Abstracts

Lamotrigine (LTG) is increasingly used as AED of choice in women, because it does not impair the effectiveness of hormonal contraception and seems to have a comparatively small teratogenic risk. The clinical relevant reduction of LTG-levels by combined contraceptives (ethinylestradiol + progestin) is possibly caused by the induction of glucuronidation by ethinylestradiol. Therefore we wanted to study the effect of a progestin only oral contraceptive in a prospective evaluation. 10 women with epilepsy on a stable LTG monotherapy received a progestin only pill containing 75 [micro]g desogestrel daily (Cerazette[reg]) continously for 12 weeks. Serial blood samples were drawn at baseline, week 1-2, 3-4, 7-8 and 10-12 and lamotrigine trough and peak levels determined by HPLC. In some patients a diurnal profile was performed and AUCs determined. In 7/10 patients LTG levels increased by 20-100% when treated with Cerazette[reg] concomitantly. Surprisingly, the increase in LTG peak levels was more pronounced than the increase in trough levels in all patients. Correspondingly, some patients suffered dose-dependant adverse effects of LTG [frac12]-3 hours after each dose of LTG. In contrast to the rapid LTG-level reducing effect of combined oral contraceptives, the increase of LTG-level caused by desogestrel occured in most women after week two and increased steadlily up to week 8-12. Previous studies that evaluated the effect of desogestrel+ethinylestradiol combined monophasic oral contraceptives on LTG showed a substantial decrease of LTG levels. Our preliminary data show the opposite effect in a clinically relevant magnitude in the majority of patients if a desogestrel only pill is used. Our data suggest that the decrease of the LTG levels seen in combined oral contraceptives is mainly an ethinylestradiol effect and not due to the progestin.
If a woman on a stable LTG regimen wants to start contraception with a desogestrel only pill, counseling on the possible occurrence of dose-dependant adverse-effects is advisable. A dose reduction of LTG might be necessary. Wether contraception with a desogestrel only pill is safe in women with epilepsy on LTG and possibly a hormonal contraception of choice remains to be determined.