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 is an increased risk of extrapyramidal and withdrawal symptoms in neonates exposed during the third trimester.

Safety Profile and Risks

Maternal Considerations

• Olanzapine is an atypical antipsychotic that crosses the placenta with variable passage ratios (7-167%) 1
• There is a potential increased risk for gestational diabetes with olanzapine use during pregnancy:
  • Women treated with high-risk metabolic second-generation antipsychotics (including olanzapine) had an adjusted risk ratio of 1.8 (95% CI 1.3-2.4) for gestational diabetes compared to untreated pregnant women 2
  • Enhanced metabolic monitoring should be considered for pregnant women using olanzapine 2

Fetal and Neonatal Risks

• Neonates exposed to antipsychotics during the third trimester are at risk for:

  • Extrapyramidal symptoms
  • Withdrawal symptoms including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorders 1
  • These symptoms vary in severity and may require prolonged hospitalization 1

• Infants exposed to olanzapine in utero may have an increased risk of being large for gestational age (adjusted risk ratio 1.6,95% CI 1.3-1.9) 2

• Exposure to second-generation antipsychotics like olanzapine has been linked to increased risk for ventricular and septal defects 3

Breastfeeding Considerations

• Olanzapine is present in human milk 1
• Adverse events reported in breastfed infants exposed to olanzapine include:
  • Somnolence (3.9%)
  • Irritability (2%)
  • Tremor (2%)
  • Insomnia (2%)
  • However, the majority of cases (82.3%) reported no adverse events 4

Monitoring and Management

During Pregnancy

1. Register patients with the National Pregnancy Registry for Atypical Antipsychotics (1-866-961-2388) 1
2. Monitor for gestational diabetes, particularly with olanzapine use 2
3. Consider additional ultrasounds (every 3-4 weeks) to document adequate fetal growth 3
4. Consider fetal umbilical artery Doppler exams if growth restriction is detected 3

After Delivery

1. Monitor neonates for extrapyramidal and withdrawal symptoms 1
2. Be prepared to manage symptoms appropriately, recognizing that some neonates recover within hours or days while others may require prolonged hospitalization 1

Clinical Decision Making

When considering olanzapine use during pregnancy:

1. Assess risk vs. benefit: Balance the risks of untreated maternal psychiatric illness (including relapse, hospitalization, and suicide) against potential risks to the fetus
2. Consider alternatives: If appropriate, consider medications with better-established safety profiles during pregnancy
3. Use lowest effective dose: If olanzapine is necessary, use the lowest effective dose to minimize fetal exposure
4. Timing considerations: Be particularly cautious during the third trimester due to the risk of neonatal extrapyramidal and withdrawal symptoms

Important Caveats

• There are no controlled clinical trials assessing the safety of olanzapine exposure to fetuses and infants 4
• Available data are primarily from observational studies and registries
• Women should notify their clinicians if they become pregnant or intend to become pregnant while being treated with olanzapine 4
• The decision to use olanzapine during pregnancy should involve shared decision-making with the patient, weighing the risks of untreated psychiatric illness against potential risks to the fetus