Psychotropic drugs carry a risk of lasting sexual dysfunction. This article pens down the mechanism of Post-SSRI sexual dysfunction PSSD along with its symptoms and clinical management.

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Psychotropic drugs affect emotions, behaviour, 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.[1]

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.[2]

However, there is an underlying risk of sexual dysfunction with this group of drugs, particularly selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants (TCAs).[2]

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The extent of post-SSRI sexual dysfunction

Board-certified psychiatrist Alex Dimitriu, MD, spoke about the prevalence of sexual dysfunction with SSRIs: “The likelihood of SSRIs inducing sexual dysfunction is about 50% while being treated.” However, he notes, that 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.[3] 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.[4]

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Mechanism of PSSD

A 2022 retrospective study describes PSSD as a "disconnection" between the brain and the genitals.[5]

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.[2] 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%).[6] Females are more likely to experience severe sexual dysfunction.[7]

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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.[2][5]

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.[4]

There are reported cases of PSSD-related changes in erectile tissue, penile curvature, and seminal volume/quality; pelvic floor dysfunction may also occur. Notably, interstitial cystitis/painful bladder syndrome that can develop is often misdiagnosed as recurrent UTIs in women, or as prostatitis in men.[4]

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:

1. 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.[2]
2. 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.”[8]
3. 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.[9]

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Beyond depression

Board-certified psychiatrist, Dr Sangeeta Hatila spoke 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 before drug use that aligns with the current symptoms, existing medical conditions, or current medication/substance misuse explaining the symptoms,” Dr Hatila continues. 

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In the clinic

To counteract sexual side effects, Dr. Dimitriu recommends starting psychotropic drugs at a low dose, and allowing “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 adding 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,"

-Dr Hatila

Relatedly, a 2024 study found that 83.81% of patients switching to vortioxetine reported improved sexual function after 3 months.[10]

Switching from one SSRI to another, such as fluvoxamine to fluoxetine, has also been found to help, due to individual pharmacogenetics.[6]

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.[7]

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Disclaimer: This story is contributed by Alpana Mohta and is a part of our Global Content Initiative, where we feature selected stories from our Global network which we believe would be most useful and informative to our doctor members.