Aripiprazole in Pregnancy
Aripiprazole can be continued during pregnancy when the benefits of treating severe mental illness outweigh potential risks, as available data do not establish a clear association with major birth defects, though neonates require monitoring for extrapyramidal and withdrawal symptoms following third-trimester exposure. 1
Key Safety Data
Malformation Risk
- Published epidemiologic studies of pregnant women exposed to aripiprazole have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes 1
- A retrospective Medicaid database study of 9,258 women exposed to antipsychotics during pregnancy did not indicate an overall increased risk for major birth defects 1
- Relatively large prospective studies and database analyses provide reassuring safety data, though definitive evidence is lacking 2
Neonatal Complications
- Neonates exposed to aripiprazole during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms following delivery, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder 1
- These symptoms vary in severity; some neonates recover within hours or days without treatment, while others require prolonged hospitalization 1
- One Australian multicentre study (n=26) found associations with pregnancy hypertension, lower birth weight, shorter gestation, and higher neonatal admission rates, though confounding factors cannot be excluded 3
Metabolic Considerations
- Aripiprazole was not associated with increased risk of gestational diabetes in available studies 3
- This favorable metabolic profile is particularly relevant given that pregnancy itself increases metabolic complication risk 3
Clinical Management Algorithm
Before Conception
- Discuss risks of untreated schizophrenia or bipolar disorder, including increased relapse, hospitalization, and suicide risk 1
- Review that schizophrenia itself is associated with adverse perinatal outcomes including preterm birth 1
- Consider that women who discontinue antipsychotics are more likely to experience relapse than those who continue treatment 1
During Pregnancy
- Continue aripiprazole if the patient has been stable on this medication, as the risk of relapse from discontinuation often exceeds potential fetal risks 1, 2
- Monitor blood pressure closely throughout pregnancy given potential hypertension risk 3
- Assess fetal growth and gestational age at regular intervals 3
- Enroll in the National Pregnancy Registry for Atypical Antipsychotics (1-866-961-2388) 1
Peripartum Management
- Prepare neonatal team for potential extrapyramidal or withdrawal symptoms in the newborn 1
- Monitor the neonate immediately after delivery for agitation, abnormal muscle tone, tremor, somnolence, respiratory distress, and feeding difficulties 1
- Be prepared for potential prolonged neonatal hospitalization if symptoms are severe 1
Long-Acting Injectable Formulation
- Aripiprazole LAI has been used successfully through pregnancy in at least one documented case, resulting in a healthy infant with no congenital malformations 4
- This formulation may be considered when treatment adherence is a concern, particularly in patients with history of relapse due to medication discontinuation 4
Important Caveats
Risk-Benefit Framework
- The estimated background risk of major birth defects in the U.S. general population is 2-4%, and miscarriage risk is 15-20% 1
- Untreated severe mental illness poses substantial risks to both mother and fetus that must be weighed against medication risks 1, 5
- Each clinical scenario requires weighing the severity of maternal illness, response to aripiprazole, and availability of alternative treatments 2
Data Limitations
- No randomized placebo-controlled trials exist for ethical reasons 2, 5
- Most available data come from observational studies, registries, and case reports rather than controlled trials 2, 6
- Confounding by indication (the underlying psychiatric illness itself) cannot be fully excluded in observational studies 3