What are the risks and recommendations for using sertraline (selective serotonin reuptake inhibitor) in a pregnant female patient with a history of depression or anxiety?

Sertraline Use in Pregnancy

Sertraline is a preferred first-line SSRI for treating moderate-to-severe depression during pregnancy, with a favorable safety profile compared to other antidepressants, particularly low transfer to breast milk, making it suitable for continuation postpartum. 1, 2

Treatment Algorithm

Mild Depression (Recent Onset ≤2 Weeks)

• Begin with non-pharmacological interventions including exercise, social support, and evidence-based psychotherapy (cognitive behavioral therapy) 1, 3
• Monitor closely for symptom progression 1
• If no improvement within 2 weeks, escalate to pharmacological treatment 1

Moderate-to-Severe Depression

• Consider antidepressants as first-line treatment, with sertraline as a preferred SSRI option 1, 2
• Antidepressants are particularly appropriate for women with: 1
  • History of severe suicide attempts
  • Previous severe depression with good medication response
  • Previous relapse when discontinuing antidepressants
  • Failed psychotherapy trials

Why Sertraline is Preferred

Among SSRIs, sertraline and citalopram demonstrate the most favorable risk profiles, while paroxetine and fluoxetine show stronger associations with adverse outcomes. 2

• Sertraline transfers to breast milk in very low concentrations, making it the preferred choice for breastfeeding mothers 4, 1, 5
• Recent evidence shows sertraline concentrations remain relatively steady during pregnancy, with only 25-33% placental passage to the infant 6
• Sertraline is one of the most commonly prescribed antidepressants for pregnant women 4, 3

Specific Risks to Discuss

Cardiac Malformations

• First-trimester sertraline exposure is associated with increased risk of atrial/ventricular defects (RR 1.34,95% CI 1.02-1.76) 7
• However, a large population-based cohort study of nearly 1 million pregnant women found no link between first-trimester antidepressant use and cardiac malformations 4
• The FDA reclassified paroxetine (not sertraline) as pregnancy category D in 2005 for cardiac concerns 4

Craniosynostosis

• Sertraline exposure shows association with craniosynostosis (RR 2.03,95% CI 1.09-3.75), though absolute numbers are small (3 exposed cases) 7

Persistent Pulmonary Hypertension of the Newborn (PPHN)

• The FDA revised its 2006 advisory in 2011, stating that conflicting findings make it unclear whether SSRIs cause PPHN 4, 1, 3
• A meta-analysis found a link between late pregnancy SSRI exposure and PPHN with a number needed to harm of 286-351 4, 1
• PPHN occurs in 1-2 per 1000 live births in the general population 5

Neonatal Adaptation Syndrome

• Occurs in approximately 30% of third-trimester SSRI exposures 1
• Symptoms include crying, irritability, tremors, poor feeding, hypertonia, tachypnea, sleep disturbance, and hypoglycemia 1, 5
• Critical reassurance: These symptoms are typically self-limiting and resolve within 1-4 weeks 1
• May require prolonged hospitalization, respiratory support, and tube feeding in some cases 5

Neurodevelopmental Outcomes

• Recent evidence provides reassurance that antidepressant use during pregnancy is unlikely to substantially increase risk of autism spectrum disorder (ASD) and ADHD 1, 3
• Associations between prenatal antidepressant exposure and neurodevelopmental problems are largely due to confounding factors rather than medication effects 3
• Studies suggesting associations with lower Apgar scores, ADHD, and speech delay lack high-quality evidence 4, 3

Preterm Birth

• Antidepressant use during pregnancy may increase risk of preterm delivery compared to untreated women with depression 4, 3
• However, untreated depression itself is associated with premature birth and decreased breastfeeding initiation 4, 3

Dosing Considerations

During Pregnancy

• Therapeutic drug monitoring may be beneficial given the 10-fold interindividual variation in sertraline concentrations 6
• Dose adjustments may be required during pregnancy due to pharmacokinetic changes 8
• The goal should be remission of symptoms using the optimal dose that produces best response with tolerable side effects 8

Third Trimester Management

• When treating during the third trimester, carefully weigh potential risks against benefits 5
• Neonates should be monitored for adaptation syndrome symptoms 1, 5

Postpartum Transition

• Dose adjustment is required at birth due to transition to the nonpregnant, breastfeeding state 8
• Sertraline can be safely continued during breastfeeding 4, 1, 2

Discontinuation Protocol

• A gradual dose reduction is recommended rather than abrupt cessation 5
• Monitor for discontinuation symptoms including dizziness, nausea, headache, and irritability 5
• If intolerable symptoms occur, resume the previous dose and taper more gradually 5

Critical Pitfall to Avoid

Do not abruptly discontinue sertraline upon discovering pregnancy. Women who discontinued antidepressants during pregnancy showed significant increase in relapse of major depression compared to those who continued treatment 5. The risk of untreated maternal depression must be weighed against medication risks on a case-by-case basis 5, 8.