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

Guidelines for Fluoxetine Use During Pregnancy

Fluoxetine should be continued during pregnancy at the lowest effective dose when benefits outweigh risks, as discontinuation may have harmful effects on the mother-infant dyad. 1

Risk Assessment for Fluoxetine in Pregnancy

Congenital Malformations

• Meta-analyses show no significant increased risk of major malformations with first-trimester fluoxetine exposure (OR 1.12,95% CI 0.98-1.28) 2
• FDA pregnancy category C: Animal studies show adverse effects but controlled human studies are lacking 3
• No consistent pattern of abnormalities has been observed in prospective studies 4

Neonatal Complications

• Third-trimester exposure can lead to neonatal complications requiring monitoring:
  • Respiratory distress, cyanosis, apnea
  • Seizures, temperature instability
  • Feeding difficulties, vomiting, hypoglycemia
  • Hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability 1, 3
• These complications typically resolve within 1-2 weeks after birth 1
• Infants exposed to fluoxetine in the third trimester have higher rates of:
  • Premature delivery (relative risk 4.8)
  • Admission to special-care nurseries (relative risk 2.6)
  • Poor neonatal adaptation (relative risk 8.7) 5

Persistent Pulmonary Hypertension of the Newborn (PPHN)

• Possible six-fold increased risk for PPHN with SSRI exposure after 20 weeks gestation 3
• This risk should be weighed against maternal benefits

Decision-Making Algorithm

1. Assess maternal mental health severity:

   • For mild depression with recent onset (<2 weeks): Consider non-pharmacological approaches first
   • For moderate-to-severe depression or mild depression not improving within 2 weeks: Consider pharmacological treatment 1

2. Consider patient-specific factors:

   • History of severe depression or suicide attempts with previous response to fluoxetine
   • Previous relapse upon discontinuation
   • Failed response to psychotherapy
   • Patient preference for medication 1

3. Timing considerations:

   • First trimester: Minimal risk of major congenital malformations
   • Third trimester: Higher risk of neonatal adaptation syndrome requiring close monitoring

4. Dosing recommendations:

   • Use lowest effective dose
   • Consider gradual tapering if discontinuation is planned
   • Avoid abrupt discontinuation due to risk of withdrawal symptoms

Breastfeeding Considerations

• Fluoxetine is excreted in breast milk
• Paroxetine, sertraline, and fluvoxamine have lower infant exposure (<10% of maternal dose) compared to fluoxetine 1
• If breastfeeding is desired while on fluoxetine, counsel mother about risks and benefits
• Monitor infant for sedation, feeding problems, and weight gain

Monitoring Recommendations

During Pregnancy:

• Regular mental health assessments
• Monitor for worsening depression or anxiety
• Consider fetal monitoring in third trimester

After Delivery:

• Arrange early follow-up after hospital discharge 1
• Monitor newborn for signs of poor neonatal adaptation syndrome:
  • Respiratory difficulties
  • Feeding problems
  • Neurological symptoms (tremors, jitteriness)
  • Temperature instability
• For severely affected infants, short-term chlorpromazine may provide relief of symptoms 1

Important Caveats

1. Risk-benefit assessment is crucial: Untreated maternal depression carries significant risks to both mother and child, including poor prenatal care, substance abuse, preterm birth, and developmental issues 1

2. Avoid polypharmacy: Combining fluoxetine with other serotonergic medications increases risk of serotonin syndrome 6

3. Genetic factors: Approximately 7% of the population are poor CYP2D6 metabolizers who may require lower doses due to slower clearance 6

4. Discontinuation risks: Abrupt discontinuation of fluoxetine during pregnancy may lead to maternal relapse and negative outcomes for both mother and infant 1

5. Timing matters: Third-trimester exposure carries higher risk of neonatal complications than first or second trimester exposure 5

By carefully weighing these factors and following appropriate monitoring protocols, clinicians can help pregnant women make informed decisions about fluoxetine use during pregnancy that prioritize both maternal mental health and fetal wellbeing.