Diagnosing Long-Term Sexual Dysfunction from SSRIs

Source: Jarun Ontakrai/Shutterstock

With more than 13.2 percent of the adult U.S. population monthly filling prescriptions for SSRI antidepressants, a figure involving at least 45 million Americans, it is disconcerting to find multiple studies conclude SSRIs “may cause sexual dysfunction in 40 to 65 percent of individuals” prescribed them. Some put the incidence rate as high as 72.7 percent (2001) and 81.4 percent (1997).

Drug-makers and regulators have long known about the condition, first known as “Antidepressant-induced sexual dysfunction.” The U.K.’s Medicines and Healthcare products Regulatory Agency (MHRA) began noting reports of sexual dysfunction after an SSRI was withdrawn in 1987, with fluvoxamine (Luvox) followed in 1991 by fluoxetine (Prozac).

Subsequent studies—including one in 2001 involving 1,022 outpatients—concluded that citalopram (Celexa) had a still-higher incidence rate at 72.7 percent, with paroxetine (Paxil) a close second at 70.7 percent.

The same study determined that “men had a higher frequency of sexual dysfunction (62.4 percent) than women (56.9 percent), following antidepressant discontinuation, “although women had higher severity.”

Overall, close to four in ten described their symptoms after SSRI treatment as intolerable, with delayed or premature ejaculation among the most common, alongside decreased sex drive, reduced or pleasure-less sexual satisfaction, anorgasmia, genital anesthesia (marked numbness of the genital area), and erectile dysfunction.

The European Medicines Agency formally recognized the iatrogenic condition as post-SSRI sexual dysfunction (PSSD) in June 2019.

In another study from 1999, an international team of 37 expert physicians in a just-published review noted, “55 percent of participants still had sexual dysfunction six months after switching from an SSRI to amineptine [a tricyclic antidepressant] compared to 4 percent who were treated solely with amineptine, a drug with no action on the serotonin system.” In addition, “close to all people taking an SRI have some alteration of genital sensitivity within an hour of starting treatment” (Healy 2021).

Hence the significance of these findings being used to formalize “Diagnostic criteria for enduring sexual dysfunction after treatment with antidepressants, finasteride, and isotretinoin,” with the same 37 experts collaborating over the largest public collection of relevant data on these conditions.

The proposed criteria—led by psychiatrist David Healy and involving senior researchers across Europe, North America, and India—provided badly needed clarity on a medical condition that poses unique challenges, in that symptoms can present or persist long after the causative drug treatment has ended and which themselves are often mistaken for relapse in depression, as reduced or lost libido is a shared characteristic.

Researchers Elizabeth Jing and Kristyn Straw-Wilson warned in 2016 that “although depression may play a role in sexual dysfunction, SSRIs may cause sexual side effects unrelated to depression.” Often overlooked or dismissed, that key distinction has in practice led to widespread diagnostic confusion over a condition that, five years later, is still “little known and poorly understood by healthcare professionals” (Healy 2021).

To address these and associated problems, Healy and colleagues noted of PSSD: “Significant sexual dysfunction can happen while on treatment and after stopping any serotonin reuptake inhibiting (SRI) drug.” They propose the following diagnostic criteria:

Necessary:

(1) Prior treatment with a serotonin reuptake inhibitor.

(2) An enduring change in somatic (tactile) or erogenous (sexual) genital sensation after treatment stops.

Additional:

(3) Enduring reduction or loss of sexual desire.

(4) Enduring erectile dysfunction (males).

(5) Enduring inability to orgasm or decreased sensation of pleasure during orgasm.

(6) The problem is present for ≥ 3 months after stopping treatment.

SSRIs Essential Reads

AI in Precision Medicine: Predicting Antidepressant Outcomes

Can the Rate of Antidepressant Prescribing Be Reversed?

There should be:

(7) No evidence of pre-drug sexual dysfunction that matches the current profile.

(8) No current medical conditions that could account for the symptoms.

(9) No current medication or substance misuse that could account for the symptoms.

PSSD can vary in severity,” they added, but generally “there is a marked escalation of genital sensory effects…. The condition may be triggered by exposures as brief as several days. The sexual dysfunction that accompanies normal antidepressant use may linger for some days or weeks following discontinuation of treatment. The present consensus is that once dysfunction lasts for three months, it is more likely to be PSSD.

The researchers provided comparable criteria for persistent genital arousal disorder (PGAD), concerning “persistent unwelcome sensations of genital arousal or irritability” during SRI treatment. They also established diagnostic criteria for post-finasteride syndrome (PFS), regarding the erectile dysfunction associated with finasteride products designed to treat male pattern baldness, and for post-retinoid sexual dysfunction (PRSD), concerning the growing number of cases of sexual dysfunction linked to isotretinoin, a retinoid medication used in the treatment of acne.

