rTMS for Schizophrenia

Overseen By Kimberly Tate

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Maryland, Baltimore

Must not be taking: Clozapine

Disqualifiers: Seizures, Substance abuse, Major illnesses, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 2 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called repetitive transcranial magnetic stimulation (rTMS) for individuals with schizophrenia spectrum disorder (SSD). Participants will undergo both real and sham rTMS sessions to assess the treatment's impact on SSD-related biological markers in the brain. It suits those diagnosed with SSD who do not have major medical issues such as seizures or certain heart conditions. As an unphased trial, this study provides participants the opportunity to contribute to groundbreaking research that could lead to new insights and treatments for SSD.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking more than 400 mg of clozapine per day.

What prior data suggests that rTMS is safe for patients with schizophrenia spectrum disorder?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) is safe and generally well-tolerated for people with schizophrenia. Studies have found that rTMS does not increase the risk of serious side effects like seizures, which is reassuring. Specifically, a review found that patients did not experience any serious side effects. This makes rTMS a promising treatment option, especially since it proved more effective than placebo treatments in reducing negative symptoms of schizophrenia. Overall, the evidence suggests that rTMS is a safe option for those considering joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about rTMS (repetitive Transcranial Magnetic Stimulation) for schizophrenia because it offers a non-invasive approach that directly targets brain activity, which is different from the traditional use of antipsychotic medications. While most treatments for schizophrenia primarily focus on balancing neurotransmitters like dopamine through medication, rTMS uses magnetic fields to stimulate specific areas of the brain, potentially reducing symptoms without the common side effects associated with drugs. This technique is promising because it could provide faster relief for patients and might also be effective for those who do not respond well to medication. Furthermore, the trial explores the potential of rTMS by comparing active and sham treatments, which could help refine its application and effectiveness.

What evidence suggests that rTMS might be an effective treatment for schizophrenia?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) can help reduce the negative symptoms of schizophrenia. In this trial, participants will receive both active rTMS and sham rTMS in different sequences. One study found that rTMS was more effective than a sham treatment in lessening these symptoms, with a statistically significant difference. Reviews also suggest that rTMS can improve cognitive skills, such as memory and language, in people with schizophrenia. Another study found that active rTMS helps stabilize brain function in individuals with schizophrenia, addressing a common challenge. These findings suggest that rTMS could be a promising treatment for managing certain symptoms of schizophrenia. ^{2 6 7 8 9}

Who Is on the Research Team?

Xiaoming Du

Principal Investigator

University of Maryland, Baltimore

Are You a Good Fit for This Trial?

This trial is for men and women aged 18-65 with schizophrenia-spectrum disorder who can consent to participate. Excluded are those with major medical conditions affecting the brain, high clozapine doses, failed TMS screening, significant head injury or surgery, pregnancy without contraception, metal implants near the head, seizure history, or recent substance abuse.

Inclusion Criteria

Diagnosed with schizophrenia-spectrum disorder and Evaluation to Sign Consent (ESC) above 10

Exclusion Criteria

I have a history of seizures.

I do not have any major illnesses affecting my brain function.

Significant alcohol or other drug use (substance dependence within 6 months or substance abuse within 1 month) other than nicotine or marijuana dependence

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sham and active rTMS in separate sessions to assess SSD-related biomarkers

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after rTMS sessions

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• rTMS

Trial Overview The study tests active versus sham (fake) repetitive transcranial magnetic stimulation (rTMS) on patients with schizophrenia. It aims to see how rTMS affects certain biomarkers related to the disorder by comparing results before and after treatment in separate sessions.

How Is the Trial Designed?

Group I: Sham rTMS first and active rTMS second Experimental Treatment 1 Intervention

Participants in this arm will receive sham rTMS in one visit first, then receive active rTMS in another visit.

