Is Abilify (aripiprazole) safe for use in bipolar disorder during pregnancy?

Safety of Abilify (Aripiprazole) for Bipolar Disorder During Pregnancy

Aripiprazole use during pregnancy requires careful consideration of risks and benefits, as it may cause extrapyramidal and/or withdrawal symptoms in neonates exposed during the third trimester, though overall data do not establish a clear drug-associated risk of major birth defects or miscarriage. 1

Risk Assessment

Fetal Safety Data

• The FDA label indicates that neonates exposed to antipsychotics like aripiprazole during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms following delivery 1
• These symptoms may include:
  • Agitation
  • Hypertonia or hypotonia
  • Tremor
  • Somnolence
  • Respiratory distress
  • Feeding disorders

Birth Defect Risk

• Published epidemiologic studies have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes 1
• The National Pregnancy Registry for Atypical Antipsychotics found that after adjustment for confounding variables, the risk of major malformations after first trimester exposure to aripiprazole was not significantly different from controls (adjusted odds ratio 1.35,95% CI = 0.43-4.20) 2

Pregnancy Complications

• A small retrospective study found aripiprazole use in pregnancy was associated with:
  • Increased risk of pregnancy hypertension
  • Lower birth weight
  • Shorter gestation at birth
  • Higher rates of neonatal admission 3
  • However, these findings need replication in larger studies to rule out confounding factors

Medication Management During Pregnancy

Dosing Considerations

• Pharmacokinetic studies suggest that plasma concentrations of aripiprazole decline dramatically during pregnancy if doses remain fixed 4
• PBPK modeling suggests that by the third trimester, aripiprazole may be entirely unable to reach its effective concentration 4
• Women may need approximately 2 times their baseline dose of aripiprazole during late pregnancy to maintain therapeutic levels 4

Monitoring Recommendations

• All pregnancies in women taking aripiprazole should be registered with the National Pregnancy Registry for Atypical Antipsychotics (1-866-961-2388) 1
• Monitor for:
  • Signs of pregnancy hypertension
  • Fetal growth
  • Maternal mental health status

Postpartum Considerations

Neonatal Monitoring

• Neonates should be monitored for extrapyramidal and/or withdrawal symptoms 1
• Symptoms have varied in severity:
  • Some neonates recover within hours or days without specific treatment
  • Others require prolonged hospitalization 1

Breastfeeding

• Limited data are available regarding aripiprazole use during breastfeeding
• The medication will likely be present in human milk due to its pharmacokinetic properties

Clinical Decision Making

Risk-Benefit Analysis

1. Consider the risks of untreated bipolar disorder during pregnancy:

   • Increased risk of relapse
   • Hospitalization
   • Suicide
   • Adverse perinatal outcomes including preterm birth 1

2. Weigh against potential risks of aripiprazole:

   • Neonatal extrapyramidal/withdrawal symptoms
   • Possible pregnancy complications

3. Consider alternative medications if appropriate based on:

   • Patient's treatment history
   • Severity of illness
   • Previous response to medications

Practical Recommendations

• If aripiprazole has been effective for managing bipolar disorder:

  • Continue medication with close monitoring
  • Consider dose adjustments as pregnancy progresses
  • Prepare for potential neonatal complications
  • Ensure coordination between psychiatric and obstetric care

• If initiating treatment during pregnancy:

  • Consider medications with more extensive safety data if appropriate for the patient's condition

In many cases, the potential benefits of aripiprazole for patients with bipolar disorder outweigh the potential risks, especially when the condition is severe and has responded well to this medication 5.