Rapid-Acting TMS for Depression

Overseen by David Spiegel, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Stanford University

Must be taking: Antidepressants

Must not be taking: Ketamine, ECT

Disqualifiers: Pregnancy, Psychotic disorder, Bipolar, others

No Placebo Group

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This study evaluates an accelerated schedule of theta-burst stimulation using a transcranial magnetic stimulation device for treatment-resistant depression. In a double-blind, randomized, sham-controlled fashion, half the participants will receive accelerated theta-burst stimulation while half will receive sham treatment.

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 TBS-DLPFC for depression?

Research shows that intermittent theta burst stimulation (iTBS), a form of transcranial magnetic stimulation (TMS), is effective for treating major depression. Studies indicate that iTBS can be as effective as traditional TMS but is delivered in a shorter time, making it a promising option for patients with treatment-resistant depression. ^{1 2 3 4 5}

Is rapid-acting TMS for depression safe for humans?

Theta burst stimulation (TBS), a form of transcranial magnetic stimulation (TMS), is generally considered safe, with most side effects being mild and occurring in about 5% of people. However, there is a small risk of seizures, so it should be used carefully, especially since it's a newer technique. ^{4 6 7 8 9}

How is the TBS-DLPFC treatment for depression different from other treatments?

TBS-DLPFC (Theta-Burst Stimulation) is a unique treatment for depression because it uses magnetic pulses to stimulate the brain in a very short time, just over 3 minutes, compared to traditional methods that take much longer. This makes it a faster option for patients, and it can be used in accelerated schedules, although the best settings for its use are still being studied. ^{1 2 4 7 10}

Research Team

David Spiegel, MD

Principal Investigator

Stanford University

Eligibility Criteria

This trial is for adults aged 22-65 with Major Depressive Disorder who haven't responded well to other treatments. Participants must be in good health, not have certain mental health conditions or severe personality disorders, and can't be using substances or have metal implants that interfere with MRI scans.

Inclusion Criteria

Your depression score is 20 or higher during the first visit of the study.

I can get rTMS treatment after the study ends.

I can get rTMS treatment after the study ends.

Exclusion Criteria

I have a stable anxiety disorder but no other major psychiatric conditions needing treatment.

You have received any experimental medications or treatments during the study timeframe.

I have a history of serious brain or nerve conditions.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

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

4-8 weeks

5 visits per week

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• TBS-DLPFC (Transcranial Magnetic Stimulation)

Trial Overview The study tests a rapid version of theta-burst stimulation (TBS) via transcranial magnetic stimulation (TMS) against a sham treatment for depression. It's randomized and double-blind, meaning neither the researchers nor participants know who gets real TBS until after the study.

Participant Groups

Group I: Active TBS-DLPFC Active Control 1 Intervention

The active group will receive theta-burst TMS stimulation.

Group II: Sham TBS-DLPFC Placebo Group 1 Intervention

The sham group will receive sham theta-burst TMS stimulation.

TBS-DLPFC is already approved in Canada for the following indications:

Approved in Canada as TBS-DLPFC for:

• Depression
• Anxiety Disorders

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Dr. Richard A. Miller

Stanford University

Chief Executive Officer since 2023

Stanford University, MD

Dr. Robert Schott

Stanford University

Chief Medical Officer since 2021

University of Michigan, MD

Findings from Research

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]

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 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]

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]

Theta burst stimulation (TBS) is a promising technique for altering brain excitability, with a review of studies showing that adverse events were mostly mild and occurred in only 5% of subjects, indicating a generally safe profile.

Despite its safety, TBS carries a theoretical higher risk of seizures compared to other stimulation methods, necessitating cautious application and further research into its dosing parameters to better understand seizure risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of theta burst transcranial magnetic stimulation: a systematic review of the literature. Oberman, L., Edwards, D., Eldaief, M., et al.[2022]

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]

Monophasic intermittent theta-burst stimulation (iTBS) was found to induce significantly greater increases in motor corticospinal excitability compared to biphasic iTBS, based on a study involving 30 healthy volunteers.

The study suggests that monophasic iTBS may have a stronger potential for functional impact in clinical applications, as it demonstrated a more pronounced physiological effect on motor neuron activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of pulse shape in theta-burst stimulation: Monophasic vs biphasic TMS. Wendt, K., Sorkhabi, MM., Stagg, CJ., et al.[2023]

In a study of 165 pediatric participants aged 6 to 18, theta-burst TMS (TBS) demonstrated a similar safety profile to single- and paired-pulse TMS (sp/ppTMS), with no severe adverse effects reported.

The overall rate of adverse effects was 10.5% for TBS and 12.4% for sp/ppTMS, with most effects rated as minimal or mild, indicating that TBS is a safe option for further investigation in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of theta burst stimulation vs. single and paired pulse transcranial magnetic stimulation: a comparative study of 165 pediatric subjects. Hong, YH., Wu, SW., Pedapati, EV., et al.[2020]

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]

References

1. 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]

2. Ireland pubmed.ncbi.nlm.nih.gov

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

3. 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]

4. 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]

5. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

Safety of theta burst transcranial magnetic stimulation: a systematic review of the literature. [2022]

7. Switzerland 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. [2023]

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

The effect of pulse shape in theta-burst stimulation: Monophasic vs biphasic TMS. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and tolerability of theta burst stimulation vs. single and paired pulse transcranial magnetic stimulation: a comparative study of 165 pediatric subjects. [2020]

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

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