JAMA Netw Open

Memantine improves social function in some youths with autism

October 3, 2025

This trial provides the first controlled evidence that memantine can improve social functioning in youths with autism spectrum disorder (ASD) without intellectual disability, with a robust number needed to treat of 3 and favorable safety profile. Elevated glutamate levels in the pregenual anterior cingulate cortex (pgACC) may predict response, suggesting a potential biomarker for future stratified treatment.

Study details: This 12-week, double-blind, parallel-design randomized trial (NCT01972074) enrolled youths aged 8 to 17 years with moderately severe ASD (without intellectual disability), meeting DSM-5 criteria and SRS-2 total raw score ≥85. Participants were randomized 1:1 to memantine (titrated to a maximum of 20 mg/day) or placebo. Primary outcome was treatment response rate, with secondary measures including changes in social responsiveness and adverse events.

Results: In the intention-to-treat analysis (n = 35), 56% of memantine-treated participants met response criteria vs. 21% with placebo (odds ratio [OR], 4.8; P = 0.03). Elevated pgACC glutamate (≥1 SD above healthy controls) was present in 54% of ASD participants and strongly predicted response: 80% responded to memantine vs. 20% with placebo (OR, 16.0; P = 0.007). Memantine was well tolerated.

Source:

Joshi G, et al. (2025, October 1). JAMA Netw Open. Memantine to Treat Social Impairment in Youths With Autism Spectrum Disorder: A Randomized Clinical Trial. https://pubmed.ncbi.nlm.nih.gov/41032298/