TMS for Schizophrenia Hallucinations

Overseen By Mark Halko, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Mclean Hospital

Disqualifiers: Substance use disorder, Neurological disorder, Seizures, others

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

Compensation: Varies

Number of Visits: 13

Duration: 1 week

68 Participants Needed

Trial Summary

What is the purpose of this trial?

This study uses a noninvasive technique called transcranial magnetic stimulation (TMS) to study how hallucinations work in schizophrenia. TMS is a noninvasive way of stimulating the brain, using a magnetic field to change activity in the brain. The magnetic field is produced by a coil that is held next to the scalp. In this study the investigators will be stimulating the brain to learn more about how TMS might improve these symptoms of schizophrenia.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research shows that repetitive transcranial magnetic stimulation (rTMS) can significantly reduce symptoms in patients with schizophrenia who experience treatment-resistant auditory hallucinations. In one study, patients receiving rTMS showed better improvement scores compared to those receiving a sham treatment, indicating its potential effectiveness. ^{1 2 3 4 5}

Is repetitive transcranial magnetic stimulation (rTMS) safe for humans?

Repetitive transcranial magnetic stimulation (rTMS) is generally considered safe for humans, with studies indicating it is largely without side effects when used for conditions like schizophrenia. ^{2 6 7 8 9}

How does TMS treatment differ from other treatments for schizophrenia hallucinations?

TMS (transcranial magnetic stimulation) is unique because it uses magnetic fields to stimulate specific areas of the brain, which can help reduce auditory hallucinations in schizophrenia. Unlike traditional medications, TMS is non-invasive and targets brain activity directly, offering a different approach for patients who do not respond well to standard treatments. ^{3 4 8 10 11}

Research Team

Mark Halko, PhD

Principal Investigator

Mclean Hospital

Eligibility Criteria

This trial is for individuals with schizophrenia or schizoaffective disorder. It's not suitable for those who've had substance use disorders recently, have ambidexterity, contraindications to TMS or MRI like neurological issues, head trauma with unconsciousness, seizures/epilepsy (or family history of it), metal in the brain/skull, implanted medical devices, or claustrophobia in MRI.

Inclusion Criteria

I have been diagnosed with schizophrenia or schizoaffective disorder.

Exclusion Criteria

I don't have a neurological disorder, head trauma, seizures, epilepsy, metal in my head, implanted devices, or claustrophobia in MRI.

You have had a problem with drugs or alcohol in the past 3 months.

Being able to use both hands equally well.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Baseline Assessment

Participants undergo baseline assessments including PANSS and MRI scans

1 week

1 visit (in-person)

Treatment

Participants undergo five days of twice daily rTMS sessions

1 week

10 visits (in-person)

Follow-up

Participants undergo follow-up MRI imaging and study assessments one week after the last rTMS session

1 week

1 visit (in-person)

Treatment Details

Interventions

• Repetitive Transcranial Magnetic Stimulation (rTMS)
• Sham Repetitive Transcranial Magnetic Stimulation (rTMS)

Trial Overview The study tests transcranial magnetic stimulation (TMS) as a noninvasive brain stimulation technique to understand and potentially improve hallucinations in schizophrenia. Participants will receive repetitive TMS (rTMS) or a sham version that mimics the procedure without actual stimulation.

Participant Groups

Group I: Active cerebellum rTMS Active Control 1 Intervention

Cerebellar targeted iTBS, twice daily, one week.

Group II: Sham cerebellum rTMS Placebo Group 1 Intervention

Cerebellar targeted sham iTBS, twice daily, one week.

Who Is Running the Clinical Trial?

Mclean Hospital

Lead Sponsor

Trials

221

Recruited

22,500+

Beth Israel Deaconess Medical Center

Collaborator

Trials

872

Recruited

12,930,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Findings from Research

In a study involving 39 patients with treatment-refractory auditory hallucinations, 10 days of low-frequency repetitive transcranial magnetic stimulation (rTMS) significantly reduced symptoms compared to sham stimulation, as measured by various scales including the Auditory Hallucination Rating Scale and Clinical Global Impression.

Both left and right temporoparietal cortex rTMS treatments showed similar improvements in symptoms, indicating that while rTMS is effective for reducing auditory hallucinations, there is no significant advantage of targeting the left side over the right.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double blind study showing that two weeks of daily repetitive TMS over the left or right temporoparietal cortex reduces symptoms in patients with schizophrenia who are having treatment-refractory auditory hallucinations. Lee, SH., Kim, W., Chung, YC., et al.[2022]

In a study involving 22 chronic schizophrenia patients, high-frequency left prefrontal repetitive transcranial magnetic stimulation (rTMS) did not show a significant therapeutic effect compared to sham treatment over 10 sessions.

