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Post-SSRI Sexual Dysfunction (PSSD)

Medically reviewed by Dr. David Healy on 28 September 2024.

What is PSSD?

Post-SSRI sexual dysfunction (PSSD) is an iatrogenic condition in which sexual function does not return to normal after the discontinuation of serotonin reuptake inhibiting antidepressants.1 This group includes:

  • selective serotonin reuptake inhibitors (SSRIs)
  • serotonin-norepinephrine reuptake inhibitors (SNRIs)
  • some tricyclic antidepressants such as clomipramine and imipramine

Most people who take an SSRI, SNRI, or related medication, will feel some degree of genital numbing, often within 30 minutes of taking the first dose. In PSSD, this genital numbing and other sexual side effects remain or do not resolve completely when the drug is stopped.2, 3 In some cases, the symptoms only appear or worsen when the medication is stopped or the dose is reduced.

PSSD affects both men and women.4, 5 It can happen after only a few days exposure to an antidepressant and can persist for months, years, or indefinitely.6 There is no known cure.

Commonly used SSRIs include:

  • paroxetine (Paxil, Seroxat)
  • fluoxetine (Prozac)
  • sertraline (Zoloft)
  • citalopram (Celexa)
  • escitalopram (Lexapro)
  • vortioxetine (Trintellix)

Common SNRIs include:

  • venlafaxine (Effexor)
  • desvenlafaxine (Pristiq)
  • duloxetine (Cymbalta)

Symptoms

Symptoms of PSSD can include:

  • reduced genital sensation
  • decreased libido
  • erectile dysfunction/decreased vaginal lubrication
  • pleasureless or weak orgasm
  • difficulty achieving orgasm
  • reduced response to sexual stimuli
  • decreased or loss of nocturnal erections
  • reduced nipple sensitivity
  • flaccid glans during erection

Some people experience a noticeable reduction in tactile sensation – genitals feel like they were exposed to an anesthetic. Others notice a reduction in sexual sensation – genital touch feels similar to being touched on any other body part.

Orgasm is experienced with a decreased or loss of pleasurable feeling, sometimes referred to as a pleasureless or muted orgasm. There can be reduced ejaculatory force in males.

Cases of premature ejaculation after stopping an SSRI have also been reported.7

Some females experience reduced vaginal lubrication, but this may not occur in all cases.8

Non-sexual symptoms that may accompany PSSD include emotional numbing, sensory problems, and cognitive impairment.

Diagnosis

Diagnostic criteria were published in 2021.9

Necessary

(1) Prior treatment with a serotonin reuptake inhibitor.

(2) An enduring change in somatic (tactile) or erogenous (sexual) genital sensation after treatment stops.

Additional

(3) Enduring reduction or loss of sexual desire.

(4) Enduring erectile dysfunction (males).

(5) Enduring inability to orgasm or decreased sensation of pleasure during orgasm.

(6) The problem is present for ≥3 months after stopping treatment.

There should be

(7) No evidence of pre-drug sexual dysfunction that matches the current profile.

(8) No current medical conditions that could account for the symptoms.

(9) No current medication or substance misuse that could account for the symptoms.

There is no simple test to diagnose PSSD. A diagnosis is made by considering several factors including medication history, onset and profile of the symptoms, and by eliminating other possible causes.

Quantitative sensory testing (QST) of the penis routinely detects reduced sensitivity in male PSSD patients, but it’s not a widely available test.10

PSSD can sometimes result in borderline testosterone or other hormones. However, testosterone treatment has not been shown to benefit the condition.

PSSD is often misdiagnosed as a psychological problem when it is actually pharmacological in origin.11 The condition is not related to depression or any other mental health disorder.

In 2024, PSSD (1340196008) was added to SNOMED CT, a comprehensive set of clinical healthcare terminology for use in electronic health records.

How common is PSSD?

It isn’t known how many people regain 100% of their original sexual function and sensation after using an antidepressant.12 It has been suggested that based on the available data, PSSD may be quite common.13

In one study, a group of patients who were experiencing sexual side effects on an SSRI were switched to the dopaminergic antidepressant, amineptine. After six months, 55% still had at least some type of sexual dysfunction. This is compared to only 4% in the control group who were treated with amineptine alone and were not exposed to an SSRI.14

A large placebo-controlled study into the use of sertraline as a treatment for premature ejaculation found that the ejaculation-delaying effect of the drug persisted for 34% of participants 6 months after it was discontinued.15

A healthy volunteer study which assessed the effects of paroxetine on sperm and sexual function reported that brief sexual function inventory (BSFI) scores for erectile and ejaculatory functions had not returned to baseline four weeks after discontinuation of the drug, with 9% of patients complaining of more than mild dysfunction.16

A number of factors have been described that make it difficult to accurately estimate the incidence and prevalence of PSSD.17 These include designing a suitable study method, patient embarrassment at raising sexual concerns, the response of healthcare professionals, inability to stop an antidepressant due to withdrawal issues, patient unawareness that their sexual difficulties are linked to prior medication, variability of online information, and a lack of information aimed at public education.

