Transcranial Magnetic Stimulation for Mental Illness

(Expedition Trial)

Recruiting at 1 trial location

Overseen By Shan Siddiqi, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Brigham and Women's Hospital

Must not be taking: Ketamine, Esketamine, ECT

Disqualifiers: Pregnancy, Cluster B disorders, PTSD, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

180 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how Transcranial Magnetic Stimulation (TMS) can treat mental illnesses such as major depressive disorder, obsessive-compulsive disorder, generalized anxiety disorder, and schizophrenia. TMS uses magnetic fields to stimulate specific brain areas, and the study aims to observe its effects on different behaviors. Participants will receive TMS at various locations in the brain's prefrontal cortex to identify the most effective treatment spots. Individuals with one of these conditions, who are either stable on their medication regimen or not taking any medication, might be suitable candidates. As a Phase 2 trial, this research measures TMS's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant findings.

Will I have to stop taking my current medications?

Participants need to have a stable medication regimen or be medication-free for 4 weeks before starting the trial. This means you may need to stop or adjust your current medications to meet this requirement.

What prior data suggests that Transcranial Magnetic Stimulation is safe for mental illness?

Research has shown that Transcranial Magnetic Stimulation (TMS) is generally safe. Studies indicate that TMS maintains a strong safety record. Common side effects are usually minor and manageable, while serious side effects are rare and often preventable.

TMS is safe and well-tolerated for various conditions. The FDA has approved TMS for treating obsessive-compulsive disorder (OCD), migraines, and aiding smoking cessation, supporting its safety.

The most serious risk with TMS is a seizure, but this occurs very rarely. Overall, TMS is considered a safe treatment option in clinical settings. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Transcranial Magnetic Stimulation (TMS) is unique because it offers a non-invasive way to potentially treat mental illnesses by directly targeting the prefrontal cortex, a key brain area involved in mood regulation. Unlike traditional medications for mental health conditions, which often take weeks to work, TMS can show effects after just a few sessions. Researchers are particularly excited about the trial's approach of using accelerated TMS, providing multiple treatments in a short period, which could lead to faster symptom relief. Additionally, this trial explores targeting specific brain regions, including ones associated with schizophrenia, which might enhance the precision and effectiveness of the treatment.

What evidence suggests that Transcranial Magnetic Stimulation could be effective for mental illness?

Research has shown that Transcranial Magnetic Stimulation (TMS) can help treat mental health issues by altering brain activity. Studies indicate that about 38% to 43% of people respond positively to this treatment. In this trial, participants will receive TMS at different locations in the prefrontal cortex to evaluate its effectiveness. For conditions like major depression, real-world data has found that symptoms significantly improve after TMS. Additionally, TMS has moderately reduced negative symptoms in various mental disorders. Overall, evidence supports TMS as a promising option for mental health treatment, although individual results may vary. ^{5 6 7 8 9}

Who Is on the Research Team?

Shan H Siddiqi, MD

Principal Investigator

Brigham and Women's

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with certain mental illnesses like major depression, OCD, anxiety, or schizophrenia. They must score above specific thresholds on clinical scales that measure the severity of their condition and have a stable medication regimen or be medication-free for at least four weeks.

Inclusion Criteria

I have been diagnosed with MDD, OCD, GAD, or schizophrenia.

My mental health medication has been stable or I've been off it for 4 weeks.

I have a mental health professional managing my care throughout the trial.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase 1

Participants receive 2 days of accelerated iTBS treatment at the first random stimulation site in the left prefrontal cortex

2 days

2 visits (in-person)

Washout Period

Participants have a 2-month break before the next treatment phase

8 weeks

Treatment Phase 2

Participants receive 2 days of accelerated iTBS treatment at the second random stimulation site in the left prefrontal cortex

2 days

2 visits (in-person)

Optional Schizophrenia-specific Treatment

Patients with schizophrenia may participate in a third arm with 2 days of accelerated iTBS to a schizophrenia-specific target, including fMRI scans and behavioral testing

2 days

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with behavioral testing and MRI scanning

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Transcranial Magnetic Stimulation

Trial Overview

The study tests Transcranial Magnetic Stimulation (TMS) targeting different areas in the left prefrontal cortex to see how it affects behavior. Participants will receive TMS at random safe sites while undergoing behavioral testing to identify which brain circuits influence specific behaviors.

How Is the Trial Designed?

Group I: TMS to random PFC location 2 Experimental Treatment 1 Intervention

After a 2-month washout following arm 1, participants will receive another two days of accelerated iTBS treatment at a different random PFC location.

Group II: TMS to random PFC location 1 Experimental Treatment 1 Intervention

Participants will receive 2 days of accelerated TMS (10 treatments per day) to a random location in the prefrontal cortex.

