Rapid-Acting TMS for Depression

Recruiting in Palo Alto (17 mi)

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 United States, European Union, Canada for the following indications:

🇺🇸 Approved in United States as TBS-DLPFC for:

• Treatment-Resistant Depression

🇪🇺 Approved in European Union as TBS-DLPFC for:

• Major Depressive Disorder
• Treatment-Resistant Depression

🇨🇦 Approved in Canada as TBS-DLPFC for:

• Depression
• Anxiety Disorders

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine Stanford, CA

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2527

Patients Recruited

17,430,000+

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] Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depression (MD). We retrospectively analyzed the efficacy of intermittent theta burst stimulation (iTBS) on the left dorsolateral prefrontal cortex (DLPFC) combined with low-frequency rTMS (LF-rTMS) on the right DLPFC as an additional therapy to standard medication treatment.

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

Prolonged intermittent theta burst stimulation in the treatment of major depressive disorder: a case series. [2022] Intermittent theta burst stimulation (iTBS) using 600 pulses is an effective and FDA-cleared transcranial magnetic stimulation (TMS) protocol for major depressive disorder (MDD). Prolonged iTBS (piTBS) using 1,800 pulses could increase the effectiveness of TMS for MDD, but its real-world effectiveness is still debated. We assessed the safety, tolerability, and preliminary effectiveness of a 3x daily piTBS 1,800 pulses protocol delivered over 2 weeks in 27 participants. Only four participants (18.2%) achieved response, two of them achieving remission (9.1%). Five participants (18.5%) experienced tolerability issues. Future studies should focus on the neurophysiological effects of TBS protocols to determine optimal parameters.

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] Intermittent theta burst stimulation (iTBS) is a newer form of repetitive transcranial magnetic stimulation (rTMS) for patients with treatment resistant depression (TRD). Applying multiple daily iTBS sessions may enable patients to achieve remission more rapidly.

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] Treatment-resistant major depressive disorder is common; repetitive transcranial magnetic stimulation (rTMS) by use of high-frequency (10 Hz) left-side dorsolateral prefrontal cortex stimulation is an evidence-based treatment for this disorder. Intermittent theta burst stimulation (iTBS) is a newer form of rTMS that can be delivered in 3 min, versus 37·5 min for a standard 10 Hz treatment session. We aimed to establish the clinical effectiveness, safety, and tolerability of iTBS compared with standard 10 Hz rTMS in adults with treatment-resistant depression.

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

Treatment of major depression with bilateral theta burst stimulation: a randomized controlled pilot trial. [2018] Current efforts to improve clinical effectiveness and utility of repetitive transcranial magnetic stimulation (rTMS) in the treatment of major depression (MD) include theta burst stimulation (TBS), a patterned form of rTMS. Here, we investigated the efficacy of bilateral TBS to the dorsolateral prefrontal cortex (dlPFC) in patients with MD in additon to ongoing medication and psychotherapy.

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

Safety of theta burst transcranial magnetic stimulation: a systematic review of the literature. [2022] Theta burst stimulation (TBS) protocols have recently emerged as a method to transiently alter cortical excitability in the human brain through repetitive transcranial magnetic stimulation. TBS involves applying short trains of stimuli at high frequency repeated at intervals of 200 milliseconds. Because repetitive transcranial magnetic stimulation is known to carry a risk of seizures, safety guidelines have been established. TBS has the theoretical potential of conferring an even higher risk of seizure than other repetitive transcranial magnetic stimulation protocols because it delivers high-frequency bursts. In light of the recent report of a seizure induced by TBS, the safety of this new protocol deserves consideration. We performed an English language literature search and reviewed all studies published from May 2004 to December 2009 in which TBS was applied. The adverse events were documented, and crude risk was calculated. The majority of adverse events attributed to TBS were mild and occurred in 5% of subjects. Based on this review, TBS seems to be a safe and efficacious technique. However, given its novelty, it should be applied with caution. Additionally, this review highlights the need for rigorous documentation of adverse events associated with TBS and intensity dosing studies to assess the seizure risk associated with various stimulation parameters (e.g., frequency, intensity, and location).

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] Intermittent theta-burst stimulation (iTBS), which is a form of repetitive transcranial magnetic stimulation (rTMS), can produce 600 pulses to the left dorsolateral prefrontal cortex (DLPFC) in a stimulation time of just over 3 min. 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-resistant depression (TRD).

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

The effect of pulse shape in theta-burst stimulation: Monophasic vs biphasic TMS. [2023] Intermittent theta-burst stimulation (i) (TBS) is a transcranial magnetic stimulation (TMS) plasticity protocol. Conventionally, TBS is applied using biphasic pulses due to hardware limitations. However, monophasic pulses are hypothesised to recruit cortical neurons more selectively than biphasic pulses, predicting stronger plasticity effects. Monophasic and biphasic TBS can be generated using a custom-made pulse-width modulation-based TMS device (pTMS).

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] Although single- and paired-pulse (sp/pp) transcranial magnetic stimulation (TMS) studies are considered minimal risk in adults and children, the safety profile for theta-burst TMS (TBS) is unknown.

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

Accelerated theta burst stimulation for the treatment of depression: A randomised controlled trial. [2022] Theta burst pattern repetitive transcranial magnetic stimulation (TBS) is increasingly applied to treat depression. TBS's brevity is well-suited to application in accelerated schedules. Sizeable trials of accelerated TBS are lacking; and optimal TBS parameters such as stimulation intensity are not established.