Jump to content

Post-SSRI sexual dysfunction

From Wikipedia, the free encyclopedia

This is an old revision of this page, as edited by Adrian Tofei (talk | contribs) at 22:26, 20 January 2023 (→‎Medications known to cause PSSD: aripriprazole added to the list, based on the quoted study). The present address (URL) is a permanent link to this revision, which may differ significantly from the current revision.

Post-SSRI sexual dysfunction
Other namesPost-SSRI syndrome
Chemical structure of sertraline (Zoloft), an SSRI that is known to cause PSSD in some users
Chemical structure of sertraline (Zoloft), an SSRI that is known to cause PSSD in some users
SymptomsSexual dysfunction (e.g. erectile dysfunction, loss of vaginal lubrication, anorgasmia), reduced libido, cognitive dysfunction, anhedonia
Usual onsetAge-independent
DurationMonths to years after stopping an SRI
CausesSerotonin reuptake inhibitor (SRI) medications, most commonly selective serotonin reuptake inhibitors (SSRIs)
Risk factorsUnknown due to lack of data
Diagnostic methodSexual dysfunction symptoms that persist longer than 3-6 months after stopping an SRI, in the absence of other conditions/medications that could account for symptoms
TreatmentNo known reliable treatment
FrequencyUnknown due to lack of data

Post-SSRI sexual dysfunction (PSSD),[1][2][3][4] also referred to as post-SSRI syndrome,[5] is a disorder in which individuals who have been administered selective serotonin reuptake inhibitors (SSRIs) or other serotonin reuptake-inhibiting (SRI) drugs experience persistent changes in sexual function for an extended period (at least three[6] to six months, up to years or decades[7]) after ceasing to take the drug. PSSD symptoms have also been reported after ceasing drugs that are not SSRI or SRI.[8]

First formally acknowledged in the medical literature in 2006,[9][10] a growing body of evidence has led PSSD to slowly gain recognition by researchers and medical professionals as a distinct clinical pathology from antidepressant discontinuation syndrome and major depressive disorder.[11][12][13] The reported symptoms of PSSD commonly include a reduction in the ability to experience sexual desire or arousal, persistent erectile dysfunction in males or loss of vaginal lubrication in females, an enduring inability to orgasm or loss of pleasurable sensation associated with orgasm, and a loss of sensitivity in the genitals or other erogenous zones. Additional non-sexual symptoms are also commonly described, including emotional numbing, anhedonia, depersonalization or derealization, and cognitive impairment.[6][14][12] These symptoms are reported in varying combinations and with varying degrees of severity by individuals who experience PSSD.[15] The disorder is very commonly reported as significantly detrimental to the sufferer's overall quality of life.[16][13]

There is currently no medical consensus on how to effectively treat PSSD.[13] To date, the mechanism by which SRIs may induce PSSD is unknown,[5][13][12] as is the exact mechanism by which SRIs induce sexual dysfunction in many patients actively taking the drug.[17] It is likewise unclear how common the problem is among individuals who have stopped taking SRIs, or what the risk factors are for developing the problem.[18] The symptoms of PSSD are largely shared with post-finasteride syndrome (PFS) and post-retinoid sexual dysfunction/post-Accutane syndrome (PRSD/PAS), two other poorly-understood iatrogenic conditions which have been suggested to share a common etiology with PSSD despite being caused by different types of medication.[19]

Symptoms and diagnosis

According to diagnostic criteria submitted by David Healy et al. in 2022, a diagnosis of PSSD requires that the subject has previously taken an SSRI or other SRI, and has experienced new (i.e. not present before starting the SRI) symptoms of sexual dysfunction for at least three months after the last dose of the SRI;[6] others have proposed a timeline of at least six months of sexual dysfunction symptoms after cessation of the SRI. Other potential causes of sexual dysfunction should be considered and excluded before a diagnosis is made.[13][6]

The following symptoms have been reported in association with PSSD:

In many cases, PSSD sufferers have reported that their symptoms will transiently improve for short periods (usually no more than one or two days) before returning to their previous state.[10]

Duration of symptoms

The length of time during which PSSD symptoms persist appears to vary among patients, with some cases resolving in a matter of months and others persisting for years or even decades; one analysis of patient reports in the Netherlands submitted between 1992 and 2021 listed a case which had reportedly persisted for 23 years.[7]

Prevalence and risk

Medications known to cause PSSD

Although PSSD is most commonly reported following cessation of SSRIs, cases have also been reported following the use of serotonin-norepinephrine reuptake inhibitors (SNRIs), SRI tricyclic antidepressants, atypical antidepressants such as mirtazapine, SRI antihistamines, tetracycline antibiotics such as doxycycline, analgesics such as tramadol, and antipsychotics such as aripriprazole.[6][11][8]

The following medications have been recorded as causing PSSD in some fraction of users:[15]

Selective serotonin reuptake inhibitors (SSRIs)

Serotonin-norepinephrine reuptake inhibitors (SNRIs)

Other medications

Frequency of PSSD

Due to a lack of large-scale, well-controlled studies, there are currently no reliable estimates of how many individuals worldwide suffer from PSSD, nor what fraction of SRI users develop PSSD after stopping the drug.

Data released in 2021 under the UK's Freedom of Information Act by the Medicines and Healthcare Products Regulatory Agency showed that in a total of 1654 cases of adverse effects from SSRIs, in 1069 cases the reaction did not continue after the drug was withdrawn, in 225 cases the reaction continued after the drug was withdrawn with the recovery time being unknown, and in 144 cases the reaction continued after the drug was withdrawn and the recovery time was known.[26]

A retrospective review published in The Journal of Urology in 2020 stated that between 2009 and 2019, 4% of the male patients whose charts were assessed in the review (43 patients total) met the criteria for PSSD, having displayed sexual dysfunction symptoms for longer than 6 months after stopping an SSRI.[27]

SRI dosage response and other risk factors

It is unclear whether there is a relationship between the amount of time a person has been taking an SRI and the likelihood of developing PSSD. In one case study published in 2006, persistent sexual dysfunction was evident for seven years after taking an SRI for a period of only five weeks;[9] there have been reports of cases developing after only a few, or even single doses of an SRI.[13]

An online survey of 135 subjects who self-reported as having PSSD found that the majority of respondents were young heterosexual males who had taken relatively high doses of an SSRI or SNRI.[28] Of these, 118 subjects exhibited sexual dysfunction symptoms while taking the drug, while 17 subjects only developed symptoms after stopping the drug.[28]

Acknowledgements and warnings issued

In medication leaflets and labels

The following SSRI medications have been issued with informational leaflets and/or labels containing warnings about post-discontinuation sexual side effects:

In Diagnostic and Statistical Manual of Mental Disorders

In the United States, the DSM-5 serves as the principal authority for psychiatric diagnoses published by American Psychiatric Association. The DSM-5 published in 2013 states that:[39]

In some cases, serotonin reuptake inhibitor induced sexual dysfunction may persist after the agent is discontinued

— page 449

In Textbook of Rare Sexual Medicine Conditions

This textbook is written and edited by international experts in the field of sexual medicine and provides multidisciplinary information for medical practitioners, including biological-psychological-social approaches to disease diagnosis and treatment.[40] The textbook includes an entire chapter dedicated to PSSD:[41]

PSSD is unrelated to any pre-existing or reactive mental health issue, medical condition, or substance abuse. PSSD is difficult to diagnose and should be done by analysing the patient’s drug history, the onset of symptoms, and sexual function before starting such a medication. Key symptoms are genital anaesthesia, erectile dysfunction, and pleasureless orgasm.

— Yacov Reisman, James G. Pfaus & Lior Lowenstein 

In Psychiatry and Sexual Medicine: A Comprehensive Guide for Clinical Practitioners

This textbook contains a section on PSSD on pages 353-371:[42][43]

Most patients will experience that the side effects will disappear when the treatment is stopped. However, a yet underinvestigated and poorly understood condition is sexual dysfunction persisting for weeks, months, or even years after the termination of pro-serotonergic treatment, named the post-serotonin reuptake inhibitor (or post-SSRI) sexual dysfunction—PSSD. Common symptoms include genital anesthesia (decrease in sensation and numbness in genital area), pleasureless or weak orgasms, decreased sexual drive, erectile dysfunction, and premature jaculation in males, and decreased vaginal lubrication and nipple sensitivity in females. The prevalence of PSSD is unknown and only case reports exist. The pathogenesis has not been established, but different mechanisms such as epigenetic gene expression theory, persisting 5-HT1A receptor downregulation, neurohormonal changes, serotonin neurotoxicity, and alteration of receptor ion channel transduction are discussed [28–30]. Symptoms of persistent genital arousal disorder (PGAD) were also reported after the cessation of SSRI treatment (see Chap. 32 for more information on PGAD)

By health and medicines agencies

On the 11th of June 2019 the Pharmacovigilance Risk Assessment Committee of the European Medicines Agency concluded that a possible relationship exists between SSRI use and persistent sexual dysfunction after cessation of use. The committee concluded that a warning should be added to the label of SSRIs and SNRIs regarding this possible risk.[44][45]

The European Medicines Agency has issued the following warning:[46]

Selective serotonin reuptake inhibitors (SSRIs)/serotonin norepinephrine reuptake inhibitors (SNRIs) may cause symptoms of sexual dysfunction (see section 4.8). There have been reports of long-lasting sexual dysfunction where the symptoms have continued despite discontinuation.

