This image is from an extraordinary blog which tells you how to sex your mouse
Breakthrough?
Most of the good ideas that RxISK has featured linked to the enduring sexual dysfunctions, whether PSSD, PRSD, PFS and PGAD, and in terms of other problems, have come from readers of these posts. Several readers have stood out in terms of contributions and this post comes from one of the most helpful contributors.
Hopefully this latest input brings us a big step closer to finding out just what is wrong in PSSD and finding a cure and at some point then the names of all those who have done so much to move this forward can be revealed. They will deserve recognition by scientific and medical bodies.
Once Upon a Time
Back in the 1850s, Wilhelm Krause, an anatomist in Germany described Kraus Corpuscles in male and female genitalia.
Even this is not as simple as it sounds. There were two Wilhelm Krauses – father and son, both anatomists. The first mystery to solve is which Wilhelm described the Corpuscles. Some leads are in the image below from Wilhelm Jrs obituary. My bet is on the father.
A second and more important turn in the plot has come 170 years later when the Corpuscles have exploded back on to the stage with a Qi, Iskols, Handler and Ginty paper revealing that they have a key function in sexual behaviour. Krause Corps respond to vibration and touch and are critical to sexual engagement. Without them nothing happens.
The Qi et al article is above. Here are synopses Thank Your Krause Corpuscles and Mysterious Structures and finally Discovered in the Clitoris and Penis. The final link here comes from New Scientist from someone who has a subscription and I hope that New Scientist and the author Anne Klein will look favourably on the urgent medical need to get this information out there. We will remove it if told to do so.
Back to the Future
This is exciting.
For lots of people, for a long time, it has seemed obvious that PSSD (in all cases where PSSD is mentioned you should also assume PFS, PRSD and PGAD) involves a peripheral neuropathy.
This is obvious in the sense that all things being equal genital numbness means genital neuropathy and not a brain or endocrine problem. You can get the same effect instantly by rubbing local anesthetic into genitals and saying the local nerves have been affected makes more sense than invoking the brain or endocrine system.
Having said that, there is clearly to PSSD in that the effect endures and the enduring aspect may involve other mechanisms.
One thing is for certain – classic pharmacological receptor theory cannot explain either the numbing or the enduring. A lot of bright people have tried out all the drugs that should be tried if this was a matter of reversing or unblocking a receptor. Nothing has helped.
There was great collaboration and trading of information on these issues on early PSSD Forums set up by Antonei Csoka, Audrey Bahrick and others, nearly 20 years ago. This led on to other fruitful hypotheses like Csoka’s epigenetic hypothesis, nearly 15 years old now.
More recently sufferers have turned to tests for peripheral neuropathy as outlined in many RxISK posts stretching back over several years. Some but not all on RxISK pinned their colours to a peripheral neuropathy mast a decade ago. (See Complex Withdrawal Model and PSSD, Withdrawal & Small Fiber Neuropathy?) A group in Finland have been most active in this area lately – see Sensory Receptors, Small Fibres and Neuropathy.
The problem for the Finns, and all the rest of us, is that neurologists have not been interested in peripheral neuropathy and until recently current Tests were pretty crude. They are usually taken around the ankle as this is the area where the peripheral neuropathies neurologists deal with tend to happen. They are taken in older folk and likely test the wrong kind of peripheral nerves to those affected in PSSD. The results have been mixed.
This led RxISK recently to push CCM testing rather than ankle biopsies. CCM looked like having a much better chance of coming up with a positive result than ankle biopsies had.
At the moment only a few people have had CCM testing and at the moment the results do not show the expected signs of something wrong – but this may be because those doing the looking have not had a clear target to look for. Do cornea’s contain Kraus Corpuscles, for instance.
A Dark Horse
Lurking in the background was Quantitative Sensory Threshold Testing (QST), flagged up by the person who has done the most RxISK work on PSSD (not me) nearly a decades ago. (The blog post “How Common is Post-SSRI Sexual Dysfunction?” noted that a form of QST testing had revealed the genital numbing effects of serotonin reuptake inhibitors in 1990 and 1999. This was subsequently highlighted in our published paper, 300 Cases.) Some PSSDers have shown abnormalities on this but it has been impossible to get neurologists to engage – too subjective they have said.
