Transcranial Magnetic Stimulation for Depression

Overseen By Daniel S Pine, M.D.

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: National Institute of Mental Health (NIMH)

Must not be taking: Seizure threshold reducers

Disqualifiers: Psychosis, Bipolar, Severe eating disorder, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore whether transcranial magnetic stimulation (TMS), combined with cognitive behavioral therapy (CBT), can effectively treat teens with major depressive disorder (MDD) who haven't found relief with other treatments. TMS uses magnetic pulses to influence brain activity and may offer a new option for those who haven't improved with standard medications and talk therapy. Adolescents aged 13 to 17 with ongoing MDD episodes who haven't responded to certain antidepressants and therapy may be eligible to participate. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to benefit from innovative therapies.

Do I have to stop taking my current medications for the trial?

Yes, participants will need to taper off their psychiatric medications for 2 to 6 weeks before starting TMS treatment. After the TMS sessions, they can begin taking their medications again.

What prior data suggests that transcranial magnetic stimulation is safe for treating depression in teens?

Research has shown that intermittent theta burst stimulation (iTBS), a type of transcranial magnetic stimulation (TMS), is generally safe and well-tolerated. Studies have found that iTBS is commonly used for treating depression and achieves success rates similar to other treatments. In everyday use, patients have also reported it to be safe.

During treatment, mild side effects might occur. These can include hearing a clicking sound or feeling a pulling sensation on the scalp where the device is placed. Some people also notice muscle twitching. These effects are usually temporary and subside after the session. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Intermittent Theta Burst Stimulation (iTBS) is unique because it offers a novel approach to treating depression by using a different pattern of magnetic pulses compared to standard repetitive transcranial magnetic stimulation (rTMS). While traditional antidepressants and therapies like SSRIs or cognitive-behavioral therapy can take weeks to show full effects, iTBS has the potential to produce quicker results, often with shorter session durations. Researchers are excited about iTBS because it targets specific brain areas more efficiently, potentially reducing side effects and treatment times while maintaining or improving effectiveness.

What evidence suggests that transcranial magnetic stimulation might be an effective treatment for depression in teens?

Research has shown that intermittent theta burst stimulation (iTBS), a type of transcranial magnetic stimulation (TMS), effectively treats depression. Studies have found iTBS to be safe, with success rates comparable to traditional TMS methods. In countries like Sweden, it is the most common TMS treatment for depression. A detailed review found iTBS to be quicker and possibly more effective than other TMS types. While TMS is approved for adults, these findings suggest it might also benefit teenagers with major depressive disorder who haven't improved with other treatments. ^{1 2 3 4 6}

Who Is on the Research Team?

Daniel S Pine, M.D.

Principal Investigator

National Institute of Mental Health (NIMH)

Are You a Good Fit for This Trial?

This trial is for teens aged 13-17 with Major Depressive Disorder (MDD) who haven't improved after trying at least two types of antidepressants and talk therapy. They must be in good health, able to follow the study plan, and under a psychiatrist's care. Teens can't join if they're pregnant, have metal implants near their head, are at high risk for seizures or have certain medical conditions.

Inclusion Criteria

The participant is currently enrolled in protocol 18-M-0037

Provision of signed and dated informed consent/assent form

Youths meet DSM 5TR criteria for Major Depressive Disorder (MDD) with a current ongoing episode

Exclusion Criteria

Electroconvulsive therapy has never worked for me.

I have previously undergone TMS therapy.

Pregnancy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Cognitive Behavioral Therapy (CBT)

Participants receive weekly CBT sessions and taper off psychiatric medications

2-6 weeks

Weekly visits (in-person)

Transcranial Magnetic Stimulation (TMS)

Participants receive daily TMS sessions for 2 weeks, with possible extension to 3 weeks

2-3 weeks

Daily visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, and resume medications

5 weeks

Weekly visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Intermittent Theta Burst Repetitive Transcranial Magnetic Stimulation (iTBS)

Trial Overview The trial tests whether Transcranial Magnetic Stimulation (TMS), combined with cognitive behavioral therapy (CBT), helps teens with treatment-resistant MDD. TMS uses magnetic pulses on the scalp to affect brain activity. Participants will receive multiple sessions over weeks while being monitored closely.

How Is the Trial Designed?

Group I: Active Experimental Treatment 1 Intervention

TMS

Intermittent Theta Burst Repetitive Transcranial Magnetic Stimulation (iTBS) is already approved in United States, European Union for the following indications:

Approved in United States as rTMS for:

• Major Depressive Disorder (MDD)
• Obsessive-Compulsive Disorder (OCD)
• Chronic Pain
• Migraine Headache Symptoms

Approved in United States as dTMS for:

• Obsessive-Compulsive Disorder (OCD)
• Major Depressive Disorder (MDD)

Approved in European Union as rTMS for:

• Major Depressive Disorder (MDD)
• Obsessive-Compulsive Disorder (OCD)

Who Is Running the Clinical Trial?

