rTMS for Treatment-Resistant Depression

Overseen By Anusha Baskaran, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Sunnybrook Health Sciences Centre

Disqualifiers: Psychosis, Pregnancy, Substance dependence, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 1 week

88 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach for people with severe depression that hasn't improved with standard treatments. It uses a method called rTMS (Repetitive Transcranial Magnetic Stimulation), a non-invasive way to stimulate the brain, to determine if it can help those who might otherwise need brain surgery. The trial aims to understand if severe depression has a unique brain pattern and whether this method can offer relief. It suits individuals who have experienced depression for 5 or more years and have not found success with multiple medications or therapies. Participants will receive an accelerated version of rTMS over five consecutive days. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could redefine treatment options for severe depression.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, since the study involves treatment-resistant depression, it might be possible to continue some medications. Please consult with the study team for specific guidance.

What prior data suggests that this protocol is safe for treating depression?

Research has shown that repetitive Transcranial Magnetic Stimulation (rTMS) is generally safe for people with treatment-resistant depression (TRD). One study found that patients with TRD who received rTMS experienced safety outcomes similar to those taking lithium, a common depression medication. Another study demonstrated that low-frequency rTMS was as effective and safe as the medication venlafaxine for TRD.

Overall, patients usually tolerate rTMS well, with most experiencing only minor side effects. Some might feel mild discomfort or a tapping sensation on the head during sessions, but serious side effects are rare. Many people notice their depression symptoms improve or even disappear after several weeks of rTMS treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about accelerated iTBS (intermittent Theta Burst Stimulation) for treatment-resistant depression because it offers a new approach compared to traditional treatments like antidepressant medications and standard rTMS (repetitive Transcranial Magnetic Stimulation). While most treatments for depression can take weeks to show effectiveness, accelerated iTBS has the potential to deliver results in just five consecutive days, which could significantly reduce the waiting time for relief. Additionally, this protocol uses a unique pattern of magnetic pulses that might enhance brain plasticity, potentially leading to more effective and longer-lasting improvements in mood. This innovative approach could be a game-changer for patients who haven't found relief through conventional methods.

What evidence suggests that rTMS might be an effective treatment for treatment-resistant depression?

Research has shown that accelerated intermittent theta-burst stimulation (a-iTBS), tested in this trial, can help people with treatment-resistant depression (TRD). In one study, 79% of participants experienced complete relief from their depression, outperforming other treatments. Another study found that 69.2% of participants showed improvement, with 46.2% experiencing complete relief four weeks after treatment. These studies suggest that a-iTBS can significantly reduce depression symptoms, even for those unresponsive to other treatments. Another trial demonstrated that the benefits lasted up to four weeks. Overall, this research supports a-iTBS as a promising option for people with severe depression. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for adults aged 20-65 with severe, long-lasting depression that hasn't improved after trying at least six different antidepressants and other treatments like psychotherapy or ECT. They must have a specific score on a depression rating scale to qualify. People can't join if they're pregnant, unable to consent, have MRI contraindications, other major medical/psychiatric issues not related to depression, history of psychosis or substance dependence recently.

Inclusion Criteria

I am between 20 and 65 years old.

I have tried at least one antidepressant without success and have never had brain stimulation treatments.

I have been diagnosed with major depression or persistent depressive disorder, and my condition is moderate to severe.

Exclusion Criteria

I cannot give my own consent for medical procedures.

Contraindications to MRI

Pregnant

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Imaging

Baseline brain imaging to localize the brain region targeted by the TMS coil

1 week

1 visit (in-person)

Treatment

Participants undergo an accelerated rTMS protocol over 5 consecutive days

1 week

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• rTMS

Trial Overview The study tests an 'accelerated' rTMS protocol using brain imaging before treatment. It aims to see if those with ultra-treatment resistant depression respond differently than those with less severe cases and whether this intense one-week rTMS treatment can help where surgery might be the next option.

How Is the Trial Designed?

Group I: Accelerated iTBS treatment Experimental Treatment 1 Intervention

accelerated iTBS treatment protocol over 5 consecutive days

rTMS is already approved in United States, European Union for the following indications:

Approved in United States as rTMS for:

• Obsessive-Compulsive Disorder (OCD)
• Major Depressive Disorder
• Migraines
• Smoking cessation

Approved in European Union as rTMS for:

• Obsessive-Compulsive Disorder (OCD)
• Major Depressive Disorder

Who Is Running the Clinical Trial?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Recruited

1,569,000+

Published Research Related to This Trial

A study involving 145 first-time patients with treatment-resistant depression found that 15-minute rTMS sessions were as effective as 30-minute sessions in achieving response and remission rates over 6 weeks.

Both treatment durations resulted in similar outcomes, with the 15-minute sessions showing a partial response rate of 28.2% and a remission rate of 21.8%, indicating that shorter sessions could allow for more patients to be treated with the same resources.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of 15 minute vs 30 minute repetitive transcranial magnetic stimulation sessions for treatment resistant depression - are longer treatment sessions more effective? Ford, H., Hahn, L., Clarke, P., et al.[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]

Repetitive transcranial magnetic stimulation (rTMS) significantly reduces depressive severity in patients with treatment-resistant depression (TRD), showing an average decrease of over 4 points on the Hamilton Depression Rating Scale compared to sham treatment.

Patients receiving rTMS are more than three times as likely to respond to treatment and over five times as likely to achieve remission compared to those receiving sham, indicating its strong efficacy as a nonpharmacologic option for those with multiple antidepressant treatment failures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation for treatment-resistant depression: a systematic review and meta-analysis. Gaynes, BN., Lloyd, SW., Lux, L., 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) has shown statistical superiority over sham therapy for treating depression, particularly with left-prefrontal high frequency stimulation, but the actual clinical benefits are often marginal.

