Is memantine (N-methyl-D-aspartate receptor antagonist) helpful in treating autism spectrum disorder?

Memantine for Autism Spectrum Disorder: Current Evidence

Based on the most recent and highest quality evidence, memantine is not recommended for treating core symptoms of autism spectrum disorder as there is insufficient evidence supporting its efficacy.

Efficacy for Core Autism Symptoms

• A 2022 Cochrane systematic review found no clear evidence of difference between memantine and placebo for core autism symptoms, with very low-certainty evidence (standardized mean difference -0.74,95% CI -2.07 to 0.58) 1
• There is no compelling evidence supporting memantine use for core symptoms of autism spectrum disorder according to recent psychiatric reviews 2
• The limited available studies have high risk of bias, small sample sizes, and short follow-up periods, making it difficult to draw definitive conclusions about memantine's efficacy in ASD 1

Specific Domains and Secondary Outcomes

• Memantine showed no significant difference compared to placebo on language outcomes in autism (low-certainty evidence) 1
• No significant differences were found for memory, adaptive behavior, hyperactivity, or irritability compared to placebo (all low-certainty evidence) 1
• A small pilot trial found memantine was not associated with improvements in apraxia or expressive language in children with ASD 3

Potential Limited Benefits in Specific Areas

• One small study suggested memantine might improve verbal recognition memory (F = 5.05, p = .03) and showed potential improvements in verbal IQ (d = 1.8) in exploratory analyses, but these findings require replication in larger studies 3
• A single-blind study of memantine as adjunct therapy to Applied Behavior Analysis (ABA) reported improvement in autism symptoms compared to ABA alone, but methodological limitations reduce confidence in these findings 4
• One study reported memantine plus risperidone showed greater reduction in irritability, stereotypic behavior, and hyperactivity compared to risperidone alone, but this represents limited evidence 5

Safety Considerations

• Adverse effects reported with memantine in autism studies include gastrointestinal symptoms, though there may be no significant difference in adverse events between memantine and placebo (OR 0.64,95% CI 0.17 to 2.39; low-certainty evidence) 1
• Dropout rates were high across treatment groups in clinical trials, which may impact interpretation of efficacy and safety data 3

Clinical Context and Recommendations

• Memantine is FDA-approved for Alzheimer's disease but not for autism spectrum disorder 6
• Non-pharmacological approaches should take precedence over medications for behavioral symptoms in developmental disorders 6
• Current evidence does not support using memantine for core autism symptoms, though research is ongoing 1, 2
• Future studies using rigorous designs, larger samples, longer follow-up, and clinically meaningful outcome measures are needed to better understand potential effects of memantine in autism 1

Common Pitfalls and Caveats

• Avoid using memantine specifically targeting core autism symptoms, as evidence does not currently support this approach 1, 2
• Be cautious about interpreting positive findings from small or methodologically limited studies until confirmed in larger, well-designed trials 1
• Consider that most studies of memantine in autism have focused on children and adolescents, with no substantial evidence in adults with ASD 1
• Recognize that dropout rates in memantine trials for autism have been high, which may indicate tolerability issues or lack of perceived benefit 3