Are citalopram (Celexa) or fluoxetine (Prozac) safe for a pregnant woman or a woman planning to become pregnant to take?

Safety of Citalopram and Fluoxetine in Pregnancy

Both citalopram and fluoxetine can be used during pregnancy when clinically indicated, but sertraline should be considered the preferred first-line SSRI due to its more established safety profile and minimal breast milk excretion. 1, 2

Primary Recommendation for SSRI Selection

• Sertraline is recommended as first-line therapy by the American Academy of Pediatrics due to minimal excretion in breast milk and low infant-to-maternal plasma concentration ratios 2
• If sertraline is not tolerated or ineffective, citalopram can be considered as an alternative according to the American Academy of Pediatrics 2
• Both citalopram and fluoxetine have acceptable safety profiles, though sertraline and citalopram show stronger evidence compared to fluoxetine based on recent systematic reviews 3

Safety Profile: Citalopram

Congenital Malformations

• Citalopram use during first-trimester embryogenesis is not associated with major teratogenic risk 4
• The FDA label notes animal studies showed cardiovascular and skeletal defects at doses 18 times the maximum recommended human dose, but no increased risk of cardiac malformations has been demonstrated in large human population-based studies 5
• One prospective study of 108 live-born infants exposed to citalopram in the first trimester found only 1 (0.9%) infant with a major malformation 4

Neonatal Adaptation

• Late pregnancy citalopram exposure is associated with poor neonatal adaptation syndrome, with a 4.2-fold increased risk of special-care nursery admission compared to unexposed infants 4
• Neonates may develop transient complications including irritability, jitteriness, tremors, feeding difficulty, sleep disturbance, and respiratory distress, typically resolving within 1-2 weeks 2

Safety Profile: Fluoxetine

Congenital Malformations

• Fluoxetine does not increase the risk of spontaneous pregnancy loss or major structural anomalies (5.5% vs 4.0% in controls) 6
• However, fluoxetine has a stronger association with negative outcomes compared to sertraline and citalopram according to systematic reviews 3

Third-Trimester Complications

• Third-trimester fluoxetine exposure significantly increases perinatal complications including:
  • Premature delivery (relative risk 4.8) 6
  • Special-care nursery admission (relative risk 2.6) 6
  • Poor neonatal adaptation with respiratory difficulty, cyanosis, and jitteriness (relative risk 8.7) 6
  • Lower birth weight and shorter birth length 6

Critical Risk-Benefit Considerations

Risks of Untreated Depression

• Untreated depression during pregnancy carries substantial documented risks including premature birth, decreased breastfeeding initiation, arterial hypertension leading to preeclampsia, suicide attempts, and harm to the mother-infant relationship 1, 7
• Women who discontinue antidepressants during pregnancy show significantly increased relapse risk of major depression 5

Treatment Continuation Principle

• SSRI treatment should be continued during pregnancy at the lowest effective dose, as withdrawal may have harmful effects on the mother-infant dyad according to the American Academy of Pediatrics 1, 2
• The decision to discontinue treatment should involve psychiatric consultation given the high relapse risk 2

Clinical Management Algorithm

For Women Already on Citalopram or Fluoxetine

1. Continue treatment at the lowest effective dose rather than discontinuing 1, 2
2. If on fluoxetine and planning pregnancy, consider switching to sertraline given the stronger evidence base 2, 3
3. Arrange early postpartum follow-up as infants are at risk for withdrawal or toxicity symptoms over the first week of life 2

For Women Requiring New Treatment

1. Start with sertraline (25-50 mg daily, titrate slowly) as first-line therapy 2
2. If sertraline fails or is not tolerated, use citalopram as second-line 2
3. Consider fluoxetine only if both sertraline and citalopram are ineffective or not tolerated 3

Monitoring Requirements

• Monitor infants carefully for irritability, feeding difficulties, respiratory symptoms, jitteriness, tremors, and sleep disturbance 2
• Inform the pediatric team about maternal SSRI use so they can anticipate and manage neonatal adaptation syndrome if it occurs 1
• Symptoms typically appear within hours to days after birth and resolve within 1-2 weeks 2

Important Caveats

• Avoid paroxetine specifically due to FDA pregnancy category D classification and cardiac malformation concerns 2, 3
• There is a possible association between late pregnancy SSRI exposure and persistent pulmonary hypertension of the newborn (PPHN), with a number needed to harm of 286-351 1, 7
• Converging evidence suggests that observed associations between prenatal antidepressant exposure and neurodevelopmental problems (autism, ADHD) are largely due to confounding factors rather than causal medication effects 8, 2
• In severely affected infants with persistent neonatal symptoms, a short-term course of chlorpromazine has provided measurable relief 2