Brain Stimulation for Depression

Overseen By Sameer Sheth, PhD, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Baylor College of Medicine

Disqualifiers: Epilepsy, Depression, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 2 weeks

58 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how brain stimulation can aid individuals with treatment-resistant depression. Researchers aim to understand how various brain activity patterns relate to mood and behavior. The study includes two groups: one with individuals undergoing brain monitoring for epilepsy and another with participants in a depression treatment study. Those scheduled for brain monitoring due to epilepsy or already in a depression study involving brain stimulation might be suitable candidates. The goal is to improve treatments for depression and potentially other mental health conditions. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could enhance future mental health treatments.

Will I have to stop taking my current medications?

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

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

Research has shown that brain stimulation treatments, like those in this trial, are safe for humans. For example, the FDA has already approved vagus nerve stimulation (VNS), a type of brain stimulation, for certain conditions. Studies have found it to be safe and effective for people with treatment-resistant depression, usually causing only mild side effects.

Another focus of this trial is sEEG (stereo-electroencephalography) stimulation. Research indicates that sEEG is less painful and risky than other methods, with fewer complications, making it a safer choice for patients. Overall, both types of brain stimulation have a strong safety record in clinical settings. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about brain stimulation and sEEG stimulation because these techniques offer new ways to tackle depression. Unlike traditional treatments like antidepressants and talk therapy, which can take weeks to show effects, brain stimulation methods have the potential to deliver more immediate results by directly targeting and altering brain activity. Additionally, these techniques can be more precisely controlled, potentially leading to fewer side effects. This precision and speed make these approaches promising options for those who haven't found relief through standard treatments.

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

Research shows that brain stimulation might be a promising way to treat depression. In this trial, participants in the Depression Cohort will receive brain stimulation treatments. Studies have found that stimulating the vagus nerve (VNS) can lead to positive outcomes in severe depression, helping people function better in their daily lives and improving their quality of life. Another method, deep brain stimulation (DBS), has effectively treated depression that doesn't respond to other treatments. Evidence also suggests that using stereo-electroencephalography (sEEG) to guide brain stimulation can help understand and treat complex mental health disorders like depression. While more research is needed, these treatments show potential in helping people with depression. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with refractory epilepsy scheduled for seizure monitoring and patients already enrolled in a deep brain stimulation (DBS) trial for treatment-resistant depression. Participants must consent to the study.

Inclusion Criteria

Depression cohort: patients enrolled in our DBS for depression trial

I am an adult with epilepsy and have agreed to undergo brain monitoring.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo intracranial neural recordings and stimulation, with mood and behavioral assessments using tasks such as Affective Bias Task and Probabilistic Cognitive Control Task

2 weeks

Daily assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Brain Stimulation
• sEEG Stimulation

Trial Overview The study tests how brain activity relates to mood states using intracranial recordings and stimulation, alongside advanced AI models. It aims to improve understanding of depression's neurobiology and refine neuromodulatory treatments.

How Is the Trial Designed?

Group I: Epilepsy Cohort Experimental Treatment 1 Intervention

Group II: Depression Cohort Experimental Treatment 1 Intervention

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

Approved in European Union as Deep Brain Stimulation for:

• Parkinson's disease
• Essential tremor
• Dystonia
• Epilepsy

Approved in United States as Deep Brain Stimulation for:

• Parkinson's disease
• Essential tremor
• Dystonia
• Epilepsy
• Obsessive-compulsive disorder

Approved in United States as Responsive Neurostimulation for:

• Epilepsy

Approved in European Union as Vagus Nerve Stimulation for:

• Epilepsy
• Depression

Approved in United States as Vagus Nerve Stimulation for:

• Epilepsy
• Depression

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

University of Minnesota

Collaborator

Trials

1,459

Recruited

1,623,000+

University of Texas

Collaborator

Trials

193

Recruited

143,000+

Published Research Related to This Trial

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]

Vagus nerve stimulation (VNS) and repetitive transcranial stimulation (rTMS) are both FDA-cleared treatments for resistant depression, but VNS devices are generally considered a contraindication for rTMS due to safety concerns.

Despite this contraindication, clinicians have reported using rTMS in patients with implanted VNS systems, suggesting that with proper precautions and consent procedures, rTMS can be safely administered, as VNS components are typically outside the electromagnetic field of rTMS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safe use of repetitive transcranial magnetic stimulation in patients with implanted vagus nerve stimulators. Philip, NS., Carpenter, SL., Carpenter, LL.[2021]

Neuromodulation techniques, including transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), are gaining attention as effective non-pharmacological treatments for major depressive disorder (MDD), with TMS showing effects comparable to traditional antidepressants.

While electroconvulsive therapy (ECT) remains the first-line treatment for severe depression, TMS and tDCS have a favorable side effect profile, and invasive methods like deep brain stimulation (DBS) and vagus nerve stimulation (VNS) may be considered for treatment-resistant cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuromodulation approaches for the treatment of major depression: challenges and recommendations from a working group meeting. Brunoni, AR., Teng, CT., Correa, C., et al.[2019]

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]

Vagus nerve stimulation (VNS) has been shown to be effective in treating epilepsy, with about 50% of patients experiencing at least a 50% reduction in seizure frequency after 2 years of treatment.

