Deep Brain Stimulation for Treatment-Resistant Depression

Overseen By Emma Meyer

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Helen Mayberg, MD

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

Compensation: Varies

Number of Visits: 1

10 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new device that sends electrical signals to the brain to help people with severe depression who don't respond to usual treatments. The device also records brain activity to understand how the treatment works. The study will involve 10 patients and last for several years. Deep brain stimulation (DBS) has been investigated for a long time as a treatment for severe, treatment-resistant depression, showing potential but requiring further research.

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

The trial information does not specify whether you need to stop taking your current medications. However, since the trial involves treatment-resistant depression, it's possible that you may need to continue your current medications. Please consult with the study team for specific guidance.

What data supports the effectiveness of this treatment for depression?

Research shows that deep brain stimulation (DBS) of the medial forebrain bundle can quickly and effectively help people with treatment-resistant depression, with many patients experiencing rapid improvements. ^{1 2 3 4 5}

Is deep brain stimulation generally safe for humans?

Deep brain stimulation (DBS) has been used for various conditions, and while it can be beneficial, there are some risks. Common complications include infections, movement of the device parts, and issues with the device itself, sometimes requiring additional surgery to fix or remove the device. ^{1 6 7 8 9}

How is the Medtronic Summit RC+S DBS system treatment different from other treatments for treatment-resistant depression?

The Medtronic Summit RC+S DBS system is unique because it involves deep brain stimulation (DBS) of the subcallosal cingulate gyrus, which is a relatively new and experimental approach for treatment-resistant depression. Unlike traditional medications, this treatment directly modulates brain activity to potentially exert an antidepressant effect. ^{10 11 12 13 14}

Research Team

Helen Mayberg, MD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

This trial is for adults aged 25-70 with severe, treatment-resistant Major Depressive Disorder (MDD), who have not responded to multiple treatments including medications and possibly ECT. They must be able to undergo an MRI, live near New York City, and have a caregiver to assist them. Pregnant individuals or those planning pregnancy, people with certain medical conditions or on anticoagulant therapy that can't be stopped are excluded.

Inclusion Criteria

Your overall level of functioning is assessed to be 50 or lower.

Ability to provide written informed consent

I have been diagnosed with Major Depressive Disorder without psychosis.

Exclusion Criteria

You have a heart device like a pacemaker or defibrillator that could be affected by the study treatment.

You have a medical condition that requires MRI scans or diathermy treatment.

I need anticoagulant therapy that can't be stopped for surgery.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Implantation and Initial Setup

Participants are implanted with the Summit RC+S system and initial device setup is conducted

1-2 weeks

1 visit (in-person)

Active Stimulation and Monitoring

Participants receive continuous active DBS stimulation and are monitored with weekly in-person assessments and twice-daily LFP data collection

1 year

Weekly visits (in-person)

Discontinuation Experiment

A brief discontinuation experiment is conducted after 6 months of stimulation to record LFP changes

1-2 weeks

Long-term Follow-up

Participants are monitored for long-term effects and device performance, expected to last up to 10 years

Up to 10 years

Treatment Details

Interventions

• Medtronic Summit RC+S DBS system

Trial Overview The study tests the Medtronic Summit RC+S DBS system's ability to alleviate symptoms of severe depression by stimulating a brain region called the subcallosal cingulate. Participants will receive this experimental device implant and their brain activity will be monitored regularly over approximately ten years.

Participant Groups

Group I: Deep Brain Stimulation (DBS) Experimental Treatment 1 Intervention

Open label active Deep Brain Stimulation (DBS)

Who Is Running the Clinical Trial?

Helen Mayberg, MD

Lead Sponsor

Trials

2

Recruited

20+

Emory University

Collaborator

Trials

1,735

Recruited

2,605,000+

Georgia Institute of Technology

Collaborator

Trials

53

Recruited

5,600+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Findings from Research

Deep Brain Stimulation (DBS) of the medial forebrain bundle (MFB) in Flinders Sensitive Line (FSL) rats, which model depressive-like behavior, improved cognitive performance, specifically in memory tasks, without affecting other behaviors like exploration or vocalization.

The study indicates that while MFB DBS did not change certain depressive behaviors, it selectively enhanced cognitive abilities, suggesting a potential mechanism of action that may involve dopamine pathways, warranting further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of bilateral, continuous, and chronic Deep Brain Stimulation of the medial forebrain bundle in a rodent model of depression. Thiele, S., Furlanetti, L., Pfeiffer, LM., et al.[2018]

Deep Brain Stimulation (DBS) is a promising treatment option for patients with treatment-resistant depression, offering a minimally invasive way to regulate brain circuits associated with depression.

The article highlights the importance of understanding the complex mechanisms of depression to improve the effectiveness of DBS, while also addressing the challenges in its application and therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The Value of Deep Brain Stimulation in Difficult-To-Treat and Treatment-Refractory Depression]. Baumann-Vogel, H., Ineichen, C., Stieglitz, L., et al.[2023]

Deep brain stimulation (DBS) has shown a significant increase in response rates and reduction in depressive symptoms compared to sham treatment, based on a meta-analysis of 190 participants from nine studies.

Despite its promise for treatment-resistant depression, DBS is still considered experimental due to potential publication bias and the occurrence of serious adverse effects in some patients, indicating the need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review and meta-analysis of deep brain stimulation for depression. Kisely, S., Li, A., Warren, N., et al.[2019]

Medial forebrain bundle (MFB) deep brain stimulation (DBS) at specific parameters (100 μA, 90 μs, and high frequency) produced significant antidepressant-like effects in rats, as evidenced by improved performance in the forced swim test, a common measure of depression.

