Rapid-Acting TMS for Depression

Overseen By Romina Nejad, MSc

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)

Approved in 3 Jurisdictions This treatment is already approved in other countries

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 method for treating depression that does not improve with standard medications. It uses a device called transcranial magnetic stimulation (TMS) to deliver quick magnetic pulses to the brain. This specific form of TMS is known as TBS-DLPFC (Theta-Burst Stimulation targeting the dorsolateral prefrontal cortex). Half of the participants will receive the actual treatment, while the other half will receive a placebo version to evaluate its effectiveness. Individuals with long-term major depression, who have not found relief with other treatments and have never tried TMS, might be suitable for this trial. As an unphased trial, this study provides a unique opportunity to explore an innovative treatment option 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 theta-burst stimulation (TBS) is generally safe and well-tolerated for treating depression. TBS uses magnetic pulses to stimulate the brain, and its side effects are similar to other types of transcranial magnetic stimulation (TMS), meaning it doesn't cause more side effects than other TMS treatments.

Previous patients found TBS effective and safe, with no major negative effects. This is promising for those considering joining a trial. Other studies have used the treatment and found it both effective and manageable for many people with depression. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about theta-burst TMS (TBS-DLPFC) for depression because it offers a rapid-acting alternative to traditional antidepressants and therapies, which often take weeks to show effects. TBS-DLPFC targets the brain's prefrontal cortex using bursts of magnetic stimulation, potentially enhancing mood regulation much faster. This method also avoids the side effects associated with medications, making it a promising option for those who haven't found relief through current treatments like SSRIs or psychotherapy.

What evidence suggests that this device is effective for treatment-resistant depression?

Research shows that theta-burst stimulation (TBS) may help treat depression. A review of studies found that TBS significantly improved depression symptoms and had a good success rate. Other research indicates that TBS effectively reduces symptoms in both unipolar and bipolar depression. Additionally, a combined analysis of studies found that TBS works just as well as traditional transcranial magnetic stimulation (TMS) for easing depression and anxiety, with similar safety. In this trial, participants will join either an active TBS-DLPFC group or a sham TBS-DLPFC group to evaluate TBS's effectiveness. These findings suggest that TBS could be a helpful option for people with depression that hasn't responded to other treatments. ^{1 2 3 5 6}

Who Is on the Research Team?

David Spiegel, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

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

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

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

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 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)

What Are the Treatments Tested in This Trial?

Interventions

• TBS-DLPFC

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.

How Is the Trial Designed?

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

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Published Research Related to This Trial

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]

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 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 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]

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]

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 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 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]

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. clinicaltrials.gov clinicaltrials.gov/study/NCT01240083

Effectiveness of Theta-burst Stimulation (TBS) in Patients ... In the proposed study we investigate whether high frequent rTMS or Theta-Burst Stimulation of the DLPFC is more effective in patients with a depressive episode.

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

Outcome of transcranial magnetic intermittent theta-burst ... The aim of this study was to investigate the effectiveness and tolerability of iTBS for unipolar and bipolar depression in the clinical setting ...

4. 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.

5. nature.com nature.com/articles/s41591-023-02764-z

Connectivity-guided intermittent theta burst versus ... - Nature Persistent decreases in depressive symptoms were seen over 26 weeks, with no differences between arms on the primary outcome GRID Hamilton ...

6. 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 ...