Deep Brain Stimulation for Depression

Overseen By Kelly Bijanki, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Baylor College of Medicine

Must be taking: Antidepressants

Must not be taking: Illicit drugs

Disqualifiers: Psychotic disorder, Bipolar, others

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: Unknown

Duration: 12 weeks

84 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how deep brain stimulation, a therapy using electrical impulses, can improve social and emotional processing in people with treatment-resistant depression. The researchers employ a new technique to record brain activity and apply stimulation to understand and potentially enhance these brain functions. They seek individuals who have experienced major depression for at least two years and have not found relief from at least four different treatments, including electroconvulsive therapy (ECT). Participants will engage in monitoring tasks and brain recordings at Baylor College of Medicine. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to new treatment options for depression.

Will I have to stop taking my current medications?

The trial requires that participants have a stable antidepressant medication regimen for the month before surgery, so you may not need to stop your current medications if they are stable. However, if you are on anticoagulant or anti-platelet agents, you may need to stop them for at least 2.5 weeks around the time of surgery.

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

Research has shown that deep brain stimulation (DBS) is generally safe for people with depression that hasn't improved with other treatments. In a study by Mayberg and colleagues, DBS proved effective and safe, with 66% of participants showing improvement after six months. Another study demonstrated strong antidepressant effects of DBS in several patient groups.

Although some individuals might experience side effects, these studies suggest that DBS is usually well-tolerated. For those considering participation in a clinical trial, these findings offer reassurance about the safety of DBS as a treatment for depression. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard care for depression, which often includes medications like SSRIs or therapy, directional deep brain stimulation (DBS) offers a unique approach by targeting specific brain areas with electrical impulses. Researchers are excited about this technique because it allows for precise modulation of brain circuits that are implicated in treatment-resistant depression. This targeted delivery could potentially lead to faster and more effective relief of symptoms, offering hope for patients who have not responded to traditional treatments.

What evidence suggests that directional deep brain stimulation is effective for depression?

Research has shown that deep brain stimulation (DBS) can help people with depression that hasn't improved with other treatments. In this trial, participants will receive Directional Deep Brain Stimulation, studied for its potential to improve depression symptoms. One study found that after a year of DBS, the connection between certain brain areas that handle emotions improved. This suggests DBS might help control mood by altering brain activity. Previous research has explored DBS as a promising option for those unresponsive to other depression treatments. Despite some challenges, DBS continues to show potential for improving depression symptoms. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for men and women aged 22-70 with treatment-resistant depression or epilepsy, who are undergoing intracranial electrode placement. Participants must have a stable mental state, no drug abuse, no severe medical conditions that could interfere with surgery, and not be pregnant. They should have tried multiple depression treatments without success.

Inclusion Criteria

I've had at least 6 weeks of psychotherapy without lasting improvement.

I am between 22 and 70 years old and not pregnant.

My depression symptoms are severe, scoring 27 or higher on the MADRS.

Exclusion Criteria

I have high blood pressure and heart disease.

Any condition that makes the subject a poor candidate

I cannot have surgery due to a medical issue like an infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo invasive intracranial monitoring and stimulation for treatment-resistant epilepsy and depression

12 weeks

Regular monitoring visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Directional Deep Brain Stimulation

Trial Overview

The study tests 'Directional Deep Brain Stimulation' (DBS) using advanced brain recording techniques in patients with resistant epilepsy and depression to understand how the brain processes social and emotional signals. It aims to improve socio-emotional functions by mapping these neural dynamics.

How Is the Trial Designed?

Group I: TRD Experimental Treatment 1 Intervention

Group II: EMU Active Control 1 Intervention

Patient's behavioral and neural activity via computer tasks and questionnaires are monitored in the Epilepsy Monitoring Unit

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

Approved in United States as Deep Brain Stimulation for:

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

Approved in European Union as Deep Brain Stimulation for:

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

Approved in Canada as Deep Brain Stimulation for:

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

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Published Research Related to This Trial

In a study of 74 patients with Parkinson's disease and essential tremor, 39-68% of patients with Parkinson's and 50-72% with essential tremor utilized directional deep brain stimulation (d-DBS) over 36 months to improve symptom control and reduce side effects.

