Editorial Note: This post returns to PSSD – post SSRI sexual dysfunction – PRSD – post retinoid sexual dysfunction – PFS – post finasteride sexual dysfunction and PGAD – persistent genital arousal disorder. See our RxISK PSSD page for the many prior posts on these conditions
There is also post on davidhealy.org – Khashoggi and Pandemrix – which might not sound like it is all about PSSD and related conditions but it is – its about how regulators pawn off responsibility for wrecking lives.
Skin
During a recent hot spell one of our regular contributors asked if atmospheric pressure could change mood or cause pain and other problems and if so how might it do it. This led her to investigate Keratinocytes – the outer layer of the skin. It turns out there is an extensive literature about atmospheric effects on keratinocytes and knock-on effects elsewhere in the body.
She then found a group in the Netherlands working on phenytoin, an old anti-convulsant with multiple effects on a range of different ion channels and autocoids – hormones within the body, who were also interested in keratinocytes and in investigating the effects of phenytoin on pain and peripheral neuropathy.
The end result has been that two of our regular contributors who have PGAD are now trying phenytoin cream to see if it might make any difference to their symptoms. We will update you if we get any useful results.
See Autocoids, Vulvodynia and Keratinocytes for more.
Flibanserin – Addyi
Three different people have been in touch about Flibanserin, a last millenium drug that is very like buspirone – Buspar – a drug lots of people with PSSD have tried with no clear benefit.
Buspirone and related drugs like flesinoxan have the opposite effects on sex to the SSRIs. Where SSRIs inhibit orgasm, buspirone and flibanserin can advance it and this underpinned company interest in this group of drugs as possible treatments to stimulate female desire and the interest of PSSDers to see if they could help.
The Flibanserin trials produced only hints of meagre benefits but despite this, FDA were willing to let it be pushed at women. It came on the market for female hypoactive sexual desire disorder under the brand name Addyi.
Trials often underestimate a drug’s effects. Whether Addyi can do more than these trials suggest, if it offers a benefit in PSSD or PRSD or PFS, this almost has to come from some difference between it and buspirone, as they are otherwise very similar drugs.
So is there a difference between Flibanserin and Buspirone on something like Sodium Channels or keratinocytes or other effects? We need you to start the search.
Trazodone
Alex from Russia pinpoints the kind of observations that can help. He took trazodone which is different to flibanserin but is also sex enhancing.
I had PSSD symptoms: loss of libido, emotions, loss of sensations in ejaculation and premature ejaculation, as well as insomnia, dilated pupils and red eyes.
After 3 weeks of taking trazodone, sleep became almost normal and the time of ejaculation also normalized. and this result so far has been holding for several months after stopping trazodone.
But my emotions and sexual sensitivity did not return, the pupils also did not come back to normal.
So I conclude that premature ejaculation and insensitivity depends on two different things. The dilated pupils, as far as I know, are a consequence of the blockade of the cholinergic receptors, and from this blockade there may also be problems with the genital sphere.
Maybe this information will help you somehow to establish the causes of PSSD symptoms. If trazodone improves libido in normals, but this does not happen in PSSD, the problems cannot just come from stimulation of 5НТ2, and 5НТ1 receptors”.
Entamoeba Histolytica
Another colleague sent the following:
“I’ve been suffering PSSD for two years now. I recently got diagnosed with a parasite called Entamoeba Histolytica. I stumbled upon a story from the Post Finasteride forums, about another guy who had been diagnosed with this parasite, and after clearing it out he found himself cured of his PFS. I’ve pasted it below.
“I’m writing this because I was one of the several people who experienced dramatically compromising side effects after taking finasteride in the form of Propecia. Said side effects included an essential collapse of my sexual system (no libido, impotence), brain fog, anxiety issues, depression, ‘emotional blunting,’ and fatigue.
It took me 11 years and several doctors, but I finally got a diagnosis and–lo and behold–I’m cured. I’m cured!
It turns out I had a parasitic protozoa called e. histolytica. It’s been mentioned on this website before and it seems exceedingly common globally. An estimated 10% of the population has it, but apparently it’s asymptomatic in most people.
I did eventually come to suspect I had a parasite when I tried an elimination diet. Wheat was fine, dairy was fine, eggs were fine, but Sugar (sucrose) triggered my symptoms to a terrible degree. The Sugar connection is what eventually led me to question parasites.
I did try a few at-home remedies, and some of them were genuinely effective in abating symptoms but none of them cured the infection. It must be treated with antibiotics.
Alternative treatments that offered release were avoiding sugar, Humaworm, and ParaGone.
I’d personally recommend ParaGone over Humaworm, but I think they’re both effective.
