Is Zoloft (sertraline) safe to use during the 3rd trimester of pregnancy?

Sertraline (Zoloft) Use in the Third Trimester of Pregnancy

Sertraline can be safely continued during the third trimester of pregnancy when clinically indicated, using the lowest effective dose, as the benefits of treating maternal depression typically outweigh the risks of neonatal complications. 1, 2

Evidence-Based Recommendation

The American Academy of Pediatrics and American Academy of Family Physicians both recommend sertraline as a first-line antidepressant during pregnancy, including the third trimester, due to its favorable safety profile compared to other SSRIs. 1, 2 This recommendation is based on:

• No increased risk of major congenital malformations with first-trimester exposure in large population-based studies 2
• Minimal placental transfer to the fetus, with infant plasma concentrations only 25-33% of maternal levels 3
• Low breast milk excretion, making it the preferred SSRI for continuation postpartum 1, 2

Risks of Third-Trimester Exposure

Neonatal Adaptation Syndrome

Third-trimester sertraline exposure may cause transient neonatal symptoms including: 2, 4, 5

• Respiratory distress and cyanosis
• Irritability, jitteriness, and tremors
• Feeding difficulties
• Sleep disturbance
• Temperature instability

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

Persistent Pulmonary Hypertension of the Newborn (PPHN)

• Late pregnancy SSRI exposure has a possible association with PPHN, but the absolute risk is very low with a number needed to harm of 286-351 1, 2
• Evidence remains conflicting, with some studies showing no association 1

Other Considerations

• Third-trimester exposure may be associated with slightly increased rates of premature delivery and special-care nursery admission, though these findings are not consistent across all studies 6, 5
• No evidence of long-term neurodevelopmental impairment in exposed infants 2

Risks of Untreated Depression

Untreated maternal depression during pregnancy poses significant documented risks: 1, 2

• Premature birth
• Decreased initiation of breastfeeding
• Harm to the mother-infant relationship
• Increased risk of postpartum depression relapse

Women who discontinue antidepressants during pregnancy show a significant increase in relapse of major depression compared to those who continue treatment. 4

Clinical Management Algorithm

For Women Already Taking Sertraline:

1. Continue sertraline through the third trimester at the lowest effective dose 1, 2, 4
2. Do not discontinue medication due to pregnancy, as withdrawal may harm the mother-infant dyad 2
3. Monitor maternal mental health closely throughout pregnancy 1

For Newborns Exposed to Sertraline:

1. Arrange early follow-up after hospital discharge to monitor for neonatal adaptation syndrome 1, 2
2. Monitor infants for signs of drug toxicity or withdrawal over the first week of life 2
3. In severely affected infants with persistent symptoms, short-term pharmacological management (such as chlorpromazine) may provide relief 2

Dosing Considerations:

• Use the lowest effective dose throughout pregnancy 1, 2, 4
• Be aware that sertraline pharmacokinetics show marked individual variation during pregnancy, with some women experiencing lower drug levels in the third trimester 7
• Consider therapeutic drug monitoring in women with poor symptom control, as there is a 10-fold interindividual variation in sertraline metabolism 3

Postpartum and Breastfeeding

Sertraline should be continued during breastfeeding as it is one of the two most commonly prescribed antidepressants during lactation due to: 1, 2

• Minimal excretion in breast milk (infant receives <10% of maternal dose) 2
• Low infant-to-maternal plasma concentration ratios 2
• No reported adverse effects in breastfed infants in most cases 1

Common Pitfalls to Avoid

• Do not discontinue sertraline solely due to pregnancy, as this significantly increases relapse risk 2, 4
• Do not avoid treatment altogether due to fear of medication risks, as untreated depression carries substantial documented risks 2
• Do not switch to paroxetine, which has FDA pregnancy category D classification due to cardiac malformation concerns 2
• Ensure neonatal monitoring is arranged before delivery to avoid missing transient adaptation symptoms 1, 2