A growing number of patients are describing the same haunting experience: even after they’ve stopped taking their antidepressants, their ability to feel sexual pleasure, sometimes even basic genital sensation, hasn’t returned. In some cases, these changes persist for months or even years, long after the last dose of a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI). This cluster of symptoms now has a name: Post-SSRI Sexual Dysfunction (PSSD).
Though acknowledged by major regulators including the European Medicines Agency (EMA), PSSD remains largely uncharted territory in clinical medicine. There is no official ICD11 code, no definitive diagnostic test, and no definitive treatment. Many physicians are unaware of the condition. Patients, in turn, often find themselves dismissed, misdiagnosed with anxiety, or caught between specialists.
Yet, the patient movement around PSSD has grown steadily. Advocacy groups and sexual health organizations have begun calling for more transparency, research, and support. The condition is no longer entirely invisible.
This article offers an updated clinical perspective on PSSD as of 2025. We’ll explore what’s officially recognized, where the mechanistic and diagnostic gaps remain, and how clinicians can offer informed, empathetic guidance to patients affected by this disabling and often misunderstood condition.
Recognition & Gaps
In 2019, the European Medicines Agency (EMA) formally acknowledged PostSSRI Sexual Dysfunction (PSSD) as a potential persistent sexual dysfunction side effect of antidepressants, even after discontinuation. Following this, manufacturers of SSRIs and SNRIs were instructed to update product information to reflect that sexual dysfunction, including anorgasmia, decreased libido, and genital numbness, could last after treatment ends. This marked a critical step in legitimizing patient experiences and served as a regulatory milestone (COSRT, 2025).
Several countries have followed suit. Health Canada, Hong Kong’s Drug Office, and Australia’s TGA have issued similar warnings or initiated similar label updates (The Guardian, 2024). In the U.K., the Royal College of Psychiatrists has also acknowledged the issue in public forums, prompting patient advocacy groups such as PSSD Network to demand formal diagnostic coding and greater research investment. However, clinical consensus and diagnostic clarity remain elusive. PSSD is not included in the ICD11, and diagnostic criteria are still informal. The 2021 international consensus statement, published in Sexual Medicine Reviews, suggested a combination of symptoms, including persistent genital sensory changes, loss of sexual desire, emotional numbing, and erectile or lubrication issues, lasting more than 3 months after SSRI/SNRI cessation (Peleg et al., 2021). Yet few clinicians are trained to recognize this pattern.
Prevalence is another major gap. No high-quality epidemiologic studies have quantified how common PSSD is. Reports vary widely: some estimate that 1–3% of users may be affected; others argue it could be higher, due to underreporting and misattribution. Compounding the problem is the lack of routine sexual function tracking during antidepressant treatment, leaving both doctors and patients unaware of baseline vs. new dysfunction (BenSheetrit et al., 2023).
Furthermore, many cases are misdiagnosed as psychogenic sexual dysfunction, especially in patients with a history of depression or anxiety. As a result, patients may be advised to restart antidepressants, often worsening the underlying condition.
Until diagnostic codes, longitudinal studies, and mechanistic clarity catch up, PSSD will continue to live in a clinical grey zone: real enough to be warned about, but still unsupported by systematic care pathways.
Mechanisms & Biological Plausibility
Despite growing clinical awareness, the biological basis of PSSD remains unresolved. However, several plausible pathways have emerged, drawing from both neurochemical theory and patient-reported phenomena. The leading hypothesis focuses on persistent alterations in serotonergic signaling, particularly involving 5HT1A and 5HT2 receptors. Chronic SSRI use increases serotonin availability in the synaptic cleft, but with long-term exposure, receptor desensitization may occur. This could disrupt downstream processes that govern sexual arousal, desire, and genital sensitivity, even after discontinuation (Peleg et al., 2021).
Another theory centers on nitric oxide (NO) inhibition. Serotonin has known inhibitory effects on NO synthase, a critical pathway for vasodilation and genital arousal. In some animal studies, SSRIs have been shown to reduce NO availability and alter penile or clitoral tissue responsiveness, leading to long-term dysfunction (Ben-Sheetrit et al., 2023).
Beyond neurotransmission, epigenetic modification has entered the conversation. Researchers such as Csoka and Melcangi have proposed that SSRIs may induce lasting changes to gene expression, particularly in genes involved in sexual signaling or endocrine function. These modifications, if triggered during developmental periods (e.g., adolescence), could permanently reshape neurosexual circuits.
Peripheral mechanisms are also considered. Reports of genital anesthesia, loss of the cremasteric reflex in males, or altered tactile response in females suggest possible neurological or microvascular injury. Although such findings are mostly anecdotal or drawn from small case series, they point to involvement beyond brain chemistry.
