Trazodone for Sleep During Pregnancy: Not Recommended
Sedatives and hypnotics, including trazodone, are not recommended during pregnancy or nursing according to clinical practice guidelines. 1
Primary Recommendation
Avoid trazodone for insomnia during pregnancy. The American Academy of Sleep Medicine explicitly states that sedatives/hypnotics are not recommended during pregnancy, and trazodone specifically lacks FDA approval for insomnia with unestablished efficacy for this indication. 1 Additionally, trazodone demonstrates only minimal clinical benefit even in non-pregnant populations—reducing sleep latency by merely 10.2 minutes and increasing total sleep time by only 21.8 minutes at the 50 mg dose, both below clinical significance thresholds. 2, 3
Safety Data in Pregnancy
Fetal Risk Profile
Animal studies show fetal harm: Trazodone caused increased fetal resorption at doses 7.3-11 times the maximum recommended human dose in rats, and increased congenital anomalies in rabbits at 7.3-22 times the human dose. 4
Human data are limited but somewhat reassuring: Published prospective cohort studies over several decades have not identified consistent associations with major birth defects, stillbirths, or low birth weight. 4, 5, 6
Possible increased abortion risk: Some studies suggest a possible association with increased risk of spontaneous and therapeutic abortions, though data are inconsistent. 5
Largest comparative study findings: A multicenter study of 221 trazodone-exposed pregnancies compared to 869 SSRI-exposed pregnancies found no significant difference in major congenital anomalies (0.6% vs 2.6%), though live birth rates were lower in the trazodone group (61% vs 73%). 6
Placental transfer is substantial: Trazodone and its active metabolite (mCPP) cross the placenta, with cord blood concentrations comparable to maternal serum levels. 7
Risk-Benefit Analysis
Why the Risks Outweigh Benefits
Minimal therapeutic benefit: The medication provides clinically insignificant improvement in sleep parameters even when used for its intended off-label purpose. 2, 3
High adverse event rate: 75% of patients experience adverse effects on trazodone versus 65.4% on placebo, including headache (30% vs 19%) and somnolence (23% vs 8%). 2, 3
Lack of efficacy data: Trazodone's efficacy for insomnia is not well established, and it is not FDA-approved for this indication. 1
Untreated insomnia may be preferable: Given the minimal benefit and potential fetal risks, the harm-benefit ratio does not favor treatment with trazodone during pregnancy. 1
Alternative Management Strategies
Non-Pharmacologic Approaches (First-Line)
Cognitive behavioral therapy for insomnia (CBT-I) should be the initial treatment approach, as it is recommended by major guidelines for chronic insomnia and carries no fetal risk. 2
Sleep hygiene optimization and behavioral interventions should be maximized before considering any pharmacotherapy. 8, 9
If Pharmacotherapy Is Absolutely Necessary
Consider the underlying condition: If insomnia is secondary to depression or anxiety requiring treatment, address the primary psychiatric condition with medications that have better pregnancy safety profiles. 4, 8
Risk of untreated psychiatric illness: Women with major depressive disorder who discontinue antidepressants during pregnancy are more likely to experience relapse, which itself carries maternal and fetal risks. 4
Alternative agents with better data: If a sedating medication is deemed essential, other options may have more established safety profiles, though all carry risks and should be used cautiously. 9
Critical Counseling Points
FDA pregnancy registry exists: Healthcare providers should register patients exposed to trazodone during pregnancy by calling 1-844-405-6185. 4
Breastfeeding considerations: Trazodone transfers into breast milk, though limited postmarketing data have not identified clear adverse effects on breastfed infants. 4, 7
Informed decision-making: Any decision to use trazodone during pregnancy must involve thorough discussion of the limited efficacy data, animal study findings, and the principle that the medication provides minimal benefit for insomnia. 4, 5
Common Pitfalls to Avoid
Do not increase the dose: Higher doses lack guideline support for insomnia and increase adverse event risk without improving efficacy. 2, 10
Do not assume safety based on widespread use: Trazodone is frequently prescribed off-label for insomnia in women of childbearing age, but this does not establish safety during pregnancy. 6
Do not ignore the minimal efficacy: The decision should account for the fact that even in non-pregnant populations, trazodone shows clinically insignificant benefits for sleep. 2, 3