USE OF SELECTIVE SEROTONIN REUPTAKE INHIBITORS IN PREGNANCY

Six selective serotonin reuptake inhibitors (SSRIs) are licensed for the treatment of various forms of anxiety and depression in the UK. 

This document summarises findings from studies which have investigated the fetal effects of prenatal exposure to SSRIs as a class and should therefore be used in conjunction with the relevant individual SSRI monograph (where available), as human pregnancy data varies both in quantity and quality for each specific SSRI, with certain pregnancy outcomes unstudied for some. There is no robust evidence to suggest that fetal or neonatal effects differ substantially for individual SSRIs, and changing from one SSRI to another in pregnancy on the basis of teratogenic concern is therefore not currently recommended.

Data regarding malformation risk for SSRIs as a class are conflicting and confounded. Some studies have suggested a small ~1.2-fold increase in absolute risk of cardiovascular malformation following exposure in utero; however, other studies have found no increased risk. Recent evidence has suggested that the increased cardiac malformation rates observed in some studies may be explained by factors common to women with health conditions for which SSRIs are prescribed, rather than SSRI exposure. Associations with various other specific congenital malformations have also been reported by some studies which analysed SSRIs as a class, but these findings have not been widely replicated. A causal association between use of SSRIs in pregnancy and any type of malformation in the offspring therefore remains unconfirmed.

Maternal SSRI use in pregnancy has been associated with an increased risk of miscarriage, low birth weight and preterm delivery in some, but not all studies. However, the available data are conflicting and, in some instances, limited by the study methods. The impact that maternal SSRI use in pregnancy has on the incidence of these outcomes therefore remains unclear. Furthermore, increased risks for all these outcomes have been associated with maternal depression; therefore, in many studies, confounding by indication cannot be excluded. The available data do not suggest that SSRI use in pregnancy increases the risk of stillbirth.

Data on neurodevelopmental impairment following maternal SSRI use in pregnancy are conflicting. Some studies have suggested possible adverse effects on early infant motor development and behaviour. However, study sample sizes are often small, and many assessments were undertaken in children under one year of age. A number of studies have suggested an association with autism spectrum disorder (ASD), but as some of these studies have also suggested, associations may exist between ASD and the underlying maternal condition; therefore, findings may be confounded. Offspring neurodevelopment following maternal use of SSRIs in pregnancy requires further investigation before additional conclusions can be provided.

In utero exposure to SSRIs in the weeks prior to delivery confers a risk of transient neonatal withdrawal syndrome and infants should be delivered in hospital and monitored for central nervous system, motor, respiratory and gastrointestinal symptoms.

An increased risk of persistent pulmonary hypertension of the newborn (PPHN) has been reported following exposure to SSRIs as a class beyond 20 weeks of gestation. The current estimate of the absolute risk of PPHN following SSRI exposure is <0.4% (background rate 0.1 to 0.2%), suggesting that it remains uncommon following exposure. However, as PPHN is potentially serious, this should be discussed with women considering SSRI use in pregnancy.

The Medicines and Healthcare products Regulatory Agency (MHRA) has advised that there is a small overall increased risk of postpartum haemorrhage (PPH) attributable to SSRI/SNRI use in the month prior to delivery, but this risk may be higher in women with other risk factors for abnormal bleeding. Studies have identified up to a 1.3-fold increased risk following gestational use of an SSRI; should this prove accurate, the absolute risk of PPH among SSRI-exposed women would range from 13 to 20% (background 10 to 15%). Careful assessment of the risk of PPH versus the risk of maternal relapse, should the medication be discontinued, is advised when considering continued SSRI/SNRI antidepressant use in late pregnancy. Prescribers are also encouraged to ensure maternal compliance with heparin self-administration in all pregnant women with risk factors for venous thromboembolism.

It is important to ensure that mental health conditions are treated appropriately. As such, SSRIs may be suitable for use in pregnancy following an individualised assessment of the risks and benefits. Where clinically appropriate, non-pharmaceutical management of depression and/or anxiety could be considered during pregnancy. However, where a patient is stabilised on an SSRI, either prior to conception or during pregnancy, the risk of discontinuing treatment, changing the medication or reducing the dose, should be carefully weighed against the risk of maternal relapse. In cases where treatment with an SSRI is continued in pregnancy, the lowest effective dose should be used.