Brain Stimulation for Depression

Overseen By Ignacio Saez

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Icahn School of Medicine at Mount Sinai

Disqualifiers: Over 80, Under 18

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: 2

Duration: 1 day

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new brain stimulation methods to treat major depressive disorder. Researchers focus on specific brain areas involved in mood and decision-making to identify new treatment targets. The trial includes epilepsy patients who also experience depression, as these conditions often co-occur. Participants must already be undergoing invasive brain monitoring for epilepsy. Those with both epilepsy and depression who meet this criterion might be suitable for the study. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could lead to new treatment options for depression.

Do I need to stop my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What prior data suggests that this brain stimulation is safe for treating depression?

Research shows that brain stimulation can safely treat depression. For example, studies have found that transcranial magnetic stimulation (TMS), a type of brain stimulation, is both effective and well-tolerated by patients. One study found that deep TMS was safe for patients who did not respond well to antidepressant medications. Similarly, transcranial electrical stimulation has shown positive results with a low risk of serious side effects.

While the research focuses on non-invasive methods, safety data suggests that brain stimulation treatments are generally safe. Although this new study uses a different method, existing safety evidence from other brain stimulation therapies is encouraging. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about brain stimulation for depression because it offers a different approach compared to traditional treatments like antidepressant medications and psychotherapy. Unlike these options, which can take weeks to show effects, brain stimulation has the potential to provide quicker relief. This method works by directly targeting brain activity, which could lead to more immediate changes in mood and symptoms. Additionally, it offers a non-invasive alternative for those who may not respond well to medications.

What evidence suggests that brain stimulation might be an effective treatment for depression?

Research has shown that brain stimulation techniques may help treat depression. This trial will explore different brain stimulation methods. Studies have found that transcranial electrical stimulation (tES) can significantly improve symptoms of depression. Another method, transcranial magnetic stimulation (TMS), effectively reduces symptoms, often providing relief after a few weeks of treatment. In a large study, more TMS sessions led to better results for people with major depressive disorder (MDD). These findings suggest that brain stimulation can be a powerful tool against depression by targeting areas of the brain that control mood. ^{1 6 7 8 9}

Who Is on the Research Team?

Ignacio Saez

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

This trial is for adults with major depressive disorder who are already undergoing invasive monitoring for epilepsy. It's open to all adult ages, except those over 80 due to cognitive decline concerns, and children under 18 because their frontal lobes aren't fully developed.

Inclusion Criteria

I am an adult with epilepsy being considered for invasive monitoring.

Exclusion Criteria

I am under 80 years old.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants complete a decision-making task and undergo baseline assessments including questionnaires for depression status

1 day

1 visit (in-person)

Treatment

Participants undergo intracranial recordings and a subset receive electrical stimulation of pre-identified anatomical targets

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Brain stimulation

Trial Overview The study is testing new brain stimulation strategies targeting limbic brain areas involved in mood regulation and decision-making. Researchers will record neural activity during tasks that involve making choices to find potential treatment targets.

How Is the Trial Designed?

Group I: Participants with depression Experimental Treatment 1 Intervention

Participants with depression to undergo brain stimulation

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

Approved in United States as Transcranial Magnetic Stimulation (TMS) for:

• Treatment-resistant depression (TRD)

Approved in United States as Deep Brain Stimulation (DBS) for:

• Treatment-resistant depression (TRD)
• Obsessive-compulsive disorder (OCD)

Approved in United States as Electroconvulsive Therapy (ECT) for:

• Severe depression
• Bipolar disorder
• Schizophrenia

Approved in European Union as Transcranial Magnetic Stimulation (TMS) for:

• Treatment-resistant depression (TRD)

Approved in European Union as Deep Brain Stimulation (DBS) for:

• Treatment-resistant depression (TRD)
• Obsessive-compulsive disorder (OCD)

Approved in European Union as Electroconvulsive Therapy (ECT) for:

• Severe depression
• Bipolar disorder
• Schizophrenia

Approved in Canada as Transcranial Magnetic Stimulation (TMS) for:

• Treatment-resistant depression (TRD)

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

University of California, Davis

Collaborator

Trials

958

Recruited

4,816,000+

Published Research Related to This Trial

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]

Transcranial magnetic stimulation (TMS) was effective in treating treatment-resistant depression, with a response rate of 50.6% and a remission rate of 24.7% after 6 weeks of treatment in a cohort of 100 patients.

TMS was well tolerated, showing a low discontinuation rate of 3% and no serious adverse events, indicating its safety as an adjunctive treatment for patients who have not responded to other antidepressant therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of transcranial magnetic stimulation in clinical practice post-FDA approval in the United States: results observed with the first 100 consecutive cases of depression at an academic medical center. Connolly, KR., Helmer, A., Cristancho, MA., et al.[2022]

In a case series of 6 patients transitioning from maintenance ECT to TMS, all participants maintained or improved their depression status over 3 to 6 months, demonstrating TMS's effectiveness as a substitute treatment.

TMS was well tolerated, with minimal side effects reported, primarily headaches and scalp discomfort, making it a safer alternative for patients who experience adverse effects from ECT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation maintenance as a substitute for maintenance electroconvulsive therapy: a case series. Cristancho, MA., Helmer, A., Connolly, R., et al.[2021]

Transcranial magnetic stimulation (TMS) is an effective and safe treatment for major depressive disorder (MDD), showing significant improvements in quality of life (QOL) and functional status in 307 outpatients after an acute treatment course.

