Theta Burst Stimulation for Teenage Depression

(SAINT-KID Trial)

Overseen By Elyse J Lemke

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Texas at Austin

Must not be taking: Antidepressants, Ketamine, ECT

Disqualifiers: Pregnancy, Anxiety, Bipolar, Autism, others

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

Compensation: Varies

Number of Visits: 7

Duration: 1 week

40 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

Yes, participants must remain antidepressant-free throughout the study, which means stopping any current antidepressant medications.

What data supports the effectiveness of the treatment Accelerated Intermittent Theta Burst Stimulation (SAINT®) for teenage depression?

Research shows that theta burst stimulation (TBS), a type of brain stimulation, has been effective in treating major depression in adults, with significant improvements in depression scores and higher response rates compared to a placebo. This suggests that similar treatments like SAINT® could potentially help with teenage depression as well. ^{1 2 3 4 5}

Is theta burst stimulation safe for teenagers?

Theta burst stimulation (TBS) has been studied mostly in adults, but some research has looked at its safety in children and teenagers. While there are still knowledge gaps, studies suggest that TBS is generally safe, though some participants may experience mild side effects. ^{5 6 7 8 9}

How is the treatment Accelerated Intermittent Theta Burst Stimulation (SAINT®) unique for teenage depression?

Accelerated Intermittent Theta Burst Stimulation (SAINT®) is unique because it is a noninvasive brain stimulation technique that delivers multiple sessions of magnetic pulses to the brain in a short period, potentially offering faster and more efficient relief from depression symptoms compared to traditional treatments. ^{1 5 10 11 12}

What is the purpose of this trial?

This is a single-site open-label clinical trial of the Stanford Accelerated Intermittent Neuromodulation Therapy (SAINT®) protocol. The goal of this clinical trial is to learn if a new form of transcranial magnetic stimulation (TMS)-known generally as accelerated intermittent theta burst stimulation (aiTBS) and specifically as SAINT®-is effective as a first-line therapy in treating adolescents aged 14-19 years-old in their first episode of depression who have not undergone a full course of depression treatment prior to starting the trial and who remain antidepressant-free throughout the trial. The main questions this trial aims to answer are: * Does SAINT® relieve symptoms of depression as a first-line therapy in adolescents? * Is SAINT® a feasible option as a first-line treatment for adolescent depression? Researchers will measure the depression symptoms in adolescent participants before and after SAINT®. Parents of the adolescent participant will also participate in the study providing information about their experience and preference for TMS as a first-line treatment. Adolescent participants will: * Remain antidepressant-free throughout the study period of 6-7 weeks. * Receive an MRI of their head for precision targeting * Receive 5 days of aiTBS (SAINT®)

Research Team

Sean J O'Sullivan, M.D., Ph. D.

Principal Investigator

University of Texas at Austin

Eligibility Criteria

This trial is for teens aged 14-19 with their first major depressive episode, who haven't had a full depression treatment before and can stay off antidepressants. They must be in good health, agree to lifestyle rules during the study, and have ongoing psychiatric care.

Inclusion Criteria

I am between 14 and 19 years old.

I can read and understand English well enough to follow study instructions and communicate with the study team.

I am generally healthy aside from my current condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 5 days of aiTBS (SAINT®) with either 5 or 10 daily sessions

1 week

5 visits (in-person)

Follow-up

Participants are monitored for changes in depressive symptoms at baseline and two follow-up visits

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• Accelerated Intermittent Theta Burst Stimulation (SAINT®)

Trial Overview The trial tests SAINT®, an accelerated form of TMS therapy called aiTBS, as a potential first-line treatment for adolescent depression. Over 5 days, participants receive targeted brain stimulation and are monitored for changes in depression symptoms.

Participant Groups

Group I: Truncated SAINT® Experimental Treatment 1 Intervention

5 daily sessions (25 total over 5-days) of SAINT® stimulation (3-pulse 50-Hz bursts at 5-Hz for 2-second trains, with trains every 10 seconds), delivered with 50-minute inter-session intervals (10-minute sessions, 50-minutes in between sessions). Stimulation will be delivered at 90% of the resting motor threshold (with depth correction to account for the distance between the scalp and cortex).

Group II: Standard SAINT® Active Control 1 Intervention

10 daily sessions (50 total over 5-days) of SAINT® stimulation (3-pulse 50-Hz bursts at 5-Hz for 2-second trains, with trains every 10 seconds), delivered with 50-minute inter-session intervals (10-minute sessions, 50-minutes in between sessions). Stimulation will be delivered at 90% of the resting motor threshold (with depth correction to account for the distance between the scalp and cortex).

Who Is Running the Clinical Trial?

University of Texas at Austin

Lead Sponsor

Trials

387

Recruited

86,100+

Magnus Medical

Industry Sponsor

Trials

5

Recruited

1,100+

Findings from Research

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]

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) shows significant efficacy in reducing depression symptoms, with a large effect size (Hedges' g = 1.0) based on a meta-analysis of 5 randomized controlled trials involving 221 subjects.