RxISK went to War with a French company who make a gadget that can do QST Testing and who even have a genital adapter to test genitals but they refused to co-operate in making it available despite pleas from me and from several PSSD sufferers. (See Sudoscan Saga & Propecia/Finasteride Survey and Device Wrecks & Regulators?)
It turns out that Krause Corpuscles respond to vibration, temperature and what we call affective touch – just the things QST testing homes in on. See very recent RxISK post on Affective Touch – Sexual Mysteries – asking just this question – are there C-affective touch nerve endings in the penis and genitalia.
If the Krauses are where the problem lies and QST picks it up, this would technically be a peripheral sensory neuropathy, possible a unique one, although the sensory system is so unexplored there may be other sensory neuropathies waiting to be discovered.
Moving Forward
We need to find out everything we can about Krause Corpuscles. I have already written to the authors of the Ginty paper but there are likely lots of other folk working on Krause Corpuscles and even checking them on biopsies of genital tissue in people not mice.
We need to check on Krause Corpuscles in the Cornea and around the ankle as they are not found in these locations testing there will just give skeptics ammunition to claim this problem is all in the mind of complainers.
Luisa Guerrini’s work on SSRIs and p63 continues to yield fascinating results that need to be written up and published. In her experimental set-up, thalidomide causes changes that fit with a peripheral neuropathy that recovers once you remove the drug. SSRIs and isotretinoin cause longer lasting changes consistent with an enduring peripheral neuropathy – but of crucial importance they do not do this by causing cell death.
We need to establish the effects of SSRIs, isotretinoin and finasteride on Krause Corpuscles. Are the effects here, if there are any, mediated through mitochondria or is it more a case of treatment leading to enduring problems cutting the Krauses off from their blood supply.
We also need to find treatments that can reverse whatever effects there are – treatments to resurrect the Krauses. This may involve an action on mitochondria – actions on which are hot news at the moment.
Treatments
In response to a query about Emoxypine from one of our most generous funders a few days ago I wrote:
Had never heard of Emoxypine. It looks similar to, related to Pyridoxal-5-Phosphate – see recent RxISK Post on this. Some people with chronic akathisia have seen it clear up on P5P.
I’ve always thought that genital numbing and emotional numbing are closely related and that drugs that cause these can also cause genital irritability up to PGAD and also cause akathisia which perhaps is the emotional counterpart of genital irritability. So I’ve asked a few people who have reported PGAD to us to try out P5P and let me know what happens.
Here is where things get interesting. There is a good case to be made that as genital nerves pass into the spinal cord that the gateways there shape whether we get genital numbing or irritability and emotional numbing and/or akathisia. In this case P5P might help with PSSD also – but I haven’t asked anyone to try it just yet.
See also the attached article – not sure where it came from – about BC007 and AXA1125. There is something about mitochondria that might be interesting and certainly about getting blood flow going again around peripheral nerve endings.
The main drugs on my radar have been anti-muscarinic drugs which look like they can regenerate nerve endings perhaps by improving blood flow, perhaps through effects on mitochondria.
I think benztropine, in the lowest possible dose taken over several months, is one of the better treatment bets.
(For more about benztropine and PSSD, see The Mysteries of Love.)
Wilhelm or Wilhelm?
This is another mystery that hopefully someone can solve.
Update: some instant super sleuthing has come up with the following.
There is only one Wilhelm – Johann Friedrich Wilhelm Krause 1833-1910. He was the son of “famous anatomist” Karl Friedrich Theodor Krause.
It seems he used a bird embryo to fake human fetal development – see Hopwood – this became a major controversy that might have shed a bad light on his other claims.
The Corpuscles look like they were first described in Die Terminalen Koerperchen. – subtitled The Sensory Nerves. This was published in 1860.
