rTMS for Suicidal Ideation in Opioid Users
Recruiting in Palo Alto (17 mi)
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Baylor College of Medicine
Disqualifiers: Unstable medical condition, Pregnant, others
No Placebo Group
Approved in 4 jurisdictions
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.
12345Is 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.
678910How 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.
1241112Eligibility 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.
+7 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Active rTMSExperimental Treatment1 Intervention
5 sessions of active rTMS
Group II: Sham rTMSPlacebo Group1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
The Menninger ClinicHouston, TX
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Who Is Running the Clinical Trial?
Baylor College of MedicineLead Sponsor
National Institute on Drug Abuse (NIDA)Collaborator
American Foundation for Suicide PreventionCollaborator
References
Default mode network mechanisms of repeated transcranial magnetic stimulation in heroin addiction. [2023]Repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) has been shown to reduce cravings in heroin-dependent (HD) individuals, but the mechanisms underlying the anti-craving effects of rTMS are unknown. Abnormalities in the default mode network (DMN) are known to be consistent findings in HD individuals and are involved in cravings. We assessed the effect of rTMS on DMN activity and its relationship to the treatment response. Thirty HD individuals were included in this self-controlled study, and all HD participants received 10-Hz rTMS 7-session during a week. Data for cravings and withdrawal symptoms and resting-state functional magnetic resonance imaging data were collected before and after rTMS treatment. Thirty demographically matched healthy individuals who did not receive rTMS were included as controls. We focused on changes in coupling seeded from the medial prefrontal cortex (MPFC), posterior cingulate cortex (PCC), and bilateral inferior parietal lobe (IPL), which are the core regions of the DMN. The craving and withdrawal symptom score of HD individuals decreased significantly after rTMS treatment. The left IPL-left middle frontal gyrus coupling and the left IPL-right inferior occipital gyrus coupling decreased significantly, and the changes in the left IPL-left middle frontal gyrus coupling were positively correlated with changes in drug-cue induced cravings. rTMS could modulate the coupling between the DMN and executive control network (ECN). Alterations of the left IPL-left middle frontal gyrus coupling may play an important mechanistic role in reducing drug cue-induced cravings.
Add-on repetitive transcranial magnetic stimulation in patients with opioid use disorder undergoing methadone maintenance therapy. [2021]Background: Repetitive transcranial magnetic stimulation (rTMS) shows potential therapeutic effects for individuals with addiction, but few studies have examined individuals with opioid use disorder (OUD).Objectives: We conducted an add-on double-blinded, sham-controlled rTMS feasibility pilot trial to examine OUD participants undergoing methadone maintenance therapy (MMT). The current report focused on the effects of rTMS on (1) craving and heroin use behavior and (2) depression, impulsivity, and attention.Methods: Active or sham rTMS treatment was applied to the left dorsolateral prefrontal cortex (DLPFC) over a total of 11 sessions in 4 weeks (15-Hz frequency, 4 seconds per train, intertrain interval of 26 seconds, 40 trains per session) in OUD participants (ClinicalTrials.gov registration number: NCT03229642). Craving, heroin use severity, urine morphine tests, the Hamilton Depression Rating Scale (HDRS), the Barratt Impulsiveness Scale-11 (BIS-11), and the Continuous Performance Tests (CPTs) were measured.Results: Twenty-two OUD participants were enrolled, of which eleven (8 males) were undergoing active rTMS and nine (8 males) were in the sham rTMS group. After 12 weeks of follow-up, the active rTMS group did not show significantly greater improvements than the sham group with respect to craving, heroin use, or urine morphine test results. However, HDRS scores, BIS-11 attentional subscales, and CPTs commission T-scores (C-TS) were significantly lower in the active rTMS group (P = .003, 0.04, and 0.02, respectively) than in the sham group.Conclusion: Add-on rTMS did not appear to improve heroin use behavior but may have benefitted depressive symptoms, impulse control and attention in OUD participants undergoing MMT.