A US/Canada survey of sexual and gender minority youth aged 15 to 29 reported that 13.2% of patients treated with antidepressants had a persistent post-treatment genital hypoesthesia compared to 0.9% of those treated with other medications.18

The condition can vary in severity between individuals. Some people may not realize they are suffering from it, particularly if they experienced an improvement in sexual function upon stopping the antidepressant. For example, a person may regain the ability to achieve orgasm after previously being unable to do so while on the medication, but it now feels weaker compared to before using antidepressants. As they are no longer on the drug, they might attribute it to another reason.

PSSD can be extremely distressing to those affected. It can lead to marriage break-up, job loss and suicide. But for some sufferers, the loss of sexual desire means they are no longer interested in sex and are unconcerned that they have the condition.

There is currently no way of determining who will develop PSSD when the antidepressant is stopped or any way to actively prevent it. Reducing the dose gradually (tapering) does not appear to prevent the condition. There is no evidence that adding another drug to an antidepressant to combat sexual side effects eg. bupropion (Wellbutrin) will prevent PSSD when the antidepressant is stopped.

Warnings

Since 2011, the US Prozac patient information sheet has warned: “Symptoms of sexual dysfunction occasionally persist after discontinuation of fluoxetine treatment”.19

The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) states: “In some cases, serotonin reuptake inhibitor-induced sexual dysfunction may persist after the agent is discontinued”.20

Persistent sexual dysfunction after treatment with an SSRI has been reported to drug regulators since 1991.21 In response to a petition from RxISK in 2018, the European Medicines Agency and Health Canada recommended changes to SSRI and SNRI product labels to include information about persistent sexual dysfunction after stopping the medication.22, 23

The petition was also submitted to the US Food and Drug Administration (FDA) with an offer to supply details of patients who were willing to be contacted for interview. Other than two standard acknowledgement letters, there has been no further response.24

On 23 May 2024, Australia’s Therapeutic Goods Administration (TGA) issued a safety update advising that all SSRIs and SNRIs are to include warnings about persistent sexual dysfunction after stopping the medication.25

Publications and studies

In some unpublished phase 1 trials of SSRIs, over 50% of healthy volunteers had severe sexual dysfunction that in some cases lasted after treatment stopped.26

PSSD was first reported in the medical literature in 2006.27, 28 Many more peer-reviewed articles have since been published, including in high-profile journals such as the BMJ, the Journal of Sexual Medicine, the Journal of Urology, and the Journal of the Royal Society of Medicine. For a full list of relevant literature, see PSSD Literature.

The Netherlands Pharmacovigilance Centre Lareb have published case studies from their database.29, 30, 31

The pathophysiology of PSSD is poorly understood. Several hypotheses have been proposed including serotonergic neurotoxicity, epigenetic alternations, and disturbances in transient receptor potential ion channels.32, 33

Animal studies

Treatment with fluoxetine has been shown to cause persistent desensitization of 5-HT1A receptors after removal of the SSRI in rats.34 In another study, the use of a 5-HT1A antagonist was shown to reverse and prevent sexual dysfunction in rats that were being administered with fluoxetine.35 However, attempts by PSSD patients to manipulate the serotonergic and dopaminergic systems in an effort to resolve the condition have proved unsuccessful.

Rodent studies have shown that treatment with SSRIs at a young age resulted in permanently decreased sexual behavior in adulthood, with the presence of long-term neurological changes.36, 37, 38 Maternal exposure to fluoxetine was also found to impair sexual motivation in adult male mice.39

A systematic review of the literature on persistent sexual dysfunction in animals after early exposure to SSRIs concluded: “Our results showed substantial and lasting effects on sexual behaviour in rats after exposure to an SSRI early in life on important sexual outcomes.”40

This raises the question of whether there might be long-term sexual consequences for human offspring exposed to antidepressants either during pregnancy or at a young age.

Animal studies have shown changes in bioelectric cell properties and neuroactive steroids after withdrawal of an SSRI.41, 42

Other studies

While on SSRIs, studies have shown side effects to include impaired semen quality and damage to sperm DNA43, 44, 45, 46 as well as issues that are often linked to the endocrine system such as hormone imbalances47, 48 and breast enlargement.49 SSRIs have also been found to have effects on sex steroids.50

Fluoxetine has been classified as a reproductive toxin by the Center for the Evaluation of Risks to Human Reproduction (CERHR), an expert panel at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.51

Treatment

There is currently no treatment for PSSD. A number of medications and supplements can produce positive sexual effects in some sufferers.52, 53 However, the results are generally very limited, inconsistent and can come with their own risks.

PDE5 inhibitors often have reduced effectiveness in patients with PSSD.54 They also have no direct effect on the loss of sensation.55

Vortioxetine is not a treatment for PSSD and has been linked to the onset or worsening of the condition.56 Psychosexual counselling and cognitive-behavioural therapy are also unsuitable.

