Will Memantine Exacerbate Seizures in People With Epilepsy? A Prospective Cohort Study

Objective To evaluate whether add‐on memantine would exacerbate seizures in people with epilepsy. Methods This was a prospective cohort study. People with epilepsy diagnosed with cognitive impairment were consecutively invited. Those who agreed were followed up for at least 24 weeks. Participants were required to be adherent to their antiseizure medication regimens, which had remained unchanged for at least 24 weeks before recruitment. Participants were prescribed memantine and categorized according to their treatment decisions (memantine group vs. non‐memantine group). Primary outcome measures were the occurrence of new‐onset bilateral tonic–clonic seizure, new‐onset status epilepticus, and increased seizure frequency (≥ 25%). The incidence of other adverse events (AEs) and 24‐week retention rate were secondary outcome measures. Results Two hundred and eleven participants were enrolled (median age, 63; male, 65%). Among them, one hundred and one (48%) started memantine. Baseline seizure characteristics were comparable between the two groups. During follow‐up, no new‐onset bilateral tonic–clonic seizure was recorded; there was one status epilepticus in the non‐memantine group. Increased seizure frequency was reported by 12 (6%) participants (memantine vs. non‐memantine, seven vs. five). Other AEs in the memantine group included headache (7%), dizziness (5%), fatigue (4%), drowsiness (2%), and anorexia (2%). The 24‐week retention rate was 91%. Interpretation Adjunctive memantine was well tolerated in people with epilepsy regarding seizure control and other AEs. Previous warnings might have been disproportionate. Large‐scale, randomized trials are required to confirm this and further elucidate its efficacy profiles in epilepsy.