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

Is Sertraline Safe in Pregnancy?

Yes, sertraline is considered safe and is the first-line SSRI for use during pregnancy and breastfeeding, though it requires monitoring for neonatal adaptation syndrome in the third trimester. 1, 2

Why Sertraline is the Preferred Choice

Sertraline should be your first-line therapy for pregnant women requiring antidepressant treatment based on recommendations from the American Academy of Pediatrics. 1, 2 The key advantages include:

• No increased risk of major congenital malformations: Large population-based studies have found no increased risk of cardiac malformations with first-trimester sertraline use. 1, 2, 3
• Minimal placental transfer: Median concentrations in infants are only 25-33% of maternal levels, indicating low placental passage. 4
• Excellent breastfeeding safety: Sertraline provides infants less than 10% of the maternal daily dose through breast milk, making it safe for continuation during lactation. 1, 2

Critical Management Principles

Dosing Strategy

• Use the lowest effective dose throughout pregnancy to minimize fetal exposure while maintaining maternal mental health. 1, 2, 5
• Do not discontinue sertraline upon discovering pregnancy, as women who stop antidepressants show a significant increase in relapse of major depression. 2, 5, 6
• Start with 25-50 mg daily and titrate slowly while monitoring. 1

Third-Trimester Considerations and Neonatal Monitoring

Approximately one-third of exposed newborns may develop neonatal adaptation syndrome when SSRIs are used in the third trimester. 5 This presents with:

• Irritability, jitteriness, tremors, restlessness 1, 5
• Feeding difficulties, poor sucking 1, 5
• Sleep disturbance, crying 1, 5
• Respiratory distress, tachypnea 1, 5
• Hypoglycemia, hypertonia, hyperreflexia 5

These symptoms typically appear within hours to days after birth and usually resolve within 1-2 weeks without intervention. 1, 5

Required Monitoring Protocol

• Monitor all exposed infants for at least 48 hours after birth for signs of neonatal adaptation syndrome. 2, 5
• Arrange early follow-up after initial hospital discharge to assess for delayed symptoms. 1, 5
• In severely affected infants with persistent symptoms, a short-term course of chlorpromazine has provided measurable relief. 1, 5

Specific Risks to Discuss

Persistent Pulmonary Hypertension of the Newborn (PPHN)

There is a possible association between late pregnancy SSRI exposure and PPHN, but the absolute risk is very small:

• Number needed to harm: 286-351 1, 5
• PPHN occurs in 1-2 per 1000 live births in the general population 6

Pharmacokinetic Changes During Pregnancy

• Sertraline plasma concentrations decrease by approximately 22% during late pregnancy compared to postpartum levels. 7
• Women with poor or intermediate CYP2C19 activity are at particular risk for subtherapeutic concentrations during pregnancy (51% decrease in drug levels). 7
• Consider therapeutic drug monitoring in women not responding adequately to treatment. 4, 7

Risk-Benefit Context: Why Treatment Should Continue

Untreated depression during pregnancy carries substantial documented risks that often exceed medication risks: 1, 2, 5

• Premature birth
• Decreased breastfeeding initiation
• Harm to the mother-infant relationship
• Significant increase in relapse of major depression if medication is discontinued

Alternative if Sertraline Fails

Consider citalopram as a second-line option if sertraline is not tolerated or ineffective. 1, 2 Citalopram has a similar safety profile with mixed evidence regarding adverse outcomes. 3

Common Pitfalls to Avoid

• Do not discontinue effective SSRI therapy upon discovering pregnancy without careful psychiatric consultation, as relapse risk is high. 2
• Do not avoid treatment altogether due to fear of medication risks, as untreated maternal depression poses greater documented risks to both mother and infant. 1, 2
• Avoid paroxetine specifically, which has FDA pregnancy category D classification due to cardiac malformation concerns. 1, 3, 8

FDA Pregnancy Classification

The FDA labels sertraline as Pregnancy Category C, meaning animal studies showed adverse effects but there are no adequate well-controlled studies in pregnant women. 6 However, this classification predates the extensive human safety data now available showing sertraline's favorable profile. 1, 2, 3