Deep Brain Stimulation for Depression

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Emory University

Disqualifiers: Schizophrenia, Panic disorder, Substance abuse, 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: 24 weeks

37 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to test the safety, efficacy and mechanism of action of subgenual cingulate (Cg25) deep brain stimulation (DBS) for major depression in patients who have not responded to prior antidepressant treatments. Participation in the study will continue for ten years or until the device receives FDA approval for depression. Forty (40) patients will be enrolled in this study.

Will I have to stop taking my current medications?

You can stay on your current medications during the study, but the doses must remain stable for certain periods. Changes will only be made if you experience intolerable side effects.

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

Deep Brain Stimulation (DBS) has shown promising results for treatment-resistant depression, with about 50% of patients experiencing long-term antidepressant effects and improved social functioning. Some studies have reported even higher response rates when targeting specific brain areas, suggesting DBS can be an effective option for those who do not respond to conventional treatments. ^{1 2 3 4 5}

Is Deep Brain Stimulation generally safe for humans?

Deep Brain Stimulation (DBS) is generally well-tolerated, but it can have some risks like infection (2-9%), bleeding in the brain (1-4%), and seizures (1-3%). Rarely, it can cause serious issues like an abscess in the brain. ^{6 7 8 9 10}

How is Deep Brain Stimulation different from other treatments for depression?

Deep Brain Stimulation (DBS) is unique because it involves implanting electrodes in specific brain areas to regulate abnormal brain circuits, which is different from medications or talk therapy. It is a minimally invasive surgical procedure used for treatment-resistant depression, where other treatments have failed. ^{1 2 11 12 13}

Research Team

Patricio Riva Posse, MD

Principal Investigator

Emory University

Eligibility Criteria

This trial is for adults with severe depression that hasn't improved after trying at least four different treatments, including medications and possibly ECT. They should have been depressed for at least two years or had more than four episodes of depression in their lifetime. Participants must be able to give consent and not be pregnant, abusing substances, or have other serious mental health conditions.

Inclusion Criteria

You have been experiencing depression for at least two years or have had more than four episodes of depression in your lifetime.

Ability to provide written informed consent.

You have a score of 20 or more on the 17-item Hamilton Depression Rating Scale (HDRS-17).

Exclusion Criteria

You have a medical condition that requires multiple MRI scans.

You are unable to handle being put to sleep for the procedure.

Substance abuse or dependence not in full sustained remission (i.e., not active for at least one year)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo deep brain stimulation (DBS) for treatment resistant depression

24 weeks

Regular visits for monitoring and adjustment

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 years or until FDA approval

Treatment Details

Interventions

• Deep Brain Stimulation

Trial Overview The study is testing Deep Brain Stimulation (DBS) targeting a brain area called the subgenual cingulate (Cg25). It aims to see if DBS can safely improve symptoms in those with treatment-resistant major depression over a ten-year period or until the device gets FDA approval.

Participant Groups

Group I: Deep Brain Stimulation Experimental Treatment 1 Intervention

Participants with treatment resistant depression will have a device implanted for deep brain stimulation.

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:

• Essential tremor
• Parkinson's disease
• Dystonia
• Obsessive-compulsive disorder
• Epilepsy
• Chronic pain
• Stroke-related motor deficits (under investigation)

Approved in European Union as Deep Brain Stimulation for:

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

Approved in Canada as Deep Brain Stimulation for:

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

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

The Dana Foundation

Collaborator

Trials

18

Recruited

980+

Findings from Research

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]

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]

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) shows promise as a treatment for patients with major depression who do not respond to conventional therapies, with about 50% of patients experiencing long-term antidepressant effects and improved social functioning.

While cognitive safety regarding attention, learning, and memory has been reported, there are potential adverse events such as wound infection and suicide, highlighting the need for larger studies to confirm safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for major depression. Schlaepfer, TE., Bewernick, BH.[2013]

In a study of 14 patients with treatment-refractory depression, closer proximity of deep brain stimulation (DBS) leads to specific white matter tracts was significantly associated with greater symptom reduction, indicating that targeting these tracts may enhance treatment efficacy.

