Abstract
Objectives
In October 2020 and March 2021, the Federal Drug Agency classified lamotrigine as class IB antiarrhythmic, announcing an increased risk of heart rhythm problems. We sought to investigate the nature of the arrhythmia signal with lamotrigine use compared to anticonvulsants with sodium and non-sodium blocking mechanisms.
Methods:
This retrospective pharmacovigilance case-non-case study used disproportionality analysis to detect signals of adverse reaction of interest reported with lamotrigine to the FDA adverse event reporting system between 1998 and 2022. Our regression model adjusted for interacting concomitant medications. Sensitivity analyses included stratifying by indication and publication date.
Results
Overall, 2917 cases of heart rhythm problems with anticonvulsants were analyzed (1557 female [58.4%] and 1109 male [41.6%]). The mean age was 43±19, the groups did not differ significantly by age. Forty cases [7.91%] in the epileptic indication included more than one concomitant medications that influence cardiac conduction. The disproportionality signal for cardiac arrest did not differ for lamotrigine compared with other anti-convulsants, [adj.ROR, 0.88; 95%CI, 0.59-1.29] in the epileptic indication. A significantly lower reporting risk for bradyarrhythmia was identified with lamotrigine users in the epileptic population, [adj.ROR, 0.45; 95%CI, 0.29-0.68]. The psychiatric indication demonstrated a six-fold reporting risk for cardiac arrest compared to the epileptic indication. Concomitant medications that affect cardiac conduction, as well as reports on overdose and suicide attempts were significant variables in psychiatric patients, [ROR, 2.45; 95%CI, 2.21-2.71], and [ROR, 1.44; 95%CI, 1.34-1.55] respectively.
Significance
Our results do not support a significant difference in the reporting risk for cardiac arrest, syncope, tachy- and bradyarrhythmia with lamotrigine in the epileptic indication. Signals of cardiac arrest in lamotrigine could be explained by confounding factors in the psychiatric indication, such as greater concomitant use of medications with cardiac adverse events, and greater reports on overdose and suicide attempts. We recommend that patients with polypharmacy undergo clinical and electrocardiographic monitoring. We illustrate the importance of examining signals for seperate indications.
JUN