Health Canada has issued a similar warning, requiring all medications to include the following warning in their leaflets:[45][47]

Health Canada will work with manufacturers to update the product safety information for all SSRIs and SNRIs to recommend that healthcare professionals inform patients about the potential risk of long lasting (possibly weeks to years) sexual dysfunction despite discontinuation of SSRIs or SNRIs.

The Hong Kong Department of Health released a warning about PSSD in 2021.[48][49]

The NHS has published the following statement regarding Sertraline (Zoloft) on their website:[50]

Long-term side effects – A few people may get sexual side effects, such as problems getting an erection or a lower sex drive. In some cases these can continue even after stopping the medicine. Speak to your doctor if you are worried.

Research and potential etiologies

The mechanism by which SRIs induce PSSD, as well as the reason why the syndrome persists long after stopping SRIs, is unknown.[12][5][13] However, a number of studies have resulted in potentially relevant findings that may point to a mechanism for PSSD. A combination of different factors may be responsible for causing PSSD.[13]

Potential role of SSRI-induced epigenetic changes

SSRIs and other antidepressants have been established to induce epigenetic changes by altering DNA and histone methylation states.[51][52] Epigenetic changes in the brain are known to play a role in memory, learning, depression, addiction and various other cognitive phenomena. DNA methylation patterns and histone methylation-dependent changes to chromatin structure in neurons can remain stable for long periods of time.[53]

In 2012, a study in rats found that both paroxetine and imipramine (a tricyclic antidepressant) indirectly reduced DNA methyltransferase 1 (DNMT1) activity via reduced expression and activity of the DNMT1-stimulating histone methyltransferase G9a; addition of recombinant G9a reversed the effects of the antidepressant on DNMT1 function.[54]

A literature review published in 2017 states that:[13]

Long-term usage of SSRIs is hypothesized to cause persistent downregulation of 5HT1A (even after discontinuation of SSRIs) by epigenetic changes in the form of increased expression of methyl binding proteins MeCP2 and MBD1. This leads to more production of HDAC2 mRNA and lowers the production of histone H3 deacetylase.

The 5-HT1A receptor is involved with a variety of neurological functions, among them modulation of sexual arousal and erectile function. Mutations within the MECP2 gene have been implicated in systemic lupus erythematosus (SLE),[55] a neurological autoimmune disorder that in some cases may be caused by drugs such as SSRIs,[56] and which is sometimes associated with autonomic dysfunction and/or sexual dysfunction.[57]

A study published in 2018 found that treatment with citalopram induced significant changes to DNA methylation at 626 gene promoters throughout the genome of human embryonic kidney (HEK293) cells, with 354 promoters being hypermethylated and 272 being hypomethylated; 24 of the affected genes are involved in neurotransmission.[58] Among the signaling pathways most affected by citalopram was the L-dopa pathway, with at least 31 affected genes identified whose products are regulated in some way by L-dopa.[58]

In 2022, a study in rats found that treatment with fluoxetine resulted in "profound" changes in both gene expression and chromatin structure in cells across multiple regions of the brain; over 4000 differentially-regulated genes were identified in the study.[59]

Potential role of endocrine disruption by SSRIs

A study published in 2017 reported that treating cultured H295R (human adrenocortical carcinoma) cells with the six most commonly used SSRIs (fluoxetine, paroxetine, escitalopram, citalopram, sertraline, and fluvoxamine) resulted in disruption of steroid synthesis; all six drugs were observed to decrease androgen production and produce a compensatory increase in estrogen production, with stimulation of CYP19 aromatase apparently being a common factor.[60] A 2021 review of published data from studies of endocrine disruption by SSRIs concluded that most SSRIs have demonstrated the potential to affect testosterone and estrogen levels in patients.[61]

In 2022, a study of the effects of finasteride in rats found that the drug reduced levels of allopregnanolone for at least one month after withdrawal, with a concurrent increase in pregnanolone also being observed;[62] finasteride is a non-SRI medication reported to occasionally induce post-finasteride syndrome (PFS), an iatrogenic condition which presents very similarly to PSSD. However, whereas finasteride is a 5-α reductase inhibitor and thus inhibits the conversion of progesterone to allopregnanolone, SSRIs do not appear to share this activity; at least one study has shown fluoxetine to have no effect on 5-α reductase activity in rat brains.[63] In further contrast to finasteride, SSRIs have been shown to actually increase allopregnanolone levels during treatment in a manner independent from their primary mechanism of action, gaining them the label of "selective brain steroidogenic stimulants" (SBSS).[64][65][66] However, at least one study in rats has indicated that withdrawal from paroxetine may reduce the expression of enzymes involved in the production of neuroactive steroids, including allopregnanolone.[67]

Potential role of persistent SSRI-induced electrophysiological changes

A study published in 2020 found that exposing planarians (flatworms) to fluoxetine over a three-day period resulted in changes to the resting potential of the flatworms' cells that persisted for at least a week after fluoxetine was removed.[68] The authors speculated that persistent effects of this kind in human neurons could play a role in the long-lasting effects sometimes observed after treatment with SSRIs.[68]

Potential correlation with small fiber neuropathy

In September 2022, a cohort of 36 Finnish individuals diagnosed with PSSD were tested for small fiber neuropathy (SFN) via skin biopsy; all subjects tested as having abnormally low intra-epidermal nerve fiber (IENF) density, consistent with SFN.[69] SFN can be caused by a number of conditions, among them diabetes and autoimmune disorders.[69] SFN has been found in some cases to be associated with autonomic dysfunction,[70][71] and more specifically with erectile dysfunction in men with type 2 diabetes.[72]

Potential role of ACE2 downregulation by SSRIs

In December 2022, Luisa Guerrini at the University of Milan reported preliminary findings to RxISK in which her research group had observed that administering sertraline (Zoloft) to human immortalized keratinocyte (HaCaT) cells resulted in persistent downregulation of the proteins p63 and ACE2.[73] Similar results were observed with isotretinoin (Accutane) and finasteride, two non-SSRI drugs which are reported to cause post-discontinuation syndromes similar to PSSD. The primary role of p63 is to regulate the replication and differentiation of epidermal skin cells, whereas ACE2 in its soluble (non-membrane-bound) form (sACE2) acts to convert the vasoconstriction-inducing hormone angiotensin II to angiotensin (1-7).

Angiotensin (1–7) is a vasodilator with antioxidant and anti-inflammatory properties; among other functions, it stimulates the increased activity of neuronal and endothelial nitric oxide synthase (NOS) enzymes, thereby increasing production of nitric oxide (NO).[74] Neuronal nitric oxide synthase (nNOS) is widely expressed in the central nervous system (CNS), and reduced expression of nNOS has been implicated in the pathologies of major depressive disorder (MDD), anxiety, memory loss, and bipolar disorder (BPD).[75] Multiple studies have indicated that nNOS interacts with the serotonin transporter (SERT), the primary target of most SSRIs, in ways that may affect serotonin uptake and signaling.[76][77] NO itself is a neurotransmitter with a variety of functions in the CNS,[78] and is notably a major contributor to erectile function in males, with impaired production and action of NO being commonly implicated in erectile dysfunction.[79] At least one study in mice has demonstrated that activation of ACE2 by the anti-protozoan compound diminazene aceturate (DIZE) results in upregulation of endothelial NOS (eNOS) and NO signaling within mammalian penile tissues.[80][81] NO is also known to act as a modulator of epigenetic regulation in some cells.[53]

ACE2, angiotensin (1-7), and the MAS receptor pathway of the Renin-Angiotensin System (RAS) have all been implicated in the pathology of anxiety and depressive disorders, and have been identified as potential therapeutic targets for treatment of anxiety and depression.[82] A study published in 2021 indicated that genetic variation within the ACE2 gene may determine the degree to which depressed patients respond favorably to treatment with SSRIs; specifically, the intronic ACE2 mutation G8790A was correlated with significantly better response to SSRI treatment.[83]

Notably, the membrane-bound form of ACE2 (mACE2) is also the receptor protein used by SARS-CoV-2 as an entry point into the cell, and binding of the SARS-CoV-2 spike protein to ACE2 has been suggested to stimulate an inflammatory response that could cause "Long COVID",[84] a post-infection syndrome exhibiting multiple overlapping symptoms with PSSD, post-finasteride syndrome (PFS) and post-Accutane syndrome (PAS), most notably cognitive dysfunction/"brain fog" and sexual dysfunction.[85][86] A 2021 study with a large patient sample size (83,584 participants) found a significant association between prior SSRI use and reduced mortality from COVID-19.[87] Another study from 2021 found that clomipramine (Anafranil), an SRI tricyclic antidepressant, inhibited infection by SARS-CoV-2 in human iPS-derived cardiomyocytes.[88]