The stimulation increased activity in brain regions associated with reward, such as the nucleus accumbens and ventral tegmental area, but interestingly did not lead to increased dopamine or serotonin release in the nucleus accumbens, suggesting a unique mechanism of action for MFB DBS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antidepressant-like Effects of Medial Forebrain Bundle Deep Brain Stimulation in Rats are not Associated With Accumbens Dopamine Release. Bregman, T., Reznikov, R., Diwan, M., et al.[2019]

Deep brain stimulation (DBS) targeting the anterior nucleus of the thalamus (ANT) and hippocampus (HC) has been shown to significantly reduce seizure frequency in drug-resistant epilepsy, with about 50% of patients experiencing a 46%-90% reduction with ANT-DBS and a 48%-95% reduction with HC-DBS.

Approximately 75% of patients receiving stimulation from ANT, HC, or centromedian nucleus of the thalamus (CMT) report at least a 50% reduction in seizures, with factors like the absence of structural brain abnormalities and specific seizure types influencing the effectiveness of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for drug-resistant epilepsy. Li, MCH., Cook, MJ.[2018]

A review of 221 unique adverse events related to deep brain stimulation (DBS) devices for Parkinson's disease revealed that the most common complications were infections (16.2%) and lead migrations (8.6%).

Over 40% of the reported adverse events required patients to return to the operating room for device explantation or revision, highlighting the need for further research to improve the safety and reliability of DBS systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterizing Complications of Deep Brain Stimulation Devices for the Treatment of Parkinsonian Symptoms Without Tremor: A Federal MAUDE Database Analysis. Bennett, J., MacGuire, J., Novakovic, E., et al.[2023]

Deep brain stimulation (DBS) for Parkinson's disease is generally safe, with a low mortality rate of 0.2% and permanent morbidity at 0.6%, but complications such as intracerebral hemorrhage (ICH) and seizures can occur in a small percentage of cases.

The study found that the type of lead used in DBS can influence complications, with Medtronic's leads associated with higher rates of perielectrode brain edema compared to Boston Scientific's, highlighting the need for further research on hardware design to improve safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications of deep brain stimulation in Parkinson's disease: a single-center experience of 517 consecutive cases. Servello, D., Galbiati, TF., Iess, G., et al.[2023]

Deep brain stimulation (DBS) targeting the subcallosal cingulate cortex (SCC) shows promising efficacy for treatment-resistant depression (TRD), with response rates ranging from 23% to 92% and remission rates between 27% and 66.7% based on a review of 14 studies involving 230 patients.

The adverse effects associated with SCC DBS are generally transient and related to stimulation, indicating a favorable safety profile for this experimental treatment in TRD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcallosal Cingulate Cortex Deep Brain Stimulation for Treatment-Resistant Depression: A Systematic Review. Sobstyl, M., Kupryjaniuk, A., Prokopienko, M., et al.[2022]

In a long-term study of 8 patients with treatment-resistant depression (TRD) who underwent deep brain stimulation (DBS), there was a significant average improvement of 44.9% in depression scores over an average follow-up of 11 years, with 50% of patients showing at least a 50% improvement.

Despite the potential benefits, the study also highlighted risks, including two patients discontinuing treatment due to lack of efficacy and one patient committing suicide after stopping stimulation, emphasizing the need for careful patient selection and monitoring in future DBS trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation of the Ventral Capsule/Ventral Striatum for Treatment-Resistant Depression: A Decade of Clinical Follow-Up. Hitti, FL., Cristancho, MA., Yang, AI., et al.[2021]

References

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

The effects of bilateral, continuous, and chronic Deep Brain Stimulation of the medial forebrain bundle in a rodent model of depression. [2018]

2. Switzerland pubmed.ncbi.nlm.nih.gov

[The Value of Deep Brain Stimulation in Difficult-To-Treat and Treatment-Refractory Depression]. [2023]

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

Deep brain stimulation to the medial forebrain bundle for depression- long-term outcomes and a novel data analysis strategy. [2018]

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

A systematic review and meta-analysis of deep brain stimulation for depression. [2019]

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

Antidepressant-like Effects of Medial Forebrain Bundle Deep Brain Stimulation in Rats are not Associated With Accumbens Dopamine Release. [2019]

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

Deep brain stimulation for treatment-resistant depression: follow-up after 3 to 6 years. [2021]

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

Deep brain stimulation for drug-resistant epilepsy. [2018]

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

Characterizing Complications of Deep Brain Stimulation Devices for the Treatment of Parkinsonian Symptoms Without Tremor: A Federal MAUDE Database Analysis. [2023]

9. Austria pubmed.ncbi.nlm.nih.gov

Complications of deep brain stimulation in Parkinson's disease: a single-center experience of 517 consecutive cases. [2023]

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

Deep Brain Stimulation Modulates Gamma Oscillations and Theta-Gamma Coupling in Treatment Resistant Depression. [2018]

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

Local neuroanatomical and tract-based proxies of optimal subcallosal cingulate deep brain stimulation. [2023]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Subcallosal Cingulate Cortex Deep Brain Stimulation for Treatment-Resistant Depression: A Systematic Review. [2022]

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

Vagus nerve stimulation for depression. [2007]

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

Deep Brain Stimulation of the Ventral Capsule/Ventral Striatum for Treatment-Resistant Depression: A Decade of Clinical Follow-Up. [2021]