Is sertraline (Zoloft) safe during pregnancy?

Safety of Sertraline During Pregnancy

Sertraline is generally considered safe during pregnancy, with the benefits of treating depression often outweighing potential risks to the mother-infant dyad. 1

Benefits vs. Risks Assessment

• Depression during pregnancy is associated with premature birth and decreased initiation of breastfeeding, making treatment important for maternal and fetal wellbeing 1
• Sertraline is one of the most commonly prescribed antidepressants during pregnancy and breastfeeding due to its favorable safety profile 1
• The FDA drug label indicates there are no adequate well-controlled studies in pregnant women, but animal studies show potential risks only at doses significantly higher than human therapeutic doses 2

Potential Risks

• Third-trimester exposure to sertraline may lead to neonatal adaptation syndrome, characterized by respiratory distress, cyanosis, feeding difficulties, and irritability in newborns 2

  • These symptoms typically appear within hours to days after birth and usually resolve within 1-2 weeks 2
  • The clinical picture may sometimes resemble serotonin syndrome 2

• Some studies suggest a possible association between SSRI use during pregnancy and persistent pulmonary hypertension of the newborn (PPHN), though evidence is conflicting 1, 2

  • A meta-analysis indicated a number needed to harm of 286-351 for PPHN with late pregnancy SSRI exposure 1

• Limited evidence suggests a small potential increased risk for specific cardiac malformations:

  • One study found an association with atrial/ventricular defects (RR 1.34) and craniosynostosis (RR 2.03), though absolute risks remain low 3
  • A large population-based cohort study found no link between first-trimester antidepressant use and cardiac malformations 1

Pharmacokinetic Considerations

• Sertraline plasma concentrations decrease during pregnancy, with levels approximately 22% lower in late pregnancy compared to postpartum 4
• Placental transfer of sertraline to the infant is relatively low, with infant concentrations measuring 25-33% of maternal levels 5
• Dose adjustments may be needed during pregnancy, particularly for women with CYP2C19 poor or intermediate metabolizer status 6, 4

Management Recommendations

• Use the lowest effective dose of sertraline during pregnancy 7
• Monitor for symptoms of depression throughout pregnancy, as untreated depression poses significant risks 1, 2
• For women already taking sertraline who become pregnant, continuation of treatment is generally recommended if clinically indicated 7, 2
• Consider monitoring sertraline levels during pregnancy, especially in women with known CYP2C19 poor or intermediate metabolizer status 6, 4
• Arrange for early follow-up after hospital discharge for infants exposed to sertraline in the third trimester to monitor for neonatal adaptation syndrome 7, 2

Breastfeeding Considerations

• Sertraline transfers in low concentrations into breast milk and is considered one of the preferred antidepressants during breastfeeding 1, 8
• Paroxetine and sertraline are the most commonly prescribed antidepressants during breastfeeding due to their favorable safety profiles 1

Clinical Decision Algorithm

1. Assess severity of depression and necessity of medication treatment
2. If treatment is indicated, sertraline is a preferred option during pregnancy 1, 8
3. Use the lowest effective dose and monitor maternal mental health closely 7
4. In the third trimester, prepare for potential neonatal adaptation syndrome 2
5. Continue sertraline during breastfeeding if clinically indicated 1