Transcranial Magnetic Stimulation for Depression

(ReDeeMD Trial)

Overseen by Jean-Philippe Miron, MD PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)

Must be taking: Antidepressants

Must not be taking: Benzodiazepines, Anticonvulsants

Disqualifiers: Substance use, Bipolar, Psychosis, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The goal of this randomized controlled trial is to he effectiveness of two different TMS techniques in TRD, repetitive TMS (rTMS) and deep TMS (dTMS). The main questions it aims to answer are: type of study: clinical trial participant population/health conditions : Major Depressive Disorder To assess the superiority of dTMS over rTMS in TRD To evaluate the predictive capacity of scalable candidate biomarkers Participants will be randomly allocated to one of the two intervention groups (rTMS or dTMS).

Will I have to stop taking my current medications?

The trial requires that you have been on a stable antidepressant regimen for the past four weeks before screening. However, if you are taking more than the equivalent of 2 mg of lorazepam daily or any dose of an anticonvulsant, you may need to stop or adjust these medications as they can affect the effectiveness of TMS.

What data supports the effectiveness of the treatment Transcranial Magnetic Stimulation for Depression?

Research shows that deep transcranial magnetic stimulation (dTMS) is effective for treating major depressive disorder (MDD) and can be used again if symptoms return. Studies also indicate that repetitive transcranial magnetic stimulation (rTMS) has short-term antidepressant effects and can be used for long-term maintenance in people with depression. ^{1 2 3 4 5}

Is Transcranial Magnetic Stimulation (TMS) safe for humans?

Transcranial Magnetic Stimulation (TMS), including its repetitive form (rTMS), is generally considered safe for humans when used within recommended guidelines. Common side effects are minor, such as headaches, and there is a low risk of seizures, which can be minimized by screening for risk factors. Long-term effects are not fully known, but the overall safety profile supports its use as a treatment for depression. ^{6 7 8 9 10}

How is transcranial magnetic stimulation different from other depression treatments?

Transcranial magnetic stimulation (TMS) is unique because it uses magnetic fields to stimulate nerve cells in the brain, which can improve symptoms of depression. Unlike medications, it is non-invasive and does not involve taking drugs, and deep TMS (dTMS) can reach deeper brain regions, potentially offering benefits for those who haven't responded to other treatments. ^{11 12 13 14 15}

Research Team

Jean-Philippe Miron, MD PhD

Principal Investigator

Centre de Recherche du Centre Hospitalier de l'Université de Montréal

Eligibility Criteria

This trial is for adults with Major Depressive Disorder who haven't improved after two different antidepressants, are on a stable medication regimen, and have a moderate to severe depression score. It's not for those who've had TMS before, have bipolar/psychosis or primary anxiety disorders, unstable medical conditions, recent substance abuse, certain implants, significant lab abnormalities or are pregnant.

Inclusion Criteria

I have been depressed for over 2 years and have tried ECT or ketamine.

HRSD-17 score of at least 18

I have been on the same antidepressant for at least 4 weeks.

Exclusion Criteria

Substance use disorder within the last three months

Intracranial implant, cardiac pacemaker or implanted medication pump

Pregnancy

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either repetitive TMS (rTMS) or deep TMS (dTMS) for Major Depressive Disorder

18 weeks

Daily sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Deep Transcranial Magnetic Stimulation (Procedure)
• Repetitive Transcranial Magnetic Stimulation (Procedure)

Trial Overview The study compares repetitive TMS (rTMS) and deep TMS (dTMS) in treating treatment-resistant depression. Participants will be randomly assigned to one of these two techniques to see if dTMS is more effective than rTMS and to test the use of biomarkers in predicting outcomes.

Participant Groups

Group I: deep Transcranial Magnetic Stimulation Experimental Treatment 1 Intervention

dTMS on a research Brainsway system equipped with an H7-Coil. Participants will receive the MDD FDA-cleared 18 Hz stimulation protocol (2 sec ON, 20 sec OFF, 55 trains; 1980 pulses per session; 20 min 10 s duration; 120% hand motor threshold)

Group II: repetitive Transcranial Magnetic Stimulation Active Control 1 Intervention

rTMS on a MagPro X100 research grade stimulator (MagVenture) equipped with a B70 fluid-cooled coil. Participant will receive the MDD FDA-approved iTBS protocol (triplet 50 Hz bursts repeated at 5 Hz, 2 s ON and 8 s OFF; 600 pulses per session; total duration of 3 min 9 s, 120% hand motor threshold)

Who Is Running the Clinical Trial?

