Sexual Dysfunction Associated with Selective Serotonin Reuptake Inhibitors: Mechanisms, Clinical Manifestations, Management Strategies, and Post-SSRI Sexual Dysfunction - A Narrative Review
DOI:
https://doi.org/10.12775/QS.2026.71.74784Keywords
selective serotonin reuptake inhibitors, antidepressant - induced sexual dysfunction, post-SSRI sexual dysfunction, PSSD, depression, anxiety disorders, sexual dysfunction, adverse effects, psychopharmacologyAbstract
Background: Selective serotonin reuptake inhibitors (SSRIs) are first-line treatments for major depressive disorder and anxiety disorders. Sexual dysfunction is among their most common adverse effects, impairing quality of life and treatment adherence. Increasing attention has focused on post-SSRI sexual dysfunction (PSSD), in which symptoms persist after antidepressant discontinuation.
Objective: To summarize current evidence on sexual physiology, mechanisms and clinical features of antidepressant-induced sexual dysfunction (AISD) and PSSD, and available management strategies.
Methods: A narrative review of English-language literature published between 2020 and 2026 was conducted using PubMed and Google Scholar. Original studies, systematic reviews, meta-analyses, randomized trials, observational studies, and relevant case reports were included, along with essential earlier landmark publications.
Results: SSRI-associated sexual dysfunction may affect desire, arousal, erection, ejaculation, orgasm, and sexual satisfaction. Prevalence estimates vary because of differences in study populations and assessment methods. Symptoms usually improve after dose reduction or discontinuation, but may persist as PSSD. Proposed mechanisms include serotonergic dysregulation, altered dopaminergic and neuroendocrine signaling, epigenetic changes, TRP ion channel dysfunction, neurotoxicity, and gut–brain axis disturbances, although none has been confirmed. Management includes dose reduction, switching to antidepressants with a lower risk of sexual adverse effects, pharmacological augmentation, and selected non-pharmacological interventions. No evidence-based treatment for PSSD has been established.
Conclusions: Sexual dysfunction is a major adverse effect of SSRI therapy. Routine assessment before and during treatment may facilitate recognition and management. High-quality prospective studies are needed to clarify the epidemiology, mechanisms, and optimal treatment of PSSD.
References
1. Atmaca M. Selective Serotonin Reuptake Inhibitor-Induced Sexual Dysfunction: Current Management Perspectives. Neuropsychiatr Dis Treat. 2020;16:1043-1050
https://doi.org/10.2147/NDT.S185757
2. Rothmore, J. (2020), Antidepressant-induced sexual dysfunction. Med. J. Aust., 212: 329-334.
https://doi.org/10.5694/mja2.50522
3. Jespersen C, Lauritsen MP, Frokjaer VG, Schroll JB. Selective serotonin reuptake inhibitors for premenstrual syndrome and premenstrual dysphoric disorder. Cochrane Database of Systematic Reviews 2024, Issue 8. Art. No.: CD001396. DOI: 10.1002/14651858.CD001396.pub4. Accessed 20 July 2026.
https://doi.org//10.1002/14651858.CD001396.pub4
4. Dagostin Ferraz, S., Kuyunga, L., Rech, P. et al. Sexual dysfunction associated with selective serotonin reuptake inhibitors in adults with depression: a systematic review and meta-analysis. Eur J Clin Pharmacol 82, 82 (2026). https://doi.org/10.1007/s00228-026-04011-z
5. Zini, J., & Turecki, G. (2026). Antidepressant-Induced Sexual Dysfunction in Adults: A Targeted Scoping Review and Clinical UpdateJournal of Clinical Psychopharmacology https://doi.org/10.1097/JCP.0000000000002210
6. Tran F D, Bichai G H, Kravetz Z, et al. (August 15, 2025) Management of Antidepressant-Induced Sexual Dysfunction: A Literature Review. Cureus 17(8): e90170. doi:10.7759/cureus.90170
7. Finnoula I O’Neill-King, Robyn A Jackowich, Caroline F Pukall, Depression, selective serotonin reuptake inhibitors, and sexual wellbeing in assigned females: exploring the moderating role of sexual flexibility, The Journal of Sexual Medicine, Volume 22, Issue 7, July 2025, Pages 1206–1215,
https://doi.org/10.1093/jsxmed/qdaf097
8. Liran C. Peleg, David Rabinovitch, Yaakov Lavie, Deya M. Rabbie, Itai Horowitz, Eyal Fruchter, Ilan Gruenwald, Post-SSRI Sexual Dysfunction (PSSD): Biological Plausibility, Symptoms, Diagnosis, and Presumed Risk Factors, Sexual Medicine Reviews, Volume 10, Issue 1, 2022, Pages 91-98, ISSN 2050-0521,
https://doi.org/10.1016/j.sxmr.2021.07.001.
