Lamotrigine: Alternate Bipolar Disorder Treatment to Lithium During Pregnancy

Results of a population-based cohort study published in the Journal of Affective Disorders show lamotrigine is not inferior to lithium in preventing severe postpartum depression in women with bipolar disorder.¹

Women with bipolar disorder have a 37% risk for relapse and recurrence in the postpartum period, and the highest lifetime risk for hospitalization for this population occurs during this period.^2,3 Mood stabilizing therapies can reduce the likelihood of illness episodes during and after pregnancy, although potential risks to the fetus must be considered with the use of such agents. The benefits often outweigh the possible risks, however, because of the sharply elevated risk for recurrence when mood stabilizers are discontinued: up to 100%, according to 1 study.⁴

Although lithium is the gold standard treatment for bipolar disorder, findings regarding its teratogenicity are inconclusive. “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,” wrote the current authors.⁵ For example, register-based studies of women with epilepsy who took lamotrigine during pregnancy found no increased risk for fetal malformations.⁶

Although some evidence supports the benefits of lamotrigine for bipolar disorder during pregnancy, it remains unclear whether the drug is also effective during the postpartum period.⁴ To that end, the present research used Danish national registers to compare the efficacy of lamotrigine and lithium in preventing severe postpartum episodes in 114 women with bipolar disorder I, II, and not otherwise specified.

In patients who used lamotrigine (n=55) during pregnancy vs those who used lithium (n=59), no significant difference was observed in the risk for postpartum psychiatric admission, even after adjustment for year of delivery, primiparity, psychiatric admission <2 years before conception, and concurrent use of antidepressants or benzodiazepines (7.3% vs 15.3%, respectively; adjusted odds ratio [OR], 0.83; 95% CI, 0.22-3.14).

Although these results require further study before firm conclusions can be drawn, these 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,” the authors concluded. 

References

1. R, Liu X, Clark CT, Kushner SA, Munk-Olsen T, Bergink V. Risk of postpartum episodes in women with bipolar disorder after lamotrigine or lithium use during pregnancy: A population-based cohort study [published online May 3, 2017]. J Affect Disord. doi: 10.1016/j.jad.2017.04.070
2. Wesseloo R, Kamperman AM, Munk-Olsen T, Pop VJ, Kushner SA, Bergink V. Risk of postpartum relapse in bipolar disorder and postpartum psychosis: a systematic review and meta-analysis [published online October 30, 2015]. Am J Psychiatry. doi: 10.1176/appi.ajp.2015.15010124
3. Munk-Olsen T, Laursen TM, Mendelson T, Pedersen CB, Mors O, Mortensen PB. Risks and predictors of readmission for a mental disorder during the postpartum period. Arch Gen Psychiatry. 2009;66:189-195. doi: 10.1001/archgenpsychiatry.2008.528
4. Newport, DJ, Stowe ZN, Viguera AC, et al. Lamotrigine in bipolar disorder: efficacy during pregnancy. Bipolar Disord. 2008;10:432-436. doi: 10.1111/j.1399-5618.2007.00565.x
5. Hayes J, Prah P, Nazareth I, et al. Prescribing trends in bipolar disorder: cohort study in the United Kingdom THIN primary care database 1995–2009 [published online December 7, 2011]. PLoS One. doi: 10.1371/journal.pone.0028725
6. Tomson T, Battino D, Bonizzoni E, et al. Dose-dependent risk of malformations with antiepileptic drugs: an analysis of data from the EURAP epilepsy and pregnancy registry [published online June 5, 2011]. Lancet Neurol. doi: 10.1016/S1474-4422(11)70107-7