The aims of the study were to characterize the magnitude of clearance changes during pregnancy for multiple antiepileptic drugs (AEDs) and to assess seizure frequency and factors increasing seizure risk in pregnant women with epilepsy. A retrospective analysis was performed for 115 pregnancies in 95 women with epilepsy followed at the Emory Epilepsy Center between 1999 and 2012. Antiepileptic drug blood levels (ABLs) obtained during routine clinical practice were used to calculate AED clearance at multiple points during pregnancy. Antiepileptic drug doses and seizure activity were also recorded. The data were analyzed for changes in clearance and dose across pregnancy and for an association between ABL and changes in seizure frequency. Significant changes in clearance during pregnancy were observed for lamotrigine (p<0.001) and levetiracetam (p<0.006). Average peak clearance increased by 191% for lamotrigine and 207% for levetiracetam from nonpregnant baseline. Marked variance was present across individual women and also across repeat pregnancies in individual women. Despite increased AED dose across most AEDs, seizures increased in 38.4% of patients during pregnancy. Seizure deterioration was significantly more likely in patients with seizures in the 12 months prior to conception (p<0.001) and those with localization-related epilepsy (p=0.005). When ABL fell >35% from preconception baseline, seizures worsened significantly during the second trimester when controlling for seizure occurrence in the year prior to conception. Substantial pharmacokinetic changes during pregnancy occur with multiple AEDs and may increase seizure risk. Monitoring of AED serum concentrations with dose adjustment is recommended in pregnant women with epilepsy. Further studies are needed for many AEDs.
Keywords: ABL; AED; AED blood level; Antiepileptic drugs; CBZ; Cl; Clearance; ESM; Epilepsy; LEV; LTG; OXC; PHT; Pharmacokinetics; Pregnancy; Seizure frequency; TPM; VPA; ZNS; antiepileptic drug; carbamazepine; clearance; ethosuximide; lamotrigine; levetiracetam; oxcarbazepine; phenytoin; topiramate; valproate; zonisamide.