9. Xie M, Huang P, Wang S, Ma J, Zeng Y, Sun J. Post-SSRI Sexual Dysfunction (PSSD): A comprehensive review of epidemiology, pathophysiology, and clinical management. International Journal of Risk & Safety in Medicine. 2026;0(0). doi:10.1177/09246479261468499
https://doi.org/10.1177/09246479261468499
10. Chinchilla Alfaro, K., van Hunsel, F., & Ekhart, C. (2022). Persistent sexual dysfunction after SSRI withdrawal: a scoping review and presentation of 86 cases from the Netherlands. Expert Opinion on Drug Safety, 21(4), 553–561. https://doi.org/10.1080/14740338.2022.2007883
11. Tarchi L, Merola GP, Baccaredda-Boy O, et al. Selective serotonin reuptake inhibitors, post-treatment sexual dysfunction and persistent genital arousal disorder: A systematic review. Pharmacoepidemiol Drug Saf. 2023; 32(10): 1053-1067. doi:10.1002/pds.5653
https://doi.org/10.1002/pds.5653
12. Healy D, Mangin D. Post-SSRI sexual dysfunction: barriers to quantifying incidence and prevalence. Epidemiology and Psychiatric Sciences. 2024;33:e40. doi:10.1017/S2045796024000441
https://doi.org/10.1017/S2045796024000441
13. Moncrieff, J., Cooper, R.E., Stockmann, T. et al. The serotonin theory of depression: a systematic umbrella review of the evidence. Mol Psychiatry 28, 3243–3256 (2023). https://doi.org/10.1038/s41380-022-01661-0
14. Weatherly S, Garazi C D, Woldenberg E, et al. (November 20, 2025) Unraveling the Cycle: A Scoping Review Exploring the Impact of Antidepressants on the Female Reproductive Cycle . Cureus 17(11): e97360. doi:10.7759/cureus.97360
15. Baik, JH. Stress and the dopaminergic reward system. Exp Mol Med 52, 1879–1890 (2020).
https://doi.org/10.1038/s12276-020-00532-4
16. Hutters CL, Giraldi A. [Sexual side effects from treatment with SSRI]. Ugeskr Laeger. 2022 Apr 4;184(14):V11210824. Danish. PMID: 35410653.
17. Johnson CF, Maxwell M, Williams B, Dougall N, MacGillivray S. Dose-response effects of selective serotonin reuptake inhibitor monotherapy for the treatment of depression: systematic review of reviews and meta-narrative synthesis. BMJ Medicine. 2022;1:e000017. https://doi.org/10.1136/bmjmed-2021-000017
18. Samantha Klaas, Jessica Barbut Siva, Maarten Bak, Mark Govers, Rudy Schreiber, The pathophysiology of Post SSRI Sexual Dysfunction – Lessons from a case study, Biomedicine & Pharmacotherapy, Volume 161, 2023, 114166, ISSN 0753-3322,
https://doi.org/10.1016/j.biopha.2022.114166.
19. Silvia Giatti, Silvia Diviccaro, Lucia Cioffi, Roberto Cosimo Melcangi, Post-Finasteride Syndrome And Post-Ssri Sexual Dysfunction: Two Clinical Conditions Apparently Distant, But Very Close, Frontiers in Neuroendocrinology, Volume 72, 2024, 101114, ISSN 0091-3022,
https://doi.org/10.1016/j.yfrne.2023.101114.
20. Qinwen Wang, Qianyue Yang, Xingyin Liu, The microbiota-gut-brain axis and neurodevelopmental disorders, Protein & Cell, Volume 14, Issue 10, October 2023, Pages 762-775,
https://doi.org/10.1093/procel/pwad026
21. De Luca, R.; Bonanno, M.; Manuli, A.; Calabrò, R.S. Cutting the First Turf to Heal Post-SSRI Sexual Dysfunction: A Male Retrospective Cohort Study. Medicines 2022, 9, 45. https://doi.org/10.3390/medicines9090045
22. Healy D, Bahrick A, Bak M, et al. Diagnostic criteria for enduring sexual dysfunction after treatment with antidepressants, finasteride and isotretinoin. International Journal of Risk & Safety in Medicine. 2022;33(1):65-76. doi:10.3233/JRS-210023
https://doi.org/10.3233/JRS-210023
23. Mengting Shen, Luyao He, Pei Chen, Lei Zhang, Duan Zeng, Yan Li, Huafang Li, Selective serotonin reuptake inhibitor and serotonin-norepinephrine reuptake inhibitor use and sexual dysfunction: a pharmacovigilance analysis, Sexual Medicine, Volume 14, Issue 2, April 2026, qfag008,
https://doi.org/10.1093/sexmed/qfag008
24. Shouying Li, Jiaxin Feng, Shilin Zhang, Male sexual dysfunction associated with selective serotonin reuptake inhibitors (SSRIs): A pharmacovigilance disproportionality analysis of FAERS data, Journal of Affective Disorders, Volume 402, 2026, 121336, ISSN 0165-0327,
https://doi.org/10.1016/j.jad.2026.121336.
