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

Trial Summary

What is the purpose of this trial?

Repetitive TMS (rTMS) is a well-established method for modulating brain activity. Through successive stimulations in the form of magnetic fields, it is possible to modify the sensitivity of neurons in the brain, also known as cortical excitability. Cortical excitability is important for the induction of brain plasticity, the ability of the brain to reorganize itself and form new connections in response to stimuli. A particular class of rTMS, intermittent theta burst TMS (iTBS), is commonly used to modulate cortical excitability and induce plasticity for therapeutic purposes, notably for treatment-resistant depression. Different iTBS stimulation parameters can be used to induce plasticity. This study will focus on two parameters, namely, the form and duration of the electromagnetic stimulation. The shape of the electromagnetic pulse refers to how the electromagnetic wave is configured over time, while the duration is simply the period during which this electromagnetic pulse remains active. These parameters are expected to influence the effectiveness of iTBS in modulating cortical activity but remain little studied. The main aim of this study will be to compare the effectiveness of different stimulation parameters in the induction of plasticity, which will then make it possible to improve the rTMS protocols used for treatment-resistant 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 data supports the effectiveness of the treatment iTBS for depression?

Research shows that intermittent theta burst stimulation (iTBS) is effective for treatment-resistant depression, with studies indicating it is as effective as traditional repetitive transcranial magnetic stimulation (rTMS) but faster to administer. It has been approved by the U.S. Food and Drug Administration for this use, and multiple daily sessions may help patients achieve remission more quickly. ^{1 2 3 4 5}

Is iTBS safe for humans?

Research shows that intermittent theta burst stimulation (iTBS) is generally safe and well-tolerated in humans, with studies reporting no adverse events in patients with depression and bipolar depression. ^{2 3 4 6 7}

How is the iTBS treatment different from other treatments for depression?

iTBS (Intermittent Theta Burst Stimulation) is a unique treatment for depression because it is a noninvasive brain stimulation that can be delivered in just over 3 minutes, compared to the longer sessions required for traditional rTMS (repetitive transcranial magnetic stimulation). It is designed to be rapid-acting and can be administered multiple times a day, potentially leading to faster remission for patients with treatment-resistant depression. ^{1 2 4 5 7}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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 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]

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]

References

1. United States 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). [2022]

2. 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]

3. 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]

4. 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]

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

Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression. [2020]

6. France pubmed.ncbi.nlm.nih.gov

Twice-daily neuronavigated intermittent theta burst stimulation for bipolar depression: A Randomized Sham-Controlled Pilot Study. [2020]

7. Switzerland 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. [2023]