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?

Psychological and existential distress are a common cause of suffering among patients nearing the end of life, and a major reason for requesting medical aid in dying. Existing treatments for psychological and existential suffering have low efficacy and are challenging to use in a palliative context. There is a need to develop scalable, brief, and rapidly effective therapeutic approaches that can reduce psychological and existential distress in patients nearing the end of life. Repetitive Transcranial Magnetic Stimulation is an effective treatment for refractory depression, and new protocols and increasing availability of rTMS may make this therapy feasible and acceptable for patients who suffer from psychological or existential distress near the end of life. Among patients with advanced illness followed by a PC provider, the study objectives are to: 1. Identify the lowest and range of therapeutic rTMS dose to relieve psychological distress, including an analysis of clinical predictors of response. 2. Test the feasibility and preliminary efficacy of rTMS for the treatment of psychological distress including: 1) ease of recruitment; 2) completion of follow-up; 3) effect size and variance estimates of treatment for primary and secondary outcomes; and 4) patient satisfaction with treatment. This study is a phase 2a dose-finding open-label clinical trial, followed by a phase 2b prospective, sham-control or sham-crossover study, depending on the therapeutic dose identified in phase 2a. The investigators will enroll eligible patients from an inpatient palliative care unit and administer rTMS according to established best practice international guidelines. Two screening tests will be conducted (one completed by patient and another by the treating physician) to ensure the patient has no contraindications to rTMS. In the open-label dose-finding study, investigators will determine the appropriate dose of treatment that leads to positive patient outcomes, assess characteristics associated with positive and rapid response to rTMS, and examine if this treatment is feasible and acceptable to patients by measuring rates of enrollment and completion of the treatment sessions. Based on results from this first phase, a phase 2b feasibility and preliminary efficacy randomized clinical trial will be conducted to measure the effect of rTMS by comparing patient symptoms before and after the rTMS intervention.

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 safety data exists for transcranial magnetic stimulation in treating psychological distress?

The safety of repetitive transcranial magnetic stimulation (rTMS) has been studied in various contexts, primarily for depression. Research indicates that common side effects are minor, such as headaches. There is a low incidence of more serious effects like accidental seizures and induced hypomania, which are associated with identifiable risk factors. Safety concerns such as effects on hearing, headache, pain, and electromagnetic exposure have been reviewed, with the overall safety profile considered good when guidelines are followed. However, long-term effects are still unknown. Studies have focused on different populations, including older adults, and have provided practical safety recommendations for clinicians. ^{1 2 3 4 5}

Is the treatment Repetitive Transcranial Magnetic Stimulation (rTMS) promising for psychological distress?

Yes, Repetitive Transcranial Magnetic Stimulation (rTMS) is a promising treatment for psychological distress. It is a non-invasive method that uses magnetic fields to stimulate specific brain areas, and it has been approved for treating major depressive disorder and obsessive-compulsive disorder. Studies show it can be effective, especially for depression, and it is generally safe and well-tolerated. ^{6 7 8 9 10}

What data supports the idea that Transcranial Magnetic Stimulation for Psychological Distress is an effective treatment?

The available research shows that Transcranial Magnetic Stimulation (TMS) is effective for treating major depressive disorder, with response rates between 40% and 60%. It is also approved for obsessive-compulsive disorder and smoking cessation. TMS is generally safe and well-tolerated, with rare serious risks. Compared to other treatments, TMS is particularly useful for those who have not responded to traditional therapies. While more research is needed for other conditions, initial studies suggest potential benefits for schizophrenia, obsessive-compulsive disorder, and post-traumatic stress disorder. ^{6 8 11 12 13}

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 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) 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]

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 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]

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]

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) 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 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]

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), 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]

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]

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]

Citations

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

Neuropsychiatric applications of transcranial magnetic stimulation: a meta analysis. [2019]

2. Korea (South) pubmed.ncbi.nlm.nih.gov

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

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

Psychiatric Applications of Repetitive Transcranial Magnetic Stimulation. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation in non-treatment-resistant depression. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation for major depressive disorder: basic principles and future directions. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Adverse events of repetitive transcranial magnetic stimulation in older adults with depression, a systematic review of the literature. [2021]

7. United States 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. [2019]

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

Transcranial magnetic stimulation (TMS) safety: a practical guide for psychiatrists. [2019]

9. England pubmed.ncbi.nlm.nih.gov

A review of the safety of repetitive transcranial magnetic stimulation as a clinical treatment for depression. [2021]

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

Consensus Recommendations for the Clinical Application of Repetitive Transcranial Magnetic Stimulation (rTMS) in the Treatment of Depression. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Regulatory Clearance and Approval of Therapeutic Protocols of Transcranial Magnetic Stimulation for Psychiatric Disorders. [2023]

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

Transcranial Magnetic Stimulation: A Clinical Primer for Nonexperts. [2021]

13. United States 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). [2022]