Is it safe to restart Selective Serotonin Reuptake Inhibitor (SSRI) in pregnancy?

Restarting SSRIs During Pregnancy

SSRIs can be safely restarted during pregnancy when the benefits of treating maternal depression outweigh the potential risks to the fetus, with sertraline and citalopram being the preferred first-line options. 1, 2

Risk-Benefit Assessment

When considering restarting SSRI therapy during pregnancy, it's important to weigh several factors:

Benefits of SSRI Treatment

• Untreated depression during pregnancy is associated with:
  • Premature birth
  • Decreased initiation of breastfeeding 1
  • Higher risk of relapse of major depression 2

Potential Risks of SSRI Treatment

1. Neonatal complications:

   • Respiratory distress
   • Irritability
   • Feeding problems
   • Tremor, jitteriness
   • Temperature instability
   • Hypoglycemia
   • Hypertonia/hypotonia 1, 2

2. Persistent pulmonary hypertension of the newborn (PPHN):

   • Approximately six-fold higher risk for infants exposed to SSRIs after 20th week of gestation
   • PPHN occurs in 1-2 per 1000 live births in general population 2

SSRI Selection Algorithm

First-line options:

• Sertraline (Zoloft) - Preferred due to:

  • Lower concentration in breast milk
  • Fewer associations with negative outcomes 3
  • Recommended for older patients with depression 1

• Citalopram (Celexa) - Also preferred due to:

  • Fewer associations with negative outcomes when controlled for maternal depression 3
  • Recommended for older patients with depression 1

Second-line options:

• Escitalopram (Lexapro) - Limited data but generally considered safe 1

Avoid if possible:

• Paroxetine (Paxil) - FDA classified as pregnancy category D due to concerns about congenital cardiac malformations 1
• Fluoxetine (Prozac) - Associated with higher risk of negative outcomes 3

Timing Considerations

• First trimester: Recent population-based cohort studies suggest no link between first-trimester antidepressant use and cardiac malformations 1

• After 20th week: Increased risk of PPHN (though absolute risk remains small) 2

• Third trimester: Neonatal complications are more common with exposure late in pregnancy 2, 4

Monitoring Recommendations

1. During pregnancy:

   • Monthly monitoring with quantitative PCR if available 1
   • Monitor for maternal depression symptoms
   • Regular prenatal care with attention to fetal growth

2. After delivery:

   • Monitor neonate for signs of poor adaptation syndrome (respiratory distress, irritability, feeding problems) 2
   • Be prepared for possible need for prolonged hospitalization, respiratory support, or tube feeding in affected infants 2

Important Caveats

• The decision to restart SSRIs should be based on severity of depression symptoms and previous response to medication
• Women with severe depression or previous suicide attempts who responded well to SSRIs may benefit more from medication than psychotherapy 1
• Most studies cannot fully separate the effects of SSRIs from those of untreated depression itself 5
• The absolute risks of most complications are small, even when relative risks are increased

Clinical Bottom Line

For women who require pharmacological treatment for depression during pregnancy, SSRIs remain a reasonable option with sertraline and citalopram as preferred agents. The risks of untreated maternal depression often outweigh the potential risks of SSRI therapy, particularly in cases of moderate to severe depression.