Accelerated Theta Burst Stimulation for Suicidal Thoughts

(COMBAT-SI Trial)

Overseen By Interventional Psychiatry

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Diego

Must not be taking: Anticonvulsants, High-dose lorazepam

Disqualifiers: Substance use disorder, Bipolar, Schizophrenia, 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: 11

Duration: 1 week

76 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new brain stimulation treatment to help people with hard-to-treat depression who have suicidal thoughts. The treatment uses magnetic pulses to stimulate specific brain areas several times. Researchers hope this will improve brain communication and reduce suicidal thoughts. This type of brain stimulation has been studied before and has shown positive effects.

Will I have to stop taking my current medications?

The trial requires that participants do not take more than 2 mg of lorazepam daily or any dose of an anticonvulsant, as these can affect the treatment's effectiveness. If you are taking these medications, you may need to adjust your dosage or stop taking them.

What data supports the effectiveness of the treatment Accelerated Theta Burst Stimulation for reducing suicidal thoughts?

Research suggests that accelerated intermittent theta burst stimulation (iTBS) can significantly decrease suicidal thoughts in people with major depressive disorder, even in those who do not respond to depression treatments. This effect was observed to last up to a month, indicating potential benefits for reducing suicide risk. ^{1 2 3 4 5}

How is Accelerated Theta Burst Stimulation (aTBS) different from other treatments for suicidal thoughts?

Accelerated Theta Burst Stimulation (aTBS) is a unique treatment that uses rapid, repetitive magnetic pulses to stimulate specific areas of the brain, which can quickly reduce suicidal thoughts in people with depression. Unlike traditional treatments, aTBS is non-invasive and can show effects within a few days, making it a promising option for those who need immediate relief. ^{2 3 4 5 6}

Eligibility Criteria

This trial is for adults aged 18-70 with major depression and ongoing suicidal thoughts, who haven't responded to at least two antidepressants. Participants must pass safety screenings for transcranial magnetic stimulation (TMS) and MRI, be outpatient-capable, and not have severe medical or neurological conditions. Pregnant women or those unable to use birth control are excluded.

Inclusion Criteria

Able to adhere to the treatment schedule

Ongoing suicidal ideation (SI) confirmed with Beck SSI score ≥4

Pass the TMS adult safety screening (TASS) questionnaire and the MRI safety screening questionnaire

Exclusion Criteria

Diagnosis of any personality disorder assessed by a study investigator to be primary and causing greater impairment than MDD

I have been diagnosed with OCD, PTSD, anxiety, or dysthymia that affects me more than my depression.

Suicidal ideation prompting emergent involuntary hospital stay (recent suicide attempt will not be exclusionary if participant can maintain voluntary and capable outpatient status)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive bilateral or unilateral accelerated theta-burst stimulation for 5 consecutive days, with a total of 10 hours a day.

1 week

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits at 1, 2, 3, and 4 weeks post-treatment, as well as 3 and 6 months after treatment completion.

6 months

6 visits (in-person)

Treatment Details

Interventions

• Accelerated Theta Burst Stimulation

Trial Overview The study tests the effectiveness of accelerated Theta Burst Stimulation (aTBS), a type of TMS therapy on suicidal ideation in people with treatment-resistant depression. It compares bilateral aTBS over the DLPFC region of the brain versus aiTBS over just the left side.

Participant Groups

Group I: Bilateral aTBS Experimental Treatment 1 Intervention

Patients will receive Bilateral accelerated theta-burst stimulation bilaterally for 5 consecutive days, with a total of 10 hours a day. treatment will be 10min with 50min of breaks in between the 10 sessions.

Group II: Unilateral aiTBS Active Control 1 Intervention

Patients will receive unilateral accelerated theta-burst stimulation to the left side for 5 consecutive days, with a total of 10 hours a day. treatment will be 10min with 50min of breaks in between the 10 sessions. There will be a right DLPFC sham component to this treatment arm for all treatment sessions.

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?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Brain & Behavior Research Foundation

Collaborator

Trials

63

Recruited

2,900+

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]

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]

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]

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

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

3. 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]

4. Croatia pubmed.ncbi.nlm.nih.gov

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

5. 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]

6. 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]