Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) used in the treatment of depression, obsessive-compulsive disorder and bulimia nervosa.
The available data regarding gestational use of fluoxetine are conflicting, with the majority of studies not demonstrating statistically significant increased risks of major malformation or of cardiac malformation specifically. It is therefore unclear whether the available findings concerning maternal fluoxetine use in pregnancy represent a risk with the individual drug, a class effect of SSRIs, or are produced due to confounding from other factors related to the maternal illness. Those studies which have indicated increased risks have generally suggested that the absolute risks remain low (up to 1.18 times the background risk for malformations overall and up to 1.6-fold for cardiac malformations).
Studies which have investigated the risk of miscarriage, intrauterine death, preterm delivery, low birth weight and neurodevelopmental delay following fluoxetine use in pregnancy are reassuring overall but are generally too limited to fully rule out increased risks.
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, overall, 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 maternal mental health conditions are treated appropriately. As such, fluoxetine 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 fluoxetine, 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 fluoxetine is continued in pregnancy, the lowest effective dose should be used.
Exposure to fluoxetine at any stage in pregnancy would not usually be regarded as medical grounds for termination of pregnancy, or any additional fetal monitoring. Other risk factors may be present in individual cases which may independently increase the risk of adverse pregnancy outcome. Clinicians are reminded of the importance of consideration of such factors when performing case-specific risk assessments.
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 NHS health care professionals who are logged in.
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.