Anticonvulsants During Pregnancy in Women with Bipolar Disorder

Unfortunately the mood stabilizers most commonly used to treat bipolar disorder (including lithium and valproic acid) can increase the risk of certain types of congenital malformations in children exposed to these medications during the first trimester of pregnancy. For women who need a mood stabilizer during pregnancy, lithium is the safest option; however, when used during the first trimester, it carries a 0.1% risk of a cardiac malformation called Ebstein’s anomaly. Although this is a potentially serious complication, it is important to keep in mind that the risk of malformation is relatively small.

Some of the anticonvulsants used to treat bipolar disorder pose a more significant risk to the developing fetus. Carbamazepine carries a 1% risk of neural tube defect. Valproic acid (Depakote) is associated with a 3-5% risk of neural tube defect, as well as an increased risk of other malformations affecting the heart, limbs, and genitals. There is also evidence that valproic acid may result in developmental delay or other neurobehavioral problems in children exposed to this medication in utero.

There is less information on the reproductive safety of newer anticonvulsants used to treat bipolar disorder, specifically gabapentin (Neurontin) and oxcarbazepine (Trileptal). However, there is a growing body of information the reproductive safety of lamotrigine (Lamictal), and this may be a useful alternative for some women. The manufacturer of Lamictal (GlaxoSmithKline) maintains a pregnancy registry for lamotrigine and has presented preliminary data regarding outcomes of children exposed to lamotrigine in utero. Out of 200 children exposed to lamotrigine alone during the first trimester, four had major birth defects, representing a 2.0% risk of major malformation, which is within the range of 2 to 4% observed in the general population absent exposure to any known teratogen. Lamotrigine polytherapy, however, seems to carry a more significant risk, with a 6.5% risk of major malformation observed in a total of 184 cases. While this preliminary information is encouraging, further study is needed to better define the risks associated with lamotrigine use during pregnancy. (Physicians may obtain information regarding this GlaxoSmithKline registry by calling (800) 336-2176.)

Information on the reproductive safety of anticonvulsants is being collected by the Anti-Epilepsy Drug (AED) Pregnancy Registry at the Massachusetts General Hospital (Dr. Lewis Holmes). The AED Registry may be contacted by calling 888-233-2334, or through their website: http://www.massgeneral.org/aed/.

Ruta Nonacs, MD, PhD