In This article

• This prospective case series included 56 women who used vortioxetine during the first trimester of pregnancy.
• No major malformations were observed among the 56 exposed pregnancies with evaluable data.
• Prospective enrollment, medical-record review, and blinded outcome assessment strengthen the findings.
• The results are reassuring, but the small sample and absence of a comparison group limit the conclusions that can be drawn.
• Continued enrollment in the National Pregnancy Registry is essential for obtaining more precise reproductive safety data on vortioxetine and other newer antidepressants.

Vortioxetine (Trintellix) is an antidepressant used for the treatment of major depressive disorder in adults. While we have a considerable amount of information supporting the reproductive safety of older antidepressants, including most selective serotonin reuptake inhibitors (SSRIs), the serotonin-norepinephrine reuptake inhibitors (SNRIs) venlafaxine and duloxetine, and bupropion, we have far less information on newer antidepressants.

Vortioxetine was approved in the United States in 2013 for the treatment of depression. Because it is a relatively newer antidepressant, the number of reported pregnancies with vortioxetine exposure has been small. Analyzing data from the MGH National Pregnancy Registry for Psychiatric Medications, Freeman and colleagues now report additional prospective data on the risk of major malformations following first-trimester exposure to vortioxetine.

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:

• Identified women enrolled in the Registry who reported taking vortioxetine during the first trimester
• Collected information about major malformations through a maternal postpartum interview and review of medical records
• Used a dysmorphologist who was blinded to medication exposure to make the final determination regarding major malformations

As of March 26, 2026, 56 women with first-trimester exposure to vortioxetine had evaluable outcome data. 

No Major Malformations Observed After First-Trimester Exposure

Among the 56 women who used vortioxetine during the first trimester, no major malformations were observed.

• Vortioxetine-exposed pregnancies: 0 of 56 with a major malformation
• Outcome assessment: Maternal postpartum interview, medical-record review, and adjudication by a dysmorphologist blinded to exposure status

These preliminary findings are reassuring. The new study did not identify a signal suggesting that vortioxetine is a major teratogen. 

Reassuring Findings, But More Research is Needed

The new Registry findings add important information to a previously sparse literature. The study provides systematically collected data because women were enrolled prospectively and outcomes were assessed through postpartum interviews and medical-record review.

At the same time, the sample remains small. Observing no malformations among 56 exposed pregnancies does not establish that vortioxetine is safe during pregnancy. These data cannot rule out a modest increase in risk, nor can they detect rare malformations. Much larger numbers of exposed pregnancies and an appropriate comparison group will be needed to generate a more precise estimate of risk.

It is also important to note that the analysis focused on major malformations after first-trimester exposure. It does not provide information on other outcomes that may be relevant when an antidepressant is used during pregnancy, including miscarriage, pregnancy complications, preterm birth, neonatal adaptation symptoms, or longer-term neurodevelopmental outcomes.

Taken together, these findings offer some reassurance regarding the risk of major malformations following first-trimester exposure to vortioxetine. However, treatment decisions must be individualized. When initiating an antidepressant in a person who is pregnant or planning pregnancy, it is reasonable to consider a medication with a better-characterized reproductive safety profile. For a patient who has responded well to vortioxetine, however, the potential benefits of switching medications must be weighed against the risk of relapse or loss of treatment response.

No two situations are identical. Decisions regarding treatment should take into account the severity and recurrence of the mother’s illness, her response to previous medications, the availability of effective alternatives, and the risks associated with untreated depression during pregnancy. 

The Registry Continues to Recruit

The National Pregnancy Registry for Antidepressants continues to enroll pregnant people age 45 and younger with a history of psychiatric illness. People who have taken an antidepressant during pregnancy, as well as those who have not taken an antidepressant, are eligible to participate.

Participation helps clinicians and patients make better-informed decisions about the use of antidepressant medications during pregnancy. To learn more, visit our website or call 1-866-961-2388. 

—Ruta Nonacs, MD PhD