TMS for Depression

Recruiting at 1 trial location

Overseen By Jessica M Ross, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: VA Palo Alto Health Care System

Must not be taking: Seizure threshold reducers

Disqualifiers: Head trauma, Seizures, Neurological disease, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 45 minutes per session

250 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how different types of brain stimulation affect brain activity in adult military Veterans with depression. Researchers compare standard transcranial magnetic stimulation (TMS) with a new approach that combines TMS and music to determine which is more effective. Veterans who have served in the military and speak English are suitable candidates for this study. Researchers will monitor participants for any side effects during the sessions to ensure safety.

As an unphased trial, this study offers Veterans the chance to contribute to innovative research that could improve future depression treatments.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on medications that lower the seizure threshold, you may not be eligible to participate.

What prior data suggests that transcranial magnetic stimulation (TMS) is safe for adult military Veterans?

Studies have shown that standard transcranial magnetic stimulation (TMS) is a safe treatment for depression. Research found that patients with depression who used TMS along with antidepressants experienced a major improvement in their symptoms. Another study noted significant benefits for patients with major depressive disorder. While TMS is generally well-tolerated, some people might experience mild side effects like headaches or scalp discomfort.

For sensory-entrained TMS (seTMS), research indicates it effectively boosts brain activity. This method combines TMS with music to enhance results. Although less information exists on seTMS compared to standard TMS, early results suggest it might be a practical and safe option. Standard TMS is already approved for depression, demonstrating a strong safety record. Researchers monitored participants in the studies for any side effects, ensuring safety during the treatment process. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these TMS treatments for depression because they offer innovative approaches to brain stimulation. Unlike traditional treatments like medication or talk therapy, Standard TMS uses precise neuro-navigation based on MRI images to target brain areas, potentially improving its effectiveness. Sensory-entrained TMS (seTMS) is even more unique, combining music with TMS to align brain oscillations, which could enhance the treatment's impact. Both methods are noninvasive and have the potential to provide relief with fewer side effects, offering new hope for individuals with depression.

What evidence suggests that this trial's treatments could be effective for depression?

Research has shown that transcranial magnetic stimulation (TMS) can effectively treat depression. In several studies, patients experienced significant improvements in their symptoms after TMS treatment. For instance, one study found that about 85% of patients did not experience a return of symptoms within 24 weeks after TMS therapy. In this trial, participants will receive either standard TMS or sensory-entrained TMS (seTMS).

Sensory-entrained TMS (seTMS) is another method tested in this trial. It combines TMS with music to boost brain activity. Early research suggests that seTMS can effectively enhance brain responsiveness, which might help treat depression. More studies are needed, but these early results are promising for those considering seTMS for depression. ^{1 2 3 4 6}

Who Is on the Research Team?

Jessica M Ross, PhD

Principal Investigator

VA Palo Alto Health Care System, Palo Alto, CA

Are You a Good Fit for This Trial?

This trial is for English-speaking military veterans of any gender, aged 18 or older, who are experiencing major depressive disorder. Participants must not have a history of seizures, neurological diseases, active substance abuse, head trauma with loss of consciousness, and cannot be pregnant or breastfeeding. They also must be able to undergo MRI scans.

Inclusion Criteria

English speaking

Military Veterans

Exclusion Criteria

I have a history of seizures or take medication that lowers my seizure threshold.

Those with a contraindication for MRIs (e.g. implanted metal)

I do not have any uncontrolled neurological or medical conditions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive transcranial magnetic stimulation (TMS) using either standard TMS or sensory-entrained TMS (seTMS) protocols

45 minutes per session

Multiple sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• TMS

Trial Overview

The study is exploring how different types of transcranial magnetic stimulation (TMS), a non-invasive brain stimulation technique, affect brain activity in adults. The aim is to tailor personalized TMS treatments for depression based on these findings.

How Is the Trial Designed?

Group I: Standard TMS Active Control 1 Intervention

A series of standard TMS protocols will be delivered to determine target engagement compared to seTMS. TMS will be delivered using neuro-navigation based on participant's own MRI images. Intensity will be set to 120% of the participant's motor threshold. Participants will be monitored during the session for adverse events and/or side effects.

Group II: Sensory-entrained TMS (seTMS) Active Control 1 Intervention

Sensory entrained TMS (seTMS) is a combination of music and TMS to align brain oscillations and enhance the effects of TMS. seTMS will be delivered to determine target engagement to noninvasive seTMS brain stimulation compared to standard TMS. TMS will be delivered using neuro-navigation based on participant's own MRI images. Intensity will be set to 120% of the participant's motor threshold. Participants will be monitored during the session for adverse events and/or side effects.

