Post-SSRI Sexual Dysfunction (PSSD): Biological Plausibility, Symptoms, Diagnosis, and Presumed Risk Factors

Post-SSRI sexual-dysfunction (PSSD) is an iatrogenic syndrome, the underlying neurobiological mechanisms of which are unclear. Symptom onset follows cessation of serotonergic antidepressants i.e. Selective Serotonin and Norepinephrine Reuptake Inhibitors (SSRI's, SNRI's), and Tricyclic antidepressants (TCA's). PSSD symptoms include genital anesthesia, erectile dysfunction and orgasmic/ejaculatory anhedonia, and should be differentiated from depression-related sexual-dysfunction. Recently, accumulated data of numerous case-reports suggest additional non-sexual symptoms including, anhedonia, apathy, and blunted affect. PSSD gained official recognition after the European medical agency concluded that PSSD is a medical condition that persists after discontinuation of SSRI's and SNRI's.To review possible underlying neurobiological mechanisms of this syndrome, update information on the pathophysiology, present a list of potential risk-factors and discuss potential management options for PSSD.Extensive literature review on the main symptom-patterns of this disorder was undertaken using PubMed. It includes introductory explications of relevant neurobiology with the objective of generating hypothesis.Precipitating factors for PSSD include previous exposure to certain drugs, genetic predisposition, psychological stress or chemical stressful reaction to antidepressants along pre-existing medical conditions affecting neuroplasticity. Different theories have been proposed to explain the pathophysiology of PSSD: epigenetic gene expression, dopamine-serotonin interactions, serotonin neurotoxicity and hormonal changes. The diagnosis of PSSD is achieved by excluding all other etiologies of sexual-dysfunction. Treatment is challenging, and many strategies have been suggested without definitive outcomes. We offer the contours of a future neurobiological research agenda, and propose several underlying mechanisms for the various symptoms of PSSD which could be the foundation for a future treatment algorithm.There is a need for well-designed neurobiological research in this domain, as well as in the prevalence, pathophysiology, and treatment of PSSD. Practitioners should be alert to the distinctive features of PSSD. Misdiagnosing this syndrome might lead to harmful treatments including reinstatement of medications which generated PSSD. Sexual Medicine Reviews. Peleg LC, Rabinovitch D, Lavie Y, et al. Post-SSRI Sexual Dysfunction (PSSD): Biological Plausibility, Symptoms, Diagnosis, and Presumed Risk Factors. Sex Med Rev 2022;10:91-98.