Deep Brain Stimulation Surgery for Treatment Resistant Depression

Recruiting at 1 trial location

Overseen By Nadia Imran

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, Los Angeles

Must be taking: Antidepressants

Disqualifiers: Psychotic disorder, Bipolar, Substance use, 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

12 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stay on your current antidepressant medication throughout the study, unless there are safety concerns.

What data supports the effectiveness of this treatment for treatment-resistant depression?

Research shows that deep brain stimulation (DBS) can help people with treatment-resistant depression, with about 50% of patients responding well to it. Some studies even suggest that targeting specific brain areas might improve response rates to over 70%. ^{1 2 3 4 5}

Is deep brain stimulation generally safe for humans?

Deep brain stimulation (DBS) has been used in various conditions like Parkinson's disease and treatment-resistant depression. While it can reduce symptoms, there are potential complications such as hardware failure and surgery-related issues. Safety data is limited, but some studies report complications related to the device and surgical procedure. ^{1 6 7 8 9}

How is the Abbott Laboratories Infinity DBS System treatment different from other treatments for treatment-resistant depression?

The Abbott Laboratories Infinity DBS System is unique because it involves deep brain stimulation (DBS), a surgical procedure that uses electrical impulses to regulate brain circuits involved in depression. Unlike medications, DBS is adjustable and reversible, offering a novel approach for patients who do not respond to traditional treatments. ^{2 3 10 11 12}

What is the purpose of this trial?

Treatment resistant depression remains a major problem for individuals and society. Surgical procedures may provide relief for some of these patients. The most frequently considered surgical approach is deep brain stimulation (DBS) of a part of the brain called the subcallosal cingulate region. However, the effectiveness and safety is not well established. The investigators will use a novel approach using advanced imaging technique (magnetic resonance tractography) to evaluate the feasibility and safety of this surgical approach. An innovative method for the definition of DBS target will be applied that redefines the concept of targeting as one of targeting a symptomatic network rather than a structural brain region using subject-based brain anatomy to define the target location. The correlation between imaging findings at baseline with the mood score changes at different time points of the study will be investigated.

Research Team

Nader Pouratian

Principal Investigator

UT Southwestern Medical Center

Eligibility Criteria

This trial is for adults aged 21-70 with treatment-resistant depression, defined as not responding to at least four different types of antidepressant treatments. Participants must have a current major depressive episode lasting over 24 months or recurrent illness, and severe symptoms measured by specific scales. They should be on stable medication for at least one month before the study and able to attend regular clinic visits for a year.

Inclusion Criteria

I am between 21 and 70 years old and not pregnant.

I will keep taking my current antidepressant unless it's unsafe.

My cognitive function is good, with a MoCA score above 25.

Exclusion Criteria

I don't have any health conditions that would make surgery risky for me.

I have had a bleeding stroke in the past.

You should not have diathermy treatment during the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Open-label Period

Participants receive open-label DBS to optimize stimulation settings

8 weeks

Randomized Discontinuation Period

Participants are randomized to either 'OFF then ON' or 'ON then OFF' DBS for 8 weeks each

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 months

Treatment Details

Interventions

• Abbott Laboratories Infinity™ implantable deep brain stimulation system

Trial Overview The trial tests the Abbott Laboratories Infinity™ deep brain stimulation system targeting the subcallosal cingulate region in the brain using magnetic resonance tractography. This novel approach aims to redefine DBS target based on individual brain anatomy and symptomatic networks rather than structural regions.

Participant Groups

Group I: Randomized Discontinuation Period: ON then OFF DBS Experimental Treatment 1 Intervention

Subjects randomized to this arm are initially "ON" DBS with optimized stimulation settings for 8 weeks after the open label period and then "OFF" DBS with gradually decreasing amplitude for 8 weeks.

Group II: Randomized Discontinuation Period: OFF then ON DBS Experimental Treatment 1 Intervention

Subjects randomized to this arm are initially "OFF" DBS after the open label period then gradually decreased in their optimized setting's amplitude for 8 weeks and then "ON" DBS for 8 weeks.

Abbott Laboratories Infinity™ implantable deep brain stimulation system is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Infinity DBS System for:

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

Approved in European Union as Infinity DBS System for:

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

Approved in Canada as Infinity DBS System for:

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

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

Nader Pouratian

Lead Sponsor

Trials

4

Recruited

20+

Findings from Research

Deep brain stimulation (DBS) has shown promising results in treating therapy-refractory major depressive disorder (MDD), with studies indicating significant reductions in depression scores: 36% for nucleus accumbens, 44% for internal capsule/ventral striatum, and 52% for subcallosal cingulate gyrus after one year.

