Brain Stimulation for Schizophrenia

Overseen By Megan A Boudewyn, Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of California, Davis

Disqualifiers: Epilepsy, Neurological disorders, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 20 minutes per session

120 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to better understand the neural correlates of higher-order cognition, both in the healthy brain and in schizophrenia, and to determine how these mechanisms are modulated by transcranial direct current stimulation (tDCS) at frontal and occipital scalp sites. Testing the effects of tDCS at these scalp sites on cognitive task performance will help us understand the roles of the brain regions corresponding to these sites during higher-order cognitive processing (language comprehension, cognitive control, and related attention and memory processes). Behavioral and electrophysiological (EEG) measures will be used to assess cognitive performance. The investigator's overarching hypothesis is that stimulating prefrontal circuits with tDCS can improve cognitive control performance, and ultimately performance on a range of cognitive tasks, as compared to stimulating a different cortical region (occipital cortex) or using sham stimulation. This study is solely intended as basic research in order to understand brain function in healthy individuals and individuals with schizophrenia. This study is not intended to diagnose, cure or treat schizophrenia or any other disease.

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

The trial does not specify if you need to stop taking your current medications. However, you must not have had any medication changes in the past month and should not anticipate any changes in the upcoming month.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires that there be no medication changes in the month before and during the trial for participants with schizophrenia.

What data supports the idea that Brain Stimulation for Schizophrenia is an effective treatment?

The available research shows that Brain Stimulation for Schizophrenia, also known as transcranial direct current stimulation (tDCS), can be effective in reducing symptoms that do not respond to medication. One study found a 34% reduction in auditory hallucinations, which are common in schizophrenia. Another study reported improvements in learning, memory, and attention. However, more research is needed to confirm these findings and understand how tDCS works in the brain. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment Transcranial Direct Current Stimulation (tDCS) for schizophrenia?

Research shows that tDCS can help reduce symptoms in people with schizophrenia, such as auditory hallucinations and negative symptoms, with some studies reporting a 34% reduction in symptoms. It has also shown positive effects on cognitive functions like learning and memory. ^{1 2 3 4 5}

What safety data exists for tDCS treatment in schizophrenia?

Existing safety data indicates that transcranial direct current stimulation (tDCS) is a safe and well-tolerated treatment for schizophrenia. Studies have shown no reports of serious adverse effects or irreversible injury across over 33,200 sessions and 1,000 subjects, including potentially vulnerable populations. This includes a study specifically on schizophrenia patients confirming its safety and tolerability. Ongoing research continues to support these findings. ^{2 6 7 8 9}

Is transcranial direct current stimulation (tDCS) safe for humans?

Research shows that transcranial direct current stimulation (tDCS) is generally safe and well-tolerated in humans, including those with schizophrenia. Studies have not reported any serious adverse effects or irreversible injuries across thousands of sessions, even in potentially vulnerable groups like children and the elderly. ^{2 6 7 8 9}

Is Transcranial Direct Current Stimulation (tDCS) a promising treatment for schizophrenia?

Yes, tDCS is a promising treatment for schizophrenia. It has shown potential in reducing symptoms like auditory hallucinations and improving cognitive functions such as memory and attention. Studies suggest that tDCS can help with symptoms that don't respond well to medication. ^{1 2 3 5 8}

How is transcranial direct current stimulation (tDCS) different from other treatments for schizophrenia?

Transcranial direct current stimulation (tDCS) is a non-invasive treatment that uses a low electrical current applied to the scalp to modulate brain activity, which is different from traditional drug treatments that involve medication. It has shown promise in reducing treatment-resistant symptoms like auditory hallucinations and negative symptoms by targeting specific brain regions, such as the prefrontal cortex, which are involved in schizophrenia. ^{1 2 3 5 8}

Eligibility Criteria

This trial is for adults with schizophrenia, schizophreniform or schizoaffective disorder who have stable mental health, no recent medication changes, and a normal IQ. They must not be on clozapine, pregnant, have uncorrected vision issues that affect testing or skin conditions at electrode sites. Participants should not have substance abuse history in the last month or metal implants.

