Theta Burst Stimulation for Treatment-Resistant Depression
(ciTBS Trial)
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Waitlist Available
Sponsor: University of Pennsylvania
No Placebo Group
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?In this proposal the investigators will use an accelerated TMS protocol that concentrates the magnetic stimulation that would usually occur over 6 weeks into 10 treatment sessions per days, for 5 consecutive days in patient with treatment-refractory depression. This protocol will build on a previously published study demonstrating clinical efficacy of intermittent theta-burst stimulation (iTBS) on left dorsolateral prefrontal cortex (L-dlPFC) in a treatment refractory population.
Do I have to stop taking my current medications for the trial?
The protocol does not specify if you must stop taking your current medications. However, you may continue your current anti-depressant medication if it doesn't exceed doses that would make TMS an increased risk, at the discretion of the principal investigator.
What data supports the idea that Theta Burst Stimulation for Treatment-Resistant Depression is an effective treatment?
The available research shows that Theta Burst Stimulation (iTBS) can be effective for people with Treatment-Resistant Depression. In one study, 28% of patients showed a significant reduction in depression symptoms after two weeks, and this increased to 38% after four weeks. Another study found that iTBS was as effective as another common treatment, repetitive transcranial magnetic stimulation (rTMS), for depression. However, some studies noted that while iTBS can quickly reduce symptoms, the effects might not last long. Overall, iTBS is a promising option for those who haven't responded to other treatments.
12345What safety data exists for Theta Burst Stimulation for depression?
The provided research does not contain safety data for Theta Burst Stimulation or its variants like Intermittent Theta Burst Stimulation (iTBS). The articles focus on gamma-hydroxybutyrate (GHB) and its effects, which are unrelated to Theta Burst Stimulation.
678910Is Intermittent Theta Burst Stimulation a promising treatment for treatment-resistant depression?
Yes, Intermittent Theta Burst Stimulation (iTBS) is a promising treatment for treatment-resistant depression. Studies show that it can lead to significant reductions in depressive symptoms and even help some patients achieve remission. It works quickly, with noticeable effects within a few weeks, and is considered safe.
13111213Eligibility Criteria
This trial is for adults aged 18-70 with major depressive disorder who haven't improved after at least two treatments. They must score ≥20 on a depression scale, speak English, and can consent to treatment. Exclusions include MRI contraindications, implanted medical devices like pacemakers, pregnancy, recent substance abuse issues, or certain neurological conditions.Inclusion Criteria
Patients must be fluent in English
Participants must have the ability to provide consent
My gender does not limit my participation.
+5 more
Exclusion Criteria
You have a health condition that makes it difficult to get accurate MRI results.
You have been struggling with alcohol or drug addiction in the past three months.
Pregnancy (Female participants)
+4 more
Participant Groups
The study tests an accelerated form of magnetic brain stimulation called intermittent Theta Burst Stimulation (iTBS), concentrating the usual 6-week protocol into five days for those with treatment-resistant depression.
1Treatment groups
Experimental Treatment
Group I: Compressed iTBS scheduleExperimental Treatment1 Intervention
Stimulation 3-pulse 50-Hz bursts at 5-Hz for 2-s trains, with trains every 10 s, for 10 minutes, 10 times a day, for 5 consecutive days.
Intermittent Theta Burst Stimulation is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as iTBS for:
- Treatment-resistant depression
🇪🇺 Approved in European Union as iTBS for:
- Treatment-resistant depression
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Department of Interventional Psychiatry, University of California San DiegoLa Jolla, CA
Center for Neuromodulation in Depression and StressPhiladelphia, PA
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Who Is Running the Clinical Trial?
University of PennsylvaniaLead Sponsor
References
Accelerated intermittent theta burst stimulation treatment in medication-resistant major depression: A fast road to remission? [2019]Although accelerated repetitive Transcranial Magnetic Stimulation (rTMS) paradigms and intermittent Theta-burst Stimulation (iTBS) may have the potency to result in superior clinical outcomes in Treatment Resistant Depression (TRD), accelerated iTBS treatment has not yet been studied. In this registered randomized double-blind sham-controlled crossover study, spread over four successive days, 50 TRD patients received 20 iTBS sessions applied to the left dorsolateral prefrontal cortex (DLPFC). The accelerated iTBS treatment procedure was found to be safe and resulted in immediate statistically significant decreases in depressive symptoms regardless of order/type of stimulation (real/sham). While only 28% of the patients showed a 50% reduction of their initial Hamilton Depression Rating Scale score at the end of the two-week procedure, this response rate increased to 38% when assessed two weeks after the end of the sham-controlled iTBS protocol, indicating delayed clinical effects. Importantly, 30% of the responders were considered in clinical remission. We found no demographic predictors for response. Our findings indicate that only four days of accelerated iTBS treatment applied to the left DLPFC in TRD may lead to meaningful clinical responses within two weeks post stimulation.
