Is Lamictal safe in pregnancy?

Lamictal, also known as lamotrigine, is an anticonvulsant medication that is frequently used in psychiatry. It has been shown to be an effective maintenance medication in bipolar disorder--that is, studies have found evidence of its effectiveness in preventing depressive episodes in people with bipolar disorder. There is weaker evidence for its effectiveness in treating acute depressive episodes. Many of our patients have asked us about whether or not Lamictal is safe in pregnancy. 

The data that are available suggest that lamotrigine monotherapy is relatively safe in pregnancy. In 1992, a lamotrigine pregnancy registry was created to monitor for major congenital malformations (i.e., birth defects) in children of mothers who took lamotrigine during the first trimester. The registry collected data from 1,558 pregnancies over 18 years, and found that major congenital malformations occurred in 2.2% of exposures, which is very similar to the baseline rate of birth defects in the general population (frequently cited as between 2-4% of all pregnancies). On the other hand, the rate of birth defects in children exposed to both Lamictal and valproic acid (also known as Depakote), was 10.7%. A prospective study found evidence that the dosage of lamotrigine used affects rates of congenital malformations, with higher doses (>300 mg/ day) leading to a birth defect rate of 4.5%, but lower doses (<300 mg/day) leading to a rate of 2.0%. 

One of frequently cited risks of taking lamotrigine during the first trimester is the development of cleft lip or palate. The formation of the palate occurs between weeks 6 and 11 of gestation. The North American AED registry looked at 684 infants exposed to lamotrigine during the first trimester and found that the risk of developing cleft palate, lip, or both, was 0.73% in the exposed population, compared to 0.07% in the unexposed population. While 0.73% is 10.4x greater than 0.07%, it's important to note that the 0.73% absolute risk of developing a cleft palate or lip with lamotrigine exposure is still quite low, provided the results are accurate. Further, it's important to take the results with a grain of salt for several other reasons, including the relatively small number of women in the study population, and the lack of addressing possible confounding variables like maternal race, habits like smoking or alcohol use, exposure to other medications, and other medical problems. 

One important consideration for a patient who does decide to use Lamictal in pregnancy is that serum levels of the drug will decrease in pregnancy. Estrogen has been shown to increase the clearance, or elimination, of Lamictal, and in pregnancy, clearance increases by 250% on average. One way that this is monitored in patients who use lamotrigine for seizure control is that serum levels are obtained prior to pregnancy, and the dosage of the drug is increased during pregnancy so that serum levels remain above 65% of the pre-pregnancy level. Obtaining levels prior to and during pregnancy is not always necessary in patients who take Lamictal for bipolar disorder, but of course, could be helpful. 

The discerning reader may wonder that if estrogen increases the clearance of Lamictal, then perhaps oral contraceptives that contain estrogen will also lead to decreased Lamictal levels. That is correct! For more on this, please click here.