Written by the RxISK Team. Reviewed by Dr. David Healy.
Last updated: 2022
Close to 100% of people who take antidepressants experience some form of sexual side effects.
Most people who take a selective serotonin reuptake inhibitor (SSRI), a serotonin-norepinephrine reuptake inhibitor (SNRI), and some tricyclic antidepressants (clomipramine and imipramine) will feel some degree of genital numbing, often within 30 minutes of taking the first dose.
Commonly used SSRIs include paroxetine (Paxil, Seroxat), fluoxetine (Prozac), sertraline (Zoloft), citalopram (Celexa), escitalopram (Lexapro), and vortioxetine (Trintellix).
Common SNRIs include venlafaxine (Effexor), desvenlafaxine (Pristiq) and duloxetine (Cymbalta).
What is post-SSRI sexual dysfunction?
Post-SSRI sexual dysfunction (PSSD) is an iatrogenic condition which can arise following antidepressant use, in which sexual function does not completely return to normal after the discontinuation of SSRIs, SNRIs and some tricyclic antidepressants.
Some patients develop sexual side effects on antidepressants which either remain in full or don’t resolve completely when the drug is stopped. For others, the condition only appears when they stop the medication or begin to reduce the dosage.
PSSD affects both men and women. It can happen after only a few days exposure to an antidepressant and can persist for months, years, or indefinitely. There is no known cure.
Symptoms of PSSD can include:
- reduced genital sensation
- erectile dysfunction / decreased vaginal lubrication
- difficulty achieving orgasm
- pleasureless or weak orgasms
- decreased libido
- reduced response to sexual stimuli
- decreased or loss of nocturnal erections
- reduced nipple sensitivity
- flaccid glans during erection
Some patients experience a noticeable reduction in tactile sensation – genitals feel like their were exposed to an anesthetic. Others notice a reduction in sexual sensation.
Orgasm is experienced with a decreased or loss of pleasurable feeling, often referred to as a pleasureless or muted orgasm. There can also be noticeably weaker muscle contractions.
Cases of premature ejaculation after stopping an SSRI have also been reported .
Ancillary non-sexual symptoms may include emotional numbing and cognitive impairment.
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. Diagnostic criteria were published in 2021 .
Quantitative sensory testing (QST) of the penis routinely detects reduced sensitivity in male PSSD patients, but it’s not a widely available test.
While PSSD can often result in lower than normal testosterone levels, this is not responsible for the condition. Restoring hormone levels back to normal with medication fails to resolve the problem.
PSSD is often misdiagnosed as a psychological problem when it is actually pharmacological in origin. Antidepressant sexual side effects are in no way related to depression or any other mental health disorder.
(1) Prior treatment with a serotonin reuptake inhibitor.
(2) An enduring change in somatic (tactile) or erogenous (sexual) genital sensation after treatment stops.
(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.
How common is PSSD?
It isn’t known how many people regain 100% of their original sexual function and sensation after using an antidepressant. Based on the available data, PSSD may be quite common.
The condition can vary in severity between individuals. Some people may not realize they are suffering from it. They might have had sexual side effects while on an antidepressant which seemed to resolve when they stopped, but they still notice that their sexual function isn’t the same as it used to be, or that sexual activity feels different.
For example, a patient can find that they can now achieve orgasm after previously being unable to do so while on the medication, but it now feels weaker compared to before using the antidepressants. As they are no longer on the drug, they might think they are imagining it or that it must be due to another reason such as a relationship issue.
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 drug is stopped or any way to actively prevent it. Stopping an antidepressant gradually (tapering) does not prevent the problem. 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.
How long do sexual side effects last?
When sexual side effects persist after the antidepressant is stopped, there is no specific timescale for recovery.
Some patients report a certain 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 with some having had the problem for over 20 years without any improvement.
For some people, PSSD may be permanent.
Publications and studies
In a study by Montejo et al, 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.
Three large placebo controlled studies into the use of SSRIs as a treatment for premature ejaculation found that the ejaculation-delaying effect of the medication persisted for a significant number of participants after the drug was discontinued [4–6].
Since 2011, the US Prozac patient information sheet has warned: “Symptoms of sexual dysfunction occasionally persist after discontinuation of fluoxetine treatment” .
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” .
In response to a petition published 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.
Treatment with fluoxetine has been shown to cause persistent desensitization of 5-HT1A receptors after removal of the SSRI in rats . 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 . 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 [43–45], with the presence of long-term neurological changes . Maternal exposure to fluoxetine was also found to impair sexual motivation in adult male mice .
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.” 
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.
While on SSRIs, studies have shown side effects to include impaired semen quality and damage to sperm DNA [50–53] as well as issues that are often linked to the endocrine system such as hormone imbalances [54, 55] and breast enlargement . SSRIs have also been found to have effects on sex steroids .
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 .
There is currently no treatment for PSSD.
A number of medications, herbs and related compounds can produce pro-sexual effects in some sufferers. 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.
The PSSD Research Fund was launched on 21 June 2022.
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 your condition
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.
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 .
- Isotretinoin (Accutane) which is used as a treatment for acne [19, 27], and is also serotonin reuptake inhibiting.
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) . 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.
- PSSD Research Fund
- Research Forum for Enduring Sexual Dysfunction
- PSSD Doctors & Specialists
- PSSD Literature
- Media articles
- Blog posts about sex and medications
- Complex Withdrawal. Hypothesis about protracted withdrawal and PSSD.
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- 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.
- Montejo AL, Llorca G, Izquierdo JA, Carrasco JL, Daniel E, Pérez-Sola V, et al. Sexual dysfunction with antidepressive agents. Effect of the change to amineptine in patients with sexual dysfunction secondary to SSRI. Actas Esp Psiquiatr (in Spanish). 1999;27(1):23-34. PMID 10380144.
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