I also experienced relief from Lactoferrin (Jarrow’s brand), and found they made the other treatments (including antibiotics) much more effective.
The antibiotics that cured me were metronidazole (500mg 3x a day for 10 days) and paromomycin (1,000mg 3x a day for 5 days). Relief came pretty quickly–I felt 90% on top of the world by day three.
I have no idea where I caught e. histolytica. I assume it was in my body for a while, and then the Propecia made it rage out of control.
If you or anyone you know is having problems with Propecia, please see a doctor about e. histolytica! I had a stool test come back negative initially, but it showed up on a retest. I’d recommend finding an infectious/tropical disease specialist in your area, or a gastroenterologist familiar with e.h”.
After doing some further reading I then found this:
“The gastrointestinal parasite Entamoeba histolytica secretes serotonin, causing a sustained secretory diarrhea in some people.[17][92] Patients infected with E. histolytica have been found to have highly elevated serum serotonin levels, which returned to normal following resolution of the infection.[93] E. histolytica also responds to the presence of serotonin by becoming more virulent.[94] This means serotonin secretion not only serves to increase the spread of entamoebas by giving the host diarrhea but also serves to coordinate their behaviour according to their population density, a phenomenon known as quorum sensing. Outside the gut of a host, there is nothing that the entamoebas provoke to release serotonin, hence the serotonin concentration is very low. Low serotonin signals to the entamoebas they are outside a host and they become less virulent to conserve energy. When they enter a new host, they multiply in the gut, and become more virulent as the enterochromaffin cells get provoked by them and the serotonin concentration increases.”
Genetics
Antonei Csoka and colleagues who have been chasing genetic and epigenetic aspects of PSSD for years have just published a Paper on their work in the International Journal of Genomics.
This is Open Access and comes with a large number of supplements on the journal website. We (and they) need someone who knows something about genetics to explore and try to pick out key leads.
It also looks worth exploring the following Genes linked papers.
Pharmacogenetics of glutamate system genes and SSRI-associated sexual dysfunction – 2012
“We examined whether polymorphisms in the GRIK2, GRIA3 and GRIA1 genes were associated with selective serotonin reuptake inhibitor (SSRI)-associated sexual dysfunction in 114 participants treated for depression. One polymorphism in GRIA1 (rs1994862) was associated with arousal dysfunction, providing further evidence for the role of GRIA1 in mechanisms underlying SSRI-associated sexual side effects.”
And linking back to Entamoeba Histolytica, there is this paper. Fluoxetine and some other SSRIs are antibiotics that can alter your gut flora – and lead to thrush and other problems as a result. There are people who have reported benefits in withdrawal and for PSSD from fecal transplants which might have some link.
Nicotinamide Riboside
Another regular contributor has been trying Nicotinamide Riboside for the last two months and has reported slow but steady improvements in cognitive abilities as well as emotional state and physical sensations through the body.
Niacin is Vitamin B3. Googling Nicotinamide which is part of B3, there are claims this is the active form of the vitamin and that Niacin does not produce the same benefits. Nicotinamide Riboside (Niagen) can now be bought in its own right but it is pretty expensive.
Again we’d be interested in any reports anyone has of benefits or problems that this might produce.
Alex says
Hello, Dr. Healy! Good that you reminded me. In fact, I would not recommend trazodone, as well as other drugs, because trazodone can cause priapism, and this is very serious. After trazodone, I actually returned to normal sleep, and premature ejaculation didn’t seem to bother me either, but something like varicose veins of the sexual organ appeared, and even after the cancellation, it still remains to some extent, which I really don’t like. The doctor told me that this was due to the fact that I drank it in a large dosage, and that it was necessary to drink no more than 1/3 pills a day and for a long time, at least for several months.
As for bupropion, instead of improving from 3 weeks of taking it, I went through female-type obesity, up to gynecomastia, and my hair also continues to fall out, so I did not drink it anymore and tested for hormones, since obviously an obvious hormonal disorder developed , and from bupropion even more aggravated. I haven’t received the test results yet, but as for the recommendations, I can’t say about Mirtazapin, because after 5 days of admission I no longer have any sweat, and I quit it, fearing that new problems will be added.
