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

6 Participants Needed

Trial Summary

What is the purpose of this trial?

This research study will investigate the safety, tolerability, and benefit of bilateral deep brain stimulation (DBS) to the lateral habenula in subjects with treatment-resistant major depression (TRD) secondary to either nonpsychotic unipolar major depressive disorder (MDD), or bipolar disorder (BD) I. Six adult subjects with TRD will be treated in this single-site study at Baylor College of Medicine; subjects will be chronically symptomatic with significant functional disability, and will have demonstrated resistance to standard somatic and pharmacotherapeutic treatments. The primary outcome measure will be the change in the 17-item Hamilton Depression Rating Scale (HDRS\^17) six months after the commencement of stimulation.

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 data supports the effectiveness of the treatment Deep Brain Stimulation (DBS) for Treatment-Resistant Depression?

Research shows that Deep Brain Stimulation (DBS) can be effective for people with treatment-resistant depression, as a meta-analysis found significant positive effects compared to a placebo treatment. Although results can vary, many studies have demonstrated the safety and potential benefits of DBS for this condition. ^{1 2 3 4 5}

Is deep brain stimulation (DBS) generally safe for humans?

Deep brain stimulation (DBS) has been studied for various conditions, including depression and obsessive-compulsive disorder. While some serious side effects like wound infection and mood changes have been reported, most side effects are mild or moderate and can often be managed by adjusting the stimulation settings. Overall, DBS is generally considered safe, but it is important to monitor for any adverse events. ^{6 7 8 9 10}

How is the treatment Deep Brain Stimulation (DBS) different from other treatments for treatment-resistant depression?

Deep Brain Stimulation (DBS) is unique because it involves a surgical procedure to implant electrodes in specific brain areas to regulate abnormal brain circuits, offering a potential option for those who haven't responded to other treatments. Unlike medications or talk therapy, DBS directly targets brain regions involved in depression, such as the subcallosal cingulate cortex, and is considered a minimally invasive neurosurgical approach. ^{1 3 5 11 12}

Research Team

Wayne K Goodman, MD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

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

I have a history of seizures or bleeding in the brain.

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

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

Timeline

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)

Treatment Details

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.

Participant Groups

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+

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) 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]

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]

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 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) 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 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]

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

Deep Brain Stimulation Is Effective for Treatment-Resistant Depression: A Meta-Analysis and Meta-Regression. [2020]

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

Long-Term Results of Deep Brain Stimulation for Treatment-Resistant Depression: Outcome Analysis and Correlation With Lead Position and Electrical Parameters. [2022]

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

Superolateral medial forebrain bundle deep brain stimulation in major depression: a gateway trial. [2023]

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

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

8. 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]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for major depression. [2013]

10. England pubmed.ncbi.nlm.nih.gov

A prospective international multi-center study on safety and efficacy of deep brain stimulation for resistant obsessive-compulsive disorder. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

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