Antiepileptic Drugs during Pregnancy in Primary Care: A UK Population Based Study

Shuk-Li Man,Irwin Nazareth,Mary Thompson,Irene Petersen,Jerson Laks

doi:10.1371/journal.pone.0052339

Shuk-Li Man, Irwin Nazareth + Show 3 more

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https://doi.org/10.1371/journal.pone.0052339

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Journal: PloS one	Publication Date: Dec 18, 2012
Citations: 80	License type: CC BY 4.0

Affiliation: University College London, Health Data Research UK

Abstract

ObjectiveAntiepileptic drugs (AEDs) are commonly prescribed for epilepsy and bipolar disorder but little is known about their use in pregnancy. We examined secular trends in AED prescribing in pregnancy and pregnancy as a determinant for stopping AED prescribing.MethodsWe identified 174,055 pregnancies from The Health Improvement Network UK primary care database. Secular trends in AED prescribing during pregnancy were examined between 1994 and 2009. We used Cox's regression analyses to compare time to discontinuation of AED prescriptions between pregnant and non-pregnant women and to identify predictors of discontinuation of AEDs in pregnancy.ResultsPrescribing of carbamazepine and sodium valproate have declined since 1994 despite being the most commonly prescribed AEDs in pregnancy up to 2004. Prescribing of lamotrigine in pregnancy has steadily increased and has been the most popular AED prescribed in pregnancy since 2004. Pregnant women with epilepsy were twice as likely to stop receiving AEDs (Hazard Ratio (HR) 2.00, 95% Confidence Interval (CI) 1.62–2.47) when compared to non-pregnant women and for women with bipolar disorder this was even higher (HR 3.07, 95% CI 2.04–4.62). For pregnant women with epilepsy, those receiving AEDs less regularly before pregnancy were more likely to stop receiving AEDs in pregnancy.ConclusionsLamotrigine has been increasingly prescribed in pregnancy over older AEDs namely carbamazepine and sodium valproate. Pregnancy is a strong determinant for the discontinuation of AED prescribing particularly for women with bipolar disorder.

Highlights

Some older antiepileptic drugs (AEDs) have been found to increase the risk of major congenital malformations (MCMs), and in particular, sodium valproate is associated with developmental delay [1,2]
We examined secular trends of prescribing common AEDs in pregnancy and assessed whether pregnancy is a major determinant for the discontinuation of AED prescribing
Secular trends in prescribing Over the late 1990 s, approximately 0.5–0.6% of pregnancies had an AED prescribed during the course of the pregnancy

Summary

Introduction

Some older antiepileptic drugs (AEDs) have been found to increase the risk of major congenital malformations (MCMs), and in particular, sodium valproate is associated with developmental delay [1,2]. Over a third of women with bipolar disorder are treated with AEDs, [4] which if untreated in pregnancy, increases the risk of mood episode relapse and postpartum psychosis [5,6,7]. The 2012 clinical guidelines from the National Institute of Health and Clinical Excellence (NICE) advised caution on the use of sodium valproate in pregnancy, but their guidance offers little other advice on which AEDs are safe to use in pregnancy. They recommend seizure freedom in pregnancy should be sought amongst women with epilepsy [3].

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