Individualized TMS for Depression

(AINT Trial)

Overseen by Joseph J Taylor, MD, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: Brigham and Women's Hospital

No Placebo Group

Prior Safety Data

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial tests aiTBS, a magnetic brain stimulation method, on patients with depression that hasn't responded to other treatments. The treatment uses magnetic pulses to reset brain activity and improve mood. Participants will receive aiTBS either guided by brain scans or by physical measurements of the head. Intermittent Theta Burst Stimulation (iTBS) is a newer form of repetitive Transcranial Magnetic Stimulation (rTMS) that has shown potential for faster and more intense effects in treating depression.

Do I have to stop taking my current medications for the trial?

No, you don't have to stop taking your current medications. You need to have a stable antidepressant medication regimen for 4 weeks before the treatment and stay on it throughout the study.

What data supports the idea that Individualized TMS for Depression is an effective treatment?

The available research shows that Individualized TMS for Depression, specifically using theta burst stimulation (TBS), can be effective. One study found that TBS was as effective as traditional high-frequency TMS in treating depression, even in cases where other treatments had failed. Another study highlighted that accelerated TMS could shorten the time it takes for patients to feel better. However, the effectiveness can vary, as seen in a case series where only a small number of participants achieved significant improvement. Overall, while TMS shows promise, its effectiveness can depend on the specific protocol used and the individual patient. ^{1 2 3 4 5}

What safety data exists for individualized TMS for depression?

The safety data for individualized TMS, including aiTBS and SAINT, indicates that these treatments have similar safety profiles to traditional high-frequency rTMS. Studies show that iTBS and its variants are generally well-tolerated, with some participants experiencing tolerability issues. Meta-analyses suggest comparable safety and acceptability between iTBS and HF-rTMS for treatment-resistant depression. However, optimal parameters for these protocols are still under investigation. ^{1 2 3 6 7}

Is aiTBS a promising treatment for depression?

Yes, aiTBS is a promising treatment for depression. It can shorten the time it takes for patients to feel better, and it is quicker to administer than traditional methods. This makes it a valuable option for people with depression. ^{1 3 8 9 10}

Research Team

Joseph J Taylor, MD, PhD

Principal Investigator

Brigham and Women's Hospital

Eligibility Criteria

This trial is for adults with major depressive disorder who haven't responded well to other treatments. They must speak English, maintain their usual caffeine intake, not use tobacco on treatment days, and avoid alcohol before MRI and TMS sessions. Pregnant individuals or those trying to become pregnant cannot participate.

Inclusion Criteria

I have been diagnosed with major depression.

I have not changed my antidepressant medication or been off it for the last 4 weeks.

Abstain from becoming pregnant from screening through end of treatment

Exclusion Criteria

Anyone presenting with psychosis

Current moderate or severe substance use disorder or demonstrating signs of acute substance withdrawal

Severe borderline personality disorder

Treatment Details

Interventions

• aiTBS (Other)

Trial Overview The study tests aiTBS (a type of brain stimulation) for depression treatment effectiveness. Participants will receive aiTBS without knowing if the targeted area was chosen using neuroimaging or standard head measurements.

Participant Groups

Group I: sham individualized resting state functional connectivity targeting Experimental Treatment 1 Intervention

Participants in this group will receive aiTBS with neuronavigation to a treatment target identified with head measurements (i.e., Beam F3)

Group II: real individualized resting state functional connectivity targeting Experimental Treatment 1 Intervention

Participants in this group will receive aiTBS with neuronavigation to a treatment target identified with individualized resting state functional connectivity.

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Dr. William Curry

Brigham and Women's Hospital

Chief Medical Officer

MD from Columbia University College of Physicians and Surgeons

Dr. Scott Schissel

Brigham and Women's Hospital

Chief Executive Officer since 2021

MD from Columbia University College of Physicians and Surgeons

Findings from Research

Repetitive transcranial magnetic stimulation (rTMS) is an established treatment for major depressive disorder (MDD), but its effect sizes are modest compared to standard treatments.

Accelerated high-frequency rTMS (arTMS) and accelerated intermittent theta burst stimulation (aiTBS) showed similar clinical efficacy, but both methods have the potential to significantly reduce the time it takes for patients to move from a depressed state to a response state, which is beneficial for patient recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated rTMS: A Potential Treatment to Alleviate Refractory Depression. Baeken, C.[2020]

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]

In a study of 27 participants, a prolonged intermittent theta burst stimulation (piTBS) protocol using 1,800 pulses showed limited effectiveness for major depressive disorder, with only 18.2% of participants achieving a response and 9.1% reaching remission.

Safety and tolerability were concerns, as 18.5% of participants experienced issues, suggesting that while piTBS is a promising approach, further research is needed to optimize its parameters and improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged intermittent theta burst stimulation in the treatment of major depressive disorder: a case series. Richard, M., Noiseux, C., Desbeaumes Jodoin, V., 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]

In a study of 61 patients with treatment-resistant depression, prolonged intermittent theta burst stimulation (piTBS) showed a significant association between theta-alpha amplitude modulation frequency and antidepressant efficacy, suggesting that this EEG measure could predict treatment response within the first two weeks.

In contrast, 10 Hz rTMS did not show a similar correlation with clinical outcomes, indicating that the neurophysiological effects of piTBS may be more closely linked to its therapeutic benefits compared to traditional rTMS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Critical role of rhythms in prefrontal transcranial magnetic stimulation for depression: A randomized sham-controlled study. Tsai, YC., Li, CT., Liang, WK., et al.[2022]

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]

In a study involving 300 patients with treatment-resistant depression, accelerated bilateral theta burst stimulation (TBS) was found to be effective and safe, with a treatment response rate of 43.7% and a remission rate of 28.2%.

The study revealed no significant differences in efficacy between different TBS intensities or when compared to traditional unilateral 10 Hz rTMS, indicating that the accelerated TBS does not provide faster antidepressant effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated theta burst stimulation for the treatment of depression: A randomised controlled trial. Chen, L., Thomas, EHX., Kaewpijit, P., 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 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 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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Accelerated rTMS: A Potential Treatment to Alleviate Refractory Depression. [2020]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Treatment of major depression with bilateral theta burst stimulation: a randomized controlled pilot trial. [2018]

3. Ireland pubmed.ncbi.nlm.nih.gov

Prolonged intermittent theta burst stimulation in the treatment of major depressive disorder: a case series. [2022]

4. United States 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). [2022]

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

Critical role of rhythms in prefrontal transcranial magnetic stimulation for depression: A randomized sham-controlled study. [2022]

6. Ireland 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. [2023]

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

Accelerated theta burst stimulation for the treatment of depression: A randomised controlled trial. [2022]

8. England 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. [2022]

9. United States 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. [2022]

10. India 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. [2022]