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Post-SSRI Sexual Dysfunction


Page updated to July 2022

  • DEFINITION
  • DRUGS
  • SEXUAL SIDE EFFECTS and PSSD
  • SYMPTOMS
  • DIAGNOSIS 
  • RECOGNITION
  • PREVALENCE
  • ETIOLOGY
  • TREATMENTS
  • SIMILAR SYNDROMES
  • REFERENCES


DEFINITION

Post-SSRI Sexual Dysfunction (PSSD) is the name for an iatrogenic condition caused by previous treatment with serotonin reuptake inhibitor drugs, particularly SSRIs and SNRIs, which are now the most prescribed classes of antidepressant, but also used for a growing variety of problems, such as anxiety and panic attacks, obsessive compulsive disorder, sleep and eating disorders, fibromyalgia and chronic pain, premature ejaculation and others.


DRUGS

The SSRI and SNRI classes include numerous active ingredients, listed below by their respective trade names:

SSRIs

  • fluoxetine (US: Prozac, UK: Prozac, Oxactin)
  • sertraline (US: Zoloft, UK: Lustral)
  • citalopram (US: Celexa, UK: Cipramil) 
  • escitalopram (US: Lexapro, UK: Cipralex)
  • fluvoxamine (US: Luvox, UK: Faverin)
  • paroxetine (US: Paxil, UK: Seroxat)
  • dapoxetine (Priligy)  

SNRIs

  • desvenlafaxine (US: Pristiq)
  • duloxetine (US: Cymbalta)

Other serotonin reuptake inhibitor (SRI) drugs include SRI tricyclic antidepressants, SRI antihistamines, tetracycline antibiotics such as doxycycline, and analgesics such as tramadol.

SEXUAL SIDE EFFECTS and PSSD

Treatment with SSRI/SNRI drugs frequently causes sexual side effects in men and women that can involve every aspect of sexual function: genital sensitivity, desire, arousal, and orgasm.

While early studies by pharmaceutical companies reported an incidence of sexual side effects in about 1 in 10 cases among users (1), more and more studies conducted after the drugs went on the market revealed that this was a greatly underestimated figure. Postmarketing studies, in fact, report estimates exceeding 50 percent among consumers (2, 3). Sexual side effects, after all, are also the most common cause for which those taking SSRIs/SNRIs decide to discontinue treatment (4).

It is generally believed that sexual side effects of SSRIs/SNRIs are dose-dependent and reversible upon discontinuation of the drug (45); but in more recent times, more and more reports received by pharmacovigilance and clinical case reports in the literature have shown that in some cases sexual dysfunction caused by serotonergic treatment has persisted and in other cases has worsened or appeared after discontinuation of treatment, resulting in Post-SSRI Sexual Dysfunction (PSSD), a term that appeared in the literature in 2006 along with the first described case reports (12, 13, 14).

In some cases, taking SSRIs and discontinuing them causes Persistent Genital Arousal Disorder (PGAD), which predominantly afflicts women and consists of irritating sensations of genital arousal unaccompanied by sexual desire, a condition that can be extremely uncomfortable for patients and currently has significant gaps on etiology and treatment (6, 7, 8, 9).

SYMPTOMS

PSSD symptomatology may manifest as a continuation of dysfunction that began during SSRI/SNRI treatment, or it may appear or worsen only at the time of treatment discontinuation and in any case persist after treatment is stopped (10).

It may set in after a few doses of treatment, as in an adverse reaction, or after years and years of treatment that gave "no particular problems." The persistence of symptoms does not have a predictable outcome; it can go on for months, years, be permanent. The mode of drug discontinuation (gradual or abrupt) for now has not been shown to be decisive on the risks of PSSD (although gradual reduction is always advisable).


