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

84 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of the study is to develop a more personalized brain stimulation using repetitive transcranial magnetic stimulation or rTMS approach to treat major depressive disorder (MDD). The investigators had previously developed a personalized rTMS treatment by examining the effectiveness of different rTMS frequency from 5 to 18 Hertz (Hz). The optimal treatment frequency is termed resonance frequency and varies across individuals. There has not been a systematic method to identify the best stimulation frequency in an individual-specific way. In this project, the investigators will identify and compare 3 rTMS frequencies, all targeting the brain region called left dorsolateral prefrontal cortex (DLPFC): 1 that engages brain circuit connectivity the most- the investigators call this resonant frequency (RF)-max (RF-max), 1 that is the lowest ranked resonance frequency called RF-min and 1 that is standard of care treatment - rTMS of 10 Hz as a point of comparison. This study is a multi-sites project that will be conducted at UCLA and Butler hospital. This study will enroll 84 participants with MDD over the course of 4.5 years. Participants will undergo a brain imaging scan or magnetic resonance imaging (MRI), 3 electroencephalograms (or EEG, a measurement of electrical activity of the brain), to identify rTMS resonance frequencies (RFs), 3 sessions of different resonant frequencies of rTMS in combination with EEG, totaling up to 7 in person visits. Participation will take up to 4 weeks.

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 data supports the effectiveness of the treatment Resonant Frequency rTMS for depression?

Research shows that repetitive transcranial magnetic stimulation (rTMS) is effective in treating major depression, with studies reporting significant improvements in depression symptoms and high remission rates. For example, one study found a 72% remission rate in patients with severe depression, while another reported response rates of over 50% after rTMS treatment. ^{1 2 3 4 5}

Is rTMS safe for humans?

Repetitive transcranial magnetic stimulation (rTMS) is generally considered safe when used according to guidelines, with common side effects being minor, like headaches. There is a low risk of seizures and mood changes, but these are rare and can be managed by screening for risk factors. ^{5 6 7 8 9}

How does Resonant Frequency rTMS treatment for depression differ from other treatments?

Resonant Frequency rTMS is unique because it uses specific frequencies of magnetic pulses to target brain areas associated with depression, offering a non-invasive alternative to medication. Unlike traditional treatments, it can be tailored to individual brain activity patterns, potentially improving effectiveness for those who haven't responded to other therapies. ^{10 11 12 13 14}

Research Team

Joe Gibbs

Principal Investigator

University of California, Los Angeles

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy of adjunctive high frequency repetitive transcranial magnetic stimulation of left prefrontal cortex in depression: a randomized sham controlled study. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation (rTMS) using different TMS instruments for major depressive disorder at a suburban tertiary clinic. [2020]

3. Ireland pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation for major depression: A naturalistic observational study in an Australian private hospital. [2020]

4. Australia pubmed.ncbi.nlm.nih.gov

Prognostic factors in major depressive disorder: comparing responders and non-responders to Repetitive Transcranial Magnetic Stimulation (rTMS), a naturalistic retrospective chart review. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation for depression. [2017]

6. England pubmed.ncbi.nlm.nih.gov

A review of the safety of repetitive transcranial magnetic stimulation as a clinical treatment for depression. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation (TMS) safety: a practical guide for psychiatrists. [2019]

8. United States 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. [2019]

9. Korea (South) pubmed.ncbi.nlm.nih.gov

Treatment-Resistant Depression Entering Remission Following a Seizure during the Course of Repetitive Transcranial Magnetic Stimulation. [2020]

10. England pubmed.ncbi.nlm.nih.gov

A randomized trial of low-frequency right-prefrontal-cortex transcranial magnetic stimulation as augmentation in treatment-resistant major depression. [2021]

11. Netherlands pubmed.ncbi.nlm.nih.gov

An update on the clinical use of repetitive transcranial magnetic stimulation in the treatment of depression. [2021]

12. Germany pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation for the treatment of depression: feasibility and results under naturalistic conditions: a retrospective analysis. [2021]

13. Ireland pubmed.ncbi.nlm.nih.gov

High (20-Hz) and low (1-Hz) frequency transcranial magnetic stimulation as adjuvant treatment in medication-resistant depression. [2022]

14. Switzerland pubmed.ncbi.nlm.nih.gov

Ultra-high-frequency left prefrontal transcranial magnetic stimulation as augmentation in severely ill patients with depression: a naturalistic sham-controlled, double-blind, randomized trial. [2012]