Intensive TMS for Bipolar Depression

Not Applicable

Completed

Interventions: Device: Intensive intermittent theta-burst stimulation (iTBS)

Brief Summary: The research study is being conducted to test whether using high dose spaced theta-burst rTMS (a form of transcranial magnetic stimulation) produces a significant reduction in depressive symptoms compared with sham. This project will recruit patients aged 18-70 with symptoms of bipolar depression who have failed (or not shown signs of improvement) after at least two prior treatments.

Detailed Description: The research study is being conducted to test whether using high dose spaced theta-burst rTMS (a form of transcranial magnetic stimulation) produces a significant reduction in depressive symptoms compared with sham. This project will recruit patients aged 18-70 with symptoms of bipolar depression who have failed (or not shown signs of improvement) after at least two prior treatments. The null hypothesis is that there will be no difference in reductions in depressive symptoms by the end of a five-day treatment period. The alternative hypothesis is that, compared with sham, active TMS will result in a greater reduction in depressive symptoms by the end of the treatment period. Participants will be randomly assigned to active or sham conditions: 50% to active and 50% to sham.

Recruitment & Eligibility

Inclusion Criteria

Bipolar depression (BP I and BP II) by Diagnostic and Statistical Manual 5 (DSM 5) criteria
Age 18-70
Right or left handed
All genders
Treatment resistant depression, as in they must have treatment resistant depression with 2 or more prior antidepressant trials that have failed to produce a response (> 50% reduction in symptoms) using ATHF criteria
Able to provide informed consent to participate in the study
Must be on a stable medication regimen, requiring at least one mood stabilizer
Depression severity as represented by scoring at least 20 on Montgomery-Asberg Depression Rating Scale (MADRS)

Exclusion Criteria

No current substance abuse disorder for the past 6 months (previous substance abuse not exclusionary)
Any psychotic disorder or current active psychotic symptoms (personality disorders not exclusionary unless in the opinion of the referring psychiatrist it would jeopardize participation)
No dementia or other major neurological disorders
Not having depression as primary disorder
No major medical illness, for example metastatic cancer, end stage renal disease
Not able to verify contact information. Participants must be able to follow through with the study & must have verified contact information and at least one verified contact
Pregnancy. While there are no known risks to a fetus this is a new use of TMS, which has not been tested, thus pregnancy is exclusionary
Score on Young Mania Rating Scale (YMRS) greater than 12 (patients with mixed features have been shown not to respond well to TMS treatment)
Rapid cycling Bipolar illness (patients with > 4 mood episodes within the past year will be excluded, as they have a higher risk of switch to mania)
Any implants, conditions, or contraindications that would be deemed unsafe for TMS or MRI
Currently using benzodiazepines (such as lorazepam) with a dose >1 mg per day or equivalent.

Arm && Interventions

Group	Intervention	Description
Sham Transcranial Magnetic Stimulation	Intensive intermittent theta-burst stimulation (iTBS)	Sham Intensive iTBS involves using the coil's electric stimulation functionality that allows for the delivery of a brief electric pulse to the scalp simultaneous to the TMS pulse, which mimics the scalp sensation from active stimulation.
Active Transcranial Magnetic Stimulation	Intensive intermittent theta-burst stimulation (iTBS)	Active Intensive iTBS involves intermittent theta-burst stimulation (iTBS), a patterned form of repetitive transcranial magnetic stimulation (rTMS) over the left dorsal lateral prefrontal cortex (L-DLPFC).

Primary Outcome Measures

Name	Time	Method
Clinical Efficacy of High Dose Spaced Theta Burst (HDS-TBS)	Through study completion, approximately 1 week	The primary outcome will be based on the set of repeated Montgomery Asberg Depression scores (10 items rated on a 0-6 scale, 0-60 possible score range, with higher scores indicating greater depressive symptomology), obtained at baseline, on each of the five treatment days and post TMS.

Secondary Outcome Measures

Name	Time	Method
Relationship Between Change in Brain Resting State Functional Connectivity and Treatment Effects	Upon study completion, approximately 1 week	The secondary outcome will be the change in the correlation between the dorsolateral prefrontal cortex (DLPFC) and the subgenual anterior cingulate cortex (sgACC) with the Montgomery-Åsberg Depression Rating Scale (MADRS), as assessed through MRI scans conducted at baseline and post-stimulation. Additionally, the change in the correlation within the entire Default Mode Network (DMN) intraconnectivity and MADRS will be measured for both groups (Active vs. Sham). The correlation is measured on a scale from -1 to +1, where -1 indicates the highest negative anticorrelation, +1 represents the highest positive correlation, and 0 signifies no correlation. MADRS is used to assess the clinical effect.