ACE2 is highly expressed in the epithelium of the intestines, where it plays a role in maintaining innate immunity and homeostasis of gut microbial communities.[89] Both SARS-CoV-2 infection[89] and treatment with SSRIs[90] have been demonstrated to cause changes in gut microbiota populations. Mice deficient in ACE2 have been shown to be significantly more prone to gut dysbiosis, colitis and amino acid malabsorption.[91] Among the amino acids that are poorly absorbed by ACE2-deficient mice is L-tryptophan, a precursor to serotonin; reduced synthesis of serotonin is also observed in these mice, presumably as a consequence of reduced L-tryptophan availability.[92]

A study published in 2021 found that ACE2 expression was abnormally low in patients with Myalgic Encephalitis/Chronic Fatigue Syndrome (ME/CFS),[93] a poorly-understood condition characterized by overwhelming fatigue. Several reported symptoms of ME/CFS overlap with PSSD, including cognitive difficulties and sexual dysfunction.[94][95]

Potential role of gut microbiome disruption by SSRIs

Multiple studies have indicated that the composition of an individual's gut microbiome may contribute to sexual dysfunction.[96][97][98][99] As mentioned previously, SSRIs are known to induce changes to the gut microbiome,[90] as is finasteride (Propecia),[62][100] another non-SRI medication known to cause post-discontinuation sexual dysfunction. SARS-CoV-2 infection is likewise known to alter gut microbe populations,[89] and is associated with a post-infection syndrome known as "Long COVID," the symptoms of which may include sexual dysfunction.[85] Isotretinoin (Accutane), a non-SRI medication which is reported to occasionally induce a post-discontinuation syndrome similar to PSSD and PFS, has not been observed to induce significant changes in gut microbiota in animal models.[101]

Potential SSRI-induced autoimmune response

In December 2022, a RxISK blog post noted the occurrence of many self-reports in which individuals with PSSD had tested as having elevated levels of auto-antibodies against muscarinic, catecholamine and ACE receptor proteins.[73] The majority of these tests were conducted by CellTrend, a German contract research organization which offers blood test panels for several auto-antibodies thought to be involved in ME/CFS, Long Covid, SFN and postural orthostatic tachycardia syndrome (POTS).[102] As of 2022, this pattern of test results has not been independently corroborated by other laboratories.

Although the role of autoimmunity in PSSD has not been confirmed, precedents exist for drug-induced autoimmune disorders,[103] as well as for autoimmune disorders that affect nervous system function.[104] Notably, the early SSRI Zimelidine was withdrawn from the market after studies found its usage to be associated with an approximately 25-fold increased risk of developing Guillain-Barré syndrome.[105] Another notable example of a drug-induced autoimmune disorder is drug-induced lupus erythematosus (DILE), which can be caused by a variety of medications including ACE inhibitors (and according to at least one case report, citalopram),[56] and which is thought to be caused at least in part by drug-induced demethylation within the genomes of CD4+ T cells.[106] Autonomic neuropathy, a condition in which nerves involved in controlling automatic bodily functions become damaged, is known to occur in lupus erythematosus[107] and Guillain-Barré syndrome, and is associated with sexual dysfunction.[108] Sexual dysfunction is also prevalent in multiple sclerosis (MS) patients, especially among male sufferers.[109]

Gut dysbiosis is known to be a causative or contributing factor in some autoimmune disorders,[110] and is a known cause of autoimmune neurological disorders such as Guillain-Barré syndrome.[111] As discussed previously, SSRIs are known to affect the gut microbiota of treated individuals.

Treatment

There is as yet no established treatment for PSSD. In an unknown fraction of cases, symptoms are reported to resolve spontaneously with time,[10] but the duration of symptoms appears to vary widely among patients. Many anecdotal self-reports exist in which various approaches, ranging from pharmacological or psychiatric treatments to dietary or lifestyle changes, allegedly correlate with improvement in PSSD symptoms, but these results have not been independently verified or replicated. Several studies have been conducted which attempt to identify viable treatment options for PSSD,[21][11][112] but in general these have suffered from a small sample size and lack of controls, limiting their informative utility.

Societal impact and support communities

Since 2006,[113][114] a number of news articles have been published by various outlets on the subject of PSSD.[115][116][117][118][119][120][121][122][123]

Multiple online support groups and networks have formed to share information among individuals affected by PSSD and/or increase public awareness of the condition. These include the PSSD Network,[124] PSSD Forum,[125] PSSD International,[126] Canadian PSSD Society,[127] and the Post SSRI Sexual Dysfunction subreddit.[1] The advocacy group RxISK is also dedicated to sharing information about PSSD and other iatrogenic disorders.[128] The website StuffThatWorks is currently collecting information from volunteers in an effort to find broadly applicable treatment strategies for PSSD and other chronic conditions.[129]

On 21 June 2022, RxISK began a research fund to support and stimulate interest in PSSD research;[130] the group has also offered a prize of $100,000 USD to anyone who can identify a reliable cure for persistent sexual side effects after stopping antidepressants, finasteride (Propecia), or isotretinoin (Accutane).[131]

Similar or relevant conditions

PSSD is one of several known iatrogenic syndromes characterized by persistent sexual dysfunction after stopping a medication; others include:[6]

In 2014, a review of 120 reports submitted to RxISK from more than 20 countries concluded that PSSD, PFS and PRSD/PAS exhibit extensively overlapping symptom profiles.[133] As described above, Long COVID shares some symptoms with PSSD, PFS and PRSD/PAS, among them cognitive dysfunction/"brain fog" and sexual dysfunction.[85]

Several studies in both humans and animals have suggested that use of SSRIs at an early age may increase the likelihood of asexuality during later development. A 2020 study in which 610 young adult individuals were surveyed found that childhood SSRI use among female participants was strongly correlated with reduced sexual desire and activity; childhood SSRI use among male participants was correlated with reduced frequency of partnered sexual activity as an adult.[134] Animal studies have found that exposure to an SSRI during pregnancy or at an early age produces sexual deficits in adulthood.[135][6]

The drug 3,4-methylenedioxymethamphetamine (MDMA), which acts to stimulate the release and inhibit the reuptake of serotonin, can in some cases produce adverse effects that persist long after the drug has been withdrawn, including neurocognitive impairments such as mood disorders[136] and sexual dysfunction.[137] The mechanism behind MDMA neurotoxicity is not fully understood,[136] but a similar mechanism has been suggested to potentially play a role in PSSD.[137]

Chemotherapy-induced peripheral neuropathy is a condition in which pain and sensory abnormalities can persist for months or years after chemotherapy treatment. Some patients may experience “coasting,” where symptoms intensify after completion of treatment.[138] As such, patients can be cancer-free and still suffer from disabling neuropathy induced by cancer treatment.[138]

Post-SSRI Sexual Dysfunction Literature

[139][140][141][142]
Year Published Title Publisher Author URL
2022 Textbook of Rare Sexual Medicine Conditions Springer Yacov Reisman, Lior Lowenstein, Francesca Tripodi [41][40]
2022 Cutting the First Turf to Heal Post-SSRI Sexual Dysfunction: A Male Retrospective Cohort Study Medicines De Luca R, Bonanno M, Manuli A, Calabrò RS [2]
2022 Screening and treatment of Post-Selective Serotonin Reuptake Inhibitors sexual dysfunctions Encephale Achour V, Masson M, Lancon C, Boyer L, Fond G [3]
2022 Post-Selective Serotonin Reuptake Inhibitor Sexual Dysfunctions (PSSD): Clinical Experience with a Multimodal Approach Journal of Men’s Health Reisman Y, Jannini TB, Jannini EA [4]
2021 (German) Psychopharmaka absetzen? Warum, wann und wie? Urban&Fischer G Gründer [4]
2021 Psychiatry and Sexual Medicine: A Comprehensive Guide for Clinical Practitioners Springer Michal Lew-Starowicz,

