Theta Burst Stimulation for Bipolar Disorder
Palo Alto (17 mi)Age: 18 - 65
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: N/A
Recruiting
Sponsor: Mary Phillips, MD MD (Cantab)
No Placebo Group
Approved in 3 jurisdictions
Trial Summary
What is the purpose of this trial?Bipolar Disorder (BD) is a common and highly debilitating psychiatric disorder, however, the predisposing brain mechanisms are poorly understood. Here, the investigators aim to examine the immediate effect of transcranial brain stimulation (TBS) on brain activity and emotions in adults with and without BD as a first stage toward understanding the predisposing brain mechanisms of BD. The investigators hypothesize that TBS will reduce brain activity while playing a game with rewards in all adults, but the TBS will reduce brain activity more in the adults with BD compared to adults without BD. Furthermore, the investigators hypothesize that this reduced brain activity will be associated with reduced BD symptoms, such as negative emotions.
What safety data exists for theta burst stimulation in treating bipolar disorder?Theta burst stimulation (TBS), including continuous theta burst stimulation (cTBS), has been studied for safety in various contexts. A systematic review of TBS safety found that most adverse events were mild, occurring in about 5% of subjects, with no reported cases of seizures or mania. However, due to its novelty, TBS should be applied with caution, and further studies are needed to confirm its long-term safety and efficacy. The safety data is primarily based on adult studies, with limited information available for children and adolescents.123810
Is continuous theta burst stimulation (cTBS) a promising treatment for bipolar disorder?Continuous theta burst stimulation (cTBS) is a type of brain stimulation that has shown some promise in treating depression, including bipolar depression. It is a newer method that can be quicker to administer than traditional treatments. Some studies suggest it might help with treatment-resistant depression, but more research is needed to confirm its effectiveness specifically for bipolar disorder.367910
Do I need to stop taking my current medications to join the trial?The trial does not require you to stop taking your current medications if you have Bipolar Disorder, as long as you are not on SNRI antidepressants or bupropion. You can continue with anxiolytics, atypical antipsychotics, lithium, other mood stabilizers, non-SNRI antidepressants, and non-benzodiazepine hypnotics if you've been taking them for more than 2 months. If you don't have Bipolar Disorder, the protocol does not specify medication restrictions.
What data supports the idea that Theta Burst Stimulation for Bipolar Disorder is an effective treatment?The available research shows mixed results for the effectiveness of Theta Burst Stimulation (TBS) in treating bipolar disorder. One study found that accelerated TBS led to significant improvement in depression symptoms for some patients, with five out of nine experiencing at least a 50% reduction in symptoms. However, another study found no significant difference between active TBS and a placebo in treating mixed depression. A pilot study on a different form of TBS showed high response and remission rates, but these results were not significantly better than the placebo. Overall, while some studies suggest potential benefits, the evidence is not consistent, and more research is needed to confirm its effectiveness.456910
Eligibility Criteria
This trial is for adults aged 18-35 with Bipolar Disorder I/II in remission or mild-moderate hypomania. They must score low on depression and mania scales, can be unmedicated or on certain stable medications (excluding antidepressant monotherapy), and have no severe psychiatric disorders, substance abuse issues, head injuries, neurological diseases, or family history of epilepsy.Inclusion Criteria
My family does not have a history of bipolar disorder.
I am not currently experiencing a depressive episode.
I am between 18 and 35 years old.
Exclusion Criteria
I am either younger than 18 or older than 35.
I am currently experiencing a depressive episode.
My diagnosis is not bipolar I or II disorder.
I am not taking SNRI antidepressants or bupropion.
I am not taking any psychotropic medications not allowed in the study.
I have been diagnosed with depression and scored 8 or higher on a depression scale.
Treatment Details
The study tests the effects of Theta Burst Stimulation (TBS) on brain activity and emotions in people with Bipolar Disorder. It compares Continuous TBS (cTBS), which is an active treatment, to a sham version that mimics the procedure without real stimulation to see if cTBS reduces symptoms like negative emotions.
