Post-SSRI Sexual Dysfunction (PSSD)

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Last updated: 2017
Medically reviewed by RxISK’s Medical Team.

Sexual side effects

 

Introduction

Close to 100% of people who take antidepressants experience some form of sexual side effects.

Most people who take an SSRI (selective serotonin reuptake inhibitor) or an SNRI (serotonin-norepinephrine reuptake inhibitor) 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 (Brintellix).

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 erogenous (sexual) sensation in genitals
  • Genital anesthesia
  • Erectile dysfunction / decreased vaginal lubrication
  • Delayed or inability to orgasm (anorgasmia)
  • Pleasureless, weak or “muted” orgasms
  • Decreased or loss of libido (sex drive)
  • Reduced response to sexual stimuli
  • Decreased or lack of nocturnal erections
  • Premature ejaculation
  • Soft glans syndrome

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.

There can be a loss of arousal which can cause difficulties with intercourse. Men can have difficulty getting and maintaining an erection. Women can have problems with lubrication.

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 soft glans syndrome. This refers to an abnormal erection in which the shaft of the penis becomes erect but the glans remains flaccid to varying degrees. It may be most noticeable on waking and can be accompanied by a feeling of discomfort or tightness.

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.

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.

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.

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 [4].

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. This creates a confusing situation for the sufferer. 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.

These issues are explored further in the blog post, How Common is Post-SSRI Sexual Dysfunction.

Can PSSD be prevented?

When using an SSRI, SNRI or some tricyclic antidepressants, 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.

It is important that anyone considering the use of antidepressants should take into account the risk of potentially permanent changes to sexual functioning when making a decision about their treatment.

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.

Is it the antidepressant medication or depression?

There are four ways to help distinguish persisting sexual side effects from any problem that might have led to treatment in the first instance.

  • You had normal sexual functioning immediately prior to starting the antidepressant.
  • You experienced a very clear onset of sexual side effects within the first few days or weeks of starting treatment, and your sexual function never fully returned to normal after stopping.
  • You are experiencing genital numbing (loss of sexual sensations and/or anesthesia) and muted orgasms. While depression can sometimes make you less interested in sex, it does not cause these symptoms which are well-known effects of serotonin reuptake inhibiting medications. In men, a reduction or loss of nocturnal erections also points to the drug rather than a psychological problem.
  • If your original depression cleared up on the antidepressant and you were doing well, on stopping treatment no new problems should appear for several months or even years. Any persisting sexual problems, or any new sexual problems that appear within days of stopping, are more likely to be caused by the drug.

Even if your sexual function responded to changes in dose while on treatment and significantly improved upon stopping, if it isn’t the same as before you started antidepressants, you may be suffering from PSSD.

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, the term “recovery” in this sense can be misleading as closer scrutiny often reveals that there hasn’t been a full return to pre-drug state.

Many sufferers fail to recover to any significant degree, with some having had the problem for over 20 years without any sign of improvement.

For some people, PSSD may be permanent.

Publications and studies

In a study by Montejo et al (1999), a group of patients who were experiencing sexual side effects on an SSRI were switched to the dopaminergic antidepressant, amineptine [5]. 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 [6-8].

Between 2006 and 2008, 8 cases of persistent sexual dysfunction following SSRI/SNRI treatment appeared in the medical literature [9-12].

In 2008 and 2009, there were published calls for epidemiological studies to investigate the prevalence of PSSD [13-14].

In 2012, the Netherlands Pharmacovigilance Center, Lareb, published details of 19 reported cases from their database, and called for further investigation into the issue [15-16].

In 2013, Stinson completed a qualitative study of 9 PSSD sufferers, examining the impact of the condition on quality of life [17].

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 [4]. Waldinger described a case of persistent genital anesthesia following paroxetine treatment that responded to low-power laser irradiation [18].

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 [19].

While on SSRIs, studies have shown side effects to include impaired semen quality and damage to sperm DNA [20-22], as well as issues that are often linked to the endocrine system such as hormone imbalances [23-24] and breast enlargement [25]. SSRIs have also been found to have effects on sex steroids [26]. However, the role of the endocrine system in persisting problems such as PSSD is currently unclear.