Annamaria Giraldi,

Tillmann H. C. Krüger

[43][42]
2021 Persistent sexual dysfunction after SSRI withdrawal: a scoping review and presentation of 86 cases from the Netherlands Expert Opinion on Drug Safety Chinchilla Alfaro K, van Hunsel F, Ekhart C [5]
2021 Diagnostic criteria for enduring sexual dysfunction after treatment with antidepressants, finasteride and isotretinoin International Journal of Risk & Safety in Medicine Healy D, Bahrick A, Bak M, Barbato A, Calabrò RS, Chubak BM, et al [6]
2021 Charactarizing Post-SSRI sexual dysfunction and its impact on quality of life through an international online survey International Journal of Risk & Safety in Medicine Studt A, Gannon M, Orzel J, Vaughan A, Pearlman AM [7]
2021 Exposure to serotonin selective reuptake inhibitors or serotonin noradrenaline reuptake inhibitors and sexual dysfunction: Results from an online survey International Journal of Risk & Safety in Medicine Patacchini A, Cosci F [8]
2021 Effects of paroxetine treatment and its withdrawal on neurosteroidogenesis Psychoneuroendocrinology Giatti S, Diviccaro S, Cioffi L, Falvo E, Caruso D, Melcangi RC [9]
2020 Post-SSRI Sexual Dysfunction: Exploration of the Sexual Domains and Symptoms Master thesis (Clinical Psychology), Utrecht University Raj S [10]
2020 Post-SSRI sexual dysfunction (PSSD): Ten year retrospective chart review The Journal of Urology Waraich A, Clemons C, Ramirez R, Yih J, Goldstein S, Goldstein I [11]
2020 Antidepressant-induced sexual dysfunction The Medical Journal of Australia Rothmore J [12]
2020 Post-SSRI sexual dysfunction The BMJ Reisman Y [13]
2020 Antidepressants and sexual dysfunction: a history Journal of the Royal Society of Medicine Healy D [14]
2020 Antidepressant Use During Development May Impair Women’s Sexual Desire in Adulthood The Journal of Sexual Medicine Lorenz TK [15]
2020 A Paradigmatic Case of Postselective Serotonin Reuptake Inhibitors Sexual Dysfunction or Withdrawal After Discontinuation of Selective Serotonin Reuptake Inhibitors? Journal of Clinical Psychopharmacology Patacchini A, Cosci [16]
2019 Life after antidepressants: Does persisting sexual dysfunction influence quality of life? Master Thesis (Clinical Psychology), Utrecht University Lüning [17]
2019 Post-SSRI Sexual Dysfunction: A Bioelectric Mechanism? Bioelectricity Healy D, LaPalme J, Levin [18]
2019 Are There Any Sex/Gender Differences in Post-Selective Serotonin Reuptake Inhibitors (SSRI) Sexual Dysfunction (PSDD)? Current Sexual Health Reports Reisman [19]
2019 Post-SSRI sexual dysfunction & other enduring sexual dysfunctions Epidemiology and Psychiatric Sciences Healy D [20]
2019 Post-SSRI sexual dysfunction: Patient experiences of engagement with healthcare professionals International Journal of Risk & Safety in Medicine Healy D, Le Noury J, Mangin D [21]
2019 Towards Improving Post-SSRI Sexual Dysfunction by Using Nutriceuticals: Lessons from a Case Study Journal of Sex & Marital Therapy Calabrò RS, De Luca R, Manuli A, Portaro S, Naro A, Quattrini F [22]
2018 Citizen petition: Sexual side effects of SSRIs and SNRIs International Journal of Risk & Safety in Medicine Healy D [23]
2018 Enduring sexual dysfunction after treatment with antidepressants, 5α-reductase inhibitors and isotretinoin: 300 cases International Journal of Risk & Safety in Medicine Healy D, Le Noury J, Mangin D [24]
2018 Post-finasteride syndrome and post-SSRI sexual dysfunction: two sides of the same coin? Endocrine Giatti S, Diviccaro S, Panzica G, Melcangi [25]
2018 Post-SSRI Sexual Dysfunction: Preclinical to Clinical Is It Fact or Fiction? Sexual Medicine Reviews Coskuner ER, Culha MG, Ozkan B, Kaleagasi EO [26]
2017 Disfunción sexual persistente tras el tratamiento con inhibidores selectivos de la recaptación de serotonina: a propósito de un caso tras la retirada de paroxetina Psiquiatría Biológica Muquebil Ali Al Shaban Rodríguez OW, Álvarez de Morales Gómez-Moreno E, Fernández Fernández J, Fresno García C, del Mar Fernández Fernández M [27]
2017 Post-SSRI Sexual Dysfunction: A Literature Review Sexual Medicine Reviews Bala A, Tue Nguyen HM, Hellstrom WJG [28]
2017 Sexual Consequences of Post-SSRI Syndrome Sexual Medicine Reviews Reisman Y [29]
2016 Persistent sexual dysfunction after early exposure to SSRIs: Systematic review of animal studies International Journal of Risk & Safety in Medicine Simonsen AL, Danborg PB, Gøtzsche PC [30]
2015 Sexual dysfunction persisting after treatment with antidepressants (In Slovak) Psychiatria pre prax Vašečková B [31]
2015 Post-SSRI Sexual Dysfunction: Clinical Characterization and Preliminary Assessment of Contributory Factors and Dose-Response Relationship Journal of Clinical Psychopharmacology Ben-Sheetrit J, Aizenberg D, Csoka AB, Weizman A, Hermesh H [32]
2014 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 Waldinger MD, van Coevorden RS, Schweitzer DH, Georgiadis J [33]
2014 One hundred and twenty cases of enduring sexual dysfunction following treatment International Journal of Risk & Safety in Medicine Hogan C, Le Noury J, Healy D, Mangin D [34]
2014 Does sexual dysfunction persist upon discontinuation of selective serotonin reuptake inhibitors? (In Dutch) Tijdschrift voor Psychiatrie Ekhart GC, van Puijenbroek EP [35]
2013 DSM-5 American Psychiatric Association American Psychiatric Association DSM-5
2013 The impact of persistent sexual side effects of selective serotonin reuptake inhibitors after discontinuing treatment: a qualitative study PhD (Doctor of Philosophy) thesis, University of Iowa Stinson RD [36]
2012 SSRIs and persistent sexual dysfunction Netherlands Pharmacovigilance Centre Lareb [37]
2009 Persistent sexual dysfunction in genitourinary medicine clinic attendees induced by selective serotonin reuptake inhibitors International Journal of STD & AIDS Farnsworth KD, Dinsmore WW [38]
2008 Sexual Side Effects of Antidepressant Medications: An Informed Consent Accountability Gap Journal of Contemporary Psychotherapy Bahrick AS, Harris MM [39]
2008 Persistent Sexual Side Effects after Discontinuation of Psychotropic Medications Primary Psychiatry Kauffman RP [143]
2008 Persistence of Sexual Dysfunction Side Effects after Discontinuation of Antidepressant Medications: Emerging Evidence The Open Psychology Journal Bahrick AS [40]
2008 Persistent sexual dysfunction after discontinuation of selective serotonin reuptake inhibitors The Journal of Sexual Medicine Csoka AB, Bahrick A, Mehtonen OP [41]
2007 Prolonged Post-Treatment Genital Anesthesia and Sexual Dysfunction Following Discontinuation of Citalopram and the Atypical Antidepressant Nefazodone The Open Women’s Health Journal Kauffman RP, Murdock A [42]
2006 Post SSRI sexual dysfunction American Society for the Advancement of Pharmacotherapy Tablet Bahrick AS [43]
2006 Persistent sexual side effects after SSRI discontinuation Psychotherapy and Psychosomatics Csoka AB, Shipko S [44]
2006 Genital anaesthesia persisting six years after sertraline discontinuation Journal of Sex & Marital Therapy Bolton JM, Sareen J, Reiss JP [45]