Patients reported statistically significant enhancements in mental and physical health across various domains, indicating that TMS not only alleviates depressive symptoms but also leads to meaningful improvements in overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation (TMS) for major depression: a multisite, naturalistic, observational study of quality of life outcome measures in clinical practice. Janicak, PG., Dunner, DL., Aaronson, ST., et al.[2022]

In a study of treatment-resistant patients with major depression, neither vagus nerve stimulation (VNS) nor repetitive transcranial magnetic stimulation (rTMS) significantly altered serum levels of brain-derived neurotrophic factor (BDNF).

The findings suggest that unlike some antidepressant medications, these brain stimulation techniques do not influence BDNF concentrations in the serum, indicating a different mechanism of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain-derived neurotrophic factor serum concentrations in depressive patients during vagus nerve stimulation and repetitive transcranial magnetic stimulation. Lang, UE., Bajbouj, M., Gallinat, J., et al.[2018]

Electroconvulsive therapy (ECT) is a well-established and effective treatment for severe depression, but it has significant side effects and ongoing research is focused on optimizing its administration methods.

Emerging treatments like magnetic seizure therapy show promise with potentially similar efficacy to ECT but fewer side effects, while techniques like vagus nerve stimulation (VNS) and repetitive transcranial magnetic stimulation (rTMS) are already available and supported by research, though they require further study to determine optimal treatment parameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-pharmacological biological treatment approaches to difficult-to-treat depression. Fitzgerald, PB.[2020]

Electroconvulsive therapy (ECT) is the most effective treatment for severe depression, particularly in cases with psychotic features and among elderly patients, due to its ability to induce seizures that significantly impact brain regions like the hippocampus.

Transcranial magnetic stimulation (TMS) and vagus nerve stimulation (VNS) have shown mixed results, with VNS being primarily used for treatment-resistant depression but with limited efficacy, while deep brain stimulation (DBS) may be beneficial in rare, severe cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Putative common pathways in therapeutic brain stimulation for affective disorders. Bolwig, TG.[2019]

In a study involving 25 severely depressed patients, repetitive transcranial magnetic stimulation (rTMS) showed similar effectiveness to electroconvulsive therapy (ECT) in improving depression symptoms, with a mean percent improvement of 55% for rTMS compared to 64% for ECT.

Both treatments resulted in comparable outcomes on the Hamilton Depression Rating Scale and other secondary measures, indicating that rTMS can be a viable alternative to ECT for patients who may not tolerate or benefit from traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation versus electroconvulsive therapy for major depression: preliminary results of a randomized trial. Janicak, PG., Dowd, SM., Martis, B., et al.[2021]

Electroconvulsive therapy (ECT) remains the most effective treatment for acute depression in patients who do not respond to medications, highlighting its importance in the landscape of depression treatments.

Repeated daily repetitive transcranial magnetic stimulation (rTMS) of the prefrontal cortex has become an established clinical treatment for acute depressive episodes after nearly 20 years of research, although the efficacy of other brain stimulation methods is still being evaluated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating the depressions with superficial brain stimulation methods. George, MS., Taylor, JJ., Short, B.[2021]

Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) show small to moderate effectiveness in treating major depression, with similar levels of acceptability compared to sham treatments.

Vagus nerve stimulation and deep brain stimulation have shown preliminary effectiveness, especially in long-term follow-ups, although they are more complex to study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Usefulness of Therapeutic Neuromodulation for Major Depression: A Systematic Meta-Review of Recent Meta-Analyses. McGirr, A., Berlim, MT.[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]

Electroconvulsive therapy (ECT) shows a significant advantage over transcranial magnetic stimulation (TMS) for treating major depression, based on a review of six randomized, prospective studies.

Current evidence does not support the idea that TMS is as effective as ECT, and further large-scale trials are needed to explore the efficacy of both treatments in different patient subgroups, such as the elderly and those with psychotic depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electroconvulsive therapy versus transcranial magnetic stimulation for major depression: a review with recommendations for future research. Rasmussen, KG.[2016]

Citations

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Transcranial Electrical Stimulation in Treatment of Depression The tES treatment was associated with a higher improvement in depressive symptoms among patients with DMC (SMD = −1.05; 95% CI, −1.67 to −0.43; ...

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an umbrella review of meta-analyses of randomized ... Electrical and magnetic brain stimulation techniques present distinct mechanisms and efficacy in the acute treatment of depression.

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Comparative efficacy of multiple non-invasive brain ... This study aimed to compare the efficacy and cognitive effects of various NIBS techniques in treating MDD in older patients.

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Transcranial magnetic stimulation If rTMS works for you, your depression symptoms may improve or go away completely. Symptom relief may take a few weeks of treatment. The ...

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Dosing transcranial magnetic stimulation in major ... In a study of 7215 MDD patients, there were powerful associations between number of TMS sessions and effectiveness.

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Brain Stimulation Therapies - National Institute of Mental Health Learn about types of brain stimulation therapies, which involve activating or inhibiting the brain with electricity, and why they are used in treatment.

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Transcranial Electrical Stimulation in Treatment of ... Transcranial direct current stimulation and transcranial alternating current stimulation was associated with positive outcomes among patients with MDD and DPC ...

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Efficacy and safety of deep transcranial magnetic ... These results suggest that dTMS constitutes a novel intervention in MDD, which is efficacious and safe in patients not responding to antidepressant medications, ...

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Transcranial Magnetic Stimulation (TMS) in the Treatment ... The result of the analysis determined that there was a 57% reduction in depression rating scale scores, 46% of patients achieved response criteria, and 31% ...