06 Oct Brain Imaging Identifies Subset of Autism Patients Who May Benefit from Alzheimer’s Medication

Memantine to Treat Social Impairment in Youths With ASD

MedicalResearch.com Interview with:

Dr. Joshi

Gagan Joshi, MD
Director, The Alan & Lorraine Bressler Clinical and Research Program for Autism Spectrum Disorder
Associate Director, The Pediatric Psychopharmacology Research Program
Associate Program Director, MGH Fellowship in Autism Spectrum Disorder
Rovee Endowed Chair in Child Psychiatry
Massachusetts General Hospital
Associate Professor of Psychiatry
Harvard Medical School

MedicalResearch.com: What is the background for this study?

Response: Intellectually capable individuals with autism often face significant challenges in social functioning, yet pharmacologic treatments specifically targeting social impairments are lacking. Our prior neuroimaging research identified abnormally elevated brain glutamate levels in intellectually capable youth with autism, suggesting a potential neurochemical pathway underlying social difficulties. Based on these findings, we examined the effects of memantine—a glutamate-modulating medication—for the treatment of autism.

MedicalResearch.com: What are the main findings?

Response:  Twelve-week treatment with memantine was well tolerated in youth with autism without intellectual disability and demonstrated efficacy in improving autism-related social impairments. Improvements in social behaviors were particularly notable among participants with abnormally elevated brain glutamate levels.

These findings indicate that memantine is both safe and effective in addressing core social challenges in intellectually capable youth with autism. Importantly, they also identify brain glutamate levels as a potential biomarker of memantine treatment response in autism.

MedicalResearch.com: What other conditions is Memantine used for?

Response: Glutamate, the brain’s primary excitatory neurotransmitter, plays a key role in neuronal development and synaptic plasticity through its activity at N-methyl-D-aspartate (NMDA) receptors. Memantine hydrochloride is a glutamatergic agent with a unique mechanism of action as a moderate-affinity, noncompetitive NMDA receptor antagonist.

Memantine is FDA-approved for the treatment of moderate to severe Alzheimer’s disease, where its safety and tolerability have been well established. 

MedicalResearch.com: What should readers take away from your report?

Response: This is the first neuroimaging-guided controlled study to demonstrate improvement in core social deficits with memantine in intellectually capable youth with autism—particularly in those with elevated brain glutamate activity. These results underscore the promise of neural biomarker–guided approaches in autism and the potential for precision pharmacologic treatment.

The improvement in social behaviors was specific to autism youth without intellectual disability and those with elevated brain glutamate activity. In contrast, earlier controlled trial that failed to demonstrate efficacy was conducted primarily in children with intellectual disability and did not account for differences in brain glutamate levels.

Memantine was well tolerated, with most participants reaching the maximum trial dose of 20 mg per day. Adverse events were transient and mild to moderate in severity, most commonly including headache, insomnia, and increased appetite.

MedicalResearch.com: What recommendations do you have for future research as a results of this study?

Response: Future studies should examine whether brain glutamate levels can serve as a reliable biomarker of memantine treatment response in youth with autism without intellectual disability, as well as in autism populations with co-occurring intellectual disability.

MedicalResearch.com: Is there anything else you would like to add?

Response: This study has identified a distinct subtype of autism in intellectually capable youth characterized by elevated brain glutamate levels and associated with treatment response to memantine. These findings advance the field toward biomarker-based, personalized treatment approaches in autism.

Disclosures: Dr. Joshi reports receiving support from the National Institute of Mental Health (NIMH) of the National Institutes of Health (NIH) under Award Number K23MH100450; research support from the Demarest Lloyd, Jr. Foundation as a primary investigator for investigator-initiated studies and Genentech and F. Hoffmann-La Roche Ltd. as a site PI for multi-site trials; speaker’s honorariums from the American Academy of Child and Adolescent Psychiatry, American Physician Institute, Asian College of Neuro-psychopharmacology, Hackensack Meridian Health, University of Colorado-Colorado Springs, Kennedy Krieger Institute, New York University, and Neuroimmune Institute; unpaid consultant for EuMentis Therapeutics; royalties from a licensed method for treating autism spectrum disorder through Mass General Brigham Innovation.reports receiving support from the National Institute of Mental Health (NIMH) of the National Institutes of Health (NIH) under Award Number K23MH100450; research support from the Demarest Lloyd, Jr. Foundation as a primary investigator for investigator-initiated studies and Genentech and F. Hoffmann-La Roche Ltd. as a site PI for multi-site trials; speaker’s honorariums from the American Academy of Child and Adolescent Psychiatry, American Physician Institute, Asian College of Neuro-psychopharmacology, Hackensack Meridian Health, University of Colorado-Colorado Springs, Kennedy Krieger Institute, New York University, and Neuroimmune Institute; unpaid consultant for EuMentis Therapeutics; royalties from a licensed method for treating autism spectrum disorder through Mass General Brigham Innovation.

Citation:

Joshi G, Gönenc A, DiSalvo M, et al. Memantine to Treat Social Impairment in Youths With Autism Spectrum Disorder: A Randomized Clinical Trial. JAMA Netw Open. 2025;8(10):e2534927. doi:10.1001/jamanetworkopen.2025.34927
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2839518

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Last Updated on October 6, 2025 by Marie Benz MD FAAD