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Wikipedia Stumbles: Post-SSRI Sexual Dysfunction

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A couple in bed with a relationship problem

Editorial Note: There was until recently a Wikipedia post on Post-SSRI Sexual Dysfunction (PSSD), which helped put this condition on the map. On January 27 it was taken down. We reproduce the original post here and in a post tomorrow we will give the debate surrounding its removal.

See our main PSSD page for more information about the condition.

Post-SSRI Sexual Dysfunction (PSSD)

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.

Symptoms

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]

Prevalence

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

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

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

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.

Etiology

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

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

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

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

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

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]

Treatment

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]

References

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Reader Interactions

Comments

  1. I wanted to add a comment re: Wikipedia. Shortly after my website, http://www.LupronVictimsHub.com, went online (October 2008), someone put a link to my site on Wiki’s “Lupron” page. It was then taken down, and later put back up, and again taken down. (I know nothing about how to add/edit Wiki, nor who was putting up or taking down the link). The “Lupron” page was discontinued about 2009 or 2010, and a “Leuprorelin / leuprolide” page put in its stead … no more links to my site were ever entered. On this page is a ‘link’ to the National Women’s Health Network’s (NWHN) 2008 cover story on Lupron (which is based on my research and highlights Lupron’s serious risks) – but in fact Wikipedia’s link brings one to Wiki’s “NWHN page”, and not to the Lupron article. I just finally asked their editorial/science desk to correct this, and provided Wikipedia the correct link (http://nwhn.org/lupron%C2%AE-%E2%80%93-what-does-it-do-women%E2%80%99s-health).

    While Wiki’s leuprolide page does indeed give a strong warning about Lupron’s use in “children and adolescents”, and gives print to the debunking of the Lupron/autism protocol scam, the drug is otherwise treated quite gently (ie “superior alternative in trans women”, soft references). No mention is made of the multitudes of adverse events, or of Lupron Victims, or of Lupron litigation; and off-label promotion is evident. Imo, Wiki’s leuprolide page is run and/or influenced by the industry.

    Reply

  2. I’m going to kill myself because of decades of depression and PSSD. I’m planning it now.

    Reply

    • PLEASE CALL 911 IMMEDIATELY! There is life after depression and PSSD and new research is coming out all the time that can help. You DO have a future and you CAN have a full life! PLEASE DO NOT KILL YOURSELF! I hope you get this message. Your life is precious and worth living.

      Reply

    • Look!I know exactly how you are feeling. I’m going through the same thing myself and have been for year’s. My situation is from effexor , but I know all to well the hell you are going through, I have been to multiple specialists spent thousands of dollars just to get shoulder shrugs. Killing yourself will solve nothing but hurt those that care for you , my goal is to make these bastards pay for the pure hell I’ve been living these past several years, our condition isn’t all that uncommon, to be getting the bullshit answers from the Doctor’s that I have been getting the Most of the Doctor’s I have spoke to are familiar with the condition but have zero clue on how to treat it. I have been from Minnesota( Mayo Clinic) and to San Diego ( Sexual Medicine Clinic. Spending time and money I don’t have to reach dead end after dead end, I didn’t have this issue before Anti- Depressants, and my battle is well documented. I’ll be honest I’ve had the same desperate thoughts that you are having, But I dont need to make my Wife and kids pay for irresponsible pharma. What we need is a Doctor that will officially diagnose this We need to connect and make enough noise that we get recognized. I’m not greedy and I don’t like to sue, but I’am angry and become more so each day. This did not occur in a vacuum, if you knew this could happen , would you have taken the drug that was prescribed to you? I sure as the hell wouldn’t have and I have more issus now then i started with,This is not a rare thing there are a lot of us in the same boat, however the nature of the disorder keeps it fairly quiet and big Pharma keeps making billions off the same poison that put you and I in this situation, I’m willing to try and get a large group to get some attention, you found me that means we can find other’s. stay strong my Friend and contact me.

