Therapeutic Neuromodulation for Depression

Overseen By Nick Bassano

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Stanford University

Must be taking: Antidepressants

Must not be taking: Ketamine, ECT

Disqualifiers: Pregnancy, Psychotic disorder, Bipolar, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 4-8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to treating depression, specifically for individuals who haven’t found relief with other treatments. It tests a type of brain stimulation called accelerated intermittent theta burst stimulation (aiTBS) to determine its effectiveness in reducing anhedonia, a lack of pleasure or interest in activities. Participants will receive one of two types of this stimulation, each targeting different brain areas. This trial suits those diagnosed with major depressive disorder who have tried other treatments without success and are currently stable on their medication. As an unphased trial, it offers a unique opportunity for patients to contribute to innovative research that could lead to new treatment options.

Will I have to stop taking my current medications?

You will need to keep your primary antidepressant medication dose stable for 6 weeks before starting the study and continue at this dose throughout the study period.

What prior data suggests that this neurostimulation strategy is safe for treating depression?

Research has shown that accelerated intermittent theta burst stimulation (aiTBS) is generally safe for people with treatment-resistant depression. In studies, patients experienced significant improvements in their depression symptoms, and the treatment was well-tolerated.

One study found that aiTBS led to better improvements in anxiety and self-reported depression without serious side effects compared to a placebo. Another study confirmed that aiTBS is both safe and effective, using a practical approach with only three sessions per day.

Overall, aiTBS appears to be a promising and safe option for those with depression who haven't found relief from other treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Accelerated Intermittent Theta Burst Stimulation (aiTBS) for depression because it offers a new way to tackle symptoms much faster than traditional treatments like antidepressants or regular Transcranial Magnetic Stimulation (TMS). Unlike these treatments, aiTBS uses a pattern of magnetic pulses that can potentially stimulate brain regions associated with mood regulation more effectively and in less time. This means patients might experience relief within days instead of weeks, which is a significant advantage for those struggling with severe depression. Additionally, the trial compares different brain targets, DLPFC and DMPFC, to see which might provide the best outcomes, paving the way for more personalized treatment approaches.

What evidence suggests that accelerated intermittent theta burst stimulation (aiTBS) could be effective for treatment resistant depression?

Research has shown that accelerated intermittent theta burst stimulation (aiTBS) can reduce symptoms of depression in individuals unresponsive to other treatments. This trial will compare two different applications of aiTBS. One group will receive aiTBS targeting the DLPFC (dorsolateral prefrontal cortex), which studies have found to be much more effective than placebo treatments. Another group will receive aiTBS targeting the DMPFC (dorsomedial prefrontal cortex), which also rapidly improves symptoms. Overall, both methods have demonstrated potential in helping individuals with severe depression that does not improve with standard treatments. ^{1 3 4 6 7}

Who Is on the Research Team?

David Spiegel, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with Major Depressive Disorder who haven't responded to standard treatments and have a MADRS score of ≥20. Participants must be TMS naive, in good health, agree to lifestyle considerations, and females must use effective contraception. Exclusions include metal implants that interfere with MRI or rTMS, seizure history, psychotic/bipolar disorders, substance abuse, severe personality disorder, recent suicide attempt or ECT without response.

Inclusion Criteria

You have a satisfactory medical record indicating that you are in good overall health.

Females of reproductive potential must have been using highly effective contraception for at least one month prior to screening and agree to continue its use during the study.

I can read and understand English well enough to follow study instructions and am willing to comply with all study requirements.

Exclusion Criteria

You currently have a serious problem with drugs or alcohol or are experiencing withdrawal symptoms.

You have a recent history of attempting suicide or are at a high risk of doing so based on the doctor's assessment.

You have received any experimental treatment or other interventions during the study period.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive theta-burst TMS DLPFC or DMPFC stimulation for 4-8 weeks

4-8 weeks

5 visits per week

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Accelerated Intermittent Theta Burst Stimulation (aiTBS)

Trial Overview

The study tests an innovative neurostimulation method called accelerated intermittent theta burst stimulation (aiTBS) targeting two brain regions: DMPFC & DLPFC. It aims to alleviate symptoms of anhedonia in treatment-resistant depression by comparing the effects of aiTBS on these areas.

How Is the Trial Designed?

Group I: Active TBS-DLPFC Active Control 1 Intervention

The active group will receive theta-burst TMS DLPFC stimulation.

Group II: Active TBS-DMPFC Active Control 1 Intervention

The active group will receive theta-burst TMS DMPFC stimulation.

