aiTBS for Depression

Overseen By Ian Kratter, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Stanford University

Must be taking: Mood stabilizers

Must not be taking: Rapid antidepressants

Disqualifiers: Epilepsy, Pregnancy, Substance abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 1 week

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to treat depression in individuals with bipolar II disorder who haven't found success with other treatments. The focus is on magnetic stimulation, known as Accelerated Intermittent Theta-Burst Stimulation (aiTBS), which targets a specific brain area to determine its effectiveness in reducing depression symptoms. Participants will be randomly assigned to receive either the actual treatment or a sham (placebo) version. The trial seeks adults diagnosed with bipolar II disorder who are currently experiencing major depressive episodes and have consistently used mood stabilizers for at least 6 weeks. As an unphased trial, this study provides a unique opportunity to explore innovative treatment options for those who have not found relief with existing therapies.

Will I have to stop taking my current medications?

The trial requires that you stay on a mood stabilizer regimen for at least 6 weeks before joining and continue it during the study. The protocol does not specify if you need to stop other medications, so it's best to discuss this with the study team.

What prior data suggests that accelerated intermittent theta-burst transcranial magnetic stimulation (aiTBS) is safe for treating depression?

Research has shown that accelerated intermittent theta-burst stimulation (aiTBS) is generally safe for people with depression unresponsive to other treatments. Studies have found that aiTBS can quickly improve symptoms in these individuals. For instance, one study demonstrated that three sessions a day were both safe and effective.

In a study with 29 participants, where some received a placebo, aiTBS proved safe and had significant positive effects. This suggests that even with more frequent sessions, the treatment is well-tolerated. Overall, aiTBS is widely used and considered safe, with real-life results mirroring those seen in clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for depression, like antidepressant medications and traditional transcranial magnetic stimulation (TMS), can take weeks to show effectiveness. However, researchers are excited about Accelerated Intermittent Theta-Burst Stimulation (aiTBS) because it has the potential to show results in just days. aiTBS is unique because it delivers rapid bursts of magnetic pulses to the brain's left dorsolateral prefrontal cortex (LDLPFC), which is thought to play a key role in depression. This technique offers a faster, possibly more efficient approach to treating depression compared to conventional methods.

What evidence suggests that aiTBS is effective for treatment-resistant depression?

Research has shown that accelerated intermittent theta-burst stimulation (aiTBS) can help reduce symptoms of depression. In this trial, participants will receive either active aiTBS or a sham (fake) aiTBS treatment. Studies have found that aiTBS is more effective than a fake treatment for people with treatment-resistant bipolar disorder. This method targets the left side of the brain, an area involved in mood control. Early results suggest that aiTBS can quickly improve symptoms in people with major depressive disorder. This non-invasive brain treatment offers hope for those who haven't found relief with other therapies. ^{1 6 7 8 9}

Who Is on the Research Team?

Nolan Williams, MD

Principal Investigator

Stanford University

Bora Kim, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with bipolar II disorder currently experiencing a major depressive episode, who haven't responded to standard treatments. They must be in good health, not have hypomania or psychosis, and women must use effective contraception. Excluded are those with metal in their head, pacemakers, substance abuse issues, severe insomnia, certain mental health conditions like anxiety disorders or personality disorders, recent suicidal behavior or thoughts.

Inclusion Criteria

In good general health, as ascertained by medical history

Able to read, understand, and provide written, dated informed consent prior to screening. Participants will be deemed likely to comply with study protocol and communicate with study personnel about adverse events and other clinically important information

Not in a current state of hypomania (as assessed by the Young Mania Rating Scale) or psychosis

Exclusion Criteria

Shrapnel or any ferromagnetic item in the head

My movement disorder won't interfere with treatment.

Any other indication the Principal Investigator feels would comprise data

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive accelerated intermittent theta-burst stimulation (aiTBS) to the left dorsolateral prefrontal cortex (L-DLPFC) with 10 sessions administered daily over 5 consecutive days

1 week

5 visits (in-person)

Follow-up

Participants are monitored for changes in depressive symptoms and neural functional connectivity

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Accelerated Intermittent Theta-Burst Stimulation (aiTBS)

Trial Overview The study tests accelerated intermittent theta-burst stimulation (aiTBS) targeting the left dorsolateral prefrontal cortex to treat treatment-resistant depression in bipolar II disorder patients. It's a double-blind trial comparing active aiTBS against sham (placebo) aiTBS using the MagPro rTMS system.

How Is the Trial Designed?

Group I: Active aiTBS Active Control 1 Intervention

Participants will be randomized to active or sham aiTBS condition, and receive 10 aiTBS to left DLPFC (LDLPFC) sessions a day for 5 days of course.

Group II: Sham aiTBS Placebo Group 1 Intervention

Participants will be randomized to active or sham aiTBS condition, and receive 10 aiTBS to left DLPFC (LDLPFC) sessions a day for 5 days of course.

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 of bipolar II disorder

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Published Research Related to This Trial

In a study involving 72 patients with major depressive disorder, two daily sessions of prolonged intermittent theta-burst stimulation (piTBS) over two weeks showed significantly more responders compared to a sham treatment, indicating its efficacy as an antidepressant option.

However, the study found no evidence that longer piTBS sessions led to greater improvements in depression scores compared to other treatments, suggesting that while piTBS is effective, increasing treatment duration does not enhance its antidepressant effects.

NCBI (Pubmed)

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. Li, CT., Cheng, CM., Lin, HC., et al.[2023]

Accelerated, high-dose intermittent theta burst stimulation (iTBS) showed promising results in treating highly treatment-resistant depression, with most patients achieving remission after treatment.