See also

References

  1. ^ Bahrick AS (5 May 2008). "Persistence of Sexual Dysfunction Side Effects after Discontinuation of Antidepressant Medications: Emerging Evidence". The Open Psychology Journal. 1 (1): 42–50. doi:10.2174/1874350100801010042.
  2. ^ Jannini TB, Lorenzo GD, Bianciardi E, Niolu C, Toscano M, Ciocca G, et al. (2022). "Off-label Uses of Selective Serotonin Reuptake Inhibitors (SSRIs)". Current Neuropharmacology. 20 (4): 693–712. doi:10.2174/1570159x19666210517150418. PMID 33998993. S2CID 234745872.
  3. ^ Waldinger MD (1 January 2015). "Chapter 27 - Psychiatric disorders and sexual dysfunction". In Vodušek DB, Boller F (eds.). Handbook of Clinical Neurology. Neurology of Sexual and Bladder Disorders. Vol. 130. Elsevier. pp. 469–489. Retrieved 6 January 2023.
  4. ^ a b c Gründer G (15 November 2021). Psychopharmaka absetzen? Warum, wann und wie? (in German). Elsevier Health Sciences. ISBN 978-3-437-06383-1.
  5. ^ a b c d Reisman Y (October 2017). "Sexual Consequences of Post-SSRI Syndrome". Sexual Medicine Reviews. 5 (4): 429–433. doi:10.1016/j.sxmr.2017.05.002. PMID 28642048.
  6. ^ a b c d e f g h i j k l m n o Healy D, Bahrick A, Bak M, Barbato A, Calabrò RS, Chubak BM, et al. (1 January 2022). "Diagnostic criteria for enduring sexual dysfunction after treatment with antidepressants, finasteride and isotretinoin". The International Journal of Risk & Safety in Medicine. 33 (1): 65–76. doi:10.3233/JRS-210023. PMC 8925105. PMID 34719438.
  7. ^ a b c Chinchilla Alfaro K, van Hunsel F, Ekhart C (April 2022). "Persistent sexual dysfunction after SSRI withdrawal: a scoping review and presentation of 86 cases from the Netherlands". Expert Opinion on Drug Safety. 21 (4): 553–561. doi:10.1080/14740338.2022.2007883. PMID 34791958. S2CID 244347777.
  8. ^ a b "Diagnostic criteria for enduring sexual dysfunction after treatment with antidepressants, finasteride and isotretinoin". National Library of Medicine. 22 February 2022. Retrieved 21 January 2023.
  9. ^ a b Csoka AB, Shipko S (2006). "Persistent sexual side effects after SSRI discontinuation". Psychotherapy and Psychosomatics. 75 (3): 187–188. doi:10.1159/000091777. PMID 16636635. S2CID 33448116.
  10. ^ a b c d Healy D (September 2019). "Post-SSRI sexual dysfunction & other enduring sexual dysfunctions". Epidemiology and Psychiatric Sciences. 29: e55. doi:10.1017/S2045796019000519. PMC 8061302. PMID 31543091.
  11. ^ a b c d De Luca R, Bonanno M, Manuli A, Calabrò RS (September 2022). "Cutting the First Turf to Heal Post-SSRI Sexual Dysfunction: A Male Retrospective Cohort Study". Medicines. 9 (9): 45. doi:10.3390/medicines9090045. PMC 9503765. PMID 36135826.
  12. ^ a b c d e f g h i Peleg LC, Rabinovitch D, Lavie Y, Rabbie DM, Horowitz I, Fruchter E, Gruenwald I (January 2022). "Post-SSRI Sexual Dysfunction (PSSD): Biological Plausibility, Symptoms, Diagnosis, and Presumed Risk Factors". Sexual Medicine Reviews. 10 (1): 91–98. doi:10.1016/j.sxmr.2021.07.001. PMID 34627736. S2CID 238580777.
  13. ^ a b c d e f g h i j k l m n o p q r s Bala A, Nguyen HM, Hellstrom WJ (January 2018). "Post-SSRI Sexual Dysfunction: A Literature Review". Sexual Medicine Reviews. 6 (1): 29–34. doi:10.1016/j.sxmr.2017.07.002. PMID 28778697. There is still no definitive treatment for PSSD. Low-power laser irradiation and phototherapy have shown some promising results.
  14. ^ a b Healy D (2018). "Citizen petition: Sexual side effects of SSRIs and SNRIs". The International Journal of Risk & Safety in Medicine. 29 (3–4): 135–147. doi:10.3233/JRS-180745. PMC 6004927. PMID 29733031.
  15. ^ a b "PSSD FAQ — Antidepressant Induced Post-SSRI Sexual Dysfunction". PSSD Network – Antidepressant Induced Post-SSRI Sexual Dysfunction. Retrieved 3 December 2022.
  16. ^ Studt A, Gannon M, Orzel J, Vaughan A, Pearlman AM (2021). "Characterizing post-SSRI sexual dysfunction and its impact on quality of life through an international online survey". The International Journal of Risk & Safety in Medicine. 32 (4): 321–329. doi:10.3233/JRS-210039. PMID 34366299. S2CID 236959687.
  17. ^ Rosen RC, Lane RM, Menza M (February 1999). "Effects of SSRIs on sexual function: a critical review". Journal of Clinical Psychopharmacology. 19 (1): 67–85. doi:10.1097/00004714-199902000-00013. PMID 9934946.
  18. ^ "How Common is Post-SSRI Sexual Dysfunction (PSSD)? | RxISK". rxisk.org. Retrieved 3 December 2022.
  19. ^ Giatti S, Diviccaro S, Panzica G, Melcangi RC (August 2018). "Post-finasteride syndrome and post-SSRI sexual dysfunction: two sides of the same coin?". Endocrine. 61 (2): 180–193. doi:10.1007/s12020-018-1593-5. PMID 29675596. S2CID 4974636.
  20. ^ Velez D, Ohlander S (September 2021). "Medical therapies causing iatrogenic male infertility". Fertility and Sterility. 116 (3): 618–624. doi:10.1016/j.fertnstert.2021.07.1202. PMID 34462096.
  21. ^ a b c Reisman Y, Jannini TB, Jannini EA (1 August 2022). "Post-Selective Serotonin Reuptake Inhibitor Sexual Dysfunctions (PSSD): Clinical Experience with a Multimodal Approach". Journal of Men's Health. 18 (8): 165. doi:10.31083/j.jomh1808165. ISSN 1875-6867. S2CID 251371080.
  22. ^ Bala A, Nguyen HM, Hellstrom WJ (January 2018). "Post-SSRI Sexual Dysfunction: A Literature Review". Sexual Medicine Reviews. 6 (1): 29–34. doi:10.1016/j.sxmr.2017.07.002. PMID 28778697.
  23. ^ a b c Reisman Y (February 2020). "Post-SSRI sexual dysfunction". BMJ. 368: m754. doi:10.1136/bmj.m754. PMID 32107204. S2CID 211557435.
  24. ^ "Post SSRI/SNRI Sexual Dysfunction (PSSD)". Sex[M]ed. 15 November 2021. Retrieved 18 January 2023.
  25. ^ Healy D (April 2020). "Antidepressants and sexual dysfunction: a history". Journal of the Royal Society of Medicine. 113 (4): 133–135. doi:10.1177/0141076819899299. PMC 7160790. PMID 31972096.
  26. ^ "Freedom of Information request on adverse sexual dysfunction reactions to SSRI use (FOI 21-232)". GOV.UK. Archived from the original on 6 January 2023. Retrieved 20 December 2022.
  27. ^ Waraich A, Clemons C, Ramirez R, Yih J, Goldstein S, Goldstein I (April 2020). "Mp78-15 post-ssri sexual dysfunction (pssd): ten year retrospective chart review". Journal of Urology. 203 (Supplement 4): e1179. doi:10.1097/JU.0000000000000964.015. S2CID 218960429.
  28. ^ a b Patacchini A, Cosci F (2021). "Exposure to serotonin selective reuptake inhibitors or serotonin noradrenaline reuptake inhibitors and sexual dysfunction: Results from an online survey". The International Journal of Risk & Safety in Medicine. 32 (3): 229–242. doi:10.3233/JRS-200074. PMID 33579876. S2CID 231909523.
  29. ^ "MHRA Products | Search results". products.mhra.gov.uk. Retrieved 14 December 2022.
  30. ^ "Package leaflet Information for the patient Sertraline 50 mg Film-coated Tablets Sertraline 100 mg Film-coated Tablets". Archived from the original on 14 December 2022.
  31. ^ "MHRA Products | Search results". products.mhra.gov.uk. Retrieved 14 December 2022.
  32. ^ "leaflet".
  33. ^ "leaflet". Archived from the original on 14 December 2022.
  34. ^ "MHRA Products | Search results". products.mhra.gov.uk. Retrieved 14 December 2022.
  35. ^ "leaflet". Archived from the original on 14 December 2022.
  36. ^ "MHRA Products | Search results". products.mhra.gov.uk. Retrieved 14 December 2022.{{cite web}}: CS1 maint: url-status (link)
  37. ^ "Package leaflet: Information for the user". Archived from the original on 14 December 2022.
  38. ^ "FDA medication leaflet" (PDF). Archived (PDF) from the original on 6 January 2023.
  39. ^ Diagnostic and Statistical Manual of Mental Disorders. USA: American Psychiatric Association. 2013. p. 449. In some cases, serotonin reuptake inhibitor induced sexual dysfunction may persist after the agent is discontinued