Accelerated Intermittent Theta Burst Stimulation (aiTBS) is already approved in United States for the following indications:

Approved in United States as aiTBS for:

• Treatment-resistant depression
• Major depressive disorder

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Published Research Related to This Trial

In a study of 26 patients with bipolar depression, active intermittent theta burst stimulation (iTBS) showed a high response rate of 72% and a remission rate of 42%, indicating its potential efficacy in treating this condition.

No adverse events were reported, demonstrating that iTBS is safe and well-tolerated, but further research with larger sample sizes is needed to confirm its superiority over sham treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Twice-daily neuronavigated intermittent theta burst stimulation for bipolar depression: A Randomized Sham-Controlled Pilot Study. Bulteau, S., Beynel, L., Marendaz, C., et al.[2020]

Intermittent theta burst stimulation (iTBS) is as effective as standard high-frequency (10 Hz) rTMS for treating treatment-resistant depression, showing non-inferiority in improving depression scores over 4-6 weeks in a study with 414 participants.

Both iTBS and 10 Hz rTMS had similar safety profiles and dropout rates, with headaches being the most common side effect, indicating that iTBS can be a viable alternative that allows for more patients to be treated in a shorter time without losing effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial. Blumberger, DM., Vila-Rodriguez, F., Thorpe, KE., et al.[2022]

In a randomized, double-blind trial involving 56 patients, intermittent theta burst stimulation (iTBS) over the dorsomedial prefrontal cortex showed a significant reduction in negative symptoms for patients with depression, but not for those with schizophrenia.

The treatment was generally safe and well-tolerated, with serious adverse events occurring only in the sham group, indicating that iTBS may be a promising intervention for depressive symptoms in certain patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dorsomedial prefrontal theta burst stimulation to treat anhedonia, avolition, and blunted affect in schizophrenia or depression - a randomized controlled trial. Bodén, R., Bengtsson, J., Thörnblom, E., et al.[2021]

In a study involving 72 patients with major depressive disorder, two daily sessions of prolonged intermittent theta-burst stimulation (piTBS) over two weeks showed significantly more responders compared to a sham treatment, indicating its efficacy as an antidepressant option.

However, the study found no evidence that longer piTBS sessions led to greater improvements in depression scores compared to other treatments, suggesting that while piTBS is effective, increasing treatment duration does not enhance its antidepressant effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The longer, the better ? Longer left-sided prolonged intermittent theta burst stimulation in patients with major depressive disorder: A randomized sham-controlled study. Li, CT., Cheng, CM., Lin, HC., et al.[2023]

Accelerated intermittent theta burst stimulation (aiTBS) has shown promising efficacy in treating major depressive episodes in patients with major depressive disorder (MDD) or bipolar depression (BD), outperforming sham stimulation in a meta-analysis of five randomized controlled trials involving 239 patients.

The results suggest that aiTBS could be a beneficial treatment option for individuals experiencing major depressive episodes, indicating its potential as an effective intervention for depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated intermittent theta burst stimulation for major depressive disorder or bipolar depression: A systematic review and meta-analysis. Cai, DB., Qin, ZJ., Lan, XJ., et al.[2023]

Accelerated, high-dose intermittent theta burst stimulation (iTBS) showed promising results in treating highly treatment-resistant depression, with most patients achieving remission after treatment.

However, the effects were short-lived, as all patients experienced relapse within two weeks, indicating a need for improved treatment strategies that enhance the durability of the therapeutic response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is accelerated, high-dose theta burst stimulation a panacea for treatment-resistant depression? Caulfield, KA.[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 50 depressed patients undergoing accelerated intermittent theta burst stimulation (aiTBS), baseline cortical thickness in the right caudal part of the anterior cingulate cortex (cACC) was found to significantly correlate with immediate clinical responses to treatment.

Longitudinal changes in cortical thickness in the right cACC also predicted delayed clinical responses, suggesting that this brain region could serve as a biomarker for determining the effectiveness of aiTBS in treating depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cortical Thickness in the Right Anterior Cingulate Cortex Relates to Clinical Response to Left Prefrontal Accelerated Intermittent Theta Burst Stimulation: An Exploratory Study. Baeken, C., van Beek, V., Vanderhasselt, MA., et al.[2022]

In a study involving 208 participants with treatment-resistant depression, both twice-daily and once-daily intermittent theta burst stimulation (iTBS) protocols showed improvements in depression scores, but there was no significant difference in efficacy between the two schedules after 10 and 30 days.

Response and remission rates were low in both treatment groups, indicating that neither protocol significantly accelerated the improvement of depressive symptoms in patients with treatment-resistant depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized sham controlled comparison of once vs twice-daily intermittent theta burst stimulation in depression: A Canadian rTMS treatment and biomarker network in depression (CARTBIND) study. Blumberger, DM., Vila-Rodriguez, F., Wang, W., et al.[2022]

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