The effects of trazodone exposure during pregnancy on fetal outcomes: a systematic review.

PURPOSE: Trazodone, a medication primarily used for anxiety and insomnia, is increasingly prescribed during pregnancy despite limited safety data. This systematic review aims to assess the effects of trazodone exposure during pregnancy on fetal outcomes.

METHODS

A search was conducted using MEDLINE and Embase databases from the year 2000 to present. Studies were limited to those involving human subjects, published in English, and investigating trazodone exposure during pregnancy. Keywords included "pregnan*," "trazodone," "malformation*," and "birth outcomes." Four reviewers independently extracted data from the selected records. Risk of bias was assessed using the Newcastle-Ottawa Scale. Data synthesis involved a qualitative analysis to summarize and interpret the findings, identifying patterns across the studies.

RESULTS

Fourteen studies met the inclusion criteria. The main outcome measures included fetal and pregnancy outcomes such as congenital malformations, developmental outcomes, poor neonatal adaptation syndrome (PNAS), persistent pulmonary hypertension of the newborn (PPHN), congenital heart defects, gestational age, birth weight, stillbirth, preterm birth, spontaneous and therapeutic abortion, and pre-eclampsia.

CONCLUSION

The review found no consistent evidence linking trazodone use during pregnancy to increased risks of congenital malformations, stillbirths, or low birth weight. However, some studies suggested a possible association with an increased risk of spontaneous and therapeutic abortions. Given the limited and varied data, further research with larger, well-controlled studies are needed to establish the safety profile of trazodone during pregnancy. Overall, clarifying the specific risks and benefits of trazodone use in pregnancy will better guide clinical decision-making and improve maternal-fetal health outcomes.

TRIAL REGISTRATION: PROSPERO number: CRD42024503611.