Full PSSD Wikipedia article

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Full PSSD Wikipedia article

Unread post by Micromegas »

I realize we already have a link to where this is posted on the RxISK site, but I figured having the full article here couldn't hurt.

Post-SSRI Sexual Dysfunction
[article was deleted from Wikipedia in January 2014]

From Wikipedia, the free encyclopedia

Post-SSRI sexual dysfunction (PSSD)[1] is a name given to a reported iatrogenic sexual dysfunction caused by the previous use of selective serotonin reuptake inhibitor (SSRI) antidepressants. While apparently uncommon, it can last for months or years after the discontinuation of SSRIs.[2] It may represent a specific subtype of SSRI discontinuation syndrome. This condition has not been well-established or studied in the field of medicine.


1 Symptoms
2 Prevalence
2.1 Study data
3 Case reports
3.1 Published reports
3.2 Surveillance and reporting
4 Etiology
4.1 Animal studies
4.2 Short-term effects
4.3 Long-term effects
4.4 Relationship to "chemical imbalance" theory
4.4.1 Other drugs
5 Treatment
6 References
7 External links


One or more of the following sexual symptoms attributed to PSSD after the discontinuation of SSRIs include:

Decreased libido
Impotence or reduced vaginal lubrication
Difficulty initiating or maintaining an erection or becoming aroused
Persistent sexual arousal syndrome despite absence of desire
Muted, delayed or absent orgasm (anorgasmia)
Reduced or no experience of pleasure during orgasm (ejaculatory anhedonia)
Premature ejaculation
Weakened penile, vaginal or clitoral sensitivity
Genital anesthesia
Loss or decreased response to sexual stimuli[3]


The true prevalence of PSSD has yet to be determined, although published calls have been made for post-marketing epidemiological studies.[4][5] It is known that SSRIs can cause various types of sexual dysfunction. Initial studies found that such side effects were reported in less than 10% of patients. When doctors have specifically asked about treatment-emergent sexual difficulties, some have found that they are present in up to 60%[6] of patients. Spontaneous reporting methods are believed to result in lower reporting rates than targeted questions, either due to recall bias or stigma regarding sexual dysfunction.[7]

Study data[edit]

While sexual dysfunction can be common while taking SSRIs, the problem of persistent dysfunction after discontinuation does not appear to be as frequent, or at least not as well-known.[8] Onset of sexual problems often occurs during, and sometimes after, extended SSRI use but there have been reports of rapid onset as well. It appears as though the majority of people regain their sexual function after stopping SSRIs,[citation needed] but some do not, and are faced with the persistent symptoms of post-SSRI sexual dysfunction (PSSD). In one study in which patients with SSRI-induced sexual dysfunction were switched to the dopaminergic antidepressant amineptine, 55% still had at least some type of sexual dysfunction after six months compared to 4% in the control group treated with amineptine alone.[9] In recent placebo controlled double-blind studies testing the efficacy of SSRIs for treating premature ejaculation, it has been noted that the ejaculation-delaying effect of the medications may last for months after discontinuation in a percentage of the trial participants.[10][11][12]

Case reports[edit]

Published reports[edit]

Three cases of hyposexuality following SSRI use[13] and a fourth case describing genital anesthesia following SSRI use were described in 2006.[14] A fifth case of similar findings was published in late 2007.[15] In early 2008, three more cases were published[2] in the Journal of Sexual Medicine, selected from a Yahoo Group composed of over 3500 PSSD sufferers. There have also been several published cases of Persistent Genital Arousal Disorder (PGAD)[16][17][18] and premature ejaculation[19] that start and last long after withdrawal from SSRIs. These symptoms are quite different from, and should not be confused with, hypersexuality.