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

Approved in United States as Transcranial Magnetic Stimulation for:

• Depression
• Anxiety disorders
• Post-traumatic stress disorder (PTSD)
• Obsessive-compulsive disorder (OCD)

Approved in European Union as Transcranial Magnetic Stimulation for:

• Depression
• Anxiety disorders
• Post-traumatic stress disorder (PTSD)
• Obsessive-compulsive disorder (OCD)

Approved in Canada as Transcranial Magnetic Stimulation for:

• Depression
• Anxiety disorders
• Post-traumatic stress disorder (PTSD)
• Obsessive-compulsive disorder (OCD)

Who Is Running the Clinical Trial?

VA Palo Alto Health Care System

Lead Sponsor

Trials

97

Recruited

58,500+

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Stanford University

Collaborator

Trials

2,527

Recruited

17,430,000+

Published Research Related to This Trial

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]

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]

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]

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]

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 a promising therapy for depression that may selectively modulate neuronal activity with fewer side effects compared to electroconvulsive therapy (ECT).

While rTMS shows potential efficacy similar to ECT in open trials for non-psychotic depression, its benefits in double-blind studies are more modest, indicating that further optimization and research are needed to fully realize its therapeutic potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation in the treatment of mood disorder: a review and comparison with electroconvulsive therapy. Hasey, G.[2017]

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 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]

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]

In a preliminary study involving four patients with relapsed major depressive disorder, rapid transcranial magnetic stimulation (rTMS) showed significant improvement in depression ratings after treatment.

The results indicated that rTMS can be effectively used again in patients who had previously responded well to this therapy, suggesting its potential for repeated use in managing relapsed depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation is effective in the treatment of relapse of depression. Dannon, PN., Schreiber, S., Dolberg, OT., et al.[2022]

In a study comparing the effects of electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) on major depression, both treatments showed similar outcomes at 3 and 6 months, with no significant differences in relapse rates or depression scores among the 41 patients involved.

Both treatment groups maintained low depression scores on the Hamilton Rating Scale and Global Assessment of Functioning, indicating that the benefits of rTMS are comparable to those of ECT over a 6-month period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three and six-month outcome following courses of either ECT or rTMS in a population of severely depressed individuals--preliminary report. Dannon, PN., Dolberg, OT., Schreiber, S., et al.[2019]

Recent studies on repetitive transcranial magnetic stimulation (rTMS) for depression have demonstrated significantly improved clinical outcomes, with a pooled effect size of -0.76 from 5 studies involving 274 patients, compared to -0.35 from earlier studies.

The findings indicate that new parameters of rTMS stimulation may enhance its antidepressant effects, suggesting a potential advancement in treatment strategies for depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Has repetitive transcranial magnetic stimulation (rTMS) treatment for depression improved? A systematic review and meta-analysis comparing the recent vs. the earlier rTMS studies. Gross, M., Nakamura, L., Pascual-Leone, A., et al.[2018]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12231655/

Sensory Entrained TMS (seTMS) Enhances Motor Cortex ...

These findings demonstrate that seTMS effectively enhances corticomotor excitability and establishes a practical, cost‐effective method for ...

2.

biorxiv.org

biorxiv.org/content/10.1101/2025.07.23.666433v1.full.pdf

Sensory Entrained TMS (seTMS) enhances motor cortex ...

Beyond motor applications, prefrontal iTBS has become an effective treatment for medication-resistant depression by inducing changes in cortical excitability in ...

3.

researchgate.net

researchgate.net/publication/386180378_Sensory_Entrained_TMS_seTMS_enhances_motor_cortex_excitability

Sensory Entrained TMS (seTMS) enhances motor cortex ...

These findings demonstrate that seTMS effectively enhances corticomotor excitability and establishes a practical, cost-effective method for ...

4.

researchgate.net

researchgate.net/publication/394047538_Sensory_Entrained_TMS_seTMS_enhances_motor_cortex_plasticity

Sensory Entrained TMS (seTMS) enhances motor cortex ...

Notably, at least 80% of participants showed larger responses with se-iTBS at all time points. se-iTBS may provide a robust and practical ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11623581/

Sensory Entrained TMS (seTMS) enhances motor cortex ...

TMS is FDA-cleared for the treatment of depression, migraines, obsessive-compulsive disorder, smoking cessation, with more under investigation in Phase III ...

6.

onlinelibrary.wiley.com

onlinelibrary.wiley.com/doi/abs/10.1002/hbm.70267

Sensory Entrained TMS (seTMS) Enhances Motor Cortex ...

These findings demonstrate that seTMS effectively enhances corticomotor excitability and establishes a practical, cost-effective method for ...