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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether deep brain stimulation, which involves electrical impulses to the brain, can aid individuals with severe depression unresponsive to other treatments. The study aims to determine the safety and effectiveness of this approach and to understand its mechanism. Suitable candidates have major depression lasting at least two years or have experienced more than four depressive episodes despite trying multiple antidepressants or therapies. Participants will have a device implanted for brain stimulation and will be monitored for up to ten years. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could lead to new treatment options for severe depression.

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 prior data suggests that this device is safe for treating depression?

Research has shown that deep brain stimulation (DBS) for treatment-resistant depression is generally safe. In earlier studies, about 67% of patients experienced side effects, also known as adverse events, which were usually moderate. However, some concerns about suicide have been noted, so awareness of this risk is crucial.

Despite these concerns, long-term evidence suggests that DBS remains a safe option for those who haven't found success with other depression treatments. When considering participation in a trial like this, it's important to weigh both the possible side effects and the potential benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about deep brain stimulation for depression because it offers a novel approach for those who haven't found relief with standard treatments like antidepressants or therapy. Unlike these conventional methods, which primarily aim to balance brain chemicals, deep brain stimulation involves implanting a device that directly stimulates specific brain areas associated with mood regulation. This targeted electrical stimulation could provide relief more quickly and effectively than traditional treatments for people with treatment-resistant depression.

What evidence suggests that deep brain stimulation is effective for depression?

Research has shown that deep brain stimulation (DBS), which participants in this trial will receive, can help people with major depression who haven't improved with other treatments. Studies indicate that about 56% of patients respond well to DBS. One study found that depression symptoms improved by 47% over time. On average, it takes about 23 months for half of the patients to experience this level of improvement. This evidence suggests that DBS is a promising option for those with treatment-resistant depression. ^{1 2 6 7 8}

Who Is on the Research Team?

Patricio Riva Posse, MD

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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) 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) 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) 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]

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) 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) 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]

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) 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8047101/

Deep Brain Stimulation in Treatment-Resistant Depression For efficacy, DBS treatment was statistically beneficial for TRD, and the response, remission, and recurrence rates were 56% (ranging from 43 to ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02046330

Deep Brain Stimulation (DBS) Therapy for Treatment ... We propose a clinical study of medial forebrain bundle DBS as a treatment in 20 patients with treatment refractory depression (TRD). Data from the ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2451902224002489

Efficacy of Deep Brain Stimulation for Treatment-Resistant ... Deep brain stimulation achieved 47% improvement in long-term depression scale scores, with an estimated time to reach 50% improvement of around 23 months.

4. nature.com nature.com/articles/s41398-024-02951-7

Cost-effectiveness and threshold analysis of deep brain ... If remission rates ≥8–19% are achieved, DBS-rc will likely be more cost-effective than TAU for TRD, with further increasing cost-effectiveness ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4413473/

Deep Brain Stimulation for Treatment-Resistant Depression ECT may be less effective in treatment-resistant patients, but it is still associated with a remission rate of 50%–60% (21–23). However, ECT can have side ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/24867326/

Deep brain stimulation for treatment-resistant depression We performed a systematic review of the literature pertaining to DBS for treatment-resistant depression to evaluate the safety and efficacy of this procedure. ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1878747923010784

Deep Brain Stimulation for Depression 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 ...

8. psychiatryonline.org psychiatryonline.org/doi/10.1176/appi.ajp.2010.10081187

Deep Brain Stimulation for Treatment-Resistant Depression These data suggest that in the long term, DBS remains a safe and effective treatment for treatment-resistant depression.