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

Trial Summary

What is the purpose of this trial?

This trial uses electrical stimulation in specific brain areas to help manage symptoms of major depressive disorder in people who also have epilepsy. By monitoring and stimulating certain brain regions, researchers aim to adjust brain activity to improve mood and decision-making.

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 data supports the effectiveness of the treatment Brain Stimulation for Depression?

Research shows that repetitive Transcranial Magnetic Stimulation (rTMS) is an effective and safe treatment for major depressive disorder (MDD), and Electroconvulsive Therapy (ECT) is considered the most effective antidepressant for patients who do not respond to medications. Both methods have been shown to change brain states and help treat depression. ^{1 2 3 4 5}

Is brain stimulation safe for treating depression?

Research shows that Transcranial Magnetic Stimulation (TMS) is generally safe for treating depression, with studies indicating it is well-tolerated and effective for patients with major depressive disorder. ^{1 5 6 7 8}

How does brain stimulation treatment for depression differ from other treatments?

Brain stimulation treatments like ECT, TMS, and DBS are unique because they directly target and stimulate specific areas of the brain to change its state, unlike medications or talk therapy. ECT is the most effective for severe depression, especially when other treatments fail, while TMS and DBS are newer options being explored for their potential benefits with fewer side effects. ^{4 9 10 11 12}

Research Team

Ignacio Saez

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. 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]

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

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

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

Repetitive transcranial magnetic stimulation versus electroconvulsive therapy for major depression: preliminary results of a randomized trial. [2021]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Treating the depressions with superficial brain stimulation methods. [2021]

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

Transcranial magnetic stimulation maintenance as a substitute for maintenance electroconvulsive therapy: a case series. [2021]

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

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

7. United States 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. [2022]

8. United States 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. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Brain-derived neurotrophic factor serum concentrations in depressive patients during vagus nerve stimulation and repetitive transcranial magnetic stimulation. [2018]

10. Australia pubmed.ncbi.nlm.nih.gov

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

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

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

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

Clinical Usefulness of Therapeutic Neuromodulation for Major Depression: A Systematic Meta-Review of Recent Meta-Analyses. [2019]