Transcranial Magnetic Stimulation for Psychological Distress

Overseen By Julie Lapenskie, MSc

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Ottawa Hospital Research Institute

Must not be taking: Seizure threshold-lowering

Disqualifiers: Seizure disorder, Brain lesions, 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: 12

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a treatment called Repetitive Transcranial Magnetic Stimulation (rTMS) to help individuals experiencing severe psychological distress at the end of life. The researchers aim to determine the optimal dose and assess the treatment's effectiveness in quickly alleviating distress. Individuals with advanced illness who feel anxious or depressed despite treatment might be suitable candidates. The study will test different doses to identify the most effective and acceptable option for patients. This research could lead to new options for those facing significant emotional challenges in palliative care settings. As an unphased trial, it offers a unique opportunity to contribute to groundbreaking research that could enhance emotional support for patients in palliative care.

Do I have to stop taking my current medications for the trial?

The protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are on medications that lower the seizure threshold.

What prior data suggests that this protocol is safe for treating psychological distress?

Research shows that repetitive transcranial magnetic stimulation (rTMS) is a safe and non-invasive treatment for various mental and brain-related conditions. This method uses magnetic fields to stimulate brain cells. Studies have found that patients generally tolerate rTMS well.

A review of multiple studies found that combining rTMS with antidepressants improved depression symptoms. This suggests that rTMS might also be effective for other mental health issues. While some patients may experience mild side effects, such as headaches or scalp discomfort, serious side effects are rare.

Overall, evidence supports the safety of rTMS, making it a promising option for treating mental health problems. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Repetitive Transcranial Magnetic Stimulation (rTMS) is unique because it uses magnetic fields to stimulate nerve cells in the brain, which is different from most traditional treatments for psychological distress, like medication or therapy. Researchers are excited about rTMS because it offers a non-invasive alternative that directly targets areas of the brain associated with mood regulation. Unlike medications which can take weeks to show improvements and may have side effects, rTMS has the potential to provide quicker relief with minimal side effects. This makes it a promising option for individuals who haven't responded well to conventional treatments.

What evidence suggests that rTMS might be an effective treatment for psychological distress?

Research has shown that Repetitive Transcranial Magnetic Stimulation (rTMS) can help treat depression, particularly when other treatments have failed. Studies indicate that rTMS can significantly improve mood and reduce mental health symptoms. Receiving 10 or more sessions of rTMS is associated with better outcomes. This method uses magnetic fields to stimulate brain cells, which can enhance mood and cognitive function. In this trial, participants will receive rTMS to address emotional and existential distress at the end of life. The success of rTMS in treating depression suggests it could be a promising option for reducing emotional distress in palliative care settings. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for English-speaking patients with advanced terminal illness who have a life expectancy of over one month and are experiencing significant psychological distress, as shown by specific scores on the Edmonton Symptom Assessment System. It's not suitable for those with brain lesions, inability to stay still during therapy, contraindications to rTMS like metallic implants or pacemakers, seizure disorders, or certain medication use.

Inclusion Criteria

Ability to understand and communicate in English

You are a patient with advanced or terminal illness in a palliative care unit or in the community.

You are not expected to live for more than one month.

Exclusion Criteria

Documented brain lesions

You are unable to sit up at a 45 degree angle and remain still during treatment.

You cannot participate if you have metal skull plates, clips, or stimulators, pacemakers or other electronic implants, are pregnant, have recurrent unexplained headaches, have had a previous skull fracture or brain surgery, or are taking medication that lowers seizure threshold.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

2 visits (in-person)

Dose-finding Treatment (Phase 2a)

Open-label dose-finding study to determine the appropriate rTMS dose

5 days

Up to 8 sessions daily

Feasibility and Efficacy Trial (Phase 2b)

Randomized clinical trial to measure the effect of rTMS with sham-control or sham-crossover design

5-10 days

Daily sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Assessments at 2, 4, and 8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Repetitive Transcranial Magnetic Stimulation

Trial Overview The study tests repetitive Transcranial Magnetic Stimulation (rTMS) to alleviate psychological distress in terminally ill patients. The trial has two phases: first determining the effective dose of rTMS and then comparing symptom changes before and after treatment using either real or sham rTMS based on earlier findings.

How Is the Trial Designed?

