Therapeutic Neuromodulation for Depression

Recruiting in Palo Alto (17 mi)

Overseen by David 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, Bipolar, 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?

You will need to keep your primary antidepressant medication dose stable for 6 weeks before starting the study and continue at this dose throughout the study period.

What data supports the effectiveness of the treatment Accelerated Intermittent Theta Burst Stimulation (aiTBS) for depression?

Research shows that intermittent theta burst stimulation (iTBS), a component of aiTBS, is effective in treating depression, comparable to traditional methods. However, while aiTBS shows promise, its effectiveness can vary greatly among individuals, and more research is needed to understand its long-term benefits. ^{1 2 3 4 5}

Is theta burst stimulation safe for humans?

Theta burst stimulation, including its accelerated form (aiTBS), has been studied for depression and bipolar depression, showing it is generally safe and well-tolerated in humans, with no significant adverse events reported in the studies. ^{1 6 7 8 9}

How is accelerated intermittent theta burst stimulation (aiTBS) different from other depression treatments?

Accelerated intermittent theta burst stimulation (aiTBS) is unique because it delivers rapid, high-frequency magnetic pulses to the brain, specifically targeting areas involved in mood regulation, and is administered more quickly than traditional treatments like repetitive transcranial magnetic stimulation (rTMS). This approach aims to provide faster relief for depression symptoms, although its effects may not last as long. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for adults aged 18-80 with Major Depressive Disorder who haven't responded to standard treatments and have a MADRS score of ≥20. Participants must be TMS naive, in good health, agree to lifestyle considerations, and females must use effective contraception. Exclusions include metal implants that interfere with MRI or rTMS, seizure history, psychotic/bipolar disorders, substance abuse, severe personality disorder, recent suicide attempt or ECT without response.

Inclusion Criteria

You have a satisfactory medical record indicating that you are in good overall health.

Females of reproductive potential must have been using highly effective contraception for at least one month prior to screening and agree to continue its use during the study.

I am between 18 and 80 years old.

Exclusion Criteria

You currently have a serious problem with drugs or alcohol or are experiencing withdrawal symptoms.

You have a recent history of attempting suicide or are at a high risk of doing so based on the doctor's assessment.

You have received any experimental treatment or other interventions during the study period.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive theta-burst TMS DLPFC or DMPFC stimulation for 4-8 weeks

4-8 weeks

5 visits per week

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

Treatment Details

Interventions

• Accelerated Intermittent Theta Burst Stimulation (aiTBS) (Neurostimulation)

Trial Overview The study tests an innovative neurostimulation method called accelerated intermittent theta burst stimulation (aiTBS) targeting two brain regions: DMPFC & DLPFC. It aims to alleviate symptoms of anhedonia in treatment-resistant depression by comparing the effects of aiTBS on these areas.

Participant Groups

Group I: Active TBS-DLPFC Active Control 1 Intervention

The active group will receive theta-burst TMS DLPFC stimulation.

Group II: Active TBS-DMPFC Active Control 1 Intervention

The active group will receive theta-burst TMS DMPFC 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 Nearby Select from list below to view details:

Stanford University Stanford, CA

Who Is Running the Clinical Trial?

Stanford University Lead Sponsor

References

1. United States pubmed.ncbi.nlm.nih.gov

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.

2. England pubmed.ncbi.nlm.nih.gov

The antidepressant effect of intermittent theta burst stimulation (iTBS): study protocol for a randomized double-blind sham-controlled trial. [2023] Intermittent theta burst stimulation (iTBS) when applied over the left dorsolateral prefrontal cortex (DLPFC) has been shown to be equally effective and safe to treat depression compared to traditional repetitive transcranial magnetic stimulation (rTMS) paradigms. This protocol describes a funded single-centre, double-blind, randomized placebo-controlled, clinical trial to investigate the antidepressive effects of iTBS and factors associated with an antidepressive response.

3. Netherlands pubmed.ncbi.nlm.nih.gov

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.

4. United States pubmed.ncbi.nlm.nih.gov

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.

5. Netherlands pubmed.ncbi.nlm.nih.gov

The longer, the better ? Longer left-sided prolonged intermittent theta burst stimulation in patients with major depressive disorder: A randomized sham-controlled study. [2023] Prolonged intermittent theta-burst stimulation (iTBS) is effective for major depressive disorder (MDD). However, whether longer piTBS treatment in a single session could have antidepressant efficacy remains elusive. Therefore, this double-blind, randomized, sham-controlled study aimed to investigate the antidepressant efficacy of 2 daily piTBS sessions for treating MDD patients with a history of poor responses to at least 1 adequate antidepressant trial in the current episode.

6. United States pubmed.ncbi.nlm.nih.gov

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.

7. England pubmed.ncbi.nlm.nih.gov

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.

8. Netherlands pubmed.ncbi.nlm.nih.gov

Accelerated intermittent theta burst stimulation for major depressive disorder or bipolar depression: A systematic review and meta-analysis. [2023] We aimed to systematically evaluate the clinical efficacy and safety of accelerated intermittent theta burst stimulation (aiTBS) for patients with major depressive disorder (MDD) or bipolar depression (BD). A random-effects model was adopted to analyze the primary and secondary outcomes using the Review Manager, Version 5.3 software. This meta-analysis (MA) identified five double-blind randomized controlled trials (RCTs) comprising 239 MDD or BD patients with a major depressive episode. Active aiTBS overperformed sham stimulation in the study-defined response. This MA found preliminary evidence that active aiTBS resulted in a greater response in treating major depressive episodes in MDD or BD patients than sham stimulation.

9. France pubmed.ncbi.nlm.nih.gov

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.