Group III: TMS to Schizophrenia location Experimental Treatment 1 Intervention

Patients with schizophrenia will be offered to participate in a third arm of the trial, during which participants will receive 2 days of accelerated iTBS to a schizophrenia-specific target.

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

High dose transcranial magnetic stimulation (rTMS) at 10 Hz significantly reduced negative symptoms in schizophrenia patients, particularly blunted affect, emotional withdrawal, and passive/apathetic social withdrawal, with an effective rate of 43.75% compared to 11.43% in the control group.

While rTMS was found to be effective, it was associated with a higher incidence of headaches (37.50% in the study group) compared to the control group, indicating a need for monitoring side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effectiveness and safety of high dose transcranial magnetic stimulation in schizophrenia with refractory negative symptoms: a randomized controlled study]. Gan, J., Duan, H., Chen, Z., et al.[2018]

In a study of 301 medication-free patients with treatment-resistant major depression, transcranial magnetic stimulation (TMS) significantly improved quality of life (QOL) and functional status compared to sham treatment during a 6-week trial.

The benefits of TMS were not only observed during the acute treatment phase but also sustained over a 24-week follow-up, indicating that TMS provides durable improvements in patients' overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement in quality of life with left prefrontal transcranial magnetic stimulation in patients with pharmacoresistant major depression: acute and six month outcomes. Solvason, HB., Husain, M., Fitzgerald, PB., et al.[2018]

Transcranial magnetic stimulation (TMS) is a non-invasive therapy that can induce small electrical currents in the brain, showing minimal side effects and potential short-term benefits for patients with depression, particularly when targeting underactive left prefrontal regions.

Higher dosages of high-frequency repetitive TMS have been associated with greater therapeutic benefits, suggesting that further research with extended treatment periods could solidify its efficacy as a treatment for depression and possibly other related disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation as therapy for depression and other disorders. Kirkcaldie, MT., Pridmore, SA., Pascual-Leone, A.[2017]

Transcranial magnetic stimulation (TMS) is a noninvasive treatment that can modulate neural activity and has shown promise in treating psychiatric disorders like major depression, schizophrenia, and anxiety.

While many clinical trials indicate that TMS can have significant effects, the benefits may be small and short-lived, highlighting the need for further research to enhance its efficacy and identify the best candidates for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Applications of TMS to therapy in psychiatry. Lisanby, SH., Kinnunen, LH., Crupain, MJ.[2019]

Transcranial magnetic stimulation (TMS) is generally considered a safe treatment option for managing symptoms of schizophrenia, particularly in reducing auditory hallucinations, based on a review of 19 studies involving 531 patients.

There are ongoing controversies regarding the effects of TMS on the cortical silent period in schizophrenia patients, with some studies showing longer or shorter periods compared to healthy controls, indicating potential GABA receptor abnormalities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Different Modalities of Transcranial Magnetic Stimulation to Manage Schizophrenia. Soltani, E., Bateni, H., Shad, MU.[2022]

Transcranial magnetic stimulation (TMS) was found to be effective in treating unipolar depression, with 4 out of 11 patients achieving remission after four weeks of active treatment compared to none in the sham group.

The study showed significant improvements in response rates at various time points, particularly at day 21 and day 28, indicating that TMS can lead to meaningful reductions in depression symptoms in patients not on antidepressant medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind sham controlled study of right prefrontal repetitive transcranial magnetic stimulation (rTMS): therapeutic and cognitive effect in medication free unipolar depression during 4 weeks. Januel, D., Dumortier, G., Verdon, CM., et al.[2022]

Transcranial magnetic stimulation (TMS), particularly repetitive TMS (rTMS), is a safe and effective non-invasive brain stimulation technique that has been shown to induce long-lasting neuroplastic effects, making it a promising treatment for conditions like treatment-resistant depression (TRD) and other psychiatric disorders.

rTMS has received regulatory approval for various conditions, including TRD, anxiety disorders, obsessive-compulsive disorder, and substance use disorders, with ongoing research suggesting its potential for treating additional psychiatric issues such as schizophrenia and post-traumatic stress disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regulatory Clearance and Approval of Therapeutic Protocols of Transcranial Magnetic Stimulation for Psychiatric Disorders. Cotovio, G., Ventura, F., Rodrigues da Silva, D., et al.[2023]

Four cases of Serotonin Syndrome (SS) were identified, all involving patients treated with multiple psychoactive drugs, with lithium implicated in three cases; however, none of these cases were severe enough to lead to lasting effects, and all patients recovered fully.