Zach says
Your text is a mess of probably sound things like neuropathy in general, and then wild guesswork – which imo is very unscientific.
Also, the focus on genitals only is not smart. Evidently the neuropathy appears often widely in autonomic system at least. Nobody says that some tissues in brain could not be harmed too.
And on what basis can you say “without cell death” if indeed the biopsy shows loss of density of fibers – ie they are not there any more. It is a totally different question which types in which circumstances can regrow (new ones).
I think you jump all over the place and lose logic, but maybe it is your intention.
Horrorshow says
I agree that the brain and other systems are involved. As someone with PFS, it felt as though my whole body was affected when I contracted the condition. As though something turned off inside the brian. Is that related to the numb and shriveled genitals? Possibly, perhaps a functioning brain and nervous system is required to maintain parts of the body as well.
MatKD says
Guesswork can provide useful lanes of investigation, especially if a solution does not exist. It’s not the same as making final claims, and certainly smarter than guarding oneself against it. Plus it is still based on actual anatomy. Your claim of unscientificness shows itself scientific incompetence aplenty and a nasty attitude.
And even if in your case the numbness is not in a specific area, it is still for many people (and this specificness is in fact one of the most confounding parts, as opposed to more systematic issues which are often researched), so your preferred focus doesn’t make it “not smart”. This type of numbness also makes peripheral issues particularly probable compared to brain damage, as it is more direct and basic (the instant sensitivity to touch doesn’t require a complex processing and maybe hardly any transmitters to start with). Either way, one investigation doesn’t rule out another one, that’s more of your incompetence.
And maybe you simply don’t know the studies he is referring to “without cell death”. Indeed those standard tests which are always used and which ignore the only or main area affected are silly in those cases and don’t provide any avenue. I certainly have no interest in arbitrarily increasing my sensitivity where I think I have more than enough.
Zach says
One thing that may be noteworthy: many people with these symptoms can feel emotions and even sexual attraction and arousal while seeing dreams. When they wake up, everything is gone instantly.
This could be a sign of peripheral sensing being a big factor of input for generating emotions too. The nervous system is integrated, and in sleep state the harmed peripheral system is disconnected and brain seems to be able to generate the emotions. In awake state the harmed peripheral system interferes with CNS and this becomes impossible.
There was also a mention about a medical procedure that harmed the ANS and it also caused emotional blunting. I am sorry l don’t have the link to that article now, l forgot how l came across it.
Antonio says
What you have mentioned is really important.
The fact that many PSSD sufferers have all their abilities back in their dreams as you mentioned really is something that is astonishing.
PSSD is a disease that might give insights into many other areas, for example what is involved in dreams and what not. Or perhaps scientists who specialize in dreams could contribute to PSSD research in some way.
Zach says
I think the point here is very logical: peripheral nervous system is damaged and it disturbs the central nervous system when awake. Less or not at all in sleep.
Science is clueless about nervous system in general, but at least the “pssd researchers” should realize that the peripheral damage causes also at least emotional numbness.
Bernard says
Would there be a way for PSSD sufferers to try anti-muscarinic drugs? You have mentioned them a few times. If they are not too dangerous, would it be possible and beneficial that some people try it?
Dr. David Healy says
At the moment the best bet is benztropine in a very low dose – the lowest you can get. Will need to be taken over time – possibly up to 6 months. There are lots of others that may be better that are in development
David
Tim says
Is this medicine somehow available in Europe?
Dr. David Healy says
You’ll have to check. Its an old well established and safe medicine – there is a rxisk post from maybe 7 years ago – linked in this post about the circumstances of its removal – it looked like it could help nerve fibres regrow and Merck thought they could bring a new version on the market and charge much more
Any treatment aimed at getting nerve regrowth will take months to show a difference and should be taken in a very low dose – nerves will not regrow in a heavy drug environment
D
Tim says
The Medicines Agency told me that benztropine does not have a marketing authorization in my country (Finland). I do not know what to do.
