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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how transcranial direct current stimulation (tDCS) affects thinking skills in individuals with schizophrenia and healthy participants. Researchers seek to determine if stimulating different brain areas can improve tasks related to attention, memory, and language comprehension. Participants will receive either real or sham (fake) stimulation on specific brain regions. This study suits English-speaking individuals with stable schizophrenia who have not recently changed their medication. As an unphased trial, it offers participants the chance to contribute to groundbreaking research that could enhance cognitive therapies for schizophrenia.

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 prior data suggests that transcranial direct current stimulation (tDCS) is safe?

Previous studies have shown that using transcranial direct current stimulation (tDCS) on the dorsolateral prefrontal cortex (DLPFC) is safe and well-tolerated in people with schizophrenia. Some studies reported mild skin irritation among participants, but no serious side effects occurred. When applied to the occipital cortex, tDCS showed similar safety results. No serious adverse effects were reported, and side effects were generally mild, such as skin irritation. Overall, research suggests that tDCS is a safe option for brain stimulation in these areas. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about transcranial direct current stimulation (tDCS) for schizophrenia because it offers a non-invasive approach that directly targets brain regions involved in the condition. Unlike standard treatments, which often include antipsychotic medications that can have significant side effects, tDCS uses mild electrical currents to potentially modulate brain activity, offering a different mechanism of action. Specifically, the stimulation of the dorsolateral prefrontal cortex and the occipital cortex seeks to enhance cognitive function and reduce symptoms without the systemic side effects of medication. This novel approach could provide a promising alternative for individuals who don't respond well to traditional treatments.

What evidence suggests that transcranial direct current stimulation is effective for cognitive performance in schizophrenia?

Research suggests that transcranial direct current stimulation (tDCS) might improve thinking skills in people with schizophrenia. In this trial, participants may receive stimulation of the dorsolateral prefrontal cortex (DLPFC). Studies have found that this can help with memory issues and might reduce negative symptoms, such as lack of motivation or social withdrawal. Another group in this trial will receive stimulation of the occipital area. Although research here is still in the early stages, some findings suggest it might enhance efforts to improve thinking skills. Overall, while tDCS appears promising, more research is needed to fully understand its effects on schizophrenia. ^{4 6 7 8 9}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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) 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5288642/

A Quantitative Review of Cognitive Outcomes - PMC As revealed by this report, due to the paucity of data available, much remains unknown regarding the clinical efficacy of tDCS in schizophrenia.

2. nature.com nature.com/articles/s41398-024-02994-w

Effect of transcranial direct current stimulation with ... Our results suggest that tDCS targeting the PPC relative to the DLPFC during concurrent cognitive performance may improve working memory in schizophrenia.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11541428/

Transcranial direct current stimulation and its effect on ... Recent studies indicate that tDCS can significantly improve cognitive functioning in individuals with schizophrenia, with effects persisting ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X25003304

Assessing tDCS efficacy in reducing negative symptoms in ... Stimulation over the left dorsolateral prefrontal cortex (lDLPFC) was significantly associated with symptom reduction (SMD = −0.30). No significant effects ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S221500131730029X

a phase II randomized sham-controlled trial The results from this trial highlight the therapeutic effects of tDCS for treatment of persistent symptoms in schizophrenia, with reduction of negative symptoms ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10464035/

a randomized, double-blind, sham-controlled, clinical trial - PMC The present research explored if cognitive function in patients with long-term hospitalized chronic schizophrenia with TD could be improved through tDCS.

7. nature.com nature.com/articles/s41537-025-00647-5

Investigating the effects of transcranial direct current ... In individuals with schizophrenia, single session studies employing anodal tDCS to the DLPFC yielded beneficial effects on WM performance, ...

8. jamanetwork.com jamanetwork.com/journals/jamapsychiatry/fullarticle/2752388

Efficacy and Safety of Transcranial Direct Current ... Frontotemporoparietal tDCS was an effective and safe add-on treatment for patients with schizophrenia with prominent negative symptoms. Our ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1935861X11000027

Tolerability of transcranial direct current stimulation in ... This study aims to investigate the tolerability aspects of tDCS in the childhood-onset schizophrenia (COS) population. Methods. Twelve participants with COS ...