Abstracts

Rationale: Antiepileptic drugs (AED) underly modified pharmacokinetics during pregnancy (preg.). Concerning Lamotrigine (LTG) a clinically relevant decrease of serum concentration levels has been reported (Tran et al., Neurology 2002). In previous EURAP-analyses differences in seizure control and dose modifications during pregnancy for the most frequent monotherapies with LTG, Carbamazepine (CBZ) and Valproate (VPA) have been found: In the 2nd and 3rd trimester (trim) compared to the 1st trim the best seizure control has been shown for VPA in monotherapy. A significantly high number of dose changes was performed in patients with LTG-monotherapy (EURAP study group, Neurology 2005). As preconceptional (precon.) data are not recorded in the EURAP-database these findings could not have been compared to the precon. seizure situation.Methods: EURAP is a prospective study to investigate pregnancies with AED-exposition. In 147 patients from 7 german EURAP-centres with completed preg. who were treated with VPA (n=43), CBZ (n=41) or LTG (n=63) in monotherapy we retrospectively investigated seizure control and dose modifications 1 year precon. and 3 month postpartal in comparison to the data obtained by the EURAP-Registry with respect to changes in the course of preg. Results: During preg. 63% of the observed patients were seizure-free compared to 56% in the year prior to conception. Compared to the precon. seizure situation the largest amount of women who experienced a change of seizure frequency in each trim was found in the LTG-group. However, this group also represented the largest portion of women with a decrease in seizure frequency in each trim (increase/decrease): Trim 1: LTG 54% (17%/37%), CBZ 39% (15%/24%), VPA 33% (7%/26%); Trim 2: LTG 56% (19%/37%) , CBZ 37% (10%/27%), VPA 39% (9%/30%); Trim 3: LTG 55% (14%/41%), CBZ 36% (7%/29%), VPA 33% (7%/26%). More dose changes were performed during preg. (48% of cases) than in the year before conception (32%). Most of these were found in the LTG-group (amount of patients, preg./precon.): LTG (68%/48%), CBZ (31%/22%) , VPA (33%/19%). Reasons for changes of dosage were recurrent seizures (LTG 59%, CBZ 38%, VPA 36%), low serum levels (LTG 60%, CBZ 46%, VPA 36%) and fear of malformation (LTG 4%, CBZ 23%, VPA 43%) (multiple nominations possible).Conclusions: Compared to LTG- and CBZ-monotherapies VPA showed the lowest risk for a deterioration of seizure frequency during preg. A positive selection due to the epilepsy-syndromes that are preferably treated with VPA might contribute to these results. An increased amount of dose changes under LTG both before and in the course of preg. is remarkable. Presumably the precon. dose changes have to be interpreted as an AED-conversion with respect to a planned preg. During preg. LTG-dose changes (predominantly increases) were mainly done due to serum levels that were considered to be too low or to recurrent seizures. By contrast VPA-dose modifications (mostly decreases) were mainly motivated by fear for malformations.