Inclusion Criteria

Must not be currently taking the antipsychotic clozapine

All subjects must have the ability to give valid informed consent.

You have been diagnosed with schizophrenia, schizophreniform or schizoaffective disorder.

Exclusion Criteria

You have vision problems that would make it difficult for you to complete cognitive tests. This includes color blindness if the test requires the ability to see different colors.

You are pregnant.

You have skin damage, such as eczema, where the electrodes will be placed.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex or occipital cortex, or sham stimulation

20 minutes per session

1 visit (in-person)

Assessment

Electrophysiological and behavioral assessments are conducted immediately following stimulation

1.5 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Transcranial Direct Current Stimulation

Trial Overview The study tests how brain function related to higher-order cognition (like language comprehension and memory) is affected by transcranial direct current stimulation (tDCS). It compares the effects of tDCS on different brain regions using behavioral tasks and EEG monitoring in both healthy individuals and those with schizophrenia.

Participant Groups

Group I: DLPFC Stimulation Experimental Treatment 1 Intervention

Intervention. 20 minutes of 2 mA direct current stimulation over the dorsolateral prefrontal cortex.

Group II: Occipital Stimulation Active Control 1 Intervention

Intervention. 20 minutes of 2 mA direct current stimulation over the occipital cortex.

Group III: Sham Stimulation Placebo Group 1 Intervention

Placebo Comparator. 0.5-1 minutes of 2 mA direct current stimulation over the dorsolateral prefrontal cortex followed by 19-19.5 minutes of sham stimulation

Transcranial Direct Current Stimulation is already approved in United States, European Union for the following indications:

Approved in United States as Transcranial Direct Current Stimulation for:

• Chronic pain management
• Depression
• Anxiety

Approved in European Union as Transcranial Direct Current Stimulation for:

• Chronic pain management
• Neurological rehabilitation

Who Is Running the Clinical Trial?

University of California, Davis

Lead Sponsor

Trials

958

Recruited

4,816,000+

Findings from Research

Transcranial direct current stimulation (tDCS) has shown promise in reducing treatment-resistant symptoms of schizophrenia, particularly auditory hallucinations, with an average symptom reduction of 34%.

tDCS also positively impacts cognitive functions such as learning, working memory, and attention in patients with schizophrenia, suggesting it may enhance overall cognitive performance alongside symptom relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Direct Current Stimulation for the Treatment of Refractory Symptoms of Schizophrenia. Current Evidence and Future Directions. Mondino, M., Brunelin, J., Palm, U., et al.[2022]

Transcranial direct current stimulation (tDCS) was applied to a woman with schizophrenia and a left prefrontal tissue lesion, but it did not improve her auditory verbal hallucinations or neuropsychological function after 20 sessions.

Electric field simulations indicated that the patient's brain showed lower activation in the dorsolateral prefrontal cortex compared to both a matched non-lesioned schizophrenia patient and healthy controls, suggesting that structural brain lesions may limit the efficacy of tDCS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

tDCS for auditory verbal hallucinations in a case of schizophrenia and left frontal lesion: efield simulation and clinical results. Mezger, E., Brunoni, AR., Hasan, A., et al.[2021]

A systematic review of 12 clinical studies on transcranial direct current stimulation (tDCS) for schizophrenia revealed that the most common electrode setup involved placing the anode over the left dorsolateral prefrontal cortex and the cathode over the temporoparietal cortex.

Computer modeling predicted that this setup activates areas linked to negative symptoms and under-activates those associated with positive symptoms, suggesting that tDCS may target specific symptom profiles in schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Understanding tDCS effects in schizophrenia: a systematic review of clinical data and an integrated computation modeling analysis. Brunoni, AR., Shiozawa, P., Truong, D., et al.[2018]

In a study of 31 adults with schizophrenia experiencing medication-refractory auditory verbal hallucinations (AVH), transcranial direct current stimulation (tDCS) showed a moderate reduction in hallucinations, with a 25%-29% improvement by the end of the second week and an additional 10% improvement maintained over four months.

