Antidepressants in pregnancy

Seek expert advice

A study investigated the correlation between the specific selective serotonin re-uptake inhibitors (SSRIs) and some birth defects and showed (1):

• citalopram and escitalopram monotherapies were not significantly associated with birth defects;
• citalopram and neural tube defects in later generations had a borderline association;
• fluoxetine was significantly associated with right ventricular outflow tract obstruction and early closure of cranial sutures;
• paroxetine was associated with anencephaly, atrial septal defect, right ventricular outflow tract obstruction, gastroschisis, and omphalocele
• sertraline was the most commonly reported SSRI, but none of the five previously reported birth defects associations with sertraline was confirmed in this study

NICE state (2):

• Starting, using and stopping treatment
  • General advice
    • before starting any treatment in pregnancy and the postnatal period, discuss with the woman the higher threshold for pharmacological interventions arising from the changing risk‑benefit ratio for psychotropic medication at this time and the likely benefits of a psychological intervention
    • if the optimal treatment for a woman with a mental health problem is psychotropic medication combined with a psychological intervention, but she declines or stops taking psychotropic medication in pregnancy or the postnatal period, ensure that:
      • she is adequately supported and
      • has the opportunity to discuss the risk associated with stopping psychotropic medication and
      • is offered, or can continue with, a psychological intervention
    • when psychotropic medication is started in pregnancy and the postnatal period, consider seeking advice, preferably from a specialist in perinatal mental health, and:
      • choose the drug with the lowest risk profile for the woman, fetus and baby, taking into account a woman's previous response to medication
      • use the lowest effective dose (this is particularly important when the risks of adverse effects to the woman, fetus and baby may be dose related), but note that sub‑therapeutic doses may also expose the fetus to risks and not treat the mental health problem effectively
      • use a single drug, if possible, in preference to 2 or more drugs
      • take into account that dosages may need to be adjusted in pregnancy
    • when a woman with severe mental illness decides to stop psychotropic medication in pregnancy and the postnatal period, discuss with her:
      • her reasons for doing so
      • the possibility of:
        • restarting the medication
        • switching to other medication
        • having a psychological intervention
        • increasing the level of monitoring and support.
      • ensure she knows about any risks to herself, the fetus or baby when stopping medication
    • when a woman with depression or an anxiety disorder decides to stop taking psychotropic medication in pregnancy and the postnatal period, discuss with her:
      • her reasons for doing so
      • the possibility of:
        • having a psychological intervention
        • restarting the medication if the depression or anxiety disorder is or has been severe and there has been a previous good response to treatment
        • switching to other medication
        • increasing the level of monitoring and support while she is not taking any medication
      • ensure she knows about any risks to herself, the fetus or baby when stopping medication
    • If a pregnant woman has taken psychotropic medication with known teratogenic risk at any time in the first trimester:
      • confirm the pregnancy as soon as possible
      • explain that stopping or switching the medication after pregnancy is confirmed may not remove the risk of fetal malformations
      • offer screening for fetal abnormalities and counselling about continuing the pregnancy
      • explain the need for additional monitoring and the risks to the fetus if she continues to take the medication.
        
        Seek advice from a specialist if there is uncertainty about the risks associated with specific drugs.
• when choosing a tricyclic antidepressant (TCA), selective serotonin reuptake inhibitor (SSRI) or (serotonin‑) noradrenaline reuptake inhibitor [(S)NRI], take into account:
  • the woman's previous response to these drugs
  • the stage of pregnancy
  • what is known about the reproductive safety of these drugs (for example, the risk of fetal cardiac abnormalities and persistent pulmonary hypertension in the newborn baby)
  • the uncertainty about whether any increased risk to the fetus and other problems for the woman or baby can be attributed directly to these drugs or may be caused by other factors
  • the risk of discontinuation symptoms in the woman and neonatal adaptation syndrome in the baby with most TCAs, SSRIs and (S)NRIs, in particular paroxetine and venlafaxine

The Medicines and Healthcare products Regulatory Agency (MHRA) note that (3):

• SSRIs and SNRIs are known to increase bleeding risks due to their effect on platelet function
• data from observational studies suggest that the use of SSRI/SNRI antidepressants during the month before delivery may result in a small increased risk of postpartum haemorrhage
• prescribers should consider this risk in the context of an individual patient’s bleeding and thrombotic risk assessment during the peripartum period and the benefits of antidepressants for the patient’s mental health during this time.

The Medicines and Healthcare products Regulatory Agency (MHRA) note that (4):

• epidemiological data suggest that the use of SSRIs in pregnancy, particularly in the later stages, may increase the risk of persistent pulmonary hypertension in the newborn (PPHN)
• healthcare professionals are encouraged to enquire about the use of SSRIs and SNRIs, particularly in women in the later stages of pregnancy
• close observation of neonates exposed to SSRIs or SNRIs for signs of PPHN is recommended after birth

Antidepressants in pregnancy and development of neurodevelopment disorders in children (5)

• results of a cohort study suggest that antidepressant use in pregnancy itself does not increase the risk of neurodevelopmental disorders in children

Notes:

• women on antidepressant treatment prior to pregnancy
  • study evidence suggests that for women with severe mental illnesses and currently receiving stable treatment, continuing antidepressant treatment during pregnancy may be beneficial (6)

The respective summary of product characteristics must be consulted before prescribing an antidepressant during pregnancy.

Reference:

1. Reefhuis J et al. National Birth Defects Prevention Study. Specific SSRIs and birth defects: bayesian analysis to interpret new data in the context of previous reports. BMJ. 2015; 351: h3190
2. NICE (February 2020). Antenatal and postnatal mental health: clinical management and service guidance
3. Drug Safety Update volume 14, issue 6: January 2021: 5.
4. Drug Safety Update May 2010, vol 3 issue 10: 2.
5. Suarez EA, Bateman BT, Hernandez-Díaz S, et al. Association of Antidepressant Use During Pregnancy With Risk of Neurodevelopmental Disorders in Children. JAMA Intern Med. Published online October 03, 2022. doi:10.1001/jamainternmed.2022.4268
6. Trinh NTH, Munk-Olsen T, Wray NR, et al. Timing of Antidepressant Discontinuation During Pregnancy and Postpartum Psychiatric Outcomes in Denmark and Norway. JAMA Psychiatry. Published online March 08, 2023. doi:10.1001/jamapsychiatry.2023.0041