What is the safety profile of fluoxetine (Selective Serotonin Reuptake Inhibitor) vs sertraline (Selective Serotonin Reuptake Inhibitor) during pregnancy?

Safety Profile of Fluoxetine vs. Sertraline During Pregnancy

Sertraline has a more favorable safety profile than fluoxetine during pregnancy and should be considered the first-line SSRI for pregnant women requiring antidepressant treatment. 1

Comparative Risk Profiles

Congenital Malformations

• Fluoxetine: Associated with higher rates of minor anomalies (15.5% vs 6.5% in controls) 2
• Sertraline: No significant association with major congenital malformations 1

Third Trimester Exposure Risks

Fluoxetine

• Higher rates of:
  • Premature delivery (relative risk 4.8) 2
  • Special care nursery admission (relative risk 2.6) 2
  • Poor neonatal adaptation including respiratory difficulty, cyanosis, and jitteriness (relative risk 8.7) 2
  • Lower birth weight and shorter birth length 2

Sertraline

• Lower risk of adverse neonatal outcomes compared to fluoxetine 1
• Recommended as first-line option for treating depression during pregnancy due to established safety profile 1
• Excreted in breast milk at <10% of maternal daily dose 1

Neonatal Adaptation Syndrome

Both medications can cause neonatal adaptation syndrome when used in the third trimester, characterized by:

• Irritability, tremors, and jitteriness
• Poor feeding and sleep disturbance
• Respiratory distress
• Hypoglycemia
• Seizures (in severe cases) 1

However, these symptoms:

• Typically resolve within 1-4 weeks after birth 1
• Are more common and severe with fluoxetine than sertraline 2, 3

Breastfeeding Considerations

• Sertraline: Preferred during breastfeeding due to minimal transfer into breast milk (<10% of maternal dose) 1
• Fluoxetine: Higher concentrations in breast milk and longer half-life, potentially increasing infant exposure 3

Long-Term Neurodevelopmental Outcomes

• Limited data on long-term neurodevelopmental effects for both medications
• Current evidence does not identify significant adverse neurodevelopmental outcomes with either medication 1

Clinical Decision Algorithm

1. First-line choice: Sertraline for women requiring SSRI treatment during pregnancy 1, 3
2. Consider fluoxetine only if:
   • Patient has previously responded well to fluoxetine
   • Sertraline is contraindicated or ineffective
3. If using either medication in third trimester:
   • Monitor for neonatal adaptation syndrome
   • Arrange early follow-up after hospital discharge
   • Consider tapering dose before delivery (discuss risk/benefit with patient)

Important Caveats

• Untreated depression during pregnancy carries significant risks including premature birth and decreased breastfeeding initiation 1
• Benefits of treating significant depression during pregnancy typically outweigh potential risks of medication 1
• Monitor infants exposed to SSRIs for irritability, poor feeding, or sleep disturbances, with particular caution for premature or low birth weight infants 1

Monitoring Recommendations

• For women taking either medication in third trimester, ensure neonatal monitoring for at least 48 hours after birth
• Watch for signs of serotonin syndrome or withdrawal in the neonate
• Consider pediatric consultation if symptoms are severe or prolonged