Sandra Leiblum described persistent genital arousal disorder based on a case where a PSSD was established.[20]

Surveillance and reporting[edit]

To establish, monitor, and regulate causation of PSSD in individual patients, one approach in use by consulation-liaison psychiatrists is to assay measurable parameters of patient health (hormone levels, sexual functioning) with a survey or laboratory tests before and after administering a psychiatric drug, based on individual patient concern regarding each of the listed side effects. If PSSD develops, a correlation can be established between assay results and PSSD, guiding further treatment for the individual patient and others. A lack of education on drug side effects and the presence of clinical depression in a patient who is a candidate for antidepressant therapy can combine to reduce the patient's ability to advocate for tests. Calls have been made for better informed consent regarding the possibility of permanent sexual dysfunction when prescribing SSRIs to potential patients.[21] Post-administration reporting of side effects may provide useful data for development of new drugs and better inform patients of their risks. In The United States, adverse effects are reported with FDA forms, 3500 for optional use (patients can self-report using this form), and 3500A, for mandatory reporting.


It is currently not known what causes PSSD. Fluoxetine (Prozac), the prototypical SSRI, is classified as a reproductive toxin[22] by the Center for the Evaluation of Risks to Human Reproduction (CERHR), an expert panel at the National Institute of Environmental Health Sciences at the National Institutes of Health.

Animal studies[edit]

Experiments with rodents have shown that chronic treatment with SSRIs at a young age results in permanently decreased sexual behavior that persists into adulthood and is similar to PSSD.[23][24] These studies found reductions in both the rate-limiting serotonin synthetic enzyme, tryptophan hydroxylase, in dorsal raphe and in serotonin transporter (SERT) expression in the cortex. It also appears as though PSSD might be transgenerationally inherited, at least in rodents, since maternal exposure to fluoxetine impairs sexual motivation in adult male mice.[25] It is not known whether these findings in rodents recapitulates the human condition, but the long term neurobehavioral consequences may be similar.[26]

Short-term effects[edit]

There are physiological changes while on SSRIs. It has been postulated that drugs can exert epigenetic effects.[27]

Changes include reduced hypothalamic-pituitary-testis axis (HPTA) function,[28] decreased testosterone levels,[29] reduced sperm counts, which showed marked improvement after discontinuation[30] and reduced semen quality with damaged sperm DNA, which is reversible after discontinuation.[31]

Long-term effects[edit]

Treatment with fluoxetine (Prozac) has been shown to cause persistent desensitization of 5HT1A receptors after removal of the SSRI in rats.[32] These long-term adaptive changes in 5-HT receptors, as well as more complex, global changes, are thought to be mediated through alterations of gene expression.[33][34][35][36][37] Some of these gene expression changes are a result of altered DNA structure caused by chromatin remodeling,[38][39] specifically epigenetic modification of histones[40] and gene silencing by DNA methylation due to increased expression of the methyl binding proteins MeCP2 and MBD1.[41] Altered gene expression and chromatin remodeling may also be involved in the mechanism of action of electroconvulsive therapy (ECT).[42][43]

Because described gene expression changes are complex, and can involve persistent modifications of chromatin structure, it has been suggested that SSRI use can result in persistently altered cerebral gene expression leading to compromised catecholaminergic neurotransmission and neuroendocrine disturbances.[13] However, without detailed neuropsychopharmacological, pharmacogenomic and toxicogenomic[44] research, the definitive cause remains unknown.

Relationship to "chemical imbalance" theory[edit]

Some critics of SSRIs claim that the widely-disseminated television and print advertising of SSRIs promotes an inaccurate message, oversimplifying what these medications actually do.[45] Much of the criticism stems from questions about the validity of claims that SSRIs work by correcting chemical imbalances. Without tools to accurately measure neurotransmitter levels and to allow for continuous monitoring during treatment, it remains difficult to know if one is correctly targeting a deficient neurotransmitter (i.e. correcting an imbalance) or reaching a desirable level of a particular neurotransmitter. It has been argued that without this knowledge for each patient, SSRIs can actually cause chemical imbalances and abnormal brain states.[46] One possible mechanism is by inhibition of dopaminergic neurotransmission,[47] resulting in described persistent sexual dysfunction.

