Reproductive Toxicity Induced by Serotonin-Norepinephrine Reuptake Inhibitors: A Pharmacovigilance Analysis From 2004 to 2023 Based on the FAERS Database

Abstract

Aim

Serotonin-norepinephrine reuptake inhibitors (SNRIs) have been extensively utilized for the treatment of depression and anxiety disorders. Clinical trials and real-world data suggest that SNRIs may cause reproductive toxicity. To comprehensively assess this association, we conducted a pharmacovigilance study.

Methods

We utilized various disproportionality analysis algorithms, including reporting odds ratio (ROR), proportional reporting ratio (PRR), bayesian confidence propagation neural network (BCPNN), and multi-item gamma poisson shrinker (MGPS), to assess the significance of reproductive toxicity-related adverse events (AEs) reported to FDA Adverse Event Reporting System (FAERS) from January 2004 to December 2023, with subgroup analysis conducted by sex and age.

Results

Duloxetine and venlafaxine were associated with 14 and 25 AE signals related to reproductive toxicity, respectively, with erectile dysfunction (ED) and retrograde ejaculation identified as shared important medical events (IMEs). ED had the highest reporting frequency, strongest in venlafaxine-treated patients under 45 years (ROR 4.34, PRR 4.33, IC 2.09, EBGM 4.25). Retrograde ejaculation was newly identified. With decreasing incidence, venlafaxine's median ED onset was 122.5 days and duloxetine's 38 days.

Conclusion

Our study provides evidence through an extensive analysis of the large-scale real-world FAERS database, aiding healthcare professionals in mitigating, and prioritizing SNRI-related reproductive toxicity AEs.