Transcranial Magnetic Stimulation for Depression

(ReDeeMD Trial)

Not currently recruiting at 1 trial location

Overseen By Véronique Desbeaumes Jodoin, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

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

Compensation: Varies

Number of Visits: Unknown

Duration: 18 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two types of transcranial magnetic stimulation (TMS) to determine which works better for people with treatment-resistant depression (TRD). Participants will receive either repetitive TMS (rTMS) or deep TMS (dTMS) to assess which method improves symptoms more effectively. The trial also seeks to identify biomarkers, measurable indicators that could predict treatment response. Individuals with major depressive disorder who have not succeeded with at least two different antidepressant treatments might be suitable for this study. As an unphased trial, it offers participants the chance to contribute to pioneering research that could lead to more effective depression treatments.

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 prior data suggests that these TMS techniques are safe for treating depression?

Studies have shown that both deep transcranial magnetic stimulation (dTMS) and repetitive transcranial magnetic stimulation (rTMS) are generally safe for treating depression. Research indicates that dTMS is safe and well-tolerated, even for those who do not respond to antidepressants and for older adults. The FDA has approved dTMS, confirming its safety.

Similarly, rTMS is considered safe, with studies supporting its use in both unipolar and bipolar depression. This non-invasive method uses magnetic fields to help improve depression symptoms. Although some studies suggest rTMS may not work for everyone, it remains a safe option. Overall, both treatments have been shown to be safe for addressing depression, especially when other treatments have failed. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Transcranial Magnetic Stimulation (TMS) treatments for depression because they offer a non-invasive alternative to traditional treatments like medication and psychotherapy. Deep Transcranial Magnetic Stimulation (dTMS) uses an H7-Coil to deliver 18 Hz stimulation deep into the brain, potentially targeting areas more effectively. Repetitive Transcranial Magnetic Stimulation (rTMS) employs a MagPro X100 stimulator with an iTBS protocol to provide rapid bursts of magnetic energy, which might lead to quicker symptom relief. Both methods aim to stimulate brain activity in ways that current treatments can't, offering hope for patients who haven't found success with conventional options.

What evidence suggests that this trial's treatments could be effective for Major Depressive Disorder?

This trial will compare deep transcranial magnetic stimulation (dTMS) and repetitive transcranial magnetic stimulation (rTMS) for treating major depressive disorder. Research has shown that dTMS is effective; one study reported that 82% of participants responded positively, and 65% experienced complete relief after 30 sessions. Another study found that dTMS significantly reduced depression symptoms compared to a fake treatment. Similarly, rTMS shows promise, with studies indicating that 35.71% of patients with depression achieved complete relief. Both dTMS and rTMS have successfully reduced depression symptoms, offering hope for those whose depression hasn't improved with other treatments. ^{1 5 6 7 8}

Who Is on the Research Team?

Jean-Philippe Miron, MD PhD

Principal Investigator

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

Are You a Good Fit for This Trial?

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.

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

I haven't improved after trying two different antidepressants.

Exclusion Criteria

Substance use disorder within the last three months

Intracranial implant, cardiac pacemaker or implanted medication pump

Pregnancy

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Deep Transcranial Magnetic Stimulation
• Repetitive Transcranial Magnetic Stimulation

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.

How Is the Trial Designed?

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)

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

Approved in United States as Deep TMS for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder
• Smoking cessation

Approved in European Union as Deep TMS for:

• Major Depressive Disorder

Who Is Running the Clinical Trial?

Centre hospitalier de l'Université de Montréal (CHUM)

Lead Sponsor

Trials

389

Recruited

143,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Published Research Related to This Trial

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]

In a study involving 10 adults with major depressive disorder, long-term maintenance therapy using repetitive transcranial magnetic stimulation (rTMS) showed that 7 participants experienced significant benefits, with some maintaining improvement without additional antidepressant medications.

The treatment was found to be safe, with no serious adverse events reported and a zero seizure rate across 1831 rTMS sessions, suggesting that rTMS could be a viable long-term option for managing depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term maintenance therapy for major depressive disorder with rTMS. O'Reardon, JP., Blumner, KH., Peshek, AD., et al.[2022]

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]

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]

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]

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 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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4329899/

Efficacy and safety of deep transcranial magnetic ... dTMS induced a 6.39 point improvement in HDRS-21 scores, while a 3.28 point improvement was observed in the sham group (p+0.008), resulting in a 0.76 effect ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S002239562400270X

Clinical efficacy of deep transcranial magnetic stimulation ... Reduction in BHS scores was greater in the dTMS group (10.8%; 95% CI: −17.8% to −3.9%) compared to the control group (0.7%; 95% CI: 7.5%–6.1%; p = 0.037; FDR <5 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11234753/

Utilization and outcomes of transcranial magnetic ... This analysis contributes to the growing body of evidence demonstrating that TMS is an effective intervention for treatment resistant MDD.

4. cognitivefxusa.com cognitivefxusa.com/blog/tms-success-rates-for-depression

TMS Success Rates for Depression: Compare TMS Types In a randomized sham-controlled trial, 82% of patients responded and 65% achieved remission after 30 sessions of dTMS. Even just 20 sessions ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0165178123004328

Real world efficacy and safety of various accelerated deep ... Accelerated Deep TMS with the H1 coil has an 80% response and 51% remission rate. · The six-month durability of accelerated Deep TMS is 93%. · Controlled dosing ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1876201824001254

Deep transcranial magnetic stimulation for treatment ... Active dTMS can be a safe and effective treatment for patients with TRD. The active dTMS group showed notably higher antidepressant response rates and ...

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

Transcranial magnetic stimulation Approved by the U.S. Food and Drug Administration (FDA), TMS usually is used only when other depression treatments haven't been effective.

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38337509/

Safety and Efficacy of Deep TMS for Late-Life Depression Deep TMS is a safe, well-tolerated and effective treatment for this expanded age range of older adults.