Is fluoxetine (Prozac) safe during pregnancy?

Fluoxetine Safety During Pregnancy

Fluoxetine (Prozac) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus, with particular caution during the third trimester due to increased risk of neonatal complications. 1

Risks Associated with Fluoxetine Use in Pregnancy

First and Second Trimester Exposure

• Major Congenital Malformations:
  • The FDA label indicates no evidence of teratogenicity in animal studies, though there were increased stillborn pups and decreased pup weight at higher doses 1
  • Meta-analyses show conflicting evidence regarding cardiac malformations, with some suggesting increased risk with fluoxetine 2
  • A systematic review found no significant increase in overall major malformations (OR 1.12,95% CI 0.98-1.28) 3

Third Trimester Exposure

• Neonatal Adaptation Syndrome: Infants exposed to fluoxetine late in pregnancy have significantly higher rates of:

  • Respiratory difficulties
  • Cyanosis on feeding
  • Jitteriness and tremors
  • Poor feeding
  • Irritability and constant crying 4, 1
  • These symptoms typically resolve within 1-4 weeks 4

• Persistent Pulmonary Hypertension of the Newborn (PPHN):

  • FDA label notes a retrospective case-control study showing approximately six-fold higher risk for PPHN in infants exposed to SSRIs after 20 weeks gestation 1
  • Current evidence shows a small but significant increased risk 2

• Obstetrical Outcomes:

  • Increased risk of premature delivery (relative risk 4.8) 5
  • Higher rates of admission to special care nurseries (relative risk 2.6) 5
  • Lower birth weight and shorter birth length 5

Breastfeeding Considerations

• Fluoxetine is excreted in human milk 1
• The FDA label states that nursing while on fluoxetine is not recommended 1
• In one sample, the concentration of fluoxetine plus norfluoxetine in breast milk was 70.4 ng/mL compared to 295 ng/mL in maternal plasma 1

Decision Algorithm for Fluoxetine Use in Pregnancy

1. Assess Maternal Depression Severity:

   • Untreated depression during pregnancy is associated with premature birth and decreased breastfeeding initiation 4
   • Women who discontinue antidepressants during pregnancy are more likely to experience relapse of major depression 1

2. Consider Gestational Timing:

   • First/Second Trimester: Lower risk of immediate neonatal complications but potential small increased risk of cardiac malformations
   • Third Trimester: Higher risk of neonatal adaptation syndrome, PPHN, and obstetrical complications

3. Alternative Options:

   • Consider psychotherapy as first-line treatment if appropriate for depression severity
   • If medication is necessary, use the lowest effective dose 4
   • Avoid abrupt discontinuation if already on fluoxetine

4. Monitoring Protocol:

   • For women continuing fluoxetine in third trimester:
     • Arrange for early follow-up after hospital discharge 4
     • Alert pediatric team about exposure to prepare for potential neonatal adaptation syndrome
     • Monitor newborn for respiratory distress, feeding difficulties, temperature instability, hypoglycemia, and neurological symptoms

Common Pitfalls and Caveats

1. Abrupt Discontinuation: Stopping fluoxetine suddenly during pregnancy can lead to maternal withdrawal symptoms and increased risk of depression relapse 1

2. Confounding by Indication: Many studies showing adverse outcomes may be affected by the underlying maternal depression rather than medication effects 2

3. Risk Communication: The absolute risks of most adverse outcomes remain small despite relative risk increases

4. Polypharmacy: Combining fluoxetine with other serotonergic medications increases the risk of serotonin syndrome 4

5. Long Half-Life: Fluoxetine has a longer half-life than other SSRIs, which may prolong neonatal exposure even if discontinued before delivery

The decision to use fluoxetine during pregnancy requires careful weighing of maternal mental health needs against potential fetal risks, with particular attention to timing of exposure and monitoring for neonatal complications if used in late pregnancy.