There have long been concerns regarding the use of the anticonvulsant valproate (Depakote) during pregnancy. First trimester use of valproate has been associated with a 3-5% risk of neural tube defects, as well as an increased risk of other malformations affecting the heart, limbs, and genitals. A recent report published in the New England Journal of Medicine indicates that in utero exposure to valproate may also result in lower IQ.   Â
Given recent discussions within our group and with our colleague, Lewis Holmes, MD, chief of the Genetics and Teratology Unit at Massachusetts General Hospital for Children and director of the North American AED (Antiepileptic Drug) Pregnancy Registry, I wanted to expand upon a previous blog post. In the initial post, I wrote that women who take certain medications, like mood stabilizers or antiepileptic drugs, are advised to take increased doses of folic acid before pregnancy and throughout pregnancy.
Lamotrigine (Lamictal) has been effectively used for the maintenance treatment of bipolar disorder. Many women suffering from bipolar disorder are of childbearing age; therefore an adequate contraception is a major concern that needs to be addressed in this population.
As many of the traditional mood stabilizers used to treat bipolar disorder, including lithium and valproic acid, carry some teratogenic risk and the reproductive safety of other medications, including the atypical antipsychotic agents, has not been well-characterized, many women with bipolar disorder decide to discontinue their treatment during pregnancy. A new study from Dr. Adele Viguera and her colleagues at the Massachusetts General Hospital and the Emory University School of Medicine helps to better define the risks associated with discontinuing treatment during pregnancy.
Early reports suggested that women with bipolar disorder may be at lower risk for onset or relapse of this disorder during pregnancy and that some women may be able to remain well during pregnancy despite medication discontinuation. However, more recent studies have suggested that recurrence of affective illness during pregnancy is relatively common among women with bipolar disorder. Dr. Adele Viguera and her colleagues at the Center for Women's Mental Health reported that among pregnant bipolar women, relapse rates were very high (58%) in those women who discontinued maintenance treatment with lithium during pregnancy (Viguera et al 2000).
Because rates of postpartum illness are very high in women with bipolar disorder, it is generally recommended that mothers continue treatment with a mood stabilizer throughout the postpartum period to reduce their risk of relapse; however, the use of medications during the postpartum period is complicated by the issue of breastfeeding. All medications are secreted into the breast milk, although their concentrations appear to vary (Chaudron and Jefferson, 2000).
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.
