Działania niepożądane w czasie ciąży i poważne wrodzone wady rozwojowe u niemowląt pacjentek z zaburzeniami afektywnymi dwubiegunowymi i zaburzeniami schizoafektywnymi leczonych lekami przeciwpadaczkowymi: przegląd systematyczny

Anna Giménez,Marc Valentí,Gerard Anmella,Norma Verdolini,Eduard Vieta,Justo E Pinzón,Susana P Gomes,Isabella Pacchiarotti,José M Goikolea,Andrea Murru,Joaquín Gil,Marta Gómez-Ramiro

doi:10.12740/pp/105906

Abstract

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. 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. 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. 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.

Highlights

Bipolar Disorder (BD) is a chronic affective disorder characterized by manic, hypomanic, depressive or mixed episodes
The few available studies focusing on pregnant patients with BD have reported that they are more likely to have low birthweight infants (9.8% vs. 5.7%), preterm births (14.2% vs. 6.9%) and small for gestational age (SGA) children (22.3% vs.15.7%) compared with pregnant women with no history of mental illness [2]
All of them were observational cohort studies. 9 studies assessed BD, and 7 of them included other psychiatric disorders such as schizoaffective disorder (SAD). 8 studies assessed outcomes related to LTG, 6 the effects of VPA, 4 studies tested CBZ, 3 included TPR, and 2 of them GBP

Summary

Introduction

Bipolar Disorder (BD) is a chronic affective disorder characterized by manic, hypomanic, depressive or mixed episodes. Lifetime prevalence of bipolar spectrum disorders has been estimated at 2.4% [1]. The few available studies focusing on pregnant patients with BD have reported that they are more likely to have low birthweight infants (9.8% vs 5.7%), preterm births (14.2% vs 6.9%) and small for gestational age (SGA) children (22.3% vs.15.7%) compared with pregnant women with no history of mental illness [2]. Some researchers have assessed the influence on these outcomes of modifiable variables such as smoking, which has found to double the risk of delivering a preterm infant, and illicit drug use, which increases the risk by almost one and half times [7]. The relationship between adverse outcomes in pregnancy and pharmacotherapy has been evaluated [8]

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