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

100 Participants Needed

Trial Summary

What is the purpose of this trial?

This study evaluates the effects of an accelerated schedule of theta-burst stimulation, termed accelerated intermittent theta-burst stimulation (aiTBS), on the neural networks underlying explicit and implicit suicidal cognition in inpatients with major depressive disorder.

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 data supports the effectiveness of the treatment Accelerated Theta Burst Stimulation for depression and suicide ideation?

Research suggests that accelerated intermittent theta burst stimulation (iTBS) can reduce suicidal thoughts and depressive symptoms in people with major depressive disorder. Studies have shown that iTBS can lead to a quick decrease in suicidal ideation, although some effects might be influenced by placebo responses. ^{1 2 3 4 5}

Is rapid acting TMS safe for humans?

Research shows that accelerated intermittent Theta Burst Stimulation (iTBS), a form of rapid acting TMS, is generally safe and well tolerated in humans, including those with depression and suicidal ideation. Studies have not reported any worsening of symptoms, and side effects are minimal, even with increased stimulation parameters. ^{2 6 7 8 9}

How is the treatment Accelerated Theta Burst Stimulation (aTBS) different from other treatments for depression and suicide ideation?

Accelerated Theta Burst Stimulation (aTBS) is a unique treatment because it uses rapid, repetitive magnetic pulses to stimulate specific areas of the brain, which may quickly reduce symptoms of depression and suicidal thoughts. Unlike traditional treatments, aTBS can be administered more frequently and in shorter sessions, potentially offering faster relief. ^{1 2 3 4 7}

Research Team

David Spiegel, MD

Principal Investigator

Stanford University

Eligibility Criteria

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

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

I can get rTMS treatment after leaving the hospital.

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

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]

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]

References

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

Effect of high frequency versus theta-burst repetitive transcranial magnetic stimulation on suicidality in patients with treatment-resistant depression. [2023]

2. Croatia pubmed.ncbi.nlm.nih.gov

The acute effects of accelerated repetitive Transcranial Magnetic Stimulation on suicide risk in unipolar depression: preliminary results. [2022]

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

Suicidality and relief of depressive symptoms with intermittent theta burst stimulation in a sham-controlled randomized clinical trial. [2023]

4. Netherlands 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. [2021]

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

Placebo aiTBS attenuates suicidal ideation and frontopolar cortical perfusion in major depression. [2020]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Accelerated Intermittent Theta Burst Stimulation for Suicide Risk in Therapy-Resistant Depressed Patients: A Randomized, Sham-Controlled Trial. [2020]

7. Ireland pubmed.ncbi.nlm.nih.gov

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

8. England pubmed.ncbi.nlm.nih.gov

Safety, tolerability and preliminary evidence for antidepressant efficacy of theta-burst transcranial magnetic stimulation in patients with major depression. [2019]

9. Netherlands 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. [2023]