Neurocognitive Outcomes from Memantine: A Pilot, Double-Blind, Placebo-Controlled Trial in Children with Autism Spectrum Disorder

Objective: Studies interrogating therapeutics which alter the excitation-inhibition balance in the treatment of autism spectrum disorder (ASD) have reported mixed results on social and behavioral outcomes. Methods: The aim of this randomized, double-blind placebo-controlled pilot trial was to evaluate neurocognitive effects of memantine over a 24-week trial. Twenty-three children ages 6-12 years old with ASD were randomized to memantine or placebo. Primary outcomes included measures of apraxia and expressive language with evaluations at midpoint (week 12) and endpoint (week 24). Secondary outcomes included memory and adaptive behavior measures. Exploratory outcomes included changes in overall cognitive functioning and behavior (e.g., Aberrant Behavior Checklist). Results: Results suggest that memantine was well-tolerated. Dropout rates were high across groups with only 14 participants completing the 6-month trial. Memantine was not associated with improvements in apraxia and expressive language. Treatment with memantine was associated with improvements in verbal recognition memory as measured by the Narrative Memory-Recognition (NEPSY-II) (F = 5.05, p = .03). In addition, exploratory analyses of changes in Intelligence quotient (IQ) suggest improvements on verbal IQ (d = 1.8). Conclusions: Results suggest future studies of memantine in ASD may benefit from shifting treatment targets from social and behavioral outcomes to exploration of effects of memantine on cognition, potentially as an adjunct to learning and educational interventions. ClinicalTrials.gov: NCT01372449.