Transcranial Magnetic Stimulation for Adolescent Suicidal Thoughts

Overseen By Charles P Lewis, MD

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Minnesota

Must not be taking: Antiepileptics, Benzodiazepines

Disqualifiers: Substance use disorder, Psychosis, Autism, 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: 3

80 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this study is to understand why some people act more impulsively when feeling negative emotions, which is called negative urgency. The researchers hope to understand how negative urgency relates to the way networks of brain cells communicate with one another. The researchers will measure negative urgency and brain signals in adolescents aged 13-21 years with depression and suicidal thoughts and behaviors. The main questions it aims to answer are: * Whether a type of brain signaling called cortical inhibition is related to negative urgency * Whether depressed adolescents with suicidal behavior have more problems with cortical inhibition than depressed adolescents with suicidal thoughts only * Whether the relationship between negative urgency and cortical inhibition changes over time Adolescents who participate in the study will complete the following activities at the time they join the study, as well as 6 months and 12 months later: * Interviews with researchers and questionnaires to learn about their thoughts, emotions, and symptoms * A questionnaire about impulsive behaviors and negative urgency * Computerized games that measure brain functions * An MRI scan of the brain * Transcranial magnetic stimulation with electroencephalography (TMS-EEG), a way to measure how brain cells communicate (cortical inhibition) using a magnet placed outside of the head and recording brain signals

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those using antiepileptic medications or chronic benzodiazepines. If you use benzodiazepines as needed, you can participate if you don't take them on the day of the TMS-EEG test.

What data supports the effectiveness of this treatment for adolescent suicidal thoughts?

Research suggests that transcranial magnetic stimulation (TMS) shows promise in reducing suicidal thoughts, particularly in individuals with depression. Some studies indicate that TMS can decrease suicidal ideation, although more specific research is needed to fully understand its impact on suicidality. ^{1 2 3 4 5}

Is transcranial magnetic stimulation (TMS) safe for humans?

Research on transcranial magnetic stimulation (TMS) shows it is generally safe for humans, with studies indicating it can reduce depression and potentially help with suicidal thoughts. However, more research is needed to fully understand its effects specifically on suicidality. ^{1 2 3 5 6}

How is transcranial magnetic stimulation (TMS) different from other treatments for adolescent suicidal thoughts?

Transcranial magnetic stimulation (TMS) is unique because it is a noninvasive treatment that uses magnetic fields to stimulate specific areas of the brain, potentially addressing underlying brain deficits linked to suicidal thoughts. Unlike traditional therapies, TMS can be administered in accelerated sessions, which may offer faster and more efficient relief. ^{1 2 3 7 8}

Research Team

Kathryn Cullen, MD

Principal Investigator

University of Minnesota

Eligibility Criteria

This trial is for adolescents aged 13-18 with depression and suicidal thoughts or behaviors. They must be able to communicate in English, provide consent (or have a guardian do so if under 18), and not have a history of suicide attempts if only experiencing suicidal thoughts.

Inclusion Criteria

I have been diagnosed with depression.

I am under 18 and can sign an agreement, and my guardian can consent too.

My sex, gender, race, or ethnicity does not limit my participation.

Exclusion Criteria

Pregnancy or suspected pregnancy in participants capable of becoming pregnant (assessed with urine pregnancy test)

Current substance use meeting diagnostic criteria for a substance use disorder within the last month on the MINI or MINI-KID diagnostic interview (with the exceptions of caffeine and nicotine)

Historical diagnosis of autism spectrum disorder or intellectual disability

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo initial assessments including clinical interviews, questionnaires, computerized games, MRI, and TMS-EEG

1-2 weeks

1 visit (in-person)

6-Month Follow-up

Participants complete follow-up assessments including clinical interviews, questionnaires, and TMS-EEG

1-2 weeks

1 visit (in-person)

12-Month Follow-up

Participants complete final follow-up assessments including clinical interviews, questionnaires, and TMS-EEG

1-2 weeks

1 visit (in-person)

Treatment Details

Interventions

• Single-/paired-pulse transcranial magnetic stimulation

Trial Overview The study tests how brain cell networks communicate during negative urgency using transcranial magnetic stimulation with EEG. It examines whether cortical inhibition relates to impulsivity in depressed teens, comparing those with suicidal behavior to those with thoughts only over time.

Participant Groups

Group I: Longitudinal Assessments Experimental Treatment 1 Intervention

Participants in both groups (Dep/SI and Dep/SB) will undergo identical assessments at baseline, 6 months, and 12 months. Assessments will include clinical interviews and rating scales, questionnaires (including a self-report scale of negative urgency), and single-/paired-pulse transcranial magnetic stimulation (sp/ppTMS) measurement of cortical inhibition.

Single-/paired-pulse transcranial magnetic stimulation is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Transcranial Magnetic Stimulation for:

• Major depressive disorder
• Obsessive-compulsive disorder
• Migraines

Approved in European Union as Transcranial Magnetic Stimulation for:

• Major depressive disorder
• Obsessive-compulsive disorder

Approved in Canada as Transcranial Magnetic Stimulation for:

• Major depressive disorder
• Obsessive-compulsive disorder

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Findings from Research

A systematic review of 11 clinical trials involving 593 participants suggests that while repetitive Transcranial Magnetic Stimulation (TMS) effectively reduces depression, its specific impact on suicidal ideation remains uncertain.

