A Deeper Shade of Blue

Women with bipolar disorder are at high risk for illness during pregnancy. Unfortunately, many of the mood stabilizers used to treat bipolar disorder, including lithium and valproic acid (Depakote), have been associated with congenital malformations (birth defects) when used during the first trimester. The U.S. Food and Drug Administration released that the use of lamotrigine (Lamictal) may also carry some risk to the developing fetus.

Preliminary data from the North American Antiepileptic Drug Pregnancy Registry suggest a possible association between exposure to lamotrigine monotherapy during the first trimester of pregnancy and cleft lip and/or cleft palate. The oral clefts reported were few and were not part of a syndrome that included other birth defects. Other pregnancy registries of similar size have not replicated this observation. The validity of this possible association cannot be established until further data are collected in the NAAED Pregnancy Registry, in other ongoing pregnancy registries, or through other research efforts. The clinical significance of this preliminary report is thus uncertain.

While this report raises concerns, it is important to put this risk into perspective. If we assume that the findings from the North American registry are true, the absolute risk of having a child with cleft lip or palate is about 0.9%. While some women may elect to discontinue treatment with lamotrigine given the magnitude of this risk, many women with more severe bipolar illness may require treatment with some type of mood stabilizer during pregnancy. However, the alternatives to lamotrigine also carry some risk. Exposure to valproate during the first trimester carries an unacceptably high risk of major malformations (over 10% in some samples), including neural tube defects. Lithium usage during the first trimester has been associated with a 0.1% risk of cardiovascular malformation. Thus, some women may elect to continue treatment with lamotrigine, acknowledging that, while there may be risks associated with this exposure, other treatment options are not risk-free.

More information on this topic from Medscape:

Pregnant women who have received or require continuing treatment with lamotrigine during pregnancy may be registered by contacting the NAAED Pregnancy Registry at 1-888-233-2334. Patients may also register in a manufacturer- sponsored registry, which is aimed at obtaining additional data regarding this potential association, by calling 1-800-336-2176.