Rapid Acting TMS for Depression and Suicide Ideation

Overseen By David Spiegel, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Stanford University

Must not be taking: Cocaine, Amphetamines, Benzodiazepines

Disqualifiers: Epilepsy, Autism, OCD, Anxiety, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach called accelerated theta burst stimulation, a form of brain stimulation therapy, to assist individuals with major depressive disorder and suicidal thoughts. The researchers aim to assess how this rapid schedule of brain stimulation influences thinking patterns related to depression and suicidal ideation. Participants will receive either real or sham (non-active) stimulation. Suitable candidates include those with major depressive disorder or bipolar disorder with suicidal thoughts who have not previously tried this type of brain stimulation. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research in brain stimulation therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it mentions that participants should not have used rapid-acting antidepressants like ketamine for the current depressive episode.

What prior data suggests that this protocol is safe for treating depression and suicide ideation?

Research has shown that accelerated theta burst stimulation (aiTBS) could be a promising treatment for major depressive disorder. Studies have found that it can quickly reduce symptoms of depression and suicidal thoughts.

Regarding safety, aiTBS is generally well-tolerated. Most people experience only mild side effects, such as headaches or discomfort at the treatment site. Serious side effects are rare. In past studies, participants reported improvement without major issues.

In summary, aiTBS appears to be a safe option for those dealing with depression and suicidal thoughts. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike typical depression treatments that often rely on medications like SSRIs, the accelerated theta burst stimulation (TBS) technique offers a non-invasive, rapid-acting alternative. Researchers are excited about this method because it targets the brain's left dorsolateral prefrontal cortex (L-DLPFC) with precise magnetic pulses, potentially reducing symptoms of depression and suicidal thoughts much faster than traditional approaches. While most treatments take weeks to show effects, this protocol could deliver results in just days, offering hope for patients needing urgent relief.

What evidence suggests that accelerated theta burst stimulation is effective for depression and suicide ideation?

Research shows that a new treatment called accelerated intermittent theta burst stimulation (aiTBS), which participants in this trial may receive, holds promise for helping people with major depressive disorder (MDD) and reducing suicidal thoughts. Studies have found that aiTBS can quickly improve mood and decrease suicidal ideas. This treatment stimulates the brain without surgery or entering the body. Compared to traditional treatments, aiTBS may work faster and be more effective. Overall, early research suggests this could be a valuable option for those dealing with these conditions. ^{1 3 5 6 7}

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 or bipolar II, experiencing suicidal thoughts. They must be TMS naive, in good health, and agree to use contraception if applicable. Excluded are those with certain mental disorders, substance abuse issues, metal implants or shrapnel in the head, seizures history, severe insomnia or who are pregnant.

Inclusion Criteria

I can get rTMS treatment after leaving the hospital.

Endorse suicidal ideation (score ≥9 on the SSI-M).

You have never received Transcranial Magnetic Stimulation (TMS) treatment before.

Exclusion Criteria

The principal investigator believes that any other condition or factor could affect the accuracy or integrity of the study data.

I have a history of epilepsy or seizures.

I want ECT and had issues with it before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive accelerated theta burst stimulation (aiTBS) or sham stimulation targeting the left dorsolateral prefrontal cortex

1 week

Daily visits (in-person)

Follow-up

Participants are monitored for changes in suicidal ideation and depression severity after treatment

1 week

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Accelerated Theta Burst Stimulation
• Sham Stimulation

Trial Overview The study tests accelerated intermittent theta-burst stimulation (aiTBS) against a sham treatment to see its effect on brain networks related to suicidal thinking in depressed patients. Participants will receive either real aiTBS or a placebo-like version without active stimulation.

How Is the Trial Designed?

Group I: Left Dorsolateral Prefrontal Cortex (L-DLPFC) Active Control 1 Intervention

The accelerated theta burst stimulation protocol will be applied to the left dorsolateral prefrontal cortex (DLPFC)

Group II: Sham Stimulation Placebo Group 1 Intervention

Sham (non-active) stimulation will be applied to the left dorsolateral prefrontal cortex (DLPFC) region

Accelerated Theta Burst Stimulation is already approved in United States for the following indications:

Approved in United States as MagVita TMS Therapy System w/Theta Burst Stimulation for:

• Major Depressive Disorder in adult patients who have failed to receive satisfactory improvement from prior antidepressant medication in the current episode

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Published Research Related to This Trial

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]

Accelerated intermittent theta burst stimulation (TBS) was found to be safe and well tolerated in 12 suicidal therapy-resistant depressed patients, showing a significant decrease in suicidal ideation over time.

However, the reduction in suicidal thoughts was not definitively linked to the active TBS treatment compared to sham stimulation, indicating that further research is needed to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The acute effects of accelerated repetitive Transcranial Magnetic Stimulation on suicide risk in unipolar depression: preliminary results. Desmyter, S., Duprat, R., Baeken, C., et al.[2022]

In a randomized, double-blind trial involving 56 patients, intermittent theta burst stimulation (iTBS) over the dorsomedial prefrontal cortex showed a significant reduction in negative symptoms for patients with depression, but not for those with schizophrenia.

