Is sertraline (selective serotonin reuptake inhibitor) safe to use during pregnancy?

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Last updated: November 19, 2025View editorial policy

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Sertraline in Pregnancy

Sertraline should be considered the first-line SSRI for treating depression during pregnancy due to its favorable safety profile, minimal breast milk excretion, and low infant-to-maternal plasma concentration ratios. 1

Why Sertraline is Preferred

  • Sertraline is specifically recommended as first-line therapy by the American Academy of Pediatrics for pregnant and breastfeeding women requiring SSRI treatment, based on its minimal excretion in breast milk (providing infants with less than 10% of maternal daily dose) and low infant-to-maternal plasma concentration ratios. 1

  • Placental passage is low, with infant plasma concentrations measuring only 25-33% of maternal levels at delivery, reducing fetal drug exposure compared to other SSRIs. 2

  • No cardiac malformations have been linked to sertraline, unlike paroxetine and fluoxetine which show stronger associations with congenital defects and should be avoided. 3

Key Risks to Discuss with Patients

Neonatal Adaptation Syndrome (Most Common Risk)

  • Third-trimester SSRI exposure causes neonatal adaptation syndrome in approximately one-third of exposed newborns, presenting with irritability, jitteriness, tremors, feeding difficulty, respiratory distress, and sleep disturbance within hours to days after birth. 1, 4

  • Symptoms typically resolve spontaneously within 1-2 weeks without intervention in most cases. 1, 4

  • Severely affected infants may require short-term chlorpromazine for symptom relief, though this is uncommon. 1

Persistent Pulmonary Hypertension of the Newborn (PPHN)

  • Late pregnancy SSRI exposure has a possible association with PPHN, though evidence remains conflicting and the FDA revised its 2006 advisory in 2011 to reflect this uncertainty. 5, 6

  • The number needed to harm is 286-351, meaning the absolute risk increase is very small (approximately 0.3-0.4%). 5, 6

Other Considerations

  • No increased risk of cardiac malformations has been demonstrated with first-trimester sertraline use in large population-based studies. 5, 6

  • Long-term neurodevelopmental outcomes appear reassuring, with several recent reviews finding no adverse neurodevelopmental effects among infants exposed to SSRIs during pregnancy. 1

Management Algorithm

Step 1: Assess Depression Severity and Treatment Necessity

  • Untreated depression during pregnancy carries significant risks including premature birth, decreased breastfeeding initiation, and harm to the mother-infant relationship. 5, 6

  • Women who discontinue antidepressants during pregnancy show significantly increased relapse rates of major depression compared to those who continue treatment. 7

Step 2: If Treatment is Indicated

  • Continue or initiate sertraline at the lowest effective dose throughout pregnancy rather than discontinuing, as withdrawal may cause more harm to the mother-infant dyad than continued treatment. 1, 6

  • Avoid paroxetine specifically, which has FDA pregnancy category D classification due to cardiac malformation concerns. 5

Step 3: Monitoring During Pregnancy

  • Use the lowest effective dose and monitor maternal mental health closely throughout pregnancy. 1, 6

  • Consider therapeutic drug monitoring given the 10-fold interindividual variation in sertraline metabolism during pregnancy, which may help identify poor metabolizers at risk for adverse effects. 2

  • Maternal sertraline concentrations remain relatively steady during pregnancy (67% relative difference between second trimester and postpartum), so dose adjustments are typically not needed based solely on gestational age. 2

Step 4: Neonatal Monitoring

  • Arrange for early follow-up after hospital discharge and monitor infants for at least 48 hours after birth for signs of neonatal adaptation syndrome including feeding difficulties, respiratory distress, irritability, and tremors. 1, 4

  • Symptoms appearing in the first week of life typically resolve within 1-2 weeks without intervention. 1, 4

Breastfeeding Continuation

  • Sertraline should be continued during breastfeeding as it transfers in very low concentrations into breast milk and is one of the two most commonly prescribed antidepressants during lactation (along with paroxetine). 5, 1, 6

  • The benefits of breastfeeding for both mother and infant are well-documented, and untreated maternal depression poses significant risks that outweigh the minimal infant drug exposure. 1

Common Pitfalls to Avoid

  • Do not discontinue sertraline abruptly upon discovering pregnancy, as this significantly increases depression relapse risk and may harm maternal-fetal outcomes more than continued treatment. 1, 7

  • Do not switch to paroxetine or fluoxetine, which have stronger associations with adverse fetal outcomes. 3, 8

  • Do not avoid treatment altogether due to fear of medication risks, as untreated maternal depression carries substantial documented risks to both mother and infant. 5, 6

References

Guideline

SSRI Use During Pregnancy and Postpartum Period

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Risks of SSRIs During Pregnancy on Neonatal Transition

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Safety of Sertraline During Pregnancy

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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