Lamotrigine and Other Sodium Channel Blocking Antiseizure Medication Use and Risk of Sudden Unexpected Death in Epilepsy
Abstract number :
1.302
Submission category :
7. Anti-seizure Medications / 7C. Cohort Studies
Year :
2021
Submission ID :
1826427
Source :
www.aesnet.org
Presentation date :
12/4/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:54 AM
Authors :
Russell Nightscales, MD - Monash University & Alfred Health; Sarah Barnard - Monash University; Juliana Laze - New York University; Gerard Tao - The Royal Melbourne Hospital; Clarissa Auvrez - The University of Melbourne; Shobi Sivathamboo - Monash University; Zhibin Chen - Monash University; Wendyl D'Souza - The University of Melbourne; Mark Cook - The University of Melbourne; Daniel Friedman - New York University; Samuel Berkovic - The University of Melbourne; Piero Perucca - The University of Melbourne; Orrin Devinsky - New York University; Terence O'Brien - Monash University
Rationale: The U.S Food and Drug Administration (FDA) has recently issued a warning that, based on in-vitro data, lamotrigine could induce arrhythmia and increase sudden death risk in patients with structural or ischaemic cardiac disease, and should be avoided in these patients. As sodium channel blockade is the predominant action of lamotrigine and multiple other anti-seizure medications (ASMs), class-wide investigations of adverse cardiac event risk were recommended. Pathophysiological understanding of sudden unexpected death in epilepsy (SUDEP) is incomplete, but post-ictal cardiac dysfunction and arrhythmia may be implicated. We hypothesized that if lamotrigine and other sodium channel modulating ASMs were associated with an increased risk of SUDEP, there would be an excess of usage amongst SUDEP cases compared to well-matched controls.
Methods: This multicentre, international, retrospective cohort study identified 48 Definite, 23 Probable, 28 Possible and 4 Near SUDEP/SUDEP-plus cases that had been admitted to one of four tertiary hospital Epilepsy Monitoring Units (EMU) in Melbourne, Australia, and New York, USA, between 1995 and 2013. These 103 cases were 2:1 matched with 201 controls by age, sex, year of EMU admission, and hospital site. Clinical and pharmacological data at time of Video EEG Monitoring (VEM) was retrieved by medical record review. All available information including autopsy findings, police and post-mortem toxicology reports were reviewed to determine SUDEP status and post-mortem ASM use. SUDEP cases were compared with controls for the proportion who were taking lamotrigine or another sodium channel modulating ASM (i.e. carbamazepine, lacosamide, oxcarbazepine, phenytoin or zonisamide).
Results: There was no significant difference at the time of EMU admission in the proportion of SUDEP cases and controls taking lamotrigine (32.0% vs. 39.3%, respectively), in those on at least one sodium channel modulating ASM (79.6% vs. 78.6%, respectively), or those on two or more sodium modulating ASMs (17.4% and 22.9%, respectively). Each of the sodium channel modulating ASMs had comparable use in each group (Table 1). Cardiovascular comorbidities were reported in 4.1% and 3.6% of SUDEP cases and controls, respectively.
Conclusions: These data demonstrated comparable use of lamotrigine and other sodium channel modulating ASMs at the time of EMU admission between future SUDEP cases and controls. Although the study is limited by a lack of information about any changes in ASMs after the EMU admission, it provides reassurance for clinicians that use of these drugs may be not associated with an increase risk of SUDEP.
Funding: Please list any funding that was received in support of this abstract.: Finding A Cure for Epilepsy and Seizures (FACES), and the Australian National Health and Medical Research Council (NHMRC).
Anti-seizure Medications