Accelerated Theta Burst for Treatment-Resistant Depression

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Stanford University

Must be taking: Antidepressants

Disqualifiers: Cardiac history, Neurological conditions, Epilepsy, OCD, others

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

Compensation: Varies

Number of Visits: 2

Duration: 4 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a faster brain stimulation treatment for people with depression who don't respond to usual treatments. The treatment uses magnetic pulses to activate underactive brain areas and improve mood. This method has been explored as an alternative treatment for depression, particularly for patients who do not respond to usual treatments.

Will I have to stop taking my current medications?

You can continue taking your current antidepressant medications, but they must be stable for 6 weeks before joining the study and remain the same throughout the study.

Is accelerated theta burst stimulation safe for humans?

Accelerated theta burst stimulation (iTBS) has been found to be safe in studies for treatment-resistant depression, with no adverse events reported in trials. It is a noninvasive brain stimulation treatment approved by the U.S. Food and Drug Administration for this condition. ^{1 2 3 4 5}

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

Intermittent Theta-Burst Stimulation (iTBS) is a noninvasive brain stimulation treatment that targets specific areas of the brain, like the dorsolateral prefrontal cortex, to help improve symptoms in treatment-resistant depression. It is unique because it uses rapid bursts of magnetic pulses to potentially alter brain connectivity and promote beneficial changes in brain networks, which is different from traditional antidepressant medications. ^{2 6 7 8 9}

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

Research shows that accelerated iTBS, a noninvasive brain stimulation technique, can significantly reduce depression symptoms in patients with treatment-resistant depression. In one study, 38% of patients experienced a 50% reduction in depression symptoms two weeks after treatment, with 30% achieving clinical remission. ^{1 2 6 9 10}

Who Is on the Research Team?

Gregory Sahlem, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for adults aged 18-75 with Major Depressive Disorder or bipolar disorder type 2, currently in a depressive episode and haven't improved with standard treatments. They must have tried rTMS before, be on a stable antidepressant dose for 6 weeks prior, and continue it during the study. Participants need to have a consistent psychiatrist throughout the trial.

Inclusion Criteria

My condition has not improved despite trying several treatments.

I have been on a stable antidepressant regimen for at least 6 weeks.

Participants are required to have a stable psychiatrist for the duration of study enrollment

Exclusion Criteria

I have a history of epilepsy.

OCD

Autism Spectrum Disorder

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive accelerated theta-burst TMS for treatment-resistant depression

4 weeks

Daily sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Follow-up every 2 weeks by telephone

What Are the Treatments Tested in This Trial?

Interventions

• Intermittent Theta-Burst Stimulation (iTBS)

Trial Overview The study tests an accelerated schedule of intermittent theta-burst stimulation (iTBS) as a re-treatment for those who didn't respond to regular depression therapies. It's an open-label design, meaning everyone knows they're getting iTBS without any placebo control.

How Is the Trial Designed?

Group I: Accelerated theta burst treatment Experimental Treatment 1 Intervention

All participants will receive theta-burst TMS.

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 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]

Intermittent theta burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex significantly decreased the N100 amplitude in participants with treatment-resistant depression, indicating a neurophysiological response to the treatment.

Responders to iTBS showed a notable decrease in N100 amplitude and higher N45 amplitude post-treatment compared to nonresponders, suggesting that these TMS-EEG markers could help predict treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identifying Neurophysiological Markers of Intermittent Theta Burst Stimulation in Treatment-Resistant Depression Using Transcranial Magnetic Stimulation-Electroencephalography. Strafella, R., Momi, D., Zomorrodi, R., et al.[2023]

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]

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]

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 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]

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]

Intermittent theta-burst stimulation (iTBS) significantly improves hand function in stroke patients, particularly in those with higher baseline motor function and the presence of motor-evoked potentials (MEPs).

The study of 72 stroke patients showed that those with MEPs and better grip strength (Group A) had the greatest improvement in motor function, suggesting that iTBS effectiveness can be predicted by these factors, allowing for more tailored neurostimulation strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Corticospinal integrity and motor impairment predict outcomes after excitatory repetitive transcranial magnetic stimulation: a preliminary study. Lai, CJ., Wang, CP., Tsai, PY., et al.[2016]

Citations

1. 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]

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

Identifying Neurophysiological Markers of Intermittent Theta Burst Stimulation in Treatment-Resistant Depression Using Transcranial Magnetic Stimulation-Electroencephalography. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

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

5. 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]

6. 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]

7. France pubmed.ncbi.nlm.nih.gov

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

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

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

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

Corticospinal integrity and motor impairment predict outcomes after excitatory repetitive transcranial magnetic stimulation: a preliminary study. [2016]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of bilateral sequential theta-burst stimulation on functional connectivity in treatment-resistant depression: First results. [2023]