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]The abnormal interactions of three key large-scale brain networks (default mode [DMN], salience and executive control [ECN]) were showed underlie dysfunctions in heroin addiction. Repetitive transcranial magnetic stimulation (rTMS) targeting the left dorsolateral prefrontal cortex (DLPFC) is a potential treatment for heroin addiction. It is unclear whether impaired coupling among the large-scale brain networks would be improved by rTMS in treated heroin-dependent individuals. Thirty-five heroin-dependent individuals were included in this sham-controlled, randomized study. The patients received either active or sham rTMS for 1 week. The craving for heroin and resting-state functional magnetic resonance imaging data were collected before and after 1-week rTMS. Twenty-two healthy subjects were included as controls not receiving rTMS. After 1-week rTMS, only the active rTMS group showed a significant decrease in spontaneous and heroin cue-induced craving. The coupling between left DLPFC (a key node of left ECN) and left parahippocampal gyrus (PHG, included in DMN) significantly increased for the active group with a tendency towards that of controls. The coupling between the right precentral gyrus and three key regions included in DMN (posterior cingulate cortex/precuneus and bilateral inferior parietal cortex) significantly decreased for the active group with a tendency towards that of healthy controls. For the active rTMS individuals, the left DLPFC-PHG coupling negatively correlated with the spontaneous craving and the drug cue-induced craving. It suggested that the rTMS could reduce heroin craving, which might be related to the modulation of ECN-DMN coupling. This finding might shed light on the mechanism of rTMS for heroin addiction treatment.
Transcranial magnetic stimulation in the treatment of substance addiction. [2022]Transcranial magnetic stimulation (TMS) is a noninvasive method of brain stimulation used to treat a variety of neuropsychiatric disorders, but is still in the early stages of study as addiction treatment. We identified 19 human studies using repetitive TMS (rTMS) to manipulate drug craving or use, which exposed a total of 316 adults to active rTMS. Nine studies involved tobacco, six alcohol, three cocaine, and one methamphetamine. The majority of studies targeted high-frequency (5-20 Hz; expected to stimulate neuronal activity) rTMS pulses to the dorsolateral prefrontal cortex. Only five studies were controlled clinical trials: two of four nicotine trials found decreased cigarette smoking; the cocaine trial found decreased cocaine use. Many aspects of optimal treatment remain unknown, including rTMS parameters, duration of treatment, relationship to cue-induced craving, and concomitant treatment. The mechanisms of rTMS potential therapeutic action in treating addictions are poorly understood, but may involve increased dopamine and glutamate function in corticomesolimbic brain circuits and modulation of neural activity in brain circuits that mediate cognitive processes relevant to addiction, such as response inhibition, selective attention, and reactivity to drug-associated cues. rTMS treatment of addiction must be considered experimental at this time, but appears to have a promising future.
Treating cocaine and opioid use disorder with transcranial magnetic stimulation: A path forward. [2023]Developing new, effective treatments for substance use disorders (SUDs), especially cocaine and opioid use disorders (CUD and OUD), are of immense importance. These are chronic, relapsing brain diseases characterized by dysregulated circuits manifesting from neuroplastic change brought on by repeated exposure to substances of abuse. A potential treatment is therapeutically inducing neuroplastic change in targeted dysregulated circuits. One such intervention, repetitive transcranial magnetic stimulation (rTMS) has gained traction over the past two decades as a method of noninvasively stimulating cortical structures in order to induce subcortical neuroplastic change. By doing so, rTMS ameliorates symptoms that are consequent of dysregulations in disease-related circuits, such as craving, and reduces drug use. Although rTMS has been successfully applied as a treatment for other clinical disorders, progress toward treatment applications for SUDs has been stymied by what we dub "known unknowns". These are fundamental lines of research within the rTMS-SUD field that have yet to be systematically understood which could help to optimize TMS as an intervention for SUDs. Because progress in treatment for CUD and OUD is imperative given the widespread severity of OUD and the lack of treatment for CUD, it is necessary to critically reflect on the ways in which rTMS research for these disorders can most effectively move forward to help patients. We articulate six "known unknowns" and outline a direction of research to address each. Briefly, the "known unknowns" in the field are: 1) Cortical target selection, 2) subcortical circuit engagement, 3) optimizing rTMS sequences, 4) rTMS as an adjuvant to existing interventions, 5) manipulating brain state, and 6) selecting outcome measures. We also outline research design approaches to address these "known unknowns" in the rTMS-SUDs field. Unification of efforts across research laboratories is necessary to develop empirically validated treatments that will benefit patients in a timely fashion.
