Brain Stimulation for Schizophrenia

Overseen By Molly A Bainbridge

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of California, Davis

Must not be taking: Clozapine

Disqualifiers: Pacemakers, Epilepsy, Pregnancy, Substance dependence, 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: Unknown

Duration: 20 minutes per session

160 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a gentle electrical treatment called transcranial direct current stimulation (tDCS) can enhance thinking skills, such as attention and memory, in people with schizophrenia. The researchers seek to discover whether using tDCS during specific activities is more effective than using it at rest and if targeting different areas of the head influences outcomes. They are also examining whether this treatment affects a brain chemical called GABA, which plays a crucial role in thinking. Suitable candidates for this trial have schizophrenia and have not recently changed their medication. As an unphased trial, this study provides a unique opportunity to explore innovative treatment options for improving cognitive function.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must not be taking the antipsychotic clozapine. Also, you should not have had any medication changes in the past month or expect any in the next month.

What prior data suggests that transcranial direct current stimulation (tDCS) is safe for improving cognitive function in people with schizophrenia?

Research has shown that transcranial direct current stimulation (tDCS) is safe and generally well-tolerated by people with schizophrenia. One study found that the most common side effects are mild, such as itching or tingling on the skin. Another study highlighted that tDCS is a safe and affordable method for treating certain symptoms of schizophrenia. Overall, evidence suggests that tDCS can be used without serious safety concerns. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using transcranial direct current stimulation (tDCS) for schizophrenia because it offers a non-invasive approach that could directly target brain function. Unlike traditional treatments like antipsychotic medications, which primarily manage symptoms through chemical pathways in the brain, tDCS involves applying a mild electrical current to specific brain areas, like the dorsolateral prefrontal cortex, which might help improve cognitive functions. This method could potentially enhance or restore neural activity without the side effects commonly associated with medication. Additionally, the ability to pair stimulation with cognitive tasks might further boost its effectiveness in treating cognitive deficits associated with schizophrenia.

What evidence suggests that transcranial direct current stimulation could be effective for cognitive problems in schizophrenia?

Research has shown that transcranial direct current stimulation (tDCS) can improve thinking skills in people with schizophrenia. In this trial, participants will receive tDCS, which sends a small electrical current to the dorsolateral prefrontal cortex (DLPFC). This method has been found to aid memory and focus. Some participants will receive active DLPFC stimulation during cognitive tasks or rest, while others will receive sham stimulation as a placebo comparator. Studies indicate that tDCS can boost mental performance during thinking exercises. It can also reduce negative symptoms and enhance overall mental abilities, with benefits lasting even after treatment ends. While not a cure, these findings suggest that tDCS could help with the thinking difficulties associated with 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've had stable medication for the past month and no expected changes in the coming month. They should have a normal IQ, not be on clozapine, able to understand English well enough for cognitive tasks, and capable of informed consent.

Inclusion Criteria

Normal IQ (>70; IQ will be measured by administering the Wechsler Abbreviated Scale of Intelligence (WASI) test)

No medication changes in the prior month

I am not currently taking the antipsychotic medication clozapine.

Exclusion Criteria

You have a pacemaker implanted in your body.

I have a history of neurological or severe psychiatric disorders.

You have vision problems that make it difficult for you to complete cognitive tests or tasks that require distinguishing colors.

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 during cognitive tasks or rest

20 minutes per session

Multiple sessions

Assessment

Electrophysiological and behavioral assessments conducted immediately following stimulation

1.5 hours per session

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 if transcranial direct current stimulation (tDCS), which applies a small electrical current to the forehead, can improve brain function and cognition in people with schizophrenia during different conditions like rest or task performance.

How Is the Trial Designed?

Group I: DLPFC Stimulation + Task Experimental Treatment 1 Intervention

Intervention. 20 minutes of 2 mA direct current stimulation over the dorsolateral prefrontal cortex during cognitive task completion.

Group II: DLPFC Stimulation + Rest Experimental Treatment 1 Intervention

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

Group III: Sham Stimulation + Task Placebo Group 1 Intervention

Placebo Comparator. 0.5-1 minutes of 2 mA direct current stimulation over dorsolateral prefrontal cortex followed by 19-19.5 minutes of sham stimulation, during cognitive task completion.

Group IV: Sham Stimulation + Rest Placebo Group 1 Intervention

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

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

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 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) 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]

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) 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) 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) 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]

Citations

1. 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 ...

2. 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, ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38084398/

Transcranial direct-current stimulation of the prefrontal ... Significant symptom-severity reduction was sustained for one week after active tDCS intervention. Sustained resting gamma stability (RGS) was ...

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

Assessing tDCS efficacy in reducing negative symptoms in ... Across studies (k = 18; total n = 709; 361 participants in the active and 348 in the sham group), tDCS significantly reduced negative symptoms of SSDs, compared ...

5. frontiersin.org frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2017.00044/full

Transcranial Direct Current Stimulation over the ... Recent research suggests transcranial direct current stimulation (tDCS) targeting the dorsolateral prefrontal cortex can potentiate cognitive improvements.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40228176/

Safety and Blinding of Transcranial Direct Current ... This study confirms that tDCS is safe and well tolerated by patients with schizophrenia. The most frequent side effects are itching/tingling ...

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

Efficacy and Safety of Transcranial Direct Current ... Transcranial direct current stimulation is an affordable, safe, and effective add-on treatment for negative symptoms in schizophrenia.

8. bmcpsychiatry.biomedcentral.com bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-023-05112-0

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

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31617873/

Efficacy and Safety of Transcranial Direct Current ... Transcranial direct current stimulation was effective and safe in ameliorating negative symptoms in patients with schizophrenia.