Essentially I want to say the following:
1) according to the hormonal system, you wrote that testosterone can be reduced with PSSD, but this does not play a special role, since with its normalization nothing improves. But why did you not write anything about other hormones, primarily about prolactin? moreover, that the symptoms of hyperprolactinemia, especially in women, almost completely coincide with the symptoms of PSSD, because SSRIs cause hyperprolactinemia with a high probability. In addition, there is still free testosterone, and it is also important, although I don’t know exactly which one, but maybe this should also be taken into account. and there is still the SHBG protein, which blocks the effects of sex hormones even at high levels. Maybe SSRIs can enhance this SHBG? The following are very important hormones of the thyroid gland, they are also associated with prolactin and may suffer from antidepressants, their violation has a strong effect, including on libido. For example, I saw a message on the forum of a person who suffered from PSSD for a long time, and then wrote that after the normalization of thyroid hormones it became much better, I don’t know if he finally cured all this, but didn’t write on the forum anymore. Further, there is a hormone cortisol, the increase of which can greatly inhibit libido, so its research is also important, the same can be said about somatotropic hormone. Maybe you already know all this, but it was not said about it, so you can also pay attention to all this.
2) as for the PSSD itself – it seems to me, most likely, this is a problem of violation not of the serotonin or dopamine system, but of the other system of the brain and the CNS – cholinergic. Why is everything weakened or lost — emotions, attraction, feelings, sensations? I think because the transmission of nerve impulses is blocked or weakened. And the cholinergic system is responsible for the transmission of a nerve impulse (although serotonin is also a inhibitory neurotransmitter). Do antidepressants have pronounced anticholinergic effects, including disorders of libido and ejaculation, dilated pupils, dry mouth, etc., and if many of these symptoms occur at the same time?
Officially, libido and emotions seem to have disappeared from stress, and antidepressants cause stress to the body, especially stimulating ones like Prozac. that is, from excessive stress so as not to burn the brain, the body has turned off factors that provoke the central nervous system, such as libido and emotions. and therefore it is necessary to get rid of anxiety by taking a long dose in small doses of drugs, and then everything will be normal. I am skeptical of such an explanation, but it is also not without meaning.
Heather R says
Alex makes an interesting statement here about the antcholinergic effects of SSRIs. The late Dr Bob Davies, psychiatrist based at Taunton, Devon, produced research on the anticholinergic effects of organo-phosphates in sheep dip, which were rendering some sheep farmers weak, with memory loss, nerve damage, prone to sudden mood swings, and many died by suicide. They often started their downward spiral with ‘sheep dippers’ flu’ which lasted about three weeks, just after dipping (usually in July to avoid fly strike for the sheep) and then as they got worse, the other sensory problems began to manifest, very similar to those described here by Alex. The Countess of Mar, a Peer, a sheep farmer herself, and affected by the dip, crossed swords with Wessley over these effects, because they were so similar to army personnel suffering CFS after their tents had been sprayed with organophosphate in the Gulf War. She felt there were common demonstrable traits, causing serious illness. In the end, these chemicals WERE removed from sheep dip, after a long fight. Dr Bob Davies’ research was meticulous and he was assisted by Goran Jamal. Their research was sidelined and they were not taken seriously, GJ’s reputation undermined, but even so, the ingredients of the dip were eventually changed. Bob Davies said the addition of antidepressants made the sheep farmers’ illness worse.
It would be interesting to know therefore whether antidepressants contain the same chemicals that were used to create mustard gas, organophosphate and to create chemotherapy drugs, which I understand do act on the cholinergic system?
Heather R says
Sorry, forgot to stress that organophosphate was absorbed through the SKIN, ( this post started with skin effects). Dippers did not drink the dip, and were supposed to wear rubber aprons and protective clothing, but it was inevitable that their faces would get splashed. One farmer we know did actually get into the dip to rescue a drowning sheep, and has suffered depression, physical fibromyalgia-type pain, burning soles of feet, insomnia, and stomach pain ever since, for many years. Farmers tend to make light of their ailments, having chosen a physically challenging life, and they reckon they are pretty hardy. But that chemical rendered many of them weak and helpless, unable to think or reason, almost in some cases appearing drunk, vague, distant. Many have died by suicide, which was suggested was caused by the loneliness of their job….
L says
Some tables summarize genetic studies related to sexual dysfunctions caused by SSRIs. This book is of 2016.
Pages 434-436: https://books.google.it/books?hl=it&id=O8UQDQAAQBAJ&q=Zourkova#v=onepage&q&f=false
Alex says
And in addition, there is information on the Internet that antidepressants block the passage of nerve impulses. And as for abnormal erection, when the head is poorly erect, this is also a consequence of a violation of the passage of a nerve impulse, and not blood circulation or something else. That is, much indicates precisely the problem of the passage of a nerve impulse.
talkingant says
Dr Healy, could you forward this question to the person who had e. histolytica:
What type of stool test did you get that gave you a false negative result? Did you get the same test twice, or was it a different one that gave you a positive result? Most PCR-based stool tests today are highly accurate, but given the uniqueness of our condition, I’m interested in hearing your specific experience.