USE OF SELECTIVE SEROTONIN REUPTAKE INHIBITORS IN PREGNANCY

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(Date of issue: January 2017, Version: 2.2)

This is a UKTIS monograph for use by health care professionals. For case-specific advice please contact UKTIS on 0344 892 0909. To report an exposure please download and complete a pregnancy reporting form. Please encourage all women to complete an online reporting form.

Summary

Six selective serotonin reuptake inhibitors (SSRIs) are licensed in the UK: citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine and sertraline. SSRIs are used in the management of various forms of anxiety and in depressive illness. Licensed indications vary for individual SSRIs.

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. It remains uncertain as to whether 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 increase in absolute risk of cardiovascular malformation following exposure in utero, however other studies have found no increased risk and recent meta-analyses have failed to confirm this association. 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 spontaneous abortion, 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, and 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, the findings may be confounded.  Offspring neurodevelopment following maternal use of SSRIs in pregnancy requires further investigation before further 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 monitored for associated central nervous system, motor, respiratory and gastrointestinal symptoms. An increased risk of persistent pulmonary hypertension (PPHN) of the newborn has also been reported following exposure to SSRIs as a class beyond 20 weeks of gestation and, although this remains an uncommon event (0.2-1.2% vs. 0.1-0.2% in the background population), it represents a potentially serious neonatal complication.

It is important to ensure that maternal mental health is treated appropriately. As such, SSRI use in pregnancy may be clinically indicated, but the risks and benefits of use must be considered on a case-by-case basis. Where possible, non-pharmaceutical management of depression and/or anxiety is preferable in pregnancy. Where a patient is stabilised on an SSRI, either prior to conception or during pregnancy, the perceived benefits  of discontinuing treatment, changing to another antidepressant, or reducing the dose, should be carefully weighed against the risk maternal relapse during pregnancy or post partum may pose to both mother and child. In cases where treatment with an SSRI is continued in pregnancy, the lowest effective dose should be used. 

Please refer to the respective monograph for guidance on fetal monitoring following exposure to individual SSRIs in pregnancy.

This document is regularly reviewed and updated. Only use full UKTIS monographs downloaded directly from TOXBASE.org to be sure you are using the most up-to-date version. The summaries of these monographs are openly available on UKTIS.org.

This is a summary of the full UKTIS monograph for health care professionals and should not be used in isolation. The full UKTIS monograph and access to any hyperlinked related documents is available to health care professionals at www.toxbase.org.

If you have a patient with exposure to a drug or chemical and require assistance in making a patient-specific risk assessment, please telephone UKTIS on 0344 892 0909 to discuss the case with a teratology specialist.

If you would like to report a pregnancy to UKTIS please click here to download our pregnancy reporting form. Please encourage all women to complete an online reporting form.

Disclaimer: Every effort has been made to ensure that this monograph was accurate and up-to-date at the time of writing, however it cannot cover every eventuality and the information providers cannot be held responsible for any adverse outcomes of the measures recommended. The final decision regarding which treatment is used for an individual patient remains the clinical responsibility of the prescriber. This material may be freely reproduced for education and not for profit purposes within the UK National Health Service, however no linking to this website or reproduction by or for commercial organisations is permitted without the express written permission of this service. This document is regularly reviewed and updated. Only use UKTIS monographs downloaded directly from TOXBASE.org or UKTIS.org to ensure you are using the most up-to-date version.