Group I: rTMS Intervention Group Experimental Treatment 1 Intervention

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

Approved in United States as rTMS for:

• Major depressive disorder
• Obsessive-compulsive disorder
• Migraines

Approved in European Union as rTMS for:

• Major depressive disorder
• Obsessive-compulsive disorder
• Anxiety disorders

Approved in Canada as rTMS for:

• Major depressive disorder
• Obsessive-compulsive disorder

Who Is Running the Clinical Trial?

Ottawa Hospital Research Institute

Lead Sponsor

Trials

585

Recruited

3,283,000+

Bruyère Health Research Institute.

Collaborator

Lotte & John Hecht Memorial Foundation

Collaborator

Trials

18

Recruited

4,600+

Bruyere Research Institute

Collaborator

Trials

35

Recruited

2,024,000+

Canadian Cancer Society (CCS)

Collaborator

Trials

84

Recruited

42,100+

Bruyère Research Institute

Collaborator

Trials

2

Recruited

3,600+

Published Research Related to This Trial

Transcranial magnetic stimulation (TMS) is an FDA-approved, noninvasive treatment for major depressive disorder, with response rates of 40%-60% in treatment-resistant cases, indicating its efficacy in improving mood and brain function.

TMS is generally safe and well tolerated, with the rarest serious risk being seizure, making it a low-risk option for patients seeking alternatives to traditional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychiatric Applications of Repetitive Transcranial Magnetic Stimulation. Marder, KG., Barbour, T., Ferber, S., et al.[2023]

Repetitive transcranial magnetic stimulation (rTMS) has shown stronger evidence of efficacy in treating major depression compared to auditory-verbal hallucinations in schizophrenia, with some studies indicating clinically relevant improvements in both conditions.

While research is limited for other psychiatric disorders, initial findings suggest rTMS may also be beneficial for negative symptoms in schizophrenia, obsessive-compulsive disorder, and post-traumatic stress disorder, highlighting the need for further investigation into its mechanisms and broader applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of repetitive transcranial magnetic stimulation for treatment in psychiatry. Aleman, A.[2022]

Repetitive transcranial magnetic stimulation (rTMS) has been studied as a treatment for major depression since the 1990s, but many patients in trials show high treatment resistance, which may affect the perceived effectiveness of rTMS.

The findings suggest that the clinical reputation of rTMS could be negatively impacted by the inclusion of treatment-resistant patients in studies, highlighting the need for further research to clarify its efficacy in less resistant populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation in non-treatment-resistant depression. Kiebs, M., Hurlemann, R., Mutz, J.[2020]

Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective treatment for major depressive disorder (MDD), with real-world response rates of 40-50% and remission rates of 25-30%, supported by over 150 randomized controlled trials and numerous meta-analyses.

The review discusses ways to enhance the accessibility and effectiveness of rTMS, including treatment personalization and the potential of accelerated rTMS (arTMS) to improve outcomes for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation for major depressive disorder: basic principles and future directions. Miron, JP., Jodoin, VD., Lespérance, P., et al.[2021]

Transcranial magnetic stimulation (TMS) has been shown to have antidepressant effects in numerous randomized controlled trials, leading to its recent FDA approval for treating depression, although the long-term effectiveness of this treatment is still debated.

Research on TMS and transcranial direct current stimulation (tDCS) for other psychiatric disorders, such as anxiety and schizophrenia, is limited and controversial, highlighting the need for further studies to determine their efficacy and optimal treatment parameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Controversy: Repetitive transcranial magnetic stimulation or transcranial direct current stimulation shows efficacy in treating psychiatric diseases (depression, mania, schizophrenia, obsessive-complusive disorder, panic, posttraumatic stress disorder). George, MS., Padberg, F., Schlaepfer, TE., 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]

Repetitive transcranial magnetic stimulation (rTMS) is generally a well-tolerated treatment for depression, with mild side effects like headaches being the most common, while severe adverse effects are rare.

Special precautions are necessary for certain groups, such as adolescents, pregnant women, and individuals with metal implants, but with proper assessment and monitoring, rTMS can be safely administered to many patients with depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation (TMS) safety: a practical guide for psychiatrists. Taylor, R., Galvez, V., Loo, C.[2019]

Repetitive transcranial magnetic stimulation (rTMS) has been shown to be a safe and effective treatment for major depressive disorder (MDD), supported by multiple randomized controlled trials and extensive literature review.

