| Post-SSRI sexual dysfunction | |
|---|---|
| Other names | Post-SSRI syndrome |
 | |
| Chemical structure of sertraline (Zoloft), an SSRI that is reported to cause PSSD in some users | |
| Symptoms | Sexual dysfunction (e.g. erectile dysfunction, loss of vaginal lubrication, anorgasmia, reduced libido), cognitive dysfunction (e.g. anhedonia, emotional blunting, memory loss, shortened attention span) |
| Duration | Months to years after stopping an SRI |
| Causes | Serotonin reuptake inhibitor (SRI) medications, most commonly selective serotonin reuptake inhibitors (SSRIs) |
| Risk factors | Unknown due to lack of data |
| Diagnostic method | Sexual dysfunction symptoms that persist longer than 3-6 months after stopping an SSRI, in the absence of other conditions/medications that could account for symptoms |
| Treatment | No known reliable treatment |
| Frequency | Unknown due to lack of data |
Post-SSRI sexual dysfunction (PSSD), also known as post-SSRI syndrome, is a disorder in which people who have taken selective serotonin reuptake inhibitors (SSRIs) or other serotonin reuptake-inhibiting (SRI) drugs report persistent changes in sexual function for an extended period (at least three to six months, up to years, decades or indefinitely) after ceasing to take the drug. Although the condition is most commonly associated with SRIs, similar or identical syndromes have also been reported after discontinuation of a variety of non-SRI drugs.
First reported in the medical literature in 2006, PSSD remains poorly-understood, with its biological mechanism, risk factors and frequency of occurrence being unknown. The reported symptoms of PSSD commonly include reduced sexual desire or arousal, erectile dysfunction in males or loss of vaginal lubrication in females, difficulty having an orgasm or loss of pleasurable sensation associated with orgasm, and a reduction or loss of sensitivity in the genitals or other erogenous zones. Additional non-sexual symptoms are also commonly described, including emotional numbing, anhedonia, depersonalization or derealization, and cognitive impairment. It is considered a distinct clinical pathology from antidepressant discontinuation syndrome, post-acute withdrawal syndrome, and major depressive disorder.
There is currently no known reliable treatment for PSSD. To date, the mechanism by which SRIs may induce PSSD is unknown, as is the exact mechanism by which SRIs induce sexual dysfunction in many patients actively taking the drugs. The symptoms of PSSD are largely shared with post-finasteride syndrome (PFS) and post-retinoid sexual dysfunction/post-Accutane syndrome (PRSD/PAS), two other poorly-understood iatrogenic conditions which have been suggested to share a common etiology with PSSD despite being caused by different types of medication.
Symptoms and diagnosis
According to diagnostic criteria submitted by David Healy et al. in 2022, a diagnosis of PSSD requires that the subject has previously taken an SSRI or other SRI, and has experienced new (i.e. not present before starting the SRI) symptoms of sexual dysfunction for at least three months after the last dose of the SRI; others have proposed a timeline of at least six months of sexual dysfunction symptoms after cessation of the SRI. Other potential causes of sexual dysfunction should be considered and excluded before a diagnosis is made.
The following symptoms have been reported in association with PSSD:
- Erectile dysfunction
- Loss of vaginal lubrication
- Genital numbness/reduced genital sensitivity (genital anesthesia)
- Inability to achieve orgasm (anorgasmia)
- Reduced pleasure associated with orgasm
- Premature ejaculation
- Reduced sexual desire/libido
- Reduced ability to become sexually aroused
- Decreased penile or testicular size
- Changes in menstrual cycle
- Testicular pain
- Decreased seminal volume and/or quality
- Anhedonia
- Emotional blunting/numbing
- Difficulty thinking or concentrating ("brain fog")
- Issues with memory and recall
- Depersonalization
- Derealization
- Pelvic floor dysfunction
- Interstitial cystitis/painful bladder syndrome, often diagnosed as recurrent urinary tract infections in females or as recurrent prostatitis in males
In many cases, PSSD sufferers report that their symptoms will transiently improve for short periods (usually no more than one or two days) before returning to their previous state.
Duration of symptoms
The length of time during which PSSD symptoms persist appears to vary among patients, with some cases resolving in a matter of months and others persisting for years or even decades; one analysis of patient reports in the Netherlands submitted between 1992 and 2021 listed a case which had reportedly persisted for 23 years.
Acknowledgements and warnings issued
The UK's Medicines and Healthcare products Regulatory Agency (MHRA) has issued informational leaflets and/or labels containing warnings about post-discontinuation sexual side effects for Sertraline (Zoloft), Citalopram (Cipramil), Paroxetine (Paxil/Seroxat), and Fluvoxamine (Luvox/Faverin). The FDA has issued a leaflet for Fluoxetine (Prozac/Sarafem) containing similar warnings.
Warnings about post-discontinuation sexual dysfunction associated with SSRIs can be found in the British National Formulary (BNF), the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-5), the Textbook of Rare Sexual Medicine Conditions, and the textbook Psychiatry and Sexual Medicine: A Comprehensive Guide for Clinical Practitioners.
On the 11th of June 2019, the Pharmacovigilance Risk Assessment Committee of the European Medicines Agency concluded that a possible relationship exists between SSRI use and persistent sexual dysfunction after cessation of use. The committee concluded that a warning should be added to the label of SSRIs and SNRIs regarding this possible risk. The Hong Kong Department of Health, Health Canada and the NHS have also issued warnings about PSSD.
