Written by the RxISK Team. Reviewed by Dr. David Healy.

Last updated: 2020

Introduction

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 [1, 2].

Some people 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 actually 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

Symptoms of PSSD can include:

Reduced genital sensation / genital anesthesia

Erectile dysfunction / decreased vaginal lubrication

Delayed or inability to orgasm (anorgasmia)

Pleasureless, weak or “muted” orgasms

Decreased libido

Reduced response to sexual stimuli

Decreased or lack of nocturnal erections

Premature ejaculation

Reduced nipple sensitivity

Soft glans

Some sufferers experience a noticeable reduction in tactile sensation – describing their genitals as feeling less sensitive or numb, as if exposed to an anesthetic. Others perceive little or no change in tactile sensation, but notice a reduction in sexual sensation. These problems can also be accompanied by reduced nipple sensitivity.

Orgasm is typically 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. Although men and women with PSSD often have more difficulty in achieving orgasm, premature ejaculation can also develop after stopping an SSRI [3].

Although less commonly reported, some male sufferers develop an issue in which the shaft of the penis becomes erect but the glans remains flaccid.

In a 2018 study, two subjects reported penile curvature as part of PSSD [27]. This symptom had not previously been reported in connection with SSRIs and so it was difficult to know whether it was an incidental finding. However, the results of a ten-year retrospective review of clinical PSSD cases published in 2020 provided further evidence that, in some cases, PSSD may result in damage to the erectile tissue of the penis [35].

Diagnosis

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 genitals routinely detects genital changes in 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.

While many doctors are aware of PSSD, others are less familiar with the condition. This not uncommonly results in PSSD symptoms being misdiagnosed as a psychological problem, when it is actually pharmacological in origin. This is not only unhelpful for the sufferer, it can also lead to further prescribing of the medications that caused the condition.

Antidepressant sexual side effects are in no way related to depression, or any other psychological or psychiatric disorder.

How common is PSSD?

It isn’t known how many people regain 100% of their original sexual functioning and sensation after using an antidepressant. Based on the available data, PSSD may be quite common.

The condition can vary in severity between individuals. It is likely that some people don’t 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 person can find that they can now achieve orgasm after previously being unable to do so while on the medication, yet it now feels weaker and less intense 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 lack of 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 after stopping?

When sexual side effects persist after the antidepressant is stopped, there is no specific timescale for recovery.

Some people report a certain degree of natural improvement over a period of time – sometimes months or years after stopping the antidepressant. However, many sufferers 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 [4]. 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 [5–7].

Between 2006 and 2008, 8 cases of persistent sexual dysfunction following SSRI/SNRI treatment appeared in the medical literature [8–11].

In 2008 and 2009, there were published calls for epidemiological studies to investigate the prevalence of PSSD [12, 13].

Since 2011, the US Prozac patient information sheet has warned: “Symptoms of sexual dysfunction occasionally persist after discontinuation of fluoxetine treatment” [14].

In 2012, the Netherlands Pharmacovigilance Center, Lareb, published a report with details of 19 reported cases of PSSD from their database [15]. The findings were subsequently published in the medical literature [16].

Published in 2013, the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) stated: “In some cases, serotonin reuptake inhibitor-induced sexual dysfunction may persist after the agent is discontinued” [17]. In the same year, a qualitative study investigated the impact of the condition [18].

In 2014, Hogan et al listed 91 cases of persistent sexual dysfunction linked to SSRIs or SNRIs, sourced from an internet portal for reporting adverse events [19]. Waldinger et al described a case of persistent genital anesthesia following paroxetine treatment that responded to low-power laser irradiation [20].

In 2015, Ben-Sheetrit et al published a study of 183 possible cases of PSSD, including 23 high-probability cases, from an on-line survey [21].

Two review articles [22, 23] and a case report were published in 2017 [24].

Another review was published in 2018 [25] followed by an article exploring commonalities between PSSD and post-finasteride syndrome [26]. Healy et al published a study of 300 cases of enduring sexual dysfunction of which 221 were after the previous use of serotonin reuptake inhibitors [27]. A published petition requesting warnings to be added to SSRI and SNRI products was submitted to the Food and Drug Administration and the European Medicines Agency [28].

In 2019, a case report described persistent sexual dysfunction after the use of citalopram which responded to a dietary supplement [29]. The European Medicines Agency recommended changes to SSRI and SNRI product labels to include information about persistent sexual dysfunction after drug withdrawal [30]. A study investigated the experiences of PSSD patients when engaging with healthcare professionals [31]. An article in Epidemiology and Psychiatric Sciences outlined the main issues [32].

In 2020, a history of antidepressants and sexual dysfunction including PSSD was published in the Journal of the Royal Society of Medicine [33]. An editorial about PSSD was published in The BMJ [34]. A ten year retrospective chart review was published in the Journal of Urology [35].

Animal studies

Treatment with fluoxetine has been shown to cause persistent desensitization of 5-HT1A receptors after removal of the SSRI in rats [36]. 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 [37].

Therefore, hypotheses for PSSD have often focused on a possible neurological model involving persisting changes to brain chemistry. However, attempts by PSSD sufferers 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 [38–40], with the presence of long-term neurological changes [38]. Maternal exposure to fluoxetine was also found to impair sexual motivation in adult male mice [41].

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.” [42]

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.

A brief exposure to an SSRI was found to induce long-lasting changes in the bioelectric cell properties of planarian flatworms (an important model for human neurophysiology and pharmacology) [43]. It was suggested that this may contribute to the enduring effect seen in PSSD.

Other studies

While on SSRIs, studies have shown side effects to include impaired semen quality and damage to sperm DNA [44–47], as well as issues that are often linked to the endocrine system such as hormone imbalances [48, 49] and breast enlargement [50]. SSRIs have also been found to have effects on sex steroids [51]. However, the role of the endocrine system in persisting problems such as PSSD is currently unclear.

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 [52].

Treatment

There is currently no viable 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 provide little or no benefit in PSSD. In some cases they have no effect at all, while in others they provide only a limited improvement in erectile function. They also offer no direct benefit to the other areas of sexual functioning that can be impaired in PSSD eg. sensation.

There is no evidence to suggest that the use of platelet rich plasma (PRP) is a suitable treatment for PSSD.

The typical strategies for managing sexual side effects usually only apply to problems that occur while on treatment, and are therefore unhelpful in PSSD. These would generally involve switching to a different antidepressant, lowering the dose, or potentially stopping the medication altogether.

On September 12, 2017, we launched our RxISK Prize campaign to raise $100,000 which will be offered to anyone who finds a cure for PSSD or related conditions involving finasteride and 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.

You might also want to report your condition to your country’s drug regulator eg. FDA’s Medwatch in the US and MHRA’s Yellow Card Scheme in the UK.

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 [53].

Isotretinoin (Accutane) which is used as a treatment for acne [4, 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) [28]. 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. Watch our PGAD video.

See also