For many women with bipolar disorder, lamotrigine (Lamictal) is an effective mood stabilizer. Given its relatively favorable reproductive safety profile, lamotrigine is a reasonable option for women who require treatment with a mood stabilizer during pregnancy.
We have received many questions regarding the appropriate dosing of lamotrigine during pregnancy and the postpartum period.
What Happens to Lamotrigine Levels During Pregnancy and the Postpartum Period?
Lamotrigine levels do shift during pregnancy. 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, lamotrigine levels may drop by as much as 50%. As there is substantial variability 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 decline. In the setting of falling levels, some women may experience clinical destabilization.
Lamotrigine serum levels return to prepregnancy values within 3 to 4 weeks after delivery. If lamotrigine doses were increased during pregnancy, blood levels may become toxic after delivery. Various signs of toxicity, manifested as diplopia, ataxia, nausea, and dizziness, may occur as early as 3 days after delivery if the dose is not decreased.
Recommendations for Dose Adjustment
Most of our data on this topic comes from women taking lamotrigine for the management of seizure disorder. A recent article proposed the following guidelines for adjusting lamotrigine (LTG) dose during pregnancy and the postpartum period:
The reference LTG plasma concentration (RC) should be determined before pregnancy or as early in pregnancy as possible. After conception, plasma concentration of LTG should be measured every 4 weeks throughout pregnancy. When the LTG plasma concentration falls below the RC, the dose of LTG should be increased by 20-25%. Postpartum, the plasma concentration of LTG should be measured within the first or second week, and if the LTG plasma concentration is higher than the RC, the LTG dose should be reduced by 20-25% and the procedure repeated until RC is re-established.
While there is no reason to believe that women with bipolar disorder metabolize lamotrigine differently than women with epilepsy, many psychiatrists do not routinely adjust lamotrigine doses during pregnancy. Because there is no established therapeutic blood level for lamotrigine, monitoring by blood level may be difficult. For women taking lamotrigine prior to pregnancy, a pre-pregnancy blood level of lamotrigine may be established as a baseline and subsequently used as a guideline for dosing during pregnancy. However, careful monitoring of clinical symptoms may be equally as effective in managing dose adjustments during pregnancy and the postpartum period. If the dose of lamotrigine is increased substantially during pregnancy, the patient should be monitored for any signs of toxicity (e.g., nausea, dizziness, vision changes, altered mental status) during the first few weeks after delivery.
There is some controversy here. Where our group typically does not increase the dose of lamotrigine prophylactically in women with bipolar disorder, there was a recent report from Clark and colleagues which recommended adjusting lamotrigine dosing according to blood levels. In a response to this article, Sharma and colleagues questioned this approach, as there was no evidence in this small case series to indicate that lower blood levels of lamotrigine were associated with relapse. It should also be noted that if recurrent symptoms do emerge during pregnancy, other medications, such as the atypical antipsychotics, may prove to be more effective than lamotrigine for managing hypomania or mania and may also act more quickly.
Ruta Nonacs, MD PhD
Clark CT, Klein AM, Perel JM, Helsel J, Wisner KL. Lamotrigine dosing for pregnant patients with bipolar disorder. Am J Psychiatry. 2013 Nov 1;170(11):1240-7.
Fotopoulou C, Kretz R, Bauer S, Schefold JC, Schmitz B, Dudenhausen JW, Henrich W. Prospectively assessed changes in lamotrigine-concentration in women with epilepsy during pregnancy, lactation and the neonatal period. Epilepsy Res. 2009 Jul;85(1):60-4.
Sabers A. Algorithm for lamotrigine dose adjustment before, during, and after pregnancy. Acta Neurol Scand. 2012 Jul;126(1):e1-4.
Sharma V, Sommerdyk C. Management issues during pregnancy in women with bipolar disorder. Am J Psychiatry. 2014 Mar;171(3):370-1.