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

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.

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.

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.

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

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

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

rate a patient's level of depression - total scores range from 0-22 with higher scores indicating worse depression

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.

Self-report measure of depressive symptoms - total scores range from 0-63 with higher scores indicating worse depression

A 10 item clinician rated measure of depressive symptoms - total scores range from 0-60 with higher scores indicating worse depression

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

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