Which selective serotonin reuptake inhibitors (SSRIs) are safe to use during pregnancy?

Safe SSRIs During Pregnancy

Sertraline is the safest and preferred SSRI for use during pregnancy, recommended as first-line therapy by the American Academy of Pediatrics due to its favorable safety profile for both mother and fetus. 1, 2

First-Line Recommendation: Sertraline

• Sertraline should be your default choice when SSRI therapy is indicated during pregnancy, as large population-based studies have found no increased risk of cardiac malformations with first-trimester use 1, 2
• Sertraline provides minimal fetal exposure and transfers less than 10% of the maternal daily dose through breast milk, making it safe for continuation during lactation 1, 2
• The American College of Obstetricians and Gynecologists specifically recommends sertraline as first-line therapy due to its well-established safety profile 2

Second-Line Option: Citalopram

• Consider citalopram as an alternative if sertraline is not tolerated or proves ineffective 1, 2
• Evidence for citalopram shows mixed associations with negative outcomes that remain generally unsubstantiated when controlled for maternal depression and associated factors 3

SSRIs to Avoid

• Avoid paroxetine specifically - it carries FDA pregnancy category D classification due to cardiac malformation concerns and has the strongest association with negative outcomes 2, 3
• Fluoxetine also shows stronger associations with birth defects compared to sertraline and citalopram 4, 3

Critical Management Principles

• Continue treatment throughout pregnancy rather than discontinuing - women who discontinue antidepressants during pregnancy show significantly increased relapse risk of major depression 1, 2, 5, 6
• Use the lowest effective dose throughout pregnancy to minimize fetal exposure while maintaining maternal mental health 1, 2, 7
• Do not discontinue effective SSRI therapy upon discovering pregnancy without careful psychiatric consultation, as relapse risk is high and untreated depression poses greater documented risks 1, 2

Third-Trimester Considerations and Neonatal Monitoring

• 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, and respiratory distress 2, 7, 5, 6
• These symptoms typically appear within hours to days after birth and usually resolve within 1-2 weeks 2, 7
• Monitor infants exposed to SSRIs for at least 48 hours after birth and arrange early follow-up after initial hospital discharge 1, 2, 7
• There is a possible association with persistent pulmonary hypertension of the newborn (PPHN), with a number needed to harm of 286-351 1, 2, 7

Risk-Benefit Context

• The risks of untreated depression outweigh medication risks - untreated depression during pregnancy carries substantial documented risks including premature birth, decreased breastfeeding initiation, and harm to the mother-infant relationship 1, 2, 8
• Multiple reviews have not identified adverse neurodevelopmental outcomes among infants born to women treated with SSRIs during pregnancy 2, 7
• Converging evidence suggests that observed associations between prenatal antidepressant exposure and autism spectrum disorder or ADHD are largely due to confounding factors (maternal psychiatric illness) rather than causal medication effects 2

Common Pitfalls to Avoid

• Do not avoid treatment altogether due to fear of medication risks - untreated maternal depression poses greater documented risks to both mother and infant than SSRI exposure 1, 2
• Do not taper off medication in early pregnancy without psychiatric consultation, as this significantly increases relapse risk 1, 2
• Inform the pediatric team about maternal SSRI use so they can anticipate and manage neonatal adaptation syndrome if it occurs 7