A retrospective analysis of 43 veterans receiving TMS treatment showed significant decreases in suicidal thoughts, indicating that improvements in suicidality may occur independently of changes in depressive symptoms, highlighting the need for more targeted research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation to reduce suicidality - A review and naturalistic outcomes. Bozzay, ML., Primack, J., Barredo, J., et al.[2022]

In a study involving 120 active-duty military participants experiencing suicidal crisis, accelerated transcranial magnetic stimulation (TMS) showed a significant reduction in suicidal ideation compared to sham treatment, with a notable decline in scores measured by the Beck Scale for Suicidal Ideation (SSI-C).

Both active and sham TMS treatments led to rapid decreases in suicidal thoughts, but the active TMS group maintained significantly lower SSI-C scores for six months, indicating a lasting antisuicidal effect and a shift to much lower suicide risk levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation Promotes Rapid Psychiatric Stabilization in Acutely Suicidal Military Service Members. Hines, CE., Mooney, S., Watson, NL., et al.[2023]

Repetitive transcranial magnetic stimulation (rTMS) shows promise in reducing suicidal ideation (SI) in patients with treatment-resistant depression, particularly in uncontrolled trials where a significant decrease in SI scores was observed (effect size g = 0.692).

In randomized controlled trials, while a decrease in SI scores was noted (g = 0.158), the effect was not statistically significant, indicating that more research is needed to fully understand the efficacy of rTMS for this purpose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Repetitive Transcranial Magnetic Stimulation on Suicidal Ideation in Treatment-Resistant Depression: A Meta-Analysis. Mehta, S., Konstantinou, G., Weissman, CR., et al.[2022]

In a study involving 19 adolescents with treatment-resistant depression, high-frequency repetitive TMS treatment significantly reduced suicidal ideation over 6 weeks, as measured by standardized scales.

However, when accounting for the severity of depression, the reduction in suicidal thoughts became non-significant, suggesting that improvements in suicidal ideation may be closely linked to overall depression symptom relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-frequency repetitive TMS for suicidal ideation in adolescents with depression. Croarkin, PE., Nakonezny, PA., Deng, ZD., et al.[2020]

In a study of 25 participants with PTSD and depression, 65% experienced a decrease in suicidal thoughts after 8 weeks of repetitive transcranial magnetic stimulation (TMS) targeting the left dorsolateral prefrontal cortex.

The reduction in suicidality was significantly correlated with changes in functional connectivity between the dorsal striatum and frontopolar cortex, suggesting that TMS may effectively alter brain connectivity related to suicidal ideation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multimodal Elements of Suicidality Reduction After Transcranial Magnetic Stimulation. Barredo, J., Berlow, Y., Swearingen, HR., et al.[2022]

A high dose of left prefrontal repetitive transcranial magnetic stimulation (rTMS) delivered over three days to suicidal inpatients was found to be feasible and safe, with minimal side effects and no increase in suicidal thoughts during the treatment.

The study indicated a trend towards rapid improvement in suicidal thinking, particularly on the first day of treatment, suggesting that rTMS may have a quick anti-suicidal effect, although further research with larger samples is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A two-site pilot randomized 3 day trial of high dose left prefrontal repetitive transcranial magnetic stimulation (rTMS) for suicidal inpatients. George, MS., Raman, R., Benedek, DM., et al.[2022]

This study aims to evaluate the effectiveness of combining repetitive transcranial magnetic stimulation (TMS) with brief cognitive behavioral therapy (BCBT) in reducing suicidal ideation and attempts among 130 veterans with recent suicidal behavior, marking the first clinical trial of its kind.

The research will assess treatment outcomes over a 12-week BCBT protocol with 30 sessions of TMS, potentially leading to improved interventions for veterans at risk of suicide if successful.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined transcranial magnetic stimulation and brief cognitive behavioral therapy for suicide: study protocol for a randomized controlled trial in veterans. Bozzay, ML., Primack, JM., Swearingen, HR., et al.[2022]

This study is the first randomized controlled trial investigating the efficacy of accelerated theta burst stimulation (aTBS) in treating suicidal ideation in adolescents with major depressive disorder (MDD), involving three daily sessions over 10 days.

The trial aims to address underlying neurotransmission deficits in the dorsolateral prefrontal cortex (DLPFC) and will measure biomarkers to understand the neurophysiological mechanisms of suicidal ideation, potentially leading to more effective treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential bilateral accelerated theta burst stimulation in adolescents with suicidal ideation associated with major depressive disorder: Protocol for a randomized controlled trial. Yuruk, D., Ozger, C., Garzon, JF., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation to reduce suicidality - A review and naturalistic outcomes. [2022]

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

Repetitive Transcranial Magnetic Stimulation Promotes Rapid Psychiatric Stabilization in Acutely Suicidal Military Service Members. [2023]

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

The Effect of Repetitive Transcranial Magnetic Stimulation on Suicidal Ideation in Treatment-Resistant Depression: A Meta-Analysis. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

High-frequency repetitive TMS for suicidal ideation in adolescents with depression. [2020]

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

Multimodal Elements of Suicidality Reduction After Transcranial Magnetic Stimulation. [2022]

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

A two-site pilot randomized 3 day trial of high dose left prefrontal repetitive transcranial magnetic stimulation (rTMS) for suicidal inpatients. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Combined transcranial magnetic stimulation and brief cognitive behavioral therapy for suicide: study protocol for a randomized controlled trial in veterans. [2022]

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

Sequential bilateral accelerated theta burst stimulation in adolescents with suicidal ideation associated with major depressive disorder: Protocol for a randomized controlled trial. [2023]