Post-SSRI sexual dysfunction (PSSD)

Post-SSRI sexual dysfunction (PSSD) is a condition that affects individuals who have discontinued the use of certain antidepressants, such as selective serotonin reuptake inhibitors (SSRIs)​1​, including amitriptyline​2,3​. Many people are prescribed amitriptyline to manage vulvovaginal or urogenital pain.

Despite stopping the medication, some people continue to experience sexual side effects of this medication, which can significantly impact quality of life​4​.

It’s known that most people who take these types of medications will experience genital numbing, often within just half an hour of a dose. In PSSD, this numbness does not resolve. Sometimes, symptoms worsen after the drug is stopped or the dose dropped.

PSSD can happen as quickly as within a few days of starting the anti-depressant medication and can weeks or months, or in some cases indefinitely. There is no cure.

Types of antidepressants that can cause PSSD​5​

  • Selective serotonin reuptake inhibitors (SSRIs)
  • Serotonin-norepinephrine reuptake inhibitors (SNRIs)
  • Some tricyclic antidepressants such as clomipramine and imipramine

SSRI types and brands

  • Paroxetine (Paxil, Seroxat)
  • Fluoxetine (Prozac)
  • Sertraline (Zoloft)
  • Citalopram (Celexa)
  • Escitalopram (Lexapro)
  • Vortioxetine (Trintellix)
  • Amitriptyline

SNRIs types and brands:

  • Venlafaxine (Effexor)
  • Desvenlafaxine (Pristiq)
  • Duloxetine (Cymbalta)

What is PSSD?

PSSD is characterised by persistent sexual dysfunction that occurs after discontinuing SSRIs or related antidepressants​1​.

Anyone can be affected, and symptoms may include reduced genital sensation, decreased libido, erectile dysfunction, and difficulty achieving orgasm.

While not everyone who takes SSRIs will develop PSSD, the condition can persist for months, years, or indefinitely in those who do.

Common symptoms of PSSD​4​

Individuals with PSSD may experience a range of symptoms, including:

  • Reduced genital sensation
  • Decreased libido
  • Decreased vaginal lubrication
  • Difficulty achieving orgasm
  • Diminished response to sexual stimuli
  • Weak orgasm
  • Reduced nipple sensitivity
  • Flaccid glans during erection, loss of night-time erections, and erectile dysfunction in penises

There may be a loss of tactile sensation, feeling like the genitals have been anesthetised, while in some cases, genital touch feels like touch elsewhere on the body. Orgasm may be less pleasurable and forceful.

Other symptoms of PSSD may include feeling emotionally numb, cognitive impairment or other sensory issues.

Diagnosis of PSSD

Diagnosing PSSD can be challenging due to the lack of specific tests. Healthcare providers typically rely on a thorough medical history, evaluation of symptoms, and exclusion of other potential causes of sexual dysfunction.

It’s essential for individuals experiencing persistent sexual side effects after discontinuing antidepressants to seek medical advice and undergo appropriate evaluation.

Diagnosis of PSSD​4,6​ entails:

Must include both prior treatment with a serotonin reuptake inhibitor, and an ongoing change in somatic (tactile) or erogenous (sexual) genital sensation after treatment has ended.

These two necessary factors may be accompanied by an ongoing reduction or loss of sexual desire, an inability to orgasm or less pleasurable orgasms, and the issue persisting for three months or longer after stopping anti-depressant treatment.

There should be no pre-drug sexual dysfunction, medical condition or medication/substance use that is equivalent to/can cause equivalent symptoms.

PSSD is not related to depression and is not psychological, and may result in borderline testosterone, but testosterone does not help.

How often is PSSD occurring?

While the exact prevalence of PSSD is unknown, research suggests that it may be more common than previously thought.

Studies have shown that a significant number of individuals continue to experience sexual dysfunction even after stopping antidepressant treatment.

For some people, PSSD is extremely distressing, while others have lost their interest in sex and are therefore unconcerned about the condition.

PSSD treatment options

Currently, there is no definitive treatment for PSSD. While some medications and supplements may provide temporary relief for some individuals, results are often inconsistent​7​.

