iTBS Optimization for Depression

Overseen By Jean-Francois Lepage, Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Université de Sherbrooke

Must not be taking: Psychotropic medications

Disqualifiers: Epilepsy, Neurological disease, 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: 3

Duration: 3 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different settings of intermittent theta burst stimulation (iTBS) can treat depression unresponsive to standard treatments. iTBS uses magnetic pulses to alter brain cell communication, potentially forming new, beneficial connections. Researchers will compare various delivery methods of these magnetic pulses to determine the most effective approach. Individuals who are generally healthy, right-handed, and aged 18 to 35 may be suitable for this study. As an unphased trial, it offers participants the chance to contribute to innovative research that could lead to new treatment options for depression.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any psychotropic medications (drugs that affect your mind, emotions, or behavior) to participate in this trial.

What prior data suggests that this iTBS method is safe for treating depression?

Research has shown that intermittent theta burst stimulation (iTBS) is generally safe and well-tolerated. Studies have found that iTBS effectively reduces symptoms of depression, offering a good balance between benefits and risks. For instance, one study suggested that just two days of active iTBS can quickly and safely lessen depression symptoms in teenagers.

Another review found iTBS to be safer compared to other similar treatments. Although some studies mention that the length and safety of daily sessions can be a limitation, the overall findings indicate that iTBS is safe for treating depression. These studies support iTBS as a promising option with a strong safety record for those considering clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the iTBS protocol for depression because it offers a potentially faster-acting alternative to traditional treatments like antidepressant medications and electroconvulsive therapy. iTBS, or intermittent theta burst stimulation, involves using magnetic fields to stimulate specific brain areas thought to be involved in depression. This method is non-invasive and may provide quicker relief from depressive symptoms, potentially within days, compared to the weeks often required for conventional treatments. By exploring different iTBS protocols, researchers hope to optimize its effectiveness and further understand how to tailor treatments to individual patients' needs.

What evidence suggests that this trial's iTBS protocols could be effective for treatment-resistant depression?

Research has shown that intermittent theta burst stimulation (iTBS) can effectively reduce symptoms of depression. Studies suggest that applying iTBS to specific brain areas can quickly and safely improve depressive symptoms, even for those unresponsive to other treatments. One trial found that multiple daily iTBS sessions significantly reduced depression severity. Compared to traditional methods, iTBS might offer a faster and possibly more effective treatment for depression. This trial will explore different iTBS protocols, with participants experiencing three distinct protocols, each separated by one week. This treatment changes brain activity patterns and helps the brain form new connections, which can improve mood. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for individuals aged 18-35, right-handed, and in good health who are experiencing depression. It's not specified if participants need to have treatment-resistant depression or any particular severity of symptoms.

Inclusion Criteria

I am right-handed.

I am in good overall health.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo 3 different iTBS protocols, each separated by one week, to compare the effectiveness of different stimulation parameters in the induction of plasticity.

3 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with measures of cortical plasticity taken pre-iTBS and every 5 minutes post iTBS intervention up to 60 minutes post intervention.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• iTBS

Trial Overview The study tests different ways of delivering iTBS, a type of brain stimulation therapy for depression. It compares monophasic (single-phase) against biphasic (dual-phase), and also looks at the effects of extending the duration with Monophasic-Long iTBS.

How Is the Trial Designed?

Group I: Intermittent theta burst stimulation (iTBS) Experimental Treatment 3 Interventions

All participants will understand 3 different iTBS protocols, each separated by one week. The order of the iTBS protocols will be randomized.

iTBS is already approved in United States for the following indications:

Approved in United States as iTBS for:

• Treatment-resistant depression
• Major depressive disorder

Who Is Running the Clinical Trial?

Université de Sherbrooke

Lead Sponsor

Trials

317

Recruited

79,300+

Published Research Related to This Trial

In a study of 60 patients with treatment-resistant unipolar depression, both intermittent theta burst stimulation (iTBS) and conventional 10 Hz rTMS showed similar efficacy in reducing depression scores and improving quality of life over a 6-month follow-up, with response rates of 36.7% for iTBS and 33.3% for rTMS.

iTBS is highlighted as a more time-efficient and cost-effective option compared to rTMS, suggesting it could be a valuable treatment alternative for patients with severe depression who have not responded to multiple antidepressant trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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). Bulteau, S., Laurin, A., Pere, M., et al.[2022]

Intermittent theta-burst stimulation (iTBS) and high-frequency rTMS (HF-rTMS) show similar efficacy in treating treatment-resistant depression (TRD), with response rates of 48.0% for iTBS and 45.5% for HF-rTMS based on two high-quality randomized controlled trials involving 474 participants.

Both iTBS and HF-rTMS have comparable safety profiles, with similar rates of discontinuation and adverse events, such as headaches, indicating that iTBS is a safe alternative to HF-rTMS for patients with TRD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of intermittent theta burst stimulation versus high-frequency repetitive transcranial magnetic stimulation for patients with treatment-resistant depression: a systematic review. Lan, XJ., Yang, XH., Qin, ZJ., 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]

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 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]

In a study of 22 participants with treatment-resistant depression, the Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) protocol, which uses high-dose intermittent theta-burst stimulation (iTBS) guided by functional connectivity MRI, showed a remarkable remission rate of 90.5%.

The treatment was well tolerated with no negative cognitive side effects reported, suggesting that SAINT could be a safe and effective option for patients who have not responded to traditional antidepressants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression. Cole, EJ., Stimpson, KH., Bentzley, BS., et al.[2020]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39761754/

Efficacy study of intermittent theta burst stimulation(iTBS) in ... The current study suggests that two days of active iTBS to the DLPFC region can rapidly, safely, and effectively improve depressive symptoms in adolescents ...

2. nature.com nature.com/articles/s41380-024-02630-5

Theta burst stimulation for depression: a systematic review ... Theta burst stimulation (TBS) presents as a more efficient and potentially more effective therapeutic modality than conventional repetitive transcranial ...

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

Efficacy and Safety of Accelerated Intermittent Theta-burst ... In this trial, a-iTBS, administered five sessions per day for ten days, is effective and safe for adolescents with non-treatment-resistant MDD.

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

Accelerated intermittent theta burst stimulation in major ... Results showed immediate reductions in depression severity symptoms. Moreover, our graph theoretical analyses revealed modularity changes after 4 days of ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT07033780

NCT07033780 | Theta-Burst Stimulation to Treat Depression The goal of this clinical trial is to explore the effects of non-invasive brain stimulation protocols using intermittent theta-burst stimulation (iTBS) on ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10423820/

Efficacy and safety of intermittent theta burst stimulation ... The objective of this systematic review was to compare the safety and efficacy of iTBS and high-frequency (≥ 5 Hz) rTMS (HF-rTMS) for patients with treatment- ...