Magnetic Stimulation for Psychosis

Recruiting at 1 trial location

Overseen By Roscoe O Brady, MD, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Mclean Hospital

Disqualifiers: Epilepsy, Pregnancy, Metal implants, others

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

Compensation: Varies

Number of Visits: 4

Duration: 3 weeks

95 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether magnetic stimulation can enhance the speed at which individuals with psychotic disorders, such as schizophrenia and bipolar disorder, solve challenging tasks. The study employs transcranial magnetic stimulation (TMS), a non-surgical method that alters brain activity, to assess its impact on processing speed. Participants will undergo brain scans and problem-solving tests before and after receiving one of two types of TMS—continuous theta burst stimulation (cTBS) or intermittent theta burst stimulation (iTBS)—or a placebo version. Individuals with stable outpatient treatment for a psychotic disorder, who have not experienced recent hospitalizations or medication changes, might be suitable candidates for this trial. As an unphased trial, this study provides participants the chance to contribute to groundbreaking research that could enhance treatment options for psychotic disorders.

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 have no recent changes in their medication regimens. This suggests you should continue your current medications without changes.

What prior data suggests that this magnetic stimulation technique is safe for psychosis?

Research has shown that both continuous theta burst stimulation (cTBS) and intermittent theta burst stimulation (iTBS) are generally safe. Studies indicate that patients usually tolerate these treatments well, with few side effects.

For cTBS, research on its use in mental health conditions suggests it is commonly used and considered safe in clinical settings. While more research is ongoing, current evidence supports its safety.

iTBS also has a good safety record. In one study, only one person reported a headache, while others had no issues. This suggests iTBS is generally safe for research purposes.

Both types of theta burst stimulation are under study for their potential to help with psychosis and improve thinking skills. Although more research is needed, current studies support their safety for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using magnetic stimulation techniques like continuous theta burst stimulation (cTBS) and intermittent theta burst stimulation (iTBS) because they offer a non-invasive approach to treating psychosis. Unlike standard treatments, which often involve antipsychotic medications targeting neurotransmitter imbalances, these methods use magnetic fields to directly influence brain activity, potentially leading to rapid improvements in symptoms. This direct brain modulation could mean fewer side effects compared to medication, and possibly faster symptom relief. Additionally, exploring different patterns of stimulation, like cTBS and iTBS, allows researchers to determine which might be the most effective or have unique benefits.

What evidence suggests that this trial's treatments could be effective for psychosis?

This trial will compare different magnetic stimulation techniques for psychosis. Research has shown that continuous theta burst stimulation (cTBS), one of the treatments in this trial, may help treat symptoms of psychotic disorders like schizophrenia. One study found that cTBS reduced auditory hallucinations in these patients. Another study suggested it might lessen certain symptoms by targeting specific brain areas.

Intermittent theta burst stimulation (iTBS), another treatment option in this trial, also shows promise for people with psychotic disorders. Research indicates that iTBS might help with symptoms like lack of motivation or social withdrawal. It has also improved some cognitive skills in these individuals. Both cTBS and iTBS are non-invasive techniques that aim to alter brain activity to improve symptoms. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-55 with a psychotic disorder (schizophrenia, schizoaffective disorder, or bipolar I). Participants must be stable outpatients who speak English and can complete study tasks. Exclusions include recent substance use disorders, certain brain conditions, metal implants not MRI-safe, pregnancy, seizure history, and progressive neurological diseases.

Inclusion Criteria

Must be able to read, speak and understand English

I have been diagnosed with schizophrenia, schizoaffective disorder, or bipolar disorder type I.

I haven't been hospitalized or changed my medications in the last 30 days.

Exclusion Criteria

You have a ventriculo-peritoneal shunt.

Pregnancy: All participants capable of becoming pregnant will be required to have a pregnancy test; any participant who is pregnant will not be enrolled in the study.

I have a worsening condition like multiple sclerosis or Parkinson's.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants complete MRI scanning and cognitive testing before TMS

1 week

1 visit (in-person)

Treatment

Participants undergo TMS (cTBS or iTBS) or sham rTMS followed by repeat cognitive testing and MRI scanning

3 weeks

3 visits (in-person)

Follow-up

Participants are monitored for changes in cognitive performance and brain activity post-TMS

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• continuous theta burst stimulation (cTBS)
• intermittant theta burst stimulation (iTBS)
• sham rTMS

Trial Overview The study tests if magnetic stimulation (iTBS/cTBS) affects cognitive processing speed in psychosis. Participants will do problem-solving tasks and have brain scans before/after transcranial magnetic stimulation (TMS), which temporarily alters brain activity.

How Is the Trial Designed?

Group I: continuous theta burst stimulation (cTBS) Active Control 1 Intervention

Participants complete MRI scanning and cognitive testing followed by rTMS (cTBS pattern) followed by repeat cognitive testing and MRI scanning

Group II: Intermittent theta burst stimulation (iTBS) Active Control 1 Intervention

Participants complete MRI scanning and cognitive testing followed by rTMS (iTBS pattern) followed by repeat cognitive testing and MRI scanning

Group III: sham rTMS Placebo Group 1 Intervention

Participants complete MRI scanning and cognitive testing followed by sham rTMS followed by repeat cognitive testing and MRI scanning

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+

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]

Theta-burst stimulation (TBS) shows promise as a rapid and effective treatment for psychiatric disorders, particularly treatment-resistant depression and auditory hallucinations, with studies indicating mild adverse effects but no severe complications like seizures or mania.

