TMS for Psychosis

Overseen By Hamdi Eryilmaz, Ph.D

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Disqualifiers: Seizures, Pregnancy, Claustrophobia, others

Compensation: Varies

Number of Visits: 2

Duration: 1 day

20 Participants Needed

Trial Summary

What is the purpose of this trial?

The main goal of this study is to investigate the neural mechanisms of working memory function in patients with early psychosis using Transcranial Magnetic Stimulation (TMS) in conjunction with functional MRI. TMS is a noninvasive method used to modulate brain activity via changing magnetic fields applied over the surface of the scalp.

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 TMS for Psychosis?

Some studies suggest that transcranial magnetic stimulation (TMS) may improve symptoms in schizophrenia, particularly negative symptoms, when compared to a placebo. However, the evidence is mixed, and more high-quality research is needed to confirm its effectiveness. ^{1 2 3 4 5}

Is transcranial magnetic stimulation (TMS) safe for humans?

Research indicates that transcranial magnetic stimulation (TMS) is generally safe for humans, with serious adverse events being rare across various neuropsychiatric conditions. ^{1 2 3 6 7}

How does TMS treatment for psychosis differ from other treatments?

TMS (Transcranial Magnetic Stimulation) is unique because it uses magnetic fields to stimulate nerve cells in the brain, which is different from traditional drug treatments. It is non-invasive and can be used as a placebo (sham) treatment, which mimics the sensation of real TMS without the actual brain stimulation, making it a novel approach in treating psychosis. ^{2 3 4 8 9}

Eligibility Criteria

This trial is for individuals within the first ten years of experiencing psychotic symptoms, diagnosed with conditions like schizophrenia, schizoaffective disorder, or bipolar with psychosis. Participants must be able to understand and agree to the study's procedures.

Inclusion Criteria

I was diagnosed with a psychotic disorder within the first 10 years of showing symptoms.

Ability to provide informed consent

Exclusion Criteria

TMS incompatibility including metallic implants in head and neck, cardiac pacemakers, history of seizures, pregnancy

MRI-incompatibility including implanted aneurism clips, cardiac pacemakers, metal implants, intrauterine devices, tattoos containing metal ink, pregnancy, and claustrophobia

Severe substance abuse within 3 months (nicotine allowed)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive single-session administration of TMS or placebo TMS with functional MRI acquired before and after the intervention

1 day

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

Treatment Details

Interventions

• Active TMS
• Placebo TMS

Trial Overview The study is testing how working memory functions in early psychosis patients using Transcranial Magnetic Stimulation (TMS) alongside brain imaging. TMS uses magnetic fields on the scalp to influence brain activity noninvasively.

Participant Groups

Group I: Active TMS Experimental Treatment 1 Intervention

Participants will receive single-session administration of TMS. Functional MRI will be acquired before and immediately after the intervention.

Group II: Placebo TMS Placebo Group 1 Intervention

Participants will also receive single session administration of placebo TMS (at least two days apart from the day of the active TMS). Functional MRI will be acquired before and immediately after the intervention.

Active TMS is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as TMS for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder
• Migraines

Approved in European Union as TMS for:

• Depression
• Migraines

Approved in United Kingdom as TMS for:

• Depression

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Findings from Research

Transcranial magnetic stimulation (TMS) showed significant benefits over sham treatment in reducing positive symptoms of schizophrenia and improving overall global state, based on a systematic review of 41 trials involving 1473 participants.

Despite these promising results, the overall quality of the trials was low, with many showing strong biases, making it difficult to recommend TMS for routine clinical use without further high-quality research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial Magnetic Stimulation for Schizophrenia. Dougall, N., Maayan, N., Soares-Weiser, K., et al.[2023]

The new real electro-magnetic placebo (REMP) device effectively simulates the scalp sensations of real repetitive transcranial magnetic stimulation (rTMS) while ensuring that it does not produce any biologically active electric fields, making it a more reliable sham for clinical trials.

In tests, naive subjects were more likely to mistake the REMP-attenuated TMS for real rTMS compared to other sham methods, indicating that the REMP device provides a superior placebo experience, which is crucial for accurately assessing the efficacy of rTMS treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A real electro-magnetic placebo (REMP) device for sham transcranial magnetic stimulation (TMS). Rossi, S., Ferro, M., Cincotta, M., et al.[2021]

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]

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]

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]

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 considered safe and shows positive effects in treating various neuropsychiatric conditions based on a meta-analysis of 52 studies from India, with moderate to large effect sizes in 'active only' treatment groups.

However, when comparing rTMS to sham treatments, the evidence for its efficacy is not significant, indicating that while rTMS may help in real treatment scenarios, it may not outperform placebo in controlled settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence from Indian studies on safety and efficacy of therapeutic transcranial magnetic stimulation across neuropsychiatric disorders- A systematic review and meta-analysis. Tikka, SK., Godi, SM., Siddiqui, MA., et al.[2023]

A systematic review of 61 randomized controlled trials involving 1328 participants with major depressive disorder found a large placebo response (effect size g=0.8) to repetitive transcranial magnetic stimulation (rTMS), indicating that many patients experience significant symptom relief even without active treatment.

The magnitude of the placebo response was linked to the improvement seen in the active treatment group, suggesting that the placebo effect may play a role in the overall therapeutic response to rTMS, and that trial designs may need to account for this effect to better assess the efficacy of rTMS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review and meta-analysis on placebo response to repetitive transcranial magnetic stimulation for depression trials. Razza, LB., Moffa, AH., Moreno, ML., et al.[2018]

The meta-analysis of 21 studies involving 303 patients revealed a significant placebo effect in the treatment of auditory verbal hallucinations (AVH) with repetitive transcranial magnetic stimulation (rTMS), with a mean effect size of 0.29, indicating that the placebo response can influence treatment outcomes.

The analysis showed that the placebo effect was notably stronger in parallel studies (effect size of 0.44) compared to crossover studies (effect size of 0.06), suggesting that study design plays a crucial role in the perceived efficacy of rTMS in treating AVH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo Response in Repetitive Transcranial Magnetic Stimulation Trials of Treatment of Auditory Hallucinations in Schizophrenia: A Meta-Analysis. Dollfus, S., Lecardeur, L., Morello, R., et al.[2022]

References

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

Transcranial Magnetic Stimulation for Schizophrenia. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

A real electro-magnetic placebo (REMP) device for sham transcranial magnetic stimulation (TMS). [2021]

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

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

4. 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]

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

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

6. 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]

7. India pubmed.ncbi.nlm.nih.gov

Evidence from Indian studies on safety and efficacy of therapeutic transcranial magnetic stimulation across neuropsychiatric disorders- A systematic review and meta-analysis. [2023]

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

A systematic review and meta-analysis on placebo response to repetitive transcranial magnetic stimulation for depression trials. [2018]

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

Placebo Response in Repetitive Transcranial Magnetic Stimulation Trials of Treatment of Auditory Hallucinations in Schizophrenia: A Meta-Analysis. [2022]