      Reply

      • I was on 2 other antidepressants that I came off and within 3 days I would have a high sex drive again but then I took pristique, (which had a motivating affect) anti depressant for a month and have been off for a month and 80% of my libido is diminished. What the hell is going on and how can I get it back? I tried horny goat weed but that is still no where close to where I was. Im lost

        Reply

    • Paxera is paroxetine (HCl) which is one of the SSRIs. All SSRIs — fluoxetine, paroxetine, sertraline, citalopram, escitalopram and so on — can cause PSSD (hence the name of the syndrome) but please note that it is not only them that are known to cause sexuality related damage. Major tranquilizers — quetiapine, risperidone, haloperidol, ziprazidone, aripiprazole, olanzapine and so forth — are also known to cause permanent sexual death.

      PSSD-like syndromes can be observed also in the case of many non-psychiatric drugs like finasteride, dutasteride, minoxidil and isotretinoin to mention a few. Concerning the immense scale of the problem in the population it is a shame that the condition is so incredibly poorly understood, studied and cared about.

      On the one hand it is understandable from psychiatry and pharmaceutical industry point of view to minimize and silence the debate and discussion concerning PSSD since if caught in the public eye the whole antidepressant and major tranquilizer consumption are in danger of going down the tube. I doubt there would be so many people willing to accept the risk of permanent brain damage in return for questionable benefit.

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  4. Can this webpage be fixed so that a person doesn’t have to scroll to see the info on PSSD?

    Some people may come to this page and only see the Wikipedia removal notice and think there is nothing else on this page.

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  5. I was on Effexor XR 300mg, Wellbutrin 300mg, and Adderall 60mg. My doctors were idiotic, I was lied to about the drugs, and these drugs were coerced by doctors while I was in custody. I was not on any drugs before these doctors did this to me. After years I got out of their custody, I quit the drugs over 1 month titrating twice down to nothing on my own. Immediately I experienced serious reaction. I had brown piss, my muscles got tighter, I became sensitive to cold experiencing constriction like I’d never had. My orgasms also stopped working for a month. I was not under the care of a doctor during this time, so I received no care, but lets face it, all they’d do is put me back in the drugs and it probably wouldn’t have fixed it. The orgasms came back a little, however, each orgasm causes extreme muscle tightening, swelling of tissue, pain, burning and stinging that lasts weeks and after weeks my muscles start to loosen a little and the pain goes down just a bit. It’s as if an orgasm activates extreme hyper tonia, aka dystonia..

    Why this is a big problem, is because I was literally in control of the CIA during this period, they began to use this problem to their advantage. Raping me, forcing ejaculation after ejaculation to assault me.

    Details on this @ http://www.obamasweapon.com/

    I am not joking.

    I recommend the symptom be added however, that a strong dystonia or shock can start to occur after orgasm, making it unsafe to orgasm..

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  6. I started taking zoloft in 1999. by the end of 2000 my sexual function was gone completely. interestingly in 2003 when i was pregnant the function came back but left again as soon as I delivered. That’s a big clue right there imo. That’s why I think Viagra might help but my doctor refuses to prescribe it to women. I stopped taking the Zoloft in spring of 2009 but still suffer to this day. I want to get together with other victims and try to start a class action law suit. i can’t afford sex therapy that’s not covered by insurance or experimental drugs. If you can sue for spilling coffee on your lap, you would think you could sue for this.

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    • I couldn’t agree more…we really need to all band together and form a class action lawsuit. Probably getting on the Yahoo PSSD Group that’s out there is the best way to get a lot of people on board. I’m beyond mad that a doctor sold me on Zoloft and now I’ve been suffering from PSSD for 9 years. Still searching for a solution…

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      • I just reposted the article on Wikipedia. I’m guessing Wikipedia felt pressure to remove due to the pharmaceutical industrial complex. I took Paxil and Zoloft for a year when I was 16 and my sex drive is absolutely shot. I have weak erections and it’s impossible for my to ejaculate. We NEED to sue these SSRI companies. They need to cough up millions for robbing the greatest gift anyone could experience.. the gift of life. Let’s start a group together guys!

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      • I have the same sexual dysfunction from 2013 due to Escitalopram, but also Isotretinoin (Accutane in USA). I would like to start or participate to a class section as well. Have you started one?

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  7. I was prescribed Fluoxetine around 2008-2009 by my occupational therapist. I was only like 16-17 at the time. I did not know what it was, she assured me that there were no side effects, even though she was not a qualified doctor and it was actually illegal for her to make a prescription, she actually got me started on it by handing me somebody else’s prescription such was her level of self importance.

