rTMS for Depression

(R01RF Trial)

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, Los Angeles

Must be taking: Antidepressants

Must not be taking: Seizure-inducing medications

Disqualifiers: Psychotic disorders, Neurological conditions, others

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

Compensation: Varies

Number of Visits: 10

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a personalized brain stimulation method to treat major depressive disorder (MDD) using repetitive transcranial magnetic stimulation (rTMS). Researchers aim to determine the optimal stimulation frequency for each participant by testing three different frequencies on the brain's left dorsolateral prefrontal cortex, a region linked to mood regulation. Individuals who have not responded to at least two types of antidepressant medications and have severe MDD might be suitable candidates. Participants will attend up to seven in-person visits over four weeks, which include brain scans and rTMS sessions. As an unphased trial, this study offers participants the chance to contribute to pioneering research that could lead to new treatment options for MDD.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants must have failed to respond to at least two different classes of antidepressant medications, suggesting that some medications might be continued. It's best to discuss your specific medications with the trial coordinators.

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

Research has shown that repetitive transcranial magnetic stimulation (rTMS) is generally safe for treating major depressive disorder (MDD). Studies have found that rTMS significantly reduces symptoms of depression. Most participants experienced only mild side effects, such as headaches or scalp discomfort, while serious side effects were rare.

One study found that low-frequency rTMS did not harm brain function in teenagers, suggesting it is safe for the brain. Another analysis showed that using 10 Hz rTMS, similar to the frequency used in this trial, was as effective as other treatments for reducing depression and anxiety symptoms, without major safety concerns.

Overall, these findings suggest that rTMS is well-tolerated, with only minor side effects reported. This provides strong evidence of its safety in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Resonant Frequency rTMS for depression because it offers a new approach compared to standard treatments like antidepressants and traditional rTMS. Unlike these existing options, Resonant Frequency rTMS tailors the frequency of stimulation to each individual's brain activity, potentially enhancing effectiveness. This personalized method could lead to faster and more significant improvements in depressive symptoms with fewer side effects. Additionally, while many antidepressants take weeks to show effects, Resonant Frequency rTMS has the potential to provide relief much sooner.

What evidence suggests that this rTMS approach is effective for depression?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) can help treat major depressive disorder (MDD). In one study, rTMS reduced depression symptoms in about 40-42% of patients. Another study found that both personalized and standard 10 Hz rTMS were equally effective in improving depressive symptoms. However, one study found no clear benefit of personalized rTMS over the standard method. In this trial, participants will undergo six 3000-pulse rTMS sessions, including two at RFMAX, two at RFMIN, and two at 10 Hz, to evaluate the effectiveness of these different approaches. Overall, rTMS is known to help relieve symptoms of MDD, but individual results may vary. ^{1 3 4 6 7}

Who Is on the Research Team?

Joe Gibbs

Principal Investigator

University of California, Los Angeles

Are You a Good Fit for This Trial?

This trial is for individuals with Major Depressive Disorder (MDD) who are interested in a novel brain stimulation treatment. Participants will need to commit to multiple sessions and assessments over 4 weeks, including MRI scans and EEGs.

Inclusion Criteria

My main diagnosis is Major Depressive Disorder.

Subjects are willing and able to adhere to the treatment schedule and required study visits

I have been diagnosed with severe depression.

Exclusion Criteria

Current diagnosis of substance use disorder

I am experiencing psychotic symptoms during my current depressive episode.

I am able to understand and give consent for my treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Assessment

Participants undergo MRI and EEG to identify resonant frequencies

1 week

3 visits (in-person)

Treatment

Participants receive six rTMS treatment sessions at different frequencies

2 weeks

6 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

• Resonant Frequency rTMS

Trial Overview

The study tests personalized repetitive transcranial magnetic stimulation (rTMS) frequencies targeting the left dorsolateral prefrontal cortex. It compares three different rTMS frequencies: one that maximizes brain circuit engagement, one that's least engaging, and a standard frequency of 10 Hz.

How Is the Trial Designed?

Group I: Experimental RF Experimental Treatment 1 Intervention

All participants will then undergo six 3000-pulse rTMS "treatment" sessions: two at RFMAX (or rTMSRF-MAX), two at RFMIN (or rTMSRF-MIN), and two at 10 Hz in random order.

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

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]

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]

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 232 depressive patients, high-frequency repetitive transcranial magnetic stimulation (rTMS) was found to be a feasible and safe treatment option, with no severe side effects reported and only four patients discontinuing due to side effects.

Patients showed an average improvement of 9.0 points on the Hamilton Depression Rating Scale after receiving an average of 13 rTMS sessions, with 53 patients experiencing a 50% or greater reduction in their depression scores, indicating significant efficacy in a real-world clinical setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation for the treatment of depression: feasibility and results under naturalistic conditions: a retrospective analysis. Frank, E., Eichhammer, P., Burger, J., et al.[2021]

In a study of 247 patients with major depressive disorder, repetitive transcranial magnetic stimulation (rTMS) achieved a high clinical remission rate of 72% within an average of 3.1 weeks, indicating its effectiveness in treating severe depression.

The study found that patients treated with the MagVenture rTMS instrument had greater remission rates compared to those treated with the NeuroStar instrument, suggesting that the choice of rTMS device and treatment parameters can influence clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation (rTMS) using different TMS instruments for major depressive disorder at a suburban tertiary clinic. Davila, MC., Ely, B., Manzardo, AM.[2020]

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]

Citations

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11913841/

A naturalistic analysis of rTMS treatment outcomes for ...

A 4–7-week course of rTMS significantly reduce symptoms of self-reported depression (42.5% response) and clinician-assessed depression (40.7% response).

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11841443/

A meta-analysis comparing the effectiveness and safety of ...

The results demonstrated that both intensive TBS and 10 Hz rTMS provided similar clinical efficacy, improving depressive and anxiety symptoms, ...

3.

sciencedirect.com

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

Effectiveness of personalized repetitive transcranial ...

This study found no evidence that personalized protocols outperform fixed protocols. Structural MRI-guided rTMS showed no advantage over fixed rTMS.

4.

brainstimjrnl.com

brainstimjrnl.com/article/S1935-861X(21)00588-X/fulltext

Identifying Resonant Frequencies for Treatment of Major ...

Background: Repetitive Transcranial Magnetic Stimulation (rTMS) is an effective treatment for Major Depressive Disorder (MDD), but therapeutic benefit is highly ...

5.

jamanetwork.com

jamanetwork.com/journals/jamanetworkopen/fullarticle/2835319

Repetitive Transcranial Magnetic Stimulation as ...

Although tapering with high-frequency rTMS was effective in preventing relapse, the relapse rate ranged from 16% to 60%. In contrast, we used ...

6.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0165032724018317

Efficacy and safety of low-frequency repetitive transcranial ...

LF-rTMS is generally safe, with mild adverse effects and no negative impact on neurocognitive performance for adolescents with FE-MDD.

7.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0165032725015745

Efficacy and safety of transcranial magnetic stimulation in ...

Conclusions. Our meta-analysis demonstrates that TMS is safe and effective for depressed children and youths, particularly HF-rTMS. Further ...