What are the guidelines for using Selective Serotonin Reuptake Inhibitors (SSRIs) in pregnancy and postpartum in Canada?

SSRIs in Pregnancy and Postpartum: Canadian Guidelines

Sertraline and citalopram should be considered first-line SSRI treatments for depression and anxiety during pregnancy and postpartum in Canada, with sertraline being preferred during breastfeeding due to minimal infant exposure.

Risks Associated with SSRIs During Pregnancy

Neonatal Effects

• SSRIs used in the third trimester can lead to a constellation of neonatal signs including:
  • Crying, irritability, tremors
  • Poor feeding, feeding difficulties
  • Hypertonia, tachypnea, sleep disturbance
  • Hypoglycemia, and rarely seizures 1
• These symptoms typically appear within hours to days after birth and usually resolve within 1-2 weeks 1
• In severely affected infants, short-term chlorpromazine may provide relief 1

Congenital Malformations

• Most SSRIs are not considered major teratogens, but some carry specific risks:
  • Paroxetine: Increased risk of cardiac defects (aOR 1.45) and ventricular/atrial septal defects (aOR 1.39) 2
  • Citalopram: Increased risk of musculoskeletal defects (aOR 1.92) and craniosynostosis (aOR 3.95) 2
  • Fluoxetine: Associated with increased risk of congenital malformations 3
  • Sertraline: Shows no evidence of increased risk for major congenital malformations 3

Other Pregnancy Complications

• SSRI use during pregnancy has been associated with:
  • Persistent pulmonary hypertension of the newborn (PPHN), though evidence is conflicting 4
  • Preterm birth 3
  • Neonatal adaptation symptoms 3

SSRIs During Breastfeeding

Safety Profiles

• Sertraline is considered the safest option during breastfeeding:
  • Very low concentration in breast milk
  • Not linked to infant complications 5
  • Relative infant dose (RID) <1% 1
• Paroxetine is also considered relatively safe during breastfeeding 1

Monitoring Recommendations

• Monitor breastfed infants for:
  • Drowsiness and hypotonia
  • Irritability, insomnia
  • Feeding difficulties 1

Decision-Making Algorithm for SSRI Use in Pregnancy and Postpartum

For New Prescriptions:

1. First-line options:

   • Sertraline: Preferred during pregnancy and breastfeeding due to minimal infant exposure and no evidence of increased malformation risk
   • Citalopram: Alternative first-line option, but with slightly higher risk of specific malformations

2. Avoid if possible:

   • Paroxetine: Due to increased risk of cardiac defects
   • Fluoxetine: Due to increased risk of congenital malformations

For Women Already on SSRIs:

1. If on sertraline or citalopram:

   • Continue current medication with appropriate monitoring

2. If on paroxetine or fluoxetine:

   • Consider switching to sertraline or citalopram if in first trimester
   • If in second or third trimester, weigh risks of switching versus continuing
   • Discuss risks and benefits with patient

Dosing Considerations:

• Start at lowest effective dose
• Adjust as needed based on symptom control
• Consider that pregnancy may alter medication metabolism, potentially requiring dose adjustments

Monitoring Recommendations

During Pregnancy:

• Regular assessment of maternal mental health symptoms
• Monitor for potential side effects
• Ultrasound monitoring for fetal development

Postpartum:

• Monitor newborn for neonatal adaptation syndrome for up to 2 weeks
• Watch for signs including irritability, tremors, feeding difficulties, respiratory issues
• Continue maternal mental health monitoring

Important Caveats

• Risk-benefit assessment is crucial: Untreated depression during pregnancy is associated with premature birth and decreased initiation of breastfeeding 1
• FDA drug labeling: Sertraline should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus 4
• Discontinuation risks: Women who discontinue antidepressant medication during pregnancy show a significant increase in relapse of major depression compared to those who remain on medication 4
• Individualized approach: The decision to use SSRIs during pregnancy must be made on a case-by-case basis, weighing maternal benefits against potential fetal risks 4

By following these guidelines, healthcare providers can make evidence-based decisions regarding SSRI use during pregnancy and postpartum, prioritizing both maternal mental health and infant safety.