Accelerated TMS for Depression

Overseen By Nick Bassano, MSW

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Stanford University

Must be taking: Antidepressants

Must not be taking: Ketamine, ECT

Disqualifiers: Pregnancy, Psychotic disorder, Bipolar, others

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

Compensation: Varies

Number of Visits: 6

Duration: 4-8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach using transcranial magnetic stimulation (TMS), a non-invasive method that uses magnetic fields to stimulate nerve cells, for individuals with depression unresponsive to other treatments. It compares an accelerated version of TMS, called theta-burst stimulation (TBS-DLPFC), to a placebo (inactive) treatment to determine its effectiveness in improving symptoms. Suitable participants include those diagnosed with major depressive disorder who have tried other treatments without success and have not previously undergone TMS.

As an unphased trial, this study provides a unique opportunity to explore innovative treatment options for depression.

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 prior data suggests that this transcranial magnetic stimulation device is safe for treatment-resistant depression?

Research has shown that active theta-burst stimulation (TBS) is generally safe. In one study, only 4.5% of participants discontinued treatment due to side effects, which were usually mild, such as brief scalp discomfort. Other studies suggest that TBS might work faster and possibly better than other types of transcranial magnetic stimulation (TMS) for treating depression. While TMS is already approved for depression, TBS is a specific type that works more quickly, offering a potential advantage. Overall, the safety profile appears promising, with most side effects being minor and temporary. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about theta-burst TMS (transcranial magnetic stimulation) for depression because it offers a potentially faster-acting solution compared to traditional treatments like antidepressants and standard TMS protocols. While typical antidepressant medications can take weeks to show benefits, theta-burst TMS might provide improvements in just a few days due to its accelerated stimulation pattern. Additionally, unlike medications that alter chemical levels in the brain, theta-burst TMS directly targets brain activity, offering a non-invasive and drug-free approach that could reduce side effects associated with pharmacological treatments.

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

Research has shown that theta-burst stimulation (TBS) targeting the left side of the brain's front part can help treat depression. In this trial, participants will receive either Active TBS-DLPFC or Sham TBS-DLPFC. Studies have linked this type of brain stimulation to positive outcomes, such as reduced depression symptoms and improved response rates. Specifically, those who received the active treatment felt less depressed compared to those who received the sham treatment. This method uses magnetic pulses to stimulate specific brain areas, potentially improving mood. Overall, TBS is considered a promising option for individuals with depression that hasn't improved with other treatments. ^{2 6 7 8 9}

Who Is on the Research Team?

David Spiegel, MD

Principal Investigator

Stanford University

Nolan Williams, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for adults aged 22-65 with treatment-resistant depression, who haven't tried TMS before. They must be able to understand English, have a stable antidepressant regimen, and not plan on pregnancy. Exclusions include unstable symptoms, certain psychiatric conditions like bipolar disorder or severe personality disorders, substance abuse issues, contraindications to MRI or rTMS (like metal in the head), and recent use of rapid acting antidepressants.

Inclusion Criteria

In good general health, as evidenced by medical history.

For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation.

I have access to psychiatric care before and after the study.

Exclusion Criteria

My mood symptoms have not worsened by 30% or more recently.

I've had more than 8 ECT sessions without improvement.

I have a history of serious brain or nerve conditions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive theta-burst TMS stimulation or sham treatment for 5 days per week

4-8 weeks

5 visits per week (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Active TBS-DLPFC
• Sham TBS-DLPFC

Trial Overview The study tests an accelerated form of theta-burst stimulation via transcranial magnetic stimulation (TBS-DLPFC) against a sham procedure in people with major depressive disorder. Participants are randomly assigned to either real or fake treatments without knowing which one they're getting.

How Is the Trial Designed?

Group I: Active TBS-DLPFC Experimental Treatment 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.

Active TBS-DLPFC is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder
• Migraines
• Smoking Cessation

Approved in European Union as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder

Approved in Canada as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Published Research Related to This Trial

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 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 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 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]

Theta-burst transcranial magnetic stimulation (TBS) is safe and well tolerated in patients with major depression, based on a study involving 33 participants over 10 consecutive days.

The study suggests that TBS may have antidepressant effects, and increasing stimulation parameters does not lead to more side effects, potentially enhancing its therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability and preliminary evidence for antidepressant efficacy of theta-burst transcranial magnetic stimulation in patients with major depression. Chistyakov, AV., Rubicsek, O., Kaplan, B., et al.[2019]

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 randomized controlled trial involving 56 patients with moderate to severe depression, bilateral theta-burst stimulation (TBS) and repetitive transcranial magnetic stimulation (rTMS) did not show significant improvements in depression scores compared to sham treatment.

However, there was a noted tendency for both active treatments to increase the responder rate, particularly for the TBS group, suggesting that further research may be needed to explore its potential benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bilateral prefrontal rTMS and theta burst TMS as an add-on treatment for depression: a randomized placebo controlled trial. Prasser, J., Schecklmann, M., Poeppl, TB., et al.[2015]

In a study involving 29 patients with major depression, continuous theta-burst transcranial magnetic stimulation (cTBS) did not show a significant overall improvement compared to sham treatment, indicating modest efficacy.

However, patients who were either medication-free or had unchanged medication status experienced a greater reduction in depression scores with active cTBS, suggesting it may be beneficial for those not responding to traditional pharmacological treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary assessment of the therapeutic efficacy of continuous theta-burst magnetic stimulation (cTBS) in major depression: a double-blind sham-controlled study. Chistyakov, AV., Kreinin, B., Marmor, S., et al.[2018]

This study involves 236 patients with major depressive disorder (MDD) and aims to confirm that bilateral theta burst stimulation (TBS) is more effective than sham treatment over six weeks, with the primary outcome being a significant reduction in depression scores.

If successful, the results will support the use of TBS as a faster, effective, and safe treatment option for MDD, potentially leading to more personalized therapy approaches based on MRI and genetic predictors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of major depressive disorder with bilateral theta burst stimulation: study protocol for a randomized, double-blind, placebo-controlled multicenter trial (TBS-D). Plewnia, C., Brendel, B., Schwippel, T., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11609094/

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, ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2667174325001727

Efficacy, effectiveness and safety of transcranial magnetic ... High and low frequency protocols on left and right DLPFC, respectively, are robustly associated with positive outcomes, with L-DLPFC iTBS ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10922157/

Lateral prefrontal stimulation of active cortex with theta ... Stimulating left dorsolateral prefrontal cortex (dlPFC) while participants perform a working memory task will provide stronger effects on subsequent activation.

4. 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 ...

5. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2777422

Efficacy of Active vs Sham Intermittent Theta Burst ... iTBS targeting the left dorsolateral prefrontal cortex is not efficacious in the treatment of acute bipolar depression and can result in mood episode switches.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/17573044/

Efficacy and safety of transcranial magnetic stimulation in ... Active TMS was well tolerated with a low dropout rate for adverse events (4.5%) that were generally mild and limited to transient scalp ...

7. 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 ...

8. cell.com cell.com/cell-reports-medicine/fulltext/S2666-3791(25)00475-6

A sequential dual-site repetitive transcranial magnetic ... Repetitive transcranial magnetic stimulation (rTMS) is approved for major depressive disorder (MDD), but it is limited by variable efficacy.

9. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2024.1504727/full

A meta-analysis comparing the effectiveness and safety of ... Objective: This study compares the safety and effectiveness of theta-burst stimulation (TBS) and repetitive transcranial magnetic stimulation (rTMS) for ...