Is fluoxetine (Prozac) safe during pregnancy?

Safety of Fluoxetine (Prozac) During Pregnancy

Fluoxetine (Prozac) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus, as third-trimester exposure is associated with neonatal complications requiring special care. 1

Risks Associated with Fluoxetine Use in Pregnancy

Neonatal Complications

• Third-trimester exposure to fluoxetine can lead to neonatal complications including:

  • Respiratory distress, cyanosis, and apnea
  • Seizures and temperature instability
  • Feeding difficulties and hypoglycemia
  • Hypotonia, hypertonia, hyperreflexia
  • Tremor, jitteriness, irritability, and constant crying 2, 1

• These symptoms typically appear within hours of delivery and usually resolve within 1-2 weeks 2

Persistent Pulmonary Hypertension of the Newborn (PPHN)

• Infants exposed to SSRIs after the 20th week of gestation may have an increased risk for PPHN
• PPHN occurs in 1-2 per 1000 live births in the general population and is associated with substantial neonatal morbidity and mortality 1

Pregnancy Outcomes

• No significant increase in major congenital malformations compared to the general population 1, 3
• Some studies suggest a possible increased risk of miscarriage, though findings are inconsistent 3, 4
• Third-trimester exposure is associated with:
  • Higher rates of premature delivery (relative risk 4.8)
  • Increased admission to special-care nurseries (relative risk 2.6)
  • Poor neonatal adaptation (relative risk 8.7)
  • Lower birth weight and shorter birth length 3

Benefits of Treatment During Pregnancy

• Untreated depression during pregnancy is associated with:
  • Premature birth
  • Decreased initiation of breastfeeding 2
  • Higher risk of relapse during pregnancy when medication is discontinued 1

Breastfeeding Considerations

• Fluoxetine is excreted in human milk
• The FDA label states that nursing while on fluoxetine is not recommended 1
• However, estimated infant exposure from breast milk is relatively low (2.4-3.8% of the maternal weight-adjusted daily dose) 5

Clinical Decision-Making Algorithm

1. Assess severity of depression:

   • For mild depression with recent onset (≤2 weeks): Consider non-pharmacological approaches first
   • For moderate-to-severe depression: Consider evidence-based treatment including medication 2

2. Consider individual risk factors:

   • History of severe depression or suicide attempts
   • Previous response to fluoxetine
   • Previous relapse when discontinuing medication 2

3. Timing of pregnancy:

   • First/second trimester: Lower risk of neonatal complications
   • Third trimester: Higher risk of neonatal complications requiring special care 3

4. If fluoxetine is needed during pregnancy:

   • Use the lowest effective dose
   • Consider tapering dose in the third trimester if clinically appropriate
   • Arrange for close monitoring of the newborn after delivery 2

Practical Recommendations

• Women taking fluoxetine during the third trimester should deliver in facilities with special care nurseries capable of managing neonatal complications 2

• Infants exposed to fluoxetine in the third trimester should be monitored for:

  • Respiratory distress
  • Feeding difficulties
  • Temperature instability
  • Neurological symptoms (tremors, jitteriness, seizures) 1

• For women who require antidepressant treatment during breastfeeding, sertraline may be preferable to fluoxetine due to its lower concentration in breast milk 2

• The American Psychiatric Association and American College of Obstetricians and Gynecologists recommend that decisions about antidepressant use during pregnancy should consider:

  • Severity of current symptoms
  • Previous mental health history
  • Patient treatment preferences 2

In conclusion, while fluoxetine use during pregnancy carries some risks, particularly in the third trimester, these must be weighed against the risks of untreated depression. The decision to use fluoxetine during pregnancy should be made on a case-by-case basis, with careful consideration of the potential benefits and risks.