Group II: Active rTMS first and sham rTMS second Experimental Treatment 1 Intervention

Participants in this arm will receive active rTMS in one visit first, then receive sham rTMS in another visit.

rTMS is already approved in United States, European Union for the following indications:

Approved in United States as rTMS for:

• Obsessive-Compulsive Disorder (OCD)
• Major Depressive Disorder
• Migraines
• Smoking cessation

Approved in European Union as rTMS for:

• Obsessive-Compulsive Disorder (OCD)
• Major Depressive Disorder

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Published Research Related to This Trial

In a study involving 25 patients with schizophrenia, bilateral high-frequency rTMS targeting the dorsolateral prefrontal cortex did not significantly reduce negative symptoms or depressive symptoms after 20 treatment sessions over 4 weeks.

The results suggest that negative symptoms of schizophrenia may not respond to rTMS treatment as currently applied, indicating a need for further optimization of treatment parameters to enhance efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized controlled trial of sequentially bilateral prefrontal cortex repetitive transcranial magnetic stimulation in the treatment of negative symptoms in schizophrenia. Barr, MS., Farzan, F., Tran, LC., et al.[2018]

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 16 patients with schizophrenia, high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) over the left dorsolateral prefrontal cortex did not show significant effects on negative symptoms compared to sham treatment.

While there was a trend for improvement in some symptoms with sham rTMS, the study concluded that HF-rTMS is not effective for treating negative symptoms of schizophrenia, suggesting the need for exploring alternative rTMS methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The double-blind sham-controlled study of high-frequency rTMS (20 Hz) for negative symptoms in schizophrenia: negative results. Novák, T., Horácek, J., Mohr, P., et al.[2006]

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]

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]

In a study involving 12 schizophrenia patients, repetitive transcranial magnetic stimulation (rTMS) significantly reduced psychiatric symptoms as measured by the Brief Psychiatric Rating Scale after 2 weeks of active treatment compared to sham stimulation.

While rTMS showed efficacy in improving overall psychiatric symptoms, it did not significantly affect depressive or anxiety symptoms, suggesting its potential as a non-pharmacological treatment specifically for psychotic symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High frequency repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex in schizophrenic patients. Rollnik, JD., Huber, TJ., Mogk, H., et al.[2022]

The study found that repetitive transcranial magnetic stimulation (rTMS) was safe for schizophrenia patients with first-rank symptoms, as no significant adverse events were reported during the 2-week treatment period.

However, the rTMS treatment did not show significant efficacy in alleviating first-rank symptoms or affecting cognitive and biological markers, indicating that this specific rTMS protocol may not be effective as an adjunctive treatment for these symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Adjunctive Θ Burst Repetitive Transcranial Magnetic Stimulation to Right Inferior Parietal Lobule in Schizophrenia Patients With First-Rank Symptoms: A Pilot, Exploratory Study. Tikka, SK., Nizamie, SH., Venkatesh Babu, GM., et al.[2022]

In a study of 47 patients with schizophrenia, active rTMS over the left dorsolateral prefrontal cortex showed no immediate effect on negative symptoms at 4 weeks, but by 8 weeks, there was a significant reduction in symptoms compared to the sham group.

These results indicate that rTMS may have a delayed therapeutic effect on negative symptoms of schizophrenia, suggesting it could be a beneficial treatment option over a longer duration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delayed effect of repetitive transcranial magnetic stimulation (rTMS) on negative symptoms of schizophrenia: Findings from a randomized controlled trial. Li, Z., Yin, M., Lyu, XL., et al.[2018]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37788803/

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).

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. 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).

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39373168/

Data From a Double-Blind, Randomized, Sham-Controlled ... Active rTMS to DLPFC reduces individual variability of brain function in people with schizophrenia. Given that individual variability is typically higher in ...

5. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2024.1390913/full

Deep transcranial magnetic stimulation for schizophrenia This systematic review suggests that dTMS does not reduce psychotic symptoms in schizophrenia, but it shows potential for improving executive functions.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11176548/

Deep transcranial magnetic stimulation for schizophrenia An open-label study found that dTMS significantly improved negative symptoms in schizophrenia (28), but recent randomized controlled trials ( ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT00564096

Transcranial Magnetic Stimulation (TMS) in Schizophrenia Generally, the TMS treatment was reported to be well tolerated. No serious adverse effects were reported by any of the patients. There is no evidence that rTMS ...

8. 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.

9. 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.