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

Sertraline Use During Pregnancy

Sertraline is considered a first-line SSRI for use during pregnancy and should be continued at the lowest effective dose when clinically indicated, as the risks of untreated maternal depression outweigh the small potential risks to the fetus. 1

Primary Recommendation

The American Academy of Pediatrics specifically recommends sertraline as first-line therapy during pregnancy due to its favorable safety profile, including minimal excretion in breast milk and low infant-to-maternal plasma concentration ratios. 1 SSRI treatment should be continued during pregnancy at the lowest effective dose rather than discontinued, as withdrawal may have harmful effects on the mother-infant dyad. 2, 1

Risk-Benefit Analysis

Risks of Untreated Depression

• Untreated depression during pregnancy is associated with premature birth, decreased initiation of breastfeeding, and potential harmful effects on the mother-infant relationship. 2, 3
• Women who discontinue antidepressant medication during pregnancy show a significant increase in relapse of major depression. 2

Potential Fetal and Neonatal Risks

Neonatal Adaptation Syndrome:

• Approximately one-third of SSRI-exposed newborns develop neonatal adaptation syndrome, with symptoms including crying, irritability, jitteriness, tremors, poor feeding, hypertonia, tachypnea, sleep disturbance, hypoglycemia, and seizures. 2
• Symptoms typically appear within hours to days after birth and usually resolve spontaneously within 1-2 weeks. 2, 1
• The FDA label confirms that neonates exposed to sertraline late in the third trimester may develop complications requiring prolonged hospitalization, respiratory support, and tube feeding. 4

Persistent Pulmonary Hypertension of the Newborn (PPHN):

• There is a possible association between late pregnancy SSRI exposure and PPHN, though evidence is conflicting. 2, 1, 3
• The number needed to harm for PPHN with late pregnancy SSRI exposure is approximately 286-351, indicating a very small absolute risk. 2, 1

Cardiac Malformations:

• No increased risk of cardiac malformations has been demonstrated with first-trimester sertraline use in large population-based studies. 1
• This contrasts with paroxetine, which should be avoided due to FDA pregnancy category D classification for cardiac malformation concerns. 1

Management Algorithm

During Pregnancy:

1. Continue sertraline if already taking it when pregnancy is discovered, rather than discontinuing. 1, 3
2. Use the lowest effective dose throughout pregnancy. 2, 1, 3
3. Monitor for symptoms of depression throughout pregnancy. 3
4. Start with low doses (25-50 mg daily) if initiating treatment, and slowly titrate upward. 1

Monitoring Newborns:

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

Postpartum and Breastfeeding:

• Continue sertraline during breastfeeding, as it is minimally excreted in breast milk, providing the infant with less than 10% of the maternal daily dose. 1, 3
• Sertraline and paroxetine are the most commonly prescribed antidepressants during breastfeeding due to their favorable safety profiles. 1, 3

Important Caveats

Pharmacokinetic Considerations:

• Sertraline crosses the placenta and can be found in amniotic fluid. 2
• Plasma sertraline concentrations may decrease during pregnancy, with a 22% reduction in concentration-to-dose ratios in late pregnancy compared to postpartum. 5
• Placental passage to the infant is low, with infant concentrations at 25-33% of maternal levels. 6

Genetic Variability:

• Pregnant individuals with poor or intermediate CYP2C19 activity may experience a 51% decrease in sertraline levels during pregnancy and are at risk for subtherapeutic concentrations. 5

Alternative Considerations:

• If sertraline is not tolerated or ineffective, citalopram can be considered as an alternative. 1

What NOT to Do

• Do not discontinue sertraline solely due to pregnancy, as this significantly increases the risk of depression relapse. 2, 1
• Do not avoid treatment altogether due to fear of medication risks, as untreated maternal depression carries substantial documented risks to both mother and infant. 1
• Do not use paroxetine as an alternative, given its association with cardiac malformations. 1