Transcranial Magnetic Stimulation for Depression

Recruiting at 1 trial location

Overseen By Sean M Nestor, MD PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Sunnybrook Health Sciences Centre

Disqualifiers: Substance use, Neurological diseases, Hypertension, 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: 5

Duration: 1 week

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called repetitive transcranial magnetic stimulation (rTMS) to assess its effects on brain function in people with depression. Researchers aim to determine if rTMS can improve symptoms by addressing brain network disruptions related to mood and behavior. The trial employs a quick brain scan method to monitor changes in brain activity and predict potential responders to the treatment. Individuals diagnosed with depression and currently receiving rTMS treatment may be suitable candidates for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants an opportunity to contribute to groundbreaking research.

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 study team or your doctor.

What prior data suggests that transcranial magnetic stimulation is safe for treating depression?

Research shows that repetitive transcranial magnetic stimulation (rTMS) is generally safe for treating depression. Studies have found that newer types of TMS, such as cluster maintenance and gradual tapering methods, are both effective and safe. For instance, one study found that rTMS significantly reduced the risk of depression recurrence, with high success rates in preventing relapse.

Another study showed that about 50% of patients experienced long-lasting benefits from repeated TMS treatments, even without additional antidepressant medication. Importantly, TMS is widely considered safe, and evidence suggests it is well-tolerated by most patients.

These findings indicate that rTMS is a promising option for treating depression, with a strong safety record. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these transcranial magnetic stimulation (TMS) treatments for depression because they offer new ways to deliver therapy that could improve patient outcomes. Unlike traditional antidepressants that rely on chemical changes in the brain, TMS uses magnetic pulses to directly stimulate brain activity, potentially offering faster and more targeted relief. The Cluster Maintenance TMS approach provides an intensive burst of treatments over two days, which may help sustain effects better than sporadic sessions. Meanwhile, the Gradual Tapering TMS approach eases patients off treatment more gradually, which might reduce the risk of relapse. These innovative protocols aim to enhance the effectiveness and convenience of depression treatment, addressing limitations of existing options like medications and electroconvulsive therapy.

What evidence suggests that repetitive transcranial magnetic stimulation (rTMS) might be an effective treatment for depression?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) effectively treats depression. Studies have found that in real-world settings, rTMS leads to improvement in 58% to 83% of people and complete relief of symptoms in 28%. In this trial, participants will receive either Cluster Maintenance TMS or Gradual Tapering TMS. Specifically, about 40.9% of people see improvement with Cluster Maintenance TMS after 12 months. Gradual Tapering TMS maintains significant improvement in about 50% of patients. Overall, rTMS is becoming a common treatment for those who do not respond to traditional depression therapies, with improvement rates between 40% and 60%. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This clinical trial is for individuals experiencing depression. Participants will undergo a non-invasive treatment called repetitive transcranial magnetic stimulation (rTMS). The study requires participants to have their brain activity monitored using a quick and easy EEG technology.

Inclusion Criteria

Able to provide informed consent and comply with the study protocol

Physically healthy

I am currently undergoing rTMS treatment for depression.

Exclusion Criteria

Moderate substance use disorder or greater severity based on DSM 5.0 criteria and confirmed by a study MD on clinical assessment

Pregnant

A major comorbid psychiatric disorder (as determined by investigators - e.g., schizophrenia or bipolar disorder) and/or psychosis at the time of study enrollment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo an accelerated rTMS protocol over five days, targeting the DLPFC, with pre-treatment imaging to localize the brain region.

1 week

5 visits (in-person)

Follow-up

Participants are monitored for recurrence of depressive symptoms and undergo maintenance TMS treatment if symptoms worsen.

12 months

Regular follow-up visits

Maintenance Treatment

Participants receive either a gradually tapering TMS protocol or a cluster protocol to maintain symptom relief.

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Repetitive Transcranial Magnetic Stimulation (rTMS)

Trial Overview The trial is testing the impact of rTMS on brain function in people with depression. Researchers are using a new, faster method of EEG to track changes in brain activity related to cognitive, emotional, and behavioral regulation during and after treatment.

How Is the Trial Designed?

Group I: Cluster Maintenance TMS Active Control 1 Intervention

Participants will receive a cluster of treatments consisting of 5 treatments over two consecutive week days (either 2 treatments on day 1 followed by 3 treatments day 2 or vice-versa, based on scheduling)

Group II: Gradual Tapering TMS Active Control 1 Intervention

Participants will receive a once daily treatment protocol delivered once weekly for 1 month, and gradually tapering the frequency of treatment to 1 treatment every 2 weeks for 2 months

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

Approved in United States as rTMS for:

• Depression
• Smoking cessation

Approved in European Union as rTMS for:

• Depression

Approved in Canada as rTMS for:

• Depression

Approved in Japan as rTMS for:

• Depression

Who Is Running the Clinical Trial?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Recruited

1,569,000+

iMediSync

Collaborator

Trials

2

Recruited

600+

Mitacs

Industry Sponsor

Trials

46

Recruited

5,200+

Published Research Related to This Trial

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]

High-frequency rTMS targeting the left dorsolateral prefrontal cortex is an effective treatment for major depressive disorder, supported by over 15 years of research and the authors' 10 years of clinical experience.

