Are selective serotonin reuptake inhibitors (SSRIs) safe to use during pregnancy, and which agents are preferred?

SSRI Safety in Pregnancy

SSRIs can be safely used during pregnancy when clinically indicated, with sertraline as the first-line agent due to its favorable safety profile for both pregnancy and breastfeeding. 1

First-Line Recommendation: Sertraline

Sertraline should be the preferred SSRI for pregnant women requiring antidepressant treatment. 1, 2

• The American Academy of Pediatrics specifically recommends sertraline due to minimal excretion in breast milk (providing infants <10% of maternal daily dose) and low infant-to-maternal plasma concentration ratios 1, 3
• Large population-based studies demonstrate no increased risk of cardiac malformations with first-trimester sertraline use 1, 2
• Sertraline can be safely continued during breastfeeding, making it ideal for continuity of care through the postpartum period 1, 2

Second-Line Option

• Consider citalopram as an alternative if sertraline is not tolerated or ineffective 1, 2

Critical Avoidance

• Avoid paroxetine specifically - it carries FDA pregnancy category D classification due to cardiac malformation concerns 2
• Studies suggest paroxetine may be associated with a small increased risk of cardiac malformations, though evidence remains somewhat inconclusive 4, 5

Dosing Strategy

Use the lowest effective dose throughout pregnancy to minimize fetal exposure while maintaining maternal mental health. 1, 3, 2

• Start with 25-50 mg daily of sertraline and titrate slowly upward while monitoring 2
• Continue treatment through pregnancy rather than discontinuing - withdrawal significantly increases relapse risk 1, 3
• Women who discontinue antidepressants during pregnancy show a significant increase in relapse of major depression 1, 6, 7

Neonatal Risks and Monitoring

Neonatal Adaptation Syndrome

• Approximately one-third of exposed newborns may develop neonatal adaptation syndrome with third-trimester SSRI exposure 1, 3
• Symptoms include crying, irritability, jitteriness, tremors, poor feeding, hypertonia, tachypnea, sleep disturbance, hypoglycemia, and seizures 3, 4
• Symptoms typically appear within hours to days after birth and usually resolve within 1-2 weeks 3, 4
• Monitor all SSRI-exposed infants for at least 48 hours after birth 1, 3, 2, 4
• Arrange early follow-up after initial hospital discharge 1, 2
• In severely affected infants, a short-term course of chlorpromazine has provided measurable relief 3, 2

Persistent Pulmonary Hypertension of the Newborn (PPHN)

• There is a possible association with PPHN, with a number needed to harm of 286-351 1, 3, 2
• The absolute risk remains very low (<1%), and some studies show higher rates even among offspring of women with untreated depression 8

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 such as maternal psychiatric illness rather than causal medication effects. 2

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

Risk-Benefit Context

Risks of Untreated Depression

Untreated depression during pregnancy carries substantial documented risks that often exceed medication risks: 1, 2

• Premature birth 1, 3
• Decreased breastfeeding initiation 1, 3
• Harmful effects on the mother-infant relationship 1, 3
• Maternal morbidity including arterial hypertension, preeclampsia, and suicide attempts 9
• Low birth weight and infant irritability 9

Benefits of Treatment

• Maintaining antidepressant treatment prevents relapse and protects both maternal and fetal health 1, 6, 7
• The risk/benefit ratio favors treatment when depression is clinically significant 10, 8

Common Pitfalls to Avoid

• Do not discontinue effective SSRI therapy upon discovering pregnancy without careful psychiatric consultation - relapse risk is high 1
• Do not avoid treatment altogether due to fear of medication risks - untreated maternal depression poses greater documented risks to both mother and infant 1, 2
• Do not switch from sertraline to paroxetine during pregnancy 2
• If switching from paroxetine to sertraline, transition directly without a washout period to prevent depressive relapse 2

FDA Labeling Information

• Sertraline animal studies at doses up to 4 times the maximum recommended human dose showed no evidence of teratogenicity 6
• There are no adequate and well-controlled studies in pregnant women; sertraline should be used during pregnancy only if the potential benefit justifies the potential risk 6
• Neonates exposed to SSRIs late in the third trimester may develop complications requiring prolonged hospitalization, respiratory support, and tube feeding 6, 7