TMS for Schizophrenia

Overseen By Dawn Detamore

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: The University of Texas Health Science Center, Houston

Must be taking: Antipsychotics

Must not be taking: Cephalosporins, Antiarrhythmics

Disqualifiers: Epilepsy, Substance abuse, Brain conditions, 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: 20

Duration: 4 weeks

140 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a treatment called repetitive transcranial magnetic stimulation (rTMS) to help individuals with schizophrenia. The goal is to determine if rTMS can reduce symptoms like auditory hallucinations (hearing voices) and improve memory and attention by targeting specific brain areas. Participants will receive either real rTMS or a sham (fake) treatment to compare results. Individuals diagnosed with schizophrenia, who experience auditory hallucinations, and have tried at least two different antipsychotic medications might be suitable for this study. As an unphased trial, this study offers a unique opportunity to contribute to pioneering research that could lead to new treatment options.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that participants should not be taking more than 400 mg of clozapine per day without anti-seizure medication. It's best to discuss your current medications with the trial staff.

What prior data suggests that this TMS technique is safe for schizophrenia patients?

Research shows that repetitive transcranial magnetic stimulation (rTMS) is safe and well-tolerated for people with schizophrenia. Studies have found that individuals with schizophrenia do not face a higher risk of side effects, including seizures, when receiving rTMS. Participants in past studies generally handled the treatment well, with no major safety concerns reported. This suggests that rTMS could be a promising option for improving symptoms like hearing voices and problems with memory and attention in schizophrenia, while maintaining safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the use of repetitive Transcranial Magnetic Stimulation (rTMS) for schizophrenia because it offers a non-invasive approach to treatment. Unlike standard antipsychotic medications that primarily target neurotransmitter systems like dopamine, rTMS uses magnetic fields to stimulate specific areas of the brain, potentially offering relief without the side effects associated with medication. This method could be particularly beneficial for patients who do not respond well to traditional treatments or who experience significant medication side effects. Additionally, the potential for rTMS to provide quicker symptom relief compared to conventional therapies is an exciting prospect for both researchers and patients.

What evidence suggests that TMS is effective for schizophrenia?

Research has shown that repetitive Transcranial Magnetic Stimulation (rTMS) can help people with schizophrenia. In this trial, participants will receive either Active rTMS stimulation or Sham rTMS stimulation. Studies have found that rTMS can reduce negative symptoms like lack of motivation and social withdrawal, common in schizophrenia. It may also improve thinking skills, such as memory and attention. Some studies suggest that targeting the prefrontal cortex, a part of the brain involved in decision-making and social behavior, can be especially beneficial. While more research is needed, early results are promising for those experiencing hearing voices and other related symptoms. ^{1 6 7 8 9}

Who Is on the Research Team?

Xiaoming Du, PhD

Principal Investigator

The University of Texas Health Science Center, Houston

Are You a Good Fit for This Trial?

This trial is for adults aged 21-62 with schizophrenia, stable on their current medication for at least 4 weeks. They must be able to consent and not have a history of seizures, family epilepsy, significant substance abuse recently (except nicotine or marijuana), or take high doses of clozapine. Pregnant women and those with metal implants near the head can't participate.

Inclusion Criteria

Medication stability for 4 weeks (same drugs at same dosages)

I am 21 or older and can sign a consent form.

I am between 21 and 62 years old.

Exclusion Criteria

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

I have a history of seizures.

I do not have a pacemaker, metal implants near my head, or unstable heart disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive functionally navigated repetitive TMS stimulations to the prefrontal cortex to modulate aberrant cortical electrical activities

4 weeks

20 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Active rTMS stimulation
• Sham rTMS stimulation

Trial Overview The study tests if targeted repetitive TMS (a non-invasive brain stimulation) to the prefrontal cortex can improve symptoms like auditory hallucinations and attention in schizophrenia patients. It compares active rTMS against sham (fake) treatment to see if it corrects abnormal brain activity.

How Is the Trial Designed?

Group I: Active rTMS stimulation Active Control 1 Intervention

Real active rTMS stimulation.

Group II: Sham rTMS stimulation Placebo Group 1 Intervention

Sham repetitive TMS stimulation.

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

Approved in United States as rTMS for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder
• Smoking Cessation

Approved in European Union as rTMS for:

• Major Depressive Disorder

Approved in United States as dTMS for:

• Treatment-Resistant Major Depressive Disorder

Approved in European Union as dTMS for:

• Treatment-Resistant Major Depressive Disorder

Who Is Running the Clinical Trial?

The University of Texas Health Science Center, Houston

Lead Sponsor

Trials

974

Recruited

361,000+

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

In a single-blind, randomized controlled study, continuous theta burst stimulation (TBS) was found to be as effective as 1 Hz repetitive transcranial magnetic stimulation (rTMS) for treating auditory verbal hallucinations in patients with schizophrenia or schizoaffective disorder.

Both therapies were administered over a 10-day treatment period, indicating that TBS may offer a comparable alternative to traditional rTMS with potentially longer-lasting effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Theta burst transcranial magnetic stimulation for the treatment of auditory verbal hallucinations: results of a randomized controlled study. Kindler, J., Homan, P., Flury, R., et al.[2022]

In a double-blind, placebo-controlled trial involving 71 patients with refractory auditory verbal hallucinations (AVH), both the TB-rTMS and placebo groups showed significant improvement in AVH severity, indicating that symptom reduction can occur even without specific treatment effects.