The findings suggest that individual variations in white matter anatomy could influence treatment response, highlighting the importance of personalized approaches, such as using diffusion magnetic resonance imaging to guide DBS lead placement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Distance to white matter trajectories is associated with treatment response to internal capsule deep brain stimulation in treatment-refractory depression. Liebrand, LC., Natarajan, SJ., Caan, MWA., et al.[2021]

Deep brain stimulation (DBS) is effective for managing parkinsonian symptoms, but in rare cases, it can lead to severe mood disruptions, as demonstrated by a 58-year-old woman who developed rapid-onset depression during a routine battery replacement procedure after 5 years of DBS treatment.

Electroconvulsive therapy (ECT) proved to be an effective treatment for the patient's severe depression, highlighting its potential as a therapeutic option for patients experiencing intractable mood disorders related to DBS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Administration of electroconvulsive therapy for depression associated with deep brain stimulation in a patient with post-traumatic Parkinson's Disease: a case study. Cunningham, MG., Yadollahikhales, G., Vitaliano, G., et al.[2018]

This study presents the first case of safely administering electroconvulsive therapy (ECT) to a patient with deep brain stimulation (DBS) by temporarily interrupting DBS only during the ECT sessions.

Previous reports indicated no adverse events when DBS was withheld for the entire ECT course, but this case suggests that short interruptions during ECT may be a safe approach, warranting further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temporary interruption of deep brain stimulation for Parkinson's disease during outpatient electroconvulsive therapy for major depression: a novel treatment strategy. Ducharme, S., Flaherty, AW., Seiner, SJ., et al.[2011]

Deep Brain Stimulation (DBS) for Parkinson's disease can lead to rare complications, such as an intracranial abscess, as demonstrated in a case involving a 59-year-old male who developed significant inflammation and required multiple surgeries after the procedure.

Despite the complications, the patient's Parkinson's symptoms improved after the abscess was surgically drained, suggesting that the abscess may have inadvertently provided some therapeutic benefit similar to a subthalomotomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracerebral abscess: a rare complication of Deep Brain Stimulation. Brandão, E., Rosas, MJ., Abreu, P., et al.[2013]

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) therapy is effective for treating movement disorders and neuropathic pain, but it carries risks of adverse events related to the implanted hardware.

In two reported cases, patients experienced sudden loss of DBS effectiveness due to battery failure, necessitating emergency hospital admission and re-implantation of the pulse generator, highlighting the importance of monitoring device functionality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Failure of chronic pallidal stimulation in dystonic patients is a medical emergency. Yianni, J., Nandi, D., Ch, M., et al.[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]

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) is an effective treatment for movement disorders, particularly Parkinson's disease, showing improvements in tremor, dyskinesia, and quality of life by 25% to 50% based on various rating scales.

While DBS has proven efficacy for neurological conditions, it has not shown significant benefits for psychiatric disorders, as evidenced by early termination of trials for depression due to lack of efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation in Neurological and Psychiatric Disorders. Coenen, VA., Amtage, F., Volkmann, J., et al.[2018]

References

1. 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]

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

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

3. 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]

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

Deep brain stimulation for major depression. [2013]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Distance to white matter trajectories is associated with treatment response to internal capsule deep brain stimulation in treatment-refractory depression. [2021]

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

Administration of electroconvulsive therapy for depression associated with deep brain stimulation in a patient with post-traumatic Parkinson's Disease: a case study. [2018]

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

Temporary interruption of deep brain stimulation for Parkinson's disease during outpatient electroconvulsive therapy for major depression: a novel treatment strategy. [2011]

8. Spain pubmed.ncbi.nlm.nih.gov

Intracerebral abscess: a rare complication of Deep Brain Stimulation. [2013]

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

Failure of chronic pallidal stimulation in dystonic patients is a medical emergency. [2022]

11. Poland pubmed.ncbi.nlm.nih.gov

[Deep brain stimulation--the newest physical method of treatment of depression]. [2018]

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

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

13. Germany pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation in Neurological and Psychiatric Disorders. [2018]