Brain Stimulation for Schizophrenia

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Centre for Addiction and Mental Health

Must be taking: Antipsychotics

Must not be taking: Psychotropics, others

Disqualifiers: Bipolar, Major depression, others

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

Compensation: Varies

Number of Visits: 1

Duration: 2 weeks

72 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to 1. assess the effect of PAS in schizophrenia in the dorsolateral prefrontal cortex (DLPFC) 2. assess the effect of PAS induced long-term potentiation (LTP) on the performance of patients with schizophrenia on a cognitive task related to DLFPC.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on antipsychotic medication, you must have had no change in dosage for at least 4 weeks before joining the study.

What data supports the effectiveness of the treatment Paired Associative Stimulation for schizophrenia?

Research on similar brain stimulation treatments, like transcranial direct current stimulation (tDCS), shows promise in improving symptoms of schizophrenia, such as negative symptoms and insight into the illness. These studies suggest that non-invasive brain stimulation can be beneficial, although more research is needed to confirm these effects specifically for Paired Associative Stimulation. ^{1 2 3 4 5}

Is brain stimulation safe for treating schizophrenia?

Studies on brain stimulation methods like transcranial direct current stimulation (tDCS) and transcutaneous vagus nerve stimulation (tVNS) for schizophrenia show they are generally well tolerated with no significant adverse effects reported. ^{2 6 7 8 9}

How is Paired Associative Stimulation different from other treatments for schizophrenia?

Paired Associative Stimulation is unique because it involves brain stimulation techniques like transcranial alternating current stimulation (tACS) that target specific brain networks to improve negative symptoms of schizophrenia, unlike traditional treatments that often focus on medication. This approach uses electrical currents to modulate brain activity, offering a novel way to address symptoms that are typically resistant to standard therapies. ^{2 4 5 10 11}

Research Team

Tarek K Rajji, MD

Principal Investigator

Centre for Addiction and Mental Health

Eligibility Criteria

This trial is for adults diagnosed with schizophrenia or schizoaffective disorder, stable in their condition and medication. They must be able to understand English, provide consent, and have adequate vision and hearing. Excluded are those with bipolar disorder, major depression, recent drug dependence, certain psychiatric diagnoses, a family history of psychosis in close relatives, unstable psychotropic medication use, left-handedness or other neurological issues.

Inclusion Criteria

People of all races and ethnicities are eligible.

You currently have a diagnosis of schizophrenia or schizoaffective disorder according to the DSM-IV TR criteria.

I haven't been hospitalized recently and my medication dose hasn't changed in the last month.

Exclusion Criteria

I have been on a stable dose of my psychotropic medication for at least 4 weeks.

A close family member has had a severe mental health disorder.

I have not had electroconvulsive therapy in the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a 2-week course of PAS-25 or PAS-100

2 weeks

Follow-up

Participants are monitored for changes in working memory using the N-back task

1 week

1 visit (1 day post-treatment), 1 visit (7 days post-treatment)

Treatment Details

Interventions

• Paired Associative Stimulation

Trial Overview The study tests the effects of brain stimulation (Transcranial Magnetic Stimulation) on the dorsolateral prefrontal cortex in schizophrenia patients. It aims to see if this can improve cognitive tasks related to that brain area by inducing long-term potentiation (LTP), which is like strengthening brain connections.

Participant Groups

Group I: PAS 25 Active Control 1 Intervention

In humans, paired associative stimulation (PAS-25) is a transcranial magnetic stimulation (TMS) protocol that has been shown to result in LTP-like plasticity (PAS-LTP) in the motor cortex (M1). PAS-LTP has been shown to be dependent on the NMDAR and to correlate significantly with performance on a motor learning task.

Group II: PAS 100 Placebo Group 1 Intervention

To control for non-specific effects of PAS protocol, the investigators will use a modified PAS protocol (PAS-100) that does not result in any neurophysiologic effects. Patients with schizophrenia and healthy controls will be assessed first with the N-back task and then randomized

Who Is Running the Clinical Trial?