Both groups experienced improvements in symptoms, but the real rTMS group had only one patient with a notable reduction in symptoms, suggesting that the observed benefits may be due to nonspecific effects rather than the rTMS treatment itself.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Left prefrontal repetitive transcranial magnetic stimulation in schizophrenia. Holi, MM., Eronen, M., Toivonen, K., et al.[2022]

A 29-year-old woman with schizophrenia experienced significant improvement in her visual hallucinations after receiving inhibitory repetitive transcranial magnetic stimulation (rTMS) on the visual cortex.

The positive effects of rTMS lasted for three months, suggesting it could be an effective treatment option for individuals suffering from refractory visual hallucinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation in Resistant Visual Hallucinations in a Woman With Schizophrenia: A Case Report. Ghanbari Jolfaei, A., Naji, B., Nasr Esfehani, M.[2020]

In a study involving 40 schizophrenia patients, low-frequency rTMS applied to the left temporoparietal cortex significantly reduced auditory hallucinations compared to a control group receiving only antipsychotic treatment.

The results indicate that rTMS may selectively influence the neurobiological factors associated with auditory hallucinations, suggesting its potential as a valuable addition to existing treatments for schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of augmentatory repetitive transcranial magnetic stimulation on auditory hallucinations in schizophrenia: randomized controlled study. Bagati, D., Nizamie, SH., Prakash, R.[2013]

Repetitive transcranial magnetic stimulation (rTMS) shows promise as a treatment for auditory verbal hallucinations (AVH) in schizophrenia patients who do not respond to antipsychotics, with several meta-analyses indicating positive effects on AVH reduction.

Further research is needed to clarify how rTMS affects language networks in the brain and to establish better methods for measuring changes in AVH, as well as to define treatment-resistant AVH more clearly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The use of repetitive transcranial magnetic stimulation (rTMS) in auditory verbal hallucinations (AVH)]. Jandl, M.[2010]

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]

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]

In a study of 50 patients with schizophrenia or schizoaffective disorder, 1-hertz left temporoparietal repetitive transcranial magnetic stimulation (rTMS) significantly reduced the frequency and severity of auditory hallucinations compared to sham stimulation, indicating its potential efficacy as a treatment.

The rTMS treatment was well-tolerated with no evidence of neurocognitive impairment, suggesting it is a safe intervention for patients experiencing distressing auditory hallucinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temporoparietal transcranial magnetic stimulation for auditory hallucinations: safety, efficacy and moderators in a fifty patient sample. Hoffman, RE., Gueorguieva, R., Hawkins, KA., et al.[2022]

Repetitive transcranial magnetic stimulation (rtms) has shown significant efficacy in reducing auditory verbal hallucinations and negative symptoms in schizophrenia compared to sham stimulation, although results can vary across studies.

Transcranial direct current stimulation (tdcs) lacks sufficient evidence to support its effectiveness for treating these symptoms, but both rtms and tdcs are considered safe with minimal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Non-invasive brain stimulation in schizophrenia: hallucinations and negative symptoms]. Aleman, A., Brummelman, J., Dlabac-de Lange, JJ., et al.[2018]

Repetitive transcranial magnetic stimulation (rTMS) shows a positive effect in reducing auditory hallucinations in schizophrenia, based on a meta-analysis of 10 double-blinded randomized sham-controlled trials.

The treatment specifically targets the left temporoparietal cortex, indicating its potential effectiveness in managing symptoms, although further studies are needed to strengthen the findings and improve sample size.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review and meta-analysis of the use of repetitive transcranial magnetic stimulation for auditory hallucinations treatment in refractory schizophrenic patients. Otani, VH., Shiozawa, P., Cordeiro, Q., et al.[2022]

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]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

A double blind study showing that two weeks of daily repetitive TMS over the left or right temporoparietal cortex reduces symptoms in patients with schizophrenia who are having treatment-refractory auditory hallucinations. [2022]

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

Left prefrontal repetitive transcranial magnetic stimulation in schizophrenia. [2022]

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

Repetitive Transcranial Magnetic Stimulation in Resistant Visual Hallucinations in a Woman With Schizophrenia: A Case Report. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Effect of augmentatory repetitive transcranial magnetic stimulation on auditory hallucinations in schizophrenia: randomized controlled study. [2013]

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

[The use of repetitive transcranial magnetic stimulation (rTMS) in auditory verbal hallucinations (AVH)]. [2010]

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. 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]

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

Temporoparietal transcranial magnetic stimulation for auditory hallucinations: safety, efficacy and moderators in a fifty patient sample. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

[Non-invasive brain stimulation in schizophrenia: hallucinations and negative symptoms]. [2018]

10. England pubmed.ncbi.nlm.nih.gov

A systematic review and meta-analysis of the use of repetitive transcranial magnetic stimulation for auditory hallucinations treatment in refractory schizophrenic patients. [2022]

11. 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]