SEXUAL SYMPTOMS

May vary from case to case both in presence and severity and include:
  • reduction or disappearance of libido (sexual desire);
  • reduction or disappearance of excitatory response, mental and physical, to sexual stimuli;
  • erectile dysfunction of penis and clitoris; reduced lubrication;
  • disappearance of spontaneous, morning and nighttime erections;
  • orgasm disorders, such as anorgasmia (orgasm becoming unattainable), alterations in the intensity of orgasm, anhedonic orgasm ("mechanical" and no longer accompanied by sensations of pleasure);
  • premature or delayed ejaculation, abnormalities in sperm quantity and consistency;
  • genital hypoesthesia, i.e., a reduction in erogenous/sexual sensations and/or even tactile sensations, to the point of true genital anesthesia;
  • alterations in skin sensitivity in other areas of the body, such as the nipples.

OTHER SYMPTOMS

In the literature, but more so in patient communities, it is becoming increasingly clear that alongside the sexual symptoms of PSSD there are often additional severe symptoms induced by previous SSRI/SNRI treatment that characterize a more complex Post-SSRI Syndrome, including:
  • emotional blunting (there may be even severe reduction in the perception of emotions and feelings);
  • anhedonia (it becomes more difficult or even impossible to perceive pleasure in hedonistic activities, even those that used to give pleasure);
  • cognitive dysfunction, difficulty in mental visualization, memory problems.

DIAGNOSIS

Those who experience such symptoms, especially in overt form, and can make a comparison with the "before treatment" will plausibly have little doubt about the pharmacological nature of such problems, so much so as to contradict any hasty diagnostic re-addressing that may unfortunately come from clinicians.

Although the symptomatology that characterizes PSSD might be judged by the latter as "symptoms of the underlying illness," and mistakenly attributed to depressive disorders, anxiety, psychosomatization, autosuggestion, etc., several elements will be helpful in discerning PSSD even to an outside eye such as that of a clinician.

Careful listening to the patient about the type of symptoms and their onset will be crucial; the 2021 paper on Diagnostic Criteria (46) also proposes the following lines:

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.

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.

Ancillary sexual symptoms may include:
  • genital pain
  • reduced nipple sensitivity
  • decreased or loss of nocturnal erections (males)
  • reduced ejaculatory force (males)
  • flaccid glans during erection (males)
  • decreased vaginal lubrication (females).
Ancillary non-sexual symptoms may include:
  • emotional numbing
  • depersonalization
  • other sensory problems involving skin, smell, taste or vision
  • cognitive impairment.

RECOGNITION

From 2006 to the present, more and more clinical cases of PSSD have been brought to the literature, with several urgings by the authors to investigate the risks and causes of the condition, to keep patients' sexual function changes monitored before, during, and after treatment, and to ensure that patients have an Informed Consent before prescribing SSRI and SNRI antidepressants because of such significant risks (41)

In June 2019, following a Petition initiated by Professor David Healy and signed by numerous researchers and specialists (42), the European Medicines Agency (EMA) concluded a review with a Recommendation for all SSRI and SNRI drug manufacturers to update package inserts with the warning that "In some cases, symptoms of sexual dysfunction may persist following discontinuation of treatment" (44).

Not long after, Health Canada and Hong Kong also took similar steps to warn physicians and patients of the risks of persistent sexual dysfunction post SSRI/SNRI.


PREVALENCE

While it has been observed that sexual side effects during treatment with SSRIs are experienced by the majority of users, the prevalence of PSSD is still unknown, and some researchers have planned an epidemiological study to address this gap.

Multiple factors make several authors agree that PSSD is an underestimated problem:
  • the sensitive nature of the topic and the stigma attached to sexuality easily lead physicians and patients to avoid the topic;
  • the stigma attached to the "psychiatric patient" might influence the type of response (denialist and "psychiatric") by physicians, as revealed by a survey of patients' experiences when they approached health professionals (43);
  • the initial erroneous estimates of antidepressant-induced sexual side effects that indicated a prevalence of only 1 in 10 cases;
  • the lack, for many years, of reference to PSSD on package inserts;
  • physicians' lack of knowledge of the syndrome and thus failure to recognize cases of PSSD;
  • the referral of patients by clinicians to psychological explanations or other psychopharmacological treatments;
  • the failure to report these adverse effects to pharmacovigilance bodies.

