Theta Burst Stimulation for Adolescent Depression

Overseen By Maya El-Outa, BSc

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: The Royal Ottawa Mental Health Centre

Must be taking: Antidepressants

Must not be taking: Illegal drugs, High-dose lorazepam

Disqualifiers: Bipolar disorder, Substance abuse, Unstable medical, 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: 5

Duration: 2-6 weeks

10 Participants Needed

Trial Summary

What is the purpose of this trial?

Repetitive transcranial magnetic stimulation (rTMS) is a Health Canada approved treatment for major depression. Theta burst stimulation (TBS), a type of rTMS, is a very promising new treatment for major depression in adults and adolescents. However, very few studies have assessed the efficacy of accelerated, three times a day TBS in comparison with standard once a day TBS in adolescents. The study aims to explore further evidence in hopes to conduct a large-scale, randomized, multisite, placebo-controlled clinical trial evaluating the effects of a functional magnetic resonance imaging (fMRI)-guided accelerated rTMS protocol vs. standard once/daily rTMS for treatment-resistant depression in adolescents.

Will I have to stop taking my current medications?

The trial requires that you have stable psychotropic medications (medications affecting mood, perception, or behavior) for at least four weeks before participating. You must also be willing to maintain your current antidepressant regimen during the study.

What data supports the effectiveness of the treatment Theta Burst Stimulation (TBS) for adolescent depression?

Research shows that Theta Burst Stimulation (TBS), a type of brain stimulation therapy, is promising for treating major depressive disorder (MDD) in youth who don't respond to other treatments. Studies have found that certain brain activity patterns can predict who will benefit most from TBS, suggesting it could be an effective option for some adolescents with depression. ^{1 2 3 4 5}

Is theta burst stimulation (TBS) safe for humans?

Research shows that theta burst stimulation (TBS) is generally safe and well tolerated in humans, with mild side effects like headaches being the most common. Studies on TBS for depression indicate it is safe, even with increased stimulation parameters, and does not lead to more side effects. ^{1 2 6 7 8}

How is Theta Burst Stimulation (TBS) different from other treatments for adolescent depression?

Theta Burst Stimulation (TBS) is a unique form of transcranial magnetic stimulation (TMS) that uses rapid bursts of magnetic pulses to target specific brain areas, potentially offering a faster and more efficient treatment for depression compared to traditional TMS. It is particularly promising for adolescents who do not respond to conventional therapies, and it can be administered in accelerated sessions for quicker results. ^{1 2 3 4 5}

Research Team

Jean-François Lepage, PhD

Principal Investigator

Sherbrooke University

Sara Tremblay, PhD

Principal Investigator

The Royal's Institute of Mental Health Research

Eligibility Criteria

This trial is for adolescents with major depression who haven't improved with standard treatments. Participants must be able to undergo fMRI scans and TBS sessions. Specific details on inclusion and exclusion criteria are not provided, but typically these would outline health conditions or medications that might interfere with the treatment.

Inclusion Criteria

I am willing and able to give my consent to participate.

Can speak and read English

My mental health treatment has been stable for at least 4 weeks.

Exclusion Criteria

Are pregnant or breastfeeding, or plan to become pregnant during treatment (pregnancy will be assessed by a urine test)

I cannot have TMS or MRI due to conditions like epilepsy or having a metal implant.

I do not have any uncontrolled major illnesses like diabetes or kidney problems.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Baseline Assessment

Participants complete clinical assessments and self-report questionnaires for baseline measurement

1 week

1 visit (in-person)

Treatment

Participants receive iTBS applied to the left DLPFC. Accelerated group: 3 times a day for 2 weeks. Standard group: once a day for 6 weeks.

2-6 weeks

Daily sessions (Mon-Fri)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with clinical assessments and self-report questionnaires

12 weeks

3 visits (in-person) at 2, 4, and 12 weeks post-treatment

Treatment Details

Interventions

• Theta Burst Stimulation

Trial Overview The study tests if using Theta Burst Stimulation (TBS), a type of brain stimulation therapy, three times a day works better than once daily for treating depression in adolescents. It's guided by fMRI scans to target specific brain areas.

Participant Groups

Group I: Accelerated iTBS Active Control 1 Intervention

Intermittent Theta Burst Stimulation (iTBS) will be applied to the left dorsolateral prefrontal cortex (DLPFC). Participants will receive daily sessions (Mon-Fri), three times a day for 10 days (2 weeks).

Group II: Standard iTBS Active Control 1 Intervention

Intermittent Theta Burst Stimulation (iTBS) will be applied to the left DLPFC. Participants will receive daily sessions (Mon-Fri), once a day for 30 days (6 weeks).

Theta Burst Stimulation is already approved in United States for the following indications:

Approved in United States as Theta Burst Stimulation for:

• Major Depressive Disorder

Who Is Running the Clinical Trial?

The Royal Ottawa Mental Health Centre

Lead Sponsor

Trials

24

Recruited

2,300+

Université de Sherbrooke

Collaborator

Trials

317

Recruited

79,300+

Findings from Research

In a randomized-controlled trial involving 32 patients with major depression, bilateral theta burst stimulation (TBS) to the dorsolateral prefrontal cortex showed a significant increase in treatment response compared to sham stimulation, with 9 responders in the TBS group versus 4 in the sham group.

