rTMS for Depression

Recruiting in Palo Alto (17 mi)

Overseen by David Spiegel, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Stanford University

Must not be taking: Ketamine, ECT

Disqualifiers: Anxiety, Insomnia, Substance use, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This study evaluates the antidepressant effects of an accelerated schedule of theta-burst stimulation, termed accelerated intermittent theta-burst stimulation (aiTBS), in individuals with borderline personality disorder (BPD) or trait and comorbid mood depressive disorder (MDD) or bipolar II disorder in a current mood depressive episode (MDE).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are using rapid-acting antidepressants like ketamine or have had a recent course of ECT, you may not be eligible to participate.

What data supports the effectiveness of the treatment for depression?

Research shows that intermittent theta burst stimulation (iTBS) applied to the left dorsolateral prefrontal cortex (DLPFC) is effective in treating major depression, similar to traditional repetitive transcranial magnetic stimulation (rTMS). Additionally, combining iTBS with low-frequency rTMS on the right DLPFC has been found to enhance treatment outcomes when added to standard medication. ^{1 2 3 4 5}

Is rTMS safe for treating depression?

Research shows that repetitive transcranial magnetic stimulation (rTMS), including intermittent theta burst stimulation (iTBS), is generally safe for treating depression. Studies have found it to be as safe as traditional rTMS methods, with no major safety concerns reported. ^{2 3 4 5 6}

How is the rTMS treatment for depression unique compared to other treatments?

The rTMS treatment for depression is unique because it uses a specific pattern called intermittent theta burst stimulation (iTBS) targeting the dorsomedial and left dorsolateral prefrontal cortex, which can be as effective as traditional rTMS but is delivered in a shorter time frame, potentially making it more convenient for patients. ^{1 2 4 5 7}

Research Team

Nolan Williams, MD

Principal Investigator

Stanford University

David Spiegel, MD

Principal Investigator

Stanford University

Eligibility Criteria

Adults aged 22-65 with Borderline Personality Disorder and a current depressive episode, who are in good health, TMS naive, agree to lifestyle guidelines, use effective contraception if applicable, can understand English for assessments/interventions. Excludes pregnant individuals or those with mania/psychosis, substance abuse issues, certain medical conditions like metal implants incompatible with MRI or history of seizures.

Inclusion Criteria

Able to read, understand, and provide written, dated informed consent prior to screening. Proficiency in English sufficient to complete questionnaires / follow instructions during fMRI assessments and aiTBS interventions. Stated willingness to comply with all study procedures, including availability for the duration of the study, and to communicate with study personnel about adverse events and other clinically important information.

I am between 22 and 65 years old.

Agreement to adhere to Lifestyle Considerations (see section 5.3) throughout study duration

Exclusion Criteria

My treatment's intensity is more than 65% of the maximum level.

Treatment with another investigational drug or other intervention within the study period

I have a hormone disorder that hasn't been treated enough.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive accelerated intermittent theta-burst stimulation (aiTBS) over the left dorsolateral prefrontal cortex (L-DLPFC) or dorsomedial prefrontal cortex (DMPFC), or sham stimulation

4 weeks

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of suicidal behaviors and depression severity

4 weeks

Treatment Details

Interventions

• Dorsomedial Prefrontal Cortex (DMPFC) (Non-invasive Brain Stimulation)
• Left Dorsolateral Prefrontal Cortex (L-DLPFC) (Non-invasive Brain Stimulation)
• Sham Stimulation (Non-invasive Brain Stimulation)

Trial Overview The trial tests an accelerated form of theta-burst stimulation (aiTBS) on the brain's left dorsolateral prefrontal cortex and dorsomedial prefrontal cortex versus sham stimulation. It aims to assess aiTBS's effectiveness in alleviating depression symptoms in participants with BPD during a depressive episode.

Participant Groups

Group I: Left Dorsolateral Prefrontal Cortex (L-DLPFC) Active Control 1 Intervention

The accelerated theta burst stimulation protocol will be applied to the left dorsolateral prefrontal cortex (L-DLPFC)

Group II: Dorsomedial Prefrontal Cortex (DMPFC) Active Control 1 Intervention

The accelerated theta burst stimulation protocol will be applied to the dorsomedial prefrontal cortex (DMPFC)

Group III: Sham stimulation Placebo Group 1 Intervention

Sham (non-active) stimulation will be applied to the left dorsolateral prefrontal cortex (DLPFC) region

Dorsomedial Prefrontal Cortex (DMPFC) is already approved in Canada for the following indications:

Approved in Canada as rTMS for:

• Major Depressive Disorder (MDD)
• Treatment-resistant depression

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Dr. Richard A. Miller

Stanford University

Chief Executive Officer since 2023

Stanford University, MD

Dr. Robert Schott

Stanford University

Chief Medical Officer since 2021

University of Michigan, MD

Findings from Research

Intermittent theta-burst stimulation (iTBS) targeting the left visual cortex (VC) was found to be non-inferior to targeting the left dorsolateral prefrontal cortex (DLPFC) in improving depressive symptoms in patients with major depressive disorder (MDD), based on a study of 75 participants over 14 days.

