For women with bipolar disorder, choosing whether to maintain or discontinue treatment with a mood stabilizer during pregnancy is challenging.  This is a process which requires careful and thoughtful consideration, weighing the risk of adverse outcomes associated with exposure to a particular drug against the risk of recurrent illness in the setting of medication discontinuation. While we have considerable information regarding the teratogenicity of various mood stabilizers, we have much less data regarding other pregnancy outcomes.  

In a recent study, Cohen and colleagues examined Medicaid Analytic eXtract data for pregnant women taking mood stabilizers in order to assess risk for several different negative pregnancy outcomes: preeclampsia, placental abruption, growth restriction and preterm birth.

The analysis included women who gave birth to a liveborn infant between 2000 and 2010 (n = 1,472,672).  Women exposed to lamotrigine, valproate, topiramate, carbamazepine, oxcarbazepine, and lithium during the first 20 weeks of pregnancy were identified. 10,575 women were exposed to monotherapy with an anticonvulsant or lithium, and 917 were exposed to polytherapy with two or more mood stabilizers. 

The reference group did not fill a prescription for an anticonvulsant or lithium during the 3 months prior to conception or the first half of pregnancy. Women who continued mood stabilizer monotherapy after 20 weeks were also compared to those who discontinued. 

In unadjusted analyses, exposure to each specific mood stabilizer and polytherapy with mood stabilizers was associated with increased risk of all four adverse outcomes listed above, as compared to no exposure (RRs ranged from 1.15 to 1.56). However, when the researchers adjusted for confounding variables, there was no difference observed between exposed and unexposed pregnancies.   

Continuation of mood stabilizers was not associated with an increased risk for any of the  outcomes compared to discontinuation; in fact, continuation of mood stabilizer was associated with reduced risk of placental abruption and growth restriction.

While previous studies have raised concerns regarding the impact of mood stabilizers on pregnancy outcomes, it has been difficult to distinguish the effects of the medication from the effects of the underlying disorder.  By controlling for potential confounders, the researchers conducting this study were able to get a better sense of the risks of medication exposure.  As was observed in a previous study from Wisner and colleagues (2019), this study found that treatment with mood stabilizers did not negatively affect pregnancy outcomes, and there is indication in both of these studies that treated women may, in fact, have better outcomes than untreated women.  

Ruta Nonacs, MD PhD

Cohen JM, Huybrechts KF, Patorno E, Desai RJ, Mogun H, Bateman BT, Hernández-Díaz S. Anticonvulsant Mood Stabilizer and Lithium Use and Risk of Adverse Pregnancy Outcomes. J Clin Psychiatry. 2019 Jun 18;80(4).

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