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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method called Theta Burst Stimulation (TBS), a form of transcranial magnetic stimulation, for treating depression in teenagers. Researchers aim to determine if TBS sessions three times a day are more effective than once-a-day sessions for adolescents whose depression hasn't improved with medication. The trial seeks teens aged 16-19 who have experienced moderate depression despite trying at least one antidepressant. As an unphased study, this trial provides a unique opportunity to explore innovative treatment options for depression.

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 prior data suggests that Theta Burst Stimulation is safe for adolescents?

Research shows that theta burst stimulation (TBS) is generally safe and well-tolerated for both adults and teenagers with depression. Studies also indicate that repetitive transcranial magnetic stimulation (rTMS), a similar treatment, is safe and effective for teenagers with major depressive disorder. Specifically, more frequent sessions of TBS, known as accelerated TBS, have proven safe for those with treatment-resistant depression.

One study found that three TBS sessions per day were safe and effective. The standard TBS method also safely improves depression symptoms in teenagers, according to research. Both accelerated and standard TBS show similar safety levels, with no major safety issues reported in studies. However, more research is needed to confirm these findings over the long term. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike traditional treatments for adolescent depression, such as antidepressant medications and talk therapy, Theta Burst Stimulation (TBS) offers a unique, non-invasive approach by directly targeting brain activity. Researchers are excited about TBS because it delivers rapid pulses of magnetic energy to the left dorsolateral prefrontal cortex, an area of the brain linked to mood regulation. This method has the potential to provide quicker relief from depressive symptoms, with the accelerated iTBS protocol showing promise in achieving results in just two weeks compared to the standard six-week treatment period. This faster potential turnaround is particularly appealing for those seeking timely improvements in mental health.

What evidence suggests that this trial's treatments could be effective for adolescent depression?

Studies have shown that theta burst stimulation (TBS) is a promising treatment for major depression. In this trial, participants will receive either accelerated intermittent TBS (iTBS), administered three times a day, or standard iTBS, given once a day. Research indicates that accelerated iTBS can greatly reduce depression symptoms; one study found a 54.7% decrease in depression scores. Standard iTBS has also quickly and effectively improved depression symptoms in teenagers. Both treatments have proven safe and effective in reducing depression, offering exciting options for those struggling with this condition. ^{1 4 6 7 8}

Who Is on the Research Team?

Sara Tremblay, PhD

Principal Investigator

The Royal's Institute of Mental Health Research

Jean-François Lepage, PhD

Principal Investigator

Sherbrooke University

Are You a Good Fit for This Trial?

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

Can speak and read English

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

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.

Organic cause of depressive symptoms (e.g. thyroid dysfunction), ruled out by the treating physician

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

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]

Citations

1. 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.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165032725000023

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 ...

3. 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 ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04701840

Sequential Bilateral Accelerated Theta Burst Stimulation in ... The purpose of this study is to gather information regarding the use of a new type of transcranial magnetic stimulation (TMS) called theta burst stimulation ...

5. jamanetwork.com jamanetwork.com/journals/jamapsychiatry/article-abstract/2830861

Accelerated Theta-Burst Stimulation for Treatment ... The active aTBS group experienced a mean reduction in Hamilton Depression Rating Scale scores of 54.7% compared to 31.87% in the sham group; ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165032725018774

Intermittent theta burst stimulation for adolescent patients ... Accumulating studies have found that conventional rTMS appear to be safe and effective in the treatment of adolescent patients with MDD or BD ( ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04701840

Sequential Bilateral Accelerated Theta Burst Stimulation in ... The investigators hope to learn if this TMS treatment improves suicidal ideation over 10 days and clinical outcomes over 1 year of follow-up. Detailed ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8617062/

A Systematic Review of the Safety and Tolerability of Theta ... TBS interventions in children may have similar safety, tolerability, and feasibility as compared to adults. However, long-term, follow-up studies of TBS are ...