Abstracts

Rationale: Lamotrigine is a commonly prescribed medication given its relatively benign side effect profile and stable steady state levels. The decrease in serum Lamotrigine levels in pregnancy secondary to increased clearance and consequently increased risk of seizures has been well documented. In few of these studies, a singular patient with serial pregnancies have been observed and studied - two patients with two pregnancies each and one patient with two pregnancies and one with three pregnancies. Though all studies had detailed analysis of patient population pregnancies, there was no comprehensive inter-pregnancy comparison for a singular patient. Here we present variation in Lamotrigine pharmacokinetics in serial pregnancies in the same patient. Our study was prompted by the observation that a higher dose of Lamotrigine was needed with each subsequent pregnancy to achieve the same serum level. Methods: N.H is a 35 year old female with localization related epilepsy and poorly characterized seizures. Since 2007 she has had three successful pregnancies and has been maintained on Lamotrigine throughout. Apparent clearance was considered as the best measure of Lamotrigine variability as it also included weight of the patient. Apparent Clearance = Daily dose (mg/kg)/ Serum Lamotrigine concentration (mg/L) Weights were obtained from neurology and obstetric clinic notes and hospital admissions. Due to frequent telephone correspondence daily dose was available for every week that was included in the study. Baseline was considered as 6 weeks prior to conception for pregnancy 1, 13 weeks prior to conception for pregnancy 2 and 6 weeks postpartum for pregnancy 3. For every Lamotrigine level, if a corresponding weight was not available it was calculated using linear extrapolation. A two way analysis of variance with main effects of trimester and pregnancy number followed by Fisher s protected least significant difference tests were applied. Results: Two way analysis of variance showed a statistically significant effect of trimester but no significant effect of the pregnancy number. Fisher s test found that clearance was elevated in the second and third trimester as compared to the baseline and first trimester. There was no significant interaction, indicating that there was no effect of pregnancy number on the changes in clearance seen over the trimesters. There was a non-significant trend towards decreased clearance during second and third trimester with serial pregnancies. Conclusions: Contrary to our initial assumption, there was a trend towards decreased clearance with subsequent pregnancies. This was a retrospective observational study and it is likely that statistical significance was not achieved due to lack of more frequent serum Lamotrigine levels. A prospective study with more frequent serum Lamotrigine levels would be needed to further delineate the differences in pregnancies.