The study also indicated a trend towards higher remission rates in the TBS group as measured by the Beck Depression Inventory, suggesting that TBS may enhance the effectiveness of ongoing medication and psychotherapy in treating major depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of major depression with bilateral theta burst stimulation: a randomized controlled pilot trial. Plewnia, C., Pasqualetti, P., Große, S., et al.[2018]

In a study of 27 participants, a prolonged intermittent theta burst stimulation (piTBS) protocol using 1,800 pulses showed limited effectiveness for major depressive disorder, with only 18.2% of participants achieving a response and 9.1% reaching remission.

Safety and tolerability were concerns, as 18.5% of participants experienced issues, suggesting that while piTBS is a promising approach, further research is needed to optimize its parameters and improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged intermittent theta burst stimulation in the treatment of major depressive disorder: a case series. Richard, M., Noiseux, C., Desbeaumes Jodoin, V., et al.[2022]

In a randomized, double-blind trial involving 56 patients, intermittent theta burst stimulation (iTBS) over the dorsomedial prefrontal cortex showed a significant reduction in negative symptoms for patients with depression, but not for those with schizophrenia.

The treatment was generally safe and well-tolerated, with serious adverse events occurring only in the sham group, indicating that iTBS may be a promising intervention for depressive symptoms in certain patients.

NCBI (Pubmed)

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. Bodén, R., Bengtsson, J., Thörnblom, E., et al.[2021]

Theta burst stimulation (TBS) is a promising treatment for youth aged 16-24 with Major Depressive Disorder (MDD) who do not respond to conventional therapies, as shown in two clinical trials with 10 and 20 daily sessions of TBS.

Baseline neurophysiology measures, specifically the N45 and P60 TMS-evoked potentials from the left dorsolateral prefrontal cortex, can predict treatment response, with greater N45 and smaller P60 values indicating a better response to TBS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baseline markers of cortical excitation and inhibition predict response to theta burst stimulation treatment for youth depression. Dhami, P., Moreno, S., Croarkin, PE., et al.[2023]

This study is the first randomized controlled trial investigating the efficacy of accelerated theta burst stimulation (aTBS) in treating suicidal ideation in adolescents with major depressive disorder (MDD), involving three daily sessions over 10 days.

The trial aims to address underlying neurotransmission deficits in the dorsolateral prefrontal cortex (DLPFC) and will measure biomarkers to understand the neurophysiological mechanisms of suicidal ideation, potentially leading to more effective treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential bilateral accelerated theta burst stimulation in adolescents with suicidal ideation associated with major depressive disorder: Protocol for a randomized controlled trial. Yuruk, D., Ozger, C., Garzon, JF., et al.[2023]

Theta-burst transcranial magnetic stimulation (TBS) is safe and well tolerated in patients with major depression, based on a study involving 33 participants over 10 consecutive days.

The study suggests that TBS may have antidepressant effects, and increasing stimulation parameters does not lead to more side effects, potentially enhancing its therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability and preliminary evidence for antidepressant efficacy of theta-burst transcranial magnetic stimulation in patients with major depression. Chistyakov, AV., Rubicsek, O., Kaplan, B., et al.[2019]

In a case series of 9 patients with major depressive disorder and bipolar disorder, accelerated theta-burst rTMS treatment over 8 days led to significant reductions in depression symptoms, as measured by the CES-D and CGI scales.

The treatment was well tolerated, with mild headaches being the most common side effect, and five patients achieving at least a 50% reduction in symptoms by the end of the treatment period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated theta-burst repetitive transcranial magnetic stimulation for depression in South Africa. Bröcker, E., van den Heuvel, L., Seedat, S.[2020]

Accelerated intermittent theta burst stimulation (TBS) was found to be safe and well tolerated in 12 suicidal therapy-resistant depressed patients, showing a significant decrease in suicidal ideation over time.

However, the reduction in suicidal thoughts was not definitively linked to the active TBS treatment compared to sham stimulation, indicating that further research is needed to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The acute effects of accelerated repetitive Transcranial Magnetic Stimulation on suicide risk in unipolar depression: preliminary results. Desmyter, S., Duprat, R., Baeken, C., et al.[2022]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Treatment of major depression with bilateral theta burst stimulation: a randomized controlled pilot trial. [2018]

2. Ireland pubmed.ncbi.nlm.nih.gov

Prolonged intermittent theta burst stimulation in the treatment of major depressive disorder: a case series. [2022]

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]

4. England pubmed.ncbi.nlm.nih.gov

Baseline markers of cortical excitation and inhibition predict response to theta burst stimulation treatment for youth depression. [2023]

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

Sequential bilateral accelerated theta burst stimulation in adolescents with suicidal ideation associated with major depressive disorder: Protocol for a randomized controlled trial. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Safety, tolerability and preliminary evidence for antidepressant efficacy of theta-burst transcranial magnetic stimulation in patients with major depression. [2019]

7. South Africa pubmed.ncbi.nlm.nih.gov

Accelerated theta-burst repetitive transcranial magnetic stimulation for depression in South Africa. [2020]

8. Croatia pubmed.ncbi.nlm.nih.gov

The acute effects of accelerated repetitive Transcranial Magnetic Stimulation on suicide risk in unipolar depression: preliminary results. [2022]