Adverse events related to VNS are rare, primarily involving surgical complications and mild stimulation side effects, suggesting a favorable safety profile for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus Nerve Stimulation for the Treatment of Epilepsy. González, HFJ., Yengo-Kahn, A., Englot, DJ.[2022]

Vagus nerve stimulation (VNS) is effective for treating refractory epilepsy and depression, but traditional methods involve surgical implantation, which carries risks such as infection and bradycardia.

New non-invasive VNS systems eliminate the need for surgery, improving safety and tolerability, and allowing patients to administer stimulation on demand, potentially expanding its use in various medical conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. Ben-Menachem, E., Revesz, D., Simon, BJ., et al.[2022]

Electroconvulsive therapy (ECT) is considered the gold standard for treating treatment-resistant depression (TRD), despite potential cognitive and cardiovascular side effects, and it remains stigmatized.

Transcranial magnetic stimulation (TMS) and vagus nerve stimulation (VNS) are effective for late-life depression, with TMS having fewer side effects, but VNS shows limited data in older patients; emerging treatments like magnetic seizure therapy and deep brain stimulation show promise but require more safety and efficacy evidence in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Efficacy and Safety of Neuromodulation Treatments in Late-Life Depression. van Rooij, SJH., Riva-Posse, P., McDonald, WM.[2022]

Deep brain stimulation (DBS) is a new treatment method for depressive disorders, first applied in 2005 by Helen Mayberg, targeting Brodmann area 25 to alleviate symptoms of depression.

Only 30-40 patients with treatment-resistant depression have undergone DBS, highlighting the experimental nature of this approach and the challenges associated with its application in psychiatric disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Deep brain stimulation--the newest physical method of treatment of depression]. Zyss, T., Zieba, A., Hese, RT., 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]

Vagus nerve stimulation (VNS) has been FDA-approved since 2005 for treating severe, recurrent unipolar and bipolar depression, showing established efficacy particularly in patients who do not respond to traditional medications.

VNS works by stimulating vagal afferent fibers, which helps modulate the brain's neural circuitry involved in depression, specifically targeting areas like the locus ceruleus and dorsal raphe nucleus, making it a promising option for integrating into existing treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus Nerve Stimulation (VNS) and Treatment of Depression: To the Brainstem and Beyond. O'Reardon, JP., Cristancho, P., Peshek, AD.[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 28 patients with chronic major depression who had not responded to multiple treatments, Vagus Nerve Stimulation (VNS) showed a 12-month response rate of 35.7%, indicating it may be an effective alternative for treatment-resistant cases.

A smaller case series of 13 patients in Dundee reported a similar response rate of 30.8%, suggesting that VNS can provide significant relief for patients who have exhausted other treatment options, with response rates at least twice that of standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vagus nerve stimulation for chronic major depressive disorder: 12-month outcomes in highly treatment-refractory patients. Christmas, D., Steele, JD., Tolomeo, S., et al.[2018]

In a study of 52 adult patients with drug-resistant epilepsy treated with neurostimulation devices, 37% exhibited neurostimulation-related artifacts in their EEGs, with the highest incidence in those using deep brain stimulation (75%).

These artifacts can mimic actual seizures or heart conditions in electrodiagnostic studies, highlighting the importance for clinicians to recognize them to prevent misdiagnosis and ensure accurate interpretation of results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electrodiagnostic artifacts due to neurostimulation devices for drug resistant epilepsy. Arafat, T., Miron, G., Strauss, I., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2990624/

Vagus Nerve Stimulation (VNS) and Treatment of Depression It was approved by the FDA for the treatment of severe, recurrent unipolar and bipolar depression in July of 2005. VNS adopts a bottom-up approach to modulating ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9169472/

A narrative review on invasive brain stimulation for treatment ... Epidural cortical stimulation, an invasive intervention with few reported cases, showed positive results (40-60% response), although more extensive trials are ...

3. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/epi.18544

A systematic review and meta‐analysis of vagus nerve ... This meta-analysis suggests that all three neuromodulation therapies are effective for seizure reduction in LGS, with DBS and RNS demonstrating potentially ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X24013822

Effects of vagus nerve stimulation on daily function and ... Effects of vagus nerve stimulation on daily function and quality of life in markedly treatment-resistant major depression: Findings from a one-year, randomized, ...

5. brainstimjrnl.com brainstimjrnl.com/article/S1935-861X(24)01390-1/fulltext

Vagus nerve stimulation in treatment-resistant depression: ... Results. Overall, 88.4 % of participants completed the trial. Percent time in MADRS response did not distinguish active from sham VNS. However, ratings from on ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S1525505022001020

Concurrent brain-responsive and vagus nerve stimulation ... Our findings suggest that concurrent treatment with VNS and RNS is safe and that the addition of RNS to VNS can further reduce seizure frequency.

7. neuropace.com neuropace.com/blog/epilepsy-neurostimulation-device-rns-vns-dbs/

RNS System, VNS, DBS | Epilepsy Neurostimulation Devices Each device treats focal onset seizures without removing or destroying brain tissue. Each stimulates the brain with adjustable electrical current, directly or ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39706521/

Vagus nerve stimulation in treatment-resistant depression VNS was found safe and effective in participants with marked TRD. Keywords: Adjunctive therapy; Efficacy; Partial response; Randomized trial; Response; ...