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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how Transcranial Magnetic Stimulation (TMS), which uses magnetic fields to influence brain activity, affects memory functioning in individuals experiencing early psychosis. Participants will receive either active TMS treatment or a placebo (a non-active version) to compare outcomes. Ideal candidates for the trial include those diagnosed with conditions like schizophrenia or bipolar disorder with psychosis within the last ten years and who can provide informed consent. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research in understanding and potentially improving memory function in early psychosis.

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 patients with early psychosis?

Research has shown that Transcranial Magnetic Stimulation (TMS) is generally safe and well-tolerated. Studies have found it to be a non-invasive treatment, meaning it doesn't involve surgery or entering the body. Most people do not experience major side effects from TMS. Some might feel mild discomfort or a slight headache, but these usually resolve quickly. Importantly, individuals with schizophrenia, a condition related to psychosis, are not at a higher risk for serious effects, such as seizures, when using TMS. Overall, evidence suggests that TMS is a safe option for many people. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about TMS (Transcranial Magnetic Stimulation) for psychosis because it offers a non-invasive approach that could provide rapid relief from symptoms without the side effects typical of antipsychotic medications. Unlike standard treatments, which often involve altering brain chemistry with drugs, TMS uses magnetic fields to stimulate nerve cells in the brain directly. This technique is particularly promising because it targets specific brain regions involved in psychosis, potentially leading to more precise and individualized treatment. Moreover, the immediate impact on brain activity, observable through functional MRI, suggests that TMS might show results much faster than traditional medications.

What evidence suggests that TMS is effective for psychosis?

This trial will compare Active TMS with Placebo TMS. Studies have shown that Transcranial Magnetic Stimulation (TMS) can improve symptoms in people with schizophrenia, particularly negative symptoms like lack of motivation or reduced emotional expression. Research indicates that TMS can also enhance cognitive skills, such as memory and decision-making, often affected in early stages of psychosis. In other studies, participants who received real TMS treatment showed better results compared to those who received a fake treatment. Overall, evidence supports that TMS may effectively improve certain symptoms in people experiencing early psychosis. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

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

I do not have any unstable illnesses that would stop me from participating in the study.

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38657896/

Repetitive transcranial magnetic stimulation can improve ... Repetitive transcranial magnetic stimulation can improve negative symptoms and/or neurocognitive impairments in the first psychosis episode: A ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165178124000155

Efficacy of repetitive transcranial magnetic stimulation ... Most reviews indicate that rTMS has an effect on negative symptoms, executive function, working memory, and language function in patients with schizophrenia.

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

Repetitive Transcranial Magnetic Stimulation for Auditory ... Participants in the active rTMS group had higher response rates than the sham treatment group at week 2 (15 of 32 [47%] vs 4 of 30 [13%]; χ2 = ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01551979

Therapeutic Efficacy of Transcranial Magnetic Stimulation ... The primary outcome is improvement in negative symptoms related to schizophrenia. The investigators are focusing on negative symptoms given their greater ...

5. mdpi.com mdpi.com/2076-3425/13/12/1665

Efficacy of Repetitive Transcranial Magnetic Stimulation ... The meta-analysis showed that active rTMS combined with psychological interventions did not produce a significantly greater improvement in depressive symptoms ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK568715/

Repetitive Transcranial Magnetic Stimulation - StatPearls - NCBI Repetitive transcranial magnetic stimulation (rTMS) is a safe and non-invasive treatment technique used to treat various psychiatric and neurological disorders.

7. mayoclinic.org mayoclinic.org/tests-procedures/transcranial-magnetic-stimulation/about/pac-20384625

Transcranial magnetic stimulation Generally, rTMS is considered safe and well-tolerated. However, it can cause some side effects. Common side effects. Side effects are generally ...

8. 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 ...

9. 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.

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

Effectiveness of Repetitive Transcranial Magnetic ... In treatment-resistant depression, repetitive transcranial magnetic stimulation had higher odds of response and remission rates compared to ...