TMS for Schizophrenia

(MESSI Trial)

Overseen By Yingxin Jia

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Francisco

Must be taking: Antipsychotics

Disqualifiers: Neurological disorder, Seizures, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 week

160 Participants Needed

Trial Summary

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 schizophrenia participants to be on a stable dose of antipsychotic medication for at least 4 weeks. It seems you can continue your current medications if they meet this stability requirement.

What data supports the effectiveness of the treatment Navigated Repetitive Transcranial Magnetic Stimulation (nrTMS) for schizophrenia?

Research shows that repetitive transcranial magnetic stimulation (rTMS) can have small but significant effects on reducing negative symptoms in schizophrenia. Studies suggest that rTMS, when added to antipsychotic therapy, may improve symptoms like lack of motivation and social withdrawal. ^{1 2 3 4 5}

Is transcranial magnetic stimulation (TMS) safe for humans?

Research suggests that repetitive transcranial magnetic stimulation (rTMS) is generally considered safe for treating mental disorders, including schizophrenia, with no major safety concerns reported in studies. ^{1 6 7 8 9}

How is the treatment nrTMS different from other treatments for schizophrenia?

Navigated Repetitive Transcranial Magnetic Stimulation (nrTMS) is unique because it uses magnetic fields to stimulate specific areas of the brain, which can help improve symptoms of schizophrenia, especially negative symptoms like lack of motivation or emotion. Unlike medications, it is a non-invasive procedure and does not involve taking drugs. ^{1 4 9 10 11}

What is the purpose of this trial?

This randomized controlled trial in healthy controls (HC) and patients with schizophrenia (SZ) aims to examine 1) the underlying cognitive and neural cause of self-agency deficits in SZ; 2) the responsiveness to a novel navigated repetitive transcranial magnetic stimulation (nrTMS) target in the medial/superior prefrontal cortex (mPFC); and 3) how modulation of mPFC activity impacts the larger self-agency network to mediate changes in self-agency judgments. Our overall hypothesis is that increased mPFC excitability by active high-frequency nrTMS in HC and SZ will induce behavioral improvements in self-agency and neural changes in the larger self-agency network that will generalize to improvements in overall cognition, symptoms and daily functioning, and will likely lead to the development of new effective neuromodulation therapies in patients with schizophrenia.

Research Team

Karuna Subramaniam, PhD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for English-speaking individuals with schizophrenia who are clinically stable on a low to moderate dose of antipsychotic medication, without neurological disorders or substance use issues. They must be in good physical health and able to undergo MRI scans. Pregnant individuals, those with implanted metal/electronic devices, scalp wounds/infections, ongoing seizures, or severe claustrophobia cannot participate.

Inclusion Criteria

You have undergone an MRI scan and the results meet the requirements for the study.

You are not currently struggling with addiction to alcohol or drugs.

I am in good overall health.

Exclusion Criteria

I have wounds or infections on my scalp.

You are afraid of being in small spaces and cannot undergo an MRI.

You have metal implants or electronic devices inside your body.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Baseline Assessment

Participants complete baseline assessments including cognitive, clinical, and daily functioning assessments, structural MRI, and MEGI scans

1 week

Multiple visits (in-person)

Treatment

Participants receive nrTMS targeting either the medial prefrontal cortex or a control posterior parietal site

1 week

Multiple visits (in-person)

Follow-up

Participants are monitored for changes in neural activity, cognition, clinical symptoms, and daily functioning after TMS

4 weeks

Multiple visits (in-person)

Treatment Details

Interventions

• Navigated Repetitive Transcranial Magnetic Stimulation (nrTMS)

Trial Overview The study tests whether high-frequency transcranial magnetic stimulation (TMS) targeting the medial prefrontal cortex can improve self-agency judgments in people with schizophrenia. It will also assess cognitive improvements and daily functioning as well as potential changes within the brain's self-agency network.

Participant Groups

Group I: Medial/Superior Prefrontal TMS Active Control 1 Intervention

10 Hz High frequency TMS applied to the mPFC

Group II: Posterior Parietal TMS Placebo Group 1 Intervention

10 Hz high frequency TMS applied to the posterior parietal cortex

Navigated Repetitive Transcranial Magnetic Stimulation (nrTMS) is already approved in European Union, United States for the following indications:

Approved in European Union as rTMS for:

• Major Depressive Disorder
• Negative symptoms in schizophrenia

Approved in United States as rTMS for:

• Major Depressive Disorder

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Findings from Research

High dose transcranial magnetic stimulation (rTMS) at 10 Hz significantly reduced negative symptoms in schizophrenia patients, particularly blunted affect, emotional withdrawal, and passive/apathetic social withdrawal, with an effective rate of 43.75% compared to 11.43% in the control group.

