Accelerated Brain Stimulation for Depression

(MediTMS Trial)

Recruiting at 1 trial location

Overseen By Dhakshin Ramanathan, MDPhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Diego

Must be taking: Antidepressants

Disqualifiers: Substance abuse, Psychotic disorders, others

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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

50 Participants Needed

Trial Summary

What is the purpose of this trial?

Repetitive Transcranial magnetic stimulation (rTMS) is an FDA-approved treatment for depression that involves brief magnetic stimulation pulses on the dorsolateral prefrontal cortex (DLPFC) brain region. The ultimate goal of this treatment is to increase excitability and long-term plasticity in DLPFC, a brain region shown to be hypo-active in depression. Unfortunately, rTMS only has low to moderate efficacy; remission rates for patients range from ~15-30% in large randomized controlled trials. The focus of this research is to develop a next-generation rTMS protocol that is guided by the basic principles underlying brain plasticity, in order to improve the efficacy of rTMS for the treatment of depression. Specifically, in this study the investigators will test rTMS paired with a depression-relevant cognitive state of internal attention.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since the trial is for those whose depression is not helped by antidepressants, you might be able to continue your current treatment.

What data supports the effectiveness of the treatment Meditation Accelerated Brain Stimulation, Repetitive Transcranial Magnetic Stimulation, rTMS, Transcranial Magnetic Stimulation, TMS for depression?

Research shows that accelerated TMS (aTMS) can improve depression symptoms, with a meta-analysis indicating a moderate effect size. Additionally, combining rTMS with mindfulness-based therapies has shown promise in managing treatment-resistant depression. ^{1 2 3 4 5}

Is accelerated brain stimulation for depression safe for humans?

Repetitive transcranial magnetic stimulation (rTMS), a form of brain stimulation, is generally considered safe for treating depression. Common side effects are minor, like headaches, and serious issues like seizures are rare and linked to specific risk factors. Long-term effects are still unknown, but when used within guidelines, rTMS has a good safety profile. ^{6 7 8 9 10}

How is the treatment Meditation Accelerated Brain Stimulation different from other treatments for depression?

Meditation Accelerated Brain Stimulation, also known as accelerated repetitive transcranial magnetic stimulation (rTMS), is unique because it involves multiple sessions per day over a few days, rather than daily sessions over several weeks. This accelerated schedule aims to provide faster relief from depression symptoms compared to standard rTMS treatments. ^{2 11 12 13 14}

Research Team

Jyoti Mishra, PhD

Principal Investigator

University of California, San Diego

Eligibility Criteria

This trial is for adults with moderate to severe depression who haven't had success with 1-3 antidepressants or can't tolerate them. Participants should not have active substance abuse, psychotic disorders, metal implants in the brain, history of stroke or seizures, and shouldn't be at immediate risk of suicide.

Inclusion Criteria

My depression hasn't improved after 1-3 antidepressants, or I couldn't tolerate 2 of them.

I have been diagnosed with moderate to severe depression.

Exclusion Criteria

Active substance abuse/dependence

I have a diagnosed psychotic disorder.

Displaying acutely suicidal behaviors on the Columbia Suicide Severity Rating Scale.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive rTMS theta-burst protocol paired with a cognitive task for depression

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Meditation Accelerated Brain Stimulation

Trial Overview The study tests a new rTMS protocol that aims to improve brain plasticity and treat depression more effectively. It involves magnetic stimulation pulses on a specific part of the brain while patients are in a state of internal attention related to their condition.

Participant Groups

Group I: Medi1TMS Experimental Treatment 1 Intervention

rTMS theta-burst protocol paired with a consistent attention-to-breath task

Group II: Medi2TMS Active Control 1 Intervention

rTMS theta-burst protocol paired with an intermittent deep breathing task

Meditation Accelerated Brain Stimulation is already approved in United States, European Union, Canada for the following indications:

Approved in United States as rTMS for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder
• Pain

Approved in European Union as rTMS for:

• Major Depressive Disorder

Approved in Canada as rTMS for:

• Major Depressive Disorder

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

Findings from Research

Accelerated transcranial magnetic stimulation (aTMS) has been shown to significantly improve depressive symptoms, with a cumulative effect size of 0.39 from randomized control trials and an even higher effect size of 1.27 when including open-label trials.

The review analyzed 18 articles from 11 distinct studies, indicating that while the methodologies were generally acceptable, there is room for improvement in sham techniques and blinding to enhance the reliability of future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated TMS for Depression: A systematic review and meta-analysis. Sonmez, AI., Camsari, DD., Nandakumar, AL., et al.[2020]

In a study of 15 medication-free subjects with major depression, 10 sessions of repetitive transcranial magnetic stimulation (rTMS) did not significantly reduce depression severity compared to sham treatment, indicating limited efficacy in this short-term application.

However, patients with a shorter duration of depressive episodes (less than 4 years) experienced a much greater response to rTMS, suggesting that treatment timing may be crucial for effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Shorter duration of depressive episode may predict response to repetitive transcranial magnetic stimulation. Holtzheimer, PE., Russo, J., Claypoole, KH., 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]

An innovative treatment model called DepS Y-MBCT, which combines yoga and mindfulness-based cognitive therapy, showed promising results in alleviating treatment-resistant depression (TRD) symptoms in 27 out of 32 patients in a pilot trial.

