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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new brain stimulation technique called accelerated theta burst stimulation (aTBS) to determine its effectiveness in reducing suicidal thoughts in individuals with treatment-resistant depression (TRD). Researchers compare two methods: one targets both sides of the brain, while the other focuses on the left side. They also investigate how this stimulation affects the brain on a physical level. Individuals who have experienced ongoing suicidal thoughts and have not found relief from at least two different antidepressants might be suitable candidates for this trial. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to new treatment options for those with TRD.

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 prior data suggests that this treatment is safe for humans?

Research has shown that theta burst stimulation, a type of brain treatment, is safe. In previous studies, treatments like bilateral accelerated theta burst stimulation (aTBS) and unilateral accelerated intermittent theta burst stimulation (aiTBS) were tested on people with depression and suicidal thoughts.

One study found that bilateral aTBS helped more patients improve their symptoms. Another study showed that this treatment was more effective at reducing suicidal thoughts and anxiety compared to some other methods. These studies suggest that bilateral aTBS is generally well-tolerated, meaning most people can undergo it without major issues.

For unilateral aiTBS, studies have shown similar positive outcomes. Side effects are usually mild and may include headaches or scalp discomfort. These findings suggest that both treatments are relatively safe options for people dealing with depression and suicidal thoughts. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about accelerated theta burst stimulation (aTBS) for suicidal thoughts because it offers a unique and potentially rapid approach compared to traditional treatments like medication or cognitive therapy. Unlike most treatments that may take weeks to show effects, aTBS can potentially provide quicker results, with daily sessions over just five days. This method involves delivering short bursts of magnetic pulses to the brain, which could offer a novel way to target brain activity related to suicidal thoughts and mood regulation. The trial is exploring two approaches: unilateral aiTBS, which focuses on the left side of the brain with a placebo component on the right, and bilateral aTBS, which stimulates both sides of the brain. These variations could help identify the most effective strategy for using aTBS to address this urgent mental health challenge.

What evidence suggests that this trial's treatments could be effective for suicidal thoughts?

Research has shown that bilateral accelerated theta burst stimulation (aTBS), a treatment available in this trial, may help reduce suicidal thoughts. Studies have found that aTBS, particularly when applied to the right side of the brain, can significantly lower suicidal thoughts and anxiety. For individuals with major depressive disorder (MDD) who experience suicidal thoughts, aTBS proved effective in several controlled studies. These findings suggest that aTBS could offer relief from these intense feelings. Another treatment arm in this trial involves unilateral accelerated theta-burst stimulation (aiTBS) to the left side, which includes a right DLPFC sham component. ^{2 4 5 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. 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 ...

2. brainstimjrnl.com brainstimjrnl.com/article/S1935-861X(25)00294-3/fulltext

Accelerated bilateral theta burst stimulation for suicidal ... The study revealed that right DLPFC-targeted accelerated cTBS significantly outperformed left DLPFC-targeted iTBS in reducing SI and anxiety symptoms within the ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05377177

Study Details | NCT05377177 | Cortical Inhibition as a ... This is a prospective clinical trial to confirm the effectiveness of bilateral accelerated theta burst stimulation (aTBS) on suicidal ideation (SI).

4. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0280010

Sequential bilateral accelerated theta burst stimulation in ... This is the first known randomized controlled trial to examine the efficacy of sequential bilateral aTBS for treating suicidal ideation in adolescents with MDD.

5. sciencedirect.com sciencedirect.com/science/article/pii/S3050529125000832

Feasibility and clinical effects of accelerated sequential ... We hypothesized that a course of accelerated bilateral TBS would reduce depressive symptoms, and these improvements would be sustained in the 4 week followup ...

6. 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 ...

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

Effect of novel accelerated intermittent theta burst ... Comparisons of accelerated continuous and intermittent theta burst stimulation for treatment-resistant depression and suicidal Ideation.