Other drugs[edit]

Antipsychotics are also known to cause sexual dysfunction that is similar to PSSD, especially because of their antagonist effects on D2 dopamine receptors, as well as H1, α1 and α2 antagonism.[48] Finasteride, which is used to treat male pattern baldness and benign prostatic hypertrophy, has also been found to cause persistent sexual dysfunction in a subset of patients that are treated with the drug.[49]


There is no known cure for PSSD, mostly because its etiology is still poorly understood. Possible treatment options for SSRI-induced sexual dysfunction have been reviewed theoretically.[50][51][52] However, there has been a lack of randomized, placebo-controlled, double-blind trials of potential treatments. Of those that have been done, there is evidence for the following management strategies: for erectile dysfunction, the addition of a PDE5 inhibitor such as sildenafil; for decreased libido, possibly adding or switching to Wellbutrin (Bupropion); and for overall sexual dysfunction, switching to nefazodone.[53]

According to a survey of psychiatrists, Bupropion is the drug of choice for the treatment of SSRI-induced sexual dysfunction, although this is not an FDA-approved indication. Thirty-six percent of psychiatrists preferred switching patients with SSRI-induced sexual dysfunction to bupropion, and 43 percent favored the augmentation of the current medication with bupropion.[54] A higher dose of bupropion (minimum 300 mg) may be necessary: a randomized study with 31 subjects that utilized a lower dose (150 mg) once daily failed to find a significant difference between bupropion, sexual therapy or combined treatment,[55] while a subsequent study with 234 subjects and employing Bupropion SR 150 mg twice daily did show a significant improvement of sexual function.[56]

Some other off-label prescriptions include pramipexole, ropinirole, yohimbine and possibly other molecules increasing the dopamine blood levels, though there have been no double blind placebo-controlled trials to show their efficacy. The chemical cabergoline, which is an agonist of D2 receptors, which in turn decreases prolactin, has fully restored orgasm in 1/3rd of anorgasmic subjects, and partially restored orgasm in another 1/3rd of subjects. [57]

Most studies of sexual dysfunction have been done in men, though some studies done in women have shown benefit from bupropion (at doses >300 mg/d). There has been 1 study showing possible benefit in orgasmic function with sildanefil, though no change in desire or arousal.[58]