The side effects of DBS have been minor, and a notable percentage of patients achieved remission, with 30% in the nucleus accumbens group and 40% in the internal capsule/ventral striatum group, suggesting that DBS could be a viable option for patients who do not respond to traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation in the treatment of depression. Blomstedt, P., Sjöberg, RL., Hansson, M., et al.[2010]

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) 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]

In a study comparing advanced Parkinson's disease patients undergoing deep brain stimulation (DBS) with matched controls, significant atrophy of deep brain nuclei was observed, but patients did not show cognitive or psychobehavioral disturbances.

The volume of the globus pallidus was positively correlated with higher mental function, suggesting that structural changes in the brain may precede clinical symptoms in Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detailed Anatomical Volumetric Study of Deep Nuclei of Brain and Other Structures Between Parkinson's Disease Patients Who Had Deep Brain Stimulation and Control Group. Goh, CH., Abdullah, JY., Idris, Z., et al.[2022]

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) 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) targeted at the ventral anterior limb of the internal capsule (vALIC) showed continued efficacy in reducing depressive symptoms in 44.4% of patients with treatment-resistant depression (TRD) after a 1-year maintenance phase following a 1-year optimization period.

While overall depression scores remained stable during the maintenance phase, self-reported symptoms improved significantly, indicating that DBS can be a viable long-term treatment option for TRD, despite some serious non-DBS-related adverse events occurring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term deep brain stimulation of the ventral anterior limb of the internal capsule for treatment-resistant depression. van der Wal, JM., Bergfeld, IO., Lok, A., et al.[2020]

Deep brain stimulation (DBS) is effective for treating Parkinson's disease and essential tremor, but hardware failure can occur due to complications like wire fractures.

In a case study of an overweight female, repositioning the implantable pulse generator (IPG) to the suprascapular area successfully prevented further fractures of the extension wire, suggesting this approach may enhance the safety and reliability of DBS in similar patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placement of the Internal Pulse Generator for Deep Brain Stimulation in the Upper Back to Prevent Fracture of the Extension Wire due to Generator Rotation: Case Report. Garg, A., Mohan, AL., Garell, PC.[2021]

In a study of 262 patients undergoing deep-brain stimulation (DBS) surgery, the procedure demonstrated a low rate of severe complications, with only 0.2% experiencing permanent neurological deficits and a 5.7% incidence of skin infections related to the implanted hardware.

Long-term follow-up of 180 patients revealed that 13.9% experienced hardware-related issues, indicating that while DBS is generally safe, infection and hardware complications are significant concerns that can lead to extended hospital stays and additional surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep-brain stimulation: long-term analysis of complications caused by hardware and surgery--experiences from a single centre. Voges, J., Waerzeggers, Y., Maarouf, 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]

Deep brain stimulation (DBS) shows a response rate of 40-70% in patients with treatment-resistant major depressive disorder (MDD), indicating it may be an effective option for those who do not respond to medication.

Despite its promise, DBS remains experimental, with only a few controlled trials conducted, and recent multicenter trials for specific targets were discontinued due to lack of efficacy, highlighting the need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for treatment-resistant depression: systematic review of clinical outcomes. Morishita, T., Fayad, SM., Higuchi, MA., et al.[2021]

Deep brain stimulation (DBS) in the subcallosal cingulate area showed significant long-term efficacy in reducing depression severity and improving functioning in patients with treatment-resistant depression (TRD), with 58% achieving remission after 2 years of active stimulation.

The study demonstrated that DBS was safe and well tolerated, with no instances of hypomanic or manic episodes, indicating it could be a viable treatment option for both major depressive disorder and bipolar II disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcallosal cingulate deep brain stimulation for treatment-resistant unipolar and bipolar depression. Holtzheimer, PE., Kelley, ME., Gross, RE., et al.[2023]

References

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

Deep brain stimulation in the treatment of depression. [2010]

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

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

4. Malaysia pubmed.ncbi.nlm.nih.gov

Detailed Anatomical Volumetric Study of Deep Nuclei of Brain and Other Structures Between Parkinson's Disease Patients Who Had Deep Brain Stimulation and Control Group. [2022]

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. Austria pubmed.ncbi.nlm.nih.gov

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

7. England pubmed.ncbi.nlm.nih.gov

Long-term deep brain stimulation of the ventral anterior limb of the internal capsule for treatment-resistant depression. [2020]

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

Placement of the Internal Pulse Generator for Deep Brain Stimulation in the Upper Back to Prevent Fracture of the Extension Wire due to Generator Rotation: Case Report. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Deep-brain stimulation: long-term analysis of complications caused by hardware and surgery--experiences from a single centre. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Deep brain stimulation for treatment-resistant depression: systematic review of clinical outcomes. [2021]

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

Subcallosal cingulate deep brain stimulation for treatment-resistant unipolar and bipolar depression. [2023]