Of note is the disconnect between emotional and physical sexual response. Many PSSD sufferers describe being able to perform sexual acts mechanically, yet feeling no desire, arousal, or orgasmic sensation. This supports the idea of disrupted reward pathways, possibly linked to mesolimbic dopamine system suppression (Arillotta et al., 2024).
No single mechanism has been proven. Most researchers agree that PSSD likely results from a convergence of central and peripheral dysfunctions, a multilayered condition that resists easy categorization.
This biological uncertainty makes treatment difficult. Yet understanding the potential pathways behind PSSD is crucial to validating patient reports and steering future therapeutic strategies.
Patient Guidance & Clinical Approach
For clinicians, the challenge of addressing PSSD lies not only in its complexity but in its clinical ambiguity. There is no standardized diagnostic test, no approved treatment, and limited formal recognition. Yet the suffering is real, and patient-centered care begins with recognition, validation, and thoughtful engagement.
The first and most critical step is acknowledgment. Patients often describe feeling dismissed or pathologized when reporting persistent sexual side effects. Phrases like “It’s all in your head” or “You’re just depressed again” compound distress. Clinicians should avoid psychologizing the complaint and instead offer empathetic language, acknowledging the biological plausibility and growing regulatory concern around PSSD (COSRT, 2025; Awais, 2024). When starting SSRIs or SNRIs, informed consent should include discussion of potential persistent sexual side effects. While the absolute risk appears low, forewarning improves trust and enables early detection. Ideally, clinicians should assess baseline sexual function before initiating antidepressants, monitor during treatment, and screen again several months after discontinuation.
In suspected cases of PSSD, management begins with differential diagnosis: rule out hormonal imbalances, neurological damage, relationship issues, or residual depression. If the clinical picture fits known PSSD criteria (persistent dysfunction beyond 3–6 months post-SSRI/SNRI) patients can be reassured that their experience has been documented, even if the path forward is uncertain.
Therapeutic options remain exploratory. Some patients report partial benefit from bupropion, dopaminergic agents, or low-dose PDE5 inhibitors. Others pursue off-label interventions such as transcranial stimulation or topical therapies. No approach is widely validated. In most cases, clinicians should adopt a supportive, harm-reduction framework, encouraging gradual experimentation and ongoing monitoring (BenSheetrit et al., 2023).
Crucially, many patients report secondary mental health issues like despair, anhedonia, even suicidality stemming from unresolved PSSD. Prompt referral to sex therapy, psychological support, and peer communities such as PSSD Network or SideFxHub may offer validation and coping tools. Clinicians are also encouraged to report cases to pharmacovigilance authorities. Data from spontaneous reporting systems like FAERS and EudraVigilance are critical for regulatory awareness and signal detection.
Until there is a cure, the most valuable thing clinicians can offer is informed, ongoing, and nonjudgmental support.
References
- Awais, A. (2024). Unraveling post-SSRI sexual dysfunction. The Carlat Report. Retrieved from https://www.thecarlatreport.com/articles/4824-unraveling-post-ssri-sexual-dysfunction
- BenSheetrit, J., Hermon, Y., Birkenfeld, S., Gutman, Y., Csoka, A. B., & Toren, P. (2023). Estimating the risk of irreversible postSSRI sexual dysfunction (PSSD) due to serotonergic antidepressants. Annals of General Psychiatry, 22(15). https://doi.org/10.1186/s12991-023-00447-0
- COSRT. (2025). PostSSRI sexual dysfunction (PSSD). College of Sexual and Relationship Therapists. Retrieved from https://www.cosrt.org.uk/latest-news/post-ssri-sexual-dysfunction-pssd/
- Peleg, L. C., Rabinovitch, D., Lavie, Y., Rabbie, D. M., Horowitz, I., & Gruenwald, I. (2021). Post-SSRI sexual dysfunction (PSSD): Biological plausibility, symptoms, diagnosis, and presumed risk factors. Sexual Medicine Reviews, 10(1), 91–98. https://doi.org/10.1016/j.sxmr.2020.07.003
- The Guardian. (2024, March 2). ‘It feels like we’ve been lobotomised’: The possible sexual consequences of SSRIs. The Guardian. Retrieved from https://www.theguardian.com/society/2024/mar/02/ssri-antidepressants-sexual-dysfunction-side-effects-consequences-libido
- U.S. National Library of Medicine. (2025). Post-SSRI Sexual Dysfunction (PSSD): Literature review and patient case reports. PubMed Central. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11450419/