· Bahrick AS (2006). "Post SSRI Sexual Dysfunction" (PDF). Tablet 7 (3): 2–10.
· Csoka AB, Bahrick AS, Mehtonen O-P (2008). "Persistent Sexual Dysfunction after Discontinuation of Selective Serotonin Reuptake Inhibitors (SSRIs)". J Sex Med. 5 (1): 227–33. doi:10.1111/j.1743-6109.2007.00630.x. PMID 18173768.
· Persistent Sexual Dysfunction after Discontinuation of Selective Serotonin Reuptake Inhibitors J Sex Med 2008;5:227–233
· Kauffman RP (2008). "Persistent Sexual Side Effects after Discontinuation of Psychotropic Medications". Primary Psychiatry 15: 24.
· Farnsworth KD, Dinsmore WW (January 2009). "Persistent sexual dysfunction in genitourinary medicine clinic attendees induced by selective serotonin reuptake inhibitors". Int J STD AIDS 20 (1): 68–9. doi:10.1258/ijsa.2008.008402. PMID 19103903.
· Zajecka J, Mitchell S, Fawcett J (1997). "Treatment-emergent changes in sexual function with selective serotonin reuptake inhibitors as measured with the Rush Sexual Inventory". Psychopharmacol Bull 33 (4): 755–60. PMID 9493488.
· Balon R (September 2006). "SSRI-associated sexual dysfunction". Am J Psychiatry 163 (9): 1504–9; quiz 1664. doi:10.1176/appi.ajp.163.9.1504. PMID 16946173.
· Bahrick AS (2008). "Persistence of Sexual Dysfunction Side Effects after Discontinuation of Antidepressant Medications: Emerging Evidence". The Open Psychology Journal 1: 42–50. doi:10.2174/1874350100801010042.
· Montejo AL, Llorca G, Izquierdo JA, et al. (1999). "[Sexual dysfunction with antidepressive agents. Effect of the change to amineptine in patients with sexual dysfunction secondary to SSRI]". Actas Esp Psiquiatr (in Spanish; Castilian) 27 (1): 23–34. PMID 10380144.
· Safarinejad MR, Hosseini SY (2006). "Safety and efficacy of citalopram in the treatment of premature ejaculation: a double-blind placebo-controlled, fixed dose, randomized study". Int. J. Impot. Res. 18 (2): 164–9. doi:10.1038/sj.ijir.3901384. PMID 16107866.
· Arafa M, Shamloul R (2006). "Efficacy of sertraline hydrochloride in treatment of premature ejaculation: a placebo-controlled study using a validated questionnaire". Int. J. Impot. Res. 18 (6): 534–8. doi:10.1038/sj.ijir.3901469. PMID 16554853.
· Safarinejad MR (October 2007). "Safety and efficacy of escitalopram in the treatment of premature ejaculation: a double-blind, placebo-controlled, fixed-dose, randomized study". J Clin Psychopharmacol 27 (5): 444–50. doi:10.1097/jcp.0b013e31814b98d4. PMID 17873675.
· Csoka AB, Shipko S (2006). "Persistent sexual side effects after SSRI discontinuation". Psychother Psychosom 75 (3): 187–8. doi:10.1159/000091777. PMID 16636635.
· Bolton JM, Sareen J, Reiss JP (2006). "Genital anaesthesia persisting six years after sertraline discontinuation". J Sex Marital Ther 32 (4): 327–30. doi:10.1080/00926230600666410. PMID 16709553. Unknown parameter |unused_data= ignored (help)
· 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.
· Goldmeier D, Leiblum SR (April 2006). "Persistent genital arousal in women -- a new syndrome entity". Int J STD AIDS 17 (4): 215–6. doi:10.1258/095646206776253480. PMID 16595040.
· 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. doi:10.1111/j.1743-6109.2006.00224.x. PMID 16490037.
· 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. doi:10.1080/00926230701636205. PMID 18224549. Unknown parameter |unused_data= ignored (help)
· Adson DE, Kotlyar M (December 2003). "Premature ejaculation associated with citalopram withdrawal". Ann Pharmacother 37 (12): 1804–6. doi:10.1345/aph.1D214. PMID 14632589.
· Leiblum, SR; Nathan, S (2001). "Persistent sexual arousal syndrome: a newly discovered pattern of female sexuality". J Sex Marital Ther 27 (4): 365–380.
· Bahrick AS, Harris MM (2008). "Sexual Side Effects of Antidepressant Medications: An Informed Consent Accountability Gap". Journal Contemp Psychother.
· Hines RN, Adams J, Buck GM, Faber W, Holson JF, Jacobson SW, Keszler M, McMartin K, Segraves RT, Singer LT, Sipes IG, Williams PL. NTP-CERHR Expert panel report on the reproductive and developmental toxicity of fluoxetine.NIH Publication No. 05-4471. 2004;1-211.
· Maciag D, Simpson KL, Coppinger D, et al. (January 2006). "Neonatal Antidepressant Exposure has Lasting Effects on Behavior and Serotonin Circuitry". Neuropsychopharmacology 31 (1): 47–57. doi:10.1038/sj.npp.1300823. PMC 3118509. PMID 16012532.
· de Jong TR, Snaphaan LJ, Pattij T, et al. (January 2006). "Effects of chronic treatment with fluvoxamine and paroxetine during adolescence on serotonin-related behavior in adult male rats". Eur Neuropsychopharmacol 16 (1): 39–48. doi:10.1016/j.euroneuro.2005.06.004. PMID 16107310.
· Gouvêa TS, Morimoto HK, de Faria MJ, Moreira EG, Gerardin DC (September 2008). "Maternal exposure to the antidepressant fluoxetine impairs sexual motivation in adult male mice". Pharmacol. Biochem. Behav. 90 (3): 416–9. doi:10.1016/j.pbb.2008.03.025. PMID 18457868.
· Maciag D, Coppinger D, Paul IA (December 2006). "Evidence that the deficit in sexual behavior in adult rats neonatally exposed to citalopram is a consequence of 5-HT1 receptor stimulation during development". Brain Res. 1125 (1): 171–5. doi:10.1016/j.brainres.2006.10.009. PMC 1762094. PMID 17101120.
· 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.
· Safarinejad MR (August 2008). "Evaluation of endocrine profile and hypothalamic-pituitary-testis axis in selective serotonin reuptake inhibitor-induced male sexual dysfunction". J Clin Psychopharmacol 28 (4): 418–23. doi:10.1097/JCP.0b013e31817e6f80. PMID 18626269.
· Cohen AJ. Antidepressant-Induced Sexual Dysfunction Associated with Low Serum Free Testosterone. Psychiatry Online 1999.
· Tanrikut C, Schlegel PN (January 2007). "Antidepressant-associated changes in semen parameters". Urology 69 (1): 185.e5–7. doi:10.1016/j.urology.2006.10.034. PMID 17270655.
· Safarinejad MR (November 2008). "Sperm DNA damage and semen quality impairment after treatment with selective serotonin reuptake inhibitors detected using semen analysis and sperm chromatin structure assay". J. Urol. 180 (5): 2124–8. doi:10.1016/j.juro.2008.07.034. PMID 18804223.
· Raap DK, Garcia F, Muma NA, Wolf WA, Battaglia G, van de Kar LD (February 1999). "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". J. Pharmacol. Exp. Ther. 288 (2): 561–7. PMID 9918559.
· Faure C, Mnie-Filali O, Haddjeri N (February 2006). "Long-term adaptive changes induced by serotonergic antidepressant drugs". Expert Rev Neurother 6 (2): 235–45. doi:10.1586/14737175.6.2.235. PMID 16466303.
· Palotás M, Palotás A, Puskás LG, et al. (December 2004). "Gene expression profile analysis of the rat cortex following treatment with imipramine and citalopram". Int. J. Neuropsychopharmacol. 7 (4): 401–13. doi:10.1017/S1461145704004493. PMID 15315716.
· Kálmán J, Palotás A, Juhász A, et al. (November 2005). "Impact of venlafaxine on gene expression profile in lymphocytes of the elderly with major depression--evolution of antidepressants and the role of the "neuro-immune" system". Neurochem. Res. 30 (11): 1429–38. doi:10.1007/s11064-005-8513-9. PMID 16341940.
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Re: Full PSSD Wikipedia article