A randomized sham controlled comparison of once vs twice-daily intermittent theta burst stimulation in depression: A Canadian rTMS treatment and biomarker network in depression (CARTBIND) study. [2022]Intermittent theta burst stimulation (iTBS) is a newer form of repetitive transcranial magnetic stimulation (rTMS) for patients with treatment resistant depression (TRD). Applying multiple daily iTBS sessions may enable patients to achieve remission more rapidly.
Is accelerated, high-dose theta burst stimulation a panacea for treatment-resistant depression? [2021]A recent study by Williams et al. (Williams NR, Sudheimer KD, Bentzley BS, Pannu J, Stimpson KH, Duvio D, Cherian K, Hawkins J, Scherrer KH, Vyssoki B, DeSouza D, Raj KS, Keller J, Schatzberg AF. Brain 141: e18, 2018) used accelerated, high-dose intermittent theta burst stimulation (iTBS) to treat highly treatment-resistant depression patients. Remarkably, most patients remitted, but the durability of therapeutic response was weak and all patients relapsed within 2 wk posttreatment. This mini-review examines the "fast on, fast off" effects of accelerated, high-dose iTBS for depression and suggests a new treatment that would combine the strengths of multiple extant iTBS protocols.
Intermittent theta burst stimulation (iTBS) versus 10 Hz high-frequency repetitive transcranial magnetic stimulation (rTMS) to alleviate treatment-resistant unipolar depression: A randomized controlled trial (THETA-DEP). [2022]Recently intermittent theta burst stimulation (iTBS) proved to be non-inferior to conventional repetitive transcranial magnetic stimulation (10 Hz rTMS) in unipolar depression after failure of one antidepressant trial, but to date no randomized control trial assessed the ability of iTBS to improve depression level and quality of life in more resistant features of depression with a long-term (6 month) follow-up in comparison to 10 Hz rTMS.
Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression. [2020]New antidepressant treatments are needed that are effective, rapid acting, safe, and tolerable. Intermittent theta-burst stimulation (iTBS) is a noninvasive brain stimulation treatment that has been approved by the U.S. Food and Drug Administration for treatment-resistant depression. Recent methodological advances suggest that the current iTBS protocol might be improved through 1) treating patients with multiple sessions per day at optimally spaced intervals, 2) applying a higher overall pulse dose of stimulation, and 3) precision targeting of the left dorsolateral prefrontal cortex (DLPFC) to subgenual anterior cingulate cortex (sgACC) circuit. The authors examined the feasibility, tolerability, and preliminary efficacy of Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT), an accelerated, high-dose resting-state functional connectivity MRI (fcMRI)-guided iTBS protocol for treatment-resistant depression.
Coma and respiratory depression following the ingestion of GHB and its precursors: three cases. [2019]Gamma hydroxybutyrate (GHB) is a product of the metabolism of both gamma butyrolactone (GBL) and 1,4-butanediol (1,4-BD). Gamma hydroxybutyrate (GHB) is an illegal agent that causes central nervous system depression. Chemical precursors of GHB, such as GBL and 1,4-BD, have been available for purchase from many health food stores and Internet websites for mood-enhancement, sleep-induction, and stimulation of growth hormone release. We report three cases of ingestion of products containing GHB and chemical precursors of GHB. All three patients had severe presentations followed by full recoveries. Some products containing GBL were withdrawn from the market after the FDA issued a warning regarding these products. Products containing 1,4-butanediol remain on the market today.
Acute poisoning from gamma-hydroxybutyrate in California. [2018]We report a series of 5 representative patients in California who experienced adverse reactions from the illicitly marketed substance gamma-hydroxybutyrate (GHB). The drug is a putative neurotransmitter marketed as a growth hormone releaser for bodybuilders. The most commonly reported symptoms included abrupt drowsiness, dizziness, and a "high". Other effects were headache, nausea, vomiting, myoclonic jerking, and short-term coma. There have been no reported deaths. If product use is discontinued, full recovery with no long-term side effects is universal. No clear dose-response effect was observed; this may be attributable to differences in susceptibility, wide variations in doses taken by the same person, or the coingestion of other substances. Case interviews confirm that, despite being banned by the US Food and Drug Administration, GHB is still widely available in the underground drug market. Athletes and bodybuilders may take drugs for which there are claims of improved performance or body image. Physicians should be alert for signs of GHB poisoning in emergency department and clinic patients.