National Institute of Mental Health (NIMH)

Lead Sponsor

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

Intermittent theta burst stimulation (iTBS) is a cost-effective alternative to conventional 10Hz rTMS for treating depression, with an average treatment cost of $1,108 compared to $1,844 for 10Hz rTMS, resulting in savings of $735 per patient.

iTBS also shows a lower average cost per remission at $3,695, compared to $6,146 for 10Hz rTMS, leading to significant savings of $2,451 per remission, making it a more efficient treatment option in healthcare systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implementation of intermittent theta burst stimulation compared to conventional repetitive transcranial magnetic stimulation in patients with treatment resistant depression: A cost analysis. Mendlowitz, AB., Shanbour, A., Downar, J., et al.[2020]

In a study of 54 patients with major depression, the combination of intermittent theta burst stimulation (iTBS) and low-frequency rTMS (LF-rTMS) significantly improved depression and anxiety symptoms more than high-frequency rTMS (HF-rTMS).

The results suggest that iTBS combined with LF-rTMS may be a promising alternative therapy for major depression, offering both efficacy and time-saving benefits compared to traditional methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Left intermittent theta burst stimulation combined with right low-frequency rTMS as an additional treatment for major depression: A retrospective study. Mi, Y., Ji, Y., Lou, Z., 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]

A review of the FDA Adverse Event Reporting System from 2004 to 2008 identified 374 cases of drug-induced torsades de pointes (TdP), with significant signals for 17 antimicrobial drugs, including levofloxacin and fluconazole, indicating a notable risk of TdP associated with these medications.

The study highlighted additional drugs like ceftriaxone and metronidazole that showed TdP cases without co-medications, suggesting the need for further investigation into their safety profiles and the importance of monitoring QT interval prolongation as a surrogate marker for TdP risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antimicrobials and the risk of torsades de pointes: the contribution from data mining of the US FDA Adverse Event Reporting System. Poluzzi, E., Raschi, E., Motola, D., et al.[2018]

From 2004 to 2007, there were 1,665 reports of Torsades de Pointes (TdP) linked to 376 different drugs, with amiodarone and methadone being the most frequently reported, indicating their significant association with this serious heart condition.

The study highlights that large databases like the FDA Adverse Event Reporting System are crucial for identifying rare adverse drug reactions, and the unexpected reports for drugs like donepezil, famotidine, and mitoxantrone suggest a need for further investigation into their potential TdP risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug-induced torsades de pointes: data mining of the public version of the FDA Adverse Event Reporting System (AERS). Poluzzi, E., Raschi, E., Moretti, U., et al.[2018]

A review of 213 terms related to drug abuse potential revealed that most terms (80%) reflect treatment-emergent adverse events rather than behaviors that motivate drug abuse, highlighting the need for careful assessment during drug development.

Only 20% of the terms were considered to indicate a strong potential for reinforcing drug-seeking behavior, suggesting that many reported adverse events may not directly correlate with actual abuse risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Categorization of Abuse Potential-Related Adverse Events. Sellers, EM., Romach, MK.[2019]

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]

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]

A study analyzing over 9 million adverse event reports identified 3,807 cases of torsades de pointes (TdP), with the highest risk associated with drugs like tolazoline, levomethadyl, and ibutilide, indicating a significant safety concern for these medications.

Notably, around half of the top drugs linked to TdP were not included in the established QT drug lists, suggesting that clinicians should be vigilant about these medications and that further research is necessary to understand their potential risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug-induced torsades de pointes: Disproportionality analysis of the United States Food and Drug Administration adverse event reporting system. Wu, Z., Zhou, P., He, N., et al.[2022]

The study confirmed that the telemetry model effectively identified all six compounds known to cause torsades de pointes (TdP) in humans, demonstrating its efficacy in predicting cardiac safety.

Using a repeated measures analysis, the method showed high statistical power to detect small increments in QT intervals, indicating its reliability for assessing drug safety in preclinical studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ILSI-HESI cardiovascular safety subcommittee dataset: an analysis of the statistical properties of QT interval and rate-corrected QT interval (QTc). Chiang, AY., Bass, AS., Cooper, MM., et al.[2013]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36841303/

Outcome of transcranial magnetic intermittent theta-burst ... In a clinical setting, iTBS was shown to be safe and tolerable and the response rate was similar to that reported from clinical trials.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0165032723002604

Outcome of transcranial magnetic intermittent theta-burst ... iTBS is the most utilized rTMS protocol for depression in Sweden. Real-life response rates of iTBS are similar to clinical trials.

3. nature.com nature.com/articles/s41591-023-02764-z

Connectivity-guided intermittent theta burst versus ... - Nature MRI-neuronavigated cgiTBS and rTMS were equally effective in patients with treatment-resistant depression over 26 weeks.

4. 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- ...

5. 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 ...

6. 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 ...