Deep Brain Stimulation for Bipolar Disorder

(DBS in TRBD Trial)

Recruiting at 3 trial locations

Overseen By Nora Vanegas, MD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Wayne Goodman MD

Must be taking: Bipolar medications

Disqualifiers: Psychotic disorder, 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: 6

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a technology called Deep Brain Stimulation (DBS) to determine its effectiveness for individuals with severe bipolar disorder unresponsive to other treatments. DBS involves placing a device in the brain to send electrical signals, potentially managing mood symptoms. The study aims to refine DBS use to enhance its effectiveness for bipolar disorder. Individuals diagnosed with bipolar disorder who have tried at least four different treatments without success may be suitable candidates. Participants should expect involvement for about 20 months, including several hospital visits and evaluations. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could improve future treatment options for bipolar disorder.

Do I have to stop taking my current medications for the trial?

The trial requires that you stay on a stable dose of your current psychotropic medications for at least four weeks before the surgery. So, you won't need to stop taking them, but you must maintain a stable dose.

What prior data suggests that Deep Brain Stimulation is safe for treating Treatment-Resistant Bipolar Depression?

Research has shown that Deep Brain Stimulation (DBS) is safely used in people with depression that doesn't respond to other treatments. In these studies, about half of the patients experienced fewer symptoms, indicating that DBS can be a well-tolerated treatment option for some individuals.

Regarding safety, research indicates that DBS is generally safe for those with severe depression. Serious risks include bleeding in the brain, occurring in 1 to 2 percent of cases, and infections from the procedure, which occur in about 3 percent of cases. Seizures can also happen in 1.2 percent of cases. Although these risks may sound serious, they are relatively rare.

DBS involves surgery and placing a device in the brain, which might seem intimidating. However, for many patients, the benefits of reducing severe symptoms can outweigh these risks. It's important to remember that while DBS shows promise, it might not work for everyone. Each person's experience with DBS can differ. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about deep brain stimulation (DBS) for bipolar disorder because it offers a unique approach compared to standard medications like mood stabilizers and antipsychotics. Unlike these typical treatments, DBS involves surgically implanting a device that sends electrical impulses to specific brain areas, potentially providing more precise control over mood regulation. This method could offer hope for those who haven't responded well to conventional treatments, offering a new avenue for managing symptoms with potentially fewer side effects.

What evidence suggests that Deep Brain Stimulation is effective for Treatment-Resistant Bipolar Depression?

Research has shown that Deep Brain Stimulation (DBS) can significantly aid individuals with depression, including bipolar disorder, that hasn't improved with other treatments. Approximately 30% of individuals experience remission, where symptoms disappear, and around 50% see symptom improvement. DBS sends electrical signals to specific brain areas, potentially balancing the circuits causing the disorder. Long-term studies suggest these benefits can last for many years. This method offers hope for those who haven't found relief with other treatments. Participants in this trial will undergo surgical implantation of the Medtronic Percept RC DBS system, with some experiencing a one-month blinded discontinuation period to assess the dependency of response on ongoing DBS. ^{1 3 4 5 6}

Who Is on the Research Team?

Wayne K Goodman, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for patients with severe Treatment-Resistant Bipolar Depression (TRBD) who haven't improved with standard treatments. Participants must be willing to undergo surgery to implant a brain stimulation device and commit to a 20-month study period, including multiple evaluations and hospital stays.

Inclusion Criteria

I have been on a steady dose of my mental health medication for at least 4 weeks.

I am between 22 and 64 years old.

My first mood disorder episode happened before I turned 40.

