Deep Brain Stimulation for Bipolar Disorder

(DBS in TRBD Trial)

Recruiting in Palo Alto (17 mi)

+3 other locations

Overseen by Wayne K Goodman, MD

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Wayne Goodman MD

Must be taking: Bipolar medications

Disqualifiers: Psychotic disorder, Substance use, others

No Placebo Group

Approved in 3 Jurisdictions

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 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.

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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.

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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.

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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)

Trial 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)

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Baylor College of Medicine Houston, TX

Massachusetts General Hospital Boston, MA

Rice University Houston, TX

University of Washington Seattle, WA

Who Is Running the Clinical Trial?

Wayne Goodman MD Lead Sponsor

National Institute of Neurological Disorders and Stroke (NINDS) Collaborator

University of Washington Collaborator

William Marsh Rice University Collaborator

Massachusetts General Hospital Collaborator

References

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

Deep brain stimulation for bipolar disorder-review and outlook. [2017] Research on deep brain stimulation (DBS) for treatment-resistant psychiatric disorders has established preliminary efficacy signals for treatment-resistant depression. There are only few studies on DBS that included patients suffering from bipolar disorder. This article gives an overview of these studies concerning DBS targets, antidepressant efficacy, and the occurrence of manic/hypomanic symptoms under stimulation. First, promising results show that all patients experienced significant improvement in depressive symptomatology. In a single case, hypomanic symptoms occurred, but they could be resolved by adjusting stimulation parameters. Furthermore, this article highlights important clinical differences between unipolar and bipolar depression that have to be considered throughout the course of treatment.

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] The use of deep brain stimulation (DBS) has been recently extended for treating resistant psychiatric disorders, but the experience in patients with schizophrenia-related disorders and bipolar disorder (BD) is scarce.

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

Neurosurgical treatment of bipolar depression: defining treatment resistance and identifying surgical targets. [2010] Bipolar disorder (BD) is a complex psychiatric disorder that is often underrecognized, misdiagnosed, and challenging to detect. During the past decade, substantial progress has been made in the development of pharmacotherapeutic and psychosocial interventions for various phases of BD. Notwithstanding these developments, the majority of BD individuals, and particularly patients with bipolar depression, receiving guideline concordant care do not experience syndromal or functional recovery, underscoring the need for novel treatments. Early success with deep brain stimulation (DBS) in the treatment of major depressive episodes as part of major depressive disorder (MDD) has provided the impetus to explore its application in other treatment-resistant psychiatric disorders, notably BD. Herein, we provide the rationale for employing DBS as an alternative treatment avenue in individuals with bipolar depression.

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] Deep brain stimulation (DBS) is an effective surgical treatment for patients with Parkinson's disease (PD). DBS therapy, particularly with the subthalamic nucleus (STN) target, has been linked to rare psychiatric complications, including depression, impulsivity, irritability, and suicidality. Stimulation-induced elevated mood states can also occur. These episodes rarely meet DSM-5 criteria for mania or hypomania.

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

Use of deep brain stimulation for major affective disorders. [2020] The multifactorial etiology of major affective disorders, such as major depression and bipolar disorder, poses a challenge for identification of effective treatments. In a substantial number of patients, psychopharmacologic treatment does not lead to effective continuous symptom relief. The use of deep brain stimulation (DBS) for treatment-resistant patients is an investigational approach that has recently produced promising results. The recent development of safer stereotaxic neurosurgery, and the combination with functional neuroimaging to map the affected brain circuits, have led to the investigation of DBS as a potential strategy to treat major mood disorders. Several independent clinical studies have recently shown that chronic DBS treatment leads to remission of symptoms in a high number of treatment-resistant patients for major depression and bipolar disorder. In conclusion, the existing proof-of-principle that DBS can be an effective intervention for treatment-resistant depression opens new avenues for treatment. However, multicenter, randomized and blind trials need to confirm efficacy and be approved after the most recent failures. Patient selection and surgical-related improvements are key issues that remain to be addressed to help deliver more precise and customized treatment.

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

Mania following deep brain stimulation for Parkinson's disease. [2022] Three patients with PD developed manic behavior after bilateral implantation of electrodes for deep-brain stimulation (DBS). Common to all three patients were manic symptoms unremitting after levodopa reduction or stimulation "off," lower electrodes positioning caudal to the subthalamic nucleus area, postoperative DBS with the lower contacts (0) of the quadripolar electrodes, and resolution of the manic episodes coinciding with stimulation through higher contacts.

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

Deep brain stimulation of a patient with psychogenic movement disorder. [2020] The long-term safety of deep brain stimulation (DBS) is an important issue because new applications are being investigated for a variety of disorders. Studying instances where DBS was inadvertently implanted in patients without a movement disorder may provide information about the safety of the therapy. We report the case of a patient with a psychogenic movement disorder treated with deep brain stimulation (DBS).

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

Pharmacological treatment of deep brain stimulation-induced hypomania leads to clinical remission while preserving motor benefits. [2013] Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for Parkinson's disease, but can lead to adverse effects including psychiatric disturbance. Little is known about the risk factors and treatment options for such effects. Here, we describe a patient who reproducibly developed stimulation-induced hypomania when using ventrally located electrodes and responded well to pharmacological intervention while leaving the stimulation parameters unchanged to preserve motor benefits. In spite of clinical remission, [¹⁵O]-positron-emission-tomography (PET) demonstrated activation patterns similar to those reported during mania. This case, therefore, highlights an important treatment option of adverse effects of DBS, but also points toward the need for investigations of its risk factors and their underlying neurobiological mechanisms.

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] Deep brain stimulation (DBS) is an effective treatment for refractory obsessive-compulsive disorder (OCD). Bipolar disorder (BD) is generally considered a contra-indication for DBS due to frequently reported transient impulsivity or (hypo)mania.