Sleep problems are relatively common while pregnant, with as much as 80% of girls reporting sleep problems throughout the first trimester and 66% to 97% of girls within the third trimester.  Many ladies ask concerning the reproductive safety of commonly used sleep medications, including sedative-hypnotic medications or Z-drugs, benzodiazepines, and trazodone.  A brand new study looks on 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 girls exposed to selective serotonin reuptake inhibitors (SSRIs).  All participating centers were members of ENTIS, a corporation of services offering expertise on possible risks related to exposure to medications while pregnant.

The evaluation included 221 trazodone and 869 SSRI-exposed pregnancies. Exposure to trazodone in the primary trimester was not related to a major difference in the danger 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 shouldn’t be statistically significant because the arrogance interval includes the worth 1.

Trazodone exposure was not related to a significantly increased risk of pregnancy termination or pregnancy loss. The speed of small for gestational age infants didn’t differ between the groups.

Is Trazodone Secure to Use During Pregnancy?

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

The collected data regarding using trazodone while pregnant are reassuring, and there is no such thing as a indication that trazodone is a significant teratogen.  Nonetheless, the variety of trazodone exposures stays small.  Ideally we would really like to have data from 600-700 exposures to get a greater estimate of risk; basing decisions regarding safety on small sample sizes can result in miscalculations of risk in either direction.  Given the limited information on the reproductive safety of trazodone, we’d proceed to recommend using, if possible, other options for the treatment of insomnia while pregnant.

Also vital to notice is that although effective non-pharmacologic options for the treatment of insomnia can be found, they’re underutilized on this setting.  There’s good evidence to support using cognitive behavioral therapy for the treatment of insomnia while pregnant.

If sleep medications are needed, the next options could also be considered.  Doxylamine is an over-the-counter medication for insomnia (contained in Unisom Sleep Tabs, 25 – 50 mg).  Doxylamine can also be one in all the ingredients of the anti-nausea medication Diclegis, an option that is perhaps particularly useful in women who even have severe nausea and vomiting.  Especially for people with anxiety, benzodiazepines, reminiscent of lorazepam and clonazepam, could also be useful with adequate data to support their reproductive safety.  Another choice to contemplate is a sedating tricylic antidepressant, for instance imipramine or amitriptyline. 

The next slideshow summarizes information regarding using trazodone while pregnant.

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.