Prevalence and risk
Medications known to cause PSSD
Although PSSD is most commonly reported following cessation of SSRIs, cases have also been reported following the use of serotonin-norepinephrine reuptake inhibitors (SNRIs), SRI tricyclic antidepressants, atypical antidepressants such as mirtazapine, SRI antihistamines, tetracycline antibiotics such as doxycycline, analgesics such as tramadol, and antipsychotics such as aripriprazole.
Frequency of PSSD
Due to a lack of large-scale, well-controlled studies, there are currently no reliable estimates of how many individuals worldwide suffer from PSSD, nor what fraction of SRI users develop PSSD after stopping the drug. The condition has been suggested to be under-reported.
Data released in 2021 under the UK's Freedom of Information Act by the Medicines and Healthcare Products Regulatory Agency showed that in a total of 1654 cases of adverse effects from SSRIs, in 1069 cases the reaction did not continue after the drug was withdrawn, in 225 cases the reaction continued after the drug was withdrawn with the recovery time being unknown, and in 144 cases the reaction continued after the drug was withdrawn and the recovery time was known.
A retrospective review published in The Journal of Urology in 2020 stated that between 2009 and 2019, 4% of the male patients whose charts were assessed in the review (43 patients total) met the criteria for PSSD, having displayed sexual dysfunction symptoms for longer than 6 months after stopping an SSRI. In 2023, a retrospective analysis of patient records across 19 years at Clalit Health Services, the largest HMO in Israel, found that 0.46% (1 in 216) of surveyed patients who had been treated with serotonergic antidepressants developed symptoms of erectile dysfunction consistent with PSSD.
In 2019, a study published by the Utrecht University (NL) on a sample of healthy adults, investigated the prevalence of persistent sexual dysfunction after the discontinuation of SSRIs antidepressant, focusing on a wider range of symptoms than other studies. The results showed that 52.6% of participants suffered from persisting sexual dysfunction while 26.3% suffered from genital anesthesia and/ or nipple insensitivity. Persisting sexual dysfunction was shown to negatively influence the perceived quality of life. These data are consistent with the findings of previous reports that reported persistent changes in sexual functioning after a treatment with SSRIs.
SRI dosage response and other risk factors
It is unknown whether there is a relationship between the amount of time a person has been taking an SRI and the likelihood of developing PSSD. In one case study published in 2006, persistent sexual dysfunction was evident for seven years after taking an SRI for a period of only five weeks; there have been reports of cases developing after only a few, or even single doses of an SRI.
Adolescence, childhood, and development
Several studies in both humans and animals have suggested that use of SSRIs at an early age may increase the likelihood of asexuality during later development. A 2020 study in which 610 young adult individuals were surveyed found that childhood SSRI use among female participants was strongly correlated with reduced sexual desire and activity; childhood SSRI use among male participants was correlated with reduced frequency of partnered sexual activity as an adult. There are reports of sexual dysfunction, often enduring, caused by SSRIs in adolescents, but the incidence of long-term consequences of adolescent SSRI exposure are unknown, possibly due to a lack of baseline sexual experience for comparison. Animal studies on the long-term effects of adolescent SSRI administration have indicated that SSRIs may produce deficits in sexual functioning that persist well after cessation of SSRI treatment and into adulthood, including significantly reduced ejaculation frequency and increased mount latency.
Treatment
There is as yet no established treatment for PSSD. In an unknown fraction of cases, symptoms are reported to resolve spontaneously with time, but the duration of symptoms appears to vary widely among patients. Many anecdotal self-reports exist in which various approaches, ranging from pharmacological or psychiatric treatments to dietary or lifestyle changes, allegedly correlate with improvement in PSSD symptoms, but these results have not been independently verified or replicated. Several studies have been conducted which attempt to identify viable treatments for PSSD, but in general these have suffered from a small sample size and lack of controls, limiting their informative utility.
Societal impact and support communities
Since 2006, a number of news articles have been published by various outlets on the subject of PSSD.
Several online support communities for PSSD exist, including the PSSD Network, PSSD forum, and the PSSD subreddit (r/PSSD on Reddit).
On 21 June 2022, the advocacy organization RxISK began a research fund to support and stimulate interest in PSSD research; the group has also offered a prize of $100,000 USD to anyone who can identify a reliable cure for persistent sexual side effects after stopping antidepressants, finasteride (Propecia), or isotretinoin (Accutane).
Several medical practitioners, including David Healy and Josef Witt-Doerring, have made efforts to increase awareness of PSSD.
Similar conditions
PSSD is one of several known iatrogenic syndromes characterized by persistent sexual dysfunction after stopping a medication; others include:
- Post-Finasteride Syndrome (PFS), a condition affecting some individuals treated with the hair-loss drug finasteride (Propecia)
- Post-Retinoid Sexual Dysfunction (PRSD) or Post-Accutane Syndrome (PAS), a condition affecting some individuals treated with the acne medication isotretinoin (Accutane)
- Hard Flaccid Syndrome (HFS), which has been reported to occur following the use of bremelanotide
In 2014, a review of 120 reports submitted to RxISK from more than 20 countries concluded that PSSD, PFS and PRSD/PAS exhibit extensively overlapping symptom profiles.
The drug 3,4-methylenedioxymethamphetamine (MDMA), which acts to stimulate the release and inhibit the reuptake of serotonin, can in some cases produce adverse effects that persist long after the drug has been withdrawn, including neurocognitive impairments such as mood disorders and sexual dysfunction. The mechanism behind MDMA neurotoxicity is not fully understood, but a similar mechanism has been suggested to potentially play a role in PSSD.