Timely in predating textual revisions to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), due in March, the collaboration over PSSD and related conditions gives greater clarity and confidence to doctors and reassurance to patients, the toll of whose long-term sexual dysfunction on relationships and individual mental health was well-captured in a 2019 study by Healy, Joanna Le Noury, and Dee Mangin.

A qualitative analysis drawing on 62 participants from 23 countries, “Post-SSRI sexual Dysfunction: Patient Experiences of Engagement with Healthcare Professionals” identified recurring areas of patient concern:

Degree of physician awareness/knowledge of the condition, not being listened to, insensitive responses, suggested a return to medication, response to published medical literature, lack of treatment, no longer mention it, and impact of invalidating responses.

Representative statements included:

I asked my new psychiatrist if he was able to provide me kindly with the letter. He agreed but seemed to feel relief at the same time that he was not pushed to directly say that SSRI caused my condition.

Another patient was told: “I have noticed from your records that you have spoken to some other doctors from here about this. I think you shouldn't keep bringing it up.”

Another participant reported that “their G.P. stated that SSRIs were ‘harm free’ and ‘laughed at the idea they could make long term changes to a patient.’”

Physician disbelief is an additional obstacle:

I talked to my primary care doctor and she doesn't believe that my symptoms could be related to the medication that was discontinued years ago. She was the doctor who prescribed the medication.

The study found concern among participants that the dysfunction they experienced

was being dismissed as a psychological issue without a proper understanding of the sexual symptoms or the specifics of the original issue: ‘I have fairly mild OCD, but OCD never made my genitals go numb, or orgasms pleasureless, or to have zero sex drive.’

Another participant reported:

I visited my psychiatrist, under whose supervision I took the drug for eight years, and when I informed him about my persistent sexual dysfunctions, he said I was talking absolute rubbish and they were my psychological constructs.

Physician failure to warn about the drugs’ common adverse effects led to frequent frustration and despair about their long-term consequences:

I'm quite angry with the doctors I have visited so far, but especially my psychiatrist who didn't inform me about the possible long term side effects the pill can cause. I never had any problems with my sexual functioning before taking the medication, and I don't think that genital anesthesia can be considered a symptom of depression.

Regarding the exact causes of PSSD and thus prospects for corrective treatment, Jing and Straw-Wilson hypothesized that “many side effects of SSRIs are attributed to the increase of serotonin at specific serotonin receptor subtypes.”

They focus on the prospects of other pharmaceuticals as adjunct or replacement treatments, such as bupropion (Wellbutrin), which, they determine, “reversed sexual dysfunction caused by SSRIs in 66 percent of the subjects when used consistently,” but which also carries a higher risk of seizure and overdose.

They also summarized a systematic review of randomized control trials determining that

phosphodiesterase 5 (PDE5) inhibitors, such as sildenafil (Viagra) and tadalafil (Cialis), improved erectile dysfunction better than placebo in male subjects with sexual dysfunction as a result of antidepressant treatment,

but stressed that neither provides a “solution to the most common SSRI-related sexual side effect, difficulty with achieving orgasm,” with unclear prospects also for treating long-term PSSD in women.

Jing and Straw-Wilson added that saffron, a spice derived from the flower Crocus sativus, “has implications of producing aphrodisiac effects in animals and humans” and that—again focusing on treatment for males—“there is some evidence that saffron may inhibit serotonin reuptake and affect the levels of nitric oxide in the body, which plays a role in achieving erection.”

Other researchers—skeptical of such hypotheses and their underpowered studies, and mindful of the substantial number of patients whose sexuality has not recovered, despite drug treatment ending months earlier—stress the risk of long-term harm as an in-built feature of SSRIs, not an exception to them, and urge prescribers to weigh the enduring risks with greater caution: “RxISK isn't aware of anything that helps PSSD.”

“The worst part” of PSSD, a patient and student of neuroscience tapering sertraline (Zoloft) summed up in recent powerful testimony about the condition, following earlier, optimistic stress on the “plasticity” of neural pathways,

is these changes can be permanent, and I fear that will be me. I’m almost all the way off sertraline and I’m seeing no change. I have no frame of reference [having taken the SSRI as prescribed since age 12], so I can’t compare my progress to a sexuality that was once there. I have nothing to miss! But I still feel I’m lacking a key aspect of intimacy that other adults can take for granted.