ETIOLOGY


The neurobiological cause underlying the persistent symptoms of PSSD/Post-SSRI Syndrome is currently unknown.

Several hypotheses have been put forward, and some lines of research are ongoing and will be able to move forward through fundraising. GoFund for Melcangi Research - Rxisk Fundraising.

Several hypotheses have been formulated from already observed mechanisms implicated in sexual side effects during antidepressant use.


Mechanisms underlying sexual dysfunction induced by serotonergic antidepressants

These mechanisms include SSRI-induced neuroendocrine alterations such as increased serotonin and prolactin, blockade of a1-adrenergic receptors, decreased dopamine, testosterone, and oxytocin, and reduced nitric oxide synthesis. (15)

In addition, some neurochemical changes related to sexual dysfunction during antidepressant use have been noted in the peripheral nervous system. This is noteworthy because 95% of serotonin receptors are located outside the brain. It has been hypothesized that PSSD symptoms see serotonin levels in the peripheral nerves involved. (15)

Ben-Sheetrit et al. hypothesized that serotonergic neurotoxicity might also play a role in PSSD by a mechanism similar to 3,4-methylenedioxymethamphetamine (MDMA), which stimulates serotonin release and inhibits serotonin uptake. MDMA can cause persistent sexual dysfunction long after its discontinuation, with axonal damage as a proposed mechanism. (16)

The authors suggested that there may be a role for individual vulnerability to serotonin because most patients on SSRIs do not develop PSSD. (17)

Other mechanisms implicated in the sexual side effects of serotonergic antidepressants are serotonin-dopamine interaction, effects on proopiomelanocortin and melanocortin, and dysregulation of the hypothalamic-pituitary-testicle axis. (18)


Epigenetic alterations

The 5-HT1A receptor is the most prevalent serotonin receptor in the nervous system (19). It acts mainly as an autoreceptor with feedback functions, decreasing the release of serotonin when it is too high (20). It is believed that in order for antidepressant drugs to exert their serotonergic effect, the autoreceptor must desensitize, thus disrupting the feedback mechanism. This would explain the latency of about 2 weeks between the first intake of the drug and the antidepressant effect of the drug (21). Desensitization and upregulation of 5-HT1A are involved in the regulation of the sexual response (22), inhibiting sexual function and dopaminergic transmission, which is responsible, among many other things, for hedonic sensations (23).

Csoka et al. hypothesized that 5-HT1A receptors may remain desensitized and persistently upregulated by alterations in gene expression following chronic exposure to SSRIs (24) and subsequently conducted a study on DNA methylation induced by the SSRI citalopram (25).


Peripheral disorders

A 2014 study by Waldinger et al. on a man with post-SSRI syndrome, who among many symptoms had severe genital anesthesia, shows that the patient partially recovered genital sensitivity to temperatures following a low-power laser treatment performed on the genitals, which leads the authors to believe that the alterations that result in some PSSD symptoms may localize in the skin, involve Transient Receptor Potential Channels (TRPs) of nerve endings and mechanothermic-and chemosensitive receptors resulting in penile anesthesia. (26)


Neuroendocrine alterations

Melcangi et al. in a 2018 review compared and noted significant symptom overlap between PSSD and Post-Finasteride Syndrome (PFS), hypothesizing that they may have etiologic aspects in common (11). The team further investigated this by looking for clues in neurosteroid and microbiota alterations in rats previously treated with the SSRI paroxetine (27, 28).


Animal studies

Some animal studies have been conducted to determine the long-term effect of SSRIs on sexual function.

