Reproductive Safety of Trazodone After Maternal Exposure in Early Pregnancy

Abstract

Purpose/Background Trazodone is indicated for the treatment of major depressive disorder, but more frequently prescribed off-label at lower doses for insomnia in women of childbearing age. The aim of this study was to assess the risks linked to trazodone exposure during pregnancy for which limited safety data are available. Methods/Procedures This multicenter, observational prospective cohort study compared pregnancy outcomes in women exposed to trazodone in early pregnancy against those in a reference group of women exposed to a selective serotonin reuptake inhibitors (SSRIs) between 1996 and 2021. Findings/Results The sample 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 (trazodone [1/169, 0.6%]; SSRI [19/730, 2.6%]; adjusted odds ratio, 0.2; 95% confidence interval, 0.03–1.77). The cumulative incidences of live birth were 61% and 73% in the trazodone and reference group, respectively (25% vs 18% for pregnancy loss and 14% vs 10% for pregnancy termination). Trazodone exposure was not associated with a significantly increased risk of pregnancy termination and pregnancy loss. The rate of small for gestational age infants did not differ between the groups. Implications/Conclusions This study did not reveal a significant difference in the risk of major congenital anomalies after first trimester exposure to trazodone, compared with SSRI exposure. Although this study is the largest so far, these results call for confirmation through further studies.

Consensus Panel Recommendations for the Pharmacological Management of Pregnant Women with Depressive Disorders

“…We also found 12 studies that evaluated malformation risk after exposure to multimodal antidepressants during pregnancy ( Table 5 ). Of these, the majority reported results not controlled for possible indication bias as follows: seven studies evaluated MM risk; one resulted in significant risk [ 85 ] while six resulted in non-significant MM risk [ 49 , 87 , 88 , 89 , 90 , 91 ]; five studies evaluated CM risk, one resulted in significant risk [ 64 ] while four resulted in non-significant CM risk [ 49 , 56 , 59 , 92 ]. After controlling for indication, or at least partially accounting for an underlying psychiatric condition, no study resulted in significant risk for MM, while two resulted in non-significant MM risk [ 85 , 93 ]; only one study reported significant CM risk [ 64 ] while three studies resulted in non-significant CM risk [ 56 , 59 , 93 ].…”

Use of GLP1 receptor agonists in early pregnancy and reproductive safety: a multicentre, observational, prospective cohort study based on the databases of six Teratology Information Services

“…For this study, additional data pertaining to diabetes severity and obesity were also collected, where available. Socioeconomic and educational data were mostly not recorded 22…”

“…Additionally, exclusion criteria encompassed exposure to angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers or tetracyclines during the second and third trimesters, presence of malignancies or malignancy-related conditions, multiple pregnancies and duplicate cases. Data sent from different TIS were analysed anonymously 22…”

Reproductive safety of trazodone

“…Animal data and available human pregnancy exposure data (based primarily on three studies involving 171 trazodone‐exposed patients during the first trimester) have provided suggestive evidence of the drug's safety when used in pregnancy, but the literature on this question remains limited. The purpose of this prospective study was to evaluate risks of trazodone exposure, including major congenital anomalies and other adverse pregnancy and neonatal outcomes, during the first trimester of pregnancy compared with reference exposure to the selective serotonin reuptake inhibitors (SSRIs) sertraline, citalopram, or escitalopram (Dao et al, 2023).…”