TMS for Depression in Autism Spectrum Disorder

Overseen By Sherab Tsheringla, MD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Yale University

Must not be taking: Cognitive drugs, Seizure drugs

Disqualifiers: Psychotic, Bipolar, Epilepsy, Substance abuse, others

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

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

Compensation: Varies

Number of Visits: 3

Duration: 1 week

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether Transcranial Magnetic Stimulation (TMS), a non-invasive treatment using magnetic fields to stimulate nerve cells, can reduce depression symptoms in people with Autism Spectrum Disorder (ASD). Participants will undergo tests such as EEG (to measure brain activity) and eye-tracking before and after a TMS session. The trial includes different groups: those with ASD with or without depression, and those without ASD but with depression. It seeks participants with ASD or depression who have been stable on any medication for at least two weeks and are willing to participate in EEG and eye-tracking tests. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could improve mental health treatments for ASD and depression.

Will I have to stop taking my current medications?

The trial requires that participants either be unmedicated or on a stable medication treatment for at least two weeks. If you are taking medications that affect cognitive processes or increase seizure risk, you may need to stop those.

What prior data suggests that Transcranial Magnetic Stimulation (TMS) is safe for individuals with Autism Spectrum Disorder and depression?

Research has shown that Transcranial Magnetic Stimulation (TMS) is generally well-tolerated by patients, including those with autism spectrum disorder (ASD). One study found that TMS helped reduce symptoms in people with ASD, and any side effects were mild. These side effects might include headaches or scalp discomfort, but they usually don't last long.

Other studies suggest that TMS can effectively reduce symptoms of depression, even in people with ASD. However, while TMS appears promising, there isn't enough evidence yet to fully support its widespread use for ASD. Researchers continue to test the treatment to understand its full potential and safety.

In summary, TMS seems safe for many people, with mild and manageable side effects. Individuals should discuss any concerns with their healthcare provider before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using Transcranial Magnetic Stimulation (TMS) for depression in individuals with Autism Spectrum Disorder (ASD) because it offers a non-invasive approach that targets brain activity directly. Unlike traditional medications, which often take weeks to show results and can have side effects, TMS potentially delivers faster relief by using magnetic fields to stimulate nerve cells in the brain. This technique could be a game-changer for people with ASD who also suffer from depression, as it might offer a quicker and safer alternative to current treatments like antidepressants and psychotherapy.

What evidence suggests that this trial's treatments could be effective for depression in Autism Spectrum Disorder?

Earlier studies have shown that Transcranial Magnetic Stimulation (TMS) holds promise for treating autism spectrum disorder (ASD) by reducing both primary and related symptoms. Research indicates that TMS is a quick and noninvasive method that might help manage depression symptoms in individuals with ASD. This trial will explore different sequences of TMS, including theta burst stimulation (iTBS), to assess its effectiveness. Some participants will receive iTBS followed by sham treatment, while others will receive sham treatment followed by iTBS. These findings suggest that TMS could effectively help with depression in those with ASD, although more research is needed to confirm these effects. ^{1 4 6 7 8}

Who Is on the Research Team?

Sherab Tsheringla, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for individuals aged 18-40 with autism spectrum disorder, including those diagnosed with autistic disorder, PDD NOS, or Asperger syndrome. Participants may have depression (with a score of at least 20 on the HDRS-17) and must be either unmedicated or on stable medication for two weeks. They should be able to undergo EEG and eye-tracking procedures and provide informed consent.

Inclusion Criteria

I have not changed my medications in the last two weeks.

If your depression score is 20 or higher on the HDRS-17 test, you will not be able to participate.

You have given your permission by signing and dating a form that explains the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Baseline Assessment

Baseline assessment of neuropsychological, cognitive, and behavioral function, along with EEG and eye-tracking

1 week

1 visit (in-person)

Treatment

Participants receive a single iTBS session or sham stimulation, with EEG and eye-tracking assessments pre-and-post stimulation

1 week

1 visit (in-person)

Crossover Treatment

Participants crossover to receive the alternate treatment (iTBS or sham) with EEG and eye-tracking assessments pre-and-post stimulation

1 week

1 visit (in-person)

Follow-up

Participants are monitored for changes in EEG, eye-tracking, and behavioral measures

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Transcranial Magnetic Stimulation (TMS)

Trial Overview The study is testing the effects of a single session using the MAGSTIM Rapid2 TMS system, specifically intermittent Theta Burst Stimulation (iTBS), to see if it can help alleviate symptoms of depression in people with Autism Spectrum Disorder. It includes assessments like clinical measures, EEGs, event-related potentials (ERPs), and eye-tracking both before and after treatment.