While rTMS was found to be effective, it was associated with a higher incidence of headaches (37.50% in the study group) compared to the control group, indicating a need for monitoring side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effectiveness and safety of high dose transcranial magnetic stimulation in schizophrenia with refractory negative symptoms: a randomized controlled study]. Gan, J., Duan, H., Chen, Z., et al.[2018]

Rhythmic transcranial magnetic stimulation (rTMS) showed significant efficacy in reducing symptoms of resistant schizophrenia, particularly in patients with depressive, hallucinatory, and negative symptoms, with reductions in PANSS scores of 24.4%, 8.3%, and 11.7% respectively after 15 sessions over 3 weeks.

However, rTMS was not effective for patients with delusional symptoms, leading to a worsening of their condition, indicating that treatment must be tailored to the specific symptoms of schizophrenia for optimal results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Augmentation therapy of resistant schizophrenia with rhythmic transcranial magnetic stimulation]. Pomytkin, AN., Tikhonov, DV., Kaleda, VG.[2023]

Bimodal repetitive transcranial magnetic stimulation (rTMS) significantly reduced symptoms of schizophrenia in 10 patients who were unresponsive to medication, with improvements noted in all subscales of the Positive and Negative Syndrome Scale (PANSS) by Day 29.

The treatment also showed potential benefits for short-term auditory verbal memory, as indicated by significant increases in neurocognitive test scores after the rTMS sessions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjunctive treatment of bimodal repetitive transcranial magnetic stimulation (rTMS) in pharmacologically non-responsive patients with schizophrenia: a preliminary study. Oh, SY., Kim, YK.[2011]

In a study involving 80 schizophrenia patients, 20 Hz rTMS significantly improved visual spatial working memory, while theta burst stimulation (TBS) notably enhanced verbal fluency, indicating that different rTMS paradigms can target specific cognitive deficits.

Both TBS and 10 Hz rTMS effectively alleviated negative symptoms of schizophrenia, while general psychopathology symptoms improved with 10 Hz and 20 Hz rTMS, suggesting that rTMS can be tailored for individual therapeutic needs in schizophrenia treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effects of repetitive transcranial magnetic stimulation with different paradigms on the cognitive function and psychotic symptoms of schizophrenia patients]. Zheng, LN., Guo, Q., Li, H., et al.[2017]

A multicenter, randomized, sham-controlled trial is being conducted to evaluate the efficacy of high-frequency rTMS as an add-on treatment for negative symptoms in schizophrenia, involving 63 patients in each group over a 3-week period with follow-up for 12 weeks.

The primary goal is to assess the reduction of negative symptoms using the PANSS score, while also examining other factors like neurocognition and quality of life to understand the mechanisms of rTMS, although challenges such as antipsychotic dosage changes may affect results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation for the treatment of negative symptoms in residual schizophrenia: rationale and design of a sham-controlled, randomized multicenter study. Cordes, J., Falkai, P., Guse, B., et al.[2021]

Repetitive transcranial magnetic stimulation (rTMS) combined with antipsychotic treatment has been shown to slightly improve negative symptoms in schizophrenia patients, based on a meta-analysis of 29 studies involving 1440 participants.

While rTMS treatment is generally well-accepted and has fewer adverse effects, it is associated with a higher rate of mild side effects, indicating the need for careful consideration in its application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy Towards Negative Symptoms and Safety of Repetitive Transcranial Magnetic Stimulation Treatment for Patients with Schizophrenia: A Systematic Review. Wang, J., Zhou, Y., Gan, H., et al.[2020]

In a study of 47 patients with schizophrenia, active rTMS over the left dorsolateral prefrontal cortex showed no immediate effect on negative symptoms at 4 weeks, but by 8 weeks, there was a significant reduction in symptoms compared to the sham group.

