What is the safety of using antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), during pregnancy?

Safety of Antidepressants During Pregnancy

Antidepressant use during pregnancy is generally safe, as evidence suggests that observed associations between prenatal antidepressant exposure and neurodevelopmental problems in children are largely due to confounding factors rather than direct medication effects. 1

Overview of Safety Profile

• Antidepressant use, particularly SSRIs, among pregnant women has been increasing, with up to 12% of pregnant women in the US filling prescriptions for SSRIs by 2013 1
• Antidepressants cross the placenta and can be found in amniotic fluid and cord blood, raising theoretical concerns about fetal exposure 1
• While rodent studies have shown adverse effects of perinatal antidepressant exposure on neurodevelopment, between-species differences limit the generalizability of these findings to humans 1

Neurodevelopmental Outcomes

• Converging evidence from multiple study designs suggests that associations between prenatal antidepressant exposure and neurodevelopmental problems (particularly ASD and ADHD) are largely due to confounding factors rather than medication effects 1
• The Journal of Child Psychology and Psychiatry review provides reassurance that antidepressant use during pregnancy is unlikely to substantially increase the risk of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) 1
• There are conflicting findings on the association between prenatal SSRI exposure and autism, with evidence being inconclusive 1, 2

Potential Risks

• SSRIs may be associated with a small increased risk of:

  • Persistent pulmonary hypertension of the newborn (PPHN), with a number needed to harm of 286-351 for late pregnancy exposure 1, 2
  • Neonatal adaptation syndrome, characterized by respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulties, and irritability 3, 4
  • Preterm birth compared to untreated women with depression 1
  • Possible cardiac malformations, particularly with paroxetine and fluoxetine (though a large cohort study of nearly 1 million pregnant women suggested no link between first-trimester antidepressant use and cardiac malformations) 1, 2

• The FDA revised its 2006 advisory on SSRI use after the 20th week of gestation in 2011, stating that conflicting findings make it unclear whether SSRIs during pregnancy cause PPHN 1

Medication-Specific Considerations

• Paroxetine was classified as pregnancy category D by the FDA in 2005 due to concerns about congenital cardiac malformations 1
• Sertraline appears to have a more favorable safety profile, with no evidence for increased risk of major congenital malformations 2
• Paroxetine and sertraline are the most commonly prescribed antidepressants during breastfeeding 1

Risk-Benefit Assessment

• The benefits of antidepressant therapy during pregnancy generally outweigh the risks when clinically indicated 5
• Untreated depression during pregnancy is associated with:
  • Premature birth and decreased initiation of breastfeeding 1
  • Increased risk of relapse during pregnancy when antidepressants are discontinued 3, 4
  • Potential negative effects on maternal and fetal well-being 6

Treatment Recommendations

• The American Psychiatric Association and American College of Obstetricians and Gynecologists recommend:

  • A stepped approach to treatment of depression during pregnancy 1
  • For mild depression with recent onset (≤2 weeks), monitoring and encouraging exercise and social support 1
  • For mild depression not improving within two weeks or moderate-to-severe depression, evidence-based treatment should be offered 1
  • Antidepressants may be a superior option for women with history of severe suicide attempts or severe depression with previous positive response to medication 1
  • Continuing antidepressants during pregnancy may be advisable for women who have previously relapsed when discontinuing treatment 1

• When selecting an antidepressant during pregnancy:

  • Sertraline may be preferred due to its more favorable safety profile 2
  • Paroxetine and fluoxetine should generally be avoided due to potential increased risk of congenital malformations 2

Clinical Decision-Making

• Treatment decisions should consider:

  • Severity of current symptoms
  • Previous mental health history
  • Patient treatment preferences
  • Risk-benefit ratio of treatment versus untreated depression 1

• Routine screening for depression during pregnancy is recommended using validated tools such as the Patient Health Questionnaire, Hospital Anxiety and Depression Scale, or Edinburgh Postnatal Depression Scale 1

• When the clinical picture warrants it, the use of many antidepressants, especially SSRIs, is favorable compared to exposing mother and child to untreated depressive illness 7