  40. ^ a b Textbook of Rare Sexual Medicine Conditions. doi:10.1007/978-3-030-98263-8.
  41. ^ a b Reisman Y, Pfaus JG, Lowenstein L (2022). "Post-SSRI Sexual Dysfunction (PSSD)". In Reisman Y, Lowenstein L, Tripodi F (eds.). Textbook of Rare Sexual Medicine Conditions. Cham: Springer International Publishing. pp. 51–63. doi:10.1007/978-3-030-98263-8_5. ISBN 978-3-030-98263-8.
  42. ^ a b Psychiatry and Sexual Medicine. doi:10.1007/978-3-030-52298-8.
  43. ^ a b "Psychiatry and Sexual Medicine". Canadian PSSD Society. Retrieved 10 January 2023.
  44. ^ Pharmacovigilance Risk Assessment Committee (PRAC). "Minutes of PRAC meeting on 13-16 May 2019" (PDF). European Medicines Agency. p. 25.
  45. ^ a b "Summary Safety Review – Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-norepinephrine Reuptake Inhibitors (SNRIs) – Assessing the Potential Risk of Sexual Dysfunction despite Treatment Discontinuation". 6 January 2021. Archived from the original on 17 January 2021.
  46. ^ "New product information wording – Extracts from PRAC recommendations on signals" (PDF). An official website of the European Union. 11 June 2019. p. 2. Archived (PDF) from the original on 20 September 2022. Selective serotonin reuptake inhibitors (SSRIs)/serotonin norepinephrine reuptake inhibitors (SNRIs) may cause symptoms of sexual dysfunction (see section 4.8). There have been reports of long-lasting sexual dysfunction where the symptoms have continued despite discontinuation.
  47. ^ "Health Canada warns about Persistent Sexual Dysfunction after SSRIs & SNRIs | RxISK". rxisk.org. Retrieved 13 December 2022.
  48. ^ "HongKong Warning". 7 January 2021. Archived from the original on 12 December 2022. {{cite web}}: |archive-date= / |archive-url= timestamp mismatch; 13 December 2022 suggested (help)
  49. ^ "Hong Kong announcement". Canadian PSSD Society. Retrieved 13 December 2022.
  50. ^ "Side effects of sertraline". nhs.uk. 3 February 2022. Archived from the original on 19 August 2022. Retrieved 13 December 2022.
  51. ^ Menke A, Binder EB (September 2014). "Epigenetic alterations in depression and antidepressant treatment". Dialogues in Clinical Neuroscience. 16 (3): 395–404. doi:10.31887/DCNS.2014.16.3/amenke. PMC 4214180. PMID 25364288.
  52. ^ Vialou V, Feng J, Robison AJ, Nestler EJ (2013). "Epigenetic mechanisms of depression and antidepressant action". Annual Review of Pharmacology and Toxicology. 53: 59–87. doi:10.1146/annurev-pharmtox-010611-134540. PMC 3711377. PMID 23020296.
  53. ^ a b Borodinova AA, Balaban PM (September 2020). "Epigenetic Regulation as a Basis for Long-Term Changes in the Nervous System: In Search of Specificity Mechanisms". Biochemistry. Biokhimiia. 85 (9): 994–966. doi:10.1134/S0006297920090023. PMID 33050846.
  54. ^ Zimmermann N, Zschocke J, Perisic T, Yu S, Holsboer F, Rein T (November 2012). "Antidepressants inhibit DNA methyltransferase 1 through reducing G9a levels". The Biochemical Journal. 448 (1): 93–102. doi:10.1042/BJ20120674. PMID 22880885.
  55. ^ Sawalha AH, Webb R, Han S, Kelly JA, Kaufman KM, Kimberly RP, et al. (March 2008). "Common variants within MECP2 confer risk of systemic lupus erythematosus". PloS One. 3 (3): e1727. doi:10.1371/journal.pone.0001727. PMC 2253825. PMID 18320046.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  56. ^ a b Röhrs S, Geiser F, Conrad R (2012). "Citalopram-induced subacute cutaneous lupus erythematosus -- first case and review concerning photosensitivity in selective serotonin reuptake inhibitors". General Hospital Psychiatry. 34 (5): 541–545. doi:10.1016/j.genhosppsych.2012.03.012. PMID 22534401.
  57. ^ Liu M, Dou J, Wang Q (July 2022). "The effect of systemic lupus erythematosus on sexual function in women: an updated meta-analysis based on cross-sectional studies". Advances in Rheumatology. 62 (1): 24. doi:10.1186/s42358-022-00257-0. PMID 35787296.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  58. ^ a b Kanherkar RR, Getachew B, Ben-Sheetrit J, Varma S, Heinbockel T, Tizabi Y, Csoka AB (25 July 2018). "The Effect of Citalopram on Genome-Wide DNA Methylation of Human Cells". International Journal of Genomics. 2018: 8929057. doi:10.1155/2018/8929057. PMC 6083487. PMID 30148158.
  59. ^ Rayan NA, Kumar V, Aow J, Rastegar N, Lim MG, O'Toole N, et al. (November 2022). "Integrative multi-omics landscape of fluoxetine action across 27 brain regions reveals global increase in energy metabolism and region-specific chromatin remodelling". Molecular Psychiatry. 27 (11): 4510–4525. doi:10.1038/s41380-022-01725-1. PMC 9734063. PMID 36056172.
  60. ^ Hansen CH, Larsen LW, Sørensen AM, Halling-Sørensen B, Styrishave B (June 2017). "The six most widely used selective serotonin reuptake inhibitors decrease androgens and increase estrogens in the H295R cell line". Toxicology in Vitro. 41: 1–11. doi:10.1016/j.tiv.2017.02.001. PMID 28179152.
  61. ^ Pavlidi P, Kokras N, Dalla C (May 2021). "Antidepressants' effects on testosterone and estrogens: What do we know?". European Journal of Pharmacology. 899: 173998. doi:10.1016/j.ejphar.2021.173998. PMID 33676942. S2CID 232141878.
  62. ^ a b Diviccaro S, Giatti S, Cioffi L, Falvo E, Herian M, Caruso D, Melcangi RC (October 2022). "Gut Inflammation Induced by Finasteride Withdrawal: Therapeutic Effect of Allopregnanolone in Adult Male Rats". Biomolecules. 12 (11): 1567. doi:10.3390/biom12111567. PMC 9687671. PMID 36358917.
  63. ^ Griffin LD, Mellon SH (November 1999). "Selective serotonin reuptake inhibitors directly alter activity of neurosteroidogenic enzymes". Proceedings of the National Academy of Sciences of the United States of America. 96 (23): 13512–13517. doi:10.1073/pnas.96.23.13512. PMC 23979. PMID 10557352.
  64. ^ Gunay A, Pinna G (1 June 2022). "The novel rapid-acting neurosteroid-based antidepressant generation". Current Opinion in Endocrine and Metabolic Research. 24: 100340. doi:10.1016/j.coemr.2022.100340. ISSN 2451-9650.
  65. ^ Pinna G (2020). "Allopregnanolone, the Neuromodulator Turned Therapeutic Agent: Thank You, Next?". Frontiers in Endocrinology. 11: 236. doi:10.3389/fendo.2020.00236/full#b7. PMID 32477260.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  66. ^ Uzunova V, Sheline Y, Davis JM, Rasmusson A, Uzunov DP, Costa E, Guidotti A (March 1998). "Increase in the cerebrospinal fluid content of neurosteroids in patients with unipolar major depression who are receiving fluoxetine or fluvoxamine". Proceedings of the National Academy of Sciences of the United States of America. 95 (6): 3239–3244. doi:10.1073/pnas.95.6.3239. PMID 9501247.
  67. ^ Giatti S, Diviccaro S, Cioffi L, Falvo E, Caruso D, Melcangi RC (October 2021). "Effects of paroxetine treatment and its withdrawal on neurosteroidogenesis". Psychoneuroendocrinology. 132: 105364. doi:10.1016/j.psyneuen.2021.105364. hdl:2434/901757. PMID 34325207. S2CID 236165173.
  68. ^ a b Healy D, LaPalme J, Levin M (March 2020). "Post-SSRI Sexual Dysfunction: A Bioelectric Mechanism?". Bioelectricity. 2 (1): 7–13. doi:10.1089/bioe.2019.0010. PMC 8370302. PMID 34471832.
  69. ^ a b "Sensory Receptors, Small Fibres and Neuropathy | RxISK". rxisk.org. Retrieved 11 December 2022.
  70. ^ Prakash, Vikram; Safder, Shaista (13 April 2021). "Small Fiber Neuropathy (SFN) Causes Autonomic Dysfunction and/or Pain/Sensory Dysfunction in Children (1720)". Neurology. 96 (15 Supplement). ISSN 0028-3878.
  71. ^ Levine TD (18 April 2018). "Small Fiber Neuropathy: Disease Classification Beyond Pain and Burning". Journal of Central Nervous System Disease. 10: 1179573518771703. doi:10.1177/1179573518771703. PMC 5912271. PMID 29706768.