Reducing the dose (tapering) isn’t useful as a preventative, and other drugs can’t be added to address sexual side effects, such as bupropion (Wellbutrin) though can be helpful in some cases​7​.

Psychosexual counselling and cognitive-behavioural therapy may also be considered as part of a comprehensive treatment approach.

Herbs and supplements that help

  • Ginkgo biloba​8​
  • Panax ginseng​9​
  • Maca root​10​
  • Saffron​11​
  • St John’s wort (Hypericum perforatum)​12​
  • Yohimbine​13​
  • Clinoptilolite/Zeolite​14​
  • EDOVIS supplement​7​
  • Pregnenolone (hormone)​15​

Supplements to avoid

  • Antidepressant medications (SSRI, SNRI)​16​
  • Withania/ashwagandha​17​
  • Bereberine (may act on 5-HT1A receptor)​18​
  • Herbal 5-HT1A partial agonists (ginger)​19​

The gut microbiome and PSSD

Research shows that SSRI drugs can negatively impact the gut microbiome​20​, with impacts on the gut-brain axis​21​ and serotonin metabolism​22,23​. It’s unclear how much impact this has on the development of PSSD, but it’s worth considering.

How and why does PSSD happen?

There are a few theories to explain exactly what happens in PSSD, including​1​:

  • Serotonin neurotoxicity
  • Dopamine-serotonin interactions
  • Hormonal changes in the peripheral and central nervous systems
  • Epigenetic gene expression
  • Cytochrome actions
  • Proopiomelanocortin (POMC) and melanocortin effects

Many 5-HT (serotonin) agonists and agents that increase 5-HT impair sexual urges, responses and behaviour​24​.

Serotonin typically inhibits, rather than encourages, biologically speaking. However, research shows that when the 5-HT2C receptors are stimulated in men, erections are increased, while ejaculation is inhibited, while when 5HT1A receptors are stimulated, the opposite is seen​25​.

The female sexual system also contains erectile tissue. Thus, if 5-HT1A receptors are activated, sexual dysfunction may be the result​26​. In theory, stimulation of 5-HT2 receptors may mediate the impacts of PSSD.

The excessive release of serotonin may cause desensitisation of 5-HT1A receptors​26​. Chronic, profound activation by serotonin down-regulates the 5-HT1A autoreceptors​27​.

Meaning, the receptors are ‘damaged’ by too much competition, and an antagonist may help restore sensitivity​27​.

Studies into these receptors show mixed results:

  • When rats were given SSRIs, the 5-HT1A receptors remained desensitised after the drug was stopped​28​.
  • A 5-HT1A antagonist reversed and prevented sexual dysfunction in rats who were given fluoxetine​28​.

But, many smart and invested sufferers and researchers have tried and tested these drugs, without benefit​29​.

Low-power irradiation produced a 20-40% improvement in one case study in a man who lost sensation and erectile function​30​.

Where to get help

Post-SSRI sexual dysfunction is a complex and challenging condition that can have a significant impact on individuals’ lives.

By increasing awareness and research efforts, we can better understand PSSD and develop more effective treatment options to improve the quality of life for those affected.

If you or someone you know is experiencing persistent sexual side effects after discontinuing antidepressants, it’s essential to seek medical advice and support.

References​1,31,32​

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    Waldinger MD, van Coevorden RS, Schweitzer DH, Georgiadis J. Penile anesthesia in Post SSRI Sexual Dysfunction (PSSD) responds to low-power laser irradiation: A case study and hypothesis about the role of transient receptor potential (TRP) ion channels. European Journal of Pharmacology. Published online April 2015:263-268. doi:10.1016/j.ejphar.2014.11.031
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Jessica Lloyd - Vulvovaginal Specialist Naturopathic Practitioner, BHSc(N)

Jessica is a degree-qualified naturopath (BHSc) specialising in vulvovaginal health and disease, based in Melbourne, Australia.

Jessica is the owner and lead naturopath of My Vagina, and is a member of the:

  • International Society for the Study of Vulvovaginal Disease (ISSVD)
  • International Society for the Study of Women's Sexual Health (ISSWSH)
  • National Vulvodynia Association (NVA) Australia
  • New Zealand Vulvovaginal Society (ANZVS)
  • Australian Traditional Medicine Society (ATMS)
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