Antidepressants and Sexual Dysfunctions: a Translational Perspective

Abstract

Purpose of Review: Antidepressants including selective serotonin re-uptake inhibitors (SSRIs) have sexual side effects contributing to treatment cessation. Animal models predicting such effects are needed to develop better antidepressants. Models of normal male rat sexual behavior and a genetic model simulating chronic SSRI-treatment, the serotonin transporter (SERT)–knockout rat, have been developed. Our goal was to use both models to improve prediction of antidepressants without sexual side effects. Recent Findings: Male rats tested weekly for sexual behavior develop a stable sexual phenotype. Normal ejaculating males were used to test antidepressants, and results fit the typical human profile: SSRIs only exert inhibiting effects after chronic administration of antidepressants. Novel SSRI-antidepressants (vilazodone, vortioxetine) with additional serotonergic mechanisms lack inhibition of sexual behavior in line with human data. SERT-KO rats display lower basal sexual behavior than wildtypes at a level comparable with chronic SSRI-treated rats. Summary: The wild-type model generates results highly translatable to human sexual behavior. The SERT-KO model provides possibilities to study non-SSRI mechanisms in antidepressants.