Clinical Twisters: Treating epilepsy in pregnancy

A 22-year-old woman, L.N., arrived at your emergency department after a "spell." Based on her symptoms and EEG findings, her physician has diagnosed the spell as a complex partial seizure that generalized to a secondary tonic-clonic seizure. L.N.'s neurological exam, physical exam, complete blood count, serum glucose, electrolytes, drug/alcohol screen, and lumber puncture were normal. However, while in the hospital, she experienced a second seizure, prompting her physician to consider antiepileptic drug (AED) therapy. Because L.N. is two months pregnant, her doctor requests a pharmacist consult. What do you recommend?

Seizures during pregnancy are a life-threatening emergency. Differential diagnoses include eclampsia, epilepsy, encephalitis, and cerebral tumor, with eclampsia the diagnosis until other causes are excluded. L.N.'s clinical status worsened with onset of a second seizure, necessitating additional tests (e.g., MRI, CT) and the start of prophylactic AED therapy. Using a single drug at the lowest effective dose is preferred. AED monotherapy reduces the risk for development of fetal anticonvulsant syndrome compared with polytherapy. Guidelines recommend monotherapy when possible and folate supplementation beginning before and continuing throughout pregnancy.

The incidence of congenital malformations born to women with epilepsy (WWE) is increased; however, it is low compared with untreated seizure disorders during pregnancy. The infant of an epileptic mother has twice the risk of other infants for a major malformation; the risk for perinatal death is 1.2 to three times greater. It should be noted that ≥ 90% of women with adequately treated epilepsy deliver a normal infant. The prevention of tonic-clonic seizures is extremely important. In addition, simple interventions (avoiding sleep deprivation, folic acid supplementation) will help optimize outcome.

WWE are at greater risk for fetal loss, and infants born to them have approximately double the risk of major malformations as other infants. Treatment of a patient having had more than one seizure is necessary, despite the concerns associated with medication exposure; the risk of uncontrolled maternal seizures is substantial. Many older AEDs are known teratogens, while the data on newer agents are more limited. In recent years, multiple medication registries for WWE who become pregnant have been established. Emerging data from these registries confirm monotherapy is generally associated with better outcomes.

Rates of fetal malformation appear highest with valproate (approximately 6%). This agent should probably be avoided when possible. Two other medications, carbamazepine and lamotrigine (Lamictal, GlaxoSmithKline), appear to be associated with comparatively minimal risk. Despite the fact that lamotrigine is not approved as monotherapy, data from comparative trials demonstrate efficacy similar to traditional first-line agents (including carbamazepine) with better tolerability. I'd recommend the physician initiate lamotrigine monotherapy with slow titration to minimize the risk of rash. However, regardless of the agent chosen, monotherapy should be used whenever possible.

Michele A. Faulkner, Pharm.D.Associate Professor of Pharmacy PracticeCreighton University School ofPharmacy and Health ProfessionsOmaha