Downright Depressing: Antidepressants Can Ruin Your Sex Life

Lasting sexual dysfunction from antidepressants is frighteningly common.

If I wanted to lift someone’s mood, the last thing I’d do is give them a drug that could ruin their sex life. But that’s exactly what doctors are routinely doing when they prescribe antidepressants. Sexual dysfunction is an exceedingly common side effect of antidepressants, with SSRIs and SSNRIs being the worst offenders.

Sexual dysfunction can be broadly divided into three phases reflecting disruption in the normal cycle of 1) sexual desire, 2) physical arousal, and 3) orgasm. Many drugs, especially those acting on the serotoninergic system, have been shown to negatively affect all three phases.

Surveys indicate that most antidepressant users experience sexual dysfunction after commencing the drugs.

Spanish researchers questioned 1,022 patients with previously normal sexual function who were being treated with antidepressants alone or antidepressants plus benzodiazepines. They found the overall incidence of sexual dysfunction was 59.1% when all antidepressants were considered as a whole. When considered individually, venlaxafine and the SSRIs were the worst culprits.

The percentage of patients experiencing sexual dysfunction on these drugs were:

• Citalopram, 72.7%;

• Paroxetine, 70.7%;

• Venlafaxine, 67.3%;

• Sertraline, 62.9%;

• Fluvoxamine, 62.3%;

• Fluoxetine, 57.7%.

The Spanish study found men had a higher frequency of sexual dysfunction (62.4%) than women (56.9%) when taking antidepressants, although women experienced more severe symptoms[1].

To get an idea of just how pervasive the problem was, researchers from the University of Bologna, Italy scoured the literature for studies reporting on sexual functioning in patients taking antidepressants[2]. Because patients are often reluctant to self-report sexual problems, the researchers sought studies that clearly specified the researchers examined sexual dysfunction through direct inquiry or a specific sexual questionnaire.

The researchers found the mean incidence of overall sexual dysfunction on placebo was 14.2%. In stark contrast, sertraline, citalopram and the SSNRI venlafaxine were associated with sexual dysfunction in around 80% of patients.

Paroxetine and fluoxetine were the next worst, with sexual dysfunction rates of over 70%.

Imipramine (an older, tricyclic antidepressant), phenelzine (a MAO inhibitor), duloxetine, escitalopram, and fluvoxamine also returned significantly higher rates of sexual dysfunction than placebo.

Meanwhile, amineptine, agomelatine, bupropion, moclobemide, nefazodone and selegiline showed a low percentage of sexual dysfunction, comparable or in some cases lower than placebo. It’s worth noting that none of these latter drugs are SSRIs. Most of them (amineptine, buproprion, moclobemide, selegiline and, to a lesser extent, nefazodone) act to increase levels of dopamine, widely celebrated as the “feel good” neurotransmitter.

This is in no way an endorsement of these drugs; amineptine and nefazodone have since been withdrawn from the market due to their potential for causing serious liver injury. Buproprion, also used as a smoking withdrawal drug, has been associated with worsening depression and suicidal behaviour[3,4]. Buproprion has become a common overdose drug, with a penchant for producing noxious outcomes in surviving patients. The US National Poison Data System shows that, in adolescents, bupropion overdoses are far more likely to be accompanied by seizure and to cause medical complications coded as a major outcome than TCA overdoses[5].

Selegiline is an interesting compound. It is a monoamine oxidase (MAO) inhibitor best known as an adjunct to L-dopa treatment for Parkinsons patients. In 2006, a transdermal patch version of selegiline was approved by the FDA for treating major depressive disorder. Research to date indicates transdermal selegiline possesses a safety profile that SSRIs and TCAs can only dream of, and it seems to be free of the detrimental sexual effects plaguing the latter drugs. In fact, a meta-analysis of four short-term (6 to 8 weeks), double-blind RCTs in patients with major depressive disorder MDD found a non-significant positive trend of transdermal selegiline on most sexual function scores and significant improvement in sexual satisfaction. For women, there was a significant positive effect on interest in sex, maintaining interest during sex, and satisfaction[6].