How Is the Trial Designed?

Group I: TD without depression, iTBS then Sham Experimental Treatment 1 Intervention

Participants that are TD without depression will undergo EEG and ET with TMS prior to and following a single iTBS session. Participants first received iTBS then sham approximately one week apart.

Group II: TD without depression, Sham then iTBS Experimental Treatment 1 Intervention

Participants that are TD without depression will undergo EEG and ET with TMS prior to and following a single iTBS session. Participants first received sham then iTBS approximately one week apart.

Group III: TD with depression, iTBS then Sham Experimental Treatment 1 Intervention

Participants that are TD with depression will undergo EEG and ET with TMS prior to and following a single iTBS session. Participants first received iTBS then sham approximately one week apart.

Group IV: TD with depression, Sham then iTBS Experimental Treatment 1 Intervention

Participants that are TD with depression will undergo EEG and ET with TMS prior to and following a single iTBS session. Participants first received sham then iTBS approximately one week apart.

Group V: ASD without depression, iTBS then Sham Experimental Treatment 1 Intervention

Participants having ASD without depression will undergo EEG and ET with TMS prior to and following a single iTBS session. Participants first received iTBS then sham approximately one week apart.

Group VI: ASD without depression, Sham then iTBS Experimental Treatment 1 Intervention

Participants having ASD without depression will undergo EEG and ET with TMS prior to and following a single iTBS session.Participants first received sham then iTBS approximately one week apart.

Group VII: ASD with depression, iTBS then Sham Experimental Treatment 1 Intervention

Participants having ASD with depression will undergo EEG and ET with TMS prior to and following a single iTBS session. Participants first received iTBS then sham approximately one week apart.

Group VIII: ASD with depression, Sham then iTBS Experimental Treatment 1 Intervention

Participants having ASD with depression will undergo EEG and ET with TMS prior to and following a single iTBS session.Participants first received sham then iTBS approximately one week apart.

Transcranial Magnetic Stimulation (TMS) is already approved in United States, European Union for the following indications:

Approved in United States as Transcranial Magnetic Stimulation (TMS) for:

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

Approved in European Union as Transcranial Magnetic Stimulation (TMS) for:

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

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

American Academy of Child Adolescent Psychiatry.

Collaborator

Trials

14

Recruited

1,000+

Published Research Related to This Trial

Transcranial magnetic stimulation (TMS) has a reported overall adverse effect (AE) prevalence of 25% in individuals with autism spectrum disorder (ASD), with most AEs being mild and transient, such as headache (10%) and irritability (21%).

No specific risk factors related to ASD were identified that influenced the prevalence of AEs from TMS, suggesting that TMS may be a safe therapeutic option for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of Adverse Effects Associated With Transcranial Magnetic Stimulation for Autism Spectrum Disorder: A Systematic Review and Meta-Analysis. Huashuang, Z., Yang, L., Chensheng, H., et al.[2022]

In a study involving 13 adults with autism spectrum disorder (ASD) and major depressive disorder (MDD), repetitive transcranial magnetic stimulation (rTMS) was found to be well tolerated, with mild side effects reported.

Participants experienced a significant reduction in depressive symptoms, with an average improvement of 13.5 points on the Hamilton rating scale for depression, and 40% achieved remission, suggesting rTMS may be an effective treatment for depression in individuals with ASD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Adults with Autism and Major Depressive Disorder Using Transcranial Magnetic Stimulation: An Open Label Pilot Study. Gwynette, MF., Lowe, DW., Henneberry, EA., et al.[2023]

In a pilot study involving 13 adults with autism spectrum disorder (ASD), intermittent theta burst stimulation (iTBS) applied over the bilateral posterior superior temporal sulcus (pSTS) showed significant immediate improvements in parent-rated autistic symptoms after 5 days of treatment.