6Treatment groups
Experimental Treatment
Group I: Left vlPFC/Left vlPFC sham/Left SSExperimental Treatment2 Interventions
A random number sequence will be generated for randomization of the 3 cTBS scan session order to which each participant is assigned:
* left vlPFC cTBS (cTBS applied to the left ventrolateral prefrontal cortex)
* left SS cTBS (cTBS applied to the left somatosensory area)
* left vlPFC sham TBS (go through the motions of applying cTBS to the left ventrolateral prefrontal cortex but very low current is administered so that the participant feels like cTBS is being administered even though the current is too low to stimulate brain cells) Participants will know that one session will be a sham, but they will be blinded to which session is the sham.
Group II: Left vlPFC sham/Left vlPFC/Left SSExperimental Treatment2 Interventions
A random number sequence will be generated for randomization of the 3 cTBS scan session order to which each participant is assigned:
* left vlPFC cTBS (cTBS applied to the left ventrolateral prefrontal cortex)
* left SS cTBS (cTBS applied to the left somatosensory area)
* left vlPFC sham TBS (go through the motions of applying cTBS to the left ventrolateral prefrontal cortex but very low current is administered so that the participant feels like cTBS is being administered even though the current is too low to stimulate brain cells) Participants will know that one session will be a sham, but they will be blinded to which session is the sham.
Group III: Left vlPFC sham/Left SS/Left vlPFCExperimental Treatment2 Interventions
A random number sequence will be generated for randomization of the 3 cTBS scan session order to which each participant is assigned:
* left vlPFC cTBS (cTBS applied to the left ventrolateral prefrontal cortex)
* left SS cTBS (cTBS applied to the left somatosensory area)
* left vlPFC sham TBS (go through the motions of applying cTBS to the left ventrolateral prefrontal cortex but very low current is administered so that the participant feels like cTBS is being administered even though the current is too low to stimulate brain cells) Participants will know that one session will be a sham, but they will be blinded to which session is the sham.
Group IV: Left ventrolateral prefrontal cortex (vlPFC)/Left SS/Left vlPFC shamExperimental Treatment2 Interventions
A random number sequence will be generated for randomization of the 3 cTBS scan session order to which each participant is assigned:
* left vlPFC cTBS (cTBS applied to the left ventrolateral prefrontal cortex)
* left SS cTBS (cTBS applied to the left somatosensory area)
* left vlPFC sham TBS (go through the motions of applying cTBS to the left ventrolateral prefrontal cortex but very low current is administered so that the participant feels like cTBS is being administered even though the current is too low to stimulate brain cells) Participants will know that one session will be a sham, but they will be blinded to which session is the sham.
Group V: Left SS/Left vlPFC/Left vlPFC shamExperimental Treatment2 Interventions
A random number sequence will be generated for randomization of the 3 cTBS scan session order to which each participant is assigned:
* left vlPFC cTBS (cTBS applied to the left ventrolateral prefrontal cortex)
* left SS cTBS (cTBS applied to the left somatosensory area)
* left vlPFC sham TBS (go through the motions of applying cTBS to the left ventrolateral prefrontal cortex but very low current is administered so that the participant feels like cTBS is being administered even though the current is too low to stimulate brain cells) Participants will know that one session will be a sham, but they will be blinded to which session is the sham.
Group VI: Left SS/Left vlPFC sham/Left vlPFCExperimental Treatment2 Interventions
A random number sequence will be generated for randomization of the 3 cTBS scan session order to which each participant is assigned:
* left vlPFC cTBS (cTBS applied to the left ventrolateral prefrontal cortex)
* left SS cTBS (cTBS applied to the left somatosensory area)
* left vlPFC sham TBS (go through the motions of applying cTBS to the left ventrolateral prefrontal cortex but very low current is administered so that the participant feels like cTBS is being administered even though the current is too low to stimulate brain cells) Participants will know that one session will be a sham, but they will be blinded to which session is the sham.
