To describe the effect of non-oral estrogen containing contraceptive methods on lamotrigine clearance and serum levels in women with epilepsy 

Previous studies demonstrate that oral hormonal contraceptives increase lamotrigine clearance through glucoronidation. This leads to variable lamotrigine serum concentrations throughout monthly cycles in women on oral contraceptives. The effects of non-oral hormonal contraception on AED pharmacokinetics are less well characterized.

Retrospective review of serum lamotrigine levels drawn from female patients with epilepsy while using a non-oral hormonal contraceptive method (estrogen patch, vaginal ring) compared to off contraception (19 lab draws from 4 patients). Exclusion criteria included pregnancy, <8 weeks post-partum, and sample obtained in setting of known missed doses. Two-tailed T-tests compared the mean apparent oral clearance rates of lamotrigine and lamotrigine levels drawn while on non-oral hormonal contraception compared to hormonal contraception in patients using a vaginal ring (N=3) or an estrogen patch (N=1).  Mean lamotrigine level/dose were also compared to control for variable dosing.

Lamotrigine clearance was higher in women while on a non-oral hormonal contraceptive device compared to while off it (p < 0.002). This effect was statistically significant in women using a vaginal ring (p < 0.003). There was no significant difference in clearance while on or off the estrogen patch (p < 0.11), though this followed the trend of increased clearance. Mean lamotrigine levels were lower while on a non-oral hormonal contraceptive (p < 0.002), as were mean lamotrigine level/dose (p < 0.007) compared to while off the contraceptive.

The findings suggest that non-oral hormonal contraceptives increase lamotrigine clearance which leads to low lamotrigine serum levels. This has important implications that lamotrigine levels may fluctuate significantly in women on non-oral hormonal contraceptive during the week off the medication.