Medication decisions during pregnancy are always a challenge, and, since many pregnancies are unplanned, considerations should start well before pregnancy occurs and should be addressed again if the patient becomes pregnant. Patients with bipolar disorder who stop medication during pregnancy can have a relapse rate of 80% for depression, 16% for mania, and 4% for mixed episodes during the postpartum period (Figure). (1) However, many bipolar medications can have harmful effects during pregnancy.
Ranking Treatment Options
Valproate is the most teratogenic bipolar medication and should be avoided in women of childbearing potential until all other options have been exhausted. (2,3) Use of valproate in pregnancy has been a source of concern internationally. (4,5) Valproate (but not lamotrigine) also is associated with lower intelligence scores in young children who were exposed to it in utero (6) and is associated with an elevated risk of autism spectrum disorder and attention-deficit/hyperactivity disorder. (7)
Carbamazepine is almost as teratogenic as valproate and is associated with increased spina bifida and vitamin K deficiencies late in pregnancy. (8) The data on lamotrigine suggest low risk of fetal harm as monotherapy, but cleft palate is a concern. (9,10)
Lithium has fewer malformation risks than valproate and carbamazepine. In a large study, the adjusted risk ratio for any cardiac abnormality was 1.65 compared with unexposed babies. (11) The risk rises with higher doses, but it still has been shown to be lower than previously thought. For Ebstein's anomaly, the risk ratio was 2.66. In absolute numbers, the risk was 0.6% for lithium-exposed infants vs 0.18% for those not exposed. In the most recent meta-analysis, the absolute risk of any cardiac abnormality was 1.2%. The increased risk was limited to lithium exposure in the...