In contrast, 13 cases of Neuroleptic Malignant Syndrome (NMS) were reported, with at least three fatalities, indicating that NMS can be more severe and potentially life-threatening, even when only one drug was involved in some cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Serotonin syndrome and malignant neuroleptic syndrome. A review based on the material from the National Board of Adverse Drug Reactions]. von Halling Laier, MG., Gram, LF.[2022]

Tardive motor syndromes (TMS) are involuntary movement disorders that can develop after long-term use of dopamine receptor blocking agents, with a diagnosis requiring at least 3 months of exposure (1 month for those over 60).

Preventive measures, including regular monitoring and early detection of symptoms, are essential for managing TMS, and treatment options like atypical antipsychotics and botulinum toxin A can help improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug-induced tardive motor syndromes. Havaki-Kontaxaki, B., Komborozos, A., Kontaxakis, V.[2014]

A survey of 30 psychiatrists revealed that they rarely inform patients about the risk of neuroleptic malignant syndrome (NMS), with only one psychiatrist consistently providing this information, despite its potential fatality.

Psychiatrists were more likely to discuss the risk of tardive dyskinesia, indicating a possible lack of awareness or knowledge about NMS and its importance in informed consent for patients on neuroleptic medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obtaining informed consent of patients at risk of neuroleptic malignant syndrome. Kleinman, I., Schachter, D.[2015]

Transcranial magnetic stimulation (TMS) is an effective and safe treatment for major depressive disorder (MDD), showing significant improvements in quality of life (QOL) and functional status in 307 outpatients after an acute treatment course.

Patients reported statistically significant enhancements in mental and physical health across various domains, indicating that TMS not only alleviates depressive symptoms but also leads to meaningful improvements in overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation (TMS) for major depression: a multisite, naturalistic, observational study of quality of life outcome measures in clinical practice. Janicak, PG., Dunner, DL., Aaronson, ST., et al.[2022]

Extrapyramidal symptoms (EPS), which include conditions like acute dystonia and tardive dyskinesia, are less common with atypical antipsychotics compared to conventional ones, but they still occur frequently in clinical practice due to insufficient screening by healthcare professionals.

Antipsychotics and antidepressants can lower the seizure threshold, with clozapine and tricyclic antidepressants posing a higher risk, and atypical antipsychotics in elderly patients with dementia are linked to increased risks of stroke and death compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurological complications of psychiatric drugs: clinical features and management. Haddad, PM., Dursun, SM.[2022]

Varenicline has been linked to serious neuropsychiatric adverse events (AEs), particularly in patients with a history of psychiatric illness, with 68% of reported cases involving such patients.

Most neuropsychiatric symptoms resolved after stopping varenicline, but the findings suggest that it should only be prescribed to mentally stable individuals and with careful monitoring due to the potential risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuropsychiatric adverse events of varenicline: a systematic review of published reports. Ahmed, AI., Ali, AN., Kramers, C., et al.[2018]

Transcranial magnetic stimulation (TMS) is a noninvasive technique that shows promise in treating various psychiatric disorders, including depression, anxiety, and schizophrenia, by modulating brain activity.

TMS is generally well-tolerated and can complement other therapies, but more research is needed to understand its cellular mechanisms and long-term effects to optimize treatment protocols for specific conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current State of Transcranial Magnetic Stimulation and its use in Psychiatry. Zorzo, C., Banqueri, M., Higarza, SG., et al.[2019]

Citations

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pmc.ncbi.nlm.nih.gov

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Efficacy of neurostimulation across mental disorders

Negative symptoms were significantly improved by both TMS and tDCS protocols with a medium effect size. However, these results were ...

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sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0165178121002833

Ten years' data of Transcranial Magnetic Stimulation (TMS)

TMS responses of all patients were evaluated 26.1% as response, 29.2% as partial response, and 44.7% as inadequate response. •. It has been determined that MDD ...

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bmcpsychiatry.biomedcentral.com

bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-024-05928-4

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nimh.nih.gov

nimh.nih.gov/news/media/2020/sarah-h-lisanby-transcranial-magnetic-stimulation-safety-and-risk

Sarah H. Lisanby: Transcranial Magnetic Stimulation Safety ...

The safety profile of TMS is excellent. The common side effects tend to be minor and are easily managed. The serious side effects are rare and can be prevented ...

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mayoclinic.org

mayoclinic.org/tests-procedures/transcranial-magnetic-stimulation/about/pac-20384625

Transcranial magnetic stimulation

The FDA also approved TMS for obsessive-compulsive disorder (OCD), migraines and to help people stop smoking when standard treatments haven't ...

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TMS is safe and well-tolerated for people with SUDs. The prevalence of side effects from TMS in people with SUDs is comparable to that in the ...

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sciencedirect.com

sciencedirect.com/science/article/pii/S0272735822001210

Efficacy and safety of transcranial magnetic stimulation for ...

Our results suggest the effects and safety of TMS in treating MDD are likely lower in some populations than previous estimates suggested. •. Future research ...