Key Takeaways

• This prospective study included 58 infants exposed to cariprazine during the first trimester and 2,098 unexposed comparison infants.
• No major malformations occurred in the cariprazine-exposed group, compared with 32 cases, or 1.53%, in the comparison group.
• Prospective enrollment, medical-record review, and blinded outcome assessment strengthen the findings.
• The results are reassuring, but the small sample cannot exclude a modest increase in risk or detect rare outcomes.
• Continued enrollment in the National Pregnancy Registry is essential for obtaining more precise reproductive safety data.

Cariprazine (Vraylar) is a second-generation antipsychotic used to treat psychotic disorders, manic or mixed episodes associated with bipolar disorder, bipolar depression, and treatment-refractory major depressive disorder as an adjunct to antidepressants. Although the use of cariprazine has increased among women of reproductive age, systematically collected information on its use during pregnancy has been lacking (Viguera et al., 2026).

Previous studies have provided reassuring information on the reproductive safety of second-generation antipsychotics as a class. However, much of the available information comes from pregnancies exposed to older and more commonly used medications, such as quetiapine, olanzapine, and aripiprazole. Data on newer medications, including cariprazine, have been extremely limited. Considerably less data is available for cariprazine.

Analyzing data from the MGH National Pregnancy Registry for Psychiatric Medications, Viguera and colleagues report on a prospective cohort study examining the risk of major malformations in infants with first-trimester exposure to cariprazine.

The National Pregnancy Registry

The National Pregnancy Registry for Psychiatric Medications is a prospective pharmacovigilance program. Pregnant women with a history of psychiatric illness are enrolled during pregnancy and followed through the postpartum period. Information is collected before the pregnancy outcome is known, an important feature that reduces the risk of recall and reporting bias.

For this analysis, the investigators:

• Compared infants with first-trimester exposure to cariprazine with infants not exposed to second-generation antipsychotic medications
• Reviewed labor and delivery records and pediatric medical records for evidence of major malformations
• Used a dysmorphologist who was blinded to medication exposure to make the final determination regarding major malformations

As of September 9, 2025, 4,125 participants had enrolled in the Registry. A total of 58 cariprazine-exposed infants and 2,098 infants in the comparison group were eligible for this analysis.

No Major Malformations Observed in Cariprazine-Exposed Group

Among the 58 infants with first-trimester exposure to cariprazine, there were no major malformations:

• Cariprazine-exposed infants: 0 of 58, or 0.00% (95% confidence interval, 0.00% to 6.16%)
• Comparison group: 32 of 2,098, or 1.53% (95% confidence interval, 1.05% to 2.15%)

These preliminary findings are reassuring. No malformations were observed in the cariprazine-exposed group, and the study did not identify a signal suggesting that cariprazine is a major teratogen.

Reassuring Findings, But More Research is Needed

These findings add important information to a previously sparse literature. The new Registry study provides systematic and more detailed information on reproductive safety, as exposed pregnancies are followed prospectively and outcomes are verified through medical record review.

At the same time, the sample remains small. While these data are reassuring, they cannot rule out a modest increase in risk, nor can they provide information about rare malformations. Much larger numbers of exposed pregnancies will be needed to generate a more precise estimate of risk.

It is also important to note that this analysis focused on major malformations after first-trimester exposure. It does not address other outcomes that may be relevant when an antipsychotic is used during pregnancy, including pregnancy complications, neonatal symptoms, or longer-term neurodevelopmental outcomes.

Taken together, these findings offer some reassurance regarding the risk of major malformations following first-trimester exposure to cariprazine. Decisions regarding treatment must take into account the severity of the mother’s illness, her previous response to medication, the risk of relapse associated with discontinuing or changing treatment, and the still-limited reproductive safety data for cariprazine.

These findings are consistent with the broader literature, which has not demonstrated a meaningful increase in the overall risk of major congenital malformations with second-generation antipsychotics as a class. 

The Registry Continues to Recruit

The National Pregnancy Registry for Atypical Antipsychotics continues to enroll pregnant people age 45 and younger with a history of psychiatric illness. Participation helps clinicians and patients make better-informed decisions about the use of psychiatric medications during pregnancy.

To learn more, visit our website or call 1-866-961-2388.

—Ruta Nonacs, MD PhD