Intensive rTMS for treatment-resistant depression patients with suicidal ideation: An open-label study. [2022]The advantages of intensive repetitive transcranial magnetic stimulation (rTMS) protocol are in the possible acute effect of the stimulation and in the possible reduction in the time required to achieve remission in depression. Here, we investigated the antidepressant effects and antisuicidal effects of a more intensive rTMS protocol for treatment-resistant depression (TRD) patients with suicidal ideation. Thirty-one outpatients were included in this study, including 22 military veterans and 9 non- militaries. The rTMS treatment consisted of 25 sessions, each session lasting 30 min (60 trains of 50 pulsations, 110 % resting motor threshold intensity) for a total of 3000 pulse. The total amount of stimulation (750,000 pulses) applied by our rTMS protocol was equivalent to that of a 5-week standard rTMS protocol. We found a significant effect of time on the 17-item Hamilton Depression Rating Scale (HAMD-17) scores and the Sheehan Disability Scale (SDS) scores. There was no difference in change in the HAMD-17 scores and SDS scores between the military veteran group and the non-military group between baseline and the week 4 assessment time point. The response rate of depression was 64.52 %, and the remission rate of depression was 51.61 % at day 5. 48.39 % and 35.48 % at week 4, respectively. All patients (100 %) met response criteria of suicidal ideation, and the remission rate was 87.09 % at day 5. The response rate was 83.87 % %, and the remission rate was 77.42 % at week 4. The accelerated high-dose rTMS treatment was well tolerated by all patients. Our intensive rTMS protocol is preliminarily safe and feasible. The TRD patients with suicidal ideation could benefit from much shorter exposure to this protocol with more efficacy in comparison with conventional rTMS protocol. In addition, intensive rTMS offers a promising treatment for military veteran populations.
Cognitive-affective processes and suicidality in response to repetitive transcranial magnetic stimulation for treatment resistant depression. [2023]Repetitive transcranial magnetic stimulation (rTMS) can elicit 45-55 % response rates and may alleviate suicidality symptoms in treatment resistant depression (TRD). Blunted anticipatory reward sensitivity and negatively biased self-referential processing may predict trajectories of depressive and suicidality symptoms in rTMS for TRD and be modulated during treatment.
Transcranial magnetic stimulation to reduce suicidality - A review and naturalistic outcomes. [2022]Although there is growing interest in the use of repetitive Transcranial Magnetic Stimulation (TMS) as a treatment for suicidality, efficacy data in this area, and knowledge of potential treatment mechanisms, remains limited. The first objective of this study was to systematically review clinical trial data examining the effectiveness of TMS as a treatment for suicidal ideation. Our secondary objective was to investigate the extent to which changes in suicidality are independent of improvements in depression in a clinical sample of veterans who received TMS treatment. In Study 1, we searched the Pubmed and biRxiv databases from inception until July 2019 to identify studies that examined the efficacy of TMS for suicidal thoughts and/or behaviors. Data regarding sample characteristics, treatment parameters, and results were synthesized from six randomized controlled trials and five unblinded trials (total n = 593). Our systematic review indicated that while TMS was consistently associated with reduced depression, its impact on suicidality is unclear. Interpretation of results related to suicidality were complicated by study design elements and modest sample sizes. In Study 2, we conducted a retrospective analysis of 43 patients who received care for depression in a neuromodulation clinic at a Veteran's Affairs hospital. Results found significant decreases in suicidal ideation, and depressive symptom change did not always account for improvements in ideation. Taken together, our literature review and clinic study indicate preliminary promise of TMS for suicide, and underscore the need for more fine-grained, suicide-specific TMS research.
