Antagonism of NMDA Receptors as a Potential Treatment for Down Syndrome: A Pilot Randomized Controlled Trial

In a 2012 pilot randomized controlled trial, researchers examined the effects of memantine, an NMDA receptor antagonist, on cognitive function in individuals with Down syndrome (DS). The study included 40 young adults with DS, with 19 receiving memantine and 19 receiving a placebo over a 16-week period. While no significant differences were observed in the primary outcome measures of episodic and spatial memory, the memantine group showed significant improvement in one secondary memory measure, the California Verbal Learning Test-II Free Recall Total score (P=0.046). Another measure, the DAS-II Recall of Digits score, approached statistical significance (P=0.051). The treatment was generally well-tolerated, with only mild adverse events reported. The study suggests potential cognitive benefits of memantine for individuals with DS, but due to the small sample size and other limitations, further research with larger samples is needed to confirm these findings.