Dr. David Healy says
you buy on the internet
or check which countries do sell and see if you know someone there who can get if for you
D
HzeTmy says
Great post thx for the news …
K says
“SSRIs and isotretinoin cause longer lasting changes consistent with an enduring peripheral neuropathy – but of crucial importance they do not do this by causing cell death.” How do you know cell death is not involved? And what can it be instead?
Dr. David Healy says
This is cutting edge research – so at the moment LG has found distinctions between thalidomide and SSRIs and drugs that kill cells. Just exactly what is the basis for these differences remains to be discovered. In cases like this involving something no one has seen before, it is important to work out how to tease out what is involved in follow up tests – all of which takes money and good personnel
D
Mmajk says
Dr. Healy, is there a realistic option for a pssd treatment in the coming year?
Dr. David Healy says
I can’t answer this but I can tell you I’m more excited than I have ever been and I think a lot of other people who can help are now starting to take the problem more seriously.
We will definitely have a better feel in terms of being able to rule some things in and some out. Ideally we will have a test that allows people to demonstrate to their doctor and others that the condition is real and not in the mind. And this in turn will shed light on just what kind of treatment is likely to help.
You shouldn’t doubt that this is one of the biggest issues in medicine today – and will be seen to be in due course. Solving it may change the way a lot of people think about health and drugs.
David
Darren says
Hi David – thank you so much for all your efforts to find a cure for the horrific affliction that is PSSD. I have a lot of genital pain (which no conventional doctor has been able to explain) along with my PSSD. I wonder about the nerve damage theory. I am going to try acupuncture to see if that will help. I will report back. Darren
Dr. David Healy says
Darren
Please let me know about your acupuncture – what type it is and whether it helps
David
Darren says
I will David. However, in the meantime, I do wonder whether you and LG may be onto something with anti-cholonergic/ anti-muscarinic drugs – on numerous PSSD forums people say their symptoms have improve vastly through cyproheptadine and/or forskolin. Both are stated to be anti-cholonergic.
Zach says
He said earlier this year “cure this year with 51% certainty” which in my opinion was a baseless thing to say with existing knowledge – when it is not even clear what this is at deep down level, and can it be cured.
At higher level neuropathy is the correct thing to say, and it is good that aware people are starting to realize this. The increasing number of biopsy results and diagnoses prove that.
Anon says
Is the idea that BC007 and AXA1125 could aid in PFS, PAS or PSSD symptoms plausible? Or is this guesswork?
Dr. David Healy says
Its based on work on BC007 where Johannes Mueller trumpets this effect. I do not know what weight to put on the claims. The AXA1125 is linked to mitochondrial activation which is a really hot area at the moment and one of the things some muscarniic drug advocates figure they might also act through. We are in watch this space country. Focussing on reactivating mitochondria makes a change from thinking about receptors which don’t seem to hold the answer
D
K says
Dr. Healy, there is a section on rxisk prize page which says there is a group of volunteers that would try any potential cure to see if it works. Did these volunteers trial benztropine for 6 months which you consider promising? What were the results? How about pirenzepine?
Dr. David Healy says
This is a good question, thanks for asking. No they didn’t. The panel was set up in part as a body to assess the merits of a proposal. It is one thing for me to think it is a good or bad proposal but those who have PSSD and are being asked to try something need to be confident it makes sense and is not unduly risky.
The panel idea came long after the benztropine proposal and I must say I didn’t put the two together. Benztropine is not available in the UK which is were the panel members are/were.
Pirenzepine seems less likely to work – at present it can only be externally applied.
At the moment the plan is still to get a panel to engage in a program of tests – one advantage of a test is that it may offer further evidence of actual nerve regrowth
David
S says
Dr. Healy,
Is it possible to obtain the full results of the Luisa Guerrini’s study by the end of 2023 or earlier? When will the research be most likely to be published?
annie says
Royal College of Psychiatrists
– somewhat of a boo boo…
Royal College of Psychiatrists
@rcpsych
Our next session on a difficult topic: Medication to manage sexual preoccupation in adults who have committed sexual offences.
