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

Trial Summary

What is the purpose of this trial?

This study will assess clinical and behavioral measures along with electroencephalogram (EEG), event-related potentials (ERPS), and eye-tracking (ET) prior to and following a single intermittent Theta Burst Stimulation (iTBS) session to provide preliminary insight into the potential of TMS as an intervention for depression in individuals with Autism Spectrum Disorder (ASD).

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 data supports the effectiveness of the treatment Transcranial Magnetic Stimulation (TMS) for depression in individuals with Autism Spectrum Disorder?

Research shows that repetitive transcranial magnetic stimulation (rTMS) can improve depression symptoms in adults with both autism and major depressive disorder, with 40% of participants achieving remission in one study. Additionally, some studies suggest potential benefits for core autism symptoms, although more research is needed to confirm these effects. ^{1 2 3 4 5}

Is TMS safe for treating depression in individuals with autism?

Research suggests that TMS, including rTMS and iTBS, is generally well tolerated and safe for individuals with autism and depression, with mild side effects reported in studies. ^{1 2 3 6 7}

How is TMS treatment different for depression in autism spectrum disorder?

Transcranial Magnetic Stimulation (TMS) is a unique treatment for depression in autism spectrum disorder because it is a non-invasive brain stimulation technique that uses magnetic fields to stimulate nerve cells in the brain, unlike traditional drug therapies. It has shown promise in improving depressive symptoms and possibly core autism symptoms, offering an alternative for those who may not respond well to medication. ^{1 2 4 5 6}

Research Team

Sherab Tsheringla, MD

Principal Investigator

Yale University

Eligibility Criteria

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 are able and willing to take part in an EEG and eye-tracking test.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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]

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]

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 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]

References

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

Treatment of Adults with Autism and Major Depressive Disorder Using Transcranial Magnetic Stimulation: An Open Label Pilot Study. [2023]

2. Switzerland 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. [2023]

3. United States 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. [2022]

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

Repetitive transcranial magnetic stimulation (rTMS) improves movement-related cortical potentials in autism spectrum disorders. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation for Treatment of Autism Spectrum Disorder: A Systematic Review and Meta-Analysis. [2020]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Prevalence of Adverse Effects Associated With Transcranial Magnetic Stimulation for Autism Spectrum Disorder: A Systematic Review and Meta-Analysis. [2022]

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

A double-blind, randomized trial of deep repetitive transcranial magnetic stimulation (rTMS) for autism spectrum disorder. [2018]