The consensus recommendations from a group of 17 expert clinicians and researchers provide detailed guidance on the clinical application of rTMS, ensuring its safe and effective use in treating MDD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Consensus Recommendations for the Clinical Application of Repetitive Transcranial Magnetic Stimulation (rTMS) in the Treatment of Depression. McClintock, SM., Reti, IM., Carpenter, LL., et al.[2022]

Transcranial magnetic stimulation (TMS) is a safe and effective treatment approved for conditions like treatment-resistant major depressive disorder and obsessive-compulsive disorder, which are common and significantly impact public health.

Despite its effectiveness, many healthcare providers are not familiar with TMS, highlighting the need for better education on its use and benefits, especially for patients with chronic conditions resistant to traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Magnetic Stimulation: A Clinical Primer for Nonexperts. Minzenberg, MJ., Yoon, JH.[2021]

In a study involving 18 subjects with major depression, repetitive transcranial magnetic stimulation (rTMS) for up to 4 weeks was found to be generally safe, with no significant mean deficits in neuropsychologic function or auditory thresholds.

However, two patients experienced mild high-frequency hearing loss, indicating that while rTMS is safe for most, individual responses may vary and warrant further investigation into long-term safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of a 2- to 4-week course of repetitive transcranial magnetic stimulation (rTMS) on neuropsychologic functioning, electroencephalogram, and auditory threshold in depressed patients. Loo, C., Sachdev, P., Elsayed, H., et al.[2019]

Repetitive Transcranial Magnetic Stimulation (rTMS) has a good overall safety profile for treating depression, with common side effects like headaches being minor and manageable.

While there is a low incidence of serious side effects such as seizures and hypomania, these are linked to specific risk factors, suggesting that proper screening can enhance patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of the safety of repetitive transcranial magnetic stimulation as a clinical treatment for depression. Loo, CK., McFarquhar, TF., Mitchell, PB.[2021]

Transcranial magnetic stimulation (TMS) is a non-invasive technique that can modulate brain activity and has shown potential as a treatment for major depression, with a meta-analysis indicating robust statistical effects, although individual responses can vary widely.

While TMS has demonstrated antidepressant properties, the overall rates of clinical response and remission are limited, and the long-term effectiveness of TMS treatments remains largely unknown.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuropsychiatric applications of transcranial magnetic stimulation: a meta analysis. Burt, T., Lisanby, SH., Sackeim, HA.[2019]

Repetitive transcranial magnetic stimulation (rTMS) is generally safe for older adults with late-life depression, with only 12.4% reporting any adverse events and serious adverse events occurring in just 1.5% of cases, based on a review of 11 studies involving 353 patients.

The most common adverse events were mild, such as headaches (6.9%) and discomfort at the stimulation site (2.7%), although some serious adverse events, including psychiatric hospitalization and increased suicidal ideation, were noted in case reports, highlighting the need for further research to ensure safety in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of repetitive transcranial magnetic stimulation in older adults with depression, a systematic review of the literature. Overvliet, GM., Jansen, RAC., van Balkom, AJLM., et al.[2021]

Citations

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Evaluating the treatment outcomes of repetitive transcranial ... The result showed that the rTMS treatment significantly improved cognitive performance on the severe impairment battery (SIB), reduced psychiatric symptoms on ...

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Repetitive Transcranial Magnetic Stimulation as ... Repetitive transcranial magnetic stimulation (rTMS) as maintenance treatment may prevent relapse of treatment-resistant depression (TRD).

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Real-world outcome of rTMS treatment for depression ... This study registered consecutive cases to elucidate the efficacy of rTMS treatment for depression within the Japanese public health insurance system.

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Trajectories of improvement with repetitive transcranial ... Repetitive transcranial magnetic stimulation (rTMS) is an established non-invasive brain stimulation treatment for major depressive disorder ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK568715/

Repetitive Transcranial Magnetic Stimulation - StatPearls - NCBI Repetitive transcranial magnetic stimulation (rTMS) is a safe and non-invasive treatment technique used to treat various psychiatric and neurological disorders.

7. 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 ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5925584/

Meta-analysis of the Efficacy and Safety of Repetitive ... After Meta-analysis, we found that treatment combined rTMS with antidepressants improves depressive symptoms in patients with depression.

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

Transcranial magnetic stimulation Transcranial magnetic stimulation (TMS) is a procedure that uses magnetic fields to stimulate nerve cells in the brain to improve symptoms of major depression.