What are the recommendations for using Selective Serotonin Reuptake Inhibitors (SSRIs) during pregnancy?

SSRIs During Pregnancy: Recommendations and Risks

SSRIs should be used during pregnancy only when the benefits of treating maternal depression outweigh the potential risks to the fetus, with sertraline and paroxetine being preferred options during breastfeeding due to their lower infant-to-maternal plasma concentration ratios. 1, 2

Risk-Benefit Assessment

• Untreated depression during pregnancy is associated with premature birth, decreased initiation of breastfeeding, and potential harmful effects on the mother-infant relationship 3, 4
• Depression affects approximately 10% of pregnant women, making appropriate treatment important for maternal and fetal wellbeing 5
• The decision to use SSRIs during pregnancy requires careful weighing of risks against the high relapse rate of depression when medication is discontinued 6, 7

Potential Risks of SSRIs During Pregnancy

Congenital Malformations

• Paroxetine has been associated with an increased risk of cardiovascular malformations, particularly ventricular septal defects (VSDs) and atrial septal defects (ASDs), with an odds ratio of 1.8 (95% CI 1.1-2.8) 6
• The FDA classified paroxetine as pregnancy category D due to concerns about congenital cardiac malformations 3
• A large population-based cohort study found no link between first-trimester antidepressant use and cardiac malformations for other SSRIs 3, 2

Neonatal Adaptation Syndrome

• Approximately one-third of newborns exposed to SSRIs in utero may develop neonatal adaptation syndrome 1
• Symptoms include crying, irritability, jitteriness, tremors, poor feeding, hypertonia, tachypnea, sleep disturbance, hypoglycemia, and seizures 1
• These symptoms typically appear within hours to days after birth and usually resolve within 1-2 weeks 1, 8

Persistent Pulmonary Hypertension of the Newborn (PPHN)

• There is a possible association between SSRI use during pregnancy and PPHN 3, 1
• A meta-analysis indicated a number needed to harm of 286-351 for PPHN with late pregnancy SSRI exposure 3, 2
• The FDA advisory on SSRIs and PPHN was revised in 2011, stating that conflicting findings make the association unclear 3

Obstetrical Outcomes

• SSRI use during pregnancy has been associated with an increased risk of preterm birth (adjusted OR 1.24,95% CI 1.09-1.41) 5
• Even when comparing depressed women on SSRIs with depressed women not on SSRIs, the risk of preterm birth remained elevated (6.8% versus 5.8%; OR 1.17,95% CI 1.10-1.25) 5

Management Recommendations

Medication Selection

• For women requiring antidepressant treatment during pregnancy, sertraline is often considered a preferred option due to its favorable safety profile 2, 4
• Paroxetine should only be initiated after consideration of other available treatment options for women who intend to become pregnant or are in their first trimester 6
• Use the lowest effective dose of SSRIs during pregnancy to minimize potential risks 1, 2

Monitoring During Pregnancy

• Monitor for symptoms of depression throughout pregnancy, as untreated depression poses significant risks 2, 4
• For women already taking SSRIs who become pregnant, continuation of treatment is generally recommended if clinically indicated 2, 6

Postpartum Considerations

• Infants exposed to SSRIs in utero should be monitored for at least 48 hours after birth for signs of neonatal adaptation syndrome 1
• Arrange for early follow-up after hospital discharge for infants exposed to SSRIs in the third trimester 1, 2

Breastfeeding Considerations

• Sertraline and paroxetine are considered to have more favorable profiles during breastfeeding due to lower infant-to-maternal plasma concentration ratios 1, 2
• These medications transfer in low concentrations into breast milk and are considered preferred options during breastfeeding 3, 1

Common Pitfalls and Caveats

• Abrupt discontinuation of SSRIs during pregnancy can lead to a high risk of depression relapse, which itself carries risks for mother and fetus 6, 7
• The observed adverse fetal effects may be related to either the medication use or the underlying maternal illness, making causality difficult to determine 9, 4
• Studies on SSRI use in pregnancy often cannot fully separate the effects of the medication from those of depression itself 4
• Women exposed to SSRIs in early pregnancy should be offered prenatal diagnosis through ultrasound examinations and fetal echocardiography to detect potential birth defects 9