Trazodone Safety During Pregnancy
Trazodone can be used during pregnancy as published data from prospective cohort studies, case series, and case reports have not identified any drug-associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes. 1
Safety Profile in Pregnancy
The FDA drug label for trazodone states that while available studies cannot definitively establish the absence of risk, published data over several decades have not identified an association between trazodone use during pregnancy and major birth defects, miscarriage, or other adverse maternal or fetal outcomes 1
A 2023 comparative cohort study by the European Network of Teratology Information Services (ENTIS) found no significant difference in the risk of major congenital anomalies after first-trimester exposure to trazodone (0.6%) compared to SSRI exposure (2.6%) 2
A multicenter prospective controlled study found no statistically significant differences in rates of major malformations, spontaneous abortions, therapeutic abortions, gestational age at birth, or birth weight between women taking trazodone/nefazodone during pregnancy compared to women taking other antidepressants or nonteratogenic drugs 3
Considerations for Use
The National Pregnancy Registry for Antidepressants encourages healthcare providers to register patients taking trazodone during pregnancy by calling 1-844-405-6185 or visiting their website 1
Animal studies have shown increased fetal resorption and other adverse effects on the fetus in rats at doses 7.3 to 11 times the maximum recommended human dose, and an increase in congenital anomalies in rabbits at 7.3 to 22 times the maximum recommended human dose 1
Consider the risk of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy, as women who discontinue antidepressants during pregnancy are more likely to experience a relapse of major depression 1
Breastfeeding Considerations
Data from published literature report the transfer of trazodone into human milk, but there are limited data on the effect of trazodone on milk production 1
A case study found that trazodone and its active metabolite (mCPP) are transferred into breast milk, with concentrations in breast milk being lower than in maternal serum 4
Limited data from post-marketing reports have not identified an association of adverse effects on the breastfed child 1
Monitoring Recommendations
For women requiring treatment for both depression and insomnia during pregnancy, careful monitoring of maternal and fetal health is recommended 5
If alternative treatments are preferred, bupropion may be considered as it does not seem to be associated with major congenital malformations or other significant adverse obstetrical outcomes 5
A systematic review highlighted the need for further research with larger, well-controlled studies to establish a more comprehensive safety profile of trazodone during pregnancy 6
Potential Risks to Consider
While not specifically associated with trazodone, some antidepressants have been linked to poor neonatal adaptation syndrome, so monitoring of the newborn may be warranted 7
All pregnancies have a background risk of birth defects (2-4%) and miscarriage (15-20%) in the U.S. general population, regardless of medication exposure 1