The treatment was generally safe and well-tolerated, with serious adverse events occurring only in the sham group, indicating that iTBS may be a promising intervention for depressive symptoms in certain patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dorsomedial prefrontal theta burst stimulation to treat anhedonia, avolition, and blunted affect in schizophrenia or depression - a randomized controlled trial. Bodén, R., Bengtsson, J., Thörnblom, E., et al.[2021]

In a study involving 45 patients with major depressive disorder, both active and placebo intermittent theta burst stimulation (aiTBS) led to rapid decreases in suicidal thoughts, indicating a potential for quick intervention.

The reduction in suicidal ideation after placebo aiTBS was linked to significant decreases in brain perfusion in the frontopolar prefrontal cortex, suggesting that even placebo treatments can influence brain activity related to cognitive processes and suicidal thoughts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo aiTBS attenuates suicidal ideation and frontopolar cortical perfusion in major depression. Baeken, C., Wu, GR., van Heeringen, K.[2020]

In a clinical trial involving patients with treatment-resistant depression, both 10 Hz repetitive transcranial magnetic stimulation (rTMS) and intermittent theta-burst stimulation (iTBS) effectively reduced suicidality, with remission rates of 43.7% and 49.1% respectively, showing no significant difference between the two methods.

There was a strong correlation between reductions in suicidality and overall depression severity, indicating that improvements in suicidal thoughts were linked to greater decreases in depressive symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of high frequency versus theta-burst repetitive transcranial magnetic stimulation on suicidality in patients with treatment-resistant depression. Mehta, S., Downar, J., Mulsant, BH., et al.[2023]

In a study involving 81 participants with major depressive disorder, accelerated intermittent theta burst stimulation (iTBS) significantly reduced suicidality and depressive symptoms over a 6-week period, indicating its potential as an effective treatment.

The intervention was found to be safe, with no serious adverse events reported, and showed particularly pronounced anti-suicidal effects in individuals with higher risk profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suicidality and relief of depressive symptoms with intermittent theta burst stimulation in a sham-controlled randomized clinical trial. Wilkening, J., Witteler, F., Goya-Maldonado, R.[2023]

Accelerated intermittent Theta Burst Stimulation (iTBS) was found to be safe and well tolerated in a study of 50 treatment-resistant depressed patients, with no worsening of suicidal ideation observed during the treatment.

The study showed a significant decrease in suicide risk, as measured by the Beck Scale of Suicide Ideation, lasting up to one month after treatment, regardless of whether patients received active or sham stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated Intermittent Theta Burst Stimulation for Suicide Risk in Therapy-Resistant Depressed Patients: A Randomized, Sham-Controlled Trial. Desmyter, S., Duprat, R., Baeken, C., et al.[2020]

Intermittent theta burst stimulation (iTBS) applied to the left dorsolateral prefrontal cortex significantly reduced suicidal ideation and depressive symptoms in adolescents with major depressive disorder over a 2-week treatment period involving 10 sessions.

The study involved 45 participants, and those with higher initial depression and suicidal ideation scores experienced greater improvements, suggesting that iTBS is particularly effective for more severely affected individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of intermittent theta burst stimulation on suicidal ideation and depressive symptoms in adolescent depression with suicide attempt: A randomized sham-controlled study. Zhao, Y., He, Z., Luo, W., et al.[2023]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11043680/

Effect of novel accelerated intermittent theta burst ... These results indicate that 20 Hz aiTBS has promising antisuicidal and antidepressant efficacy in adolescents. A recent study examining 50 Hz ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0165178123003797

Accelerated intermittent theta burst stimulation in major ... aiTBS is a promising form of non-invasive brain stimulation [NIBS] with rapid antidepressant and antisuicidal effects in major depressive disorder [MDD].

3. 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 ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37053246/

Sequential bilateral accelerated theta burst stimulation in ... This is a randomized, double-blind, sham-controlled trial of sequential bilateral aTBS in adolescents with major depressive disorder (MDD) and suicidal ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04701840

Sequential Bilateral Accelerated Theta Burst Stimulation in ... The investigators hope to learn if this TMS treatment improves suicidal ideation over 10 days and clinical outcomes over 1 year of follow-up. Detailed ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006322325013563

Efficacy and Safety of Accelerated Intermittent Theta-burst ... Major depressive disorder (MDD) first onset during adolescence often signals a lifelong risk of recurrence and functional impairment, ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27729854/

Accelerated Intermittent Theta Burst Stimulation for Suicide ... We aimed to examine the effects and safety of accelerated intermittent Theta Burst Stimulation (iTBS) on suicide risk in a group of treatment-resistant ...