Exclusion Criteria

Currently meets criteria for a manic or hypomanic episode or rapid cycling

Lifetime history of a psychotic disorder or psychotic symptoms outside of bipolar mood episodes

Alcohol/substance use disorder, moderate or severe, within the previous 12 months (excluding nicotine)

Timeline for a Trial Participant

Screening and Baseline

Participants are screened for eligibility to participate in the trial

8 weeks

2 visits (in-person)

Surgical Procedures

Implantation of a brain stimulation system with bilateral leads targeting specific brain areas

1 week

1 visit (in-person)

Post-Surgery Recovery and Device Activation

Recovery from surgery and initial activation of the DBS device

2 weeks

2 visits (in-person)

DBS Programming and Optimization

Initial DBS programming and optimization sessions, including monopolar survey and programming adjustments

6 weeks

Multiple visits (in-person)

Chronic DBS Programming and Monitoring

Monthly visits for chronic DBS programming optimization and monitoring of efficacy and safety

7 months

Monthly visits (in-person)

Blinded Discontinuation Period

Blinded discontinuation of DBS to assess dependency on ongoing stimulation

1 month

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 months

Monthly visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Deep Brain Stimulation

Trial Overview The trial tests Deep Brain Stimulation (DBS) using the Medtronic Percept RC System on TRBD. It involves surgical implantation of electrodes in the brain, followed by regular follow-ups for programming and psychiatric testing over 20 months.

How Is the Trial Designed?

Group I: One Month Blinded Discontinuation Period Experimental Treatment 1 Intervention

The investigators will use blinded discontinuation at 12 months rather than sham control to establish evidence that response is dependent on ongoing DBS.

Group II: Medtronic Percept RC System Implantation for TRBD Experimental Treatment 1 Intervention

All subjects will receive surgical implantation of Percept RC DBS system

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+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

University of Washington

Collaborator

Trials

1,858

Recruited

2,023,000+

William Marsh Rice University

Collaborator

Trials

50

Recruited

28,400+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

Published Research Related to This Trial

In a one-year study involving four treatment-resistant patients with schizophrenia and bipolar disorder, deep brain stimulation (DBS) led to significant clinical improvements, including reduced scores on the Clinical Global Impression and Hamilton Depression Rating Scale.

DBS was found to be safe, with no side effects or cognitive changes reported, and allowed three patients to discontinue maintenance electroconvulsive therapy, suggesting it may be a viable treatment option for complex psychiatric disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation and digital monitoring for patients with treatment-resistant schizophrenia and bipolar disorder: A case series. Bioque, M., Rumià, J., Roldán, P., et al.[2023]

A case study of a patient with a psychogenic movement disorder who underwent 5 years of deep brain stimulation (DBS) for presumed Parkinson's disease showed no adverse effects or benefits from the treatment, indicating a lack of negative impact on neural tissue.

The patient's normal dopamine transporter scan and PET scan results suggest that DBS may be safe even when used inappropriately, providing insights into its long-term safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation of a patient with psychogenic movement disorder. Langevin, JP., Skoch, JM., Sherman, SJ.[2020]

Deep brain stimulation (DBS) has shown promising efficacy in significantly improving depressive symptoms in patients with treatment-resistant bipolar disorder, although research in this area is limited.

While there was a case of hypomanic symptoms occurring during DBS treatment, these were successfully managed by adjusting the stimulation parameters, indicating a need for careful monitoring and adjustment in bipolar patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for bipolar disorder-review and outlook. Gippert, SM., Switala, C., Bewernick, BH., et al.[2017]

Deep brain stimulation (DBS) of the ventral anterior limb of the internal capsule significantly improved symptoms of obsessive-compulsive disorder (OCD) and depression in five patients with treatment-refractory OCD and comorbid bipolar disorder, with notable reductions in Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and Hamilton Depression Rating Scale (HAM-D) scores over a follow-up period of 15 to 68 months.

While transient hypomanic symptoms occurred in 4 out of 5 patients, these symptoms were manageable and did not lead to serious adverse effects, suggesting that bipolar disorder should not be an absolute contraindication for DBS in OCD patients, although careful monitoring is essential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is deep brain stimulation effective and safe for patients with obsessive compulsive disorder and comorbid bipolar disorder? Graat, I., van Rooijen, G., Mocking, R., et al.[2021]

In a study of 82 Parkinson's disease patients treated with deep brain stimulation (DBS), 11% experienced stimulation-induced elevated mood states, particularly after programming changes, highlighting a potential psychiatric complication of this treatment.

