Antidepressant use during pregnancy

: what are the outcomes?

Abstract

Antidepressant use is rising globally, including during pregnancy. Although
antidepressants have been used in clinical practice for decades, there is still uncertainty
over whether they confer risks to the fetus when used during pregnancy.
In this thesis, I systematically review and meta-analyse the literature surrounding
antidepressant use during pregnancy and both miscarriage and stillbirth (Chapter 3). I then
use the UK’s Clinical Practice Research Datalink (CPRD) GOLD to describe patterns of
antidepressant prescribing around pregnancy (Chapter 4). In the following two chapters, I
first explore the association between antidepressant use during trimester one and
miscarriage using CPRD GOLD (Chapter 5). Then, leveraging data from the UK, Norway, and
Sweden, I examine antidepressant use any time during pregnancy and birth outcomes,
including stillbirth and gestational age (Chapter 6).
In the systematic review and meta-analyses, I show that antidepressant use during
pregnancy is associated with an increased risk of miscarriage and stillbirth, but risk of bias
is high in many included studies. From 1996 to 2018, I show upwards of 8% of individuals
were prescribed antidepressants during pregnancy in CPRD GOLD. First trimester
antidepressant use is associated with a clinically insignificant increase in risk of miscarriage
(adjusted hazard ratio 1.04, 95% confidence interval 1.02–1.06). Across the UK, Norway,
and Sweden, antidepressant use during pregnancy is associated with an increased risk of
stillbirth, preterm delivery, and low Apgar score, although estimated absolute risk remains
low.
As antidepressant use during pregnancy increases, so does the requirement for
ongoing safety monitoring to aid evidence-based decision making. Overall, my findings
suggest that antidepressants are associated with small increases in risk of certain adverse
outcomes, but absolute risks remain low and residual confounding cannot be ruled out.

Date of Award	18 Mar 2025
Original language	English
Awarding Institution	University of Bristol
Supervisor	Dheeraj Rai (Supervisor), Gemma C Sharp (Supervisor), Harriet Forbes (Supervisor) & Kayleigh E Easey (Supervisor)