Brain Stimulation for Schizophrenia

Overseen By Philip Gerretsen, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Centre for Addiction and Mental Health

Must be taking: Antipsychotics

Disqualifiers: Seizures, Suicidal ideation, Substance dependence, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: 20

Duration: 2 weeks

106 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a non-invasive brain stimulation method called transcranial direct current stimulation (tDCS) to determine if it can help people with schizophrenia adhere to their medication plans. The treatment involves 20 sessions where a mild current is applied to the head. Some participants will receive actual stimulation, while others will experience a sham (inactive) session. The trial seeks participants diagnosed with schizophrenia or schizoaffective disorder who have been stable on their medication for at least two months. As an unphased trial, this study offers a unique opportunity to contribute to innovative research that could enhance treatment adherence for schizophrenia.

Will I have to stop taking my current medications?

The trial requires that you stay on a stable dose of your current antipsychotic and other medications for at least 2 months before and during the study.

What prior data suggests that this method is safe for patients with schizophrenia?

Research has shown that transcranial direct current stimulation (tDCS) is safe for people with schizophrenia. Studies have found it to be generally well tolerated, with the most common side effects being mild, such as itching or tingling on the skin. These effects are usually temporary and not harmful.

Other studies have safely used tDCS as an additional treatment for schizophrenia, particularly for negative symptoms like lack of motivation or social withdrawal. This suggests that tDCS can be a safe option when used alongside other treatments. ^{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 way to potentially alleviate symptoms by directly altering brain activity. Unlike current medications, which often come with a range of side effects and primarily target neurotransmitter imbalances, TDCS uses a mild electrical current to stimulate specific brain areas, possibly leading to fewer side effects. Additionally, TDCS can be targeted to specific regions of the brain, such as the parietal regions, which may be crucial for addressing the cognitive deficits associated with schizophrenia. This approach represents a novel mechanism of action, providing hope for more tailored and effective treatments.

What evidence suggests that tDCS is effective for improving medication adherence in schizophrenia?

Research has shown that transcranial direct current stimulation (tDCS) can help people with schizophrenia. In this trial, participants will receive either Active tDCS or Sham tDCS. Studies have found that tDCS can improve thinking skills and awareness of one's condition. It also helps with negative symptoms, which are difficult to treat. The benefits of tDCS often continue even after the treatment ends, suggesting long-lasting effects. Overall, tDCS is considered a safe additional treatment for schizophrenia, highlighting its potential usefulness. ^{2 3 6 7 8}

Who Is on the Research Team?

Philip Gerretsen, MD, PhD

Principal Investigator

Centre for Addiction and Mental Health

Are You a Good Fit for This Trial?

This trial is for adults with schizophrenia or schizoaffective disorder who are on a stable medication regimen and can consent to participate. It's not for pregnant individuals, those with certain learning difficulties, severe thought disorders, recent substance dependence (except caffeine/nicotine), metal implants/pacemakers, acute suicidal/homicidal thoughts, or other major medical/neurological illnesses.

Inclusion Criteria

My gender or race does not limit my participation.

I have been diagnosed with schizophrenia or schizoaffective disorder.

I've been on a steady dose of my psychiatric medication for 2+ months.

Exclusion Criteria

Metal implants or pacemaker precluding an MRI scan or other contraindications to MRI (eg., claustrophobia)

Formal thought disorder rating ≥3 on the Positive and Negative Syndrome Scale (PANSS) P2 conceptual disorganization item

You have been addicted to drugs or alcohol (except caffeine and nicotine) within the past month.

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) twice-daily for 10 days, excluding weekends, to improve medication adherence

2 weeks

20 sessions (in-person)

Follow-up

Participants are monitored for medication adherence and insight into psychosis for 3 months after the treatment phase

3 months

Regular assessments (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

• TDCS

Trial Overview The study tests transcranial direct current stimulation (tDCS) as an additional treatment to help patients with schizophrenia stick to their antipsychotic medication schedule. Participants will receive either the active tDCS or a sham (fake) version in 20 sessions to compare effects on medication adherence.

How Is the Trial Designed?

Group I: Active TDCS Experimental Treatment 1 Intervention

In the active condition, a constant current of 2 mA intensity will be applied for 20 min to the parietal regions, using P3 as the cathode and P4 as the anode.

Group II: Sham TDCS Placebo Group 1 Intervention

In the sham condition, stimulation will be administered using the same parameters at the site of active treatment, but the current will be turned off after 30 seconds.

Who Is Running the Clinical Trial?

Centre for Addiction and Mental Health

Lead Sponsor

Trials

388

Recruited

84,200+

Published Research Related to This Trial

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]

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]

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]

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 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]

Citations

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

Investigating the effects of transcranial direct current ... While preliminary, these findings indicate that tDCS could support cognitive training outcomes in schizophrenia. Larger randomized controlled ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9673267/

Efficacy of Transcranial Direct Current Stimulation to ... These findings suggest that, although tDCS was associated with improvements in insight (current study) and other symptoms of schizophrenia (eg,) ...

3. 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 ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2215001324000362

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 beyond the ...

5. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2025.1617068/full

Adjunctive transcranial direct current stimulation for ... Discussion: This exploratory meta-analysis revealed that tDCS in the treatment of schizophrenia appears capable of improving cognitive function and effectively ...

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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38816583/

Effects and safety of transcranial direct current stimulation ... tDCS was effective for people with stroke, obsessive-compulsive disorder, fibromyalgia, disease of consciousness, schizophrenia, migraine, attention-deficit/ ...

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.