rTMS for Major Depressive Disorder

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Unity Health Toronto

Must be taking: Antidepressants

Must not be taking: Benzodiazepines

Disqualifiers: Pregnancy, Bipolar, Psychosis, Drug abuse, 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: 6 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores repetitive transcranial magnetic stimulation (rTMS) for individuals with major depressive disorder (MDD) who haven't found relief from standard antidepressants or therapy. rTMS uses magnetic pulses to stimulate less active brain areas in those with depression, potentially improving symptoms. Researchers are also examining how brain activity and certain proteins in saliva relate to rTMS effectiveness. Suitable candidates have moderate to severe depression and haven't succeeded with at least one antidepressant medication. As an unphased trial, this study offers a unique opportunity to enhance understanding of rTMS and its potential benefits for treatment-resistant depression.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must not have started or changed the dose of any psychotropic medication in the four weeks before joining the study.

What prior data suggests that rTMS is safe for treating Major Depressive Disorder?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) is generally safe for treating depression. One study found that 40–50% of people with major depressive disorder (MDD) responded well to rTMS, indicating it helps many patients. Another study found that rTMS works as well and is as safe as lithium, a common treatment for depression.

Some side effects occur, but they are usually mild. Patients might feel a tapping on their head or experience a headache after treatment. Serious side effects are rare. Overall, rTMS is considered a well-tolerated option for those who haven't found relief with other treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Repetitive Transcranial Magnetic Stimulation (rTMS) is unique because it offers a non-invasive way to treat Major Depressive Disorder by using magnetic fields to stimulate nerve cells in the brain. Unlike traditional treatments like antidepressants, which can take weeks to show results and often come with side effects, rTMS targets specific brain regions directly and may provide faster relief. Researchers are excited about rTMS as it has the potential to be a game-changer for individuals who haven't responded well to other treatments, providing a new hope in managing depression with minimal side effects.

What evidence suggests that rTMS is effective for Major Depressive Disorder?

Research shows that repetitive transcranial magnetic stimulation (rTMS), which participants in this trial may receive, effectively treats major depressive disorder (MDD). Studies indicate that about 36% of patients experience remission, with significant decreases in depression symptoms, compared to only about 8% of those not receiving rTMS. Real-world evidence supports this, showing that 40-50% of people respond positively to the treatment. Additionally, around 85% of patients using only rTMS can prevent symptom recurrence over six months. This treatment stimulates less active brain areas linked to depression, potentially improving symptoms by boosting brain activity in these regions. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for English-speaking adults aged 18-65 with moderate to severe depression, diagnosed as per specific criteria and who haven't responded well to antidepressants. Participants should not have had medication changes or started psychotherapy recently. Pregnant individuals, those at acute suicide risk, with certain psychiatric or major medical conditions, drug abuse history, or contraindications for rTMS or MRI are excluded.

Inclusion Criteria

I have been in stable psychotherapy for depression for at least 3 months with no expected changes.

I have never taken antidepressants.

I have depression and haven't responded well to at least two different antidepressants.

Exclusion Criteria

I do not have major health issues needing immediate treatment, a pacemaker, or an implanted medication pump.

I have never had psychosis, schizophrenia, schizoaffective disorder, or delusional disorder.

I have not had ECT for my current depressive episode.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive repetitive transcranial magnetic stimulation (rTMS) targeting the dorsolateral prefrontal cortex (DLPFC) to improve depression symptoms

6 weeks

5 visits per week (in-person)

Follow-up

Participants are monitored for safety and effectiveness after rTMS treatment, including brain scans and saliva sample analyses

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Brain Scan
• Repetitive Transcranial Magnetic Stimulation
• Research Interview, Questionnaires
• Saliva Samples

Trial Overview The study tests if stimulating the brain's dorsolateral prefrontal cortex (DLPFC) using repetitive transcranial magnetic stimulation (rTMS) can improve symptoms of treatment-resistant depression. It involves brain scans before and after treatment to observe changes in DLPFC activity and saliva samples to identify biomarkers related to response.

