Deep Brain Stimulation for Depression

Overseen By Bashar Asir, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: The University of Texas Health Science Center, Houston

Must be taking: Psychotropic medications

Must not be taking: Anticoagulants

Disqualifiers: Psychotic disorders, Neurological disorders, Substance abuse, others

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

Compensation: Varies

Number of Visits: Unknown

16 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

We propose a clinical study of medial forebrain bundle DBS as a treatment in 20 patients with treatment refractory depression (TRD). Data from the University of Bonn indicates that surgical lesions of the medical forebrain bundle can produce therapeutic benefits in patients with depressive disorders, and suggest that DBS at the same site may also reduce symptomatology in these TRD patients (Schaepfer, 2013). Depression affects up to 10% of the US population and of those at least 10-15% do not benefit from therapies hence why we must explore new treatments. The Percept™ PC system manufactured by Medtronic Neurological will be used in this study. Study subjects will be between the ages of 22 and 70 years of age and suffer from TRD, have failed multiple treatment regimens, including ECT, and remain symptomatic. Those identified as TRD patients will then be enrolled in a clinical pilot study investigating DBS, targeting the MFB.

Will I have to stop taking my current medications?

No, you will not have to stop taking your current medications. Participants must be on a stable drug regimen of psychotropic medication for at least 6 weeks before entering the study and cannot change their medication during the study.

Is deep brain stimulation generally safe for humans?

Deep brain stimulation (DBS) is generally well-tolerated, but some reported complications include infections, lead migrations, and device malfunctions. Adverse events like wound infections, suicidality, and hypomania have been noted, and some cases required additional surgery. Cognitive safety has been reported, but larger studies are needed to confirm these findings. ^{1 2 3 4 5}

How is deep brain stimulation different from other treatments for depression?

Deep brain stimulation (DBS) is a unique treatment for depression that involves implanting electrodes in specific brain areas to modulate brain activity, unlike traditional treatments like medication or therapy. It is particularly used for treatment-resistant depression, where other methods have failed, and targets brain regions involved in mood regulation and reward processing. ^{2 6 7 8 9}

What data supports the effectiveness of the treatment Deep Brain Stimulation Model 3387 Model 3389 for depression?

Deep Brain Stimulation (DBS) has shown promising results in early studies for people with depression who haven't responded to other treatments. About half of the patients experienced long-term improvements in mood and social functioning, and their brain activity became more normal. However, these findings are based on small studies, and larger studies are needed to confirm these results. ^{2 8 9 10 11}

Who Is on the Research Team?

Joao Quevedo, MD, PhD

Principal Investigator

The University of Texas Health Science Center, Houston

Giovana Zunta Soares, MD

Principal Investigator

The University of Texas Health Science Center, Houston

Jair C Soares, MD

Principal Investigator

The University of Texas Health Science Center, Houston

Are You a Good Fit for This Trial?

This trial is for adults aged 22-70 with severe, treatment-resistant depression (TRD) who have tried multiple medications, psychotherapy, and possibly ECT without success. Participants must be in generally good health and not currently abusing substances. Pregnant women or those at risk of pregnancy without effective contraception are excluded.

Inclusion Criteria

Able to give written informed consent

Global Assessment of Function (GAF) score of 45 or less

My depression has recurred 4+ times or lasted 2+ years, starting over 5 years ago.

Exclusion Criteria

I do not have any brain-related health issues like dementia.

I've had surgery to target a specific area in my brain before.

Any clinically significant abnormality on preoperative magnetic resonance imaging (MRI)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Phase

A 1 month period with no stimulation following surgical implantation

4 weeks

Variable Staggered Phase

Blinded stimulation onset starting from 1 month to 3 months post implant, with optimal parameter determination

8 weeks

Initial Chronic Phase

Blinded bilateral stimulation, lasting at least three months

12 weeks

Continuation Phase

Unblinded active bilateral or unilateral stimulation to maximize clinical response

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Deep Brain Stimulation Model 3387 Model 3389

Trial Overview The study tests Deep Brain Stimulation (DBS) using the Percept™ PC system by Medtronic Neurological to target the medial forebrain bundle in patients with TRD. The goal is to see if DBS can reduce depressive symptoms in those who haven't responded to other treatments.

How Is the Trial Designed?

Group I: Deep Brain Stimulation Experimental Treatment 1 Intervention

Device implantation (Deep Brain Stimulation Model 3387 Model 3389)

Who Is Running the Clinical Trial?

The University of Texas Health Science Center, Houston

Lead Sponsor

Trials

974

Recruited

361,000+

Medtronic

Industry Sponsor

Trials

627

Recruited

767,000+

Geoff Martha

Medtronic

Chief Executive Officer since 2020

Finance degree from Penn State University

Dr. Richard Kuntz

Medtronic

Chief Medical Officer since 2023

MD, MSc

Published Research Related to This Trial

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) 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) 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) 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]

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]

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) 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]

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]

Citations

1. Netherlands pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for major depression. [2013]

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

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

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. Switzerland pubmed.ncbi.nlm.nih.gov

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

5. Poland pubmed.ncbi.nlm.nih.gov

Deep brain stimulation of the medial forebrain bundle for treatment-resistant depression - a narrative literature review. [2023]

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

Pallidal stimulation-induced psychosis and suicidality in Parkinson's disease. [2023]

10. Poland pubmed.ncbi.nlm.nih.gov

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

11. 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]