SSRI-induced Sexual Dysfunction Can Be Permanent

Unfortunately, sexual dysfunction doesn’t necessarily disappear upon cessation of antidepressants. In fact, sexual impairment continuing long after SSRI termination is so common it even has its own acronym: PSSD (post-SSRI sexual dysfunction).

PSSD can be frighteningly persistent, with numerous permanent cases recorded in the medical literature[7-9]. In 2014, researchers published an analysis of 300 PSSD cases reported on independent drug safety website RxISK.org caused by antidepressants, the anti-baldness drug finasteride and the acne drug isotretinoin (which, like SSRIs, have displayed an alarming penchant for causing PSSD).

The analysis revealed eight subjects suffering PSSD for at least 10 years since stopping SSRIs, and 1 subject reporting continued PSSD despite stopping fluoxetine over 20 years ago. There were consistent reports that the condition made it difficult or impossible to engage in normal romantic relationships, with twenty-five reporting the condition led to the breakup of a relationship, including 9 marriages. Ninety subjects reported their work had been affected, including 12 who had lost jobs[10].

University of Iowa researchers distributed surveys to an online support group for individuals with PSSD. Of 239 respondents, 92% had a history of SSRI use compared to 8% who had only used SNRI or atypical antidepressants. The overall severity of symptoms improved for 45% and worsened or remained the same for 37% of respondents after discontinuing SSRI treatment. The majority rated the effect of PSSD on their quality of life as "extremely negative" (59%) or "very negative" (23%). In keeping with the medical profession’s rose-colored glasses approach to antidepressants, only 12% of respondents reported being warned that sexual dysfunction was a potential side effect of the drugs[11].

The scary thing about PSSD is that researchers still aren’t sure exactly what causes it, but given the benign effect of dopaminergic antidepressants researchers believe the impact of SSRIs and SNRIs on the serotonergic system is to blame.

The other sad reality is that, for many sufferers, an effective remedy remains elusive. There is still no official cure or even accepted treatment.

Despite seriously impaired sexual function, PSSD patients will routinely exhibit normal blood work and healthy hormone levels, and pass physical examinations with flying colours.

In 2008, for example, researchers reported on three otherwise healthy males who suffered irreversible PSSD[12]. The longest-standing case involved a 29-year-old who had been prescribed fluoxetine at age 18. Within 3–4 days of initiating the drug, he went from being an easily aroused teenager to impotent. He no longer experienced nocturnal or morning erections and could not become erect without being physically stimulated. Ejaculation became difficult as "it required a great deal of stimulation to achieve even a weak erection, which would immediately diminish once stimulation was withdrawn." The problem persisted during the eleven years since stopping fluoxetine, but no psychological or physical health problems were found in consultations by two family practice physicians, three urologists, two neurologists, an endocrinologist, and a radiologist. All physical examinations and blood work including testosterone, estrogens, prolactin, and glucose were normal. Ultrasound and infusion studies by the radiologist showed arterial blood flow to the penis was “extremely good” and evinced no leakage from the veins.

To add insult to injury, Prozac did not help his anxiety – the reason for which he was originally prescribed the drug. Instead, it produced weight loss, sleepiness, and short-term memory problems. After two months, his dosage was doubled to 40 mg daily, but this only increased his sleepiness and lethargy. After being on Prozac for a total of four months, he discontinued the drug, but his erectile dysfunction remained.

Otherwise healthy women can also experience significant deterioration of their sexual function. A 2006 case report described a 27-year-old female who, in December 1998, was prescribed 20 mg daily of fluoxetine after presenting with chronic insomnia, anxiety and moderate depression[13]. Within three days of starting the drug, she experienced a dramatic loss of libido, a marked reduction of genital and nipple sensitivity, and loss of orgasm. Despite this, she persisted with the therapy, finally quitting Prozac after seven months of treatment. Seven years later, her sexual dysfunction remained. The ability to reach orgasm did return upon discontinuing fluoxetine, but at a dramatically reduced intensity and with an inability to achieve further orgasm until several days had passed. Her tactile sensitivity had only partially returned. Her loss of libido loss was almost total, compared to a very high libido since puberty. Blood work performed in 2000 and 2005 showed her serum testosterone and estradiol to be in the normal range.

