Abstracts

Rationale: Estrogen induced hepatic glucuronidation has been implicated in the drop of lamotrigine (LTG) levels during the active pill phase of combined oral contraceptive (COC) use. The possibility of a similar effect of COC on valproate (VPA) serum levels has been raised by the involvement of glucuronidation in VPA metabolism and by the report of a single case in which serum VPA levels were substantially lower on active COC than on inactive pill and associated with cyclic seizure flares (Herzog AG, Farina EL, Blum AS. Epilepsia 2005;46:970-1). The purpose of this investigation was to determine if COC use affects serum levels of VPA and LTG and to distinguish COC effects from the potential effects of the naturally occurring high (mid luteal) and low (early-mid follicular) steroid level phases of the menstrual cycle.Methods: This is a cross-sectional, observational, pilot investigation of serum AED levels at two time points during a single menstrual cycle in 48 women with epilepsy. Complete data were available for the first 33 of the 48 subjects at the time of this interim analysis. The women were aged 13-45 years. The design was to recruit 4 groups: 12 on VPA (VPA), 12 on VPA plus COC (VPA-COC), 12 on LTG (LTG) and 12 on LTG plus COC (LTG-COC). All were maintained on stable VPA or LTG monotherapy with or without concomitant COC use for at least one month. Trough VAL and LTG levels were checked during the 3rd week of active pill use and at the end of the week of inactive pill use in women on COC. Women not on COC had two levels measured at comparable high and low steroid level times of the cycle during the mid luteal phase (Day 20-24) and the early-mid follicular (Day 3-7) phase. Comparisons of serum AED levels for the 4 groups were carried out using Wilcoxon matched-pairs tests. Results: Both VPA and LTG serum levels were substantially and significantly lower on active COC than on inactive pill (Table 1). Serum LTG levels also showed a notable, albeit not significant (p = .117), drop in levels among non users of COCs during the mid luteal phase compared to the early-mid follicular phase of the cycle. Conclusions: The preliminary findings of this prospective study suggest that VPA as well as LTG may show substantially lower serum levels while women take active COCs as compared to inactive pills. Larger sample size will be required to determine whether LTG levels may also drop significantly during the luteal (high steroid) phase of the natural menstrual cycle.