Advice for healthcare professionals:
- SSRIs and SNRIs are known to increase the bleeding risk; observational data suggest that the use of some antidepressants in the last month before delivery may increase the risk of postpartum haemorrhage
- continue to consider the benefits and risks for use of antidepressants during pregnancy, and the risks of untreated depression in pregnancy
- healthcare professionals, including midwives, should continue to enquire about the use of antidepressant medicines, particularly in women in the later stages of pregnancy
- consider the findings of the review in the context of individual patient risk factors for bleeding or thrombotic events
- do not stop anticoagulant medication in women at high risk of thrombotic events in reaction to these data but be aware of the risk identified
- report any suspected adverse reactions associated with medicines taken during pregnancy via the Yellow Card scheme
Review of bleeding risks
Selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) are two classes of commonly used antidepressant medicines. These medicines have been known for some time to increase the general risk of bleeding. This is thought to be due to serotonergic effect impairing platelet aggregation. Bleeding abnormalities associated with use of these medicines have been reported rarely and the absolute risk is thought to be low.
A recent EU review considered spontaneous data in the context of a wider literature review for SSRI and SNRI medicines. The review identified observational studies reporting an increased risk of postpartum haemorrhage in association with antidepressant use in late pregnancy, particularly for SSRIs and SNRIs.
Despite heterogeneous data and differences in definitions of postpartum haemorrhage, the review concluded that the data suggested a slightly increased risk of postpartum bleeding with use of SSRIs and SNRIs during the month before delivery. The review concluded that this risk might also apply to the newest antidepressant vortioxetine.
Following the review, warnings are being added to the product information for these medicines (list of products below) to advise that they may increase the risk of postpartum haemorrhage.
Information around risks
Rates of postpartum haemorrhage vary by geographical region with one study suggesting rates in Europe of 12.7% with a blood loss greater than 500 millilitres and 2.8% with a blood loss greater than 1000 millilitres.
The review estimated that the use of antidepressant medicines in the month before delivery increases the risk by less than two-fold. The severity of cases was not reported, but no fatalities were flagged in the dataset reported by the European review. Some datasets in the meta-analyses considered in the review defined all postpartum haemorrhage as blood loss of 500 millilitres or higher; some as 1000 millilitres.
Although the added risk of postpartum haemorrhage related to use of SSRI/SNRI antidepressants is small, it may be significant in individual patients when combined with other risk factors for post-partum haemorrhage. Updates to the patient information leaflets will include the increased risk, especially for patients with bleeding disorders. The leaflets will advise that the midwife or doctor should be made aware they are taking these medicines.
In the UK we have received a very small number of suspected adverse drug reactions (ADRs) reporting postpartum haemorrhage in association with antidepressant medicines. We ask clinicians to continue to be vigilant for ADRs associated with any medicines used during pregnancy and report them via the Yellow Card scheme (see below).
Assessment of thrombotic and bleeding risks for the peripartum period
The Commission on Human Medicines’ Medicines in Women’s Health Expert Advisory Group (MWHEAG) has considered the review findings and advised on the need to make healthcare professionals aware of the potential increased risk of bleeding in women who take SSRI/SNRI antidepressants in the month before delivery. They advised that these risks should be incorporated into the standard clinical risk assessment for bleeding and thrombotic risk.
MWHEAG advised that prescribers should encourage compliance with heparin self-administration in all patients with risk factors for venous thromboembolism (clinical guideline from RCOG). Clinical experience suggests approximately one-third of patients require heparin in the postpartum period after caesarean section to reduce the risk of venous thromboembolic events.
The benefits and risk of all medicines should be carefully considered, and the new data carefully communicated in the context of the risk of thromboembolic events. Thromboembolic events in the peripartum period can have potentially fatal consequences. Women who have been prescribed heparin should be encouraged to adhere closely to the recommended dose and frequency of administration of heparin as advised by their doctor even if they are also taking SSRI or SNRIs.
Taking the evidence into account, the review considered there to be sufficient evidence to update the product information for:
SSRIs: citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline
SNRIs: desvenlafaxine, milnacipran, venlafaxine
Reminder of advice for use of antidepressants in pregnancy
Mental health conditions such as depression, particularly severe depression, can have serious consequences for both maternal and neonatal health. Healthcare professionals should continue to consider the benefits and risks for use of antidepressants during pregnancy, and the risks of untreated depression during pregnancy.
Use of SSRIs and SNRIs is associated with a risk of persistent pulmonary hypertension in the newborn and neonatal withdrawal and toxicity reactions. In 2010, we encouraged healthcare professionals to enquire about the use of SSRIs and SNRIs during pregnancy, particularly in women in the later stages of pregnancy.
Close observation of neonates exposed to SSRIs or SNRIs for signs of persistent pulmonary hypertension and withdrawal or toxicity effects is recommended after birth. The risks to newborn babies of exposure to SSRIs and SNRIs during pregnancy must be balanced with the risk to the mother and baby of untreated depression during pregnancy.
Report on a Yellow Card
Please continue to report suspected adverse drug reactions (ADRs) associated with antidepressants or any other medicines via the Yellow Card scheme.
Reporting for medicines in pregnancy
Please report any suspected ADRs associated medicines taken during pregnancy or breastfeeding experienced by the woman and any suspected effects on the baby or child.
When reporting ADRs related to medicines used in pregnancy, the following information is particularly valuable for our assessment of the report:
Timings of when the medicine was taken during the pregnancy
The outcome of the pregnancy (when known)
Details of any relevant family history, including any obstetric history
Please include any other relevant information; including other medications or substances taken during the pregnancy, as well as folic acid intake.
Where to report ADRs
Healthcare professionals, patients, and caregivers are asked to submit reports using the Yellow Card scheme electronically using:
When reporting please provide as much information as possible, including information about batch numbers, medical history, any concomitant medication, onset, treatment dates, and product brand name.
Report suspected side effects to medicines, vaccines or medical device and diagnostic adverse incidents used in coronavirus (COVID-19) using the dedicated Coronavirus Yellow Card reporting site or the Yellow Card app. See the MHRA website for the latest information on medicines and vaccines for COVID-19.
Article citation: Drug Safety Update volume 14, issue 6: January 2021: 5.