Royal College of Psychiatrists
@rcpsych
The medications used in people that commit sexual offences
#RCPsychIC
Royal College of Psychiatrists
@rcpsych
Evidence of medication effectiveness #RCPsychIC
https://twitter.com/rcpsych/status/1679070369058103296
Royal College of Psychiatrists
@rcpsych
Day 2 of #RPCpsychIC is in the bag!
https://twitter.com/rcpsych
Cometh the hour, commeth the halfwits…
Amr Essam says
how is this related to low libido? my libido & genital sensitivity are always linked to each other and they are always fluctuating (i think i have a mild PSSD case)
Horrorshow says
Hello everyone,
Are we sure the cells being quiescent is through the mitochondria and not the traditional process of cells entering quiescence?
Thanks to anyone that knows.
Beloved_one_of_sufferer says
Very intersting findings!
I am wondering, how those researchers modified the mice to eliminate the Krause corpuscles – maybe there is a way vice versa?!
Crazy off-topic-theory here:
Those Krause corpuscles are also found in the eyes – and according to Alicia Klein’s paper, they are responding on vibration.
As some know: Light is not just a wave, but also behaves like particles. Maybe those Krause corpuscles catch the vibration of light particles in the eye.
Who knows…
Darren says
Dr Healy, here’s a few more things from me just now in case helpful:
1. Are you aware that many, many, many people on PSSD forums actually got their “PSSD” from Ashwaganda (rather than SSRIs)? All the same symptoms as PSSD – sexual and emotional blunting, anhedonia, erectile dysfunction, no libido etc etc. so I guess we should call that “PASD”.
2. One such person who got PASD is Lucas Aoun. He posted on PSSD forums years ago as “Lokzo”. He now runs a health company in Australia. He posted about trying many things and said that cyproheptadine and a particular type of St Johns Wort helped. My guess is he may be worth LG speaking to him, he probably has a lot of useful knowledge from things he tried, what worked and what made things made worse.
3. I have tried cyproheptadine too and it does seem to have a positive effect – but only for short windows. What I have noticed from my “windows” is that all my symptoms (sexual and emotional) all got better during those windows – so, for me, they are all connected. For example, I could feel emotion and enjoy music.
Hope this is helpful.
Darren
Dr. David Healy says
Darren
Cyproheptadine is very like mianserin and mirtazapine – both of which in some cases can cause enduring sexual dysfunction but also unlike SSRIs which tend to kill libido on average they increase libido
Neither seem to be a treatment for PSSD – but what I don’t have details for is the other point cholinergic point you bring up – it may be cyproheptadine has more effects on the cholinergic system that mianserin and mirtazapine.
Cyproheptadine has an interesting history – it ran into a scandal around 1961 when its appetite stimulant properties seemed to be promoted as a response to developing world malnutrition problems. This got it labeled as a Bad Drug – but it was bad marketing rather than a bad drug per se
David
Darren says
Dr Healy
Thanks for your reply. Sounds like I should score cyproheptadine off the list of possible cures…..
Interestingly, I have just been prescribed (but am yet to receive/ start) oxybutynin for my over active bladder (OAB). From looking at the NHS website, it describes oxybutynin as an anti-cholonergic/ anti-muscarinic. Sounds like it may be similar to the benztropine you mentioned in another post? May be interesting to see if it helps my PSSD as well as OAB.
Re my acupuncture, I will be starting the week after next and will keep you posted. For me the PSSD symptoms all seem to boil down to a loss of sensation – physical (sexual and non-sexual) and emotional. Therefore, it seems to me (though a complete lay-man) very possible (and maybe even most likely) that PSSD comes from some form of enduring harm to the nerves/ nervous system. On that basis, I will explain to the acupuncturist and may ask that we do acupuncture which is focussed on trying to repair damage to the peripheral nervous system (PNS). I know you are not giving medical advice but does that sound like a reasonable place to start to see if it helps in this quest?
Thank you so much for your continuing efforts on PSSD. It means so much to so many of us PSSD sufferers.
