TMS for Schizophrenia
Recruiting in Palo Alto (17 mi)
Overseen byXiaoming Du, PhD
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
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
Approved in 4 Jurisdictions
Trial Summary
What is the purpose of this trial?The purpose of the study is to test the hypothesis that functionally navigated repetitive TMS stimulations to the prefrontal cortex (PFC) modulate aberrant cortical electrical activities at PFC circuitry. The TMS location of the PFC site will be individually localized by the symptom-related functional connectivity between PFC and symptom related areas (such as the auditory and language processing cortex). The investigators predict that such modulation will correct abnormal activities in patients with schizophrenia, reduce symptoms, especially auditory hallucination, and improve working memory/sustained attention performance.
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 data supports the effectiveness of the treatment for schizophrenia?
Research suggests that transcranial magnetic stimulation (TMS), including theta burst stimulation (TBS), can help improve symptoms in schizophrenia, such as auditory hallucinations and negative symptoms. Studies have shown that TBS is well-tolerated and can be effective in reducing symptoms when used alongside medication.
12345Is transcranial magnetic stimulation (TMS) safe for humans?
Research shows that transcranial magnetic stimulation (TMS), including theta burst stimulation (TBS), is generally well-tolerated and safe for humans, with few adverse effects reported.
15678How is TMS treatment different from other treatments for schizophrenia?
TMS (Transcranial Magnetic Stimulation) is unique because it uses magnetic fields to stimulate specific areas of the brain, offering a non-invasive option for treating schizophrenia symptoms. Unlike traditional medications, TMS can target negative symptoms and cognitive deficits with fewer side effects, and deep-TMS can reach deeper brain areas for potentially greater effectiveness.
125910Eligibility Criteria
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.
+1 more
Exclusion Criteria
I have a history of seizures.
Significant alcohol or other drug use (substance dependence within 6 months or substance abuse within 1 month) other than nicotine or marijuana dependence
I do not have a pacemaker, metal implants near my head, or unstable heart disease.
+7 more
Trial Timeline
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
Participant Groups
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.
2Treatment groups
Active Control
Placebo Group
Group I: Active rTMS stimulationActive Control1 Intervention
Real active rTMS stimulation.
Group II: Sham rTMS stimulationPlacebo Group1 Intervention
Sham repetitive TMS stimulation.
Active rTMS stimulation is already approved in United States, European Union, 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
The University of Texas Health Science Center at HoustonHouston, TX
Loading ...
Who Is Running the Clinical Trial?
The University of Texas Health Science Center, HoustonLead Sponsor
University of Maryland, BaltimoreLead Sponsor
National Institute of Mental Health (NIMH)Collaborator
References
The use of theta burst stimulation in patients with schizophrenia - A systematic review. [2023]Transcranial magnetic stimulation (TMS) can offer therapeutic benefits and provide value in neurophysiological research. One of the newer TMS paradigms is theta burst stimulation (TBS) which can be delivered in two patterns: continuous (cTBS - inducing LTD-like effects) and intermittent (iTBS - inducing LTP-like effects). This review paper aims to explore studies that have utilized TBS protocols over different areas of the cortex to study the neurophysiological functions and treatment of patients with schizophrenia. PubMed was searched using the following keywords "schizophrenia", "schizoaffective", or "psychosis", and "theta burst stimulation". Out of the 90 articles which were found, thirty met review inclusion criteria. The inclusion criteria included studying the reported effect (clinical, physiological, or both) of at least one session of TBS on human subjects, and abstracts (at minimum) must have been in English. The main target areas included prefrontal cortex (12 studies - 10 dorsolateral prefrontal cortex (DLPFC), 2 dorsomedial prefrontal cortex (DMPFC)) vermal cerebellum (5), and temporo-parietal cortex (8). Other target areas included inferior parietal lobe (2), and motor cortex (3). TBS neurophysiological effect was explored in 5 studies using functional magnetic resonance image (fMRI), magnetic resonance spectroscopy (MRS), electroencephalography (EEG), electromyography (EMG) and positron emission topography (PET) scan. Overall, TBS can offer great therapeutic potential as it is well-tolerated, feasible, and has few, if any, adverse effects. TBS may be targeted to treat specific symptomatology, as an augmenting intervention to pharmacotherapy, or even improving patient's insight into their diagnosis.
