Sexual Dysfunction, Depression and Antidepressants: A Translational Approach

Abstract

Major depression is frequently associated with sexual dysfunctions. Most antidepressants, especially selective serotonin reuptake inhibitors (SSRIs), induce additional sexual side effects and, although effective antidepressants, deteriorate sexual symptoms, which are the main reason that patients stop antidepressant treatment. Many strategies have been used to circumvent the additional sexual side effects, but results are rather disappointing. Recently, new antidepressants have been introduced, vilazodone and vortioxetine, which seem to lack sexual side effects in the early registration trials. Much research with large numbers of depressed patients and adequate methodological tools still has to confirm in daily use the absence of sexual side effects of new antidepressants. Animal models that in an early phase of drug development may predict putative sexual side effects of new antidepressants are extremely useful and could speed up development of new antidepressants. A rat model of sexual behavior is described that has a very high predictive validity for sexual side effects in man. Several characteristics of present antidepressants with regard to sexual dysfunctions are also present in the rat model and establish its validity. The animal model can also be used in the search for new psychotropics without sexual side effects or for drugs with sexual stimulating activity.

Tramadol’s Inhibitory Effects on Sexual Behavior: Pharmacological Studies in Serotonin Transporter Knockout Rats

“…Figure 1 illustrates that the “vehicle” (placebo) values (e.g., of ejaculation frequency) of the three genotype groups are very constant over time (at least 26 weeks; Supplementary Table 1 ). These findings are in line with our earlier experiments using tramadol ( Olivier et al, 2017a ) and others ( Olivier et al, 2017b ).…”

“…Remarkably, the SERT +/- rats never deviated in any aspect or under any pharmacological treatment from SERT +/+ rats, confirming earlier data ( Chan et al, 2011 ). The basal level of sexual behavior in SERT -/- rats is comparable to that of chronically SSRI-treated rats ( de Jong et al, 2005a , b , 2006 ; Olivier et al, 2017b ). Acute administration of SSRIs at doses that reach >80% SERT occupancy, does not reliably induce inhibition of sexual behavior.…”

“…SSRIs hardly enhance 5-HT after acute administration, e.g., in the frontal cortex ( Beyer et al, 2002 ; Beyer and Cremers, 2008 ). This phenomenon possibly causes the lack of sexual inhibitory effects of SSRIs after acute administration ( Olivier et al, 2017b ). Pharmacological experiments with the (+)- and (-)-enantiomers of tramadol have not been performed but might be helpful in further determining the role of the noradrenergic vs. the serotonergic uptake properties of tramadol on sexual behavior.…”

Irisin Improves High-Fat Diet-Induced Sexual Dysfunction in Obese Male Rats

“…For a value equal to or lower than 0.30, the rat was accepted as normal, and for a value higher than 0.30, the rat was accepted as obese. The number of ejaculations per 30 min is known to be a good enough safe and predictive measure of sexual performance in male rats [43]. Therefore, after the establishment of the HFD-induced obesity model, HFD-induced sexual dysfunction was confirmed by the number of ejaculations.…”