Authors :
Presenting Author: Peiyu Wang, MD – West China Hospital, Sichuan University
Lu Lu, MD – Department of Neurology, West China Hospital, Sichuan University
Weixi Xiong, MD – West China Hospital, Sichuan University
Dong Zhou, MD – West China Hospital of Sichuan University, Sichuan, China
Rationale:
Cognitive disorders are increasingly prevalent in people with epilepsy as the population ages, emphasizing the need for cognitive enhancing treatment in epilepsy management. However, selecting an appropriate cognitive enhancer for people with an existing susceptibility to unprovoked seizures could be challenging. Both memantine and acetylcholinesterase inhibitors (AChIs) carry a warning for their association with a lowered seizure threshold. Memantine has an overall better safety profile than AChIs regarding seizures. Clinical reports on whether memantine predisposes to seizure yielded ambiguous conclusions. Several studies supported the safety of memantine to be used in people with epilepsy, but the evidence was preliminary and was restricted by the limited sample size and lack of proper control. This pilot study is designed to provide better evidence of the safety profile of memantine in people with epilepsy in a prospective cohort.
Methods: This is a prospective cohort study. People with epilepsy who were diagnosed with cognitive impairment at West China Hospital were consecutively invited and agreed to participate. They were followed up for at least 24 weeks with a four-week interval. Participants were adherent to their ASM regimens, and these were 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) after discussing potential risks. Primary outcome measures were the occurence of new-onset generalized tonic-clonic seizure, new-onset status epilepticus, and increased seizure frequency (≥25.0%). The incidence of other treatment-emergent adverse events (TEAEs) and the 24-week retention rate were secondary outcome measures.
Results: A total of 178 participants were enrolled (median age, 63; male, 65%). Among them, eighty-five (48%) started memantine. Epilepsy etiology, ASM regimens, and baseline seizure frequency were comparable between groups. Median follow-up duration was 51 (24-81) weeks. During follow-up, no event of new-onset generalized tonic-clonic seizure was recorded; one event of new-onset status epilepticus was recorded in the non-memantine group. Increased seizure frequency was reported by nine (5%) participants (memantine vs. non-memantine, 5 vs. 4). Seizure frequency remained stable during the follow-up period in the memantine group compared to baseline. The most frequently reported TEAEs in the memantine group included headache (7%), dizziness (5%), fatigue (4%), and drowsiness (2%). The 24-week retention rate was 91%. Reasons for discontinuation included intolerable TEAEs (n=4) and unsatisfactory treatment response (n=4).
Conclusions: Adjunctive memantine was well-tolerated in people with epilepsy regarding seizure and other TEAEs, with a satisfying 24-week retention rate. A large-scale controlled trial is required to confirm its safety profiles and to guide cognition-enhancing treatment in people with epilepsy.
Funding:
This work was supported by the National Natural Science Foundation of China (NSFC Grants No. U21A20393) and the postdoctoral research fund of West China Hospital, Sichuan University (Grants No. 2024HXBH095).