    I remember asking her if it could cause erection problems or hair loss she laughed that off and said: “No of course not!” but I was told by an adult I knew that it could.

    After discontinuing the drug the side effects remained, I’d describe it as for a few years I had brain fog, that’s mostly gone now, I had incredibly painful migraines that were usually concentrated in the left side of my head, I had scalp pains that were incredible and came with hair loss (nobody in my family has suffered from hair loss including my extended family on both sides such as cousins and second cousins, my dad is in his 50’s still has hair my mothers daddied in his 70’s with hair), I would fart and it would be incredibly painful like a chemical burning sensation in my rectum, I would burp and it would feel like a chemical burning sensation in my throat, chest and scalp. I come down with colds and the flu a lot now, I can’t get an erection except maybe if I eat the right foods, don’t masturbate for weeks and take viagra at the same time together, I also got anxiety attacks (I can’t even describe how bad they were), repeated De Ja Vu about 10-15 times a day while I was on the drug and tinnitus that was extreme and regular to the point it effected my balance, blurred vision, incredible muscle twitching like a shock was being sent through my body, my balls shrunk for a period.

    My penus is a fraction of the size it was, there is decreased sensitivity.

    Currently now at 23 I’m still impotent without drugs like viagra, I still suffer throat, scalp and chest pains, still suffer hair loss (not anything like when I was on the drug however), still get migraines (terrible but not as bad as when I was on the drug where it felt so bad that I would want to be sedated), and I still have a weakened immune system that makes me ill (I also have bad asthma and Hayfever now). The other side effects have not gone entirely but they are at a much reduced and less frequent state.

    This is all from two short spells on the drug in my mid-late teens. I know what it has done to me and I’d be happy to say it to anyone, if anybody wants to sue me that’s fine let them try. I have really contemplated suicide so many times over the side effects.

    I don’t know how common the side effects I have suffered are but my advise to anyone being prescribed this drug is avoid it. There may be a 1% chance it will happen to you, there may be a 5-10% chance there may be a 20-30% chance but we don’t know.

    My guess is 5-10% suffer the same side effects as me upon discontinuing the drug but it is impossible to prove as we never get honest impartial surveys done.

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  8. I want to share an article found on forum