Fluoxetine (Prozac) 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 [27].

The US Prozac patient information sheet warns that “Symptoms of sexual dysfunction occasionally persist after discontinuation of fluoxetine treatment” [28].

Animal studies

Treatment with fluoxetine (Prozac) has been shown to cause persistent desensitization of 5-HT1A receptors after removal of the SSRI in rats [29]. 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 [30].

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 chronic treatment with SSRIs at a young age resulted in permanently decreased sexual behavior in adulthood, with the presence of long-term neurological changes [31-32]. Maternal exposure to fluoxetine was also found to impair sexual motivation in adult male mice [33].

A systematic review of the literature on persistent sexual dysfunction in animals after early exposure to SSRIs was published in 2016 [34]. It 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.

Other drugs and conditions

There are a number of other medications that 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
  • Finasteride (Propecia) which is used to treat male pattern baldness and benign prostatic hyperplasia. The condition is called Post-Finasteride Syndrome (PFS) [35-38].
  • Isotretinoin (Accutane) which is used as a treatment for acne [4], and is also serotonin reuptake inhibiting.

SSRI antidepressants can also cause the equally distressing condition, Persistent Genital Arousal Disorder (PGAD) [39-41]. 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. (Note that not all cases of PGAD are caused by medications.)

Are there any treatments?

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 such as sildenafil, tadalafil and vardenafil 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.

A 2014 paper by Waldinger et al, reported that a PSSD sufferer with severe penile anesthesia experienced some improvement in tactile and temperature sensation after the use of Low Power Laser Irradiation (LPLI) [16]. This type of treatment is generally used for pain issues and is also known as low level laser therapy or cold laser therapy. It was hypothesized that SSRI-induced genital anesthesia may be due to disturbances of Transient Receptor Potential (TRP) Ion Channels. The improvement in this case did not extend to any aspects of sexual responsiveness.

In relation to PGAD, the use of transcutaneous electrical nerve stimulation (TENS) has been discussed in the literature [42], though not specifically for SSRI related problems. Its effectiveness in cases of SSRI-induced PGAD remains unclear.

Reporting your condition

If you are suffering from PSSD, you can tell us about it by completing a RxISK Report, even if you aren’t interested in the causality score or taking the report to your doctor. 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.

See also

Mind, one of the UK’s leading mental health charities warns that “Sometimes these side effects persist after you’ve come off the drug, and might continue indefinitely.”

On March 11th, 2014, the Dutch newspaper Volkskrant featured an article about PSSD on its front page following concerns raised by Lareb, the Netherlands Pharmacovigilance Centre.

The Daily Mail published an article about PSSD on March 20, 2017. An article about long-term antidepressant use published by The Guardian on May 6, 2017 also covered the issue.

References

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  2. Bahrick AS. Persistence of sexual dysfunction side effects after discontinuation of antidepressant medications: Emerging evidence. The Open Psychology Journal. 2008;1:42-50. doi:10.2174/1874350100801010042.
  3. Adson DE, Kotlyar M. Premature ejaculation associated with citalopram withdrawal. Ann Pharmacother. 2003 Dec;37(12):1804-6. doi:10.1345/aph.1D214. PMID 14632589.
  4. Hogan C, Le Noury J, Healy D, Mangin D. One hundred and twenty cases of enduring sexual dysfunction following treatment. Int J Risk Saf Med. 2014;26(2)109–16. doi:10.3233/JRS-140617. PMID 24902508.
  5. Montejo AL, Llorca G, Izquierdo JA, 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; Castilian). 1999 Jan-Feb;27(1):23-34. PMID 10380144.
  6. Safarinejad MR, Hosseini SY (2006). Safety and efficacy of citalopram in the treatment of premature ejaculation: a double-blind placebo-controlled, fixed dose, randomized study. Int J Impot Res. 18 (2): 164–9. doi:10.1038/sj.ijir.3901384. PMID 16107866.
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