Psychotropic drugs affect emotions, behavior, and the mind, encompassing antidepressants, antipsychotics, mood stabilizers, anxiolytics, stimulants, and hypnotics. Among these, antidepressants are the most commonly prescribed. In 2023, nearly 24% of women and 11% of men in the US were either suffering from depression or receiving treatment for it.

Percentage of adults in the United States who currently had or were being treated for depression in 2017 and 2023, by gender. Statistica.com. November 29, 2023.

 

Antidepressants treat a range of conditions beyond major depressive disorder (MDD), including anxiety, obsessive-compulsive disorder (OCD), eating disorders, PTSD, insomnia, premature ejaculation, and chronic pain.

Ben-Sheetrit J, Hermon Y, Birkenfeld S, et al. Estimating the risk of irreversible post-SSRI sexual dysfunction (PSSD) due to serotonergic antidepressants. Ann Gen Psychiatry. 2023;22(1):15.

 

 

The extent of post-SSRI sexual dysfunction

 

Board-certified psychiatrist Alex Dimitriu, MD, spoke with MDLinx about the prevalence of sexual dysfunction with SSRIs: “The likelihood of SSRIs inducing sexual dysfunction is about 50% while being treated.” However, he notes, in some cases, this issue persists even after stopping the medication; this is known as post-SSRI sexual dysfunction (PSSD).

Reports of prolonged sexual dysfunction following SSRI use were brought to regulators' attention as early as 1991, but PSSD as a term wasn’t introduced in the medical literature until 2006.

Healy D. Post-SSRI sexual dysfunction & other enduring sexual dysfunctions. Epidemiol Psychiatr Sci. 2019;29:e55.

PSSD is defined as any sexual dysfunction that emerges after starting SSRIs and persists even after drug discontinuation despite no prior sexual issues at the onset of treatment.

Healy D, Bahrick A, Bak M, 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.

 

 

Mechanism of PSSD

 

A 2022 retrospective study describes PSSD as a "disconnection" between the brain and the genitals.

De Luca R, Bonanno M, Manuli A, et al. Cutting the first turf to heal post-SSRI sexual dysfunction: a male retrospective cohort study. Medicines (Basel). 2022;9(9):45.

 

The incidence and severity of PSSD depend upon the medication type, duration, patient gender, and individual factors. It can occur after as little as 4 days of use and persist for up to 16 years after stopping the medication.

Ben-Sheetrit J, Hermon Y, Birkenfeld S, et al. Estimating the risk of irreversible post-SSRI sexual dysfunction (PSSD) due to serotonergic antidepressants. Ann Gen Psychiatry. 2023;22(1):15.

A 2023 review noted that SSRIs with higher 5-HT selectivity ratios have higher rates of sexual dysfunction, as found for citalopram (72.7%), fluvoxamine (62.3%), and fluoxetine (57.7%).

Moses TEH, Javanbakht A. Resolution of selective serotonin reuptake inhibitor-associated sexual dysfunction after switching from fluvoxamine to fluoxetine. J Clin Psychopharmacol. 2023;43(1):71-73.

Females are more likely to experience severe sexual dysfunction.

Lalegani E, Eissazade N, Shalbafan M, et al. Safety and efficacy of drug holidays for women with sexual dysfunction induced by selective serotonin reuptake inhibitors (SSRIs) other than fluoxetine: an open-label randomized clinical trial. Brain Sci. 2023;13(10):1397.

 

 

Symptoms

 

Symptoms include reduced libido, genital numbness, delayed or pleasureless orgasm, and anorgasmia. Women may experience dyspareunia, while men may suffer varying degrees of erectile dysfunction.

Ben-Sheetrit J, Hermon Y, Birkenfeld S, et al. Estimating the risk of irreversible post-SSRI sexual dysfunction (PSSD) due to serotonergic antidepressants. Ann Gen Psychiatry. 2023;22(1):15.

De Luca R, Bonanno M, Manuli A, et al. Cutting the first turf to heal post-SSRI sexual dysfunction: a male retrospective cohort study. Medicines (Basel). 2022;9(9):45.

 

Additional symptoms include genital pain, reduced nipple sensitivity, loss of nocturnal erections, decreased ejaculatory force, flaccid glans during erection, and reduced vaginal lubrication. Non-sexual symptoms include emotional numbness, depersonalization, sensory issues (eg, skin, smell, taste, vision), and cognitive impairment.