The study also noted a small but significant 11% improvement in overall symptoms as measured by the Positive and Negative Syndrome Scale (PANSS-N), indicating that tDCS may provide lasting benefits for patients with persistent AVH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation for refractory auditory hallucinations in schizophrenia: Acute and 16-week outcomes. Kumar, PNS., Krishnan, AG., Suresh, R., et al.[2022]

In a study involving nine patients with schizophrenia, the combination of transcranial direct current stimulation (tDCS) and cognitive training did not show significant improvements in psychotic symptoms as measured by the Positive and Negative Syndrome Scale (PANSS).

The lack of effectiveness suggests that this specific tDCS protocol may not enhance clinical outcomes in schizophrenia, highlighting the need for larger studies to explore the potential of electric and cognitive stimulation therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of transcranial direct current stimulation (tDCS) over the prefrontal cortex combined with cognitive training for treating schizophrenia: a sham-controlled randomized clinical trial. Shiozawa, P., Gomes, JS., Ducos, DV., et al.[2022]

Transcranial Direct Current Stimulation (tDCS) has been shown to be safe, with no reports of Serious Adverse Effects or irreversible injuries across over 33,200 sessions involving more than 1,000 subjects, including vulnerable populations.

Safety assessments indicate that the current densities used in conventional tDCS (≤4 milliamperes) are significantly lower than those that could potentially cause brain injury, suggesting that tDCS protocols are well within safe limits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. Bikson, M., Grossman, P., Thomas, C., et al.[2022]

Transcranial direct current stimulation (tDCS) is a safe and well-tolerated non-invasive treatment that shows potential effectiveness in alleviating both positive and negative symptoms of schizophrenia, based on a review of 27 randomized controlled trials.

The research indicates that tDCS may also positively influence cognitive symptoms in schizophrenia, but further studies are necessary to confirm these findings and refine treatment parameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Literature Mini-Review of Transcranial Direct Current Stimulation in Schizophrenia. Stuchlíková, Z., Klírová, M.[2022]

Transcranial direct current stimulation (tDCS) is a low-cost and easy-to-use neuromodulation technique that may help patients with schizophrenia, particularly those experiencing treatment-resistant auditory verbal hallucinations (AVH) and cognitive deficits, although results have been inconclusive.

While tDCS has shown little to no adverse effects, its effectiveness for negative symptoms remains limited unless used with a higher frequency of sessions, indicating a need for further research to optimize treatment parameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive direct current stimulation for schizophrenia: a review. Lindenmayer, JP., Fitapelli, B.[2021]

Transcranial Direct Current Stimulation (tDCS) is confirmed to be a very safe and well-tolerated treatment for patients with paranoid schizophrenia, based on an analysis of 219 treatment sessions.

While mild to moderate adverse effects like itching, burning, and heat sensations were reported, they were transient and resolved quickly, indicating that tDCS can be administered with minimal risk to patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and Safety of 219 Transcranial Direct Current Stimulation (TDCS) 2.0 mA Sessions in Adult Patients with Schizophrenia. Wysokiński, A.[2023]

References

1. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Transcranial Direct Current Stimulation for the Treatment of Refractory Symptoms of Schizophrenia. Current Evidence and Future Directions. [2022]

2. England pubmed.ncbi.nlm.nih.gov

tDCS for auditory verbal hallucinations in a case of schizophrenia and left frontal lesion: efield simulation and clinical results. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Understanding tDCS effects in schizophrenia: a systematic review of clinical data and an integrated computation modeling analysis. [2018]

4. India pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation for refractory auditory hallucinations in schizophrenia: Acute and 16-week outcomes. [2022]

5. Brazil pubmed.ncbi.nlm.nih.gov

Effect of transcranial direct current stimulation (tDCS) over the prefrontal cortex combined with cognitive training for treating schizophrenia: a sham-controlled randomized clinical trial. [2022]

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

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

A Literature Mini-Review of Transcranial Direct Current Stimulation in Schizophrenia. [2022]

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

Noninvasive direct current stimulation for schizophrenia: a review. [2021]

9. Croatia pubmed.ncbi.nlm.nih.gov

Tolerability and Safety of 219 Transcranial Direct Current Stimulation (TDCS) 2.0 mA Sessions in Adult Patients with Schizophrenia. [2023]