Abstracts

Rationale: Recent reports (Petrenaite et all., 2005; Pennell et al. 2008) have documented significant increases in lamotrigine (LTC) clearance beginning early in pregnancy and peaking in the third trimester. It is known that about one third of women with epilepsy may experience an increase in seizure frequency during pregnancy; this increased seizure activity is thought to be more common in those patients with uncontrolled seizures. In women taking LTG increased seizure frequency during pregnancy may be associated with drops in LTG serum levels and preemptive increases in LTG dosage seem warranted. This report documents the dosage adjustments and seizure histories of a cohort of pregnant women managed in an epilepsy center where frequent LTG serum monitoring and preemptive dosage adjustments were made. Methods: From 2004 until present, all women with epilepsy taking lamotrigine and planning pregnancy had lamotrigine levels drawn prior to pregnancy. Each pregnant woman had drug levels subsequently drawn on a monthly basis. The LTG dosage was increased based on the comparison between the baseline level and the most recent results using the best judgment of the treating physicians (GKB, NC) and nurse (RF). Increases in dose were made even in patients with well controlled seizures if levels had fallen below pre-pregnancy levels. Patients reported any seizure activity. Results: All 18 patients on LTG who became pregnant were studied; two patients miscarried in the first two months. Of the 16 patients who went to term, 13 were on LTG monotherapy, 3 patients were on levetiracetam co-therapy, no patients were on other AEDs. Prior to conception, 15 of the 16 patients had total seizure control (i.e. no seizures in > 1 year). One woman had intractable seizures prior to pregnancy. Nine of the 16 patients continued to be seizure free throughtout pregnancy and delivery. Five of the 16 patients with previously well-controlled seizures had seizures during their pregnancies despite monitoring and adjustments of the LTG dosage. The average increase during pregnancy in LTG dose was 107% ± 15% (SEM). During the first trimester, one patient had two generalized tonic-clonic seizures(GTCSs); another patient had one partial seizure. In the second trimester, there were a total of 9 partial seizures and 5 GTCSs in 5 patients. In the third trimester, there were a total of 6 partial seizures in two patients with one GTCS in another patient. All patients with seizure breakthroughs had LTG levels below pre-pregnancy baseline, although in some instances the difference in levels was small. No children (n=17; one set of twins) had major birth defects; one child had polydactyly. Conclusions: Total daily LTG doses will need to be at least doubled during the course of pregnancy if pre-pregnancy levels are to be maintained. Breakthrough seizures can occur during all three trimesters. The changes in lamotrigine clearance during pregnancy can have a significant impact on seizure control even in patients with previous seizure freedom on AED monotherapy.