Anti-Suicidal Efficacy of Repetitive Transcranial Magnetic Stimulation in Depressive Patients: A Retrospective Analysis of a Large Sample. [2020]Background: Suicide is a major public health problem. About 90% of suicide victims have one or more major psychiatric disorder, with a reported 20-fold increased risk for suicide in patients with affective disorders in comparison with healthy subjects. Repetitive transcranial magnetic stimulation (rTMS) has been established as an effective alternative or adjunctive treatment option for patients with depressive disorders, but little is known about its effects on suicide risk. Objective: For the assessment of the effectiveness of rTMS on suicidal ideation and behaviors, we performed a retrospective analysis of a large sample of patients with depressive disorders, who were treated with rTMS. Methods: We analyzed the records of 711 TMS in- and out-patients with depressive affective disorders in a tertiary referral hospital between 2002 and 2017. Out of these patients we were able to collect Hamilton depression rating scale (HAMD) data of 332 patients (180 females, 152 males; age range 20 to 79 years; mean age 47.3 ± 12.3) for which we analyzed the change of suicidal ideation by using item 3 (suicidality) of HAMD. Results: Out of all 711 patients treated with rTMS for their depression, one patient (0.1%) committed suicide during the TMS treatment. In the statistical analysis of the subsample with 332 patients there was an overall amelioration of depressive symptoms accompanied by a significant decrease in the suicidality item with a medium effect size. Decrease in suicidality was not inferior to changes in other items as indicated by effect sizes. Forty-seven percent of patients showed an amelioration in suicidality, 41.3% of patients did not show a change in their suicidality's scores, and 11.7% of patients showed an increase in suicidality's scores from baseline to final rating. Correlation of item 3 (suicidality) and item 7 (drive) demonstrated a significant positive association, revealing improved drive with a parallel decreased suicidality. Conclusion: Based on the proposed data, there is no evidence that rTMS increases the risk for suicide during the course of the treatment. Conversely, rTMS tends to reduce suicidal ideation. Our findings call for further rTMS controlled studies using large sample sizes and specific suicidality assessment measures to obtain more conclusive results.
The Effect of Repetitive Transcranial Magnetic Stimulation on Suicidal Ideation in Treatment-Resistant Depression: A Meta-Analysis. [2022]Objective: To quantitatively synthesize the literature on the effects of repetitive transcranial magnetic stimulation (rTMS) on suicidal ideation (SI) in patients with treatment-resistant depression.
Repetitive transcranial magnetic stimulation and drug addiction. [2019]Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that is now being tested for its ability to treat addiction. This review discusses current research approaches and results of studies which measured the therapeutic use of rTMS to treat tobacco, alcohol and illicit drug addiction. The research in this area is limited and therefore all studies evaluating the therapeutic use of rTMS in tobacco, alcohol or illicit drug addiction were retained including case studies through NCBI PubMed ( http://www.ncbi.nlm.nih.gov ) and manual searches. A total of eight studies were identified that examined the ability of rTMS to treat tobacco, alcohol and cocaine addiction. The results of this review indicate that rTMS is effective in reducing the level of cravings for smoking, alcohol, and cocaine when applied at high frequencies to the dorsolateral prefrontal cortex (DLPFC). Furthermore, these studies suggest that repeated sessions of high frequency rTMS over the DLPFC may be most effective in reducing the level of smoking and alcohol consumption. Although work in this area is limited, this review indicates that rTMS is a promising modality for treating drug addiction.
Transcranial Magnetic Stimulation of Medial Prefrontal and Cingulate Cortices Reduces Cocaine Self-Administration: A Pilot Study. [2022]Previous studies have shown that repetitive transcranial magnetic stimulation (rTMS) to the dorsolateral prefrontal cortex may serve as a potential treatment for cocaine use disorder (CUD), which remains a public health problem that is refractory to treatment. The goal of this pilot study was to investigate the effect of rTMS on cocaine self-administration in the laboratory. In the self-administration sessions, CUD participants chose between cocaine and an alternative reinforcer (money) in order to directly measure cocaine-seeking behavior. The rTMS was delivered with the H7 coil, which provides stimulation to the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC). These brain regions were targeted based on previous imaging studies demonstrating alterations in their activation and connectivity in CUD.