Examining psychiatric and cognitive adverse effects of brivaracetam, clobazam, lacosamide, eslicarbazepine, and perampanel in a veteran population

Abstract

Introduction: Epilepsy is a chronic neurological disorder, affecting approximately 50 million people worldwide. There is limited data on the use of newer anti-seizure medicines (ASMs) and their cognitive and psychiatric adverse effects (AEs), despite increasing use. We aimed to describe the AE profile of newer ASMs in the real-world veteran population with Epilepsy comparing those who develop cognitive or psychiatric AEs to those who did not.

Methods: A retrospective analysis of veterans (n = 2636) diagnosed with epilepsy via ICD-10 codes was conducted in collaboration with the Veterans Affairs (VA) Office Quality and Patient Safety Analytics and Performance Integration program. Neurology notes of veterans diagnosed with epilepsy, between January 2011 and June 2022 across the VA system were sampled to evaluate cognitive and psychiatric AEs. For this index study, only patients who were prescribed any of the five newer anti-seizure medications (brivaracetam, clobazam, lacosamide, eslicarbazepine, and perampanel) were included. Selection of these ASMs were made a priori as these were the most recently approved ASMs for use in the VA.

Results: Among the 2636 Veterans that were included in the index study, median age (Q1-Q3) was 64 (50-73) years with 88.1 % male participants, a population known to have higher prevalence of psychiatric and cognitive disorders. Overall, 70.7 % White Veterans, and 6.5 % Hispanic. 86.8 % were prescribed lacosamide while only 4.1 %, 4.3 %, 4.4 %, and 4.8 % were prescribed perampanel, clobazam, brivaracetam, and eslicarbazepine respectively. Overall, 63 (2.4 %) and 39 (1.5 %) Veterans reported cognitive and psychiatric AEs, respectively. Veterans with epilepsy were more likely to experience cognitive AEs if they were independently older (p = 0.004) and on Perampanel (OR 2.58, p = 0.03). Similarly, psychiatric AEs were more likely among those on Perampanel (OR 4.49), whereas they were less frequent in those taking frequent lacosamide (OR 0.38). Cognitive or psychiatric AEs often lead to treatment discontinuation in this population.

Conclusion: In a population of veterans with epilepsy, clinicians should exercise caution in monitoring for cognitive and psychiatric adverse effects prescribed with the newer ASMs. Further research could help elucidate the dosage and delay at which these side effects would occur after treatment initiation.

Keywords: Antiseizure medication; Brivaracetam; Clobazam; Epilepsy psychiatric and cognitive adverse effects; Eslicarbazepine; Lacosamide; Perampanel.