25. Antonio Carlos Queiroz de Aquino, Ayane Cristine Alves Sarmento, Raphaell Lucas de Araújo Teixeira, Tâmilly Nascimento Batista, Cijara Leonice de Freitas, José Manuel Pérez Mármol, Lucia Alves Silva Lara, Ana Katherine Gonçalves, Pharmacological treatment of antidepressant-induced sexual dysfunction in women: A systematic review and meta-analysis of randomized clinical trials, Clinics, Volume 80, 2025, 100602, ISSN 1807-5932,
https://doi.org/10.1016/j.clinsp.2025.100602.
26. Lipman K, Betterly H, Botros M (April 10, 2024) Improvement in Selective Serotonin Reuptake Inhibitor-Associated Sexual Dysfunction With Buspirone: Examining the Evidence. Cureus 16(4): e57981. doi:10.7759/cureus.57981
27. Concerto, C.; Rodolico, A.; Meo, V.; Chiappetta, D.; Bonelli, M.; Mineo, L.; Saitta, G.; Stuto, S.; Signorelli, M.S.; Petralia, A.; et al. A Systematic Review on the Effect of Nutraceuticals on Antidepressant-Induced Sexual Dysfunctions: From Basic Principles to Clinical Applications. Curr. Issues Mol. Biol. 2022, 44, 3335-3350. https://doi.org/10.3390/cimb44080230
28. Lalegani, E.; Eissazade, N.; Shalbafan, M.; Salehian, R.; Shariat, S.V.; Askari, S.; Orsolini, L.; Soraya, S. Safety and Efficacy of Drug Holidays for Women with Sexual Dysfunction Induced by Selective Serotonin Reuptake Inhibitors (SSRIs) Other than Fluoxetine: An Open-Label Randomized Clinical Trial. Brain Sci. 2023, 13, 1397. https://doi.org/10.3390/brainsci13101397
29. Alipour-Kivi, A., Eissazade, N., Shariat, S.V. et al. The effect of drug holidays on sexual dysfunction in men treated with selective serotonin reuptake inhibitors (SSRIs) other than fluoxetine: an 8-week open-label randomized clinical trial. BMC Psychiatry 24, 67 (2024). https://doi.org/10.1186/s12888-024-05507-7
30. Marks S. A clinical review of antidepressants, their sexual side-effects, post-SSRI sexual dysfunction, and serotonin syndrome. Br J Nurs. 2023;32(14):678-682. doi:10.12968/bjon.2023.32.14.678
https://doi.org/10.12968/bjon.2023.32.14.678
31. Healy D, LaPalme J, Levin M. Post-SSRI Sexual Dysfunction: A Bioelectric Mechanism? Bioelectricity. 2020 Mar 1;2(1):7-13. doi: 10.1089/bioe.2019.0010. Epub 2020 Mar 18. PMID: 34471832; PMCID: PMC8370302.
https://doi.org/10.1089/bioe.2019.0010
32. Zhao Y, Zhang Y, Yang L, Zhang K, Li S. Safety Profile of Selective Serotonin Reuptake Inhibitors in Real-World Settings: A Pharmacovigilance Study Based on FDA Adverse Event Reporting System. Annals of Pharmacotherapy. 2024;58(11):1105-1116. doi:10.1177/10600280241231116
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Magdalena Mortka, Hubert Bednarz, Gabriela Piotrowska, Agnieszka Anna Gaczoł, Paulina Kopcińska, Michał Kawa, Kamil Idzik, Dominika Grzybowska, Aleksander Urbaś, Tomasz Kilian, Michał Kurnik, Weronika Grzyb-Kurnik, Maja Kopyto
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Stats
Number of views and downloads: 50
Number of citations: 0
