Are Selective Serotonin Reuptake Inhibitors (SSRIs) safe to use during pregnancy?

SSRIs During Pregnancy: Safety and Recommendations

Sertraline is the preferred SSRI during pregnancy when treatment is necessary, as it has the most established safety profile and lowest risk of adverse outcomes. 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
   • High risk of depression relapse (stopping antidepressants during pregnancy significantly increases relapse risk) 1

2. SSRI-associated risks:

   • Neonatal adaptation syndrome with third trimester exposure
   • Small increased risk of persistent pulmonary hypertension of the newborn (PPHN) - number needed to harm: 286-351 1
   • Potential cardiac malformations (particularly with paroxetine) 1, 2
   • Possible developmental effects including speech delay and ADHD (evidence conflicting) 1

SSRI Selection Algorithm

First-line options:

• Sertraline: Most established safety profile during pregnancy 1
• Citalopram: Generally considered safe 1

Avoid if possible:

• Paroxetine: FDA pregnancy category D due to concerns about congenital cardiac malformations 1
• Fluoxetine: Associated with increased stillborn pups, decreased pup weight, and increased pup deaths in animal studies 2

Timing Considerations

• First trimester: Population studies show conflicting results regarding SSRI use and cardiac malformations 1
• Third trimester: Increased risk of neonatal adaptation syndrome and PPHN 1, 2

Monitoring Recommendations

For infants exposed to SSRIs during pregnancy, monitor for:

• Neonatal adaptation syndrome: crying, irritability, tremors, poor feeding, hypertonia, tachypnea, sleep disturbance, hypoglycemia, and seizures 1, 2
• Signs of drug toxicity or withdrawal during the first week of life 1
• Arrange early follow-up after initial hospital discharge 1

Breastfeeding Considerations

• Sertraline and fluvoxamine: <10% of maternal daily dose excreted in breast milk 1
• Paroxetine: Infant to maternal plasma concentration ratio <0.10 1
• Monitor breastfed infants for irritability, poor feeding, or sleep disturbances 1
• Exercise particular caution with premature or low birth weight infants 1

Important Caveats

• FDA labels indicate fluoxetine should be used during pregnancy only if potential benefit justifies potential risk to the fetus 2
• Neonates exposed to SSRIs late in the third trimester may develop complications requiring prolonged hospitalization, respiratory support, and tube feeding 2
• Recent evidence suggests that many associations between prenatal antidepressant exposure and neurodevelopmental problems may be due to confounding factors 1
• The absolute risk of complications remains small for most outcomes 3

Clinical Pearls

• When treating depression in pregnant women, always consider non-pharmacological approaches first
• For women already on an SSRI who become pregnant, abrupt discontinuation can lead to high relapse rates 1
• If medication is necessary, sertraline provides the best balance of efficacy and safety 1, 4
• Document thorough informed consent discussions regarding risks and benefits