DBS for Treatment-Resistant Depression

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Wayne Goodman MD

Must be taking: Mood stabilizers

Disqualifiers: Schizophrenia, OCD, PTSD, 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: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to help people with depression that hasn't improved with standard treatments. It uses deep brain stimulation (DBS), where a device is implanted to send electrical signals to specific brain areas. This trial targets individuals who have experienced major depression for over two years, have not responded to other treatments, and face significant daily challenges due to their symptoms. Participants will receive the DBS implant and, if they respond well, may enter a phase where the device's usage is adjusted to test its continued effectiveness.

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 does not specify if you need to stop taking your current medications. However, it mentions that participants should have a stable antidepressant regimen before surgery and anticipate maintaining a stable psychotropic medication regimen for the next 24 months.

What prior data suggests that this deep brain stimulation is safe for treatment-resistant depression?

Previous studies have shown that deep brain stimulation (DBS) can cause some side effects. About 67% of patients experienced unwanted effects, mostly common and moderate. However, some concerns about suicidal thoughts have been noted. These effects can vary for each person. Overall, other research has demonstrated that DBS can help improve depression symptoms for many people. Prospective trial participants should discuss any concerns with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike standard treatments for treatment-resistant depression, such as antidepressants and psychotherapy, Deep Brain Stimulation (DBS) offers a novel approach by directly targeting brain circuits involved in mood regulation. Researchers are excited about DBS because it involves implanting a device that sends electrical impulses to specific brain areas, potentially offering relief when other treatments have failed. This method is unique because it allows for real-time adjustments to the intensity of stimulation, providing a personalized treatment experience that can adapt to each patient's needs.

What evidence suggests that deep brain stimulation might be an effective treatment for treatment-resistant depression?

Research has shown that deep brain stimulation (DBS) can help people with depression that hasn't improved with other treatments. In this trial, all participants will receive the Activa Tremor Control System, a DBS implant, to assess its effectiveness. One study found that DBS improved depression symptoms by 47% over the long term, with about 56% of patients experiencing significant benefits, meaning their depression symptoms greatly improved or disappeared. DBS sends electrical signals to specific parts of the brain to help control mood. While DBS isn't suitable for everyone, these findings suggest it could be a promising option for those who haven't had success with other treatments. ^{1 2 6 7 8}

Who Is on the Research Team?

Wayne K Goodman, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

Adults aged 21-70 with treatment-resistant major depression, having chronic or recurrent episodes and not responding to multiple treatments. Participants must have a stable mental state, no substance abuse in the last 6 months (except prescribed/nicotine/cannabis), no neurological diseases like Parkinson's, seizure disorders, or recent participation in other trials. Pregnant women and those planning pregnancy are excluded.

Inclusion Criteria

My last manic or hypomanic episode was over 2 years ago and I am on a mood stabilizer.

My depression hasn't improved after trying three different treatments.

My antidepressant medication has not changed in the last month.

Exclusion Criteria

Current implanted stimulation devices including cardiac pacemakers, defibrillators, and neurostimulators

Lack of adequate family/friend support as determined by psychological screening and/or interview

Abnormal brain MRI

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Pre-operative Evaluation

Medical, psychiatric, and cognitive evaluations including MRI scans and neuropsychological testing

4 weeks

Multiple visits (in-person)

Implantation

Surgical implantation of the brain stimulation system in two stages

2-4 weeks

2 surgeries (in-person)

Optimization

Adjustment of stimulation parameters to achieve optimal symptom response

8 weeks

Frequent visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Monthly visits (in-person)

Randomized, Staggered Withdrawal

For responders, double-blind discontinuation of stimulation to assess treatment response

3 months

Biweekly visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Deep Brain Stimulation

Trial Overview

The trial is testing deep brain stimulation (DBS) of the lateral habenula for safety and effectiveness in treating major depression that hasn't improved with standard treatments. Six adults at Baylor College will undergo DBS implant surgery and be monitored using the Hamilton Depression Rating Scale over six months.

How Is the Trial Designed?

Group I: Randomized, staggered withdrawal phase Experimental Treatment 1 Intervention

For responders only: double blind discontinuation will be attempted on either the 12 or 13 month visit. Stimulation intensity will be decreased by 50% and then completely discontinued two weeks later. Subjects will be seen biweekly until 15 months post activation or escape criteria are met. These escape criteria include relapse at 2 visits, hospitalization, active suicidal ideation, or withdrawing consent. If any of these criteria are met, the blind will be broken and open treatment will be resumed.

Group II: Activa Tremor Control Sys (DBS Implant) Experimental Treatment 1 Intervention

all subjects will receive bilateral surgical implantation of DBS system. Those who respond at 12 months will enter a randomized, staggered withdrawal phase.

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?

Wayne Goodman MD

Lead Sponsor

Trials

3

Recruited

20+

Published Research Related to This Trial

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) 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]

In a study of 30 patients with severe, treatment-refractory OCD, deep brain stimulation (DBS) showed a 42% reduction in obsessive-compulsive symptoms after 12 months, with a responder rate of 60%.

While all patients experienced adverse events (195 total), most were mild or moderate, and the serious adverse events were primarily transient anxiety and worsening of affective symptoms, suggesting that the benefits of DBS may outweigh the risks in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective international multi-center study on safety and efficacy of deep brain stimulation for resistant obsessive-compulsive disorder. Menchón, JM., Real, E., Alonso, P., et al.[2022]

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]

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]

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) 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]

Citations

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Emory joins national study investigating deep brain ...

Emory has joined a new national clinical trial exploring the use of deep brain stimulation for treatment-resistant depression.

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Data from the Sequenced Treatment Alternatives to Relieve Depression study (STAR*D) demonstrated that approximately 33% of patients failed to achieve remission ...

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Open-label studies of DBS at various targets show comparable response rates of on average 50% in severely treatment resistant patients provided there has been ...