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NMDA Receptor Antagonists in Pediatric Autism Spectrum Disorder: A Systematic Review

Nihit Gupta1, Noah Parker1,2, Azl Saeed3

  • 1Wright State University, Dayton, Ohio.

The Primary Care Companion for CNS Disorders
|July 14, 2026
PubMed

Insights

Memantine and amantadine show promise for autism spectrum disorder (ASD) but lack conclusive efficacy data. Further large-scale trials are needed to establish their therapeutic potential and usage guidelines in children with ASD.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Developmental Pediatrics

Background:

  • Autism Spectrum Disorder (ASD) presents complex challenges in core symptoms and comorbidities.
  • NMDA receptor antagonists, such as memantine and amantadine, are being investigated for potential therapeutic benefits in ASD.
  • Existing evidence on their efficacy and safety in pediatric populations is limited and requires systematic evaluation.

Purpose of the Study:

  • To systematically review conclusive evidence on the usage, efficacy, and side effects of memantine and amantadine in children with ASD.
  • To determine the effectiveness of these NMDA receptor antagonists in treating core ASD symptoms and associated comorbid conditions.
  • To identify gaps in current research and guide future therapeutic strategies for ASD.

Main Methods:

  • A comprehensive literature search was performed across multiple electronic databases using specific keywords related to ASD and the studied medications.
  • Eleven studies were selected after initial screening, with eight meeting the inclusion criteria for qualitative synthesis and systematic review.
  • Inclusion criteria focused on pediatric ASD populations, placebo-controlled or treatment-as-usual comparisons, and reported clinical improvements; exclusion criteria involved unpublished data and redundant reports.

Main Results:

  • Memantine and amantadine exhibited favorable safety profiles in the reviewed studies.
  • Evidence for the efficacy of these agents in addressing core ASD symptoms was inconclusive.
  • Memantine suggested potential cognitive and behavioral benefits, while amantadine showed promise as an adjunctive therapy for disruptive behaviors, though with methodological limitations and outcome variability.

Conclusions:

  • Current evidence on the efficacy of memantine and amantadine for core ASD symptoms is inconclusive.
  • The safety profiles of both drugs are generally favorable, but robust efficacy data is lacking.
  • Large-scale, multicenter, double-blind, randomized controlled trials with standardized assessments are crucial to establish definitive therapeutic guidelines for memantine and amantadine in ASD.

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