iTBS for Depression

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Disqualifiers: Bipolar, Psychotic disorders, Seizures, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4-6 weeks

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how Intermittent Theta Burst Stimulation (iTBS) can assist individuals with Major Depressive Disorder (MDD) by targeting specific brain networks. The researchers aim to personalize and enhance depression treatments by understanding the effects on brain connectivity and behavior. Participants will receive iTBS targeting different brain areas or a placebo (inactive treatment) to compare outcomes. Those currently experiencing a major depressive episode that affects daily life might be suitable for this study. As an unphased trial, this study provides a unique opportunity to contribute to pioneering research that could lead to more personalized depression treatments.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that intermittent theta burst stimulation (iTBS) is generally safe for patients. In 2018, the FDA approved iTBS for treating depression, indicating it meets certain safety standards. Studies comparing iTBS to other treatments, such as high-frequency transcranial magnetic stimulation (rTMS), found similar side effects. Patients typically experience mild and temporary side effects, such as headaches or scalp discomfort. Overall, current research supports the safety of iTBS for treating depression. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Intermittent Theta Burst Stimulation (iTBS) for depression because it offers a novel approach compared to standard treatments like antidepressants and traditional repetitive transcranial magnetic stimulation (rTMS). Unlike conventional rTMS, iTBS uses short bursts of high-frequency stimulation that mimic natural brain rhythms, potentially enhancing its effectiveness and efficiency. This technique targets specific brain networks, such as the default, control, salience, and limbic-reward networks in the prefrontal cortex, allowing for a more personalized treatment plan. Additionally, iTBS can be administered multiple times a day, which might accelerate the therapeutic effects and reduce the time needed to see improvements in depressive symptoms.

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

Research has shown that Intermittent Theta Burst Stimulation (iTBS) could be a promising treatment for depression. A large study found that about 42.1% of patients with depression responded well to iTBS, comparable to other effective treatments. iTBS is considered safe and tolerable, with few side effects. It uses magnetic pulses to stimulate specific brain areas that influence mood. This trial will explore different iTBS targets, including the default network A, control network, salience network, default network B, and limbic-reward network, along with a SHAM stimulation group. Some studies suggest that iTBS might work better and faster than traditional methods. Overall, iTBS shows strong potential to help people with depression. ^{3 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 who are currently experiencing a major depressive episode. It's open to those with additional anxiety or personality disorders, as long as depression is the main issue. Participants must be able to understand and agree to the study's terms.

Inclusion Criteria

I am able to understand and agree to the study's requirements.

I am currently experiencing a major depressive episode.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo repetitive transcranial magnetic stimulation (rTMS) targeting specific brain networks, with each target stimulated four times on separate days.

4-6 weeks

Multiple visits (in-person) for each target stimulation

Follow-up

Participants are monitored for changes in network connectivity and behavior using various tests and MRI assessments.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Intermittent Theta Burst Stimulation (iTBS)

Trial Overview The trial tests Intermittent Theta Burst Stimulation (iTBS), a non-invasive brain stimulation technique, on people with Major Depressive Disorder. The goal is to see how targeting specific brain networks can improve symptoms by changing network connectivity and behavior.

How Is the Trial Designed?

Group I: vmPFC limbic-reward network target Experimental Treatment 1 Intervention

iTBS delivered four times daily to an individually defined reward network representation in left ventromedial prefrontal cortex (vMPFC).

Group II: dmPFC Default network B target Experimental Treatment 1 Intervention

iTBS delivered four times daily to an individually defined default network B representation in left dorsomedial prefrontal cortex (DMPFC).

Group III: DLPFC Salience network target Experimental Treatment 1 Intervention

iTBS delivered four times daily to an individually defined salience network representation in left dorsolateral prefrontal cortex (DLPFC).

Group IV: DLPFC Default network A target Experimental Treatment 1 Intervention

iTBS delivered four times daily to an individually defined default network A representation in left dorsolateral prefrontal cortex (DLPFC).

