Magnetic Stimulation for Psychosis
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18 - 65
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Mclean Hospital
No Placebo Group
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.
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.
12589What 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.
23578Is 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.
456910Will 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.
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
I am between 18 and 55 years old.
I have been diagnosed with schizophrenia, schizoaffective disorder, or bipolar disorder type I.
Exclusion Criteria
I have had fainting spells that might be seizures.
I have a worsening condition like multiple sclerosis or Parkinson's.
I am experiencing symptoms of high pressure inside my skull.
I have had a head injury that caused me to lose consciousness for more than 15 minutes.
I have a brain condition due to genetics (like Neurofibromatosis) or an event (like a stroke).
I don't have uncontrolled chronic conditions like heart issues or asthma.
I have a tumor in my brain.
I have had multiple seizures or have been diagnosed with epilepsy.
Participant Groups
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.
3Treatment groups
Active Control
Placebo Group
Group I: continuous theta burst stimulation (cTBS)Active Control1 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 Control1 Intervention
Participants complete MRI scanning and cognitive testing followed by rTMS (iTBS pattern) followed by repeat cognitive testing and MRI scanning
Group III: sham rTMSPlacebo Group1 Intervention
Participants complete MRI scanning and cognitive testing followed by sham rTMS followed by repeat cognitive testing and MRI scanning
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
McLean HospitalBelmont, MA
Beth Israel Deaconess Medical CenterBoston, MA
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Who is running the clinical trial?
Mclean HospitalLead Sponsor
Beth Israel Deaconess Medical CenterCollaborator
References
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.
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.
Effect of antipsychotic pharmacotherapy on clinical outcomes of intermittent theta-burst stimulation for refractory depression. [2018]Theta-burst stimulation is an emerging protocol for repetitive transcranial magnetic stimulation that takes 1-3 min to administer, yet offers equal/superior potency to conventional protocols lasting 30-60 min. However, preclinical evidence suggests that D2 receptor blockade may abolish the acute effects of theta-burst stimulation on synaptic facilitation or inhibition. As many patients presenting for repetitive transcranial magnetic stimulation are taking antipsychotic medications as augmentation for treatment-resistant depression, this finding is potentially concerning for the implementation of theta-burst stimulation in clinical settings. Here, we examined whether treatment-resistant depression patients taking antipsychotics have worse outcomes after a course of intermittent theta-burst stimulation. A chart review identified 105 treatment-resistant depression patients who underwent dorsomedial prefrontal-intermittent theta-burst stimulation; clinical outcomes on Hamilton Depression Rating Scale and Beck Depression Inventory were compared for those taking and not taking antipsychotics. The 29 of 105 patients who were taking antipsychotics showed non-significantly better response and remission rates, and non-significantly larger percentage improvements on both scales, with a positive but non-significant correlation between higher antipsychotic dose and larger percentage improvement. Contrary to expectations, outcomes were not significantly worse, and in some analyses trended towards being better, in patients taking antipsychotics. Future randomized controlled studies of repetitive transcranial magnetic stimulation combined with standardized dopaminergic manipulations may be justified and warranted.
Safety and Efficacy of Theta-Burst Stimulation in the Treatment of Psychiatric Disorders: A Review of the Literature. [2019]Theta-burst stimulation (TBS) is a form of repetitive transcranial magnetic stimulation and is thought to induce more rapid and longer-lasting effects on synaptic plasticity than conventional repetitive transcranial magnetic stimulation protocols. TBS is being used as an investigational and more recently as a therapeutic tool. The purpose of this review is to describe and discuss the studies that have evaluated the safety and efficacy of this technique in the treatment of various psychiatric disorders such as depression, schizophrenia, obsessive-compulsive disorder, Tourette's disorder, nicotine and cocaine addiction, and pathological gambling. Studies have reported mild adverse effects but no cases of seizures or mania. Despite the fact that studies were heterogeneous in terms of design and results, some of them are promising mostly for treatment-resistant depression and auditory hallucinations. Future well-designed sham-controlled studies are needed to confirm the long-term safety and efficacy of TBS in the treatment of such conditions.
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.
Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial. [2022]Treatment-resistant major depressive disorder is common; repetitive transcranial magnetic stimulation (rTMS) by use of high-frequency (10 Hz) left-side dorsolateral prefrontal cortex stimulation is an evidence-based treatment for this disorder. Intermittent theta burst stimulation (iTBS) is a newer form of rTMS that can be delivered in 3 min, versus 37·5 min for a standard 10 Hz treatment session. We aimed to establish the clinical effectiveness, safety, and tolerability of iTBS compared with standard 10 Hz rTMS in adults with treatment-resistant depression.
Intermittent theta burst stimulation for negative symptoms of schizophrenia-A double-blind, sham-controlled pilot study. [2021]Optimal noninvasive brain stimulation parameters for the treatment of negative symptoms of schizophrenia remain unclear. Here, we aimed to investigate the clinical and biological effects of intermittent theta burst transcranial magnetic stimulation (iTBS) in patients with treatment-resistant negative symptoms of schizophrenia (NCT00875498). In a randomized sham-controlled 2-arm study, 22 patients with schizophrenia and treatment-resistant negative symptoms received 20 sessions of either active (n = 12) or sham (n = 10) iTBS. Sessions were delivered twice a day on 10 consecutive working days. Negative symptom severity was assessed 5 times using the Scale for the Assessment of Negative Symptoms (SANS): before iTBS, after iTBS, and 1, 3, and 6 months after iTBS. As a secondary objective, we explored the acute effects of iTBS on functional connectivity of the left dorsolateral prefrontal cortex (DLPFC) using seed-based resting-state functional connectivity MRI (rsFC fMRI) images acquired before and after iTBS. Active iTBS over the left DLPFC significantly decreased negative symptoms severity compared to sham iTBS (F(3,60) = 3.321, p = 0.026). Post hoc analyses revealed that the difference between groups was significant 6 months after the end of stimulation sessions. Neuroimaging revealed an increase in rsFC between the left DLPFC and a brain region encompassing the right lateral occipital cortex and right angular gyrus and a right midbrain region that may encompass dopamine neuron cell bodies. Thus, iTBS over the left DLPFC can alleviate negative symptoms of schizophrenia. The effect might be driven by significant modulation of dopamine transmission.
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.
Prolonged intermittent theta burst stimulation in the treatment of major depressive disorder: a case series. [2022]Intermittent theta burst stimulation (iTBS) using 600 pulses is an effective and FDA-cleared transcranial magnetic stimulation (TMS) protocol for major depressive disorder (MDD). Prolonged iTBS (piTBS) using 1,800 pulses could increase the effectiveness of TMS for MDD, but its real-world effectiveness is still debated. We assessed the safety, tolerability, and preliminary effectiveness of a 3x daily piTBS 1,800 pulses protocol delivered over 2 weeks in 27 participants. Only four participants (18.2%) achieved response, two of them achieving remission (9.1%). Five participants (18.5%) experienced tolerability issues. Future studies should focus on the neurophysiological effects of TBS protocols to determine optimal parameters.
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]Intermittent theta-burst stimulation (iTBS), which is a form of repetitive transcranial magnetic stimulation (rTMS), can produce 600 pulses to the left dorsolateral prefrontal cortex (DLPFC) in a stimulation time of just over 3 min. The objective of this systematic review was to compare the safety and efficacy of iTBS and high-frequency (≥ 5 Hz) rTMS (HF-rTMS) for patients with treatment-resistant depression (TRD).