  72. ^ Dhage S, Ho JH, Ferdousi M, Kalteniece A, Azmi S, Adam S, et al. (March 2020). "Small fibre pathology is associated with erectile dysfunction in men with type 2 diabetes". Diabetes/Metabolism Research and Reviews. 36 (3): e3263. doi:10.1002/dmrr.3263. PMID 31833632.
  73. ^ a b "A Cure for PSSD, PFS and Post-Isotretinoin Syndrome | RxISK". rxisk.org. Retrieved 11 December 2022.
  74. ^ Sampaio WO, Souza dos Santos RA, Faria-Silva R, da Mata Machado LT, Schiffrin EL, Touyz RM (January 2007). "Angiotensin-(1-7) through receptor Mas mediates endothelial nitric oxide synthase activation via Akt-dependent pathways". Hypertension. 49 (1): 185–192. doi:10.1161/01.HYP.0000251865.35728.2f. PMID 17116756. S2CID 25243946.
  75. ^ Zhou QG, Zhu XH, Nemes AD, Zhu DY (December 2018). "Neuronal nitric oxide synthase and affective disorders". IBRO Reports. 5: 116–132. doi:10.1016/j.ibror.2018.11.004. PMC 6303682. PMID 30591953.
  76. ^ Garthwaite J (May 2007). "Neuronal nitric oxide synthase and the serotonin transporter get harmonious". Proceedings of the National Academy of Sciences of the United States of America. 104 (19): 7739–7740. Bibcode:2007PNAS..104.7739G. doi:10.1073/pnas.0702508104. PMC 1876516. PMID 17483475.
  77. ^ Sun N, Qin YJ, Xu C, Xia T, Du ZW, Zheng LP, et al. (October 2022). "Design of fast-onset antidepressant by dissociating SERT from nNOS in the DRN". Science. 378 (6618): 390–398. doi:10.1126/science.abo3566. PMID 36302033. S2CID 253184435.
  78. ^ Picón-Pagès P, Garcia-Buendia J, Muñoz FJ (August 2019). "Functions and dysfunctions of nitric oxide in brain". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1865 (8): 1949–1967. doi:10.1016/j.bbadis.2018.11.007. PMID 30500433. S2CID 54525442.
  79. ^ Toda N, Ayajiki K, Okamura T (May 2005). "Nitric oxide and penile erectile function". Pharmacology & Therapeutics. 106 (2): 233–266. doi:10.1016/j.pharmthera.2004.11.011. PMID 15866322.
  80. ^ Fraga-Silva RA, Faye Y, Costa-Fraga FP, Shenoy V, Montecucco F, Mach F, et al. (1 September 2013). "Abstract 186: ACE2 Activation Protects Corpus Cavernosum Impairment Induced by Hypercholesterolemia". Hypertension. 62 (suppl_1): A186. doi:10.1161/hyp.62.suppl_1.A186. S2CID 74556113.
  81. ^ Fraga-Silva RA, Costa-Fraga FP, Montecucco F, Sturny M, Faye Y, Mach F, et al. (February 2015). "Diminazene protects corpus cavernosum against hypercholesterolemia-induced injury". The Journal of Sexual Medicine. 12 (2): 289–302. doi:10.1111/jsm.12757. PMID 25411084.
  82. ^ de Melo LA, Almeida-Santos AF (2020). "Neuropsychiatric Properties of the ACE2/Ang-(1-7)/Mas Pathway: A Brief Review". Protein and Peptide Letters. 27 (6): 476–483. doi:10.2174/0929866527666191223143230. PMID 31868143.
  83. ^ Firouzabadi N, Farshadfar P, Haghnegahdar M, Alavi-Shoushtari A, Ghanbarinejad V (February 2022). "Impact of ACE2 genetic variant on antidepressant efficacy of SSRIs". Acta Neuropsychiatrica. 34 (1): 30–36. doi:10.1017/neu.2021.32. PMID 34602110. S2CID 238256135.
  84. ^ Schieffer E, Schieffer B (2022). "The rationale for the treatment of long-Covid symptoms - A cardiologist's view". Frontiers in Cardiovascular Medicine. 9: 992686. doi:10.3389/fcvm.2022.992686. PMC 9520195. PMID 36186977.
  85. ^ a b c Subramanian A, Nirantharakumar K, Hughes S, Myles P, Williams T, Gokhale KM, et al. (August 2022). "Symptoms and risk factors for long COVID in non-hospitalized adults". Nature Medicine. 28 (8): 1706–1714. doi:10.1038/s41591-022-01909-w. PMC 9388369. PMID 35879616.
  86. ^ Sansone A, Mollaioli D, Limoncin E, Ciocca G, Bắc NH, Cao TN, et al. (April 2022). "The Sexual Long COVID (SLC): Erectile Dysfunction as a Biomarker of Systemic Complications for COVID-19 Long Haulers". Sexual Medicine Reviews. 10 (2): 271–285. doi:10.1016/j.sxmr.2021.11.001. PMC 8604714. PMID 34933829.
  87. ^ Hoertel N (November 2021). "Do the Selective Serotonin Reuptake Inhibitor Antidepressants Fluoxetine and Fluvoxamine Reduce Mortality Among Patients With COVID-19?". JAMA Network Open. 4 (11): e2136510. doi:10.1001/jamanetworkopen.2021.36510. PMID 34779851. S2CID 244115807.
  88. ^ Kato Y, Yamada S, Nishiyama K, Satsuka A, Re S, Tomokiyo D, et al. (14 March 2021). "Clomipramine suppresses ACE2-mediated SARS-CoV-2 entry". biorxiv: 2021.03.13.435221. doi:10.1101/2021.03.13.435221. S2CID 232283079.
  89. ^ a b c Yu Z, Yang Z, Wang Y, Zhou F, Li S, Li C, et al. (July 2021). "Recent advance of ACE2 and microbiota dysfunction in COVID-19 pathogenesis". Heliyon. 7 (7): e07548. doi:10.1016/j.heliyon.2021.e07548. PMC 8270732. PMID 34296023.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  90. ^ a b Shen Y, Yang X, Li G, Gao J, Liang Y (July 2021). "The change of gut microbiota in MDD patients under SSRIs treatment". Scientific Reports. 11 (1): 14918. Bibcode:2021NatSR..1114918S. doi:10.1038/s41598-021-94481-1. PMC 8295378. PMID 34290352. S2CID 236174457.
  91. ^ Hashimoto T, Perlot T, Rehman A, Trichereau J, Ishiguro H, Paolino M, et al. (July 2012). "ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation". Nature. 487 (7408): 477–481. Bibcode:2012Natur.487..477H. doi:10.1038/nature11228. PMC 7095315. PMID 22837003.
  92. ^ Panariello F, Cellini L, Speciani M, De Ronchi D, Atti AR (2020). "How Does SARS-CoV-2 Affect the Central Nervous System? A Working Hypothesis". Frontiers in Psychiatry. 11: 582345. doi:10.3389/fpsyt.2020.582345. PMC 7701095. PMID 33304284.
  93. ^ Malato J, Sotzny F, Bauer S, Freitag H, Fonseca A, Grabowska AD, et al. (August 2021). "The SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) in myalgic encephalomyelitis/chronic fatigue syndrome: A meta-analysis of public DNA methylation and gene expression data". Heliyon. 7 (8): e07665. doi:10.1016/j.heliyon.2021.e07665. PMC 8320404. PMID 34341773.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  94. ^ Blazquez A, Alegre J, Ruiz E (2009). "Women with chronic fatigue syndrome and sexual dysfunction: past, present, and future". Journal of Sex & Marital Therapy. 35 (5): 347–359. doi:10.1080/00926230903065179. PMID 20183003. S2CID 9130273.
  95. ^ Chao CH, Chen HJ, Wang HY, Li TC, Kao CH (July 2015). "Increased risk of organic erectile dysfunction in patients with chronic fatigue syndrome: a nationwide population-based cohort study". Andrology. 3 (4): 666–671. doi:10.1111/andr.12052. PMID 26198797. S2CID 23913092.
  96. ^ Okamoto T, Hatakeyama S, Imai A, Yamamoto H, Yoneyama T, Mori K, et al. (August 2020). "The association between gut microbiome and erectile dysfunction: a community-based cross-sectional study in Japan". International Urology and Nephrology. 52 (8): 1421–1428. doi:10.1007/s11255-020-02443-9. PMID 32193686. S2CID 213182193.
  97. ^ Geng Q, Chen S, Sun Y, Zhao Y, Li Z, Wang F, et al. (December 2021). "Correlation between gut microbiota diversity and psychogenic erectile dysfunction". Translational Andrology and Urology. 10 (12): 4412–4421. doi:10.21037/tau-21-915. PMC 8749073. PMID 35070823.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  98. ^ Li G, Li W, Song B, Wang C, Shen Q, Li B, et al. (February 2021). "Differences in the Gut Microbiome of Women With and Without Hypoactive Sexual Desire Disorder: Case Control Study". Journal of Medical Internet Research. 23 (2): e25342. doi:10.2196/25342. PMC 7952237. PMID 33629964.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  99. ^ Russo GI, Bongiorno D, Bonomo C, Musso N, Stefani S, Sokolakis I, et al. (April 2022). "The relationship between the gut microbiota, benign prostatic hyperplasia, and erectile dysfunction". International Journal of Impotence Research: 1–6. doi:10.1038/s41443-022-00569-1. PMID 35418604. S2CID 248121210.
