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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how transcranial magnetic stimulation (TMS) might reduce hallucinations in people with schizophrenia. TMS uses a magnetic field to stimulate specific brain areas, potentially improving symptoms. Participants will receive either active TMS treatment or a sham (fake) version to compare effects. Ideal candidates are those diagnosed with schizophrenia or schizoaffective disorder, but they should not have recent substance use issues or certain medical conditions, such as a history of seizures.

As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to new treatment options.

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 prior data suggests that transcranial magnetic stimulation (TMS) is safe for treating schizophrenia hallucinations?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) is safe and well-tolerated for people with schizophrenia. Studies indicate that these individuals do not face a higher risk of side effects, such as seizures, when using rTMS. This noninvasive method uses magnets to stimulate the brain. Evidence suggests that rTMS does not cause serious problems and is generally easy for patients to handle. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for schizophrenia hallucinations, like antipsychotics, focus on balancing brain chemicals. But repetitive Transcranial Magnetic Stimulation (rTMS) offers a different approach by using magnetic fields to stimulate specific brain areas. Researchers are excited because rTMS targets the cerebellum, which is not the usual focus for hallucinations. This technique could provide a non-invasive alternative with potentially fewer side effects compared to medication. Plus, it might work faster and more precisely, offering new hope for those who haven't found relief with traditional treatments.

What evidence suggests that this technique is effective for schizophrenia hallucinations?

Research shows that repetitive transcranial magnetic stimulation (rTMS) can help reduce hallucinations in people with schizophrenia. In this trial, participants will receive either active cerebellum rTMS or sham cerebellum rTMS. Some studies have found that patients who received rTMS experienced a noticeable decrease in hearing voices compared to those who received a sham treatment. For example, one study found that rTMS was more effective than sham at reducing negative symptoms of schizophrenia. Another study showed that patients whose hallucinations did not improve with medication got better after rTMS sessions. Overall, these findings suggest that rTMS might be a promising option for managing certain symptoms of schizophrenia. ^{3 4 6 7 8}

Who Is on the Research Team?

Mark Halko, PhD

Principal Investigator

Mclean Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

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 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]

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]

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 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]

Citations

1. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2825941

Repetitive Transcranial Magnetic Stimulation for Auditory ... The findings of this randomized clinical trial suggest that imaging-navigated rTMS may effectively and safely alleviate AVH in patients with schizophrenia.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39527055/

Repetitive Transcranial Magnetic Stimulation for Auditory ... The findings of this randomized clinical trial suggest that imaging-navigated rTMS may effectively and safely alleviate AVH in patients with schizophrenia.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4146020/

Repetitive transcranial magnetic stimulation for hallucination ... They reported an improvement of hallucination in three schizophrenia patients with medication-resistant hallucinations after a total of 40 minutes of 1 Hz ...

4. psychiatrist.com psychiatrist.com/pcc/effectiveness-repetitive-transcranial-magnetic-stimulation-depression-schizophrenia-obsessive-compulsive-disorder-umbrella-meta-analysis/

Effectiveness of Repetitive Transcranial Magnetic ... rTMS was superior to sham in the reduction of negative symptoms of schizophrenia (mean difference [MD]: 0.47; 95% CI, 0.23–0.7; P < .0001).

5. sciencedirect.com sciencedirect.com/science/article/pii/S0165178119324849

Efficacy of repetitive transcranial magnetic stimulation on ... Auditory hallucinations improved more in the rTMS group than in the sham group (SMD = -0.27, 95%CI = -0.51 to -0.03). However, this result was not stable after ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3656498/

Safety and tolerability of repetitive transcranial magnetic ... The published data suggest rTMS for the treatment or diagnosis of pathologic positive sensory phenomena appears to be a relatively safe and well-tolerated ...

7. academic.oup.com academic.oup.com/schizophreniabulletin/article/51/2/392/7758322

Safety of rTMS for Schizophrenia: A Systematic Review and ... rTMS is safe and well tolerated for people with schizophrenia. Individuals with schizophrenia are not at increased risk for adverse effects, including seizure.

8. nature.com nature.com/articles/s41398-024-03106-4

Targeting auditory verbal hallucinations in schizophrenia Meta-analysis of the effects of repetitive transcranial magnetic stimulation (rTMS) on negative and positive symptoms in schizophrenia.