Deep Brain Stimulation for Schizophrenia

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Johns Hopkins University

Must be taking: Antipsychotics

Disqualifiers: Drug abuse, Neurological condition, 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: 1 year

6 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to assist individuals with schizophrenia who haven't improved with standard treatments. It employs deep brain stimulation (DBS), which sends electrical impulses to specific brain areas, targeting symptoms like auditory hallucinations and delusions. Suitable participants must have had schizophrenia or schizoaffective disorder for at least a year, continue to experience these symptoms despite multiple treatments, and be able to walk independently. The goal is to determine if DBS can provide relief when other options have failed. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to new treatment options for schizophrenia.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, since it involves deep brain stimulation for treatment-resistant schizophrenia, it's possible that you may need to continue your current antipsychotic medications.

What prior data suggests that this method is safe for treatment-resistant schizophrenia?

Research has shown that deep brain stimulation (DBS) has been used for many conditions, with over 100,000 patients treated worldwide, suggesting it is generally safe. It has improved symptoms and quality of life in other difficult-to-treat disorders.

Although DBS is not yet approved for schizophrenia, early studies found it safe for patients with treatment-resistant schizophrenia, with no major safety issues reported. As this is a new treatment for schizophrenia, ongoing monitoring is important to ensure it remains safe and effective.

Overall, DBS is usually well-tolerated, but each person's experience can differ. It is essential to discuss potential risks and benefits with a doctor before deciding to join a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about deep brain stimulation for schizophrenia because it offers a novel approach compared to traditional treatments like antipsychotic medications. Unlike medications that target neurotransmitter systems throughout the brain, this technique works by directly stimulating specific brain regions, such as the substantia nigra pars reticulata, which may help manage symptoms in treatment-resistant cases. This precise targeting could potentially reduce side effects and improve outcomes for those who haven't responded well to existing therapies.

What evidence suggests that deep brain stimulation might be an effective treatment for schizophrenia?

Research has shown that deep brain stimulation (DBS) can help people with schizophrenia who haven't responded to other treatments. In some studies, many patients felt better after undergoing DBS. For instance, one study found that 58% of patients improved when electrodes were placed in specific brain areas. Although DBS isn't yet approved for treating schizophrenia, it has shown promise for other mental health conditions by easing symptoms and improving quality of life. This trial will specifically investigate the effects of DBS on treatment-resistant schizophrenia by targeting the substantia nigra pars reticulata. This method adjusts brain circuits related to schizophrenia symptoms, offering hope for those who haven't found relief with standard treatments. ^{1 2 3 6 7}

Who Is on the Research Team?

Nicola Cascella

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for adults at least 22 years old with severe, treatment-resistant schizophrenia who have not responded to multiple antipsychotic medications. Participants must be able to walk, understand English, consent to the study, and use birth control if necessary. They can't join if they've had recent major surgery, drug abuse issues within the last six months, or any medical conditions that could interfere with the study.

Inclusion Criteria

I have been diagnosed with schizophrenia or schizoaffective disorder.

I can walk on my own.

A psychiatrist confirmed I can make my own medical decisions.

Exclusion Criteria

Subject has a medical illness/condition, co-morbid psychiatric illness, and/or abnormal diagnostic finding that would interfere with the completion of the study, confound the results of the study, or pose risk to the patient

Subject has participated in another investigational drug trial or therapeutic trial within 30 days of Baseline Visit 1

Subject has a diagnosis of mental retardation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Deep brain stimulation of the substantia nigra pars reticulata for treatment-resistant schizophrenia

1 year

Frequent monitoring and clinical assessment with psychiatric scales

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Deep Brain Stimulation

Trial Overview The trial tests Deep Brain Stimulation (DBS) using Medtronic's Percept with SensSight System targeting a brain area called substantia nigra pars reticulata (SNr). It aims to help those whose schizophrenia doesn't improve with medication by potentially altering neural circuits involved in the disorder.

How Is the Trial Designed?

Group I: Deep Brain Stimulation Implant Experimental Treatment 1 Intervention

Unblinded treatment arm, deep brain stimulation of the substantia nigra pars reticulata for treatment resistant schizophrenia.

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?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

Deep brain stimulation (DBS) is being explored as a potential treatment for schizophrenia (SZ), a condition that currently has significant unmet needs due to issues like relapse and ineffective treatments for negative and cognitive symptoms.

Research suggests that SZ may be a circuit disorder, and DBS could help by modulating striatal dysregulation, with ongoing clinical trials assessing its efficacy and ethical considerations for patients with severe symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Approaches to neuromodulation for schizophrenia. Gault, JM., Davis, R., Cascella, NG., et al.[2022]

Deep brain stimulation (DBS) has shown promise in treating treatment-resistant schizophrenia, with four out of seven patients meeting symptomatic response criteria after stimulation in either the subgenual anterior cingulate cortex or the nucleus accumbens.