Centre for Addiction and Mental Health

Lead Sponsor

Trials

388

Recruited

84,200+

National Alliance for Research on Schizophrenia and Depression

Collaborator

Trials

97

Recruited

4,100+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Findings from Research

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]

A study involving 20 stable schizophrenia patients tested the safety and efficacy of transcutaneous vagus nerve stimulation (tVNS) over 26 weeks, finding that the treatment was well tolerated with no significant adverse effects.

However, the study did not show a statistically significant improvement in schizophrenia symptoms compared to sham stimulation, suggesting that while tVNS is safe, it may not be effective for this condition in the current trial setup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous noninvasive vagus nerve stimulation (tVNS) in the treatment of schizophrenia: a bicentric randomized controlled pilot study. Hasan, A., Wolff-Menzler, C., Pfeiffer, S., et al.[2018]

A review of 119 studies on non-invasive brain stimulation (NIBS) for treatment-resistant schizophrenia revealed a low quality of assessment, with an average score of only 3.38 out of 11, indicating inadequate reporting of treatment resistance.

Most studies inadequately defined treatment resistance, often focusing on a single symptom without considering factors like treatment adherence and functional impairment, which limits the understanding of NIBS's true efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of treatment resistance criteria in non-invasive brain stimulation studies of schizophrenia. Kronick, J., Sabesan, P., Burhan, AM., et al.[2022]

Deep brain stimulation (DBS) is being explored as a potential treatment for schizophrenia (SZ), a condition that currently has significant unmet needs due to issues like relapse and ineffective treatments for negative and cognitive symptoms.

Research suggests that SZ may be a circuit disorder, and DBS could help by modulating striatal dysregulation, with ongoing clinical trials assessing its efficacy and ethical considerations for patients with severe symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Approaches to neuromodulation for schizophrenia. Gault, JM., Davis, R., Cascella, NG., et al.[2022]

In a preliminary study of ten patients with treatment-resistant schizophrenia, high-frequency transcranial random noise stimulation (hf-tRNS) significantly reduced auditory hallucinations by an average of 36.1%, indicating its potential efficacy as a noninvasive treatment.

The study involved 10 sessions of hf-tRNS targeting specific brain areas, suggesting that this method may offer a promising alternative to conventional treatments, although further sham-controlled studies are necessary to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Frequency Transcranial Random Noise Stimulation for Auditory Hallucinations of Schizophrenia: A Case Series. Mondino, M., Janin, D., Galvao, F., et al.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Improvement of Insight with Non-Invasive Brain Stimulation in Patients with Schizophrenia: A Systematic Review. [2022]

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

Prefrontal Transcranial Direct Current Stimulation for Treatment of Schizophrenia With Predominant Negative Symptoms: A Double-Blind, Sham-Controlled Proof-of-Concept Study. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Modulation of self-appraisal of illness, medication adherence, life quality and autonomic functioning by transcranial direct current stimulation in schizophrenia patients. [2021]

4. 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]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Online Left-Hemispheric In-Phase Frontoparietal Theta tACS for the Treatment of Negative Symptoms of Schizophrenia. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

Transcutaneous noninvasive vagus nerve stimulation (tVNS) in the treatment of schizophrenia: a bicentric randomized controlled pilot study. [2018]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Assessment of treatment resistance criteria in non-invasive brain stimulation studies of schizophrenia. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Approaches to neuromodulation for schizophrenia. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

High-Frequency Transcranial Random Noise Stimulation for Auditory Hallucinations of Schizophrenia: A Case Series. [2023]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Transcranial direct current stimulation influences probabilistic association learning in schizophrenia. [2022]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Treatment of negative symptoms of schizophrenia using repetitive transcranial magnetic stimulation in a double-blind, randomized controlled study. [2022]