Active TBS resulted in higher response rates compared to sham TBS (35.6% vs. 17.5%), although there was no significant difference in remission rates, indicating that while TBS is promising, further research is needed to optimize treatment parameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of theta burst stimulation (TBS) for major depression: An exploratory meta-analysis of randomized and sham-controlled trials. Berlim, MT., McGirr, A., Rodrigues Dos Santos, N., et al.[2018]

In a randomized controlled trial involving 56 patients with moderate to severe depression, bilateral theta-burst stimulation (TBS) and repetitive transcranial magnetic stimulation (rTMS) did not show significant improvements in depression scores compared to sham treatment.

However, there was a noted tendency for both active treatments to increase the responder rate, particularly for the TBS group, suggesting that further research may be needed to explore its potential benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bilateral prefrontal rTMS and theta burst TMS as an add-on treatment for depression: a randomized placebo controlled trial. Prasser, J., Schecklmann, M., Poeppl, TB., et al.[2015]

Continuous theta burst stimulation (cTBS) was found to be safe and well-tolerated in patients with major depressive disorder (MDD) or bipolar depression (BD), with no significant differences in adverse events compared to sham treatment.

However, the meta-analysis of three randomized controlled trials involving 78 participants showed no significant improvement in depression scores or response rates with cTBS compared to sham, indicating that cTBS may not provide a therapeutic advantage for treating major depressive episodes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjunctive continuous theta burst stimulation for major depressive disorder or bipolar depression: A meta-analysis of randomized controlled studies. Cai, DB., Qin, XD., Qin, ZJ., et al.[2023]

Theta burst stimulation (TBS) appears to be safe and tolerable for children and adolescents, with reported adverse events mostly being mild, such as headaches, similar to those seen in adults.

Despite the promising safety profile, there is a lack of long-term studies on TBS in younger populations, highlighting the need for further research to better understand its effects and potential risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review of the Safety and Tolerability of Theta Burst Stimulation in Children and Adolescents. Elmaghraby, R., Sun, Q., Ozger, C., et al.[2023]

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]

Theta-burst stimulation (TBS) was found to be safe for children, with no serious adverse events reported among 40 participants aged under 18, including those with Tourette syndrome and typically developing children.

Only 11.6% of participants experienced mild, self-limited side effects, such as finger twitching and headaches, indicating that TBS is well tolerated in this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of theta-burst transcranial magnetic stimulation in children. Wu, SW., Shahana, N., Huddleston, DA., et al.[2012]

Theta burst stimulation (TBS) is as effective and safe as standard repetitive transcranial magnetic stimulation (rTMS) for treating depression, based on a meta-analysis of nine randomized controlled trials involving 1124 patients.

The study found no significant differences in response rates or adverse events between TBS and rTMS, suggesting that TBS could be a viable alternative due to its shorter treatment sessions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Theta Burst vs Repetitive Transcranial Magnetic Stimulation for the Treatment of Depression: A Meta-Analysis of Randomized Controlled Trials. Liu, C., Li, L., Li, B., 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 involving 50 patients with treatment-resistant depression (TRD), accelerated intermittent theta burst stimulation (aiTBS) significantly reduced depression symptoms over time, indicating its potential efficacy as a noninvasive treatment option.

The treatment was associated with changes in brain network organization, specifically a reduction in modularity of structural networks, suggesting that aiTBS may promote beneficial neuroplasticity effects in the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated intermittent theta burst stimulation in major depression induces decreases in modularity: A connectome analysis. Caeyenberghs, K., Duprat, R., Leemans, A., 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]

References

1. 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]

2. Netherlands pubmed.ncbi.nlm.nih.gov

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

3. England pubmed.ncbi.nlm.nih.gov

Efficacy of theta burst stimulation (TBS) for major depression: An exploratory meta-analysis of randomized and sham-controlled trials. [2018]

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

Bilateral prefrontal rTMS and theta burst TMS as an add-on treatment for depression: a randomized placebo controlled trial. [2015]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Adjunctive continuous theta burst stimulation for major depressive disorder or bipolar depression: A meta-analysis of randomized controlled studies. [2023]

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

A Systematic Review of the Safety and Tolerability of Theta Burst Stimulation in Children and Adolescents. [2023]

7. Ireland pubmed.ncbi.nlm.nih.gov

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

8. England pubmed.ncbi.nlm.nih.gov

Safety and tolerability of theta-burst transcranial magnetic stimulation in children. [2012]

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

Efficacy and Safety of Theta Burst vs Repetitive Transcranial Magnetic Stimulation for the Treatment of Depression: A Meta-Analysis of Randomized Controlled Trials. [2023]

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

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

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

Accelerated intermittent theta burst stimulation in major depression induces decreases in modularity: A connectome analysis. [2023]

12. 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]