Is sertraline (Zoloft) safe to use during pregnancy?

Safety of Sertraline During Pregnancy

Sertraline is one of the preferred antidepressant options during pregnancy due to its favorable safety profile, and should be continued at the lowest effective dose if clinically indicated as the benefits of treating depression often outweigh potential risks to the mother-infant dyad. 1

Benefits of Treating Depression During Pregnancy

• Untreated depression during pregnancy is associated with premature birth, decreased initiation of breastfeeding, and potential harmful effects on the mother-infant relationship 1, 2
• Women who discontinue antidepressant medication during pregnancy show a significant increase in relapse of major depression 3
• Treatment of depression is important for both maternal and fetal wellbeing 1

Safety Profile of Sertraline During Pregnancy

• Sertraline is one of the most commonly prescribed antidepressants during pregnancy due to its favorable safety profile 1, 4
• The FDA label states that sertraline should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus 3
• Placental passage of sertraline to the infant is low, with median concentrations in infants at 33% and 25% of their mothers', measured in cord blood and infant plasma respectively 5

Potential Risks and Considerations

Neonatal Adaptation Syndrome

• Third-trimester use of sertraline may lead to neonatal adaptation syndrome in approximately one-third of exposed newborns 2
• Symptoms include crying, irritability, jitteriness, tremors, poor feeding, hypertonia, tachypnea, sleep disturbance, hypoglycemia, and seizures 2
• These symptoms typically appear within hours to days after birth and most resolve within 1-2 weeks 2

Persistent Pulmonary Hypertension of the Newborn (PPHN)

• Some studies suggest a possible association between SSRI use during pregnancy and PPHN, though evidence is conflicting 1, 3
• A meta-analysis indicated a number needed to harm of 286-351 for PPHN with late pregnancy SSRI exposure 1, 2
• The FDA label notes that several recent epidemiologic studies suggest a positive statistical association between SSRI use (including sertraline) in pregnancy and PPHN, while other studies do not show a significant statistical association 3

Pharmacokinetic Considerations

• Sertraline clearance is reduced by 42% in CYP2C19 poor metabolizers compared to other phenotypes 6
• During pregnancy, sertraline concentration-to-dose ratios are decreased and remain consistently low until after delivery 7
• Mean sertraline concentration-to-dose ratios during the last 4 weeks of pregnancy are 22% lower than at ≥8 weeks after delivery 7

Management Recommendations

• Use the lowest effective dose of sertraline during pregnancy 1, 3
• Monitor for symptoms of depression throughout pregnancy 1, 2
• For women already taking sertraline who become pregnant, continuation of treatment is generally recommended if clinically indicated 1, 3
• Infants exposed to sertraline in utero should be monitored for at least 48 hours after birth for signs of neonatal adaptation syndrome 2
• Arrange for early follow-up after hospital discharge for infants exposed to sertraline in the third trimester 1, 2

Breastfeeding Considerations

• Sertraline transfers in low concentrations into breast milk and is considered one of the preferred antidepressants during breastfeeding 1, 6
• Median daily infant dosage through breast milk is approximately 6.9 μg/kg after a 50 mg maternal daily dose, representing only 0.95% of the weight-adjusted maternal dose 6
• Sertraline and paroxetine are considered to have more favorable profiles during breastfeeding due to lower infant-to-maternal plasma concentration ratios 2

Common Pitfalls and Caveats

• Failing to recognize that untreated depression poses significant risks to both mother and baby 1, 2
• Abruptly discontinuing sertraline during pregnancy, which may lead to relapse of depression 3
• Not monitoring infants exposed to sertraline in the third trimester for neonatal adaptation syndrome 2
• Overlooking the need for potential dose adjustments during pregnancy, as sertraline clearance changes throughout pregnancy 7