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

SSRIs During Pregnancy: Safety Considerations

SSRIs can be used during pregnancy when the benefits outweigh the risks, but they are associated with neonatal adaptation syndrome in approximately one-third of exposed newborns and require careful monitoring. 1

Risks of SSRI Use During Pregnancy

Neonatal Adaptation Syndrome

• SSRIs used during pregnancy can cause neonatal adaptation syndrome in approximately one-third of exposed newborns, with symptoms including crying, irritability, jitteriness, tremors, poor feeding, hypertonia, tachypnea, sleep disturbance, hypoglycemia, and seizures 1
• Symptoms typically begin within hours to days after birth and usually resolve spontaneously within 1-2 weeks 1
• In severely affected infants, pharmacological intervention may be required 1

Persistent Pulmonary Hypertension of the Newborn (PPHN)

• There is a possible association between SSRI use during pregnancy and PPHN 1
• The number needed to harm for PPHN with late pregnancy SSRI exposure is approximately 286-351 1, 2
• FDA labeling for fluoxetine notes that infants exposed to SSRIs in late pregnancy may have an increased risk for PPHN 3

Birth Defects

• According to FDA labeling, fluoxetine showed no evidence of teratogenicity in animal studies, but there was increased stillborn pups and pup mortality in rats at doses higher than human therapeutic doses 3
• Studies examining individual SSRIs suggest a small but higher risk for birth defects with maternal fluoxetine and paroxetine use 4

Benefits of SSRI Treatment During Pregnancy

• Untreated depression during pregnancy is associated with premature birth, decreased initiation of breastfeeding, and potential harmful effects on the mother-infant relationship 1, 2
• Women who discontinue antidepressant medication during pregnancy show a significant increase in relapse of major depression 1, 3
• The American Academy of Pediatrics recommends that SSRI treatment should be continued during pregnancy at the lowest effective dose when clinically indicated 1

Management Recommendations

Monitoring

• Infants exposed to SSRIs in utero should be monitored for at least 48 hours after birth 1
• Arrange for early follow-up after hospital discharge 1, 2
• Monitor for symptoms of neonatal adaptation syndrome including respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying 3

Medication Selection

• Use the lowest effective dose of SSRI during pregnancy 1, 2
• Sertraline and paroxetine are considered to have more favorable profiles during breastfeeding due to lower infant-to-maternal plasma concentration ratios 1, 5
• For women already taking SSRIs who become pregnant, continuation of treatment is generally recommended if clinically indicated 2

Breastfeeding Considerations

• Sertraline, paroxetine, and fluvoxamine are minimally excreted in human milk and provide the infant <10% of the maternal daily dose 1, 5
• The American Academy of Pediatrics notes that paroxetine is the only SSRI for which the ratio of infant to maternal plasma concentrations is consistently low and uniformly <0.10 5
• Fluoxetine is excreted in human milk, and nursing while taking fluoxetine is not recommended according to FDA labeling 3

Risk-Benefit Assessment

• The overall benefit of treatment often outweighs the potential risks 6
• Every pregnant woman being treated with an SSRI should carefully weigh the risks of treatment against the risk of untreated depression for both herself and her child 4
• Pregnant women exposed to any SSRI in early pregnancy should be offered options for prenatal diagnosis through ultrasound examinations and fetal echocardiography to detect the presence of birth defects 4

Specific SSRI Considerations

• Sertraline is one of the most commonly prescribed antidepressants during pregnancy and breastfeeding due to its favorable safety profile 2, 7
• Paroxetine and fluoxetine have shown stronger associations with negative outcomes in some studies 7
• Sertraline and citalopram should be considered as first-line SSRI treatments for anxiety and depression in pregnant women 7