Sexual side effects of serotonergic antidepressants: Mediated by inhibition of serotonin on central dopamine release?

Antidepressant-Induced Sexual Side Effects: Incidence, Assessment, Clinical Implications, and Management

“…3,6 These antidepressants may additionally cause inhibitory effects on dopamine by enhancing an inhibitory effect on the raphe nuclei or impairing sexual function through prolactin elevation. 7 They may also inhibit nitrous oxide synthetase, thereby decreasing nitrous oxide availability (needed for erection).…”

Sexual Dysfunction, Depression and Antidepressants: A Translational Approach

“…Because noradrenaline exerts facilitatory effects in sexual behavior in humans [31], one might hypothetically expect that this may contrast the inhibitory effects of the SSRI-component in venlafaxine. Although at lower doses (that are antidepressant in animal depression models) venlafaxine does not affect sexual behavior, at the higher dose tested it does, indicating that the SSRI activity becomes dominant in venlafaxine's action.…”

“…DA activity in mesolimbic areas is involved in motivational and copulatory aspects of sexual behavior. There is a strong 5-HT/DA interaction in the brain, which modulates motivational aspects of sexual performance [31] and adding a dopaminergic stimulating mechanism to an inhibiting serotonergic mechanism (e.g., SSRI) might result in amelioration of the inhibitory action of the latter [31]. DOV 216,303 is a triple monoaminergic reuptake inhibitor (TRI) that blocks noradrenergic, serotonergic, and dopaminergic transporters [35,36].…”

“…S32006 is a very selective 5-HT 2C receptor antagonist, has antidepressant effects in preclinical depression models and elevates extracellular DA and NA, but not 5-HT [53,54]. S32006 was completely devoid of any effect on sexual behavior after acute, sub-chronic and chronic administration [31], suggesting that 5-HT 2C receptors are not (directly) involved in sexual effects induced by SSRIs.…”

The Janu-faced serotonergic antidepressant nature: mental versus sexual health!

“…Increases in dopamine in MPOA disinhibit genital reflexes via a member of D2 receptors and facilitate parasympathetically mediated erections and copulatory behavior via D1-like receptor [4]. Thus, it has been recently suggested that the sexual side effects of serotonergic antidepressants may be best explained by the inhibitory effects of serotonin on dopaminergic activity [5].Trazodone has been demonstrated to positively modulate the dopamine/ serotonin ratio, thanks to its action on ventral tegmental area and locus ceruleus [6], and this may be the reason why it has low sexual side effects.Physicians involved in mental health should consider sexual function when prescribing antidepressants, since most of them, with regard to SSRI, may cause SD, leading to a worsening of patients' quality of life. …”