Age- and sex-associated variability in lamotrigine prescription patterns and clearance

Objective: Lamotrigine is one of the most widely prescribed antiseizure medication (ASM) and mood stabilizer in the United States due to its favorable side-effect profile, lower risk of teratogenicity, and minimal drug–drug interactions. This study aimed to examine age- and sex-associated variability in prescribing and pharmacokinetics, focusing on postmenopausal women. Methods: Data were from electronic health records. Individuals were included if ≥18 years and received an ASM between January 1, 2015 and December 31, 2021. Lamotrigine prescriptions were compared based on age, sex, epilepsy diagnosis, and monotherapy/polytherapy. Statistical comparisons of proportions were conducted using two-proportion tests. To characterize age- and sex-related differences in LTG apparent oral clearance and assess the impact of covariates, linear mixed-effects modeling was employed. Results: Records were available for 314 890 individuals, with 23 906 patients being prescribed lamotrigine at least once (as monotherapy or polytherapy) for both epilepsy and non-epilepsy diagnoses. The lamotrigine prescription rate was lower in postmenopausal women compared to younger women but higher than in older men, irrespective of diagnosis. Notably, lamotrigine was prescribed as monotherapy more frequently to patients without epilepsy than those with epilepsy, regardless of sex and age. The clearance of lamotrigine was 22% lower in postmenopausal women compared to younger women and 9% in older men. Lamotrigine clearance increased by 49% and 11% with co-administration of inducers or the presence of smoking, respectively. Lamotrigine clearance decreased by 51% in the presence of an inhibiting medication. Significance: Prescription rates for lamotrigine varied between patients with epilepsy and those with non-epilepsy conditions. Age and sex differences in pharmacokinetics suggest the need for lamotrigine dose adjustments, highlighting the importance of therapeutic drug monitoring in personalized epilepsy care. Lamotrigine use was less frequent in postmenopausal women compared to younger women but higher compared to older men. Postmenopausal women were prescribed lamotrigine as monotherapy to a lesser extent than younger women and older men.