Is olanzapine (atypical antipsychotic) safe to use during pregnancy?

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 limited evidence regarding its safety during pregnancy. 1

Safety Profile in Pregnancy

Fetal Risks

• The FDA pregnancy registry data indicates that neonates exposed to antipsychotics like olanzapine during the third trimester are at risk for:

  • Extrapyramidal symptoms
  • Withdrawal symptoms (including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorders) 1

• Available data from published epidemiologic studies have not established a drug-associated risk of:

  • Major birth defects
  • Miscarriage
  • Other adverse maternal or fetal outcomes 1

Maternal Considerations

• There are risks to the mother associated with untreated schizophrenia or bipolar disorder during pregnancy, including:
  • Increased risk of relapse
  • Hospitalization
  • Suicide 1

Evidence from Safety Surveillance

• A worldwide safety database review of 610 prospectively identified pregnancies with olanzapine exposure reported:

  • 66% normal births
  • 9.8% premature births
  • 8% perinatal conditions 2
  • These rates did not differ significantly from those in the general population 2

• In an earlier safety review, outcomes from 23 prospectively ascertained olanzapine-exposed pregnancies showed:

  • 13% spontaneous abortion
  • 5% stillbirth
  • 0% major malformations
  • 5% prematurity 3

Breastfeeding Considerations

• In 102 pregnancies where olanzapine was used during breastfeeding, the most common adverse events in infants were:
  • Somnolence (3.9%)
  • Irritability (2%)
  • Tremor (2%)
  • Insomnia (2%)
  • However, 82.3% of cases reported no adverse events 2

Clinical Recommendations

1. Pregnancy Planning:

   • Women should notify their clinicians if they become pregnant or intend to become pregnant while taking olanzapine 2
   • Consider the risks of untreated psychiatric illness versus medication exposure

2. Monitoring During Pregnancy:

   • Monitor for potential side effects including water retention and hypertension, as there has been a case report of olanzapine-associated preterm preeclampsia 4
   • Regular fetal assessment is recommended, particularly in the third trimester

3. Delivery Planning:

   • Monitor neonates for extrapyramidal and/or withdrawal symptoms after delivery 1
   • Be prepared to manage these symptoms appropriately if they occur

4. Breastfeeding Considerations:

   • Olanzapine should only be considered during breastfeeding when the potential benefit justifies the potential risk to the infant 2
   • Monitor breastfed infants for somnolence, irritability, and other neurological symptoms 2

Important Caveats

• Most evidence comes from observational data and case reports rather than controlled clinical trials

• Individual risk-benefit assessment is crucial, considering:

  • Severity of the mother's psychiatric condition
  • Previous response to olanzapine
  • Available treatment alternatives
  • Gestational age
  • Presence of other risk factors

• There is one case report of developmental dysplasia of the hip in an infant exposed to olanzapine during pregnancy, but the association remains questionable 5

• Pharmacokinetic modeling suggests only minor decreases (less than 28%) in maternal olanzapine exposure throughout pregnancy, suggesting dose adjustments may not be necessary if treatment was effective before pregnancy 6