Are selective serotonin reuptake inhibitors (SSRIs) safe to use during pregnancy in a female patient with a history of depression or anxiety?

SSRI Safety in Pregnancy

SSRIs can be safely used during pregnancy when clinically indicated, with sertraline as the preferred first-line agent due to its favorable safety profile and extensive evidence base. 1, 2

First-Line Recommendation: Sertraline

• Sertraline should be the preferred SSRI for pregnant women requiring antidepressant treatment, as recommended by the American Academy of Pediatrics due to its favorable safety profile during both pregnancy and breastfeeding. 1

• Large population-based studies have found no increased risk of cardiac malformations with first-trimester sertraline use. 1, 2

• Sertraline provides infants less than 10% of the maternal daily dose through breast milk, making it safe for continuation during lactation. 1, 2

Second-Line Option

• Citalopram should be considered as an alternative if sertraline is not tolerated or ineffective. 1, 2

Critical Management Principles

• Continue SSRI treatment throughout pregnancy rather than discontinuing, as women who discontinue antidepressants during pregnancy show a significantly increased relapse risk of major depression (up to 68% relapse rate versus 26% in those who continue). 1, 3

• Use the lowest effective dose throughout pregnancy to minimize fetal exposure while maintaining maternal mental health. 1, 2, 4

• The risks of untreated maternal depression—including premature birth, decreased breastfeeding initiation, and harm to the mother-infant relationship—often outweigh the small absolute risks associated with SSRI exposure. 1, 2, 4

Neonatal Monitoring Requirements

• Monitor all SSRI-exposed infants for at least 48 hours after birth for signs of neonatal adaptation syndrome. 2, 4

• Approximately one-third of exposed newborns may develop neonatal adaptation syndrome with third-trimester SSRI exposure, presenting with irritability, jitteriness, tremors, feeding difficulty, sleep disturbance, respiratory distress, hypoglycemia, or seizures. 2, 4

• Symptoms typically appear within hours to days after birth and usually resolve spontaneously within 1-2 weeks. 2, 4

• Arrange early follow-up after initial hospital discharge for continued monitoring. 2, 4

Specific Risks to Discuss

Third-Trimester Considerations:

• There is a possible association with persistent pulmonary hypertension of the newborn (PPHN), though the absolute risk remains small with a number needed to harm of 286-351. 1, 4

• PPHN occurs in 1-2 per 1000 live births in the general population and is associated with substantial neonatal morbidity and mortality. 3, 5

First-Trimester Considerations:

• While one study suggested sertraline may be associated with atrial/ventricular defects and craniosynostosis, large population-based studies have not confirmed increased cardiac malformation risk. 1, 6

• The absolute excess risk for any specific malformation remains very small even when associations are found. 7, 6

Medications to Avoid

• Paroxetine should be avoided during pregnancy due to FDA pregnancy category D classification and concerns about cardiac malformations. 2, 8

• Fluoxetine has stronger associations with negative outcomes compared to sertraline and citalopram. 8

Common Pitfalls to Avoid

• Do not discontinue effective SSRI therapy upon discovering pregnancy without careful psychiatric consultation, as the relapse risk is high (up to 68%) and poses documented risks to both mother and infant. 1, 2

• Do not avoid treatment altogether due to fear of medication risks, as untreated maternal depression carries substantial documented risks including premature birth and impaired mother-infant bonding. 1, 2

• Do not switch medications unnecessarily during pregnancy, as this increases the risk of depressive relapse during the transition period. 2

Neurodevelopmental Outcomes

• Converging evidence from multiple study designs suggests that observed associations between prenatal antidepressant exposure and neurodevelopmental problems (including autism spectrum disorder and ADHD) are largely due to confounding factors rather than causal medication effects. 9

• Several recent reviews have not identified adverse neurodevelopmental outcomes among infants born to women treated with SSRIs during pregnancy. 2

Severe Neonatal Adaptation Syndrome Management

• In severely affected infants with persistent symptoms of neonatal adaptation syndrome, a short-term course of chlorpromazine has provided measurable relief. 2, 4