Raap et al. found that fluoxetine treatment on rats results in persistent desensitization of 5HT1A even after discontinuation of the drug. (32)

Sukoff-Rizzo et al. observed that 5-HT1A antagonists reversed and prevented sexual dysfunction in rats given fluoxetine. (33) Further studies have suggested that SSRI administration in young rats results in persistent sexual side effects in adulthood. (34, 35)

Gouvêa et al. administered fluoxetine to pregnant rats and observed impaired sexual motivation in the offspring of these rats once they became adults. (36)

A systematic review of animal studies documented evidence of persistent sexual behavioral changes in rats that had been exposed to SSRIs at a young age. (37)

Healy et al. observed persistent alterations in cell bioelectricity (resting potential) in planaria subjected to brief SSRI exposures, which could result in long-term changes in electrophysiology and signaling. (38)


TREATMENTS

Medications that are sometimes used as antidotes to the side effects of SSRI antidepressants while taking them (e.g., bupropion) have not been found to be a viable solution for PSSD.

In the web community such as SubReddit and the PSSDforum, one can find many experiences on the effects of numerous treatments, drugs and supplements taken as an attempt to treat PSSD symptoms; however, the overall picture is confusing and varied, and the effects are subjective and not without risk.

There are just a couple of case reports in the literature on subjects who derived some benefits on PSSD symptoms: a man who partially recovered sensitivity to genital temperatures through a low-power laser treatment (26), and a boy with PSSD who recovered sexual function with an l-citrulline supplement (40).


SIMILAR SYNDROMES

Some reviews (10, 11) have pointed out a significant overlap between the persistent symptoms of PSSD, those of Post-Finasteride Syndrome (PFS), which affects some young men who have used finasteride to counteract androgenetic alopecia, and Post-Accutane Syndrome (PAS) caused by isotretinoin taken as an anti-acne treatment, formulating the hypothesis that these syndromes may have a common etiopathogenesis (mechanism of action) yet to be elucidated. (39, 11, 6).



REFERENCES

1) J. B. Herman, A. W. Brotman, M. H. Pollack, “Fluoxetine-induced sexual dysfunction”, The Journal of Clinical Psychiatry, vol. 51, nº 1, 1º gennaio 1990, pp. 25–27. PMID: 2295587

2) Agnes Higgins, Michael Nash, Aileen M Lynch, “Antidepressant-associated sexual dysfunction: impact, effects, and treatment”, Drug, healthcare and patient safety, vol. 2, 9 settembre 2010, pp. 141–150. DOI:10.2147/DHPS.S7634

3) Mitra Safa, Saeid Sadr, Firouzeh Talischi, “Study of effects of selective serotonin reuptake inhibitors on stages of sexual function in Iranian patients with major depressive disorder”, Therapeutic Advances in Psychopharmacology, vol. 3, nº 6, 1º dicembre 2013, pp. 306–313. DOI:10.1177/2045125313488906

4) Kennedy SH, Rizvi S (April 2009). “Sexual dysfunction, depression, and the impact of antidepressants”, Giornale di psicofarmacologia clinica, 29 (2): 157–64. doi:10.1097/jcp.0b013e31819c76e9. PMID 19512977. S2CID 739831.

5) David Healy, “Antidepressants and sexual dysfunction: a history”, Journal of the Royal Society of Medicine; 0(0) 1–3. PMID: 31972096 DOI: 10.1177/0141076819899299

6) David Healy, “Post-SSRI sexual dysfunction & other enduring sexual dysfunctions”, Epidemiol Psychiatr Sci. 2019 Sep 23;29:e55. PMID: 31543091 DOI: 10.1017/S2045796019000519

7) Goldmeier D, Leiblum SR (April 2006). “Persistent genital arousal in women — a new syndrome entity”. Int J STD AIDS 17 (4): 215–6. PMID 16595040 DOI:10.1258/095646206776253480