How Is the Trial Designed?

Group I: Depression Group Experimental Treatment 4 Interventions

Group II: Control Group Experimental Treatment 3 Interventions

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?

Unity Health Toronto

Lead Sponsor

Trials

572

Recruited

470,000+

Published Research Related to This Trial

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]

Repetitive transcranial magnetic stimulation (rTMS) has been shown to have a clear clinical effect in treating major depressive disorder, particularly with left high-frequency rTMS, based on a review of 24 meta-analyses.

The study suggests that rTMS is a justified treatment option for some patients with depression, while also highlighting the need for further research on its efficacy in different stimulation methods and in patients who have not previously received medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A happiness magnet? Reviewing the evidence for repetitive transcranial magnetic stimulation in major depressive disorder. Pridmore, W., Pridmore, S.[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]

A meta-analysis of 24 studies involving 911 patients found that maintenance rTMS can help stabilize mood symptoms for up to 5 months after an initial acute rTMS treatment for depression.

Patients receiving monthly or more frequent maintenance rTMS experienced sustained benefits for up to 6-12 months, while those without maintenance showed only minor changes in mood symptoms over the same period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trajectory of changes in depressive symptoms after acute repetitive transcranial magnetic stimulation: A meta-analysis of follow-up effects. Brian Chen, YC., Chou, PH., Tu, YK., et al.[2023]

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 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]

Repetitive transcranial magnetic stimulation (rTMS) has shown statistically significant effects in treating major depression, with 29 studies reviewed indicating that factors like high treatment resistance and advanced age negatively predict treatment response.

Effective rTMS treatment parameters include using stimulation intensity above 100% of the motor threshold and more than 1000 stimulations per session, with older patients requiring higher intensity due to cortical atrophy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Repetitive transcranial magnetic stimulation in major depression: response factor]. Dumas, R., Padovani, R., Richieri, R., et al.[2012]

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]

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]

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]

In a study of 40 patients with major depressive disorder (MDD), electroconvulsive therapy (ECT) was found to be more effective than repetitive transcranial magnetic stimulation (rTMS), especially in patients with MDD and psychosis.

For patients with MDD without psychosis, rTMS showed similar efficacy to ECT, suggesting that rTMS could be a viable treatment option for this subgroup, but further blinded studies are needed to clarify its role.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation is as effective as electroconvulsive therapy in the treatment of nondelusional major depressive disorder: an open study. Grunhaus, L., Dannon, PN., Schreiber, S., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10375664/

Efficacy of repetitive transcranial magnetic stimulation ... Data on remission rates were available from 9 studies. The overall remission rate was 35.71% (120/336) in the active rTMS group and 8.37% (18/ ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8474312/

Repetitive transcranial magnetic stimulation for major ... Real world data has also confirmed the effectiveness of rTMS for MDD in clinical practice, with the most recent literature indicating response rates of 40–50% ...

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

Repetitive Transcranial Magnetic Stimulation as ... The relapse prevention success rate at 24 weeks in the rTMS monotherapy group was approximately 85%, whereas prior literature indicates that the ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165032725005890

Effectiveness of personalized repetitive transcranial ... This double-blind RCT demonstrated that this approach resulted in a substantial improvement in depressive symptoms, with a reduction rate of 62 ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0165032720325933

Clinical outcomes in a large registry of patients with major ... Randomized clinical trials have demonstrated that Transcranial Magnetic Stimulation (TMS) is an effective treatment for episodes of major depressive disorder ( ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0272735822001210

Efficacy and safety of transcranial magnetic stimulation for ... Our results suggest the effects and safety of TMS in treating MDD are likely lower in some populations than previous estimates suggested. Future research ...

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

Transcranial magnetic stimulation Transcranial magnetic stimulation (TMS) is a procedure that uses magnetic fields to stimulate nerve cells in the brain to improve symptoms of major depression.