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

Trazodone Use During Pregnancy

Trazodone can be used during pregnancy when clinically indicated, as available evidence does not demonstrate an increased risk of major congenital malformations above baseline population rates.

Safety Profile Based on Available Evidence

The FDA label states that published prospective cohort studies, case series, and case reports over several decades have not identified drug-associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes with trazodone use during pregnancy 1. This represents the most comprehensive regulatory assessment available.

Major Malformation Risk

• The rate of major congenital anomalies with first-trimester trazodone exposure is not significantly elevated 1, 2
• The largest comparative study (221 trazodone-exposed pregnancies vs 869 SSRI-exposed) found a major malformation rate of 0.6% in the trazodone group compared to 2.6% in the SSRI group, with no statistically significant difference 2
• A prospective multicenter study of 147 pregnancies found a 1.6% major malformation rate, which does not exceed the baseline population rate of 1-3% 3
• A 2025 systematic review confirmed no consistent evidence linking trazodone to increased risks of congenital malformations 4

Pregnancy Loss and Other Outcomes

• Some evidence suggests a possible association with spontaneous and therapeutic abortions, though data are inconsistent 4
• The comparative study showed cumulative live birth rates of 61% for trazodone versus 73% for SSRIs, with 25% versus 18% pregnancy loss rates, though this difference was not statistically significant 2
• No increased risk of stillbirth, low birth weight, or small for gestational age infants has been consistently demonstrated 4, 2

Critical Considerations for Clinical Decision-Making

Risk of Untreated Depression

The FDA label explicitly warns that women who discontinued antidepressants during pregnancy were more likely to experience relapse of major depression compared to those who continued treatment 1. This represents a crucial consideration when weighing treatment decisions, as untreated maternal depression carries its own risks to both mother and fetus.

Neonatal Monitoring

• While not specifically documented with trazodone, antidepressants as a class have been associated with poor neonatal adaptation syndrome 5
• One case report documented transient respiratory disturbance in a neonate exposed to trazodone in utero, though no long-term adverse effects were observed 6
• Newborns exposed to trazodone in the third trimester should be monitored for withdrawal-emergent symptoms including tremor, jitteriness, irritability, feeding problems, and somnolence 5, 6

Placental and Breast Milk Transfer

• Trazodone and its active metabolite (mCPP) cross the placenta, with cord blood concentrations comparable to maternal serum levels 6
• Both compounds transfer into breast milk at lower concentrations than serum (50.2 ng/mL trazodone and 3.2 ng/mL mCPP in milk versus 267.6 ng/mL and 22.8 ng/mL in cord blood) 6

Alternative Treatment Considerations

If alternative treatments are preferred for women requiring treatment of both depression and insomnia during pregnancy, bupropion may be considered, as it does not appear to be associated with major congenital malformations or other significant adverse obstetrical outcomes according to ACOG 7, 5. However, bupropion does not address insomnia and may actually worsen sleep disturbances.

Common Pitfalls to Avoid

• Do not abruptly discontinue trazodone upon discovering pregnancy without psychiatric consultation, as the risk of maternal depression relapse may outweigh theoretical fetal risks 1
• Do not assume all antidepressants carry equal risks—the evidence for trazodone specifically shows reassuring safety data compared to baseline population rates 1, 2, 3
• Do not neglect to counsel patients about the pregnancy exposure registry (1-844-405-6185) to contribute to ongoing safety surveillance 1

Monitoring Recommendations

• Careful monitoring of maternal mental health throughout pregnancy is essential 5
• Fetal growth and development should be monitored per standard obstetric care 5
• Neonatal observation for at least 48-72 hours after delivery is warranted to detect any withdrawal-emergent symptoms or adaptation difficulties 5, 6