Accelerated Transcranial Magnetic Stimulation for Schizophrenia

Overseen By Deepak Sarpal

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Deepak K. Sarpal, M.D.

Must be taking: Clozapine

Must not be taking: Bupropion

Disqualifiers: Neurologic condition, Suicidal risk, Pregnancy, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 month

30 Participants Needed

Trial Summary

What is the purpose of this trial?

In this study, the investigators will examine whether a type of repetitive transcranial magnetic stimulation called accelerated intermittent theta burst stimulation (iTBS) can augment neurocognition in individuals who receive treatment with clozapine. Following a baseline evaluation and magnetic resonance imaging (MRI), participants will undergo a session of iTBS +MRI and session of sham delivery + MRI. The order for these sessions will be blinded and randomized. The investigators predict that accelerated iTBS will enhance neurocognition relative to sham delivery.

Do I have to stop taking my current medications for the trial?

The trial requires participants to continue their current clozapine treatment. If you are taking both bupropion and clozapine, you cannot participate. Other medications, like serotonin and norepinephrine reuptake inhibitors, will be reviewed individually.

What data supports the effectiveness of the treatment Accelerated Transcranial Magnetic Stimulation for Schizophrenia?

Research on similar treatments, like repetitive transcranial magnetic stimulation (rTMS), shows it can help with symptoms of schizophrenia, especially when other medications don't work. Studies have found that rTMS can improve negative symptoms, which are things like lack of motivation or social withdrawal. ^{1 2 3 4 5}

Is accelerated transcranial magnetic stimulation safe for humans?

Repetitive transcranial magnetic stimulation (rTMS) is considered a safe and noninvasive treatment for mental disorders, including schizophrenia. It is generally well-tolerated by patients, with research indicating it is a promising method for treating symptoms without significant safety concerns. ^{5 6 7 8 9}

How is accelerated transcranial magnetic stimulation different from other treatments for schizophrenia?

Accelerated transcranial magnetic stimulation (TMS) is unique because it uses magnetic fields to stimulate specific areas of the brain, which can help reduce negative symptoms of schizophrenia that are often resistant to medication. Unlike traditional drug treatments, TMS is non-invasive and involves sessions where magnetic pulses are applied to the scalp, offering a different approach for patients who do not respond well to standard medications. ^{1 3 4 5 10}

Research Team

Deepak K Sarpal, M.D.

Principal Investigator

University of Pittsburgh

Eligibility Criteria

This trial is for individuals aged 18-50 with schizophrenia or schizoaffective disorder, who have tried at least two antipsychotic treatments without success and are on a stable dose of clozapine. It's not suitable for those with cognitive impairments, recent pregnancy, MRI contraindications like pacemakers, previous negative reactions to TMS, serious brain-affecting conditions, high suicide risk, severe substance use disorders or seizures.

Inclusion Criteria

I have been diagnosed with schizophrenia or schizoaffective disorder.

I have been treated with clozapine for at least 4 months.

I am able to understand and willing to sign the consent form.

Exclusion Criteria

Cognitive or language limitations, or any other factor that would preclude subjects providing informed consent

Contraindications for magnetic resonance imaging (e.g., a pacemaker)

I am currently taking bupropion and clozapine.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Evaluation

Participants undergo baseline evaluation and magnetic resonance imaging (MRI)

1 week

1 visit (in-person)

Treatment

Participants receive sessions of iTBS + MRI and sham delivery + MRI in a randomized order

1 month

Multiple sessions (in-person)

Follow-up

Participants are monitored for changes in brain functional connectivity and working memory network activation

1 month

Treatment Details

Interventions

• Accelerated Transcranial Magnetic Stimulation

Trial Overview The study tests if accelerated intermittent theta burst stimulation (iTBS), a type of transcranial magnetic stimulation (TMS), can improve thinking abilities in people taking clozapine. Participants will receive iTBS and sham (fake) treatment in random order while blinded to the type they're getting; both sessions include an MRI scan.

