rTMS for Depression

Overseen By Nick Bassano, MSW

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Stanford University

Must not be taking: Ketamine, ECT

Disqualifiers: Anxiety, Insomnia, Substance use, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new brain stimulation technique called accelerated intermittent theta-burst stimulation (aiTBS) to evaluate its effectiveness for people with depression, particularly those with borderline personality disorder or bipolar II disorder. The treatment targets specific brain areas linked to mood regulation. Participants will receive either active brain stimulation or a sham (inactive) version for comparison. Suitable candidates for this trial include individuals diagnosed with major depressive disorder or bipolar II, currently experiencing a depressive episode, and who have not previously undergone transcranial magnetic stimulation (TMS). As an unphased study, this trial offers the chance to contribute to groundbreaking research that could enhance future depression treatments.

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 prior data suggests that this protocol is safe for treating depression?

Research has shown that treatments targeting the Dorsomedial Prefrontal Cortex (DMPFC) and the Left Dorsolateral Prefrontal Cortex (L-DLPFC) are generally safe and well-tolerated. Specifically, for the DMPFC, both 10 Hz and intermittent theta burst stimulation (iTBS) are safe at specific intensity levels. For the L-DLPFC, theta burst stimulation (TBS) is considered safe and acceptable, even for individuals with long-term health conditions.

These treatments have been tested in various studies and are used for multiple conditions, demonstrating a strong safety record. However, individual experiences may vary, so discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the rTMS protocol for depression because it offers a potentially faster-acting alternative to traditional antidepressants and therapy. Unlike standard treatments, which often require weeks to take effect, rTMS uses accelerated theta burst stimulation aimed at specific brain areas, such as the dorsomedial and left dorsolateral prefrontal cortex, to quickly modulate brain activity. This non-invasive approach could provide quicker relief from depressive symptoms, which is a significant advantage for those seeking faster improvement in their mental health.

What evidence suggests that this trial's treatments could be effective for depression?

Research shows that stimulating certain brain areas might help manage depression and anxiety. In this trial, participants will receive different types of stimulation. Specifically, studies have found that high-dose intermittent theta-burst stimulation (iTBS) on the dorsomedial prefrontal cortex (DMPFC) is safe and may help treat depression that hasn't responded to other treatments, with benefits increasing over time. For the left dorsolateral prefrontal cortex (L-DLPFC), evidence suggests that theta-burst stimulation (TBS) can significantly improve depression symptoms. These findings offer hope for using these brain areas in treating depression, especially when traditional methods haven't worked. ^{2 3 5 6 7}

Who Is on the Research Team?

Nolan Williams, MD

Principal Investigator

Stanford University

David Spiegel, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Dorsomedial Prefrontal Cortex (DMPFC)
• Left Dorsolateral Prefrontal Cortex (L-DLPFC)
• Sham 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.

How Is the Trial Designed?

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 United States, Canada for the following indications:

Approved in United States as rTMS for:

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

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+

Published Research Related to This Trial

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]

In a randomized-controlled trial involving 32 patients with major depression, bilateral theta burst stimulation (TBS) to the dorsolateral prefrontal cortex showed a significant increase in treatment response compared to sham stimulation, with 9 responders in the TBS group versus 4 in the sham group.

The study also indicated a trend towards higher remission rates in the TBS group as measured by the Beck Depression Inventory, suggesting that TBS may enhance the effectiveness of ongoing medication and psychotherapy in treating major depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of major depression with bilateral theta burst stimulation: a randomized controlled pilot trial. Plewnia, C., Pasqualetti, P., Große, S., et al.[2018]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36484844/

Antidepressant effects of prolonged intermittent theta-burst ... The dorsomedial prefrontal cortex (DMPFC) plays a pivotal role in depression and anxiosomatic symptom modulation. However, DMPFC stimulation ...

2. brainstimjrnl.com brainstimjrnl.com/article/S1935-861X(24)01009-X/fulltext

a double-blind randomized controlled trial High-dose iTBS targeting the connectivity-guided DMPFC is a safe and potentially effective treatment for TRD, with therapeutic benefits increasing over time.

3. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X14003490

rTMS of the Dorsomedial Prefrontal Cortex for Major ... Both 10 Hz and iTBS DMPFC-rTMS appear safe and tolerable at 120% resting motor threshold. The effectiveness of 6 min iTBS and 30 min 10 Hz protocols appears ...

4. nature.com nature.com/articles/s41380-024-02630-5

Theta burst stimulation for depression: a systematic review ... Theta burst stimulation (TBS) presents as a more efficient and potentially more effective therapeutic modality than conventional repetitive transcranial ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0166432820305337

Intermittent theta burst stimulation over the dorsomedial ... 30 patients with an ongoing depressive episode were recruited and randomized to 20 sessions at target intensity of either active or sham intermittent theta ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25465290/

rTMS of the dorsomedial prefrontal cortex for major ... Both 10 Hz and iTBS DMPFC-rTMS appear safe and tolerable at 120% resting motor threshold. The effectiveness of 6 min iTBS and 30 min 10 Hz protocols appears ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9735131/

Antidepressant effects of prolonged intermittent theta-burst ... Antidepressant effects of prolonged intermittent theta-burst stimulation monotherapy at the bilateral dorsomedial prefrontal cortex for medication