Patients with pre-existing psychiatric risk factors were more likely to develop these elevated mood states, suggesting that thorough preoperative psychiatric evaluations are crucial for identifying individuals at risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elevated Mood States in Patients With Parkinson's Disease Treated With Deep Brain Stimulation: Diagnosis and Management Strategies. Seritan, AL., Spiegel, LL., Weinstein, JL., et al.[2022]

Deep brain stimulation (DBS) has shown promising results in treating treatment-resistant major depression and bipolar disorder, with several studies indicating that it can lead to remission of symptoms in many patients.

The advancement of safer neurosurgery techniques and the use of functional neuroimaging to target specific brain circuits have enhanced the potential of DBS, but further multicenter, randomized trials are needed to confirm its efficacy and refine patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of deep brain stimulation for major affective disorders. Mi, K.[2020]

In a study of three patients with Parkinson's disease (PD), manic behavior developed after deep-brain stimulation (DBS) due to specific electrode positioning and stimulation settings.

Manic symptoms persisted despite reducing levodopa and turning off stimulation, but they resolved when stimulation was adjusted to higher electrode contacts, suggesting that electrode placement and stimulation parameters are critical in managing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mania following deep brain stimulation for Parkinson's disease. Kulisevsky, J., Berthier, ML., Gironell, A., et al.[2022]

Deep brain stimulation (DBS) of the subthalamic nucleus can effectively treat Parkinson's disease but may cause psychiatric side effects like hypomania, as seen in a patient with ventrally located electrodes.

The patient responded well to pharmacological treatment for hypomania while maintaining the same stimulation settings, suggesting that managing side effects without altering DBS parameters is a viable strategy, though further research is needed to understand the underlying mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological treatment of deep brain stimulation-induced hypomania leads to clinical remission while preserving motor benefits. Schilbach, L., Weiss, PH., Kuhn, J., et al.[2013]

Deep brain stimulation (DBS) shows promise as a novel treatment for bipolar depression, particularly for patients who do not respond to conventional therapies, as it has demonstrated acute and sustained antidepressant effects in similar conditions like major depressive disorder.

Research indicates that depressive symptoms in bipolar disorder are often more burdensome and less responsive to current treatments, highlighting the need for innovative approaches like DBS that target specific neural circuits involved in mood regulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurosurgical treatment of bipolar depression: defining treatment resistance and identifying surgical targets. Lipsman, N., McIntyre, RS., Giacobbe, P., et al.[2010]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10210071/

Brain stimulation treatment for bipolar disorder - PMC A meta‐analysis of six prospective and retrospective studies found remission rates of 50.9% (n = 402/790) in patients with major depressive disorder (MDD) and ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06599099

Study Details | NCT06599099 | Deep Brain Stimulation of ... This research study is to investigate the use of technology called Deep Brain Stimulation (DBS) to potentially improve Treatment-Resistant Bipolar Depression ( ...

3. mountsinai.org mountsinai.org/about/newsroom/2019/long-term-follow-up-data-shows-deep-brain-stimulation-is-an-effective-treatment-for-treatment-resistant-depression

Long-Term Follow-Up Data Shows Deep Brain Stimulation ... Response and remission rates were maintained at or above 50 percent and 30 percent, respectively, through years 2-8 of the follow-up period.

4. sciencedirect.com sciencedirect.com/science/article/pii/S0165032725008134

Pre-operative predictors of response to deep brain ... Deep Brain Stimulation (DBS) for treatment-resistant depression (TRD) results in about 50 % response and 30 % remission. Response prediction may optimize ...

5. clinicbarcelona.org clinicbarcelona.org/en/news/deep-brain-stimulation-improves-symptoms-in-patients-with-treatment-resistant-schizophrenia-and-bipolar-disorder

Deep brain stimulation improves symptoms in patients with ... The study shows that the technique can be a safe and effective alternative for complex cases that do not respond to therapies.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01476527

Deep Brain Stimulation for the Treatment of Refractory ... Our primary objective is to establish the safety of deep brain stimulation in a patient population with treatment refractory bipolar disorder. Official ...