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

Trial Summary

What is the purpose of this trial?

This trial is testing whether a small electrical current to the forehead can help improve thinking skills in people with schizophrenia. The study will see if doing this during tasks or at rest makes a difference, and if targeting the front or back of the head is more effective. It also looks at changes in a brain chemical important for thinking. This method has been shown to enhance cognitive performance in both healthy individuals and patients with schizophrenia.

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.

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 and other conditions. Studies have not reported any serious adverse effects or irreversible injuries across thousands of sessions. ^{1 2 3 4 5}

How does transcranial direct current stimulation (tDCS) differ from other treatments for schizophrenia?

Transcranial direct current stimulation (tDCS) is a non-invasive treatment that uses a mild electrical current to stimulate specific areas of the brain, 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 the brain's frontotemporal regions, offering a novel approach for patients who do not respond well to standard antipsychotic medications. ^{4 5 6 7 8}

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, especially those who don't respond well to medication. It has been found to decrease auditory hallucinations by about 34% and improve cognitive functions like memory and attention. ^{5 6 7 8 9}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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) 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]

References

1. India pubmed.ncbi.nlm.nih.gov

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

2. 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]

3. 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]

4. 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]

5. England pubmed.ncbi.nlm.nih.gov

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

6. 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]

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

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

8. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

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