10 item clinician rated measure of depressive symptoms - total scores range from 0-60 with higher scores indicating worse depression | Pretreatment, immediately post-treatment, 4 weeks post-treatment |