  100. ^ Borgo F, Macandog AD, Diviccaro S, Falvo E, Giatti S, Cavaletti G, Melcangi RC (June 2021). "Alterations of gut microbiota composition in post-finasteride patients: a pilot study". Journal of Endocrinological Investigation. 44 (6): 1263–1273. doi:10.1007/s40618-020-01424-0. PMC 8124058. PMID 32951160.
  101. ^ Becker E, Schmidt TS, Bengs S, Poveda L, Opitz L, Atrott K, et al. (September 2017). "Effects of oral antibiotics and isotretinoin on the murine gut microbiota". International Journal of Antimicrobial Agents. 50 (3): 342–351. doi:10.1016/j.ijantimicag.2017.03.017. PMID 28689869.
  102. ^ "POTS - CFS/ME - SFN - Long Covid". CellTrend Luckenwalde. Retrieved 27 December 2022.
  103. ^ Olsen NJ (October 2004). "Drug-induced autoimmunity". Best Practice & Research. Clinical Rheumatology. 18 (5): 677–688. doi:10.1016/j.berh.2004.05.006. PMID 15454126.
  104. ^ Bhagavati S (14 April 2021). "Autoimmune Disorders of the Nervous System: Pathophysiology, Clinical Features, and Therapy". Frontiers in Neurology. 12: 664664. doi:10.3389/fneur.2021.664664. PMC 8079742. PMID 33935958.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  105. ^ Fagius J, Osterman PO, Sidén A, Wiholm BE (January 1985). "Guillain-Barré syndrome following zimeldine treatment". Journal of Neurology, Neurosurgery, and Psychiatry. 48 (1): 65–69. doi:10.1136/jnnp.48.1.65. PMC 1028185. PMID 3156214.
  106. ^ Solhjoo M, Goyal A, Chauhan K (2022). Drug-Induced Lupus Erythematosus. Treasure Island (FL): StatPearls Publishing. PMID 28722919. Retrieved 3 January 2023. {{cite book}}: |work= ignored (help)
  107. ^ Handa R, Deepak KK, Bhatia M, Aggarwal P, Pandey RM (July 2006). "Autonomic dysfunction in systemic lupus erythematosus". Rheumatology International. 26 (9): 837–840. doi:10.1007/s00296-005-0093-0. PMID 16365754.
  108. ^ "Diseases And Conditions". St. Clair Health. Retrieved 3 January 2023.
  109. ^ Dastoorpoor M, Zamanian M, Moradzadeh R, Nabavi SM, Kousari R (January 2021). "Prevalence of sexual dysfunction in men with multiple sclerosis: a systematic review and meta-analysis". Systematic Reviews. 10 (1): 10. doi:10.1186/s13643-020-01560-x. PMC 7789133. PMID 33407874.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  110. ^ Maynard, Craig L.; Elson, Charles O.; Hatton, Robin D.; Weaver, Casey T. (September 2012). "Reciprocal interactions of the intestinal microbiota and immune system". Nature. 489 (7415): 231–241. doi:10.1038/nature11551. ISSN 1476-4687.
  111. ^ Nian, Di; Shi, Peng; Qu, Hongdang; Sun, Junjie; Li, Qiang; Li, Qianqian; Wang, Chun; Ye, Ming (9 May 2021). "Pathogenic mechanism of intestinal microbiota involved in Guillain-Barre syndrome and with Bifidobacterium intervention". Archives of Medical Science. doi:10.5114/aoms/128103. ISSN 1734-1922.
  112. ^ Waldinger MD, van Coevorden RS, Schweitzer DH, Georgiadis J (April 2015). "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. Mood disorders-preclinical, clinical and translational aspects. 753: 263–268. doi:10.1016/j.ejphar.2014.11.031. PMID 25483212.
  113. ^ "Media Articles: PSSD & Related Conditions | RxISK". rxisk.org. Retrieved 27 December 2022.
  114. ^ "PSSD in the Media". UK PSSD Association. Retrieved 18 January 2023.
  115. ^ Baskerville K (1 December 2022). "What is post-SSRI Sexual Dysfunction (PSSD) and what do I need to know about it?". Mashable. Retrieved 16 December 2022.
  116. ^ Anonymous (8 June 2018). "My life in sex: 'After taking antidepressants, my genitals felt numb'". The Guardian. Retrieved 16 December 2022.
  117. ^ Brown D (3 November 2018). "Antidepressants were supposed to help me but they ended up making me impotent". Metro. Retrieved 27 December 2022.
  118. ^ "For Some People, the Sexual Side Effects of SSRIs Never Go Away". MEL Magazine. 30 June 2022. Retrieved 27 December 2022.
  119. ^ Wyton M (2 November 2021). "'Something So Sacred Has Been Taken Away from Me'". The Tyee. Retrieved 10 January 2023.
  120. ^ ""Despair takes a young man's life"". Canadian PSSD Society. Retrieved 10 January 2023.
  121. ^ "I Started Taking Zoloft Five Years Ago. I Haven't Felt Sexual Sensation Since". Narratively. 6 September 2016. Retrieved 18 January 2023.
  122. ^ "Disfunzione sessuale persistente dopo terapia anti-depressiva - Quotidiano Sanità". www.quotidianosanita.it. Retrieved 18 January 2023.
  123. ^ "THIS STORY HAS BEEN FORMATTED FO". psychrights.org. Retrieved 18 January 2023.
  124. ^ "PSSD Network - Antidepressant Induced Post-SSRI Sexual Dysfunction". PSSD Network - Antidepressant Induced Post-SSRI Sexual Dysfunction. Retrieved 16 December 2022.
  125. ^ "PSSD Forum - Index page". www.pssdforum.org. Retrieved 16 December 2022.
  126. ^ "Activism". PSSD International. Retrieved 16 December 2022.
  127. ^ "Mission Statement". Canadian PSSD Society. Retrieved 27 December 2022.
  128. ^ "RxISK | Prescription Drug Side Effects". rxisk.org. Retrieved 16 December 2022.
  129. ^ "Figuring out together which treatments work best". www.stuffthatworks.health. Retrieved 16 December 2022.
  130. ^ "Post-SSRI Sexual Dysfunction (PSSD) Research Fund | RxISK". rxisk.org. Retrieved 3 December 2022.
  131. ^ "RxISK Prize: Sexual problems after antidepressants, finasteride & isotretinoin | RxISK". rxisk.org. Retrieved 17 December 2022.
  132. ^ Leiblum SR, Nathan SG (2001). "Persistent sexual arousal syndrome: a newly discovered pattern of female sexuality". Journal of Sex & Marital Therapy. 27 (4): 365–380. doi:10.1080/009262301317081115. PMID 11441520. S2CID 216088649.
  133. ^ Hogan C, Le Noury J, Healy D, Mangin D (1 January 2014). "One hundred and twenty cases of enduring sexual dysfunction following treatment". The International Journal of Risk & Safety in Medicine. 26 (2): 109–116. doi:10.3233/JRS-140617. PMID 24902508.
  134. ^ Lorenz TK (March 2020). "Antidepressant Use During Development May Impair Women's Sexual Desire in Adulthood". The Journal of Sexual Medicine. 17 (3): 470–476. doi:10.1016/j.jsxm.2019.12.012. PMC 7197954. PMID 31937517.
  135. ^ Simonsen AL, Danborg PB, Gøtzsche PC (March 2016). "Persistent sexual dysfunction after early exposure to SSRIs: Systematic review of animal studies". The International Journal of Risk & Safety in Medicine. 28 (1): 1–12. doi:10.3233/jrs-160668. PMID 27176752.
  136. ^ a b Sarkar S, Schmued L (2010). "Neurotoxicity of Ecstasy (MDMA): An Overview". Current Pharmaceutical Biotechnology. 11 (5): 460–469. doi:10.2174/138920110791591490. PMID 20420572.
  137. ^ a b Ben-Sheetrit J, Aizenberg D, Csoka AB, Weizman A, Hermesh H (June 2015). "Post-SSRI Sexual Dysfunction: Clinical Characterization and Preliminary Assessment of Contributory Factors and Dose-Response Relationship". Journal of Clinical Psychopharmacology. 35 (3): 273–278. doi:10.1097/JCP.0000000000000300. PMID 25815755. S2CID 2523437.
  138. ^ a b Zajączkowska R, Kocot-Kępska M, Leppert W, Wrzosek A, Mika J, Wordliczek J (March 2019). "Mechanisms of Chemotherapy-Induced Peripheral Neuropathy". International Journal of Molecular Sciences. 20 (6): 1451. doi:10.3390/ijms20061451. PMC 6471666. PMID 30909387.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  139. ^ "Post-SSRI Sexual Dysfunction Literature | RxISK". rxisk.org. Retrieved 18 January 2023.
  140. ^ "Academic Sources". Canadian PSSD Society. Retrieved 18 January 2023.
  141. ^ "Academic Sources". PSSD International. Retrieved 18 January 2023.
  142. ^ "LETTERATURA MEDICA". LETTERATURA MEDICA. Retrieved 18 January 2023.
  143. ^ Kauffman RP (2008). "Persistent sexual side effects after discontinuation of psychotropic medications". Primary Psychiatry. 15: 24.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Post-SSRI_sexual_dysfunction&oldid=1134827244"