In one patient, a moderate degree of penile sensitivity was regained following treatment with low-power laser irradiation, but there was no improvement in sexual responsiveness.57

Some people report a degree of natural improvement over a period of time – sometimes months or years after stopping the antidepressant. However, many fail to recover to any significant degree. Some people have had the condition for over 20 years without any improvement.

Our PSSD Research Fund was launched on 21 June 2022 with the aim of better understanding the biology of the condition and hopefully finding treatments.

The RxISK Prize of $100,000 USD is offered to anyone who can provide a cure for persistent sexual side effects after stopping antidepressants, finasteride, or isotretinoin.

Reporting

If you are suffering from PSSD, you can report it to us by completing a RxISK Report. Please provide as much detail as possible including the dates that you started and stopped the drug.

You might also want to report your condition to your country’s drug regulator. Some links are provided below.

The Medical Dictionary for Regulatory Activities (MedDRA) added a code for post-SSRI sexual dysfunction (10086208) in 2021. When reporting, you might want to specifically mention this code in addition to providing details of your symptoms.

Other drugs and conditions

A number of other medications can also cause persisting sexual side effects after the drug has been stopped:

  • Antihistamines that are serotonin reuptake inhibiting
  • Ziprasidone – an antipsychotic which is also a serotonin reuptake inhibitor
  • Some antibiotics (that may be serotonin reuptake inhibiting) such as tetracycline and doxycycline
  • FDA updated the product information for finasteride products in 2011 to warn of persisting sexual side effects after discontinuation of treatment, with further warnings added in 2012.58
  • Isotretinoin (Accutane) which is used as a treatment for acne, and is also serotonin reuptake inhibiting.59

The use of SSRIs or SNRIs, and often their withdrawal, has consistently been reported as one of the triggers of persistent genital arousal disorder (PGAD).60 This is essentially the opposite of PSSD, causing a relentless sense of arousal and discomfort in the genitals, but without any accompanying feeling of desire.

See also

References

  1. Healy D, Le Noury J, Mangin D. Enduring sexual dysfunction after treatment with antidepressants, 5α-reductase inhibitors and isotretinoin: 300 cases. Int J Risk Saf Med. 2018;29(3-4):125-134. PMID: 29733030. ↩︎
  2. Farnsworth KD, Dinsmore WW. Persistent sexual dysfunction in genitourinary medicine clinic attendees induced by selective serotonin reuptake inhibitors. Int J STD AIDS. 2009;20(1):68-9. PMID: 19103903. ↩︎
  3. Bala A, Tue Nguyen HM, Hellstrom WJG. Post-SSRI Sexual Dysfunction: A Literature Review. Sex Med Rev. 2018;6(1):29-34. PMID: 28778697. ↩︎
  4. Muquebil Ali Al Shaban Rodríguez OW, Álvarez de Morales Gómez-Moreno E, Fernández Fernández J, Fresno García C, del Mar Fernández Fernández M. Disfunción sexual persistente tras el tratamiento con inhibidores selectivos de la recaptación de serotonina: a propósito de un caso tras la retirada de paroxetina. Psiquiatría Biológica. 2017;24(2):70-72. ↩︎
  5. Kauffman RP, Murdock A. Prolonged Post-Treatment Genital Anesthesia and Sexual Dysfunction Following Discontinuation of Citalopram and the Atypical Antidepressant Nefazodone. The Open Women’ Health Journal. 2007;1:1-3. ↩︎
  6. Ben-Sheetrit J, Aizenberg D, Csoka AB, Weizman A, Hermesh H. Post-SSRI Sexual Dysfunction: Clinical Characterization and Preliminary Assessment of Contributory Factors and Dose-Response Relationship. J Clin Psychopharmacol. 2015;35(3):273-8. PMID: 25815755. ↩︎
  7. Adson DE, Kotlyar M. Premature ejaculation associated with citalopram withdrawal. Ann Pharmacother. 2003;37(12):1804-6. PMID: 14632589. ↩︎
  8. Patacchini A, Cosci F. Exposure to serotonin selective reuptake inhibitors or serotonin noradrenaline reuptake inhibitors and sexual dysfunction: Results from an online survey. Int J Risk Saf Med. 2021;32(3):229-242. PMID: 33579876. ↩︎
  9. Healy D, Bahrick A, Bak M, Barbato A, Calabrò RS, Chubak BM, et al. Diagnostic criteria for enduring sexual dysfunction after treatment with antidepressants, finasteride and isotretinoin. Int J Risk Saf Med. 2022;33(1):65-76. PMID: 34719438. ↩︎
  10. Waraich A, Clemons C, Ramirez R, Yih J, Goldstein S, Goldstein I. Post-SSRI sexual dysfunction (PSSD): Ten year retrospective chart review. J Urol. 2020;203(4):e1179. ↩︎
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