Risk of postpartum episodes in women with bipolar disorder after lamotrigine or lithium use during pregnancy: A population-based cohort study

Highlights

• Women with bipolar disorder are at high risk for relapse postpartum.

• There is evidence for efficacy of lithium peripartum.

• Lamotrigine was not inferior to lithium in preventing severe postpartum relapse.

Abstract

Background

Women with bipolar disorder are at high risk for relapse/recurrence postpartum. Among all mood stabilizers, lithium has the largest evidence base for efficacy in the peripartum period, but lamotrigine is increasingly prescribed for bipolar spectrum disorders during pregnancy. The aim of this study was to investigate whether lamotrigine use during pregnancy is as effective as lithium in the prevention of severe episodes postpartum.

Methods

Danish national registries were used to identify pregnancies of women with a diagnosis of bipolar spectrum disorders at the time of conception who used lamotrigine or lithium during pregnancy. We compared the risk of inpatient psychiatric admission within three months postpartum between women who used lamotrigine (N=55) versus lithium (N=59) during pregnancy. A logistic regression model was used to calculate crude and adjusted odds ratios.

Results

We did not find a significant difference in the risk of postpartum psychiatric admission between women who used lamotrigine versus lithium during pregnancy (7.3% versus 15.3% respectively, adjusted OR 0.83; 95% CI 0.22–3.14). We adjusted for year of delivery, parity, previous admissions and antidepressant/benzodiazepine use during pregnancy. Other variables did not differ substantially between groups.

Limitations

We used an observational design and therefore patients were not randomized to lamotrigine or lithium. The study has a small sample size.

Conclusions

Lamotrigine was not inferior to lithium in the prevention of severe postpartum episodes. Our findings suggest lamotrigine could be a reasonable alternative treatment option for bipolar disorder during pregnancy in patients with vulnerability for depression and may prevent severe episodes postpartum.

Introduction

Guiding women with bipolar disorder through pregnancy and the postpartum period is a challenge for psychiatrists and obstetricians, especially because these women are at very high risk for relapse and recurrence postpartum (37%, 95% confidence interval 29% −45%) (Wesseloo et al., 2016). Treatment with a mood stabilizer increases the likelihood of maintaining mood stability during pregnancy and preventing postpartum episodes (Newport et al., 2008, Viguera et al., 2007). However, the benefits of medication use during pregnancy need to be carefully weighed against the risks to the fetus. Lithium is the most effective known mood stabilizer and therefore remains the gold standard for the treatment of bipolar disorder (Geddes and Miklowitz, 2013). However, data on lithium teratogenicity have been inconclusive, thereby complicating decision-making for women with bipolar disorder during pregnancy. In a recent meta-analysis, the association between lithium use during pregnancy and fetal malformations was non-significant, but the results were mainly based on small case-control studies (total n=264, range n=13–89 cases) (McKnight et al., 2012). Over the past couple of decades, lamotrigine has increasingly been used during pregnancy as an alternative treatment option to lithium, due to its more favorable reproductive profile (Christensen et al., 2013, Hayes et al., 2011). Large register-based studies including women with epilepsy (n=1019 and n=1280) reported finding no evidence for an increased risk of fetal malformations associated with in utero lamotrigine exposure (Mølgaard-Nielsen and Hviid, 2011; Tomson et al., 2011). However, the efficacy of lamotrigine during the peripartum period is largely unknown (Newport et al., 2008). Therefore, the aim of this study was to compare mood stabilization during pregnancy with lamotrigine versus lithium in the prevention of severe postpartum episodes.