Effect of γ-hydroxybutyrate (GHB) on driving as measured by a driving simulator. [2019]Label="RATIONALE" NlmCategory="BACKGROUND">Gamma-hydroxybutyrate acid (GHB), a GABAB receptor agonist approved for treatment of narcolepsy, impairs driving ability, but little is known about doses and plasma concentrations associated with impairment and time course of recovery.
Pharmacologic, Pharmacokinetic, and Clinical Assessment of Illicitly Used γ-Hydroxybutyrate. [2019]γ-Hydroxybutyrate (GHB) is a common drug of abuse and poses important health risks to users in the form of respiratory, cardiovascular, mental, or traumatic adverse events. GHB has non-dose-proportional effects and pharmacologic effects such as sedation and retrograde amnesia, which can incapacitate people targeted for assault. It has Krebs cycle metabolism, rapid clearance, relative hydrophilicity, and unique drug interactions. Promptly seeking medical attention during intentional or inadvertent overdose is critical to survival, as is prompt supportive care once medical personnel are alerted. People drugged before assault also need to promptly notify authorities because the period to detect the drug in the urine or blood is brief and the ultimate metabolites are carbon dioxide and water. After acute treatment has passed, withdrawal could be severe in chronic abusers that could harm the patient directly or drive them back into reuse.
Effect of chronic γ-hydroxybutyrate (GHB) administration on GHB toxicokinetics and GHB-induced respiratory depression. [2018]Label="BACKGROUND">γ-hydroxybutyrate (GHB) has a high potential for illicit use; overdose of this compound results in sedation, respiratory depression and death. Tolerance to the hypnotic/sedative and electroencephalogram effects of GHB occurs with chronic GHB administration; however, tolerance to respiratory depression has not been evaluated. GHB toxicodynamic effects are mediated predominantly by GABAB receptors. Chronic treatment may affect monocarboxylate transporters (MCTs) and alter the absorption, renal clearance and brain uptake of GHB.
Dorsomedial prefrontal theta burst stimulation to treat anhedonia, avolition, and blunted affect in schizophrenia or depression - a randomized controlled trial. [2021]Intermittent theta burst stimulation (iTBS) over the dorsomedial prefrontal cortex (DMPFC) has shown promise in open-label trials of depression.
Efficacy of prefrontal theta-burst stimulation in refractory depression: a randomized sham-controlled study. [2022]Theta-burst transcranial magnetic stimulation could modulate cortical excitability and has the potential to treat refractory depression. However, there has been a lack of large randomized studies of the antidepressant efficacy of different forms of theta-burst stimulation, such as intermittent and continuous theta-burst stimulation. A randomized sham-controlled study was conducted to investigate antidepressant efficacy of theta-burst stimulation and to compare efficacy among left-prefrontal intermittent theta-burst stimulation, right-prefrontal continuous theta-burst stimulation and a combination of them in patients showing different levels of antidepressant refractoriness. A group of 60 treatment-refractory patients with recurrent major depressive disorder were recruited and randomized to four groups (Group A: continuous theta-burst stimulation; Group B: intermittent theta-burst stimulation; Group C: a combination of continuous and intermittent theta-burst stimulation; and Group D: sham theta-burst stimulation; 15 patients were included in each group). After 2 weeks of theta-burst stimulation treatment, depression improved in all groups. Groups B and C had better antidepressant responses (as reflected by % decreases in depression score) than Groups A and D (P = 0.001, post hoc analysis: B > A, B > D, C > A, and C > D), even after controlling for age and refractoriness scores. The mean antidepressant effect was highest in Group C and followed by that in Group B. Additionally, a significant placebo effect was found in patients with low refractoriness; this disappeared in patients with moderate-to-high refractoriness. A significant correlation existed between refractoriness scores and treatment responses. Treatment refractoriness was a significant factor negatively predicting efficacy of theta-burst stimulation (P = 0.039). This randomized sham-controlled study demonstrated that active theta-burst stimulation is a well-tolerated form of repetitive transcranial magnetic stimulation and has good antidepressant efficacy, particularly in depressed subjects within a certain range of treatment refractoriness.
Identifying Neurophysiological Markers of Intermittent Theta Burst Stimulation in Treatment-Resistant Depression Using Transcranial Magnetic Stimulation-Electroencephalography. [2023]Intermittent theta burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex is effective for treatment-resistant depression, but the effects of iTBS on neurophysiological markers remain unclear. Here, we indexed transcranial magnetic stimulation-electroencephalography (TMS-EEG) markers, specifically, the N45 and N100 amplitudes, at baseline and post-iTBS, comparing separated and contiguous iTBS schedules. TMS-EEG markers were also compared between iTBS responders and nonresponders.