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

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to learn about cognition in psychotic disorders (schizophrenia, bipolar disorder, and schizoaffective disorder). The main question it aims to answer is: Can we use magnetic stimulation to change processing speed (how quickly people can solve challenging tasks). Participants will be asked to perform cognitive tasks (problem-solving) and undergo brain scans before and after transcranial magnetic stimulation (TMS). TMS is a way to non-invasively change brain activity. Forms of TMS are FDA-approved to treat depression and obsessive compulsive disorder. In this study, we will use a different form of TMS to temporarily change brain activity to observe how that changes speed in problem-solving.

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 data supports the effectiveness of the treatment for psychosis?

Research suggests that intermittent theta burst stimulation (iTBS) can reduce negative symptoms of schizophrenia, with significant improvements observed up to six months after treatment. Additionally, continuous theta burst stimulation (cTBS) has shown potential in reducing auditory hallucinations in schizophrenia, although more large-scale trials are needed to confirm these findings. ^{1 2 3 4 5}

Is theta burst stimulation (TBS) safe for humans?

Theta burst stimulation (TBS), including its forms like continuous (cTBS) and intermittent (iTBS), has been studied for various psychiatric conditions and is generally considered safe, with mild side effects reported and no cases of seizures or mania. However, more well-designed studies are needed to confirm its long-term safety. ^{2 6 7 8 9}

How does magnetic stimulation differ from other treatments for psychosis?

Magnetic stimulation, specifically using theta burst protocols, is unique because it targets brain activity directly through non-invasive magnetic pulses, potentially offering quicker and more effective relief for auditory hallucinations in schizophrenia compared to traditional methods. Unlike medications, it does not involve drugs and focuses on reducing brain hyperactivity associated with these symptoms. ^{1 2 5 9 10}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

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]

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 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]

References

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

Theta Burst Transcranial Magnetic Stimulation for Auditory Verbal Hallucinations: Negative Findings From a Double-Blind-Randomized Trial. [2022]

2. Germany 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. [2018]

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

Effect of antipsychotic pharmacotherapy on clinical outcomes of intermittent theta-burst stimulation for refractory depression. [2018]

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

Intermittent theta burst stimulation for negative symptoms of schizophrenia-A double-blind, sham-controlled pilot study. [2021]

5. Netherlands 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). [2022]

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

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

7. Switzerland 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. [2023]

8. England 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. [2022]

9. Ireland pubmed.ncbi.nlm.nih.gov

Prolonged intermittent theta burst stimulation in the treatment of major depressive disorder: a case series. [2022]

10. Ireland pubmed.ncbi.nlm.nih.gov

Theta burst transcranial magnetic stimulation for the treatment of auditory verbal hallucinations: results of a randomized controlled study. [2022]