Directional stimulation was preferred initially in essential tremor patients due to simpler programming, but as experience grew, more Parkinson's patients also benefited from d-DBS, highlighting its potential for better therapeutic outcomes compared to traditional omnidirectional stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Clinical Experience with Directional Deep Brain Stimulation Programming: A Retrospective Review. Karl, JA., Joyce, J., Ouyang, B., et al.[2022]

In a study of 53 patients with advanced Parkinson's disease, directional deep brain stimulation (dDBS) led to a significant 44% improvement in motor symptoms (measured by UPDRS-III) and a 43% reduction in medication dosage over 6 months, with sustained benefits at 18 months.

dDBS not only improved motor symptoms but also alleviated non-motor symptoms, demonstrating its effectiveness and safety in real-life clinical settings, with minimal adverse effects reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-Life Experience on Directional Deep Brain Stimulation in Patients with Advanced Parkinson's Disease. Koivu, M., Scheperjans, F., Eerola-Rautio, J., et al.[2022]

In a study of 18 patients with directional deep brain stimulation (DBS) electrodes, the orientation of the leads remained stable over time, with an average change of only -1.1 ± 3.9° from the initial measurement.

This stability suggests that once implanted, the directional leads do not significantly drift in orientation, which is important for optimizing stimulation settings and ensuring consistent therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temporal Stability of Lead Orientation in Directional Deep Brain Stimulation. Dembek, TA., Asendorf, AL., Wirths, J., et al.[2021]

In a study of 51 patients with Parkinson's disease, dystonia, and tremor, 54.9% were using advanced features of directional deep brain stimulation (DBS) after 15 months, indicating a significant uptake of these features among patients who were selected based on specific clinical characteristics.

Advanced DBS features were particularly beneficial for patients implanted in the Vim region, with 92% utilizing these features, compared to 44% in the STN and 40% in the GPi, suggesting that the choice of target may influence the need for advanced stimulation options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The actual use of directional steering and shorter pulse width in selected patients undergoing deep brain stimulation. Zitman, FMP., Janssen, A., van der Gaag, NA., et al.[2022]

In a study involving six parkinsonian patients, directional leads for deep brain stimulation (DBS) showed a low incidence of adverse effects, particularly when stimulating in the posteromedial direction of the subthalamic nucleus (STN).

DBS significantly improved motor function and reduced dyskinesia, as evidenced by a decrease in Unified Parkinson's Disease Rating Scale (UPDRS) scores from 30.2 to 7.2 for motor symptoms and from 3.3 to 0.5 for dyskinesia after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot Study for Considering Subthalamic Nucleus Anatomy during Stimulation Using Directional Leads. Asahi, T., Ikeda, K., Yamamoto, J., et al.[2020]

Directional deep brain stimulation (dDBS) was effectively implemented in 42 patients with movement disorders, showing a significant average reduction of 35.4% in levodopa-equivalent daily dose for Parkinson's disease patients six months post-implantation.

Despite the benefits of dDBS, accurate surgical placement is crucial, as 10 leads in 6 patients required revision due to electrode malposition, highlighting the importance of precision in achieving optimal clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Institutional Experience of Directional Deep Brain Stimulation and a Review of the Literature. Mishra, A., Unadkat, P., McBriar, JD., et al.[2023]

Directional deep brain stimulation (DBS) using novel leads allows for more precise targeting of electrical stimulation, which can reduce unintended side effects and improve treatment outcomes for drug-resistant involuntary movements.

The complexity of programming these directional leads necessitates new strategies, including image-guided programming and potential future use of local field potentials for optimal stimulation, enhancing the effectiveness of DBS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical Strategy for Directional Deep Brain Stimulation. Masuda, H., Shirozu, H., Ito, Y., et al.[2022]

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We found vALIC DBS to be effective in 32% of patients with TRD (ITT) after approximately 2 years of follow-up compared with 40% after optimisation, with no ...