Centre hospitalier de l'Université de Montréal (CHUM)

Lead Sponsor

Trials

389

Recruited

143,000+

Dr. Réjean Lapointe

Centre hospitalier de l'Université de Montréal (CHUM)

Chief Medical Officer since 2023

MD from Université de Montréal

Dr. Fabrice Brunet

Centre hospitalier de l'Université de Montréal (CHUM)

Chief Executive Officer since 2015

MD from Université de Montréal

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Dr. Paul C. Hébert

Canadian Institutes of Health Research (CIHR)

Chief Executive Officer

MD, University of Ottawa

Dr. Paul C. Hébert

Canadian Institutes of Health Research (CIHR)

Chief Medical Officer

MD, University of Ottawa

Findings from Research

Recent studies on repetitive transcranial magnetic stimulation (rTMS) for depression have demonstrated significantly improved clinical outcomes, with a pooled effect size of -0.76 from 5 studies involving 274 patients, compared to -0.35 from earlier studies.

The findings indicate that new parameters of rTMS stimulation may enhance its antidepressant effects, suggesting a potential advancement in treatment strategies for depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Has repetitive transcranial magnetic stimulation (rTMS) treatment for depression improved? A systematic review and meta-analysis comparing the recent vs. the earlier rTMS studies. Gross, M., Nakamura, L., Pascual-Leone, A., et al.[2018]

In a study of 29 patients with major depressive disorder, deep repetitive transcranial magnetic stimulation (deep-TMS) showed significant and sustained reductions in depression symptoms over 22 weeks, with a response rate increasing from 46.15% after acute treatment to 81.12% by the end of the study.

The treatment was well tolerated with no reported adverse events, indicating that deep-TMS is a safe and feasible long-term continuation option for maintaining antidepressant effects after initial treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

H-coil repetitive transcranial magnetic stimulation for treatment resistant major depressive disorder: An 18-week continuation safety and feasibility study. Harel, EV., Rabany, L., Deutsch, L., et al.[2014]

In a study of 17 patients with Major Depressive Disorder, the long-term durability of deep transcranial magnetic stimulation (dTMS) was evaluated over a follow-up period of 9.3 months, revealing a relapse rate of 5.6 per 100 person-months, which is comparable to traditional treatments like pharmacotherapy and ECT.

Despite some patients relapsing, most continued to show improvement in their depression scores (HDRS) after dTMS treatment, indicating that dTMS can provide lasting benefits even after the treatment has ended.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Follow-up of MDD Patients Who Respond to Deep rTMS: A Brief Report. Rosenberg, O., Dinur Klein, L., Gersner, R., et al.[2017]

In a study involving 59 patients with major depression, repetitive transcranial magnetic stimulation (rTMS) did not show significant effectiveness compared to sham treatment, with no meaningful differences in depression scores between the two groups.

While there were slightly higher response and remission rates in the real rTMS group (32% and 25%, respectively) compared to the sham group (10% for both), these differences were not statistically significant, indicating that rTMS may not provide a clear benefit over placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized controlled trial with 4-month follow-up of adjunctive repetitive transcranial magnetic stimulation of the left prefrontal cortex for depression. Mogg, A., Pluck, G., Eranti, SV., et al.[2022]

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) 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) 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]

A patient with treatment-resistant depression (TRD) showed unexpected improvement after experiencing a seizure during repetitive transcranial magnetic stimulation (rTMS), suggesting a potential link between seizure activity and therapeutic effects in TRD.

While rTMS is generally safe, known adverse events include headaches and seizures; this case highlights an unusual outcome where a seizure may have contributed to the patient's improvement, warranting further investigation into the mechanisms of rTMS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment-Resistant Depression Entering Remission Following a Seizure during the Course of Repetitive Transcranial Magnetic Stimulation. Kim, JW., Bae, KY., Kim, SW., et al.[2020]

High-frequency rTMS targeting the left dorsolateral prefrontal cortex is an effective treatment for acute episodes of major depressive disorder, supported by over 20 years of clinical trials.