The effectiveness of iTBS on cognitive flexibility and clinical symptoms was influenced by individual factors such as baseline social-communicative impairment, cognitive performance, and concurrent psychotropic medication use, highlighting the need for personalized approaches in future trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

5-day multi-session intermittent theta burst stimulation over bilateral posterior superior temporal sulci in adults with autism-a pilot study. Ni, HC., Lin, HY., Chen, YL., et al.[2022]

In a study involving 28 adults with autism spectrum disorder, deep repetitive transcranial magnetic stimulation (rTMS) targeting the dorsomedial prefrontal cortex showed a significant reduction in social relating symptoms compared to a sham treatment.

Participants receiving active rTMS also experienced decreased anxiety in social situations, suggesting that this technique may improve both social functioning and emotional responses in individuals with ASD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, randomized trial of deep repetitive transcranial magnetic stimulation (rTMS) for autism spectrum disorder. Enticott, PG., Fitzgibbon, BM., Kennedy, HA., et al.[2018]

A systematic review of 23 studies on repetitive Transcranial Magnetic Stimulation (rTMS) for Autism Spectrum Disorder (ASD) showed a moderate effect in improving repetitive behaviors, social behavior, and executive function tasks, but results should be interpreted cautiously due to potential biases in the studies.

Only a few studies indicated that the benefits of rTMS could last for up to 6 months, highlighting the need for more rigorous, controlled trials to better understand the treatment's efficacy and optimal parameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation for Treatment of Autism Spectrum Disorder: A Systematic Review and Meta-Analysis. Barahona-Corrêa, JB., Velosa, A., Chainho, A., et al.[2020]

A retrospective analysis of 18 individuals with autism spectrum disorder (ASD) who did not respond to traditional depression treatments showed that intermittent theta burst stimulation (iTBS) therapy may help alleviate depressive symptoms.

While the results are promising, they are based on a small case series, highlighting the need for larger, randomized trials to confirm the efficacy of TMS therapies for treating depression in individuals with ASD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Case Series of Intermittent Theta Burst Stimulation Treatment for Depressive Symptoms in Individuals with Autistic Spectrum Disorder: Real World TMS Study in the Tokyo Metropolitan Area. Noda, Y., Fujii, K., Mimura, Y., et al.[2023]

In a study involving 11 participants with autism spectrum disorders (ASD), repetitive transcranial magnetic stimulation (rTMS) was found to enhance movement-related cortical potentials (MRCPs), indicating improved motor function.

Specifically, rTMS applied to the supplementary motor area (SMA) increased early MRCP components, while stimulation of the left primary motor cortex (M1) affected later components, suggesting that rTMS may influence cortical inhibitory processes to enhance motor activity in individuals with ASD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation (rTMS) improves movement-related cortical potentials in autism spectrum disorders. Enticott, PG., Rinehart, NJ., Tonge, BJ., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8264904/

Repetitive transcranial magnetic stimulation (rTMS) in autism ... This multisite randomised controlled trial will be the largest trial of repetitive transcranial magnetic stimulation (rTMS) in autism spectrum ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2405844024082823

A systematic review of transcranial magnetic stimulation ... Transcranial magnetic stimulation (TMS) is a promising and emerging tool for the intervention of ASD by reducing both core and associate symptoms.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4956084/

Transcranial magnetic stimulation in autism spectrum disorder TMS is a promising, emerging tool for the study and potential treatment of ASD. Recent studies suggest that TMS measures provide rapid and noninvasive ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05271357?tab=table

Transcranial Magnetic Stimulation for Depression in Autism ... The overarching goal of this study is to examine treatment effects and elucidate the physiological biomarkers of a newer form of non-invasive brain stimulation ...

5. link.springer.com link.springer.com/article/10.1007/s10803-024-06244-2

Accelerated Theta Burst Transcranial Magnetic Stimulation ... We studied the use of accelerated theta burst stimulation (ATBS) for the treatment of refractory MDD in ASD (3 treatments daily x 10 days).

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4519010/

Use of Transcranial Magnetic Stimulation in Autism Spectrum ... Though preliminary data suggests promise, there is simply not enough evidence yet to conclusively support the clinical widespread use of TMS in ASD, neither ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06670040

Theta Burst Stimulation for Refractory Depression in Autism ... The overall goal of this study is to treat major depressive disorder (MDD) rapidly and effectively in individuals with autism spectrum disorder (ASD).

8. aetna.com aetna.com/cpb/medical/data/400_499/0469.html

Transcranial Magnetic Stimulation and Cranial Electrical ... The member had previously had at least a 50% reduction in depressive symptoms with TMS, as documented by standardized rating scales that reliably measure ...