Rationale and study design of a trial to assess rTMS add-on value for the amelioration of negative symptoms of schizophrenia (RADOVAN). [2022]Schizophrenia is a severe and often difficult to treat psychiatric illness. In many patients, negative symptoms dominate the clinical picture. Meta-analysis has suggested moderate, but significant effects of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) on these symptoms. For treatment of depression a much shorter protocol - intermittent theta burst stimulation (iTBS) - has shown to be non-inferior to conventional high-frequency rTMS. This randomized, sham-controlled, rater-blinded clinical trial assesses the effects of conventional HF-rTMS as well as of iTBS of the left dorsolateral prefrontal cortex in comparison with sham.
Treatment of auditory hallucinations with bilateral theta burst stimulation (cTBS): protocol of a randomized, double-blind, placebo-controlled, multicenter trial. [2018]Auditory verbal hallucinations (AH) are core symptoms of schizophrenia. They are often severely distressing and refractory to therapy. Their perception is associated with increased activity in temporoparietal areas of the brain. Repetitive transcranial magnetic stimulation (rTMS) can reduce focal brain hyperactivity and has been shown to ameliorate AH. However, controlled multicenter clinical trials are still missing, effect sizes are moderate, and the treatment with rTMS is time consuming. Continuous theta burst stimulation (cTBS) is a quicker and potentially more effective technique to reduce cortical hyperactivity. First case and pilot studies indicate effectiveness in the treatment of AH. In this randomized, sham-controlled, double-blind multicenter clinical trial, 86 patients with schizophrenia spectrum disorder will be randomized to either cTBS or sham to the left and right temporoparietal cortex during three consecutive weeks (15 sessions totally). In each session, both hemispheres will be stimulated sequentially. The order in the first session (left-right or right-left, respectively) will be determined by randomization and alternated in all following sessions. Primary outcome is the reduction of mean PSYRATS-AH score after cTBS as compared to sham treatment. Follow-up measurements will be performed 1, 3 and 6 months after the end of the treatment. Statistical analysis will be based on the intention-to-treat population including all randomized patients using an analysis of covariance. This multicenter-controlled clinical trial will be able to provide decisive evidence for the efficacy of cTBS in the treatment of AH. The results will be suitable to clarify the role of this innovative, pathophysiology-based therapeutic approach in treatment guidelines for AH.
Single Session Transcranial Magnetic Stimulation Ameliorates Hand Gesture Deficits in Schizophrenia. [2021]Social interaction is impaired in schizophrenia, including the use of hand gestures, which is linked to poor social perception and outcome. Brain imaging suggests reduced neural activity in a left-lateralized frontoparietal network during gesture preparation; therefore, gesturing might be improved through facilitation of left hemispheric brain areas or via disruption of interhemispheric inhibition from the right homolog. This study tested whether repetitive transcranial magnetic stimulation (rTMS) protocols would improve gesture performance in schizophrenia. This randomized, placebo-controlled, double-blind, crossover trial applied 3 different protocols of rTMS separated by 48 h. Twenty right-handed schizophrenia patients and 20 matched healthy controls received facilitatory intermittent theta burst stimulation (iTBS) over the left inferior frontal gyrus (IFG), inhibitory continuous theta burst stimulation (cTBS) over right inferior parietal lobe (IPL), and placebo over left IPL in randomized order. Primary outcome was change in the test of upper limb apraxia (TULIA), rated from video recordings of hand gesture performance. Secondary outcome was change in manual dexterity using the coin rotation task. Participants improved on both tasks following rTMS compared with baseline. Only patients improved gesture performance following right IPL cTBS compared with placebo (P = .013). The results of the coin rotation parallel those of the TULIA, with improvements following right IPL cTBS in patients (P = .001). Single sessions of cTBS on the right IPL substantially improved both gesture performance accuracy and manual dexterity. The findings point toward an inhibition of interhemispheric rivalry as a potential mechanism of action.
Theta Burst Transcranial Magnetic Stimulation for Auditory Verbal Hallucinations: Negative Findings From a Double-Blind-Randomized Trial. [2022]Auditory verbal hallucinations (AVH) in schizophrenia are resistant to antipsychotic medication in approximately 25% of patients. Treatment with repetitive transcranial magnetic stimulation (rTMS) for refractory AVH has shown varying results. A stimulation protocol using continuous theta burst rTMS (TB-rTMS) showed high efficacy in open label studies. We tested TB-rTMS as a treatment strategy for refractory AVH in a double-blind, placebo-controlled trial.