The VC group experienced lower rates of suicidal ideation and fewer adverse events, such as eye discomfort and pain, suggesting that VC-targeted iTBS may be a safer option for treating MDD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-inferiority of intermittent theta burst stimulation over the left V1 vs. classical target for depression: A randomized, double-blind trial. Kong, Y., Zhou, J., Zhao, M., et al.[2023]

In a study of 71 participants with Major Depressive Disorder who had limited response to high-frequency left-sided stimulation, subthreshold intensity intermittent theta-burst stimulation priming (iTBS-P) led to a greater reduction in depressive symptoms compared to suprathreshold intensity stimulation.

The results suggest that iTBS-P may work through homeostatic plasticity mechanisms, indicating that lower intensity stimulation could be more effective for clinical improvement in depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subthreshold stimulation intensity is associated with greater clinical efficacy of intermittent theta-burst stimulation priming for Major Depressive Disorder. Lee, JC., Corlier, J., Wilson, AC., et al.[2021]

A clinical trial involving 96 outpatients with moderate depression will investigate the effectiveness of intermittent theta burst stimulation (iTBS) on reducing depressive symptoms, comparing it to a sham treatment over ten sessions.

The study will also explore various factors, including genetic and neuropsychological measures, that may influence the response to iTBS, ensuring a thorough safety screening and adherence to ethical guidelines throughout the trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The antidepressant effect of intermittent theta burst stimulation (iTBS): study protocol for a randomized double-blind sham-controlled trial. Ørbo, MC., Grønli, OK., Larsen, C., et al.[2023]

In a study of 54 patients with major depression, the combination of intermittent theta burst stimulation (iTBS) and low-frequency rTMS (LF-rTMS) significantly improved depression and anxiety symptoms more than high-frequency rTMS (HF-rTMS).

The results suggest that iTBS combined with LF-rTMS may be a promising alternative therapy for major depression, offering both efficacy and time-saving benefits compared to traditional methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Left intermittent theta burst stimulation combined with right low-frequency rTMS as an additional treatment for major depression: A retrospective study. Mi, Y., Ji, Y., Lou, Z., et al.[2022]

This study involves 236 patients with major depressive disorder (MDD) and aims to confirm that bilateral theta burst stimulation (TBS) is more effective than sham treatment over six weeks, with the primary outcome being a significant reduction in depression scores.

If successful, the results will support the use of TBS as a faster, effective, and safe treatment option for MDD, potentially leading to more personalized therapy approaches based on MRI and genetic predictors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of major depressive disorder with bilateral theta burst stimulation: study protocol for a randomized, double-blind, placebo-controlled multicenter trial (TBS-D). Plewnia, C., Brendel, B., Schwippel, T., et al.[2022]

In a study involving 14 neurotypical participants, different doses of intermittent theta-burst stimulation (iTBS) did not significantly affect the modulation of cortical activity in the left dorsolateral prefrontal cortex, indicating that higher doses may not enhance the effects of TMS.

All doses of iTBS successfully modulated brain activity by affecting TMS-evoked potentials and reducing intracortical inhibition, suggesting that iTBS is effective in altering DLPFC activity regardless of the number of pulses used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-response of intermittent theta burst stimulation of the prefrontal cortex: A TMS-EEG study. Desforges, M., Hadas, I., Mihov, B., et al.[2022]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Treatment of major depression with bilateral theta burst stimulation: a randomized controlled pilot trial. [2018]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Non-inferiority of intermittent theta burst stimulation over the left V1 vs. classical target for depression: A randomized, double-blind trial. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Subthreshold stimulation intensity is associated with greater clinical efficacy of intermittent theta-burst stimulation priming for Major Depressive Disorder. [2021]

4. England pubmed.ncbi.nlm.nih.gov

The antidepressant effect of intermittent theta burst stimulation (iTBS): study protocol for a randomized double-blind sham-controlled trial. [2023]

5. India pubmed.ncbi.nlm.nih.gov

Left intermittent theta burst stimulation combined with right low-frequency rTMS as an additional treatment for major depression: A retrospective study. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

Treatment of major depressive disorder with bilateral theta burst stimulation: study protocol for a randomized, double-blind, placebo-controlled multicenter trial (TBS-D). [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Dose-response of intermittent theta burst stimulation of the prefrontal cortex: A TMS-EEG study. [2022]