Can memantine treat autism? Answers from preclinical and clinical studies

Autism Spectrum Disorder (ASD) represents a clinical challenge due to its diverse behavioral symptoms and complex neuro-pathophysiology. Finding effective treatments that target the fundamental mechanisms of ASD remains a top priority. This narrative review presents the potential of the NMDA-receptor blocker memantine in managing ASD symptoms. Preclinical studies indicate that memantine could abrogate excitotoxicity, GABA/glutamate imbalance, reduced levels of brain-derived neurotrophic factor (BDNF), blood-brain barrier (BBB) leakage, and neuroinflammation, offering hope for managing core deficits associated with ASD like impaired social interaction and repetitive behaviors. However, clinical trials yield conflicting results, with some showing slight improvements in symptom severity and cognitive function, while others demonstrate limited efficacy. Further exploration of memantine's neurobiological mechanisms and refinement of treatment approaches are crucial for comprehensively tackling ASD complexities. Drawing from both animal models and clinical data, this review examines memantine's impact on core ASD symptoms, cognitive function, and potential mechanisms of action. Lastly, it identifies research gaps and proposes avenues for future investigations to enhance our understanding and utilization of memantine in ASD management.