Is sertraline (Zoloft) safe to use during pregnancy in a woman with a history of depression or anxiety?

Sertraline Safety in Pregnancy

Sertraline is safe to use during pregnancy and is considered a first-line SSRI for treating depression and anxiety in pregnant women, with the benefits of treatment typically outweighing the risks when clinically indicated. 1, 2

Key Safety Evidence

Malformation Risk

• No increased risk of major congenital malformations, including cardiac defects, has been demonstrated with first-trimester sertraline exposure in large population-based studies. 1, 2
• Sertraline should be preferred over paroxetine, which carries FDA pregnancy category D classification due to cardiac malformation concerns. 2
• Among SSRIs, sertraline and citalopram have the strongest safety profiles, with associations between these agents and negative outcomes remaining mixed and generally unsubstantiated when controlled for maternal depression effects. 3

Persistent Pulmonary Hypertension of the Newborn (PPHN)

• There is a possible association between late pregnancy SSRI exposure and PPHN, but the absolute risk remains very low with a number needed to harm of 286-351. 4, 1, 2
• The FDA label notes that PPHN occurs in 1-2 per 1000 live births in the general population, and epidemiologic evidence regarding SSRI association remains conflicting. 5

Neonatal Adaptation Syndrome

• Approximately one-third of newborns exposed to SSRIs in late pregnancy may develop neonatal adaptation syndrome, with symptoms including irritability, jitteriness, tremors, feeding difficulties, respiratory distress, hypoglycemia, and seizures. 4, 2
• These symptoms typically appear within hours to days after birth and resolve spontaneously within 1-2 weeks in most cases. 4, 2
• Infants should be monitored for at least 48 hours after birth, with early follow-up arranged after hospital discharge. 4, 2
• In severely affected infants, a short-term course of chlorpromazine may provide symptom relief. 4, 2

Clinical Decision Algorithm

When to Continue Sertraline

• Women with severe depression or history of relapse when discontinuing treatment should continue sertraline during pregnancy, as untreated depression poses significant risks. 2
• Untreated maternal depression is associated with premature birth, decreased breastfeeding initiation, low fetal growth, and impaired mother-infant bonding. 4, 1, 6
• Women who discontinue antidepressants during pregnancy show significantly increased relapse rates of major depression. 2, 5

Dosing Recommendations

• Use the lowest effective dose throughout pregnancy. 4, 1, 2
• Monitor for symptoms of depression throughout pregnancy to ensure adequate control. 1
• Sertraline plasma concentrations remain relatively steady during pregnancy, though there is substantial 10-fold interindividual variation. 7
• Therapeutic drug monitoring may assist in identifying poor metabolizers at risk for adverse effects. 7
• CYP2C19 poor metabolizers have 42% reduced sertraline clearance and may be at risk for subtherapeutic concentrations during pregnancy. 8, 9

Breastfeeding Considerations

• Sertraline is one of the two most preferred antidepressants during breastfeeding due to minimal excretion in breast milk (less than 10% of maternal dose reaches infant). 2
• Sertraline has low infant-to-maternal plasma concentration ratios, with placental passage to infants being only 25-33% of maternal concentrations. 2, 7
• The 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. 9
• Continue sertraline during breastfeeding rather than discontinuing, as the benefits of both breastfeeding and treating maternal depression outweigh minimal infant exposure risks. 2

Important Caveats

• The FDA label states there are no adequate and well-controlled studies in pregnant women, and sertraline should be used only if potential benefits justify potential risks. 5
• However, multiple recent reviews have not identified adverse neurodevelopmental outcomes among infants born to women treated with SSRIs during pregnancy. 2
• Do not discontinue treatment due to fear of medication risks, as untreated maternal depression carries substantial documented risks to both mother and infant. 2
• The decision to use sertraline must weigh both the potential risks of SSRI exposure against the established benefits of treating depression. 5