Abstracts

Pregnancy in women with epilepsy (WWE) is accompanied by increased fetal risks due to both antiepileptic drug (AED) exposure and maternal seizures (sz). Relatively low rates of major malformations on lamotrigine (LTG) has led to its increased use during childbearing years. However, observational studies indicate that LTG clearance (Cl) markedly increases during pregnancy, and sz worsening has been reported in 45-75% of women on LTG monotherapy. Maternal seizures, especially of the convulsive type, have been associated with fetal loss, fetal hypoxia, and poor neurodevelopmental outcomes., WWE on AEDs either during or planning a pregnancy were consented to participate in a prospective study. Subset analysis was performed on all WWE on LTG monotherapy who had adequate baseline information about sz frequency and preconception target LTG concs (n=30). Although no specific protocol was mandated by the study, results of LTG concs were actively used for therapeutic drug monitoring (TDM). Recommendations to adjust LTG dose were made according to the pt[apos]s sz type(s), epilepsy syndrome, sz frequency, history of LTG-related side effects, gestational age, and what was considered that individual[apos]s target conc. For each trimester (TM), we coded relative frequency of all-type sz[apos]s as 1 if number of sz[apos]s was greater than baseline, and 0 otherwise. For each TM, we calculated the ratio to target concentration (RTC) as LTG conc / target LTG conc from baseline., Seizures worsened during pregnancy in 28% of pts and convulsive seizures worsened in 10% (Figure 1). RTC values of pts with worsened sz frequency were lower than RTC values of those with stable seizures in the 2^nd TM ([italic]p[/italic] [lt]0.001) and the 3^rd TM ([italic]p [/italic]= 0[italic].[/italic]05) but not the 1^st TM. Similar significant findings occurred if definitions were 1.5x and 2x increase in sz frequency. Convulsive seizures doubled in 10% of pregnancies; impact of RTC was not significant., This analysis demonstrates that seizure worsening during pregnancy is associated with a low RTC, and that improved results for sz control can be achieved with an active TDM approach. However, this extent of sz control is not ideal and development of a population pharmacokinetic model that will define a treatment plan and dosing paradigm for LTG use during pregnancy, adaptable to the individual patient, is necessary to improve the maternal and fetal well-being of our patients further.[figure1], (Supported by Specialized Center of Research P50 MH 68036.)