Abstracts

Lamotrigine (LTG) serum levels decrease by approx. 50% in women with epilepsy using combined oral contraceptives (COC) and fluctuate considerably depending on whether the patient is in the 3 weeks on or the 1 week off the COC pill. When on the pill LTG levels decrease over time with the lowest LTG levels seen at the end of week 3, followed by an increase of LTG levels in the contraceptive-free week (Stodieck SRG, Schwenkagen AM. Epilepsia 45(S7):187, 2004). This appeared to be of clinical relevance in about 1/4 of our patients (risk of seizure recurrence in week 2 and 3 on the COC or adverse effects at the end of the COC-free week). Since LTG is increasingly used as an AED of choice in woman, a practical solution to this clinical problem is needed. We wanted to prospectively evaluate if it is possible to stabilize LTG levels if the COC is used continuously (long-cycle therapy) and LTG doses are adapted in a standardized way to avoid the expected decrease of LTG levels. 10 women (age 18-36) with well controlled epilepsy on a stable therapy with LTG monotherapy (7) or a combination of LTG with levetiracetam (3) wishing hormonal contraception received a COC (30mcg ethinylestradiol in combination with 2 mg dienogest (8) or 3 mg drospirenon ) continuously over at least 42 days. LTG daily doses were increased from baseline (200-800mg) to 125% on day 3, to 150% on day 7 and to 175% on day 10 after starting the COC. At day 22-25 the LTG dose could be adapted according to the plasma levels at day 20 in order to approximately maintain baseline levels. Blood samples were drawn at baseline, day 2, 6, 9, 20 and 40 and every 20-30 days thereafter for lamotrigine trough and, whenever possible, peak levels. In all 10 patients LTG levels remained comparatively stable. Fluctuations of LTG trough levels as compared to baseline were between -19% and +32% (median
-4%) during the first 20 days. At day 22-25, in 1 patient LTG dose was reduced to 150% and in 2 patients increased to 200% in order to maintain baseline LTG levels. No dose dependant adverse effect of LTG or loss of seizure control was observed. 1 patient discontinued long-cycle COC therapy after 42 days because of breakthrough bleedings, 1 patient after 63 days because of no contraception needed. The remaining 8 patients are still on continuous COC therapy for 65-198 days and showed less than +/-15% fluctuation in LTG levels after day 40. Our data suggest that it is possible to stabilize LTG levels in women using oral contraception if the LTG dose is increased in a standardized way when the oral contraceptive is started and if the COC is used continuously (long-cycle). LTG has a small influence on some contraceptive steroids. In addition to stabilizing LTG levels long-cycle contraception increases contraceptive safety and might be an interesting option for women on LTG.