Trazodone Use in Pregnancy
Trazodone can be used during pregnancy, as available evidence does not demonstrate an increased risk of major congenital malformations above baseline rates, though data remain limited and alternative agents with more robust safety profiles should be considered first.
Evidence Quality and Safety Profile
The FDA label for trazodone 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 1. This represents the highest-quality regulatory guidance available.
Key Safety Data:
Major Malformations: The largest comparative study (221 trazodone-exposed pregnancies) found no significant increase in major congenital anomalies compared to SSRI exposure (0.6% vs 2.6%; adjusted OR 0.2,95% CI 0.03-1.77) 2
Pregnancy Outcomes: A systematic review of 14 studies found no consistent evidence linking trazodone to increased risks of congenital malformations, stillbirths, or low birth weight 3
Baseline Risk: A multicentre prospective study of 147 pregnancies exposed to trazodone/nefazodone found major malformation rates of 1.6%, which does not exceed the baseline population risk of 1-3% 4
Clinical Decision Algorithm
When Trazodone May Be Appropriate:
Patient already stable on trazodone when pregnancy is discovered - consider continuing given lack of clear teratogenic signal 1, 2
Treatment-resistant insomnia in pregnancy where first-line options have failed 5
Depression with prominent insomnia requiring dual symptom management 6
Important Caveats:
Spontaneous abortion: Some studies suggest possible association with increased risk of spontaneous and therapeutic abortions, though confounding by indication (underlying psychiatric illness) cannot be ruled out 3
Limited data: Despite decades of use, sample sizes remain relatively small compared to other antidepressants 2, 4
Animal data concerns: Trazodone caused increased fetal resorption in rats at 7.3-11 times the maximum recommended human dose and congenital anomalies in rabbits at 7.3-22 times the human dose 1
Alternative Considerations
Bupropion may be preferred for women requiring treatment for both depression and insomnia during pregnancy, as it does not appear associated with major congenital malformations or significant adverse obstetrical outcomes 5. However, bupropion has less robust evidence for treating insomnia specifically.
Risk of Untreated Depression
The FDA label emphasizes that women who discontinued antidepressants during pregnancy were more likely to experience relapse of major depression than those who continued treatment 1. The risk of untreated maternal depression must be weighed against theoretical medication risks, as maternal mental health directly impacts fetal and neonatal outcomes.
Practical Prescribing Approach
- Confirm pregnancy status before initiating trazodone in women of childbearing age
- If already taking trazodone: Continue if clinically stable, as switching medications introduces additional risks 1
- If newly prescribing: Consider alternatives with more robust pregnancy data first (SSRIs for depression, behavioral interventions for insomnia)
- Dosing: Use lowest effective dose; typical antidepressant dosing is 150-300 mg at bedtime 7
- Monitoring: Standard prenatal care with attention to fetal growth and development 1
Documentation and Counseling
Inform patients that: