Lamotrigine clearance increases by 5 weeks gestational age: Relationship to estradiol concentrations and gestational age

Ashwin Karanam, Page B. Pennell, Jacqueline A. French, Cynthia L. Harden, Stephanie Allien, Connie Lau, Sarah Barnard, Samuel P. Callisto, Angela K. Birnbaum

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Objective: To determine how early lamotrigine clearance (LTG-CL/F) increases during early pregnancy in women with epilepsy and to quantify the relationship of LTG-CL/F to estradiol concentrations and gestational week. Methods: This was a multicenter, observational study of pregnant women with epilepsy on lamotrigine and no interacting concomitant medications, employing frequent blood sampling prior to and early in pregnancy. A population mixed-effects modeling approach was used to describe the relationship between LTG-CL/F and gestational week and between LTG-CL/F and estradiol. Akaike information criterion (AIC) compared goodness of fit between final models and a generalized estimating equation to compare differences between low and high percentage LTG-CL/F change groups (p < 0.05). Results: Twenty-five pregnancies (22 participants) were available. Increases in LTG-CL/F were present at 5 weeks gestational age. Both estradiol and gestational week were highly correlated with LTG-CL/F changes; LTG-CL/F increased at the rate of 0.115l/h for every gestational week and 0.844l/h for every 1ng/ml of estradiol, with women in the high LTG-CL/F percentage change group changing at a faster rate (p < 0.001). Models using gestational week performed better than models using estradiol. Interpretation: Gestational week was a better predictor of changes in LTG-CL/F than estradiol concentration and may reflect additional factors, although neither was robust enough to use clinically due to substantial interpatient variability. Changes in LTG-CL/F begin as early as the 5th gestational week, often before women know they are pregnant, emphasizing the importance of planning and early detection of pregnancy and consideration of early implementation of therapeutic drug monitoring. Ann Neurol 2018;84:556–563.

Original languageEnglish (US)
Pages (from-to)556-563
Number of pages8
JournalAnnals of Neurology
Issue number4
StatePublished - Oct 2018

Bibliographical note

Funding Information:
This study was funded by the Epilepsy Foundation, the Patricia L. Nangle Fund, and the Milken Foundation.

Publisher Copyright:
© 2018 American Neurological Association


Dive into the research topics of 'Lamotrigine clearance increases by 5 weeks gestational age: Relationship to estradiol concentrations and gestational age'. Together they form a unique fingerprint.

Cite this