While rTMS is effective for unipolar and likely bipolar depression, there is limited evidence for its effectiveness in the maintenance phase of treatment, indicating a need for ongoing research and practitioner education.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the clinical use of repetitive transcranial magnetic stimulation in the treatment of depression. Fitzgerald, PB.[2021]

In a preliminary study of 24 drug-resistant patients with bipolar disorder or recurrent major depressive disorder, deep transcranial magnetic stimulation (dTMS) significantly reduced depressive symptoms after 4 weeks of treatment, as measured by the Hamilton Depression Rating Scale (HDRS).

Patients who received maintenance dTMS sessions showed stable HDRS scores over 12 months, while those who did not receive maintenance experienced a significant increase in depressive symptoms, suggesting that ongoing dTMS may help prevent relapses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintenance Deep Transcranial Magnetic Stimulation Sessions are Associated with Reduced Depressive Relapses in Patients with Unipolar or Bipolar Depression. Rapinesi, C., Bersani, FS., Kotzalidis, GD., et al.[2020]

In a small study of six patients with resistant depression who had previously undergone electroconvulsive therapy (ECT), deep transcranial magnetic stimulation (TMS) showed potential efficacy, with two patients responding to treatment, including one achieving full remission.

The study suggests that deep TMS may benefit a specific group of patients who did not respond to ECT, but emphasizes the need for larger studies to confirm these findings due to the small sample size.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response to deep TMS in depressive patients with previous electroconvulsive treatment. Rosenberg, O., Zangen, A., Stryjer, R., et al.[2016]

Repetitive transcranial magnetic stimulation (rTMS) has been primarily used to treat major depressive disorder (MDD), highlighting its importance in addressing a significant global health challenge.

Recent advancements in rTMS include exploring new stimulation patterns, targets, and personalized treatment approaches, which aim to enhance the effectiveness and response rates of rTMS in treating MDD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation treatment for depressive disorders: current knowledge and future directions. Baeken, C., Brem, AK., Arns, M., et al.[2020]

A network meta-analysis of 81 studies involving 4233 patients found that priming low-frequency and bilateral rTMS are the most effective and acceptable treatments for major depressive disorder (MDD), significantly outperforming sham treatments.

Novel rTMS interventions, such as accelerated and deep rTMS, did not show any additional efficacy compared to sham, indicating that more traditional methods remain the preferred options for treating MDD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation for the Acute Treatment of Major Depressive Episodes: A Systematic Review With Network Meta-analysis. Brunoni, AR., Chaimani, A., Moffa, AH., et al.[2022]

References

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

Long-term maintenance therapy for major depressive disorder with rTMS. [2022]

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

Has repetitive transcranial magnetic stimulation (rTMS) treatment for depression improved? A systematic review and meta-analysis comparing the recent vs. the earlier rTMS studies. [2018]

3. England pubmed.ncbi.nlm.nih.gov

H-coil repetitive transcranial magnetic stimulation for treatment resistant major depressive disorder: An 18-week continuation safety and feasibility study. [2014]

4. Israel pubmed.ncbi.nlm.nih.gov

Long-term Follow-up of MDD Patients Who Respond to Deep rTMS: A Brief Report. [2017]

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

A randomized controlled trial with 4-month follow-up of adjunctive repetitive transcranial magnetic stimulation of the left prefrontal cortex for depression. [2022]

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

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

7. 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]

8. 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]

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

Treatment-Resistant Depression Entering Remission Following a Seizure during the Course of Repetitive Transcranial Magnetic Stimulation. [2020]

11. Netherlands pubmed.ncbi.nlm.nih.gov

An update on the clinical use of repetitive transcranial magnetic stimulation in the treatment of depression. [2021]

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

Maintenance Deep Transcranial Magnetic Stimulation Sessions are Associated with Reduced Depressive Relapses in Patients with Unipolar or Bipolar Depression. [2020]

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

Response to deep TMS in depressive patients with previous electroconvulsive treatment. [2016]

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

Repetitive transcranial magnetic stimulation treatment for depressive disorders: current knowledge and future directions. [2020]

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

Repetitive Transcranial Magnetic Stimulation for the Acute Treatment of Major Depressive Episodes: A Systematic Review With Network Meta-analysis. [2022]