Evaluation of memantine's efficacy and safety in the treatment of children with autism spectrum disorder: A systematic review and meta‐analysis

Abstract

Background:The United States Food and Drug Administration has approved drugs that address only autism-related symptoms rather than the underlying impairments.N-Methyl-D-Aspartate receptor antagonists have recently emerged as a promising treatment option for a variety of neurologic and developmental problems, including autism. Aims:To review (systematically), for the first time, the medical literature that explores the safety in and efficacy of memantine in autism. Methods and procedures:A comprehensive electronic search for relevant randomized controlled trials was conducted in four databases. Using RevMan software, we extracted and pooled data as a risk ratio (RR) or normalized mean differences in an inverse variance strategy.Results: This systematic review and meta-analysis includes five trials. There was no difference in enhancing social responsiveness when compared to placebo, though memantine lowered the likelihood of anxiety (RR = 0.25; 95% Confidence interval: [0.07; 0.87], p = 0.03). However, memantine aggravated impulsive behaviors.Additionally, in another trial that compared memantine added to risperidone versus risperidone added to placebo, memantine was found to be effective and safe. Conclusion:Memantine showed safety in reducing acute symptoms of anxiety and other symptoms encountered in pediatric patients with autism spectrum disorders. However, memantine does not improve the core symptoms of autism. Nevertheless, further long-term trials are needed to explore its potential efficacy.

NMDA Receptors in Health and Disease

“…One approach is to inhibit the release of glutamate, as seen with the drug riluzole. Another strategy is to decrease glutamate signaling through the use of NMDAR antagonists, such as acamprosate (which also antagonizes mGluR5 and GABAB) and memantine [60,61]. While some studies have shown promising results for glutamate therapy in improving ASD symptoms and cognitive function, more research is needed to establish its safety and efficacy.…”

Possible role of NO/NMDA pathway in the autistic-like behaviors induced by maternal separation stress in mice

“…In this regard, Won et al, have shown that enhancing NMDA-R function can improve autistic-like behavior in genetically mutated mice (Shank2-mutant) [ 83 ]. On the contrary, some evidence demonstrated that elevated NMDAR function is also involved in ASDs and administration of NMDA-R antagonists improved ASD-related symptoms [ 20 , 21 ]. Several previous studies have shown that MS increased the gene expression of NMDA-R subunits (NR2A and NR2B) in the brain [ 84 , 85 ].…”

“…On the contrary, some evidence demonstrated that elevated NMDA-R function is also involved in ASDs. In this concept, it has been shown that Memantine, an NMDA-R antagonist, improved ASD-related symptoms [ 20 , 21 ].…”