Transcranial Magnetic Stimulation for Prolonged Grief Disorder

Overseen By Nadia Polskaia, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Bruyere Research Institute

Disqualifiers: Seizure disorder, Brain lesions, Substance abuse, others

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

Compensation: Varies

Number of Visits: 5

Duration: 5 days

15 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Repetitive Transcranial Magnetic Stimulation (rTMS) for Prolonged Grief Disorder?

Research shows that repetitive transcranial magnetic stimulation (rTMS) is effective in treating major depression, which shares some symptoms with prolonged grief disorder. This suggests that rTMS might also help with prolonged grief disorder, although more specific studies are needed. ^{1 2 3 4 5}

Is transcranial magnetic stimulation (TMS) safe for humans?

Transcranial magnetic stimulation (TMS) is generally safe and well tolerated in humans. The most serious risk is a seizure, but this occurs very rarely. TMS has been used safely in various conditions, including depression and obsessive-compulsive disorder. ^{6 7 8 9 10}

How does the treatment rTMS differ from other treatments for Prolonged Grief Disorder?

Repetitive Transcranial Magnetic Stimulation (rTMS) is unique because it uses magnetic fields to stimulate specific areas of the brain non-invasively, which is different from traditional treatments like medication or talk therapy. While commonly used for depression, its application for Prolonged Grief Disorder is novel, as there are no standard treatments specifically for this condition. ^{1 2 6 11 12}

What is the purpose of this trial?

Grief is a normal response after the death of a loved one. With time, the grief response decreases and people learn to cope with their loss. However, for some, the response becomes more intense and distressing. This is called prolonged grief disorder (PGD). People with PGD experience emotional pain and a deep longing for their loved one. PGD normally occurs \<10% of people after a loss, but it has become more common since the COVID-19 pandemic (\~30%). If left untreated, PGD leads to poor quality of life and increased risk of death. Treatment options such as medication and therapy are available; however, they can cause negative side effects and take a long time to work. To help individuals with PGD, we need treatments that work well and quickly. Repetitive transcranial magnetic stimulation (rTMS) is a safe, non-invasive treatment that delivers magnetic pulses to brain areas responsible for mood. rTMS has been approved in Canada to treat mood disorders. There is research to show that rTMS is safe and well-tolerated, and that works well in treating Post-Traumatic Stress Disorder (PTSD), a condition with similar symptoms to PGD. To determine whether rTMS is effective for treating PGD, we first need to determine if rTMS as a treatment for PGD is safe and feasible among grieving individuals.

Eligibility Criteria

This trial is for individuals experiencing prolonged grief disorder (PGD), which is intense emotional pain and longing after losing a loved one. It's more common since COVID-19, affecting about 30% of grieving people. Participants should have PGD symptoms that significantly impact their life.

Inclusion Criteria

Score greater than 25 on the Inventory of Complicated Grief

I am 18 or older and have recently lost someone close to me.

Must have a primary care physician

Exclusion Criteria

Pregnancy or lactation, or trying to conceive

Documented brain lesions

Contraindications to TMS (i.e., metallic skull plates, clips, stimulators, pacemakers)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive repetitive transcranial magnetic stimulation (rTMS) to treat prolonged grief disorder

5 days

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Monthly visits

Long-term Follow-up

Participants are monitored for long-term safety and efficacy outcomes

Up to 16 months

Treatment Details

Interventions

• Repetitive Transcranial Magnetic Stimulation (rTMS)

Trial Overview The trial tests repetitive Transcranial Magnetic Stimulation (rTMS), a non-invasive treatment using magnetic pulses on the brain to improve mood. It's already used for mood disorders in Canada and may help with PGD by targeting similar brain areas as those affected in PTSD.

Participant Groups

Group I: rTMS Intervention Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Bruyere Research Institute

Lead Sponsor

Trials

35

Recruited

2,024,000+

Findings from Research

Repetitive transcranial magnetic stimulation (rTMS) showed a statistically significant but small improvement in depression scores compared to sham treatment, with a weighted mean difference of 2.31 points, which is below the clinically important threshold of 3.5 points.

In comparison to electroconvulsive therapy (ECT), rTMS was less effective, with ECT showing a greater improvement in depression scores and higher rates of remission and response, indicating that ECT may be a more effective option for treatment-resistant depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. [2022]

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]

In a study of 15 medication-free subjects with major depression, 10 sessions of repetitive transcranial magnetic stimulation (rTMS) did not significantly reduce depression severity compared to sham treatment, indicating limited efficacy in this short-term application.

However, patients with a shorter duration of depressive episodes (less than 4 years) experienced a much greater response to rTMS, suggesting that treatment timing may be crucial for effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Shorter duration of depressive episode may predict response to repetitive transcranial magnetic stimulation. Holtzheimer, PE., Russo, J., Claypoole, KH., et al.[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]

In a study involving 20 patients with unipolar depression, the pain associated with left prefrontal repetitive transcranial magnetic stimulation (rTMS) decreased by 48% over 15 treatment sessions, indicating that discomfort may lessen with continued use.

The reduction in pain was most significant in the first few days but continued steadily throughout the treatment, suggesting that patients may tolerate rTMS better over time, which could encourage ongoing treatment despite initial discomfort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decreasing procedural pain over time of left prefrontal rTMS for depression: initial results from the open-label phase of a multi-site trial (OPT-TMS). Anderson, BS., Kavanagh, K., Borckardt, JJ., et al.[2021]

Repetitive transcranial magnetic stimulation (rTMS) has gained popularity for its ability to modulate brain activity, but safety considerations are crucial, especially with the recent updates to safety guidelines published in 2021.

The guidelines emphasize the importance of screening for risks, monitoring for adverse events, and specific safety measures when using rTMS, particularly in patients with conditions like stroke and traumatic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. Kim, WS., Paik, NJ.[2023]

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) significantly improves treatment-resistant depression, showing over three times higher odds of response compared to sham treatments, and nearly three times higher odds of achieving remission.

rTMS also effectively reduces symptoms of obsessive-compulsive disorder (OCD) and negative symptoms of schizophrenia, although it does not significantly impact auditory hallucinations, indicating varying efficacy based on the specific psychiatric condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of Repetitive Transcranial Magnetic Stimulation in Depression, Schizophrenia, and Obsessive-Compulsive Disorder: An Umbrella Meta-Analysis. Patel, S., Silvi, S., Desai, S., et al.[2023]

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]

References

1. Canada pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. [2022]

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

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

3. Canada pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation for the treatment of major depressive disorder: an evidence-based analysis. [2023]

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

Shorter duration of depressive episode may predict response to repetitive transcranial magnetic stimulation. [2019]

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

The effect of deep repetitive transcranial magnetic stimulation with an H1 coil on hopelessness in patients with major depressive disorder: A randomized controlled trial. [2023]

6. 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]

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

Decreasing procedural pain over time of left prefrontal rTMS for depression: initial results from the open-label phase of a multi-site trial (OPT-TMS). [2021]

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

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. [2023]

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

Psychiatric Applications of Repetitive Transcranial Magnetic Stimulation. [2023]

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

Effectiveness of Repetitive Transcranial Magnetic Stimulation in Depression, Schizophrenia, and Obsessive-Compulsive Disorder: An Umbrella Meta-Analysis. [2023]

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

A Clinical Program to Implement Repetitive Transcranial Magnetic Stimulation for Depression in the Department of Veterans Affairs. [2022]

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

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