Is fluoxetine (Prozac) safe to use during pregnancy?

Fluoxetine (Prozac) Use During Pregnancy

Fluoxetine can be used during pregnancy when clinically indicated, though sertraline is preferred as first-line SSRI therapy due to superior safety data and minimal breast milk excretion. 1

Key Safety Considerations

Major Malformations and Teratogenicity

• No increased risk of major congenital malformations or cardiac defects has been demonstrated with first-trimester fluoxetine exposure in large population-based studies 2, 3
• The FDA classifies fluoxetine as Pregnancy Category C, indicating animal studies showed adverse effects but no definitive human teratogenicity 2
• One older prospective study found no significant difference in major structural anomalies between fluoxetine-exposed (5.5%) versus control pregnancies (4.0%) 3

Third Trimester Complications - Critical Pitfall

Third-trimester exposure carries specific risks that require monitoring:

• Poor neonatal adaptation syndrome occurs in approximately 23.6% of exposed infants versus 13.5% of unexposed, manifesting as respiratory distress, jitteriness, tremors, feeding difficulty, irritability, and constant crying 1
• 4.8-fold increased risk of premature delivery when exposed during third trimester 3
• 2.6-fold increased risk of special-care nursery admission 3
• Symptoms typically appear within hours to days after birth and resolve within 1-2 weeks 1

Persistent Pulmonary Hypertension of the Newborn (PPHN)

• Late pregnancy SSRI exposure carries a possible 6-fold increased risk of PPHN, though the absolute risk remains low (1-2 per 1000 live births baseline) 2
• The number needed to harm is 286-351 for sertraline, suggesting small absolute risk 1

Clinical Decision Algorithm

When to Use Fluoxetine

1. Continue fluoxetine if already established and effective - discontinuing antidepressants during pregnancy increases relapse risk of major depression, which carries substantial risks including premature birth and impaired mother-infant bonding 2
2. Use lowest effective dose throughout pregnancy to minimize fetal exposure 1, 2
3. Consider switching to sertraline if initiating new SSRI therapy, as it provides less than 10% of maternal dose to infant via breast milk 1

Monitoring Requirements

• Arrange early follow-up after delivery for all SSRI-exposed infants 1
• Monitor newborns closely during first week of life for signs of neonatal adaptation syndrome: respiratory distress, jitteriness, feeding difficulties, temperature instability 1, 2
• For severely affected infants with persistent symptoms, short-term chlorpromazine has provided relief 1

Pharmacokinetic Considerations

• CYP2D6 activity increases dramatically during pregnancy, causing decreased serum concentrations of fluoxetine 4
• This may necessitate dose adjustments to maintain therapeutic efficacy, though the goal remains using the lowest effective dose 4

Risk-Benefit Balance

The critical principle: untreated maternal depression poses documented substantial risks to both mother and infant that often outweigh medication risks 1, 2. Women who discontinued antidepressants during pregnancy experienced higher relapse rates than those who continued treatment 2.

Documented Risks of Untreated Depression

• Premature birth 1
• Decreased breastfeeding initiation 1
• Harm to mother-infant relationship 1
• Interference with activities of daily living and infant care 5

Breastfeeding Considerations

• Fluoxetine is excreted in human milk (concentration 70.4 ng/mL in one sample with maternal plasma 295 ng/mL) 2
• The FDA label states nursing while on fluoxetine is not recommended 2
• If breastfeeding is desired, sertraline is strongly preferred due to minimal excretion and well-established safety profile 1