DBS was associated with significant changes in glucose metabolism in various brain regions, suggesting that it may improve symptoms by modulating activity in the cortico-basal-thalamic-cortical circuit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain metabolic changes in patients with treatment resistant schizophrenia treated with deep brain stimulation: A series of cases. Roldán, A., Portella, MJ., Sampedro, F., et al.[2021]

A systematic review of 96 studies found that the most common complications from Deep Brain Stimulation (DBS) procedures include infections (5.12% of patients) and lead migration (1.60%), highlighting the importance of monitoring for these issues post-surgery.

Patients with conditions like dystonia and off-label indications such as Tourette's syndrome are at a higher risk for hardware-related complications, suggesting that these patients should receive thorough pre-surgical counseling and close follow-up care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review of hardware-related complications of Deep Brain Stimulation: Do new indications pose an increased risk? Jitkritsadakul, O., Bhidayasiri, R., Kalia, SK., et al.[2022]

Deep brain stimulation (DBS) targeting the nucleus accumbens (NAcc) and subgenual anterior cingulate cortex (subgenual ACC) shows potential therapeutic effects in treatment-resistant schizophrenia, with 58% improvement in PANSS scores for NAcc and 68% for subgenual ACC among patients who met improvement criteria.

While physical side effects were rare, two patients experienced persistent psychiatric adverse effects, highlighting the need for larger trials to assess the safety and efficacy of DBS in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation in treatment resistant schizophrenia: A pilot randomized cross-over clinical trial. Corripio, I., Roldán, A., Sarró, S., et al.[2021]

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]

In a comparison of surgical outcomes, patients with schizophrenia/schizoaffective disorder (SZ/SAD) showed lower postsurgical mortality rates (1.01-4.11% lower) than those with Parkinson's disease (PD), suggesting that surgical risks may not be as high as previously thought for DBS in SZ/SAD.

While morbidity was slightly higher in SZ/SAD patients (1.91-2.73% higher), there was no increase in serious complications like hemorrhages or infections, indicating that DBS could be a viable option for these patients under careful selection criteria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postsurgical morbidity and mortality favorably informs deep brain stimulation for new indications including schizophrenia and schizoaffective disorder. Gault, JM., Hosokawa, P., Kramer, D., et al.[2023]

Deep brain stimulation (DBS) of the habenula has shown promise as a safe and effective treatment for severe, chronic, and treatment-resistant schizophrenia in two young adult male patients, with initial improvements in symptoms observed within the first 6 months after surgery.

While one patient maintained clinical benefits at the 12-month follow-up, the other experienced a worsening of symptoms, highlighting that while DBS may be beneficial for some, it does not guarantee long-term success for all patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Habenula deep brain stimulation for intractable schizophrenia: a pilot study. Wang, Y., Zhang, C., Zhang, Y., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6953640/

Deep brain stimulation in treatment resistant schizophrenia Of the remaining 7 patients, 2/3 with NAcc and 2/4 with subgenual ACC electrode placements met the symptomatic improvement criteria (58% and 86% ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12536682/

Effectiveness of deep brain stimulation in alleviating ... Findings indicate that deep brain stimulation effectively alleviates symptoms in a significant proportion of individuals with treatment- ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2667049625000274

Review Deep brain stimulation in neuropsychiatric disorders DBS proves effective in refractory neuropsychiatric disorders, modulating specific symptoms and improving quality of life. Methodological ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02377505

Deep Brain Stimulation in Treatment Resistant Schizophrenia This study aims at assessing efficacy and safety of Deep Brain Stimulation (DBS) for treatment of patients with treatment resistant schizophrenia, ...

5. hopkinsmedicine.org hopkinsmedicine.org/news/articles/2021/12/a-new-application-of-deep-brain-stimulation-for-treatment-resistant-schizophrenia

A New Application of Deep Brain Stimulation for Treatment ... Johns Hopkins researchers report the first known use of DBS in a certain portion of the brain for treatment-resistant schizophrenia.

6. bmcpsychiatry.biomedcentral.com bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-025-07128-0

Ethical considerations of deep brain stimulation for treatment ... Excitement about deep brain stimulation (DBS) has grown from widespread safe and effective treatment of over 100,000 patients worldwide, ...

7. psychiatrictimes.com psychiatrictimes.com/view/dbs-a-solution-to-treatment-resistant-schizophrenia

DBS: A Solution to Treatment-Resistant Schizophrenia DBS shows promise for treatment-resistant schizophrenia, but ethical, cost, and acceptability issues hinder its widespread use. Dora's case ...