Is duloxetine (Cymbalta) safe to use during pregnancy?

Duloxetine Use During Pregnancy

Duloxetine (Cymbalta) should be used with caution during pregnancy as it may increase the risk of postpartum hemorrhage and may cause neonatal complications requiring prolonged hospitalization, respiratory support, and tube feeding when used late in the third trimester. 1

Safety Profile During Pregnancy

Maternal Risks

• Duloxetine use in the month before delivery is associated with an increased risk of postpartum hemorrhage 1
• There may be an increased risk of spontaneous abortion with duloxetine exposure during pregnancy 2

Fetal/Neonatal Risks

• Neonates exposed to duloxetine late in the third trimester may develop complications requiring prolonged hospitalization, respiratory support, and tube feeding 1
• A trend toward increased risk of preterm birth has been observed with duloxetine exposure, although not consistently statistically significant across all comparisons 3
• Most preterm births (79.2%) associated with duloxetine exposure occur in weeks 33-36 of gestation 3
• No clear evidence of increased risk for infants being born small for gestational age 3

Congenital Malformations

• Current data have not identified a clear drug-associated risk of major birth defects or other adverse developmental outcomes 1
• Limited surveillance data suggest that the frequency of abnormal outcomes reported in duloxetine pregnancy cases is generally consistent with historic control rates in the general population 4

Decision-Making Algorithm for Duloxetine Use in Pregnancy

1. Assess the severity of maternal condition

   • Consider the risks of untreated depression or anxiety during pregnancy
   • Untreated depression is associated with increased risk of relapse 1

2. Consider alternative treatments

   • For depression: SSRIs like sertraline may have more pregnancy safety data
   • For pain conditions: non-pharmacological approaches first

3. If duloxetine is deemed necessary:

   • Use the lowest effective dose
   • Consider discontinuing or switching medication before the third trimester if clinically appropriate
   • Monitor closely for signs of postpartum hemorrhage if used near delivery
   • Prepare for potential neonatal complications if used late in pregnancy

Breastfeeding Considerations

• Duloxetine is excreted into breast milk, but infant exposure appears to be less than 1% of the maternal weight-adjusted dose 2
• Monitor breastfed infants for sedation, poor feeding, and poor weight gain 1
• Limited data suggest duloxetine can be used during breastfeeding with appropriate monitoring 5, 2

Important Caveats

• The FDA notes that there are no adequate and well-controlled studies of duloxetine in pregnant women 1
• Long-term neurodevelopmental outcomes in children exposed to duloxetine in utero have not been adequately studied 5, 6
• Patients with a history of seizure disorder should be monitored closely as duloxetine may affect seizure threshold 7, 1
• Women who discontinue antidepressants during pregnancy are more likely to experience relapse of depression 1

Pregnancy Registry

Women exposed to duloxetine during pregnancy should be encouraged to enroll in pregnancy registry programs to help gather more data on safety 1