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

Trazodone Safety During Pregnancy

Trazodone should be considered relatively safe during pregnancy as there is no evidence of increased risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes compared to the general population. 1

Evidence on Trazodone in Pregnancy

FDA Labeling and Safety Data

• 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
• The estimated background risk of major birth defects in the general population is 2-4%, and miscarriage is 15-20%, with no evidence that trazodone increases these risks 1
• Animal studies showed adverse effects on fetuses only at doses 7.3-22 times the maximum recommended human dose 1

Clinical Research Evidence

• A 2023 comparative cohort study (the largest to date) 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 multicentre prospective controlled study found no statistically significant differences in rates of major malformations, spontaneous abortions, or birth weight between women taking trazodone/nefazodone during pregnancy compared to women taking other antidepressants or non-teratogenic drugs 3

Risk-Benefit Assessment

Benefits of Treatment

• Untreated depression during pregnancy is associated with premature birth and decreased initiation of breastfeeding 4
• Women who discontinue antidepressants during pregnancy are more likely to experience a relapse of major depression than women who continue antidepressants 1

Potential Risks

• While trazodone appears relatively safe, some studies suggest a possible association with an increased risk of spontaneous and therapeutic abortions, though this finding is not consistent across all studies 5
• Limited data are available specifically on trazodone compared to more commonly prescribed antidepressants

Breastfeeding Considerations

• Trazodone transfers into human milk, but limited data from post-marketing reports have not identified an association of adverse effects on breastfed children 1

Clinical Approach to Trazodone Use in Pregnancy

Decision Algorithm:

1. Assess severity of depression/insomnia symptoms

   • If severe with significant functional impairment or suicidal ideation, benefits of treatment likely outweigh potential risks

2. Consider gestational timing

   • First trimester: Organogenesis period, but evidence does not suggest increased malformation risk
   • Later trimesters: Monitor for potential neonatal adaptation issues near delivery

3. Evaluate alternative treatments

   • If used primarily for insomnia, consider non-pharmacological approaches first
   • If needed for depression, trazodone appears to have a favorable safety profile compared to some alternatives

4. Monitoring recommendations

   • Register patients with the National Pregnancy Registry for Antidepressants (1-844-405-6185)
   • Regular prenatal care with attention to fetal growth and development

Important Caveats

• Most studies on antidepressant use in pregnancy have methodological limitations, including small sample sizes and inconsistent comparator groups 1
• The safety profile of trazodone appears favorable, but additional research with larger cohorts would strengthen the evidence base 5, 2
• When prescribing any medication during pregnancy, the risk of untreated maternal illness must be weighed against potential medication risks

In conclusion, while no medication can be guaranteed completely safe during pregnancy, the available evidence suggests trazodone has a relatively favorable safety profile with no demonstrated increase in major congenital malformations or other adverse pregnancy outcomes.