Theta burst transcranial magnetic stimulation for the treatment of auditory verbal hallucinations: results of a randomized controlled study. [2022]One Hertz (1 Hz) repetitive transcranial magnetic stimulation (rTMS) is an effective therapy for auditory verbal hallucinations (AVH). Theta burst protocols (TBS) show longer after-effects. This single-blind, randomized controlled study compared continuous TBS with 1Hz rTMS in a 10-day treatment. Patients were diagnosed with schizophrenia or schizoaffective disorder. TBS demonstrated equal clinical effects compared to 1Hz TMS.
[Effectiveness and safety of high dose transcranial magnetic stimulation in schizophrenia with refractory negative symptoms: a randomized controlled study]. [2018]To evaluate the efficacy and safety of high dose transcranial magnetic stimulation (rTMS) in patients with schizophrenia with refractory negative symptoms.
Efficacy and safety of intermittent theta-burst stimulation in patients with schizophrenia: A meta-analysis of randomized sham-controlled trials. [2022]Theta-burst stimulation is a non-invasive brain stimulation technique that was introduced as a potential augmentation treatment for patients with schizophrenia. The purpose of this meta-analysis was to investigate the therapeutic efficacy and safety of intermittent theta-burst stimulation in patients with schizophrenia. Following the PRISMA guidelines, the MEDLINE, Embase, Cochrane, Scopus, Web of Science, and CNKI databases were searched for relevant studies from database inception to 9 January 2022. Change in symptom severity among patients with schizophrenia was the primary outcome, and changes in cognitive function and safety profiles, including the discontinuation rate and adverse events, were secondary outcomes. In total, 13 double-blind randomized sham-controlled trials with 524 patients were included. Intermittent theta-burst stimulation adjunct to antipsychotics was associated with significantly improved psychopathology in patients with schizophrenia, particularly for negative symptoms and general psychopathology but not for positive symptoms or cognitive function. The stimulation parameters influenced the effectiveness of intermittent theta-burst stimulation. A more favorable effect was observed in patients who received theta-burst stimulation at the left dorsolateral prefrontal cortex, with ≥1800 pulses per day, for ≥20 sessions, and using an inactive sham coil as a placebo comparison in the study. The intermittent theta-burst stimulation is well tolerated and safe in patients with schizophrenia. Intermittent theta-burst stimulation adjunct to antipsychotics treatment is associated with significant improvement in negative symptoms and favorable tolerability in patients with schizophrenia. This meta-analysis may provide insights into the use of intermittent theta-burst stimulation as an additional treatment to alleviate the negative symptoms of schizophrenia.
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. [2007]The potential effect of repetitive transcranial magnetic stimulation (rTMS) on core positive and negative symptoms in schizophrenia has not yet been clearly established. The aim of this study was to examine the efficacy of adjuvant 10 Hz, suprathreshold left prefrontal rTMS in negative symptoms of schizophrenia in a double-blind sham-controlled design. Additionally, our study also investigated the suitability of applying the same stimulus condition on positive symptoms. Ten right-handed schizophrenia patients received sham or active 10 Hz suprathreshold rTMS to the left dorsolateral prefrontal cortex with psychopathology, depression and global improvement ratings before and after rTMS sessions. Compared to sham, active rTMS significantly improved negative symptoms, irrespective of change in depressive symptoms.
Deep transcranial magnetic stimulation add-on for treatment of negative symptoms and cognitive deficits of schizophrenia: a feasibility study. [2016]Treatment for negative symptoms and cognitive deficits, core elements of schizophrenia, remains inadequate. Stimulation of the prefrontal cortex via transcranial magnetic stimulation (TMS) yields only moderate results, possibly due to limited stimulation depth. Deep-TMS enables deeper and wider stimulation than before. This preliminary study is the first to examine deep-TMS as a possible add-on treatment for negative symptoms and cognitive deficits of schizophrenia. The effect of 20 daily deep-TMS sessions (20 Hz, 120% motor threshold) over the prefrontal cortex of 15 patients indicated improvement in cognition and negative symptoms that was maintained at 2-wk post-treatment follow-up.