Despite the initial promise of TB-rTMS for treating AVH, the study found no significant difference in outcomes between the TB-rTMS and placebo groups, suggesting that the observed improvements may be attributed to placebo effects rather than the treatment itself.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Theta Burst Transcranial Magnetic Stimulation for Auditory Verbal Hallucinations: Negative Findings From a Double-Blind-Randomized Trial. Koops, S., van Dellen, E., Schutte, MJ., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) targeting the right inferior parietal lobe (IPL) significantly improved gesture performance and manual dexterity in patients with schizophrenia, indicating a potential therapeutic approach for social interaction deficits.

The study involved 20 schizophrenia patients and 20 healthy controls, and the results suggest that inhibiting interhemispheric rivalry through cTBS may enhance motor functions related to social gestures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single Session Transcranial Magnetic Stimulation Ameliorates Hand Gesture Deficits in Schizophrenia. Walther, S., Kunz, M., Müller, M., et al.[2021]

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]

Intermittent theta-burst stimulation, when used alongside antipsychotic medications, significantly improves negative symptoms and general psychopathology in patients with schizophrenia, based on a meta-analysis of 13 trials involving 524 patients.

The treatment is well tolerated and safe, with optimal results observed when stimulation is applied to the left dorsolateral prefrontal cortex using at least 1800 pulses per day over a minimum of 20 sessions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of intermittent theta-burst stimulation in patients with schizophrenia: A meta-analysis of randomized sham-controlled trials. Goh, KK., Chen, CH., Wu, TH., et al.[2022]

This study is a randomized, sham-controlled, double-blind trial involving 86 patients with schizophrenia spectrum disorder, testing the efficacy of continuous theta burst stimulation (cTBS) on reducing auditory verbal hallucinations (AH).

The primary goal is to measure the reduction in AH symptoms using the PSYRATS-AH score after treatment, with follow-up assessments at 1, 3, and 6 months, which will help determine the effectiveness of cTBS compared to sham treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of auditory hallucinations with bilateral theta burst stimulation (cTBS): protocol of a randomized, double-blind, placebo-controlled, multicenter trial. Plewnia, C., Brendel, B., Schwippel, T., et al.[2018]

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]

Theta burst stimulation (TBS) is a promising therapeutic approach for schizophrenia, showing potential benefits in treating specific symptoms and improving patient insight, based on a review of 30 studies that utilized various neuroimaging techniques.

TBS is well-tolerated and has few adverse effects, making it a feasible option for augmenting traditional pharmacotherapy in patients with schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of theta burst stimulation in patients with schizophrenia - A systematic review. Poorganji, M., Goeke, K., Zomorrodi, R., et al.[2023]

This clinical trial will compare the effects of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) and intermittent theta burst stimulation (iTBS) on negative symptoms of schizophrenia in 90 patients, aiming to provide a new treatment option for this challenging condition.

The study will also explore the impact of these treatments on depressive symptoms, cognitive performance, and smoking behavior, while using MRI and EEG to identify potential neural markers for treatment success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and study design of a trial to assess rTMS add-on value for the amelioration of negative symptoms of schizophrenia (RADOVAN). Hebel, T., Langguth, B., Schecklmann, M., et al.[2022]

A preliminary study involving 15 patients with schizophrenia showed that 20 daily sessions of deep transcranial magnetic stimulation (deep-TMS) significantly improved cognitive deficits and negative symptoms.

The improvements in symptoms were sustained for at least two weeks after the treatment, suggesting that deep-TMS could be a promising add-on therapy for managing these challenging aspects of schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep transcranial magnetic stimulation add-on for treatment of negative symptoms and cognitive deficits of schizophrenia: a feasibility study. Levkovitz, Y., Rabany, L., Harel, EV., et al.[2016]

Citations

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2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11581676/

Theta Burst Stimulation Protocols for Schizophrenia Schizophrenia, a severe mental illness affecting approximately 1% of the population, is characterized by positive, negative, cognitive, and ...

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

Efficacy of repetitive transcranial magnetic stimulation ... Schizophrenia is a serious psychosis that is among the top 10 causes of global disability and may affect all areas of life (Velligan and Rao, 2023).

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

Deep transcranial magnetic stimulation for schizophrenia The efficacy and safety of deep transcranial magnetic stimulation (dTMS) as an intervention for schizophrenia remain unclear.

5. nature.com nature.com/articles/s41380-024-02630-5

Theta burst stimulation for depression: a systematic review ... Oral and long-acting antipsychotics for relapse prevention in schizophrenia-spectrum disorders: a network meta-analysis of 92 randomized trials ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01551979

Therapeutic Efficacy of Transcranial Magnetic Stimulation ... The primary outcome is improvement in negative symptoms related to schizophrenia. ... High-frequency repetitive transcranial magnetic stimulation in schizophrenia ...

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. clinicaltrials.gov clinicaltrials.gov/study/NCT01315587

Repetitive Transcranial Magnetic Stimulation and ... In a randomized, double blind clinical trials, 30 patients with schizophrenia in Razi psychiatric hospital will be assigned to receive repetitive TMS; theta ...

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

Safety and tolerability of repetitive transcranial magnetic ... Effect of augmentatory repetitive transcranial magnetic stimulation on auditory hallucinations in schizophrenia: randomized controlled study. Aust N Z J ...