    Looking for a cure: are why focusing on the right way?
    Everyone knows the main theory about the pathogenesis of PSSD: the excessive release of serotonin (which has a mixed but essentially inhibitory role on sexual functions) by the serotonergic neurons (concentrated in the raphe nuclei of the midbrain) caused the “desensitization” of 5-HT1A autoreceptors (that act as sentinels that regulate the release of a substance according on how much there is already in circulation, this mechanism is also called negative feedback) .
    The “down regulation” of the 5-HT1A autoreceptors is instead caused by chronic and excessive activation by its natural “agonist” (serotonin) that is made available in abnormal quantities by the use of SSRIs. It is therefore natural to think to the autoreceptors as something that is “damaged” by excessive competition and that can be cured using an antagonist that lead him to be again “sensitive.”
    At this point that we have to do a reflection: the autoreceptor is a sentinel, a switch that if “on” sends a chemical signal. What the cell (neuron) have to do when it receives this chemical signal is written in the genes, that is in the sequence of the DNA; how much it should do (that is, how much to increase or decrease the release of serotonin) it depends on the genes expression.
    Essentially two mechanism regulate gene expression:
    • Binding of chemical groups directly to DNA (covalently) that function as silencers or activators. The main inhibitor is the methyl group that, binding at particular points of the promoter sequences, silences gene expression. The protein that bind methyl groups to DNA is the DNMT.
    • The other is the tangling of the DNA around proteins (called histones): if the DNA is wrapped on itself, the molecular machines that should read the instruction contained in the DNA, cannot bind the DNA because there isn’t sufficient space. The ability of a histone to compact a DNA molecules (and thus repress gene expression) depends on the presence of particular molecules bound to the histone. The main one is the acetate group: if it binds to histone, forces him to expand and so molecular machines can come in and gene expression is activated.
    The acetyl groups are linked to histone by HAT and detached from it by HDAC. Also histones can be methylated in some particular positions, and this has mixed effects on gene expression.
    SSRIs activate gene silencing
    It’s well known that SSRIs activate the gene-silencing mechanisms. During the assumption has been seen :
    • Increase in the expression of certain proteins that carry methyl groups (called MeCP2 and MBD1)
    • Increase the mRNA synthesis of HDAC2 gene (the HDAC of a particular subtype of histone)
    • There’s a decreased acetylation in the histone “H3” in three areas of serotonin projection: the caudate-putamen (striatum), the frontal cortex and the dentate gyrus (5-HT neurons are extensively arborized, and their axons reach all brain areas).
    All this suggests the induction of gene silencing.
    Now we can rethink to the neuron such a stubborn person who does something of wrong: we told him to correct his behavior (the autoreceptor send his message to the cell) but he will not change his behavior (excessive release of serotonin) because he is a person who does not listen what we told to him (reduced gene expression).
    So we cannot think to reactivate the negative feedback mechanism only binding them an antagonist because who is stuck in a situation of “off” is not the autoreceptor, but the DNA is to be.
    The right strategy therefore have to be the reactivation of gene plasticity which can then be guided in the right direction by the use of an antagonist of the 5-HT1A autoreceptors.
    A possible partial theoretical confirmation of this hypothesis is the results of a study in which rats whit an animal model of tardive dyskinesia (a disorder in some ways similar to the PSSD) had a partial remission of the disease using a HDAC inhibitor .
    How to induce gene expression plasticity
    Firstly, we recall the main objectives:
    • To promote the demethylation of DNA by inhibiting DNMT: the new synthesized DNA is less methylated and then whit an increased gene expression.
    • Inhibit the deacetylation of histones, in particular inhibiting HDAC
    • Encourage the acetylation of histones, in particular by increasing the activity of HAT
    It has also been seen that the increase of histone acetylation is accompanied by a demethylation of DNA, that is, the two events have a synergistic effect . It ‘important to note first of all that these effects are time and dose dependent, ie the effects are proportional to the dose taken and manifests itself after some time.
    Several compounds can do this. Most of them are natural occuring compounds and found in green tea but this does not mean that they are little effective: some are very promising for the treatment of other diseases in which the gene expression change is crucial. Other are drugs are already used for other purposes .
    Unlucky, often they have a low biodisponibility and a short half-life, than high and multiple doses should be necessary.
    Most promising are listed for first.
    EPIGALLOCATECHINE GALLATE (EPCG)
    One of most studied, well caracterized and most effective natural compound that influence gene expression. Is one of major component of green tea extract. It can easily cross blood-brain barrier and is demonstrated that directly bind DNA19 . It is DNMT1, DNMT3, HDAC1 inhibitor and a MeCP2 inhibitor using Mg2+ as cofactor. Increase amount of glutathione and indirectly the acetilation of histone H3 and H4. Unlucky it is also a weak inhibitor of HAT, has a very low biodisponibility and may be hepatotoxic. Has been demonstrated that minimum effective dose in order to induce genetic effect is 800 mg 2 times a day. The ingestion of high grade, dried green extract, which contains a lot of different catechine, gallate and flavonoid, is more effective then the ingestion of pure EPGC: all the “gallate” and “chatechin” compounds are generally HDAC and DNMT inhibitor and they have a synergistic effect. They’re generally recognized as safe.
    QUERCITINE
    A flavonoid, is a strong enhancer of H3 and H4 histone acetylation, thus activates SIRT1 and SIRT6 mediated deacetylation; Inhibit DNMT and LSD1 (histone demethylating protein). It is also a weak MAOI. Was found to be active at a concentration of 75-100 um.
    GENISTEINA (and less DAIDZEINE and BIOCIANINE A)
    They are phytoestrogens and belongs to the category of isoflavones. They are strong inhibitor of HDAC (mostly HDAC1) and DNMT (mostly DNMT1 and DNMT3); less strong inhibitor of MeCP2. Was proved to demethylate ipermethylated genomes without lead to ipomethylation. It has a strong and synergic effect whit other DNMT and HDAC inhibitor.
    It is an estrogen receptor agonist and then may produce non-hormonal effects.
    SODIUM BUTIRRATE
    It is a strong and natural occurring HDAC inhibitor and one of most studied. It has a lot of other positive effects and has been demonstred to be neuroprotective.
    VALPROATE and SULPIRIDE
    Valproate is an anticonvulsive and a mood stabilizer drug that act as a strong HDAC inhibitor and this may account of its anticonvulsive and mood stabilizing effects. Sulpiride is a very effective antidepressant (I want to recommend to everyone because is a fantastic drug whit a rapid onset and persisting effect specially on ruminative though, anxiety and bad feeling). It was found that a combination of the two drugs in clinically relevant doses activate brain demethylation. This effect was studied on GABA neurons but may occur also in other type of neurons .
    CURCUMINE
    Strong inhibitor of HDAC, HAT, DNMT, MeCP2. Has been shown to be able to induce demetilation of hypermethylated zone of DNA, in a stronger way than genisteine. Because its potent HAT inhibitor activity it may be a second line treatment or can be used to prevent ssri’s induced modification of genetic expression.
    LUTEOLINE
    Luteolin is a flavone, a type of flavonoid. Increase histone acetylation, particularly H3 e H4, inhibiting their HDAC and activating SIRT6-mediated deacetylation; Inhibit DNMT and LSD1 (histone demetylating protein). Thus, weak diminish phosporylation on H3 and H4 and is a weak indirect antagonist of DNMT.
    APIGENINE
    A flavone, is a HDAT inhibitor (soprattuto H1 and H3) and weak activator of SIRT6 mediated deacetylation. Apigenin may also stimulate adult neurogenesis. Concentration over 5-10 um are not recommended because gaba agonism and other central effects. It is a weak MAOI.
    DIALLIL SULFIDE, ANACARDIC ACID and GARLIC
    A lot of compounds in garlic and broccoli are HDAC and DNMT inhibitor, then high grade dried garlic extract and to eat broccoli may be strongly recommended.
    SAM, vitamins B and ZINC
    S-Adenosil-Methionine is the natural transporter of methyl groups and work in a synergic way whit DNMT, than induce methylation. Its natural counterpart is S-Adenosil-Omocisteine, a strong demethylating agent which expression increase during the use of HDAC inhibitor: this mean that there’s a synergistic effect between increase of acetylation and the activation of demethylation. For this reason, the supplement of SAMe is not recommended.
    The vitamins of group B are used to carrier and bind methyl group, then supplementation of high amount of B vitamins is not recommended if the increase of demethylation is wanted.
    The Zn2+ ion is he natural cofactor of HDAC, then the uses of Zn2+ supplements may increase their activities.
    I hope that a combination of the induction of gene’s plasticity and the antagonism to serotonin receptors may help to recover from the disease.

