BACKGROUND AND PURPOSE:

• Duloxetine (Cymbalta) is a selective serotonin-norepinephrine reuptake inhibitor (SNRI) used to treat depression, anxiety and pain disorders
• Huybrechts et al. (BMJ, 2020) assessed the risk for adverse perinatal outcomes following prenatal exposure to duloxetine

METHODS:

• Cohort study
  • Using a nationwide database
• Participants
  • Pregnant women | Ages 18 to 55 their liveborn infants
• Exposures
  • Duloxetine exposure during the etiologically relevant time window (e.g., first trimester more relevant for congenital anomalies, while late exposure may be more important for PPH or preterm birth)
  • No exposure to duloxetine
  • Exposure to selective serotonin reuptake inhibitors
  • Exposure to venlafaxine (Effexor) to compare individual effects of duloxetine vs another SNRI
  • Exposure to duloxetine before but not during pregnancy
• Primary outcomes
  • Congenital malformations overall
  • Cardiac malformations
  • Preterm birth
  • Small for gestational age infant
  • Preeclampsia
  • Postpartum hemorrhage

RESULTS:

• Source cohort size: 8,410,882 pregnant women
• All baseline characteristics were well balanced for all exposure contrasts, following adjustment for measured potential confounders

Comparing duloxetine vs unexposed pregnancies

• Overall congenital malformations
  • Adjusted relative risk (RR) 1.11 (95% CI, 0.93 to 1.33)
• Cardiovascular malformations
  • aRR 1.29 (95% CI, 0.99 to 1.68) 
  • When analysis was performed using 2 dispensings of duloxetine in the first trimester adjusted risk estimates strengthened
• Preterm birth
  • Early exposure; aRR 1.01 (95% CI, 0.92 to 1.10) for early exposure
  • Late exposure: aRR 1.19 (95% CI, 1.04 to 1.37)
• SGA
  • Early exposure: aRR 1.14 (95% CI, 0.92 to 1.41)  
  • Late exposure: aRR 1.20 (95% CI, 0.83 to 1.72) 
• Preeclampsia  
  • Early exposure: aaRR 1.12 (95% CI, 0.96 to 1.31)  
  • Late exposure: RR 1.04 (95% CI, 0.80 to 1.35) 
• PPH
  • Late exposure: aRR 1.53 (95% CI, 1.08 to 2.18)

CONCLUSION:

• Duloxetine is unlikely to be a major teratogen
• There may be an increased risk for cardiovascular anomalies  
• There was an increased risk for PPH | Duloxetine depletes platelet serotonin
• The authors state that the

…potential small increases in risk of relatively uncommon outcomes that we observed must be weighed against the benefits of treating depression and pain during pregnancy for both the mother’s and the infant’s health, a trade-off that is likely to be different for each individual patient.

Learn More – Primary Sources:

Maternal and fetal outcomes following exposure to duloxetine in pregnancy: cohort study

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