These results indicate that rTMS may have a delayed therapeutic effect on negative symptoms of schizophrenia, suggesting it could be a beneficial treatment option over a longer duration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delayed effect of repetitive transcranial magnetic stimulation (rTMS) on negative symptoms of schizophrenia: Findings from a randomized controlled trial. Li, Z., Yin, M., Lyu, XL., et al.[2018]

A preliminary study involving 15 patients with schizophrenia showed that 20 daily sessions of deep transcranial magnetic stimulation (deep-TMS) significantly improved cognitive deficits and negative symptoms.

The improvements in symptoms were sustained for at least two weeks after the treatment, suggesting that deep-TMS could be a promising add-on therapy for managing these challenging aspects of schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep transcranial magnetic stimulation add-on for treatment of negative symptoms and cognitive deficits of schizophrenia: a feasibility study. Levkovitz, Y., Rabany, L., Harel, EV., et al.[2016]

In a study involving 10 right-handed schizophrenia patients, active repetitive transcranial magnetic stimulation (rTMS) at 10 Hz significantly improved negative symptoms of schizophrenia compared to sham treatment.

The improvement in negative symptoms occurred independently of any changes in depressive symptoms, suggesting that rTMS specifically targets negative symptoms in schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of adjuvant high frequency repetitive transcranial magnetic stimulation on negative and positive symptoms of schizophrenia: preliminary results of a double-blind sham-controlled study. Goyal, N., Nizamie, SH., Desarkar, P.[2007]

Transcranial magnetic stimulation (TMS) is generally considered a safe treatment option for managing symptoms of schizophrenia, particularly in reducing auditory hallucinations, based on a review of 19 studies involving 531 patients.

There are ongoing controversies regarding the effects of TMS on the cortical silent period in schizophrenia patients, with some studies showing longer or shorter periods compared to healthy controls, indicating potential GABA receptor abnormalities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Different Modalities of Transcranial Magnetic Stimulation to Manage Schizophrenia. Soltani, E., Bateni, H., Shad, MU.[2022]

Transcranial magnetic stimulation (TMS) has shown promise in treating persistent auditory hallucinations in schizophrenia, particularly with 1-Hz TMS applied to the left temporoparietal cortex, indicating its potential as a short-term therapeutic option.

High-frequency TMS targeting the left prefrontal cortex may help improve negative and cognitive symptoms of schizophrenia, although the effects are inconsistent and generally small, highlighting the need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigational and Therapeutic Applications of Transcranial Magnetic Stimulation in Schizophrenia. Mehta, UM., Naik, SS., Thanki, MV., et al.[2022]

References

1. China pubmed.ncbi.nlm.nih.gov

[Effectiveness and safety of high dose transcranial magnetic stimulation in schizophrenia with refractory negative symptoms: a randomized controlled study]. [2018]

2. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Augmentation therapy of resistant schizophrenia with rhythmic transcranial magnetic stimulation]. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Adjunctive treatment of bimodal repetitive transcranial magnetic stimulation (rTMS) in pharmacologically non-responsive patients with schizophrenia: a preliminary study. [2011]

4. China pubmed.ncbi.nlm.nih.gov

[Effects of repetitive transcranial magnetic stimulation with different paradigms on the cognitive function and psychotic symptoms of schizophrenia patients]. [2017]

5. Germany pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation for the treatment of negative symptoms in residual schizophrenia: rationale and design of a sham-controlled, randomized multicenter study. [2021]

6. China pubmed.ncbi.nlm.nih.gov

Efficacy Towards Negative Symptoms and Safety of Repetitive Transcranial Magnetic Stimulation Treatment for Patients with Schizophrenia: A Systematic Review. [2020]

7. Ireland pubmed.ncbi.nlm.nih.gov

Delayed effect of repetitive transcranial magnetic stimulation (rTMS) on negative symptoms of schizophrenia: Findings from a randomized controlled trial. [2018]

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

Deep transcranial magnetic stimulation add-on for treatment of negative symptoms and cognitive deficits of schizophrenia: a feasibility study. [2016]

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

Efficacy of adjuvant high frequency repetitive transcranial magnetic stimulation on negative and positive symptoms of schizophrenia: preliminary results of a double-blind sham-controlled study. [2007]

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

Different Modalities of Transcranial Magnetic Stimulation to Manage Schizophrenia. [2022]

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

Investigational and Therapeutic Applications of Transcranial Magnetic Stimulation in Schizophrenia. [2022]