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  9. How many of the people that commented here and experienced PSSD did also have silver amalgam tooth fillings at the time they took the antidepressant? Maybe PSSD might not be caused by the antidepressent itself, but more an effect of the interaction between the antidepressant and the mercury in the body. In that case, even after discontinuing the antidepressent, the sexual dysfunction might still go on as the fillings and the mercury are still around. I realized that most people I met with PSSD do also have mercury amalgam tooth filling, which are considered harmful by some speacialists. Therefore it would be enlightening to know if you guys also have silver amalgam tooth fillings! I am looking forward to your responses!

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    • Hi, I have PSSD, and I don’t have amalgam tooth fillings. I had some, but they were removed about a decade ago – long before antidepressant poisoning.

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  10. i started taking lexapro for moderate OCD when i was 17 years old for 3 months. It completely deteriorated me both physically and emotionally. I am now left with severe depression, anxiety, worsened OCD, anhedonia and a complete emotional detachment from people. I also suffer from PSSD an can hardly maintain an erection yet alone achieve orgasm. I had none of these problems before and know for sure it was caused by the medication. Can someone explain to me what causes the side effects from these medications to linger with some people after discontinuation? A few years back after the lexapro I tried anafranil and that actually helped a lot. I prematurely discontinued it and when i went back on it i found no relief. Also the physical side effects stuck with me(worsened pssd and dry mouth) after using it the second time. I have been off all medication for almost 2 years and am now 20 years old. Things have not improved at all and I am becoming increasingly suicidal. Can anyone explain to me why the anafranil stopped working after i tried it the second time and is there anything I can do to make it work again? Also, has anyone experimented with WAY100635? Any input is appreciated, thanks.