Healy D, Bahrick A, Bak M, 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.

 

 

Researchers are only beginning to quantify long-term sexual issues related to SSRI use, as clinical trials often lack long-term follow-up, leaving a gap in understanding PSSD's true extent.

Consider the following:

• A 2023 study found that treatment with serotonergic antidepressants more than tripled the risk of needing PDE-5 inhibitors for erectile dysfunction. PSSD developed in 0.46% of patients (1 in 216), with a prevalence of 4.30 per 100,000.

  Ben-Sheetrit J, Hermon Y, Birkenfeld S, et al. Estimating the risk of irreversible post-SSRI sexual dysfunction (PSSD) due to serotonergic antidepressants. Ann Gen Psychiatry. 2023;22(1):15.

   

• In a survey distributed to an online support group for patients with PSSD, 37% of the respondents reported symptoms persisting or worsening after stopping antidepressants, and only 12% were informed about potential risks. Notably, 82% of respondents rated PSSD's impact on their quality of life as either “very negative” or “extremely negative.”

  Studt A, Gannon M, Orzel J, et al. Characterizing post-SSRI sexual dysfunction and its impact on quality of life through an international online survey. Int J Risk Saf Med. 2021;32(4):321-329.

   

• Another survey, among LGBTQ+ individuals aged 15 to 29, revealed that those who had discontinued antidepressants were 14 times more likely to report enduring genital numbness compared with those who had never used them.

  Pirani Y, Delgado-Ron JA, Marinho P, et al. Frequency of self-reported persistent post-treatment genital hypesthesia among past antidepressant users: a cross-sectional survey of sexual and gender minority youth in Canada and the US. OSF Preprints. March 11, 2024.

   

 

Beyond depression

 

Board-certified psychiatrist Dr. Sangeeta Hatila spoke to MDLinx about the relationship between depression and PSSD, saying, "Depression and SD [sexual dysfunction] can reinforce each other. Depressed patients might have low libido as part of their somatic symptom profile, and those with SD could end up being diagnosed with depression because sexual problems can act like a stressor themselves.” 

The role of medication is simple, she explains: “Dopamine boosts libido, while serotonin dampens it, which is why antidepressants can cause sexual dysfunction."

“For diagnosing PSSD, there should be no signs of SD present prior to drug use that align with the current symptoms, existing medical conditions, or current medication/substance misuse explaining the symptoms,” Dr. Hatila continues. 

 

 

In the clinic

 

To counteract sexual side effects, Dr. Dimitriu recommends starting psychotropic drugs at a low dose, and to allow “enough time to assess the full response to the medication before increasing it.”

The following include other options for managing sexual dysfunction in patients who are prescribed these medications.

Add-on therapy

Dr. Dimitriu advises to add buspirone or bupropion for counteracting SSRI-induced SD, but warns bupropion may increase anxiety in some cases. Dr. Hatila suggests, “You can add sildenafil or tadalafil to alleviate SSRI-induced erectile dysfunction.”

Switch medication

"For persistent cases, consider switching patients to antidepressants with a reduced serotonergic effect, such as agomelatine and desvenlafaxine, or those with a multimodal mechanism of action like vortioxetine and vilazodone," says Dr. Hatila.

Switching from one SSRI to another, such as fluvoxamine to fluoxetine, has also been found to help, due to individual pharmacogenetics.

Moses TEH, Javanbakht A. Resolution of selective serotonin reuptake inhibitor-associated sexual dysfunction after switching from fluvoxamine to fluoxetine. J Clin Psychopharmacol. 2023;43(1):71-73.

 

Drug holidays

Skipping SSRIs for 2 consecutive days per week improved sexual health, arousal, orgasm, desire, lubrication, and satisfaction in an RCT with women aged 18 to 50. However, this method is ineffective for fluoxetine due to its long half-life.

Lalegani E, Eissazade N, Shalbafan M, et al. Safety and efficacy of drug holidays for women with sexual dysfunction induced by selective serotonin reuptake inhibitors (SSRIs) other than fluoxetine: an open-label randomized clinical trial. Brain Sci. 2023;13(10):1397.