What are the guidelines for using fluoxetine (selective serotonin reuptake inhibitor) during pregnancy?

Fluoxetine Use During Pregnancy

Primary Recommendation

Sertraline, not fluoxetine, should be considered first-line SSRI therapy during pregnancy and breastfeeding due to its superior safety profile, minimal breast milk excretion, and low infant-to-maternal plasma concentration ratios. 1

Key Clinical Considerations for Fluoxetine

Pregnancy Safety Profile

Fluoxetine is FDA Pregnancy Category C and can be used during pregnancy when benefits justify potential risks, but it is not the preferred SSRI. 2

• No increased risk of major congenital malformations has been demonstrated in large studies, though some older research suggested possible concerns with cardiac defects 3, 4
• Avoid paroxetine specifically due to FDA Category D classification and documented cardiac malformation risks; fluoxetine is safer than paroxetine but less preferred than sertraline 1

Third Trimester Complications

Third-trimester fluoxetine exposure carries significant risks for neonatal complications that require careful monitoring:

• Poor neonatal adaptation syndrome occurs in exposed infants with symptoms including respiratory distress, cyanosis, jitteriness, tremors, feeding difficulty, irritability, hypoglycemia, and temperature instability 2, 3
• These symptoms typically appear within hours to days after birth and usually resolve within 1-2 weeks 1
• Increased risk of premature delivery (relative risk 4.8), special-care nursery admission (relative risk 2.6), and poor neonatal adaptation (relative risk 8.7) compared to first/second trimester exposure only 3
• Possible association with persistent pulmonary hypertension of the newborn (PPHN) with approximately 6-fold increased risk after 20th week exposure, though absolute risk remains low (1-2 per 1000 live births baseline) 2

Pharmacokinetic Considerations

Fluoxetine metabolism increases during pregnancy, potentially leading to subtherapeutic levels:

• Increased demethylation by CYP2D6 during late pregnancy results in 2.4-fold higher norfluoxetine/fluoxetine ratios and relatively low trough concentrations 5
• Clinicians must monitor for therapeutic failure and undertreated depression, which itself carries substantial risks 5

Treatment Algorithm

For Women Already on Fluoxetine Who Become Pregnant:

1. Continue treatment rather than discontinue - withdrawal carries harmful effects on the mother-infant dyad that often outweigh medication risks 1
2. Use the lowest effective dose throughout pregnancy 1
3. Consider switching to sertraline if clinically appropriate, particularly before third trimester 1
4. Arrange prenatal surveillance including ultrasound examinations and fetal echocardiography to detect potential birth defects 4

For Newly Diagnosed Depression in Pregnancy:

1. Start with sertraline 25-50 mg daily as first-line therapy, titrating slowly 1
2. Consider citalopram as alternative if sertraline is not tolerated or ineffective 1
3. Reserve fluoxetine for cases where other SSRIs have failed 6

Monitoring Requirements

Arrange early follow-up after delivery and monitor infants for signs of drug toxicity or withdrawal over the first week of life: 1

• Watch for respiratory distress, feeding difficulties, jitteriness, irritability, and temperature instability 2
• In severely affected infants with persistent symptoms, short-term chlorpromazine has provided measurable relief 1
• Prolonged hospitalization, respiratory support, and tube feeding may be required 2

Breastfeeding Considerations

Fluoxetine is less ideal for breastfeeding compared to sertraline:

• At delivery, infant plasma fluoxetine and norfluoxetine concentrations reach 65% and 72% of maternal levels respectively 5
• Estimated infant exposure from breast milk is 2.4-3.8% of maternal weight-adjusted dose 5
• Sertraline provides infant with less than 10% of maternal daily dose and is the preferred agent during lactation 1

Critical Pitfall to Avoid

Do not discontinue antidepressant treatment due to pregnancy concerns without weighing risks of untreated depression, which include premature birth, decreased breastfeeding initiation, harm to mother-infant relationship, and high relapse rates (up to 68% with discontinuation) 1, 4. The absolute excess risk from medication is small and must be balanced against substantial documented risks of untreated maternal depression.