Are selective serotonin reuptake inhibitors (SSRIs) safe during pregnancy?

Safety of SSRIs During Pregnancy

SSRIs can be used during pregnancy when the benefits outweigh the risks, with sertraline being the preferred first-line option due to its established safety profile. 1

Risk-Benefit Assessment

The decision to use SSRIs during pregnancy requires careful consideration of:

1. Risks of untreated depression:

   • Premature birth
   • Decreased breastfeeding initiation
   • Increased risk of maternal depression relapse 1

2. Potential risks of SSRI exposure:

   • Neonatal adaptation syndrome in third trimester exposure
   • Possible small increased risk of persistent pulmonary hypertension of the newborn (PPHN)
   • Potential cardiac malformations (particularly with paroxetine) 2, 3

SSRI Selection During Pregnancy

Preferred Options:

• Sertraline - First-line recommendation due to favorable safety profile 1
• Citalopram - Generally considered safe 2

Options to Avoid:

• Paroxetine - FDA classified as pregnancy category D due to concerns about congenital cardiac malformations 2
• Fluoxetine - Higher risk of neonatal adaptation syndrome due to longer half-life 3

Neonatal Considerations

Neonatal Adaptation Syndrome

• Occurs with third-trimester exposure
• Symptoms: crying, irritability, tremors, feeding difficulties, respiratory distress, sleep disturbance
• Typically resolves within 1-4 weeks after birth 1

Monitoring Recommendations

• Monitor infants exposed to SSRIs for signs of drug effects during the first week of life
• Arrange early follow-up after initial hospital discharge
• Watch for irritability, poor feeding, or sleep disturbances in breastfed infants 1

Breastfeeding Considerations

SSRIs transfer in low concentrations into breast milk:

• Paroxetine and Sertraline: <10% of maternal daily dose transfers to infant 1
• Monitoring of breastfed infants recommended for irritability, poor feeding, or sleep disturbances 1

Long-Term Outcomes

Current evidence does not identify adverse neurodevelopmental outcomes among infants born to women treated with SSRIs during pregnancy 1. However, studies have suggested possible associations with:

• Speech delay
• Attention-deficit/hyperactivity disorder
• Conflicting findings regarding autism 2

Important Caveats

1. Discontinuation Risk: Stopping antidepressants during pregnancy is associated with high risk of depression relapse 3

2. PPHN Risk: Meta-analysis showed a link between late pregnancy SSRI exposure and PPHN, with a number needed to harm of 286-351 2

3. Cardiac Malformations: Population-based studies have shown conflicting results regarding the link between first-trimester SSRI use and cardiac malformations 2, 4

4. Individual Assessment: The decision to use SSRIs during pregnancy should balance maternal mental health needs against potential fetal risks 1

In summary, while SSRIs carry some risks during pregnancy, the consequences of untreated depression often outweigh these risks. Sertraline represents the safest option when antidepressant treatment is necessary during pregnancy.