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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to assist individuals with treatment-resistant depression using intermittent theta-burst stimulation (iTBS), a type of brain stimulation therapy. The researchers aim to assess its effectiveness when administered on an accelerated schedule. The trial is open to individuals with major depressive disorder or bipolar disorder experiencing a current major depressive episode who have not found success with other treatments. Participants should have previously tried repetitive transcranial magnetic stimulation (rTMS) and maintain a stable medication routine. Individuals with certain heart, neurological, or other specific conditions are ineligible. As an unphased trial, this study provides a unique opportunity to contribute to innovative research that could lead to new treatment options.

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.

What prior data suggests that intermittent theta-burst stimulation is safe for treatment-resistant depression?

Research has shown that intermittent theta-burst stimulation (iTBS) is generally safe for individuals with mental health conditions. One study found that iTBS was effective and manageable for teenagers with depression, even when other treatments had failed. Another report highlighted that a simpler iTBS method was both safe and effective for individuals with treatment-resistant depression.

The FDA has approved iTBS for treating depression, indicating its safety for this use. Overall, these findings suggest that iTBS is a promising and safe option for those dealing with depression. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for treatment-resistant depression involve medications like antidepressants, which can take weeks to show results. However, Intermittent Theta-Burst Stimulation (iTBS) is unique because it uses a non-invasive brain stimulation technique that targets specific brain areas associated with mood regulation. This method is faster, with the potential to show improvements in just a few days. Researchers are excited about iTBS because it offers a promising alternative for patients who haven't found relief from traditional therapies, potentially providing quicker and more effective results.

What evidence suggests that intermittent theta-burst stimulation is effective for treatment-resistant depression?

Research shows that intermittent theta-burst stimulation (iTBS) can help treat depression. Studies have found that iTBS reduces depression symptoms more effectively than a placebo. One study compared iTBS to another brain stimulation method and found it to be just as effective, if not better, at improving mood in individuals whose depression hasn't responded to other treatments. Other research confirms that iTBS effectively treats both unipolar and bipolar depression, making it a versatile option. Additionally, iTBS is generally well-tolerated, allowing most people to undergo the treatment without major side effects. ^{3 6 7 8 9}

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.

I have a neurological condition.

OCD

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 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 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 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) 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]

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) 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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40509535/

Real-World Effectiveness and Tolerability of Prolonged ... Left-sided DLPFC iTBS1800 may be a feasible option for treating older patients with TRD due to its favorable effect and shorter treatment period.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35609816/

Intermittent theta burst stimulation (iTBS) versus 10 Hz high ... The aim of our study was to compare the efficacy of 10 Hz rTMS and iTBS in treatment-resistant unipolar depression on response rates.

3. sciencedirect.com sciencedirect.com/science/article/pii/S0165032723002604

Outcome of transcranial magnetic intermittent theta-burst ... The aim of this study was to investigate the effectiveness and tolerability of iTBS for unipolar and bipolar depression in the clinical setting ...

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2830095

Accelerated Intermittent Theta-Burst Stimulation for ... They found that active aiTBS was significantly more effective than sham stimulation for depressive symptoms, supporting the clinical efficacy of ...

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

Theta burst stimulation for depression: a systematic review ... The current study outcomes included the response rate (primary), depression symptom improvement, remission rate, all-cause discontinuation rate, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10423820/

Efficacy and safety of intermittent theta burst stimulation ... This result was consistent with a previous review that reported that iTBS as an add-on therapy was relatively safe for psychiatric disorders and ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006322325013563

Efficacy and Safety of Accelerated Intermittent Theta-burst ... In this trial, a-iTBS, administered five sessions per day for ten days, is effective and safe for adolescents with non-treatment-resistant MDD.

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40042840/

Accelerated Theta-Burst Stimulation for Treatment ... A pragmatic aTBS protocol using only 3 iTBS sessions per day and a nonexpensive, non-neuronavigated approach was found to be safe and effective for TRD.

9. psychiatryonline.org psychiatryonline.org/doi/full/10.1176/appi.ajp.2021.21121221

Accelerated Intermittent Theta Burst Stimulation In terms of the primary outcomes, the authors reported an impressive 69.2% response rate and a 46.2% remission rate 4 weeks after treatment, ...