rTMS for Suicidal Ideation in Opioid Users

Overseen By Taylor Ly

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Baylor College of Medicine

Disqualifiers: Unstable medical condition, Pregnant, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 1 week

80 Participants Needed

Trial Summary

What is the purpose of this trial?

Suicide is the 10th leading cause of death for Americans of all ages and more people in the United States now die from suicide than die from car accidents. Although death by firearm remains the most common cause of suicide in the United States, an intentional overdose of substance usage such as prescription opioids accounts for over 5,000 suicides per year. In 2017, more than 70,000 drug overdose deaths occurred, making it the leading cause of injury-related death, and well over half (67.8%) involved opioids. The dramatic increase in opioid overdose raises concerns about their contribution to suicidal outcomes (e.g., suicidal behavior, ideation, and attempts). Abuse of prescription opioids is characterized by the persistence of opioid use despite negative consequences. The neurobiology of opioid abuse involves the mesolimbic dopamine systems as the main neural substrate for opioid reward, and altered dopamine release in this system plays a role in opioid abuse. Moreover, the cortico-striatal system, especially the orbitofrontal cortex (OFC), has been associated with the abuse of many substances, including opioids and alcohol. Structural brain alterations in frontal areas, particularly the OFC, may cause executive control dysfunctions of mood which are highly associated with suicidal ideation. Recent preclinical work has shown that higher input from the OFC to the dorsal striatum (dSTR) is associated with compulsive reward-seeking behavior despite negative effects (e.g., punishment). In this study, the investigators propose that OFC/dSTR connectivity may be one neural differentiator that distinguishes between those who become compulsive users after initial opioid use and those that do not. Moreover, suicidal patients among those who become compulsive users may have higher OFC/dSTR connectivity compared to non-suicidal patients.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the research team for guidance.

What data supports the effectiveness of the treatment Repetitive Transcranial Magnetic Stimulation (rTMS) for suicidal ideation in opioid users?

Research shows that rTMS can reduce cravings and improve depressive symptoms in individuals with opioid use disorder, suggesting it may help with related issues like suicidal thoughts. While direct evidence for suicidal ideation is limited, rTMS has shown promise in treating other conditions by modulating brain activity. ^{1 2 3 4 5}

Is rTMS safe for humans?

Research shows that repetitive transcranial magnetic stimulation (rTMS) is generally safe for humans. Studies involving patients with depression, including those with suicidal thoughts, indicate that rTMS is well-tolerated and does not increase the risk of suicide during treatment. ^{6 7 8 9 10}

How is rTMS treatment different for suicidal ideation in opioid users?

Repetitive Transcranial Magnetic Stimulation (rTMS) is unique because it is a non-invasive treatment that uses magnetic fields to stimulate specific areas of the brain, such as the dorsolateral prefrontal cortex, which may help improve depressive symptoms and impulse control in opioid users. Unlike traditional drug treatments, rTMS does not involve medication and is still considered experimental for addiction, but it shows promise in reducing cravings and improving cognitive functions. ^{1 2 4 11 12}

Eligibility Criteria

This trial is for adults aged 18-60 with active suicidal thoughts, enrolled in The Menninger Clinic, experiencing depression, and have used opioids. They must understand the study and consent to participate. Women can't be pregnant or nursing. Participants cannot have metal implants that interfere with MRI or TMS procedures.

Inclusion Criteria

You have previously participated in a trial called H-22611.

You understand the consent form, can provide your consent in writing, and agree to complete all study procedures.

You are eligible for TMS treatment, as long as you do not have any metal in your head or within 12 inches of the TMS coil.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 5 sessions of either active or sham rTMS targeting the OFC

1 week

5 visits (in-person)

Follow-up

Participants are monitored for changes in functional connectivity and psychiatric symptoms

4 weeks

Treatment Details

Interventions

• Repetitive Transcranial Magnetic Stimulation (rTMS)
• sham rTMS

Trial Overview The study tests if Repetitive Transcranial Magnetic Stimulation (rTMS), a non-invasive brain stimulation technique, affects brain connectivity related to compulsive behavior and mood control in opioid users with suicidal tendencies compared to sham (fake) treatment.

Participant Groups

Group I: Active rTMS Experimental Treatment 1 Intervention

5 sessions of active rTMS

Group II: Sham rTMS Placebo Group 1 Intervention

5 sessions of sham rTMS

Repetitive Transcranial Magnetic Stimulation (rTMS) is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as rTMS for:

• Depression
• Smoking cessation

Approved in European Union as rTMS for:

• Depression

Approved in Canada as rTMS for:

• Depression

Approved in Japan as rTMS for:

• Depression

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

American Foundation for Suicide Prevention

Collaborator

Trials

36

Recruited

10,500+

Findings from Research

In a study of 30 heroin-dependent individuals receiving 10 sessions of rTMS over one week, treatment significantly reduced cravings and withdrawal symptoms, indicating its efficacy in managing addiction.

The study found that rTMS altered the coupling between brain regions in the default mode network, particularly the left inferior parietal lobe, which correlated with reduced cravings, suggesting a potential mechanism for its anti-craving effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Default mode network mechanisms of repeated transcranial magnetic stimulation in heroin addiction. Jin, L., Yuan, M., Zhang, W., et al.[2023]

In a pilot trial involving 22 participants with opioid use disorder undergoing methadone maintenance therapy, repetitive transcranial magnetic stimulation (rTMS) did not significantly reduce cravings or heroin use compared to a sham treatment.

However, rTMS was associated with significant improvements in depressive symptoms, impulse control, and attention, suggesting potential benefits for mental health aspects in individuals with opioid use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Add-on repetitive transcranial magnetic stimulation in patients with opioid use disorder undergoing methadone maintenance therapy. Tsai, TY., Wang, TY., Liu, YC., et al.[2021]

In a study of 35 heroin-dependent individuals, active rTMS targeting the left dorsolateral prefrontal cortex significantly reduced both spontaneous and cue-induced cravings for heroin after just one week of treatment.

