Is duloxetine (Cymbalta) safe to use during pregnancy?

Safety of Duloxetine During Pregnancy

Duloxetine should be used with caution during pregnancy due to limited safety data, with potential risks including increased risk of postpartum hemorrhage and possible spontaneous abortion, though it does not appear to significantly increase the risk of major congenital malformations. 1, 2

Safety Profile and Risks

• Duloxetine has not been clearly associated with major congenital malformations, including cardiac malformations, though data are limited 3, 4
• A large population-based study from Denmark and Sweden found no increased risk of major or minor congenital malformations or stillbirth with duloxetine exposure during pregnancy 3
• The FDA label warns that duloxetine use in the month before delivery may increase the risk of postpartum hemorrhage 1
• There may be a possible increased risk for spontaneous abortion, though confounding by indication cannot be ruled out 2

Timing of Exposure Considerations

• Late pregnancy exposure to duloxetine may be associated with:
  • Poor neonatal adaptation syndrome, though the magnitude of this risk is not known 2
  • A slightly increased risk of preterm birth (relative risk 1.19,95% CI 1.04 to 1.37) 4
  • Neonatal complications requiring prolonged hospitalization, respiratory support, and tube feeding immediately upon delivery 1

Maternal Disease Considerations

• Untreated depression during pregnancy is associated with increased risks of adverse outcomes 1
• Women who discontinue antidepressants during pregnancy are more likely to experience a relapse of major depression than women who continue antidepressants 1
• The risk of untreated depression should be weighed against the potential risks of medication exposure 1, 2

Long-term Outcomes

• Limited data are available on long-term developmental outcomes for children exposed to duloxetine in utero 2

Clinical Approach

• For women requiring treatment for depression during pregnancy:
  • Conduct a thorough risk-benefit assessment considering the severity of maternal depression and potential risks of medication 1, 2
  • Consider alternative antidepressants with more established safety profiles during pregnancy if appropriate for the patient's condition 2
  • If duloxetine is continued during pregnancy, monitor closely for signs of postpartum hemorrhage, especially if used in the month before delivery 1
  • For women exposed to duloxetine in late pregnancy, ensure appropriate monitoring of the neonate for poor adaptation syndrome 1, 2

Breastfeeding Considerations

• Infant exposure to duloxetine in breast milk is less than 1% of the maternal weight-adjusted dose 2
• Limited data suggest duloxetine can be safely administered to a woman who is breastfeeding her infant 2