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rTMS Investigated in Autism Spectrum Disorder

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Key clinical point: rTMS, a brain stimulation technology, might help improve executive function in older teens and young adults with autism spectrum disorder.

Major finding: rTMS can be successfully studied in autistic patients; MRI data suggest that executive function in autism might be associated with white matter patterns known to affect executive function in other disorders.

Data source: A double-blind clinical trial randomizing 18 patients with ASD to rTMS or sham treatment for 20 sessions over 4 weeks.

Disclosures: Two coauthors disclosed industry funding.


 

AT THE AACAP ANNUAL MEETING

References

SAN ANTONIO Results from a pilot randomized double-blind trial suggest that repetitive transcranial stimulation, or rTMS, a technology currently approved to treat depression that is being investigated in a range of psychiatric disorders, might be a viable treatment strategy to improve executive function in young people with autism spectrum disorder (ASD).

The findings were presented by Dr. Stephanie Ameis of the Campbell Family Mental Health Research Institute in Toronto at the annual meeting American Academy of Child and Adolescent Psychiatry.

Impairments in executive function are common among higher functioning people with ASD. Previous studies have found executive function impairments to have common neurobiologic underpinnings. No studies to date have investigated rTMS on executive function in autism, but previous research by Dr. Ameis’s colleague and coauthor on the study, Dr. Z. Jeff Daskalakis, found that a course of rTMS significantly improved executive function among people with schizophrenia (Biol Psychiatry. 2013;73[6]:510-7).

Dr. Ameis and her colleagues hypothesized that a similar treatment approach might be feasible in people with ASD with known executive function impairment.

The researchers randomized 18 patients aged 16-35 years to 4 weeks of rTMS (20Hz) to the dorsolateral prefrontal cortex or sham treatment. All subjects were clinically stable, with an IQ greater than 70 (mean 95) and a qualifying measure of disability on the BRIEF (Behavior Rating Inventory of Executive Functions) assessment tool used to measure real-world impairment.

MRI and cognitive assessment were performed at baseline and 1 month after the treatment period ended. Baseline analysis of diffusion MRI indicated a trend toward a significant positive association between working memory scores on the BRIEF and white matter structures along the anterior thalamic radiation. Though white matter integrity in this part of the brain has been linked to executive function in other disorders, Dr. Ameis cautioned that the MRI findings in her study were preliminary and that it was too early to draw conclusions from them.

Mean age in the study was 23 years. Dr. Ameis said she hopes to continue to recruit a younger cohort, but that recruitment challenges led the group to expand an initial targeted age range of 16-25 years up to 35 years.

“We want to focus our intervention on the transition period to adulthood, as this is a time where effective interventions can really make an impact on individuals’ successful transition to work and school as young adults.”

The goal, Dr. Ameis said, “is to see if rTMS is feasible for this particular indication or treatment target, and so it’s the first study that’s really used a rigorous sham study design for this indication. We’re seeing whether people are interested and able to tolerate the 4-week protocol, as well as the other aspects of our study and secondarily, whether we are changing things with regard to [executive function].”

The protocol was well tolerated, the researchers found, with the time commitment – about 30 minutes a day, 5 days a week – being the biggest demand on subjects. rTMS was associated with no adverse effects except headaches around treatment times.

The pilot study established tolerability and feasibility in this patient group, Dr. Ameis said. Now the investigators will measure differences in executive function after a second year of recruitment to double the current sample size.

Dr. Ameis reported no conflicts of interest related to the findings. A coauthor on the study, Dr. Paul E. Croarkin, reported funding from Pfizer, and study supplies and genotyping from Assurex. Dr. Daskalakis acknowledged funding from Neuronetics.

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