Risk of postpartum episodes in women with bipolar disorder after lamotrigine or lithium use during pregnancy: A population-based cohort study
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.
Section snippets
Methods
We conducted a population-based cohort study using Danish national registers. This was possible as all live births and residents in Demark are assigned an unique personal identification number and registered in the Danish Civil Registration System, which allows linkage of data at the individual level within and between registers (Pedersen, 2011). Women with a history of bipolar spectrum disorder (including bipolar disorder I, II and not otherwise specified classifications) were identified in
Results
We identified N=891 women with bipolar spectrum disorders and N=1201 corresponding pregnancies. In the majority of pregnancies (N=1066) women received prescriptions of antidepressants, antipsychotics, other mood stabilizers, a combination of these prescriptions or no medication. In N=135 pregnancies, women received lamotrigine or lithium prescriptions. We excluded N=21 pregnancies because prescriptions were restricted to the first trimester (lamotrigine N=10, lithium N=0) or because women were
Discussion
In this population-based study, we found similar postpartum inpatient admission risks after lamotrigine and lithium use during pregnancy. If replicated, this finding is of clinical importance, since lamotrigine is considered to be a more favorable option than lithium with regard to the risk of adverse neonatal outcomes (Chisolm and Payne, 2016). In line with a previous study from the United Kingdom (Hayes et al., 2011), we found an increase in lamotrigine use over the last decades in Denmark.
Conclusions
Management of bipolar disorder during and after pregnancy is challenging, especially because the postpartum period is associated with the highest lifetime risk of hospitalization for women with bipolar disorder (Munk-Olsen et al., 2009). In this study, lamotrigine was not inferior to lithium in the prevention of severe postpartum episodes. Lamotrigine could be a reasonable alternative treatment option for bipolar disorder during pregnancy in patients with vulnerability for depression and may
Acknowledgements
No conflict of interest, no acknowledgements.
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2020, Asian Journal of PsychiatryCitation Excerpt :Therefore, in spite of prophylactic treatment with lamotrigine, the overall recurrence rate of mood episodes during pregnancy was 41.2 %. The largest data on the postpartum peirod were reported by Wesseloo et al. (2017). In this study, reported risk of postpartum episodes in 55 patients using lamotrigine during pregnancy was 7.3 %.
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Authors share last authorship.