Continuous Theta Burst Stimulation (cTBS) is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Transcranial Magnetic Stimulation (TMS) for:
- Major Depressive Disorder (MDD)
- Obsessive-Compulsive Disorder (OCD)
🇪🇺 Approved in European Union as Transcranial Magnetic Stimulation (TMS) for:
- Major Depressive Disorder (MDD)
- Obsessive-Compulsive Disorder (OCD)
🇨🇦 Approved in Canada as Transcranial Magnetic Stimulation (TMS) for:
- Major Depressive Disorder (MDD)
- Obsessive-Compulsive Disorder (OCD)
Find a clinic near you
Research locations nearbySelect from list below to view details:
University of PittsburghPittsburgh, PA
Loading ...
Who is running the clinical trial?
Mary Phillips, MD MD (Cantab)Lead Sponsor
National Institute of Mental Health (NIMH)Collaborator
References
Safety of theta burst transcranial magnetic stimulation: a systematic review of the literature. [2022]Theta burst stimulation (TBS) protocols have recently emerged as a method to transiently alter cortical excitability in the human brain through repetitive transcranial magnetic stimulation. TBS involves applying short trains of stimuli at high frequency repeated at intervals of 200 milliseconds. Because repetitive transcranial magnetic stimulation is known to carry a risk of seizures, safety guidelines have been established. TBS has the theoretical potential of conferring an even higher risk of seizure than other repetitive transcranial magnetic stimulation protocols because it delivers high-frequency bursts. In light of the recent report of a seizure induced by TBS, the safety of this new protocol deserves consideration. We performed an English language literature search and reviewed all studies published from May 2004 to December 2009 in which TBS was applied. The adverse events were documented, and crude risk was calculated. The majority of adverse events attributed to TBS were mild and occurred in 5% of subjects. Based on this review, TBS seems to be a safe and efficacious technique. However, given its novelty, it should be applied with caution. Additionally, this review highlights the need for rigorous documentation of adverse events associated with TBS and intensity dosing studies to assess the seizure risk associated with various stimulation parameters (e.g., frequency, intensity, and location).
Safety and tolerability of theta-burst transcranial magnetic stimulation in children. [2012]Theta-burst stimulation (TBS) is a lower intensity, high-frequency repetitive transcranial magnetic stimulation technique developed recently for quantifying and modulating cerebral cortical function. Nearly all published studies have involved adults. The aim of this study was to obtain safety data as a basis for evaluating potential risks versus benefits of TBS research in children.
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.
Twice-daily neuronavigated intermittent theta burst stimulation for bipolar depression: A Randomized Sham-Controlled Pilot Study. [2020]The safety and efficacy of neuronavigated intermittent theta burst stimulation (iTBS) in patients with bipolar depression has not yet been investigated. We hypothesized the superiority of active iTBS over sham. Twenty-six patients were randomly allocated to receive either active (n=12) or sham (n=14) iTBS. Response and remission rates according to changes in depression MADRS score were high following active iTBS (72% and 42% for response and remission rates, respectively), but no significant difference was found after sham stimulation (42%and 25%). No adverse events were observed. This study revealed the safety and tolerability of twice daily iTBS in patients with bipolar depression. Larger controlled studies are warranted to prove iTBS superiority in treatment-resistant bipolar depression.
Accelerated theta-burst repetitive transcranial magnetic stimulation for depression in South Africa. [2020]This case series documents local experience using accelerated theta-burst repetitive transcranial magnetic stimulation (rTMS) as a supplementary treatment for depression in both major depressive disorder (MDD) and bipolar disorder (BD). Nine consenting patients (MDD = 7; BD = 2) each received 20 accelerated theta-burst sessions over 8 days. Improvement was monitored using the Centre for Epidemiological Studies Depression (CES-D) Scale and the Clinical Global Impression (CGI) Scale at baseline, at day 5 and at day 8 of rTMS treatment. We performed a Wilcoxon matched-pairs signed-rank test to determine whether there was a difference in scores from baseline to post-treatment. The CES-D scores decreased significantly from baseline to post-treatment (Z = -2.547, p = 0.011) with five patients experiencing at least a 50% symptom reduction on the CES-D. CGI severity scores also decreased significantly between baseline and post-treatment (Z = -2.547, p = 0.011). The most commonly reported adverse effect was mild headaches, lasting a few hours during and after rTMS treatment. The findings suggest that the accelerated theta-burst rTMS protocol for depression is well tolerated with most patients also experiencing symptomatic improvement by day 8.
