Is it safe to take Zoloft (sertraline) during pregnancy?

Sertraline (Zoloft) Use During Pregnancy

Sertraline can be continued during pregnancy when clinically indicated, as the benefits of treating depression typically outweigh the potential risks to both mother and infant, though it should be used at the lowest effective dose. 1, 2

Risk-Benefit Framework

Risks of Untreated Depression

• Depression during pregnancy is associated with premature birth and decreased initiation of breastfeeding, making treatment essential for maternal and fetal health 1
• Women who discontinue antidepressants during pregnancy show a significant increase in relapse of major depression compared to those who continue treatment 2

Fetal and Neonatal Considerations

Third-Trimester Exposure Effects:

• Neonates exposed to sertraline late in the third trimester may develop neonatal adaptation syndrome requiring prolonged hospitalization, respiratory support, and tube feeding 2
• Clinical findings include: respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying 2
• These complications can arise immediately upon delivery 2
• The clinical picture may be consistent with either direct toxic effects or drug discontinuation syndrome 2

Persistent Pulmonary Hypertension (PPHN):

• Infants exposed to SSRIs in pregnancy may have an increased risk for PPHN, which occurs in 1-2 per 1000 live births and is associated with substantial neonatal morbidity and mortality 2
• Several epidemiologic studies suggest a positive statistical association between SSRI use (including sertraline) and PPHN, though other studies do not show significant association 2

Teratogenicity:

• Animal studies at doses up to 4 times the maximum recommended human dose showed no evidence of teratogenicity 2
• Delayed ossification was observed in animal fetuses, but clinical significance is unknown 2

Comparative Safety Profile

Sertraline is a preferred first-line SSRI for pregnancy:

• Among SSRIs, sertraline and citalopram should be first-line drug treatments for anxiety and depression in pregnant women, as they have the most favorable safety profiles 3
• Paroxetine and fluoxetine have the strongest associations with negative outcomes (significant malformations, PPHN, and neonatal adaptation syndrome) and paroxetine should be avoided in pregnancy 4, 3
• Sertraline has low placental passage to the infant (median infant concentrations are 25-33% of maternal levels) 5

Dosing and Monitoring Recommendations

Pharmacokinetic Changes:

• Sertraline clearance increases up to 143% by 40 weeks gestational age due to pregnancy-related physiological changes 6
• Mean sertraline concentration-to-dose ratios decrease by 22% in late pregnancy compared to postpartum, potentially leading to subtherapeutic levels 7
• Sertraline concentrations remain consistently low throughout pregnancy until after delivery 7

Practical Dosing Guidance:

• Use the lowest effective dose throughout pregnancy 1, 2
• Consider therapeutic drug monitoring, as interindividual variation is 10-fold, to identify poor metabolizers at risk for adverse effects 5
• Pregnant women with poor or intermediate CYP2C19 activity may experience 51% decrease in sertraline levels and are at risk for subtherapeutic concentrations 7
• Dose adjustments may be needed during pregnancy to maintain therapeutic efficacy 7, 6

Clinical Management Algorithm

For Women Already on Sertraline:

1. Continue treatment if clinically indicated, as discontinuation significantly increases depression relapse risk 2
2. Optimize to the lowest effective dose 1, 2
3. Monitor closely throughout pregnancy, particularly in third trimester 2
4. Arrange for early follow-up after hospital discharge for the infant 8

Neonatal Monitoring:

• Alert neonatal team about third-trimester exposure 2
• Monitor newborns for neonatal adaptation syndrome symptoms, which typically appear within hours to days after birth 8
• Most symptoms resolve within 1-2 weeks 8
• In severely affected infants, short-term pharmacological management may be required 8

Discontinuation Considerations:

• If discontinuation is attempted, use gradual dose reduction rather than abrupt cessation to minimize withdrawal symptoms 2
• If intolerable symptoms occur, resume the previous dose and decrease more gradually 2

Critical Caveats

• The FDA states sertraline "should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus" 2
• There are no adequate and well-controlled studies in pregnant women 2
• The decision must consider both the potential risks of SSRI use and the established benefits of treating depression 2
• Sertraline can be continued during breastfeeding as concentrations in breast milk are very low and not linked to infant complications 3