Trying to Find an Effective Treatment

The independent drug discussion website RxISK launched The PSSD Research Fund in June 2022. The RxISK Prize of US $100,000 is also offered to anyone who can provide a cure for persistent sexual side effects after stopping antidepressants, finasteride, or isotretinoin[14].

In a September 2022 paper, Italian researchers claimed partial success in treating PSSD with a variety of strategies, including vortioxetine, bupropion, tadalafil (Cialis), nutraceuticals, and "Vibra-Plus" pelvic vibration in one individual[15]. The sample size was small (13 male patients, mean age 29.5) and the treatments were administered in open-label fashion (ie this was not randomized, blinded research).

They claimed the greatest success was obtained with vortioxetine (Brintillex), an eyebrow-raising claim considering that the drug is an SSRI, developed by Takeda and approved by the FDA in 2013[16].

When one Reddit PSSD-sufferer recently posted that "10mg of vortioxitine has me 95% cured", other posters quickly rebutted that the drug did the exact opposite for them. One user said "made my penis go completely numb" while another complained "Vortioxetine chemically castrated me I have been living with sexual dysfunction, ahnedonia and cognitive impairment since 2019."[17]

In 2019, the same group of Italian researchers published a case study involving an otherwise healthy 23-year-old man with erectile dysfunction and anejaculation that began immediately after he was prescribed citalopram (20 mg/day) for panic disorder[18]. The sexual dysfunction persisted for a year after drug discontinuation, at which point he visited the authors' clinic. His hormonal profile, including prolactin, total and free testosterone, follicle-stimulating hormone, luteinizing hormone, sex hormone-binding globulin, and 17-b-estradiol, were within the normal range.

The authors first tried to treat the patient with mirtazapine, then trazodone and bupropion, without success. The authors then prescribed EDOVIS, an Italian dietary supplement containing L-Citrulline (3 g), tribulus terrestris, peruvian maca, turnera diffusa, muira puama, and folic acid. The authors reported "a nearly complete restoration of sexual function after about 4 months of treatment". At one year-follow up he did not experience any other sexual dysfunction, and his partner was reportedly satisfied with their sexual life.

In 2015, Dutch researchers used low-power laser irradiation to treat a male patient with paroxetine-induced persistent penile anesthesia. Glans penis sensitivity was partially improved, but anejaculation and erectile difficulties remained unchanged[19].

Prior to the recognition of PSSD, researchers had already been conducting research on treating sexual dysfunction in patients concurrently taking antidepressants. Sildenafil, yohimbine, pycnogenol and buproprion (women) are items that achieved some success, but to this author’s knowledge they have not been studied specifically for PSSD[20-22].

Arginine has been shown in some studies to improve low sexual desire in women, but again has not been studied to my knowledge for the treatment of PSSD[23].

Conclusion

When it comes to antidepressants, an ounce of prevention is worth a tanker load of cure. They are a truly garbage class of drug that do not work beyond placebo and active placebo effects. As I will explain in a future project, studies showing their inefficacy have either been quietly shelved or had their endpoints deftly manipulated – and in some cases outright fabricated.

It is hard to achieve truly double-blind conditions in antidepressant studies because the drugs frequently exert numerous recognizable side effects. When trial subjects experience these side effects, they assume they are in the antidepressant group and therefore more likely to believe they are feeling better. Studies comparing antidepressants to active placebo drugs (i.e. non-antidepressant drugs that replicate some of the side effects of antidepressants) show no difference in efficacy.

These drugs do not work because they completely miss the point. Depression and anxiety are not caused by a “chemical imbalance” in the brain – no such chemical imbalance has ever been documented. The “serotonin deficiency/chemical imbalance” hypothesis is a marketing fairy tale. These conditions are caused by such feelings as hopelessness, a lack of connectedness, a lack of meaning to one’s life – all syndromes that are greatly exacerbated by our increasingly dysfunctional, degenerate and polarizing society and culture.

References

1. Montejo AL, et al. Incidence of sexual dysfunction associated with antidepressant agents: a prospective multicenter study of 1022 outpatients. Spanish Working Group for the Study of Psychotropic-Related Sexual Dysfunction. Journal of Clinical Psychiatry, 2001; 62 (Suppl 3): 10-21.

2. Serretti A, Chiesa A. Treatment-emergent sexual dysfunction related to antidepressants: a meta-analysis. Journal of Clinical Psychopharmacology, 2009; 29 (3): 259–266.