Participant Groups

Group I: iTBS, then Sham Experimental Treatment 2 Interventions

Group II: Sham, then iTBS Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

Deepak K. Sarpal, M.D.

Lead Sponsor

Trials

2

Recruited

140+

Deepak Sarpal

Lead Sponsor

Trials

1

Recruited

30+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Findings from Research

In a study involving 51 schizophrenic subjects, 20 sessions of high-frequency (10 Hz) repetitive transcranial magnetic stimulation (rTMS) significantly reduced negative symptoms of schizophrenia compared to placebo and low-frequency (1 Hz) treatments.

The results suggest that rTMS could be a promising noninvasive add-on treatment for managing negative symptoms in schizophrenia, although secondary cognitive measures did not show significant improvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation (rTMS) as an augmentation treatment for the negative symptoms of schizophrenia: a 4-week randomized placebo controlled study. Schneider, AL., Schneider, TL., Stark, H.[2022]

In a case study of a 42-year-old patient with schizophrenia, high-frequency repetitive transcranial magnetic stimulation (rTMS) significantly reduced negative and depressive symptoms compared to sham treatment over a 6-week period.

The results suggest that rTMS targeting the left dorsolateral prefrontal cortex may serve as a beneficial addition to traditional antipsychotic medications for managing negative symptoms in schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influencing negative symptoms of schizophrenia with repetitive transcranial magnetic stimulation: a case study. Prikryl, R., Skotakova, S., Kasparek, T., et al.[2016]

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]

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]

Repetitive transcranial magnetic stimulation (rTMS) is a promising noninvasive treatment for schizophrenia that is safe, effective, and economical, providing an alternative to traditional antipsychotic medications.

Current antipsychotic drugs often fail to address negative symptoms and cognitive dysfunction in schizophrenia, highlighting the potential of rTMS as a complementary therapy to improve overall patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update Research Advances in the Application of Transcranial Magnetic Stimulation in the Treatment of Schizophrenia. Wu, Y., Yang, Z., Cui, S.[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]

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 multicenter trial involving 175 patients with schizophrenia, 10-Hz rTMS applied to the left dorsolateral prefrontal cortex did not show a significant improvement in negative symptoms compared to sham treatment, indicating it may not be an effective option for this specific symptom cluster.

While rTMS was well tolerated, there was a small but statistically significant improvement in positive symptoms at day 21, suggesting that while it may not help with negative symptoms, it could have some effect on other aspects of schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Left prefrontal high-frequency repetitive transcranial magnetic stimulation for the treatment of schizophrenia with predominant negative symptoms: a sham-controlled, randomized multicenter trial. Wobrock, T., Guse, B., Cordes, J., et al.[2015]

In an open study involving four subjects with schizophrenia, high-frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex led to significant reductions in negative symptoms and improvements in function after 20 sessions over 4 weeks.

The benefits observed from rTMS were maintained one month after treatment, suggesting that this intervention is feasible, safe, and potentially beneficial for treating the deficit syndrome of schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation for the deficit syndrome of schizophrenia: a pilot investigation. Sachdev, P., Loo, C., Mitchell, P., et al.[2006]

References

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

Repetitive transcranial magnetic stimulation (rTMS) as an augmentation treatment for the negative symptoms of schizophrenia: a 4-week randomized placebo controlled study. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Influencing negative symptoms of schizophrenia with repetitive transcranial magnetic stimulation: a case study. [2016]

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

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

4. 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]

5. 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]

6. England pubmed.ncbi.nlm.nih.gov

Update Research Advances in the Application of Transcranial Magnetic Stimulation in the Treatment of Schizophrenia. [2022]

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

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

8. 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]

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

Left prefrontal high-frequency repetitive transcranial magnetic stimulation for the treatment of schizophrenia with predominant negative symptoms: a sham-controlled, randomized multicenter trial. [2015]

10. Australia pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation for the deficit syndrome of schizophrenia: a pilot investigation. [2006]