However, the effects were short-lived, as all patients experienced relapse within two weeks, indicating a need for improved treatment strategies that enhance the durability of the therapeutic response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is accelerated, high-dose theta burst stimulation a panacea for treatment-resistant depression? Caulfield, KA.[2021]

In a study of 50 depressed patients undergoing accelerated intermittent theta burst stimulation (aiTBS), baseline cortical thickness in the right caudal part of the anterior cingulate cortex (cACC) was found to significantly correlate with immediate clinical responses to treatment.

Longitudinal changes in cortical thickness in the right cACC also predicted delayed clinical responses, suggesting that this brain region could serve as a biomarker for determining the effectiveness of aiTBS in treating depression.

NCBI (Pubmed)

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. Baeken, C., van Beek, V., Vanderhasselt, MA., et al.[2022]

Intermittent theta burst stimulation (iTBS) is as effective as standard high-frequency (10 Hz) rTMS for treating treatment-resistant depression, showing non-inferiority in improving depression scores over 4-6 weeks in a study with 414 participants.

Both iTBS and 10 Hz rTMS had similar safety profiles and dropout rates, with headaches being the most common side effect, indicating that iTBS can be a viable alternative that allows for more patients to be treated in a shorter time without losing effectiveness.

NCBI (Pubmed)

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. Blumberger, DM., Vila-Rodriguez, F., Thorpe, KE., et al.[2022]

In a study involving 50 patients with major depressive disorder (MDD), accelerated intermittent theta-burst stimulation (aiTBS) did not significantly affect reward responsiveness during a learning task, regardless of the patients' levels of anhedonia.

However, brain imaging revealed that aiTBS treatment altered neural activity in the reward system differently based on anhedonia severity, with low anhedonic patients showing decreased activity and high anhedonic patients showing increased activity after one week of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated iTBS treatment in depressed patients differentially modulates reward system activity based on anhedonia. Duprat, R., Wu, GR., De Raedt, R., et al.[2019]

In a study of 26 patients with bipolar depression, active intermittent theta burst stimulation (iTBS) showed a high response rate of 72% and a remission rate of 42%, indicating its potential efficacy in treating this condition.

No adverse events were reported, demonstrating that iTBS is safe and well-tolerated, but further research with larger sample sizes is needed to confirm its superiority over sham treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Twice-daily neuronavigated intermittent theta burst stimulation for bipolar depression: A Randomized Sham-Controlled Pilot Study. Bulteau, S., Beynel, L., Marendaz, C., et al.[2020]

A clinical trial involving 96 outpatients with moderate depression will investigate the effectiveness of intermittent theta burst stimulation (iTBS) on reducing depressive symptoms, comparing it to a sham treatment over ten sessions.

The study will also explore various factors, including genetic and neuropsychological measures, that may influence the response to iTBS, ensuring a thorough safety screening and adherence to ethical guidelines throughout the trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The antidepressant effect of intermittent theta burst stimulation (iTBS): study protocol for a randomized double-blind sham-controlled trial. Ørbo, MC., Grønli, OK., Larsen, C., et al.[2023]

In a study involving 208 participants with treatment-resistant depression, both twice-daily and once-daily intermittent theta burst stimulation (iTBS) protocols showed improvements in depression scores, but there was no significant difference in efficacy between the two schedules after 10 and 30 days.

Response and remission rates were low in both treatment groups, indicating that neither protocol significantly accelerated the improvement of depressive symptoms in patients with treatment-resistant depression.

NCBI (Pubmed)

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. Blumberger, DM., Vila-Rodriguez, F., Wang, W., et al.[2022]

Citations

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Accelerated Intermittent Theta-Burst Stimulation for ... They found that active aiTBS was significantly more effective than sham stimulation for depressive symptoms, supporting the clinical efficacy of ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38985492/

Accelerated Intermittent Theta-Burst Stimulation and ... In this randomized clinical trial, aiTBS was more effective than sham stimulation for depressive symptom reduction in patients with treatment-resistant BD.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05849402

Accelerated Intermittent Theta-Burst Stimulation (aiTBS) in ... The aim of this study is to assess the efficacy of aiTBS applied to the left dorsolateral prefrontal cortex (L-DLPFC) in reducing depressive symptoms in ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0165178123003797

Accelerated intermittent theta burst stimulation in major ... aiTBS is a promising form of non-invasive brain stimulation [NIBS] with rapid antidepressant and antisuicidal effects in major depressive disorder [MDD].

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6372023/

Accelerated intermittent theta burst stimulation in major ... Accelerated noninvasive neurostimulation has shown promise to rapidly improve clinical symptoms in patients suffering from treatment-resistant depression.

6. sciencedirect.com sciencedirect.com/science/article/pii/S0165032723002604

Outcome of transcranial magnetic intermittent theta-burst ... iTBS is the most utilized rTMS protocol for depression in Sweden. Real-life response rates of iTBS are similar to clinical trials.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40042840/

Accelerated Theta-Burst Stimulation for Treatment ... A pragmatic aTBS protocol using only 3 iTBS sessions per day and a nonexpensive, non-neuronavigated approach was found to be safe and effective for TRD.

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006322325013563

Efficacy and Safety of Accelerated Intermittent Theta-burst ... Evidence suggests that increasing the number of treatment sessions and the total pulse dose substantially improves clinical outcomes(13, 14).

9. psychiatryonline.org psychiatryonline.org/doi/10.1176/appi.ajp.2021.21121221

Accelerated Intermittent Theta Burst Stimulation study demonstrates safety and significant efficacy of Stanford neuromodulation therapy (SNT) in a placebo-controlled design with 29 participants ...