8) Leiblum SR, Goldmeier D (2008). “Persistent genital arousal disorder in women: case reports of association with anti-depressant usage and withdrawal”. J Sex Marital Ther 34 (2): 150–9. PMID: 18224549 DOI: 10.1080/00926230701636205

9) Goldmeier D, Bell C, Richardson D (March 2006). “Withdrawal of selective serotonin reuptake inhibitors (SSRIs) may cause increased atrial natriuretic peptide (ANP) and persistent sexual arousal in women?”. J Sex Med 3 (2): 376. PMID: 16490037 DOI: 10.1111/j.1743-6109.2006.00224.x

10) David Healy, Joanna Le Noury, Derelie Mangin, “Enduring sexual dysfunction after treatment with antidepressants, 5α-reductase inhibitors and isotretinoin: 300 cases”, International Journal of Risk & Safety in Medicine, Preprint, Preprint, 1º maggio 2018, pp. 1–10. PMID: 29733030, PMCID: PMC6004900, DOI: 10.3233/JRS-180744

11) Silvia Giatti, Silvia Diviccaro, Giancarlo Panzica, “Post-finasteride syndrome and post-SSRI sexual dysfunction: two sides of the same coin?”, Endocrine, 19 aprile 2018, DOI:10.1007/s12020-018-1593-5.

12) Bolton JM, Sareen J, Reiss JP (2006). “Genital anaesthesia persisting six years after sertraline discontinuation”. J Sex Marital Ther 32 (4): 327–30. PMID 16709553 DOI:10.1080/00926230600666410.

13) Csoka AB, Shipko S (2006). “Persistent sexual side effects after SSRI discontinuation”. Psychother Psychosom 75 (3): 187–8. DOI:10.1159/000091777, PMID 16636635

14) Audrey S. Bahrick (2008) “Persistence of Sexual Dysfunction Side Effects after Discontinuation of Antidepressant Medications: Emerging Evidence” The Open Psychology Journal, 1, Article 42-50. DOI:10.2174/1874350100801010042

15) Antonei Csoka, Audrey Bahrick, Olli-Pekka Mehtonen, “Persistent Sexual Dysfunction after Discontinuation of Selective Serotonin Reuptake Inhibitors”, The Journal of Sexual Medicine, vol. 5, nº 1, 1º gennaio 2008, pp. 227–233, DOI:10.1111/j.1743-6109.2007.00630.x/abstract.

16) Parrott A., “Recreational ecstasy/MDMA, the serotonin syndrome, and serotonergic neurotoxicity”, Pharmacol Biochem Behav. 2002;71:837–844. PMID: 11888574 DOI: 10.1016/s0091-3057(01)00711-0

17) Kauffman RP, Murdock A (2007). “Prolonged Post-Treatment Genital Anesthesia and Sexual Dysfunction Following Discontinuation of Citalopram and the Atypical Antidepressant Nefazodone”. The Open Women's Health Journal 1: 1–3

18) Areeg Bala, Hoang Minh Tue Nguyen e Wayne J. G. Hellstrom, “Post-SSRI Sexual Dysfunction: A Literature Review”, Sexual Medicine Reviews, 1º agosto 2017, DOI:10.1016/j.sxmr.2017.07.002.

19) Jiang Z., Qi W., Wang J., Luo F., “Chronic Administration of 5-HT1A Receptor Agonist Relieves Depression and Depression-Induced Hypoalgesia”, The Scientific World Journal, 2014 Jan 23;2014:405736, PMID: 24592167, PMCID: PMC3921963, DOI: 10.1155/2014/405736.

