What selective serotonin reuptake inhibitor (SSRI) is recommended during pregnancy and the postpartum state?

Recommended SSRIs During Pregnancy and Postpartum Period

Sertraline (Zoloft) is the preferred SSRI for use during pregnancy and the postpartum period due to its low transfer to infants through placenta and breast milk. 1, 2, 3

Selection of SSRIs in Pregnancy

First-line Options

• Sertraline (Zoloft) should be considered first-line therapy due to minimal excretion in breast milk (<10% of maternal dose) and low infant-to-maternal plasma concentration ratios 4, 3
• Citalopram (Celexa) is also a reasonable first-line option with generally unsubstantiated negative outcomes when controlled for maternal depression 3

SSRIs to Avoid

• Paroxetine (Paxil) has the strongest association with negative outcomes including significant malformations and should be avoided 3
• Fluoxetine (Prozac) also shows stronger associations with adverse outcomes compared to other SSRIs 3

Considerations for SSRI Use During Pregnancy

Neonatal Risks

• Third-trimester SSRI use may lead to neonatal signs including irritability, jitteriness, tremors, feeding difficulty, sleep disturbance, and respiratory distress 4
• These symptoms typically appear within hours to days after birth and usually resolve within 1-2 weeks 4, 5
• Poor neonatal adaptation syndrome (PNAS) occurs in approximately one-third of newborns exposed to SSRIs in utero but is generally mild and self-limiting 5

Maternal Benefits vs. Risks

• SSRI treatment should be continued during pregnancy at the lowest effective dose, as withdrawal of medication may have harmful effects on the mother-infant dyad 4
• Untreated or incompletely managed depression and anxiety during pregnancy also carry risks for the newborn 5, 6

Postpartum and Breastfeeding Considerations

Sertraline in Breastfeeding

• Sertraline is minimally excreted in breast milk, providing the infant with <10% of the maternal daily dose (normalized for weight) 4, 2
• Model-based simulations suggest a median daily infant dosage of 6.9 μg/kg after a 50 mg maternal daily dose, representing only 0.95% of the weight-adjusted maternal dose 2
• Sertraline can be continued during breastfeeding as concentrations found in breast milk are very low and have not been linked to infant complications 3

Factors Affecting Infant Exposure

• CYP2C19 poor metabolizer status reduces sertraline clearance by 42% compared to other phenotypes 2
• Breast milk fat content influences drug transfer - doubling milk fat content increases the milk-to-plasma ratio by 95% 2

Monitoring and Follow-up

Neonatal Monitoring

• Clinicians should arrange for early follow-up after initial hospital discharge for infants exposed to SSRIs 4
• Monitor infants for signs of drug toxicity or withdrawal over the first week of life 4
• In severely affected infants with persistent symptoms, a short-term course of chlorpromazine has provided measurable relief 4

Long-term Outcomes

• Several recent reviews have not identified adverse neurodevelopmental outcomes among infants born to women treated with SSRIs during pregnancy 4
• Inconsistencies in the literature regarding neurodevelopmental outcomes (autism spectrum disorder, ADHD) likely relate to other factors such as genetics, maternal depression, lifestyle, and comorbidities, rather than SSRI exposure 5

Clinical Decision Algorithm

1. Assess severity of maternal depression/anxiety and need for pharmacological treatment
2. If SSRI treatment is indicated, select sertraline as first-line therapy
3. If sertraline is not tolerated or ineffective, consider citalopram as an alternative
4. Avoid paroxetine and fluoxetine if possible due to higher risk profiles
5. Use the lowest effective dose throughout pregnancy and postpartum
6. Continue treatment through pregnancy rather than discontinuing
7. Support breastfeeding for mothers on sertraline due to minimal infant exposure
8. Monitor newborns for signs of poor neonatal adaptation syndrome in the first week of life