Unread post by SingleCell »

Is there a way to get it posted back up on Wikipedia?
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Re: Full PSSD Wikipedia article

Unread post by Micromegas »

SingleCell wrote:Is there a way to get it posted back up on Wikipedia?
Good question. Sonny lobbied to keep it from being removed when the removal process was taking place, but someone was making a focused effort to get it taken down. They ended up merging part of it with the main SSRI article.
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Re: Full PSSD Wikipedia article

Unread post by PZS1234 »

Do we have anyone leading the effort to bring back the wikipedia page?


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Re: Full PSSD Wikipedia article

Unread post by Ghost »

I'm going to start now and not rest until the page is back up. I have no idea how to work wikipedia, but I'm about to find out. This has gone on long enough.
- Medical Student & Friendly poltergeist - Lexapro Sept '14. [Hx] [PSSD Lab] [r/PSSD] [Treatment Plan] - Add "Ghost" in replies so I see it :)
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Re: Full PSSD Wikipedia article

Unread post by Bigmum »

In other countries it still exist....:/
Sorry for my bad (terrible) English.
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Re: Full PSSD Wikipedia article

Unread post by Ghost »

It's already back up. It can be found with a simple google search, or here:

- Medical Student & Friendly poltergeist - Lexapro Sept '14. [Hx] [PSSD Lab] [r/PSSD] [Treatment Plan] - Add "Ghost" in replies so I see it :)
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Re: Full PSSD Wikipedia article

Unread post by Juvo »

Ghost wrote:It's already back up. If you want to see my shit job at editing (or to help me create it), it can be found with a simple google search, or here:

Nice job ghost. Now, it would be a miracle if we can get it linked to the main SSRI page.
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Re: Full PSSD Wikipedia article

Unread post by sjv16477 »

Until now the most extensive and reliabel wikipedia article on PSSD is this

https://it.wikipedia.org/wiki/Disfunzio ... _post-SSRI

Please translate it to your languages!
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