20) Yevtushenko O.O., Reynolds G.P., “Functional Pharmacogenetics of Serotonin Receptors”, Psychiatric Drug Action. In Müller C.P., Jacobs B.L. Handbook of Behavioral Neuroscience. Volume 21, (pp 791-806). DOI: 10.1016/S1569-7339(10)70110-7

21) Castro E., M., Diaz, A., del Olmo, E., and Pazos, A., “Chronic fluoxetine induces opposite changes in G protein coupling at pre and postsynaptic 5-HT1A receptors in rat brain”, Neuropharmacology. 2003 Jan;44(1):93-101, PMID: 12559126 DOI: 10.1016/s0028-3908(02)00340-4

22) Popova NK, Amstislavskaya TG, “Involvement of the 5-HT(1A) and 5-HT(1B) serotonergic receptor subtypes in sexual arousal in male mice”, Psychoneuroendocrinology. 2002 Jul;27(5):609-18, PMID: 11965359 DOI: 10.1016/s0306-4530(01)00097-x

23) Berridge K.C., Kringelbach M.L., “Pleasure systems in the brain”. Neuron, 2015 May 6; 86(3): 646–664, PMID: 25950633 PMCID: PMC4425246 DOI: 10.1016/j.neuron.2015.02.018

24) Csoka AB, Szyf M (November 2009). “Epigenetic side-effects of common pharmaceuticals: a potential new field in medicine and pharmacology”. Med. Hypotheses 73 (5): 770–80.doi:10.1016/j.mehy.2008.10.039. PMID 19501473.

25) Kanherkar RR, Getachew B, Ben-Sheetrit J, Varma S, Heinbockel T, Tizabi Y, Csoka AB, “The Effect of Citalopram on Genome-Wide DNA Methylation of Human Cells”, Int J Genomics. 2018 Jul 25;2018:8929057. DOI: 10.1155/2018/8929057. eCollection 2018.

26) Marcel D. Waldinger, Ruben S. van Coevorden, Dave H. Schweitzer, “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, vol. 753, 15 aprile 2015, pp. 263–268, DOI:10.1016/j.ejphar.2014.11.031.

27) Silvia Giatti, Silvia Diviccaro, Lucia Cioffi, Eva Falvo, Donatella Caruso, Roberto C. Melcangi, “Effects of paroxetine treatment and its withdrawal on neurosteroidogenesis”, Psychoneuroendocrinology, Volume 132, October 2021, 105364.

28) Silvia Diviccaro, Silvia Giatti, Lucia Cioffi, Eva Falvo, Rocco Piazza, Donatella Caruso, Roberto C. Melcangi, “Paroxetine effects in adult male rat colon: Focus on gut steroidogenesis and microbiota”, Psychoneuroendocrinology, Volume 143, September 2022, 105828.

29) Irwig MS, Kolukula S., “Persistent sexual side effects of finasteride for male pattern hair loss”, J Sex Med. 2011 Jun;8(6):1747-53. DOI: 10.1111/j.1743-6109.2011.02255.x. Epub 2011 Mar 18.

30) Melcangi RC. et al, "Neuroactive steroid levels and psychiatric and andrological features in post-finasteride patients", J Steroid Biochem Mol Biol. 2017 Jul;171:229-235. doi: 10.1016/j.jsbmb.2017.04.003. Epub 2017 Apr 10.

31) Melcangi RC. et al, "Altered methylation pattern of the SRD5A2 gene in the cerebrospinal fluid of post-finasteride patients: a pilot study", Endocr Connect. 2019 Aug; 8(8): 1118–1125. doi: 10.1530/EC-19-0199 PMCID: PMC6652249 PMID: 31272082


32) D. K. Raap, F. Garcia, N. A. Muma, “Sustained desensitization of hypothalamic 5-Hydroxytryptamine1A receptors after discontinuation of fluoxetine: inhibited neuroendocrine responses to 8-hydroxy-2-(Dipropylamino)Tetralin in the absence of changes in Gi/o/z proteins”, The Journal of Pharmacology and Experimental Therapeutics, vol. 288, nº 2, 1º febbraio 1999, pp. 561–567, PMID: 9918559.