While other rTMS techniques, such as low-frequency stimulation to the right prefrontal cortex, show potential, they need further evaluation in larger trials to confirm their efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A practical guide to the use of repetitive transcranial magnetic stimulation in the treatment of depression. Fitzgerald, PB., Daskalakis, ZJ.[2022]

Repetitive transcranial magnetic stimulation (rTMS) is a promising therapy for depression that may selectively modulate neuronal activity with fewer side effects compared to electroconvulsive therapy (ECT).

While rTMS shows potential efficacy similar to ECT in open trials for non-psychotic depression, its benefits in double-blind studies are more modest, indicating that further optimization and research are needed to fully realize its therapeutic potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation in the treatment of mood disorder: a review and comparison with electroconvulsive therapy. Hasey, G.[2017]

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 shown clinically relevant antidepressant effects, making it a promising treatment option for patients with therapy-resistant depression, who often have limited alternatives.

While rTMS should be introduced into clinical practice, it is essential to continue research and evaluation to ensure its effectiveness and manage patient expectations appropriately.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is it time to introduce repetitive transcranial magnetic stimulation into standard clinical practice for the treatment of depressive disorders? Fitzgerald, P.[2017]

In a 6-month follow-up study of 31 patients with major depression who completed a 4-week rTMS trial, 63.64% of those who initially did not respond to treatment became late responders, indicating potential for continued improvement after treatment ends.

The study also found a low relapse rate of only 10% among those who initially responded to rTMS, with an overall high rate of maintained response at 90%, suggesting that rTMS can have lasting effects in treating major depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 6-month follow-up study on response and relapse rates following an acute trial of repetitive transcranial magnetic stimulation in patients with major depression. Arici, C., Benatti, B., Cafaro, R., et al.[2022]

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]

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]

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]

In a sham-controlled study involving 29 patients with depression (79% treatment-resistant), fast, left frontal repetitive transcranial magnetic stimulation (rTMS) was found to be more effective than sham treatment, with a response rate of 77% compared to 55% (P<0.05).

The treatment was generally well tolerated, and the improvements in depression symptoms were maintained for up to 12 weeks, suggesting that rTMS could be a valuable addition to existing depression therapies, although further research is needed to optimize treatment parameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjunctive fast repetitive transcranial magnetic stimulation in depression. Anderson, IM., Delvai, NA., Ashim, B., et al.[2018]

In a study involving 19 patients who had previously responded to rTMS, treatment for 30 episodes of depressive relapse showed significant improvement in symptoms, indicating its effectiveness for recurring depression.

The results suggest that rTMS maintains its efficacy over time, with patients benefiting from both low-frequency right-sided and high-frequency left-sided stimulation during their treatment courses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naturalistic study of the use of transcranial magnetic stimulation in the treatment of depressive relapse. Fitzgerald, PB., Benitez, J., de Castella, AR., 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10273734/

Maintenance repetitive transcranial magnetic stimulation ... Applying the Weibull distribution to the 3- and 6-month response rates, the 12-month response rate was estimated to be 40.9% for the maintenance ...

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2835319

Repetitive Transcranial Magnetic Stimulation as ... This randomized clinical trial of 75 participants with TRD showed that rTMS and lithium had comparable efficacy in preventing TRD relapse.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5802466/

Clustered repetitive transcranial magnetic stimulation for ... The acute and short-term antidepressant efficacy of rTMS has been well established in both depressed patients and experimental animal models.

4. sciencedirect.com sciencedirect.com/science/article/pii/S1388245724003766

Consensus review and considerations on TMS to treat ... One large, retrospective study (n = 5,010) of “real-world” patients receiving rTMS for depression reported response rates of 58–83 % and remission rates of 28– ...

5. aetna.com aetna.com/cpb/medical/data/400_499/0469.html

Transcranial Magnetic Stimulation and Cranial Electrical ... TMS or tDCS combined with MAT significantly reduced craving-related measures relative to sham stimulation (Hedges' g = -0.42, CI: -0.73 to -0.11, p < 0.01).

6. tandfonline.com tandfonline.com/doi/full/10.1080/15622975.2024.2416385

Weekly transcranial magnetic stimulation (TMS) maintenance Of those with MDD, 60% will experience a relapse and 90% of those who experience three episodes will suffer further episodes (Lye et al.