rTMS Therapy for Depression

(SUNSET Trial)

Overseen By Tien Dam

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Francisco

Disqualifiers: Psychotic disorders, Neurological conditions, Substance 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: 33

Duration: 6-8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how repetitive transcranial magnetic stimulation (rTMS) can help treat Major Depressive Disorder (MDD). Researchers aim to identify brain markers that indicate a person's response to this treatment. Participants will undergo brain scans before, during, and after daily rTMS sessions, scheduled either in the morning or afternoon. Ideal candidates are those with moderate to severe depression who haven't found relief after trying 1-4 antidepressant medications. As an unphased trial, this study offers a unique opportunity for patients to contribute to groundbreaking research that could lead to new treatment insights.

Will I have to stop taking my current medications?

The trial does not require you to stop taking your current medications. If you are on a regimen of psychotropic medication, you should not make any changes to it during the study.

What prior data suggests that rTMS therapy is safe for treating depression?

Studies have shown that rTMS therapy is generally safe for treating depression. Research indicates that the risk of serious side effects, such as seizures, is less than 1%. Most side effects are mild and temporary, like headaches. A review of several studies found that combining rTMS with antidepressants can improve symptoms in people with depression. These findings suggest that patients tolerate rTMS well. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about rTMS therapy for depression because it offers a non-invasive alternative to traditional treatments like antidepressant medications and psychotherapy. Unlike these common options, rTMS directly targets the dorsolateral prefrontal cortex in the brain using magnetic pulses to potentially alter brain activity more precisely. This approach might lead to faster results and fewer side effects, making it a promising option for individuals who haven't responded well to standard treatments. By monitoring brain changes through EEG and MRI scans, researchers hope to better understand how rTMS impacts brain structure and function over time.

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

Research has shown that repetitive transcranial magnetic stimulation (rTMS) can help treat depression. Studies found that about 85% of patients using only rTMS prevented their depression from returning after 24 weeks. Other research indicates that about 36% of people experienced a significant reduction or complete disappearance of their depression symptoms with rTMS. This means that for some, their depression improves or even resolves. Results can vary, and improvement might take a few weeks to notice. Overall, rTMS appears promising, especially for those whose depression hasn't improved with other treatments. In this trial, participants will receive rTMS treatment either in the morning or afternoon to evaluate the effectiveness of different timing schedules. ^{2 3 6 7 8}

Who Is on the Research Team?

Andrew Krystal, MD, MS

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for adults aged 18-70 with Major Depressive Disorder currently experiencing a depressive episode without psychotic features. Participants must have moderate to severe depression, have tried 1-4 antidepressants without success, and be stable on current medications if any. They should be able to undergo non-invasive brain stimulation and commit to research visits for about 8 weeks.

Inclusion Criteria

I am willing and able to have a treatment that involves stimulating my brain without surgery.

I've tried 1-4 antidepressants without success in this episode.

Has MADRS of > 19 at baseline, corresponding with moderate to severe depression

Exclusion Criteria

Presence of an implanted magnetic-sensitive medical device in or near the head, including but not limited to pacemaker, vagus nerve stimulator, or metal aneurysm clips or coils, staples, or stents

Inability to comply with study daily visits

Inability to speak and/or read English

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Evaluation

Participants undergo baseline evaluation including resting-state fMRI, DTI, and EEG scans prior to TMS treatment

1 week

1 visit (in-person)

Treatment

Participants receive 30-40 daily sessions of rTMS to the dorsolateral prefrontal cortex, with mid- and post-treatment fMRI, DTI, and EEG scans

6-8 weeks

30-40 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including post-treatment evaluations

4 weeks

1-2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• rTMS therapy

Trial Overview

The study tests the effectiveness of rTMS therapy in treating Major Depressive Disorder by monitoring changes in brain activity through imaging techniques. It aims to identify reliable biomarkers that can predict treatment response and aid clinical diagnosis.