The current research on TBS is varied in design and outcomes, highlighting the need for more rigorous sham-controlled studies to better assess its long-term safety and efficacy in treating various psychiatric conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Theta-Burst Stimulation in the Treatment of Psychiatric Disorders: A Review of the Literature. Rachid, F.[2019]

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]

Intermittent theta-burst stimulation (iTBS) and high-frequency rTMS (HF-rTMS) show similar efficacy in treating treatment-resistant depression (TRD), with response rates of 48.0% for iTBS and 45.5% for HF-rTMS based on two high-quality randomized controlled trials involving 474 participants.

Both iTBS and HF-rTMS have comparable safety profiles, with similar rates of discontinuation and adverse events, such as headaches, indicating that iTBS is a safe alternative to HF-rTMS for patients with TRD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of intermittent theta burst stimulation versus high-frequency repetitive transcranial magnetic stimulation for patients with treatment-resistant depression: a systematic review. Lan, XJ., Yang, XH., Qin, ZJ., et al.[2023]

In a study involving 22 patients with treatment-resistant negative symptoms of schizophrenia, intermittent theta burst transcranial magnetic stimulation (iTBS) significantly reduced symptom severity compared to a sham treatment, with effects lasting up to 6 months after the sessions ended.

Neuroimaging results indicated that iTBS increased functional connectivity in the brain regions associated with dopamine transmission, suggesting that the therapeutic effects of iTBS may be linked to enhanced dopamine activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent theta burst stimulation for negative symptoms of schizophrenia-A double-blind, sham-controlled pilot study. Bation, R., Magnin, C., Poulet, E., et al.[2021]

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]

In a study of 27 participants, a prolonged intermittent theta burst stimulation (piTBS) protocol using 1,800 pulses showed limited effectiveness for major depressive disorder, with only 18.2% of participants achieving a response and 9.1% reaching remission.

Safety and tolerability were concerns, as 18.5% of participants experienced issues, suggesting that while piTBS is a promising approach, further research is needed to optimize its parameters and improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged intermittent theta burst stimulation in the treatment of major depressive disorder: a case series. Richard, M., Noiseux, C., Desbeaumes Jodoin, V., 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]

In a study of 105 patients with treatment-resistant depression undergoing theta-burst stimulation, those taking antipsychotics did not have worse outcomes compared to those not on these medications, and some results even suggested better response and remission rates.

The findings indicate that the use of antipsychotics may not hinder the effectiveness of theta-burst stimulation, which is promising for patients who are on these medications, warranting further research into combined treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of antipsychotic pharmacotherapy on clinical outcomes of intermittent theta-burst stimulation for refractory depression. Schulze, L., Remington, G., Giacobbe, P., et al.[2018]

Intermittent theta burst stimulation (iTBS) is as effective as standard high-frequency (10 Hz) rTMS for treating treatment-resistant depression, showing non-inferiority in improving depression scores over 4-6 weeks in a study with 414 participants.

Both iTBS and 10 Hz rTMS had similar safety profiles and dropout rates, with headaches being the most common side effect, indicating that iTBS can be a viable alternative that allows for more patients to be treated in a shorter time without losing effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial. Blumberger, DM., Vila-Rodriguez, F., Thorpe, KE., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11366629/

The efficacy and safety of continuous theta burst ... Secondary outcomes include the rate of adverse events as measured by the Global Index of Safety (GIS), changes in other psychotic symptoms as ...

2. thelancet.com thelancet.com/journals/lanpsy/article/PIIS2215-0366(25)00202-0/fulltext

Theta burst stimulation of temporo-parietal cortex regions ... Outcomes. The primary outcome was the change in the auditory hallucinations subscale of the Psychotic Symptom Rating Scales (PSYRATS-AH) from ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37921353/

A Double-Blind, Randomized, Sham-Controlled Clinical Trial Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China ...

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2825296

Theta Burst Stimulation Protocols for Schizophrenia A recent MRI study found that ECT may reduce positive psychotic symptoms in patients with schizophrenia by preferentially targeting limbic brain ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03288779

NCT03288779 | Theta Burst Stimulation for Schizophrenia Schizophrenia Spectrum and Other Psychotic Disorders. Mental Disorders. Schizophrenia. Psychotic Disorders. Plan for Individual Participant Data (IPD). Plan to ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8617062/

A Systematic Review of the Safety and Tolerability of Theta ... Theta burst stimulation (TBS) is often used in clinical practice and research protocols for adults with neuropsychiatric disorders.

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

Theta burst stimulation for depression: a systematic review ... The study outcomes included response rate (primary), depression symptom improvement, remission rate, all-cause discontinuation rate, incidence ...