What is the safest Selective Serotonin Reuptake Inhibitor (SSRI) to use during pregnancy?

Safest SSRI During Pregnancy

Sertraline is the safest SSRI to use during pregnancy due to its established safety profile and lower risk of adverse outcomes. 1

Evidence-Based Rationale for SSRI Selection

First-Line Option: Sertraline

• Sertraline is recommended as the preferred first-line SSRI during pregnancy by the American Academy of Family Physicians and the American Academy of Pediatrics 1
• It has the most established safety profile among SSRIs for use during pregnancy 1
• Sertraline shows low placental transfer to the infant (25-33% of maternal concentrations) 2
• The drug is excreted in human milk at less than 10% of the maternal daily dose 1

Second-Line Option: Citalopram

• Citalopram is generally considered safe and is another reasonable option 1
• However, it has less robust safety data compared to sertraline

SSRI to Avoid: Paroxetine

• Paroxetine is FDA classified as pregnancy category D due to concerns about congenital cardiac malformations 1
• Should be avoided as a first-line agent during pregnancy

Potential Risks of SSRI Use During Pregnancy

Neonatal Adaptation Syndrome

• Occurs with third-trimester exposure to SSRIs 1, 3
• Symptoms include crying, irritability, tremors, poor feeding, hypertonia, tachypnea, sleep disturbance, hypoglycemia, and seizures
• These symptoms are typically mild and transient 4

Persistent Pulmonary Hypertension of the Newborn (PPHN)

• Small increased risk with SSRI exposure (number needed to harm: 286-351) 1
• Extremely rare consequence of fetal exposure 4

Congenital Malformations

• Meta-analyses suggest a generally small risk of congenital malformations with SSRIs 5
• When controlling for maternal depression and associated factors, the risk is often not statistically significant 5, 6
• Paroxetine has the strongest association with cardiac malformations 1, 6

Monitoring Recommendations

During Pregnancy

• Regular prenatal care with attention to fetal development
• Consider maintaining the lowest effective dose
• Avoid abrupt discontinuation of medication, as untreated depression is associated with premature birth and decreased breastfeeding initiation 1

Neonatal Period

• Monitor exposed infants for signs of drug toxicity or withdrawal during the first week of life 1
• Arrange early follow-up after initial hospital discharge 1
• Observe newborns with late-pregnancy exposure to SSRIs in hospital for at least 48 hours 4

Clinical Decision-Making Algorithm

1. Assess severity of maternal depression/anxiety

   • Consider non-pharmacological options first (e.g., Cognitive Behavioral Therapy) for mild cases 1

2. If medication is necessary:

   • Choose sertraline as first-line option 1, 6
   • Consider citalopram as an alternative if sertraline is not tolerated 1
   • Avoid paroxetine due to increased risk of cardiac malformations 1, 6

3. Dosing considerations:

   • Start with the lowest effective dose
   • Monitor for therapeutic response
   • Consider therapeutic drug monitoring due to high interindividual variation in sertraline concentrations during pregnancy 2

4. Timing considerations:

   • If possible, avoid introducing new SSRIs in the third trimester to reduce risk of neonatal adaptation syndrome
   • Do not discontinue effective treatment due to pregnancy, as untreated depression poses significant risks 1, 3

Important Caveats

• The decision to use SSRIs during pregnancy should balance maternal mental health needs against potential fetal risks 1, 3, 7
• Untreated depression during pregnancy is associated with premature birth, decreased breastfeeding initiation, and increased risk of relapse 1
• All SSRIs are FDA category C (except paroxetine - category D), meaning they should be given only if potential benefits justify the potential risk to the fetus 1
• The interindividual variation in maternal sertraline concentrations during pregnancy is significant (up to 10-fold), which may affect both efficacy and safety 2