Adverse outcomes during pregnancy and major congenital malformations in infants of patients with bipolar and schizoaffective disorders treated with antiepileptic drugs: A systematic review

Background. Antiepileptic drugs (AEDs), which are commonly used as a treatment for acute phases and prevention of relapses in bipolar disorder (BD) and schizoaffective disorder (SAD), have been often associated to adverse outcomes in pregnancy and major congenital malformations (MCM). We aimed to summarize available evidence assessing these outcomes when AEDs are used in pregnant women with BD and/or SAD. Methods. We searched four databases from inception to 18 January, 2019. We included peer-reviewed observational studies on the use of AEDs in pregnant women with BD or SAD. We excluded studies not reporting data on BD or SAD, not specifying the AED or not assessing pregnancy outcomes or MCM. Results. The pooled records amounted to 2,861. After duplicate removal and inclusion/exclusion criteria application, we included 9 observational studies assessing patients with BD and SAD. The AEDs evaluated were lamotrigine (LTG), valproate (VPA), carbamazepine (CBZ), oxcarbazepine (OXC), topiramate (TPR), and gabapentin (GBP). VPA and CBZ were the AED most commonly associated to MCM. LTG showed the best safety profile. Higher rates of complications during pregnancy were observed in treated and untreated women with BD compared to healthy controls. Conclusions. AEDs may produce adverse outcomes in pregnancy and MCM in children of pregnant women with BD or SAD, showing higher risks at higher doses. LTG could be considered in this type of patients, given the low rate of adverse events. VPA and CBZ use should be avoided during pregnancy.