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

Trial Summary

What is the purpose of this trial?

This study is only enrolling at Baylor College of Medicine. The other research locations listed serve to support data analysis only. This research study is to investigate the use of technology called Deep Brain Stimulation (DBS) to potentially improve Treatment-Resistant Bipolar Depression (TRBD) symptoms in patients with severe cases. DBS involves the surgical implantation of leads and electrodes into specific areas of the brain, which are thought to influence the disease. A pack implanted in the chest, called the neurotransmitter, keeps the electrical current coursing to the brain through a wire that connects the neurotransmitter and electrodes. It is believed DBS may restore balance to dysfunctional brain circuitry implicated in TRBD. The goal of this study is to enhance current approaches to DBS targeting in the brain and to use a novel approach to find a better and more reliable system for TRBD treatment. Its important for participants to understand that this is an investigational study where there could be a lack of effectiveness in improving TRBD symptoms. There may be no directly benefit from taking part in this study. This study is expected to last 20 months and involves 3 main steps. 1. Medical, psychiatric, and cognitive evaluations. 2. Implantation of a brain stimulation system. 3. Follow up after implantation of device, including programming, recording, and psychiatric testing. There are risks and benefits to this study which need to be considered when deciding to participate or not. Some of the risks are from surgery, the DBS device and programming, the tests involved, and potential loss of confidentiality, as well as other unknown risks. Some of the more serious risks involved in this study and the percentage that they occur: 1. Bleeding inside the Brain (1 to 2 percent). 2. Infection from the procedures (3 percent) 3. Seizure caused from the procedures (1.2 percent) However, the benefit of this study is that it may help relieve or decrease TRBD symptoms. This form of treatment has shown to reduce symptom severity in other cases. This could potentially improve quality of life and activities in daily routines. There is also a potential benefit to society in that the data the investigators will obtain from this study may help increase the understanding of the mechanisms underlying TRBD symptoms, as well as enhanced Deep Brain Stimulation techniques. Study participation is expected to last 20 months from the time the DBS device is activated and should include approximately 23 visits. These visits also include 8 separate, 24 hour stays at the Menninger NeuroBehvaioral Monitoring Unit (NBU). These 24-hour sessions will occur at multiple points throughout the study (1 week prior to surgery, the week preceding device activation, the week following activation, then after 2 weeks, 4 weeks, 6 months, 9 months, and 12 months). Participants will need to stay locally for the week of the NBU stay (typically Monday through Friday). Study visits will include clinician administered assessments and questionnaires, subject reported assessments, neuropsychological testing, and mobile behavioral assessments which will occur around 23 visits over the course of 20 months.

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 safety data exists for DBS in treating bipolar disorder?

Safety data for DBS in treating bipolar disorder is limited but includes reports of psychiatric side effects such as hypomanic symptoms, which can often be managed by adjusting stimulation parameters. Studies on DBS for Parkinson's disease also report psychiatric complications like mania and hypomania, which are sometimes resolved by changing electrode positioning or using pharmacological treatments. These findings suggest that while DBS can be effective, it may lead to psychiatric side effects that require careful management. ^{1 2 3 4 5}

Is Deep Brain Stimulation a promising treatment for Bipolar Disorder?

Deep Brain Stimulation (DBS) shows promise as a treatment for Bipolar Disorder, as studies indicate significant improvement in depressive symptoms for patients. Although there are few studies, the results are encouraging, with manageable side effects. ^{1 2 3 6 7}

What data supports the idea that Deep Brain Stimulation for Bipolar Disorder (also known as: Deep Brain Stimulation, DBS, Deep Brain Stimulation Therapy) is an effective treatment?

The available research shows that Deep Brain Stimulation (DBS) has shown promising results for treating bipolar disorder, especially in cases where other treatments have failed. One study mentioned that all patients experienced significant improvement in their depressive symptoms after receiving DBS. Although there was a case of hypomanic symptoms, these were managed by adjusting the treatment settings. Additionally, DBS has been successful in treating major depressive episodes in other conditions, which suggests it could be effective for bipolar disorder as well. However, more extensive studies are needed to confirm these findings. ^{1 2 6 8 9}

Research Team

Wayne K Goodman, MD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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) 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) 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]

References

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

Deep brain stimulation for bipolar disorder-review and outlook. [2017]

2. Spain pubmed.ncbi.nlm.nih.gov

Deep brain stimulation and digital monitoring for patients with treatment-resistant schizophrenia and bipolar disorder: A case series. [2023]

3. Denmark pubmed.ncbi.nlm.nih.gov

Neurosurgical treatment of bipolar depression: defining treatment resistance and identifying surgical targets. [2010]

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

Elevated Mood States in Patients With Parkinson's Disease Treated With Deep Brain Stimulation: Diagnosis and Management Strategies. [2022]

5. Greece pubmed.ncbi.nlm.nih.gov

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

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

Mania following deep brain stimulation for Parkinson's disease. [2022]

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

Deep brain stimulation of a patient with psychogenic movement disorder. [2020]

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

Pharmacological treatment of deep brain stimulation-induced hypomania leads to clinical remission while preserving motor benefits. [2013]

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

Is deep brain stimulation effective and safe for patients with obsessive compulsive disorder and comorbid bipolar disorder? [2021]