Treatment of mixed depression with theta-burst stimulation (TBS): results from a double-blind, randomized, sham-controlled clinical trial. [2023]Mixed depression is probably different in terms of clinical course and response to treatment. Repetitive transcranial magnetic stimulation (rTMS) is well established in non-mixed depression, and theta-burst stimulation (TBS) protocol is replacing conventional protocols because of noninferiority and reduced delivery time. However, TBS has not been adequately studied in mixed states. This study was a double-blind, six-week, sham-controlled, and randomized clinical trial of bilateral TBS targeting the right and left dorsolateral prefrontal cortex, respectively. Adults with bipolar and major depressive disorder experiencing an acute mixed depression were eligible if they had not benefited from a first- or second-line treatment for acute unipolar or bipolar depression recommended by the Canadian Network for Mood and Anxiety Treatments. Out of 100 patients included, 90 composed modified intention-to-treat sample, which was patients that completed at least one week of the intervention. There were no significant differences in Montgomery-Asberg depression rating scale score changes (least squares mean difference between groups at week 3, -0.06 [95% CI, - 3.39 to 3.51; P = 0.97] in favor of sham TBS). Response and remission rates per MADRS were also not statistically different among active and sham groups (35.7% vs. 43.7%, and 28.5% vs. 37.5% respectively at week 6, ps > 0.51). No other analyses from baseline to weeks 3 or 6 revealed significant time x group interaction or mean differences among groups in the mITT sample. Bilateral TBS targeting the DLPFC is not efficacious as an add-on treatment of acute bipolar and unipolar mixed depression. ClinicalTrials.govIdentifier: NCT04123301.
Accelerated theta burst stimulation for the treatment of depression: A randomised controlled trial. [2022]Theta burst pattern repetitive transcranial magnetic stimulation (TBS) is increasingly applied to treat depression. TBS's brevity is well-suited to application in accelerated schedules. Sizeable trials of accelerated TBS are lacking; and optimal TBS parameters such as stimulation intensity are not established.
A Systematic Review of the Safety and Tolerability of Theta Burst Stimulation in Children and Adolescents. [2023]Theta burst stimulation (TBS) is often used in clinical practice and research protocols for adults with neuropsychiatric disorders. There are substantial knowledge gaps related to the application of TBS in children and adolescents. This systematic review examined the safety and tolerability of TBS in children and adolescents.
Safety and Efficacy of Continuous Theta Burst "Intensive" Stimulation in Acute-Phase Bipolar Depression: A Pilot, Exploratory Study. [2023]Repetitive transcranial magnetic stimulation efficacy in unipolar depression is known, but its efficacy in acute-phase bipolar depression is at best modest. Citing differential right dorsolateral prefrontal cortex hyperconnectivity implicated in BD, we aimed to study the effect of novel continuous theta burst stimulation (cTBS) targeting right dorsolateral prefrontal cortex in a randomized rater blinded placebo control design.
Adjunctive continuous theta burst stimulation for major depressive disorder or bipolar depression: A meta-analysis of randomized controlled studies. [2023]As a novel type of theta burst stimulation (TBS), continuous TBS (cTBS) has been shown to have mixed therapeutic effects for major depressive disorder (MDD) or bipolar depression (BD). Thus, we performed a meta-analysis of randomized controlled trials (RCTs) of cTBS for treating major depressive episodes in patients with MDD or BD.