33) Sukoff Rizzo SJ et al., "5-HT(1A) receptor antagonism reverses and prevents fluoxetine-induced sexual dysfunction in rats", Int J Neuropsychopharmacol. 2009 Sep;12(8):1045-53. Epub 2009 May 13. PMID: 19435548 DOI: 10.1017/S1461145709000406

34) Trynke R. de Jong, Liselore J.A.E. Snaphaan, Tommy Pattij, Jan G. Veening, Marcel D. Waldinger, Alexander R. Cools, Berend Olivier, “Effects of chronic treatment with fluvoxamine and paroxetine during adolescence on serotonin-related behavior in adult male rats”, European Neuropsychopharmacology, vol. 16, nº 1, --, pp. 39–48, PMID: 16107310 DOI:10.1016/j.euroneuro.2005.06.004.

35) Maciag D, Simpson KL, Coppinger D, et al. (Gennaio 2006), “Neonatal Antidepressant Exposure has Lasting Effects on Behavior and Serotonin Circuitry”. Neuropsychopharmacology 31 (1): 47–57, PMC 3118509. PMID 16012532. DOI:10.1038/sj.npp.1300823

36) Gouvêa TS, Morimoto HK, de Faria MJ, et al., “Maternal exposure to the antidepressant fluoxetine impairs sexual motivation in adult male mice”, Pharmacol Biochem Behav 2008;90:416-419. PMID: 18457868 DOI: 10.1016/j.pbb.2008.03.025.

37) Anders Lykkemark Simonsen, Pia Brandt Danborg, Peter Christian Gøtzsche, “Persistent sexual dysfunction after early exposure to SSRIs: Systematic review of animal studies”, The International Journal of Risk & Safety in Medicine, vol. 28, nº 1, 16 marzo 2016, pp. 1–12, PMID: 27176752 DOI:10.3233/JRS-160668.

38) David Healy, Joshua LaPalme, Michael Levin, “Post-SSRI Sexual Dysfunction: A Bioelectric Mechanism?”, Bioelectricity, 12 Dec 2019, doi.org/10.1089/bioe.2019.0010

39) C. Hogan, J. Le Noury, D. Healy, D. Mangin (2014). "One hundred and twenty cases of enduring sexual dysfunction following treatment", Archiviato il 1º agosto 2014 in Internet Archive. International Journal of Risk & Safety in Medicine 26 (2014) 109–116 DOI:10.3233/JRS-140617. PMID 24902508.

40) Calabrò RS et al., “Towards Improving Post-SSRI Sexual Dysfunction by Using Nutriceuticals: Lessons from a Case Study”, J Sex Marital Ther. 2019;45(6):562-565. PMID: 30640584 DOI: 10.1080/0092623X.2018.1556755. Epub 2019 Feb 13.

41) Bahrick AS, Harris MM (2009). “Sexual Side Effects of Antidepressant Medications: An Informed Consent Accountability Gap”. Journal of Contemporary Psychotherapy 39, 135–143.

42) David Healy, “Citizen petition: Sexual side effects of SSRIs and SNRIs”, International Journal of Risk & Safety in Medicine, Preprint, Preprint, 1º maggio 2018, pp. 1–13. PMID: 29733031 DOI:10.3233/JRS-180745

43) David Healy, Joanna Le Noury, Dee Mangin, “Post-SSRI sexual dysfunction: Patient experiences of engagement with healthcare professionals”, The International Journal of Risk & Safety in Medicine, vol. 30, nº 3, 2019, pp. 167–178. PMID: 31450514 DOI: 10.3233/JRS-191005.


45) Jody Rothmore, “Antidepressant‐induced sexual dysfunction”, Med J Aust 2020; 212 (7), DOI: 10.5694/mja2.50522

46) David Healy et al., “Diagnostic criteria for enduring sexual dysfunction after treatment with antidepressants, finasteride and isotretinoin”, International Journal of Risk & Safety in Medicine, vol. 33, no. 1, pp. 65-76, 2022, DOI: 10.3233/JRS-210023