The review suggests a tiered approach for TRD, recommending the use of ketamine and rTMS for rapid symptom relief, while DepS Y-MBCT can help maintain remission and prevent relapse, addressing the limitations of existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine, Transcranial Magnetic Stimulation, and Depression Specific Yoga and Mindfulness Based Cognitive Therapy in Management of Treatment Resistant Depression: Review and Some Data on Efficacy. Pradhan, B., Parikh, T., Makani, R., et al.[2022]

In a study involving 18 patients with treatment-resistant major depression, fast repetitive transcranial magnetic stimulation (rTMS) at 10 Hz showed improvements in verbal memory performance, indicating its safety and potential cognitive benefits.

However, the study found that neither fast nor slow rTMS demonstrated clinically meaningful antidepressant effects, as only a marginal reduction in depression scores was observed, suggesting that rTMS may not be effective for this patient group at the tested parameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation (rTMS) in pharmacotherapy-refractory major depression: comparative study of fast, slow and sham rTMS. Padberg, F., Zwanzger, P., Thoma, H., et al.[2019]

In a study of 93 patients with major depressive disorder, augmentative rTMS treatment led to a significantly greater reduction in depression (48% decrease) and anxiety symptoms (53% decrease) compared to standard therapy alone (24% and 30% decrease, respectively).

The study found that rTMS treatment resulted in a 33% higher rate of remission compared to standard therapy, with a number needed to treat (NNT) of 3, indicating that rTMS is an effective and safe option for enhancing treatment outcomes in MDD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, Safety and Tolerability of Augmentative rTMS in Treatment of Major Depressive Disorder (MDD): A Prospective Cohort Study in Croatia. Filipcic, I., Milovac, Z., Sucic, S., et al.[2019]

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 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 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) 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 transcranial magnetic stimulation (TMS) protocols, which involve multiple sessions per day over a few days, aim to enhance the effectiveness of treatment for major depressive disorder (MDD) and reduce the overall treatment duration compared to conventional TMS.

The review highlights that while accelerated TMS shows promise in improving antidepressant efficacy and safety, nearly half of MDD patients still do not respond to TMS, indicating a need for further research and optimization of treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated transcranial magnetic stimulation for major depressive disorder: A quick path to relief? Tang, N., Shu, W., Wang, HN.[2023]

In a study involving 115 outpatients with major depressive disorder, accelerated rTMS did not show significant differences in remission or response rates compared to standard rTMS, indicating similar efficacy between the two treatment schedules.

While accelerated rTMS was feasible, it was associated with a higher rate of treatment discomfort, suggesting that while it may be effective, patient comfort should be considered in treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated repetitive transcranial magnetic stimulation in the treatment of depression. Fitzgerald, PB., Hoy, KE., Elliot, D., et al.[2022]

In a pilot study involving six medication-resistant depressed inpatients, daily left prefrontal rTMS significantly improved depression scores, with Hamilton Depression Scores decreasing from an average of 23.8 to 17.5 after treatment.

The treatment was found to be safe and well-tolerated, with two subjects experiencing substantial mood improvements, including one who achieved complete remission of symptoms for the first time in three years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daily repetitive transcranial magnetic stimulation (rTMS) improves mood in depression. George, MS., Wassermann, EM., Williams, WA., et al.[2022]

In a study of 61 active-duty service members with treatment-resistant depression who underwent at least 20 sessions of repetitive transcranial magnetic stimulation (rTMS), there was a statistically significant reduction in depressive symptoms, as indicated by a decrease in average PHQ-9 scores from 15.8 to 12.6 (P < 0.001).

Approximately 69% of participants experienced a reduction in their depressive ratings, with 20% achieving a level of improvement that placed them in the nondysfunctional range, suggesting that rTMS is a promising treatment option for major depression in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression in Active-Duty Service Members Improves Depressive Symptoms. Roach, AE., Hines, C., Stafford, J., et al.[2022]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Accelerated TMS for Depression: A systematic review and meta-analysis. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Shorter duration of depressive episode may predict response to repetitive transcranial magnetic stimulation. [2019]

3. United States 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. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Ketamine, Transcranial Magnetic Stimulation, and Depression Specific Yoga and Mindfulness Based Cognitive Therapy in Management of Treatment Resistant Depression: Review and Some Data on Efficacy. [2022]

5. Ireland pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation (rTMS) in pharmacotherapy-refractory major depression: comparative study of fast, slow and sham rTMS. [2019]

6. Croatia pubmed.ncbi.nlm.nih.gov

Efficacy, Safety and Tolerability of Augmentative rTMS in Treatment of Major Depressive Disorder (MDD): A Prospective Cohort Study in Croatia. [2019]

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

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

8. England pubmed.ncbi.nlm.nih.gov

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

9. 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]

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

Adverse events of repetitive transcranial magnetic stimulation in older adults with depression, a systematic review of the literature. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

Accelerated transcranial magnetic stimulation for major depressive disorder: A quick path to relief? [2023]

12. England pubmed.ncbi.nlm.nih.gov

Accelerated repetitive transcranial magnetic stimulation in the treatment of depression. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Daily repetitive transcranial magnetic stimulation (rTMS) improves mood in depression. [2022]

14. United States pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression in Active-Duty Service Members Improves Depressive Symptoms. [2022]