Neuromodulation for Treatment-Resistant Depression

Overseen By David Spiegel, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Stanford University

Must be taking: Antidepressants

Must not be taking: Ketamine, ECT

Disqualifiers: Pregnancy, Psychotic disorder, Substance use, 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: 6

Duration: 4-8 weeks

79 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will investigate the anti-anhedonic efficacy of a novel neurostimulation strategy termed accelerated intermittent theta burst stimulation (aiTBS) in participants with treatment resistant depression (TRD).

Will I have to stop taking my current medications?

No, you will not have to stop taking your current medications. Participants must be on a stable antidepressant regimen for 6 weeks before joining the study and agree to continue it throughout the study.

What data supports the effectiveness of the treatment Accelerated Intermittent Theta Burst Stimulation (aiTBS) for treatment-resistant depression?

Research shows that aiTBS can significantly reduce depression symptoms in patients with treatment-resistant depression. In a study, patients receiving aiTBS showed a notable decrease in depression severity over time, suggesting its potential as a noninvasive treatment option. ^{1 2 3 4 5}

Is accelerated intermittent theta burst stimulation (aiTBS) safe for humans?

Research indicates that accelerated intermittent theta burst stimulation (aiTBS) is generally safe for humans, with studies showing no adverse events in patients with bipolar depression and treatment-resistant depression. ^{2 4 5 6 7}

How is the treatment Accelerated Intermittent Theta Burst Stimulation (aiTBS) unique for treatment-resistant depression?

Accelerated Intermittent Theta Burst Stimulation (aiTBS) is a unique treatment for treatment-resistant depression because it is a noninvasive brain stimulation technique that rapidly reduces depression symptoms by altering brain network connectivity, specifically targeting the left dorsolateral prefrontal cortex. Unlike traditional treatments, aiTBS can lead to significant improvements in just a few days, although the effects may not be long-lasting without further intervention. ^{1 2 3 4 7}

Research Team

David Spiegel, MD

Principal Investigator

Stanford University

Eligibility Criteria

This trial is for adults aged 18-80 with treatment-resistant depression, defined by a specific score on the Maudsley Staging Method. Participants must be in good health, have ongoing psychiatric care, and women of childbearing age should use effective contraception. Exclusions include substance abuse issues, recent suicide attempts or ideation, certain neurological diseases or head trauma, metal implants incompatible with MRI or rTMS treatments.

Inclusion Criteria

MADRS score of ≥20 at screening (Visit 1)

I have been diagnosed with MDD or Bipolar II and am currently experiencing a major depressive episode.

In good general health, as evidenced by medical history

Exclusion Criteria

Active suicidal ideation (defined as an MSSI > 8) or a suicide attempt within the past 90 days

I have used ketamine or had ECT for depression recently.

I don't have metal in my head, a seizure history, or known brain lesions.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

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

4-8 weeks

5 visits per week (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

1 visit (in-person)

Treatment Details

Interventions

• Accelerated Intermittent Theta Burst Stimulation (aiTBS)

Trial Overview The study tests an innovative neurostimulation approach called accelerated intermittent theta burst stimulation (aiTBS) targeting different brain regions to alleviate symptoms of severe depression that hasn't responded to standard treatments. It compares active aiTBS at two brain sites versus sham (placebo-like) treatment.

Participant Groups

Group I: Active TBS-DLPFC Active Control 1 Intervention

The active group will receive theta-burst TMS stimulation.

Group II: Active TBS-DMPFC Active Control 1 Intervention

The active group will receive theta-burst TMS stimulation.

Group III: Sham Comparator: Sham TBS-DLPFC or DMPFC Placebo Group 1 Intervention

The sham group will receive sham theta-burst TMS 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+

Findings from Research

In a study involving 50 patients with treatment-resistant depression (TRD), accelerated intermittent theta burst stimulation (aiTBS) significantly reduced depression symptoms over time, indicating its potential efficacy as a noninvasive treatment option.

The treatment was associated with changes in brain network organization, specifically a reduction in modularity of structural networks, suggesting that aiTBS may promote beneficial neuroplasticity effects in the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated intermittent theta burst stimulation in major depression induces decreases in modularity: A connectome analysis. Caeyenberghs, K., Duprat, R., Leemans, A., 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 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]

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]

In a study of 22 participants with treatment-resistant depression, the Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) protocol, which uses high-dose intermittent theta-burst stimulation (iTBS) guided by functional connectivity MRI, showed a remarkable remission rate of 90.5%.

The treatment was well tolerated with no negative cognitive side effects reported, suggesting that SAINT could be a safe and effective option for patients who have not responded to traditional antidepressants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression. Cole, EJ., Stimpson, KH., Bentzley, BS., et al.[2020]

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]

Accelerated intermittent Theta-burst Stimulation (iTBS) applied to the left dorsolateral prefrontal cortex in 50 patients with Treatment Resistant Depression (TRD) was found to be safe and led to significant reductions in depressive symptoms immediately after treatment.

While 28% of patients achieved a 50% reduction in depression scores during the treatment, this response rate increased to 38% two weeks post-treatment, with 30% of responders reaching clinical remission, suggesting delayed therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated intermittent theta burst stimulation treatment in medication-resistant major depression: A fast road to remission? Duprat, R., Desmyter, S., Rudi, de R., et al.[2019]

References

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

Accelerated intermittent theta burst stimulation in major depression induces decreases in modularity: A connectome analysis. [2023]

2. United States 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. [2022]

3. Netherlands 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. [2021]

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

Is accelerated, high-dose theta burst stimulation a panacea for treatment-resistant depression? [2021]

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

Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression. [2020]

6. France pubmed.ncbi.nlm.nih.gov

Twice-daily neuronavigated intermittent theta burst stimulation for bipolar depression: A Randomized Sham-Controlled Pilot Study. [2020]

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

Accelerated intermittent theta burst stimulation treatment in medication-resistant major depression: A fast road to remission? [2019]