Is trazodone (an antidepressant medication) safe to use during pregnancy?

Trazodone Use During Pregnancy

Trazodone appears to be relatively safe during pregnancy with no established association with major birth defects, miscarriage, or other adverse maternal or fetal outcomes, though data are limited and caution is advised. 1

Safety Profile in Pregnancy

• The FDA drug label indicates that published prospective cohort studies, case series, and case reports over several decades have not identified any drug-associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes with trazodone use during pregnancy 1
• A 2023 comparative cohort study found no significant difference in the risk of major congenital anomalies after first-trimester exposure to trazodone (0.6%) compared with SSRI exposure (2.6%) 2
• Animal studies have shown increased fetal resorption and other adverse effects on the fetus in rats at doses 7.3-11 times the maximum recommended human dose, and increased congenital anomalies in rabbits at 7.3-22 times the human dose 1

Pregnancy Outcomes

• A 2003 multicenter prospective controlled study of 147 pregnant women exposed to trazodone or nefazodone found no statistically significant differences in major malformations, spontaneous abortions, or birth weight compared to women taking other antidepressants or nonteratogenic drugs 3
• The cumulative incidence of live births in trazodone-exposed pregnancies was 61% compared to 73% in SSRI-exposed pregnancies, with pregnancy loss rates of 25% vs 18% and pregnancy termination rates of 14% vs 10%, though these differences were not statistically significant 2
• A 2025 systematic review found no consistent evidence linking trazodone use during pregnancy to increased risks of congenital malformations, stillbirths, or low birth weight, but suggested a possible association with increased risk of spontaneous and therapeutic abortions 4

Placental Transfer and Breastfeeding

• Trazodone and its active metabolite (mCPP) do cross the placenta, with cord blood concentrations comparable to maternal serum levels 5
• The FDA notes that trazodone transfers into human milk, but limited data from post-marketing reports have not identified an association of adverse effects on breastfed children 1
• In a case report, trazodone and mCPP were detected in breast milk at concentrations of 50.2 and 3.2 ng/mL, respectively, collected 7.2 hours after maternal dosing 5

Risk-Benefit Considerations

• The FDA recommends considering the risk of untreated depression when discontinuing or changing antidepressant medication during pregnancy and postpartum 1
• A prospective longitudinal study found that women who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressants 1
• Healthcare providers are encouraged to register patients in the National Pregnancy Registry for Antidepressants for ongoing monitoring of outcomes 1

Clinical Recommendations

• When considering trazodone use during pregnancy, weigh the benefits of treating maternal depression or insomnia against the potential risks to the fetus 1, 2
• For women requiring treatment for both depression and insomnia during pregnancy, bupropion may be considered as an alternative, as it does not seem to be associated with major congenital malformations or other significant adverse obstetrical outcomes 6
• Monitor neonates exposed to trazodone during pregnancy for potential withdrawal symptoms or poor neonatal adaptation 5

While the available evidence suggests trazodone is relatively safe during pregnancy, the data are still limited, and larger, well-controlled studies are needed to establish a more definitive safety profile.