Women with bipolar disorder are at increased risk for recurrence of illness during pregnancy. Therefore, many women with bipolar disorder elect to continue treatment with medications during pregnancy after weighing the risks and benefits of various treatment options with their physicians. Lamotrigine (Lamictal) is an anticonvulsant used to treat bipolar disorder. While the safety data on this relatively new anticonvulsant in pregnancy is limited, pregnancy registry data suggests that lamotrigine may pose less of a risk to the developing fetus than with older anticonvulsants, such as valproate (Depakote). With lamotrigine emerging as an effective and relatively safe treatment for pregnant women with bipolar disorder, more attention is now being paid to the effects of pregnancy on lamotrigine levels.
Estrogen increases the clearance of lamotrigine by inducing the liver enzymes involved in its metabolism. Thus, more rapid metabolism results in lower, and possibly sub-therapeutic, levels of lamotrigine. As estrogen levels gradually rise over the course of pregnancy, the clearance of lamotrigine may increase by as much as 200 to 300 percent. Because there are substantial differences in lamotrigine clearance between individuals, some women may experience a large drop in lamotrigine blood levels during pregnancy while others may experience a more modest decrease. It is not yet clear what accounts for these differences between individuals.
Psychiatrists do not routinely adjust lamotrigine doses during pregnancy. As we learn more about the risks and benefits of dose adjustment, however, we may begin to consider ways in which we should monitor and adjust lamotrigine doses during pregnancy. Because there is no established therapeutic blood level for lamotrigine, monitoring by blood level can be difficult. For women taking lamotrigine prior to pregnancy, a pre-pregnancy blood level of lamotrigine could be established as a baseline and subsequently used as a guideline. However, careful monitoring of clinical symptoms may be equally as effective in managing dose adjustments in pregnancy.
Blood levels of lamotrigine will rise postpartum but do so gradually. If a woman’s lamotrigine dose is not increased during pregnancy, it should rise to pre-pregnancy levels following delivery, putting her at very low risk of postpartum toxicity. If a significant increase in lamotrigine dose is made during pregnancy, however, a taper should be initiated at the time of delivery. Symptoms of lamotrigine toxicity include dizziness, lack of coordination and/or blurred or double vision; any woman experiencing these symptoms after delivery should contact her doctor immediately.
Julia Wood, M.D.
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