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  11. @chris : lexapro probably induced gene expression change, genes which regulate serotonin neurons certainly, these changes allow the neurons to release too much serotonin resulting in pssd

    personnaly i’m dealing only with pssd and blunted love and affection feelings but unlike you pssd also decrease to zero my depression and also my feelings of loneliness but there is no change about my social phobia and bdd

    epigenetics change are probably permanent but like the poste above yours said, it may be possible to reverse with a 5ht1a antagonist along with molecules which can modulate gene expression like polyphenols in green tea

    not sure it will works but it’s worth it, i didn’t try way100,635, it’s pretty expensive, you can find it on tht.co though it’s not sure if theirs is legit or just vitamin c

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  12. Hello to all persons suffering from PSSD.
    I really do believe that there is a conspiracy of silence from the drug manufacturers and the medical profession.
    I have been taking Effexor XR for nearly 15 years along with Wellbutrin, for a combination of depression and panic disorder, which came out of nowhere when I was 40. I am fortunate that I have never been suicidal and that the medication was effective so I could function in my profession and as a parent. My spouse, barely two years after my episode, developed a nine-year co-dependency on alcohol after being unsuccessfully treated for depression for several years.
    Her depression did not respond to ECT therapy, but later it developed into a schizo-affective disorder, which is a disease of the brain, resulting in cognitive difficulties and audio hallucinations. She had to quit her nursing profession and apply for SSD. That is how disabling the disease had become.She found expert care and her drinking eventually stopped after 9 years and multiple gastric surgeries, repairing the damage of pancreatitis and her heavy alcoholic intake. She was eventually able to perform simple retail work on a part time basis after being sober for three years. She admits to no sexual feelings and finds it difficult to show and feel spontaneous emotion, including grief. She did not cry after the deaths of two wonderful parents and an older brother. Fortunately,after the drinking stopped her relations with our children normalized. When drinking she was downright emotionally abusive toward me, but my three kids needed me more than ever. But the stress took a toll on my health, hence, the continuation on drugs and many episodes of heavy drinking and eating unhealthy foods.
    Many times, I have been angry and lonely for affection, but have stayed true. Having been a child of divorce and having been a divorce lawyer, I saw divorce as a last resort if she became dangerous towards our children. Many times it became a very close call.
    It has taken years for me to realize that love is more than an emotion. It is demonstrated by what we do-especially as we sacrifice our love of self by doing more for the ones we love. Maybe, one needs a faith based belief system or be in late middle age to realize this, since I did not feel this way between the ages of 40 and 60. I did not know of this post SSRI system; perhaps, it would have made me even more sick.
    I guess it helps to believe there is a larger meaning to love than sex. I understand the feelings of those who feel victimized by the system, especially for those who really want to desire sex to form a loving partnership. All I can say, is that maybe as more people come to the fore, there will be valid research and studies that become recognized. I hope someday, there will be successful class actions against Big Pharma, just as it took so many years to get judgements against tobacco manufacturers. There should be more scientific exploration of natural means and substances to control depression after an acute phase has been successfully treated. I will keep the intentions of the victims and their partners in my prayers-I really don’t know what else to do for those who are suffering.
    There have been no breakthrough drugs that are without these life changing side effects, nor any drugs that have proven to be more effective in handling depression. Why? Because of the increased incidence of depression in each successive generation-including pre-teens and traumatized children has increased the demand for these same drugs and the huge profits continue to be made from old, old drug research. Even the generics are expensive due to collusion among BIg Pharma to pay smaller drug companies to stop manufacturing generics. Trace amounts of anti-depressants are increasing in our public water systems, since they are excreted by all humans.

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  13. How many more people will they castrate before they end this witch practice called psychiatry and back it up with pseudo science and paid lab research by Stooges of big pharma. I curse my doctor and wish the worst upon her and her family. I really hope she and her whole family suffers the same for the rest of their lives.

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  14. 5 Years later as a result of the evidence the EMA has acknowleged PSSD and PGAD after SSRI’s and SNRI’s. It was difficult to edit Wikipidia as someone seems to have removed chunks of material on one site recently and the topic has been moved to another. But have managed to put edits on the Selective Serotin Reuptake Inhibitor page =side effects= and PGAD Persistent Sexual Arousal page under =edits=epidemiology –

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