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

Sex Med Rev. 2021 Oct 6;S2050-0521(21)00060-3. doi: 10.1016/j.sxmr.2021.07.001. Online ahead of print.


Introduction: Post-SSRI sexual-dysfunction (PSSD) is an iatrogenicsyndrome, the underlying neurobiological mechanisms of which areunclear. Symptom onset follows cessation of serotonergicantidepressants i.e. Selective Serotonin and Norepinephrine ReuptakeInhibitors (SSRI's, SNRI's), and Tricyclic antidepressants (TCA's). PSSDsymptoms include genital anesthesia, erectile dysfunction andorgasmic/ejaculatory anhedonia, and should be differentiated fromdepression-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.

Objective: To review possible underlying neurobiological mechanisms ofthis syndrome, update information on the pathophysiology, present a listof potential risk-factors and discuss potential management options forPSSD.

Methods: Extensive literature review on the main symptom-patterns ofthis disorder was undertaken using PubMed. It includes introductoryexplications of relevant neurobiology with the objective of generatinghypothesis.

Results: 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 by excluding all other etiologies of sexual-dysfunction. Treatment is challenging, and many strategies have been suggested without definitive outcomes. We offerthe 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.

Conclusion: 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 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 2021;XX:XXX-XXX.

Keywords: Diagnosis; Post SSRI Sexual Dysfunction; Risk Factors; Symptoms.

Publication types

  • Review