What are the guidelines for using anxiolytics, such as benzodiazepines (BZD) or selective serotonin reuptake inhibitors (SSRIs), during pregnancy?

Guidelines for Using Anxiolytics During Pregnancy

SSRIs should be continued during pregnancy at the lowest effective dose when clinically indicated, as withdrawal of medication may have harmful effects on the mother-infant dyad, while benzodiazepines should be used with caution and avoided during the first trimester and lactation when possible. 1

SSRI Use in Pregnancy

Safety Profile

• SSRIs do not appear to be associated with major congenital malformations or adverse neurodevelopmental outcomes 1
• Third-trimester use of SSRIs may lead to neonatal adaptation syndrome including:
  • Crying, irritability, jitteriness, tremors
  • Feeding difficulties, sleep disturbance
  • Respiratory distress, hypoglycemia
  • Symptoms typically resolve within 1-2 weeks after birth 1

Management Recommendations

• Continue SSRI treatment during pregnancy at the lowest effective dose
• Monitor infants for signs of drug toxicity or withdrawal during the first week of life
• Arrange early follow-up after initial hospital discharge 1

Benzodiazepines in Pregnancy

Safety Concerns

• FDA labeling for clonazepam indicates insufficient evidence to assess teratogenicity risk in humans 2
• Animal studies show a pattern of malformations (cleft palate, limb defects) at various doses 2
• Late pregnancy use can result in:
  • Neonatal hypothermia, hypotonia, respiratory depression
  • Feeding difficulties
  • Neonatal dependence and withdrawal 2

Recommendations for Benzodiazepines

• Avoid use during first trimester if possible 3
• If needed, use drugs with established safety records at lowest effective dosage
• Divide daily dosage to avoid high peak concentrations 3
• Use as monotherapy rather than in combination with other medications
• Consider level 2 ultrasonography to rule out visible forms of cleft lip 4

Comparative Risks of Specific Anxiolytics

SSRIs

• Paroxetine has the lowest ratio of infant to maternal plasma concentrations (<0.10) 1
• Sertraline and fluvoxamine are minimally excreted in human milk (<10% of maternal daily dose) 1

Benzodiazepines

• Diazepam appears safe during pregnancy but not during lactation (can cause lethargy, sedation, weight loss in infants) 3
• Chlordiazepoxide seems safer during both pregnancy and lactation 3
• Alprazolam should be avoided during pregnancy and lactation 3

Breastfeeding Considerations

• For SSRIs: Consider the ratio of infant to maternal plasma drug concentration

  • Paroxetine has consistently low ratio (<0.10) 1
  • Sertraline and fluvoxamine provide infant <10% of maternal daily dose 1

• For benzodiazepines:

  • Clonazepam: Effects on breastfed infant unknown; weigh developmental benefits of breastfeeding against potential adverse effects 2
  • Avoid diazepam during lactation 3

Common Pitfalls and Considerations

1. Abrupt discontinuation risk: High discontinuation rates (up to 71% for alprazolam) may lead to untreated maternal mental health conditions 5

2. Confounding by indication: Many studies cannot rule out whether adverse outcomes are due to medication or underlying maternal condition 6

3. Balancing risks: Untreated perinatal depression and anxiety disorders have significant negative impacts on both maternal and fetal health 7

4. Monitoring needs: Infants exposed to SSRIs should be monitored for signs of drug toxicity or withdrawal during the first week of life 1

5. Individual medication selection: When anxiolytic treatment is necessary, choose medications with established safety records and longer clinical experience 3