What are the guidelines for using olanzapine (atypical antipsychotic) in pregnant women?

Olanzapine Use During Pregnancy

Olanzapine should be used during pregnancy only when the potential benefit justifies the potential risk to the fetus, as there are concerns about fetal exposure and neonatal complications. 1

Safety Profile in Pregnancy

Fetal Outcomes

• The FDA label indicates that neonates exposed to antipsychotics like olanzapine during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms following delivery 1
• These symptoms can include:
  • Agitation, hypertonia, hypotonia, tremor, somnolence
  • Respiratory distress and feeding disorders
  • Severity varies; some neonates recover within hours/days, others require prolonged hospitalization 1

Congenital Malformations

• Overall available data from published epidemiologic studies have not established a drug-associated risk of major birth defects or miscarriage with olanzapine 1
• However, exposure to second-generation antipsychotics like olanzapine has been linked to increased risk for ventricular and septal defects 2

Metabolic Risks

• Olanzapine is associated with increased risks for gestational diabetes (adjusted risk ratio 1.8,95% CI 1.3-2.4) 3
• Infants exposed to olanzapine in utero have an increased risk of being large for gestational age (adjusted risk ratio 1.6,95% CI 1.3-1.9) 3
• Enhanced metabolic monitoring should be considered for pregnant women using olanzapine 3

Pregnancy Registry

• Healthcare providers are encouraged to register pregnant patients taking olanzapine in the National Pregnancy Registry for Atypical Antipsychotics (1-866-961-2388) 1

Breastfeeding Considerations

• Olanzapine is present in human milk 1
• Reports indicate potential adverse effects in breastfed infants including:
  • Excess sedation (3.9%)
  • Irritability (2%)
  • Tremor (2%)
  • Insomnia (2%)
  • Poor feeding
  • Extrapyramidal symptoms 1, 4
• The majority of infants (82.3%) exposed through breastfeeding reported no adverse events 4

Clinical Decision-Making Algorithm

1. Assessment of Necessity:

   • Evaluate the severity of the psychiatric condition
   • Consider the risk of untreated mental illness (increased risk of relapse, hospitalization, suicide) 1
   • Assess potential alternatives with better safety profiles

2. If Treatment is Necessary:

   • Use the lowest effective dose
   • Monitor for metabolic complications, particularly gestational diabetes 3
   • Consider PBPK modeling suggests minor changes in olanzapine exposure (less than 28%) throughout pregnancy, potentially not requiring dose adjustments 5

3. Third Trimester Considerations:

   • Prepare for potential neonatal complications
   • Arrange for appropriate neonatal monitoring after delivery
   • Consider tapering dose before delivery if clinically feasible

4. Postpartum Planning:

   • Evaluate risks/benefits of breastfeeding while on olanzapine
   • Monitor infant for sedation, irritability, poor feeding, and extrapyramidal symptoms if breastfeeding 1

Monitoring Recommendations

• Regular blood glucose monitoring during pregnancy due to increased risk of gestational diabetes 3
• Fetal growth monitoring for potential large-for-gestational-age status 3
• Neonatal monitoring for extrapyramidal and withdrawal symptoms after delivery 1

Common Pitfalls to Avoid

1. Abrupt Discontinuation: Stopping olanzapine suddenly may lead to psychiatric relapse, which carries its own risks to mother and fetus
2. Ignoring Metabolic Monitoring: Failing to screen for gestational diabetes in women taking olanzapine
3. Inadequate Neonatal Preparation: Not preparing the pediatric team for potential neonatal complications
4. Overlooking Breastfeeding Risks: Not discussing the potential effects of olanzapine exposure through breast milk

While the data on olanzapine use in pregnancy is limited, the available evidence suggests cautious use with appropriate monitoring when the benefits outweigh the risks of untreated psychiatric illness.