How Is the Trial Designed?

Group I: Morning rTMS treatment Experimental Treatment 1 Intervention

Eligible participants will be assigned to the afternoon treatment group. Prior to the onset of rTMS treatment, EEG scans and magnetic resonance imaging (MRI) sessions including diffusion weighted imaging will be recorded as baseline measures. These measures will also be repeated at treatment midpoint and within one month of rTMS discontinuation in order to track structural and functional changes that occur over the course of treatment. Participants will complete an initial screening followed by 30-40 daily sessions of repetitive transcranial magnetic stimulation (rTMS) to the dorsolateral prefrontal cortex (DLPFC), completed with their TMS provider.

Group II: Afternoon rTMS treatment Experimental Treatment 1 Intervention

Eligible participants will be assigned to the afternoon treatment group. Prior to the onset of rTMS treatment, EEG scans and magnetic resonance imaging (MRI) sessions including diffusion weighted imaging will be recorded as baseline measures. These measures will also be repeated at treatment midpoint and within one month of rTMS discontinuation in order to track structural and functional changes that occur over the course of treatment. Participants will complete an initial screening followed by 30-40 daily sessions of repetitive transcranial magnetic stimulation (rTMS) to the dorsolateral prefrontal cortex (DLPFC), completed with their TMS provider.

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

Approved in United States as rTMS therapy for:

• Major Depressive Disorder (MDD)
• Treatment-resistant depression

Approved in European Union as rTMS therapy for:

• Major Depressive Disorder (MDD)
• Treatment-resistant depression

Approved in Canada as rTMS therapy for:

• Major Depressive Disorder (MDD)
• Treatment-resistant depression

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Published Research Related to This Trial

A systematic review of 98 randomized controlled trials on repetitive transcranial magnetic stimulation (rTMS) for major depressive disorder revealed that none of the interventions were fully described, which hinders their implementation in clinical practice.

After contacting authors for additional information, only 10.4% of interventions were completely described, highlighting the need for better adherence to reporting guidelines like the TIDieR checklist to ensure clarity and efficacy in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Completeness of Descriptions of Repetitive Transcranial Magnetic Stimulation Intervention: A Systematic Review of Randomized Controlled Trials of rTMS in Depression. Chantebel, R., Chesneau, A., Tavernier, E., et al.[2019]

Repetitive transcranial magnetic stimulation (rTMS) has shown effectiveness in treating depression, particularly in patients who have not responded well to conventional drug treatments.

A case study highlighted in the report demonstrates that a patient who experienced multiple relapses with standard medications responded positively to rTMS at three different times, suggesting its potential as a reliable alternative treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation is effective following repeated courses in the treatment of major depressive disorder--a case report. Dannon, PN., Grunhaus, L.[2014]

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]

Repetitive Transcranial Magnetic Stimulation (rTMS) shows potential efficacy in treating depression in older patients, with some studies indicating a decrease in depression scores, although only about 25% of patients experienced significant remission.

rTMS is generally safe and does not lead to cognitive deficits, even in elderly patients with cerebrovascular disease, but factors like older age and reduced frontal gray matter volume may negatively impact treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapeutic efficacy and safety of repetitive Transcranial Magnetic Stimulation in depressions of the elderly: a review]. Jalenques, I., Legrand, G., Vaille-Perret, E., et al.[2010]

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 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]

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]

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]

Accelerated rTMS treatment, involving 15 sessions over 3 days, led to a more rapid improvement in depressive symptoms compared to sham treatment, indicating its efficacy for patients with major depressive disorder (MDD).

The safety profile of accelerated rTMS was comparable to that of conventional rTMS, suggesting that it is a viable and more accessible treatment option for MDD patients, without increased adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid Symptom Improvement in Major Depressive Disorder Using Accelerated Repetitive Transcranial Magnetic Stimulation. Kim, SJ., Son, SJ., Jang, M., 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 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]

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]

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]

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