3. Thomas KH, et al. Reporting of drug induced depression and fatal and non-fatal suicidal behaviour in the UK from1998 to 2011. BMC Pharmacology and Toxicology, 2014; 15: 54.

4. Kriikku P, Ojanperä I. The relationship between bupropion and suicide in post-mortem investigations. Forensic Science International, 2016 Sep; 266: 343-348.

5. Sheridan DC, et al. Suicidal bupropion ingestions in adolescents: increased morbidity compared with other antidepressants. Clinical Toxicology, May, 2018; 56 (5): 360-364.

6. Clayton AH, et al. Symptoms of sexual dysfunction in patients treated for major depressive disorder: a meta-analysis comparing selegiline transdermal system and placebo using a patient-rated scale. Journal of Clinical Psychiatry, Dec, 2007; 68 (12): 1860-1866.

7. Bolton JM, et al. Genital anaesthesia persisting six years after sertraline discontinuation. Journal of Sex & Marital Therapy, 2006; 32: 327–330.

8. Kauffman RP, Murdock A. Prolonged Post-Treatment Genital Anesthesia and Sexual Dysfunction Following Discontinuation of Citalopram and the Atypical Antidepressant Nefazodone. The Open Women’ Health Journal, 2007; 1: 1-3.

9. Adson DE, Kotlyar M. Premature ejaculation associated with citalopram withdrawal. Annals of Pharmacotherapy, 2003; 37: 1804–1806.

10. Healy D, et al. Enduring sexual dysfunction after treatment with antidepressants, 5α-reductase inhibitors and isotretinoin: 300 cases. International Journal of Risk & Safety in Medicine, 2018; 29: 125–134.

11. Studt A, et al. Characterizing post-SSRI sexual dysfunction and its impact on quality of life through an international online survey. International Journal of Risk & Safety in Medicine, 2021; 32 (4): 321-329.

12. Csoka A, et al. Persistent Sexual Dysfunction after Discontinuation of Selective Serotonin Reuptake Inhibitors. Journal of Sexual Medicine, 2008; 5: 227–233.

13. Csoka AB, Shipko S. Persistent sexual side effects after SSRI discontinuation. Psychotherapy and Psychosomatics, 2006; 75: 187–188.

14. See: https://rxisk.org/post-ssri-sexual-dysfunction-pssd/

15. De Luca R, et al. Cutting the First Turf to Heal Post-SSRI Sexual Dysfunction: A Male Retrospective Cohort Study. Medicines, Sep, 2022; 9 (9): 45.

16. D’Agostino, A, et al. Vortioxetine (Brintellix): A New Serotonergic Antidepressant. P T. Jan, 2015; 40 (1): 36–40.

17. r/PSSD thread. "After 5 years of PSSD, 10mg of vortioxitine has me 95% cured. Please please try this." Reddit.com (accessed Sep 25, 2023). https://www.reddit.com/r/PSSD/comments/16lpn94/after_5_years_of_pssd_10mg_of_vortioxitine_has_me/

18. Calabrò S, et al. Towards improving post-SSRI sexual dysfunction by using nutriceuticals: Lessons from a case study. Journal of Sex & Marital Therapy, 2019: 1–7.

19. Waldinger MD, et al. 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, Apr 15, 2015; 753: 263-268.

20. Luft MJ, et al. Pharmacologic interventions for antidepressant-induced sexual dysfunction: a systematic review and network meta-analysis of trials using the Arizona sexual experience scale. CNS Spectrums, 2021.

21. Taylor MJ, et al. Strategies for managing sexual dysfunction induced by antidepressant medication. Cochrane Database of Systematic Reviews, 2013, Issue 5. Art. No.: CD003382. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003382.pub3/epdf/full

22. Smetanka A, et al. Pycnogenol supplementation as an adjunct treatment for antidepressant-induced sexual dysfunction. Physiology International, 2019; 106 (1): 59–69.

23. Cieri-Hutcherson, NE, et al. Systematic Review of l-Arginine for the Treatment of Hypoactive Sexual Desire Disorder and Related Conditions in Women. Pharmacy, Jun, 2021; 9 (2): 71.