A Randomized Double-Blind Placebo-Controlled Crossover Trial of Memantine In The Treatment of Children With Epileptic Encephalopathy

Objectives: Memantine is an NMDA receptor antagonist, approved for dementia treatment. There is limited evidence of memantine showing benefit for children with neurodevelopmental phenotypes, particularly those caused by pathogenic variants in NMDA receptor subunit genes. We aimed to evaluate the safety and efficacy of memantine in treatment of epileptic encephalopathy

Methods: A randomized double-blind placebo-controlled crossover trial of memantine for the treatment of children with epileptic encephalopathy. Patients received memantine/placebo for 6 weeks, followed by 2-week washout phase, then a second 6-week treatment period of placebo/memantine. The primary outcome measure was classification as a “responder,” defined as having at least 2 of: reduction in seizure frequency, EEG improvement, caregiver impression of improvement, or clear improvement on neuropsychologic evaluation.

Results: Thirty-one patients enrolled; however, four withdrew or were removed from analysis. Of the remaining 27 patients, nine (33%) were classified as responders to memantine versus two (7%) in the placebo group (p < 0.02). EEG improvement was seen in eight patients while on memantine compared to only two on placebo (p < 0.04). Seizure improvement was observed in eight patients on memantine and only two on placebo (p < 0.04). Caregivers reported clinical improvement in 10 patients while taking memantine compared to 7 while taking placebo (not significant). One patient did not complete the second treatment phase (while taking placebo) due to a marked increase in seizures.

Conclusions: Memantine is safe and effective for children with epileptic encephalopathy, having the potential to improve both seizure control and cognitive function.