The improvement in cravings was associated with enhanced coupling between the left DLPFC and the left parahippocampal gyrus, suggesting that rTMS may help restore normal brain network interactions involved in addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation modulates coupling among large-scale brain networks in heroin-dependent individuals: A randomized resting-state functional magnetic resonance imaging study. Jin, L., Yuan, M., Zhang, W., et al.[2022]

Transcranial magnetic stimulation (TMS) has been explored in 19 studies involving 316 adults for its potential to reduce drug cravings and use, particularly targeting the dorsolateral prefrontal cortex with high-frequency pulses.

While some studies showed promising results, such as decreased smoking and cocaine use, the treatment is still experimental, and the exact mechanisms and optimal parameters for rTMS in addiction treatment remain unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation in the treatment of substance addiction. Gorelick, DA., Zangen, A., George, MS.[2022]

Repetitive transcranial magnetic stimulation (rTMS) shows promise as a noninvasive treatment for substance use disorders (SUDs) like cocaine and opioid use disorders by inducing neuroplastic changes in the brain, which can help reduce cravings and drug use.

The field faces several 'known unknowns' that need to be addressed to optimize rTMS for SUDs, including selecting the right cortical targets, understanding subcortical circuit engagement, and determining the best treatment sequences, highlighting the need for collaborative research efforts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating cocaine and opioid use disorder with transcranial magnetic stimulation: A path forward. Steele, VR., Maxwell, AM.[2023]

An intensive rTMS protocol consisting of 25 sessions significantly improved depression symptoms in treatment-resistant patients, achieving a response rate of 64.52% and a remission rate of 51.61% by day 5.

The treatment was well tolerated and showed a remarkable 100% response rate for suicidal ideation, with an 87.09% remission rate at day 5, indicating its potential as a rapid and effective intervention for both military veterans and non-military patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensive rTMS for treatment-resistant depression patients with suicidal ideation: An open-label study. Wang, Q., Huang, H., Li, D., et al.[2022]

In a study of 55 individuals with treatment-resistant depression, low-frequency rTMS applied to the right dorsolateral prefrontal cortex showed potential to improve self-referential processing, leading to a more positive self-view after treatment.

Baseline measures of anticipatory reward sensitivity and negative self-referential processing were linked to higher depressive symptoms and suicidality, suggesting these factors could help predict treatment outcomes with rTMS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive-affective processes and suicidality in response to repetitive transcranial magnetic stimulation for treatment resistant depression. Terpstra, AR., Vila-Rodriguez, F., LeMoult, J., et al.[2023]

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 of 711 patients with depressive disorders treated with repetitive transcranial magnetic stimulation (rTMS), only one patient (0.1%) committed suicide during treatment, suggesting that rTMS does not increase suicide risk.

The analysis of 332 patients showed a significant reduction in suicidal ideation, with 47% experiencing improvement, indicating that rTMS may effectively reduce suicidal thoughts in patients with depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-Suicidal Efficacy of Repetitive Transcranial Magnetic Stimulation in Depressive Patients: A Retrospective Analysis of a Large Sample. Abdelnaim, MA., Langguth, B., Deppe, M., et al.[2020]

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]

Repetitive transcranial magnetic stimulation (rTMS) has shown effectiveness in reducing cravings for tobacco, alcohol, and cocaine when applied at high frequencies to the dorsolateral prefrontal cortex (DLPFC), based on a review of eight studies.

Repeated sessions of high-frequency rTMS over the DLPFC may be particularly beneficial for decreasing smoking and alcohol consumption, suggesting that rTMS could be a promising treatment option for drug addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation and drug addiction. Barr, MS., Farzan, F., Wing, VC., et al.[2019]

In a pilot study involving 18 participants with cocaine use disorder, high-frequency rTMS (10 Hz) significantly reduced cocaine-seeking behavior compared to baseline, indicating its potential as a treatment option.

No significant effects were observed in the low-frequency (1 Hz) or sham groups, suggesting that the efficacy of rTMS may depend on the frequency of stimulation applied to the prefrontal cortex.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Magnetic Stimulation of Medial Prefrontal and Cingulate Cortices Reduces Cocaine Self-Administration: A Pilot Study. Martinez, D., Urban, N., Grassetti, A., et al.[2022]

References

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

Default mode network mechanisms of repeated transcranial magnetic stimulation in heroin addiction. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Add-on repetitive transcranial magnetic stimulation in patients with opioid use disorder undergoing methadone maintenance therapy. [2021]

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

Repetitive transcranial magnetic stimulation modulates coupling among large-scale brain networks in heroin-dependent individuals: A randomized resting-state functional magnetic resonance imaging study. [2022]

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

Transcranial magnetic stimulation in the treatment of substance addiction. [2022]

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

Treating cocaine and opioid use disorder with transcranial magnetic stimulation: A path forward. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Intensive rTMS for treatment-resistant depression patients with suicidal ideation: An open-label study. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Cognitive-affective processes and suicidality in response to repetitive transcranial magnetic stimulation for treatment resistant depression. [2023]

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

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

9. Switzerland pubmed.ncbi.nlm.nih.gov

Anti-Suicidal Efficacy of Repetitive Transcranial Magnetic Stimulation in Depressive Patients: A Retrospective Analysis of a Large Sample. [2020]

10. 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]

11. England pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation and drug addiction. [2019]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Transcranial Magnetic Stimulation of Medial Prefrontal and Cingulate Cortices Reduces Cocaine Self-Administration: A Pilot Study. [2022]