Factors such as younger age, absence of treatment-resistant depression, and no psychotic features are associated with a better response to rTMS, highlighting the need for further research to optimize treatment parameters and confirm its clinical utility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation for depression. Mitchell, PB., Loo, CK.[2017]

In a pilot study involving 7 treatment-resistant depression patients, accelerated low-frequency right-sided rTMS was found to be safe, with all participants completing the treatment without adverse effects.

While there were significant reductions in depression scores (MADRS and BDI-II) by the end of the 10-day treatment, no patients achieved full response or remission, indicating the need for further research to confirm efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot Study of Accelerated Low-Frequency Right-Sided Transcranial Magnetic Stimulation for Treatment-Resistant Depression. Tor, PC., Gálvez, V., Goldstein, J., et al.[2017]

In a study involving 141 patients with treatment-resistant depression, 30.5% achieved remission after receiving an average of 26 fast left rTMS treatments, indicating that a higher number of stimulations may be necessary for effective treatment.

Additionally, 26% of patients who did not respond to fast left rTMS found remission when switched to slow right rTMS, suggesting that alternative rTMS protocols can be beneficial for those who initially fail to respond.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving the antidepressant efficacy of transcranial magnetic stimulation: maximizing the number of stimulations and treatment location in treatment-resistant depression. McDonald, WM., Durkalski, V., Ball, ER., et al.[2022]

In a study of 13 patients with treatment-resistant major depression, those who responded to repetitive transcranial magnetic stimulation (rTMS) had higher baseline blood flow in the left dorsolateral prefrontal cortex (DLPFC) compared to non-responders.

The findings suggest that baseline cerebral perfusion patterns may serve as potential biomarkers for predicting rTMS treatment response, although the study's small sample size limits the generalizability of these results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prefrontal cortical blood flow predicts response of depression to rTMS. Weiduschat, N., Dubin, MJ.[2022]

This study is a large-scale, multicenter clinical trial involving 360 Veterans with treatment-resistant major depression (TRMD) to evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) compared to sham treatment over 30 sessions.

The trial uniquely includes Veterans with posttraumatic stress disorder (PTSD) and substance abuse histories, aiming to assess a wide range of predictors for treatment response, with the primary outcome being the remission rate measured by the Hamilton Rating Scale for Depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant major depression (TRMD) Veteran patients: study protocol for a randomized controlled trial. Mi, Z., Biswas, K., Fairchild, JK., et al.[2018]

In a study of 22 outpatients with treatment-resistant depression, repetitive transcranial magnetic stimulation (rTMS) was found to be safe and effective, with 50% of participants responding positively and 40.9% achieving remission after 4 weeks of treatment.

The treatment led to a significant reduction in depression scores, with no major side effects reported, indicating that rTMS could be a viable option for patients who have not responded to traditional antidepressant medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation (5 and 10 Hz) With Modified Parameters in the Treatment of Resistant Unipolar and Bipolar Depression in a Private Practice Setting. Rachid, F., Moeglin, C., Sentissi, O.[2019]

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 18 medication-resistant depressed subjects, both real and sham rTMS treatments led to significant mood improvements over 2 weeks, but there was no notable difference in effectiveness between the two groups.

The 4-week course of rTMS was found to be safe, indicating that while it may not be more effective than sham treatment, it does not pose additional risks to patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind controlled investigation of transcranial magnetic stimulation for the treatment of resistant major depression. Loo, C., Mitchell, P., Sachdev, P., et al.[2021]

In a pilot study involving 19 medication-resistant depressed subjects, bilateral prefrontal repetitive transcranial magnetic stimulation (rTMS) did not show superior efficacy compared to sham treatment over 3 weeks, as both groups experienced similar improvements in mood.

Despite the lack of significant differences in mood improvement, rTMS was found to be safe, with no neuropsychological impairments reported in either the active or sham treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind controlled investigation of bilateral prefrontal transcranial magnetic stimulation for the treatment of resistant major depression. Loo, CK., Mitchell, PB., Croker, VM., et al.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40042840/

Accelerated Theta-Burst Stimulation for Treatment ... A pragmatic aTBS protocol using only 3 iTBS sessions per day and a nonexpensive, non-neuronavigated approach was found to be safe and effective for TRD.

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2830095

Accelerated Intermittent Theta-Burst Stimulation for ... Within-group improvements for active aiTBS indicated a significant and sustained reduction in depression severity at 1 and 4 weeks. Several ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006322325013563

Efficacy and Safety of Accelerated Intermittent Theta-burst ... In this trial, a-iTBS, administered five sessions per day for ten days, is effective and safe for adolescents with non-treatment-resistant MDD.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11238064/

Accelerated Intermittent Theta-Burst Stimulation and ... Ten sessions per day for 5 days achieved 79% remission in a sham-controlled randomized clinical trial—substantially better than remission rates ...

5. psychiatryonline.org psychiatryonline.org/doi/full/10.1176/appi.ajp.2021.21121221

Accelerated Intermittent Theta Burst Stimulation In terms of the primary outcomes, the authors reported an impressive 69.2% response rate and a 46.2% remission rate 4 weeks after treatment, ...

6. 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.

7. 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 ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25192980/

the results from a large multicenter French RCT Conclusion: Low frequency rTMS appears to be as effective as venlafaxine and as effective as the combination of both treatments for TRD. Because of its short ...

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

Transcranial magnetic stimulation Results. If rTMS works for you, your depression symptoms may improve or go away completely. Symptom relief may take a few weeks of treatment.

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

Efficacy of repetitive transcranial magnetic stimulation ... Based on the 9 analyzed studies, nearly 36% of the TRD patients with rTMS treatment achieved remission, while barely 8% in the placebo group ( ...