Sleep problems are relatively common during pregnancy, with up to 80% of women reporting sleep problems during the first trimester and 66% to 97% of women in the third trimester.  Many women ask about the reproductive safety of commonly used sleep medications, including sedative-hypnotic medications or Z-drugs, benzodiazepines, and trazodone.  A new study looks at the reproductive safety of trazodone.  

In a multicenter, observational prospective cohort study, researchers compared pregnancy outcomes in women exposed to trazodone in early pregnancy to outcomes in a reference group of women exposed to selective serotonin reuptake inhibitors (SSRIs).  All participating centers were members of ENTIS, an organization of services offering expertise on possible risks related to exposure to medications during pregnancy.

The analysis included 221 trazodone and 869 SSRI-exposed pregnancies. Exposure to trazodone in the first trimester was not associated with a significant difference in the risk of major congenital anomalies: for trazodone 1/169 (0.6%) vs. for SSRIs 19/730 (2.6%).  The adjusted odds ratio was 0.2 with a 95% confidence interval, 0.03-1.77; this difference is not statistically significant because the confidence interval includes the value 1.

Trazodone exposure was not associated with a significantly increased risk of pregnancy termination or pregnancy loss. The rate of small for gestational age infants did not differ between the groups.

Is Trazodone Safe to Use During Pregnancy?

While trazodone is commonly used for the treatment of insomnia, data regarding its reproductive safety are relatively limited. This observational prospective study is the largest study to date evaluating the reproductive safety of trazodone.  With this study, the published medical literature includes the outcomes of 309 pregnancies.  

The accumulated data regarding the use of trazodone during pregnancy are reassuring, and there is no indication that trazodone is a major teratogen.  However, the number of trazodone exposures remains small.  Ideally we would like to have data from 600-700 exposures to get a better estimate of risk; basing decisions regarding safety on small sample sizes can lead to miscalculations of risk in either direction.  Given the limited information on the reproductive safety of trazodone, we would continue to recommend using, if possible, other options for the treatment of insomnia during pregnancy.

Also important to note is that although effective non-pharmacologic options for the treatment of insomnia are available, they are underutilized in this setting.  There is good evidence to support the use of cognitive behavioral therapy for the treatment of insomnia during pregnancy.

If sleep medications are needed, the following options may be considered.  Doxylamine is an over-the-counter medication for insomnia (contained in Unisom Sleep Tabs, 25 – 50 mg).  Doxylamine is also one of the ingredients of the anti-nausea medication Diclegis, an option that might be particularly useful in women who also have severe nausea and vomiting.  Especially for individuals with anxiety, benzodiazepines, such as lorazepam and clonazepam, may be useful with adequate data to support their reproductive safety.  Another option to consider is a sedating tricylic antidepressant, for example imipramine or amitriptyline. 

The following slideshow summarizes information regarding the use of trazodone during pregnancy.


Trazodone and Pregnancy by Ruta Nonacs, MD PhD

Ruta Nonacs, MD PhD

Dao K, Shechtman S, Diav-Citrin O, George N, Richardson JL, Rollason V, Pistelli A, Eleftheriou G, Berlin M, Ekobena P, Rousson V, Addor MC, Baud D, Buclin T, Panchaud A, Winterfeld U. Reproductive Safety of Trazodone After Maternal Exposure in Early Pregnancy: A Comparative ENTIS Cohort Study. J Clin Psychopharmacol. 2023 Jan-Feb 01;43(1):12-19.

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