Group V: DLPFC Control network target Experimental Treatment 1 Intervention

iTBS delivered four times daily to an individually defined control network representation in left dorsolateral prefrontal cortex (DLPFC).

Group VI: SHAM stimulation Placebo Group 1 Intervention

SHAM iTBS delivered four times daily to an individually defined SHAM region in left dorsolateral prefrontal cortex (DLPFC).

Intermittent Theta Burst Stimulation (iTBS) is already approved in United States, European Union for the following indications:

Approved in United States as rTMS for:

• Major Depressive Disorder (MDD)
• Obsessive-Compulsive Disorder (OCD)
• Migraines
• Smoking Cessation

Approved in European Union as rTMS for:

• Major Depressive Disorder (MDD)

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

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]

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]

Intermittent theta burst stimulation (iTBS) and high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) are equally effective and safe for treating patients with treatment-resistant major depressive disorder, based on a comprehensive meta-analysis.

iTBS may be a more practical option in clinical settings because it requires less stimulation intensity and shorter treatment times compared to HF-rTMS, making it potentially more accessible for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent theta burst stimulation vs. high-frequency repetitive transcranial magnetic stimulation for major depressive disorder: A systematic review and meta-analysis. Kishi, T., Sakuma, K., Matsuda, Y., et al.[2023]

Intermittent theta-burst stimulation (iTBS) and high-frequency rTMS (HF-rTMS) show similar efficacy in treating treatment-resistant depression (TRD), with response rates of 48.0% for iTBS and 45.5% for HF-rTMS based on two high-quality randomized controlled trials involving 474 participants.

Both iTBS and HF-rTMS have comparable safety profiles, with similar rates of discontinuation and adverse events, such as headaches, indicating that iTBS is a safe alternative to HF-rTMS for patients with TRD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of intermittent theta burst stimulation versus high-frequency repetitive transcranial magnetic stimulation for patients with treatment-resistant depression: a systematic review. Lan, XJ., Yang, XH., Qin, ZJ., et al.[2023]

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]

In a study of 60 patients with treatment-resistant unipolar depression, both intermittent theta burst stimulation (iTBS) and conventional 10 Hz rTMS showed similar efficacy in reducing depression scores and improving quality of life over a 6-month follow-up, with response rates of 36.7% for iTBS and 33.3% for rTMS.

iTBS is highlighted as a more time-efficient and cost-effective option compared to rTMS, suggesting it could be a valuable treatment alternative for patients with severe depression who have not responded to multiple antidepressant trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent theta burst stimulation (iTBS) versus 10 Hz high-frequency repetitive transcranial magnetic stimulation (rTMS) to alleviate treatment-resistant unipolar depression: A randomized controlled trial (THETA-DEP). Bulteau, S., Laurin, A., Pere, M., et al.[2022]

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-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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36841303/

Outcome of transcranial magnetic intermittent theta-burst ... In a clinical setting, iTBS was shown to be safe and tolerable and the response rate was similar to that reported from clinical trials.

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

Outcome of transcranial magnetic intermittent theta-burst ... In this first national register-based cohort study of iTBS for depression we observed a clinician rated response rate of 42.1 %, being on par ...

3. 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 ...

4. 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.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT07033780

NCT07033780 | Theta-Burst Stimulation to Treat Depression The goal of this clinical trial is to explore the effects of non-invasive brain stimulation protocols using intermittent theta-burst stimulation (iTBS) on ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11841443/

A meta-analysis comparing the effectiveness and safety of ... Both rTMS and TBS are similarly effective in reducing depression and anxiety symptoms, with comparable side effect profiles.

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

Efficacy and Safety of Accelerated Intermittent Theta-burst ... The U.S. Food and Drug Administration (FDA) has cleared high-frequency repetitive transcranial magnetic stimulation (rTMS) therapy for adults ...

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

Efficacy and safety of intermittent theta burst stimulation ... The objective of this systematic review was to compare the safety and efficacy of iTBS and high-frequency (≥ 5 Hz) rTMS (HF-rTMS) for patients with treatment- ...