Sexual side effects of serotonergic antidepressants: Mediated by inhibition of serotonin on central dopamine release? (2013)

Pharmacol Biochem Behav. 2013 Oct 12. pii: S0091-3057(13)00238-4. doi: 10.1016/j.pbb.2013.10.004.

Bijlsma EY, Chan JS, Olivier B, Veening JG, Millan MJ, Waldinger MD, Oosting RS.


Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Sorbonnelaan 16, 3584CA Utrecht, The Netherlands.


Antidepressant-induced sexual dysfunction adversely affects the quality of life of antidepressant users and reduces compliance with treatment. Animal models provide an instructive approach for examining potential sexual side effects of novel drugs. This review discusses the stability and reproducability of our standardized test procedure that assesses the acute, subchronic and chronic effects of psychoactive compounds in a 30minute mating test. In addition, we present an overview of the effects of several different (putative) antidepressants on male rat sexual behavior, as tested in our standardized test procedure. By comparing the effects of these mechanistically distinct antidepressants (paroxetine, venlafaxine, bupropion, buspirone, DOV 216,303 and S32006), this review discusses the putative mechanism underlying sexual side effects of antidepressants and their normalisation.

This review shows that sexual behavior is mainly inhibited by antidepressants that increase serotonin neurotransmission via blockade of serotonin transporters, while those that mainly increase levels of dopamine and noradrenaline are devoid of sexual side effects. Those sexual disturbances can not be normalized by simultaneously increasing noradrenaline neurotransmission, but are normalized by increasing both noradrenaline and dopamine neurotransmission. Therefore, it is hypothesized that the sexual side effects of selective serotonin reuptake inhibitors may be mediated by their inhibitory effects on dopamine signalling in sex brain circuits. Clinical development of novel antidepressants should therefore focus on compunds that simultaneously increase both serotonin and dopamine signalling.