Neuromodulation for Treatment-Resistant Depression
Recruiting in Palo Alto (17 mi)
Overseen byDavid Spiegel, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Stanford University
Must be taking: Antidepressants
Must not be taking: Ketamine, ECT
Disqualifiers: Pregnancy, Psychotic disorder, Substance use, others
No Placebo Group
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?
This study will investigate the anti-anhedonic efficacy of a novel neurostimulation strategy termed accelerated intermittent theta burst stimulation (aiTBS) in participants with treatment resistant depression (TRD).
Will I have to stop taking my current medications?
No, you will not have to stop taking your current medications. Participants must be on a stable antidepressant regimen for 6 weeks before joining the study and agree to continue it throughout the study.
What data supports the effectiveness of the treatment Accelerated Intermittent Theta Burst Stimulation (aiTBS) for treatment-resistant depression?
Is accelerated intermittent theta burst stimulation (aiTBS) safe for humans?
How is the treatment Accelerated Intermittent Theta Burst Stimulation (aiTBS) unique for treatment-resistant depression?
Accelerated Intermittent Theta Burst Stimulation (aiTBS) is a unique treatment for treatment-resistant depression because it is a noninvasive brain stimulation technique that rapidly reduces depression symptoms by altering brain network connectivity, specifically targeting the left dorsolateral prefrontal cortex. Unlike traditional treatments, aiTBS can lead to significant improvements in just a few days, although the effects may not be long-lasting without further intervention.12347
Eligibility Criteria
This trial is for adults aged 18-80 with treatment-resistant depression, defined by a specific score on the Maudsley Staging Method. Participants must be in good health, have ongoing psychiatric care, and women of childbearing age should use effective contraception. Exclusions include substance abuse issues, recent suicide attempts or ideation, certain neurological diseases or head trauma, metal implants incompatible with MRI or rTMS treatments.Inclusion Criteria
MADRS score of ≥20 at screening (Visit 1)
I have been diagnosed with MDD or Bipolar II and am currently experiencing a major depressive episode.
In good general health, as evidenced by medical history
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Exclusion Criteria
Active suicidal ideation (defined as an MSSI > 8) or a suicide attempt within the past 90 days
I have used ketamine or had ECT for depression recently.
I don't have metal in my head, a seizure history, or known brain lesions.
See 11 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive theta-burst TMS stimulation or sham stimulation for 4-8 weeks
4-8 weeks
5 visits per week (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
1 week
1 visit (in-person)
Treatment Details
Interventions
- Accelerated Intermittent Theta Burst Stimulation (aiTBS) (Neurostimulation)
Trial OverviewThe study tests an innovative neurostimulation approach called accelerated intermittent theta burst stimulation (aiTBS) targeting different brain regions to alleviate symptoms of severe depression that hasn't responded to standard treatments. It compares active aiTBS at two brain sites versus sham (placebo-like) treatment.
Participant Groups
3Treatment groups
Active Control
Placebo Group
Group I: Active TBS-DLPFCActive Control1 Intervention
The active group will receive theta-burst TMS stimulation.
Group II: Active TBS-DMPFCActive Control1 Intervention
The active group will receive theta-burst TMS stimulation.
Group III: Sham Comparator: Sham TBS-DLPFC or DMPFCPlacebo Group1 Intervention
The sham group will receive sham theta-burst TMS stimulation.
Accelerated Intermittent Theta Burst Stimulation (aiTBS) is already approved in United States for the following indications:
🇺🇸 Approved in United States as aiTBS for:
- Treatment-resistant depression
- Major depressive disorder
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Department of Psychiatry and Behavioral Sciences, Stanford School of MedicineStanford, CA
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Who Is Running the Clinical Trial?
Stanford UniversityLead Sponsor
References
Accelerated intermittent theta burst stimulation in major depression induces decreases in modularity: A connectome analysis. [2023]Accelerated intermittent theta burst stimulation (aiTBS) is a noninvasive neurostimulation technique that shows promise for improving clinical outcome in patients suffering from treatment-resistant depression (TRD). Although it has been suggested that aiTBS may evoke beneficial neuroplasticity effects in neuronal circuits, the effects of aiTBS on brain networks have not been investigated until now. Fifty TRD patients were enrolled in a randomized double-blind sham-controlled crossover trial involving aiTBS, applied to the left dorsolateral prefrontal cortex. Diffusion-weighted MRI data were acquired at each of three time points (T1 at baseline; T2 after the first week of real/sham aiTBS stimulation; and T3 after the second week of treatment). Graph analysis was performed on the structural connectivity to examine treatment-related changes in the organization of brain networks. Changes in depression severity were assessed using the Hamilton Depression Rating Scale (HDRS). Baseline data were compared with 60 healthy controls. We observed a significant reduction in depression symptoms over time (p < 0.001). At T1, both TRD patients and controls exhibited a small-world topology in their white matter networks. More importantly, the TRD patients demonstrated a significantly shorter normalized path length (p AUC = 0.01), and decreased assortativity (p AUC = 0.035) of the structural networks, compared with the healthy control group. Within the TRD group, graph analysis revealed a less modular network configuration between T1 and T2 in the TRD group who received real aiTBS stimulation in the first week (p < 0.013). Finally, there were no significant correlations between changes on HDRS scores and reduced modularity. Application of aiTBS in TRD is characterized by reduced modularity, already evident 4 days after treatment. These findings support the potential clinical application of such noninvasive brain stimulation in TRD.
Cortical Thickness in the Right Anterior Cingulate Cortex Relates to Clinical Response to Left Prefrontal Accelerated Intermittent Theta Burst Stimulation: An Exploratory Study. [2022]Accelerated intermittent theta burst stimulation (aiTBS) is a promising treatment option for depressed patients. However, there is a large interindividual variability in clinical effectiveness and individual biomarkers to guide treatment outcome are needed.
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.
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.
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.
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 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.