Is fluoxetine (selective serotonin reuptake inhibitor) safe to take during pregnancy?

Safety of Fluoxetine During Pregnancy

Fluoxetine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus, as it is associated with neonatal complications when used in the third trimester. 1

Risks Associated with Fluoxetine Use During Pregnancy

Congenital Malformations

• The FDA drug label indicates that animal studies show no evidence of teratogenicity at doses up to 1.5 times the maximum recommended human dose 1
• However, meta-analyses have found evidence for a significant increase in the risks for major congenital malformations with fluoxetine exposure 2
• Particularly, fluoxetine has been associated with congenital heart defects in some studies 2

Third Trimester Exposure Risks

• Neonates exposed to fluoxetine late in the third trimester have developed complications requiring prolonged hospitalization 1
• Clinical findings include:
  • Respiratory distress, cyanosis, apnea
  • Seizures, temperature instability
  • Feeding difficulties, vomiting, hypoglycemia
  • Hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability 3, 1
• Infants exposed to fluoxetine during the third trimester have higher rates of:
  • Premature delivery (4.8 times higher risk)
  • Admission to special-care nurseries (2.6 times higher risk)
  • Poor neonatal adaptation (8.7 times higher risk) 4
  • Lower birth weight and shorter birth length 4

Persistent Pulmonary Hypertension of the Newborn (PPHN)

• Infants exposed to SSRIs after the 20th week of gestation have approximately six-fold higher risk for developing PPHN 1
• PPHN is associated with substantial neonatal morbidity and mortality 1

Breastfeeding Considerations

• Fluoxetine is excreted in human milk, with concentrations detected in both breast milk and infant plasma 1
• Case reports have documented adverse effects in nursing infants including crying, sleep disturbance, vomiting, and watery stools 1
• The FDA label recommends that nursing while on fluoxetine is not recommended 1

Physiological Mechanisms of Concern

• Fluoxetine crosses the placenta, directly exposing the fetus 5
• It can cause an acute increase in plasma serotonin levels, potentially leading to:
  • Reduction in uterine blood flow
  • Reduced delivery of oxygen and nutrients to the fetus
  • Possible mechanism for reduced growth and/or preterm delivery 5
• Fluoxetine may interfere with normal fetal neurodevelopment by altering fetal behavioral states 5

Clinical Approach to Fluoxetine Use in Pregnancy

First and Second Trimester

• Lower risk of immediate neonatal complications compared to third trimester exposure 4
• Still carries potential risk of congenital malformations, particularly cardiac defects 2

Third Trimester

• Highest risk period for neonatal complications 1, 4
• Consider tapering or discontinuing if clinically appropriate before the third trimester
• If continued through delivery, arrange for early follow-up after hospital discharge 3
• Be prepared for potential neonatal complications requiring special care 4

Important Considerations

• Untreated depression during pregnancy carries its own risks to mother and fetus
• Women who discontinue antidepressant medication during pregnancy are more likely to experience relapse of major depression 1
• The decision to use fluoxetine during pregnancy should weigh the risks of untreated depression against the potential risks of medication exposure
• If fluoxetine is continued during pregnancy, use the lowest effective dose 3

Monitoring Recommendations

• For infants exposed to fluoxetine in utero, especially in the third trimester:
  • Monitor for signs of poor neonatal adaptation for at least the first week of life
  • Watch for respiratory distress, feeding difficulties, temperature instability, and neurological symptoms 3, 1
  • Arrange early follow-up after initial hospital discharge 3