Accelerated Brain Stimulation for Depression

(MediTMS Trial)

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach to treating depression using brain stimulation. It combines repetitive transcranial magnetic stimulation (rTMS), which uses magnetic pulses to activate specific brain areas, with meditation-focused tasks to enhance effectiveness. The goal is to boost brain activity in areas less active in people with depression. It targets individuals with moderate to severe depression who haven't found success with antidepressants in their current episode. As an unphased trial, this study provides a unique opportunity to explore innovative treatment options for depression.

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 prior data suggests that this protocol is safe for treating depression?

Studies have shown that repetitive transcranial magnetic stimulation (rTMS) is generally safe for treating depression. The FDA has approved it for this use, indicating it has undergone safety testing. Research suggests that increasing the frequency of rTMS sessions might enhance results without raising risk. One study found that this approach significantly reduced depression symptoms and was well-tolerated by patients. While some side effects, such as headaches or discomfort during treatment, may occur, they are usually mild. Overall, this method appears promising for being both safe and effective. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the accelerated brain stimulation treatments for depression because they aim to enhance traditional approaches like medication and psychotherapy. Unlike standard treatments that can take weeks to show effects, these protocols use a theta-burst stimulation paired with breathing tasks, potentially offering quicker relief. The Medi2TMS arm combines brain stimulation with deep breathing, while the Medi1TMS arm uses consistent attention-to-breath tasks, both of which might improve the brain's response to treatment. These innovative techniques could provide faster and more effective options for managing depression, offering hope for those who don’t respond well to current therapies.

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

Research has shown that accelerated repetitive transcranial magnetic stimulation (rTMS) can reduce depression symptoms more quickly than traditional methods. Studies have found that it significantly lessens symptoms of obsessive-compulsive disorder (OCD) and depression, outperforming placebo treatments. In one study, 33% of participants felt better after just one week, increasing to 43% after four weeks. This suggests that this faster treatment could help people with depression feel better sooner.

In this trial, participants will receive one of two variations of accelerated rTMS. The Medi2TMS arm involves an rTMS theta-burst protocol paired with an intermittent deep breathing task. Meanwhile, the Medi1TMS arm uses an rTMS theta-burst protocol paired with a consistent attention-to-breath task. These approaches aim to increase brain activity in areas less active in depression, potentially enhancing treatment effectiveness. ^{2 3 4 5 6}

Who Is on the Research Team?

Jyoti Mishra, PhD

Principal Investigator

University of California, San Diego

Are You a Good Fit for This Trial?

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

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

I have a diagnosed psychotic disorder.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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 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]

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) 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]

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 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]

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]

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]

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. clinicaltrials.gov clinicaltrials.gov/study/NCT04586699

Meditation Accelerated Brain Stimulation for Depression Specifically, in this study the investigators will test rTMS paired with a depression-relevant cognitive state of internal attention. Detailed Description.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10188211/

Accelerated Repetitive Transcranial Magnetic Stimulation to ... Accelerated rTMS reduces time demands, improves clinical efficiency, and potentially induces faster onset of antidepressant effects.

3. sciencedirect.com sciencedirect.com/science/article/pii/S1876201825000632

Efficacy and safety of accelerated transcranial magnetic ... Accelerated TMS significantly reduced OCD and depressive symptoms, and increased response rate compared to sham aTMS.

4. nature.com nature.com/articles/s41386-023-01599-z

Accelerated TMS - moving quickly into the future of ... Overall, accelerated TMS appears to hold promise to reduce treatment time and achieve rapid reduction in depressive symptoms, but at this time ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12090592/

Accelerated repetitive transcranial magnetic stimulation in ... Results indicated that accelerated rTMS is well-tolerated and safe, leading to a 33% response rate at week 1 and an increase to 43% at week 4 [ ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06783361

Accelerated Transcranial Magnetic Stimulation in ... Transcranial magnetic stimulation (TMS) is a promising form of non-invasive brain stimulation with rapid antidepressant and suicide prevention effects in MDD.