Darren
Dr. David Healy says
Darren
Its very interesting to hear you are starting oxybutynin – let me know what happens. In order to work out does it help anything besides your bladder you will need to be on it for several months. There might be an immediate bladder benefit but the real benefits if we are thinking regrowing nerve endings will take months – and ideally you should not be taking a high dose.
David
Darren says
Thanks Dr Healy and noted on the low dose re oxybutynin.
It’s fair to say my trust in western medications is very low at this point after nearly a decade on SSRIs and/or Quetiapine at various points (off them all completely as of 3/4 months ago) so I will be taking the minimum dose possible of oxybutynin to ease my OAB symptoms.
I do absolutely agree with the line of thinking that PSSD and related symptoms (anhedonia etc) must be caused by nerve and nervous system damage. All my blood and urine tests are normal (so the doctors are at a loss) and it seems people have spent decades exploring the neurotransmitter theories and taking supplements to try to “re-balance” the brain chemistry. My brain feels ok, I just cannot access emotions. The doctors say my body is ok – I just have unexplained genital pain and numbness plus ED etc. I also agree that is the lack of sensation which is more likely causing a feeling of low libido (and not the other way round).
As I said in another post, all my symptoms are better or worse as one – sexual and non-sexual. It is all part of the same one thing.
Based on all that I am going to try:
1. Oxybutynin (low dose);
2. (R) Alpha lipoic acid – which I read on numerous sites is good for nerve damage/ nerve repair. I have ordered the purest supplement I can find online;
3. I will continue to take magnesium glycinate – the most effective thing I have tried for my nerve/ muscle pain;
4. I will do the acupuncture – targeting repair to damaged nerves;
5. I am going to order and try using a TENS machine. Interestingly, I read that one of the settings on a TENS machine is basically electro-acupuncture and that the use of electro-current can help regenerate nerves 5 x faster than without electro-stimulation. That claim could obviously be overstated however TENS and electro-acupuncture have been around for a while.
This is my strategy, we shall see if it improves my symptoms.
Darren
Dr. David Healy says
D
Keep us posted on what happens
D
Darren says
Hi Dr Healy / all
It’s Darren, I haven’t posted in months but thought I’d give an update though not particularly upbeat. I didn’t try oxybutynin in the end but did try a TENS machine – which my body seemed to react really badly to and which seemed to set me back significantly in any PSSD recovery. I also tried acupuncture but it didn’t seem to help.
When I reflect on my own experience of the last 21 months of PSSD, the only thing which seems to have given me any “windows” (i.e. periods where my physical and emotional anhedonia symptoms improve) is when I have taken cyproheptadine. I thought previously it was the use of a massage cushion but actually think it was cyproheptadine. In the absence of any other ideas I’m going to trial that again and see how I get on..
I suspect you are aware but it seems many people with PSSD/ related conditions get these “windows” (where symptoms improve) from time to time. To me, those windows must give us a clue into what type of condition/ cure is or isn’t possible or likely. It gives me hope that I have had periods where libido and ability to feel emotion/ enjoy music returns to some extent (not fully) and the general anhedonia recedes a bit. It must mean the ability to return to some normality is there. It is just a struggle to turn those windows into more significant and sustained improvements.
Why does cyproheptadine help sometimes? Is it the serotonin antagonism? Is it some kind of anti-inflammatory effect? I have read that some people with long covid (which seems to have many of the same symptoms as PSSD) have also been helped by antihistamines.
Lastly, I’m sure this is very much on your radar but I think it’s very, very, very important to put or keep front and centre that PSSD is really in my opinion a very unhelpful misnomer. The sexual dysfunction is just one part of it – it is also complete physical, emotional and intellectual anhedonia and chronic fatigue (amongst other things). If you go into the “PSSD” forum on “Reddit” (which has over 10,700 members) you will very quickly see, as I did recently, that almost all PSSD sufferers seem to have all the other non-sexual symptoms I describe too – anhedonia, chronic fatigue, insomnia etc.
I’m no doctor but I do feel the “over-feeding” of serotonin receptors is still maybe a lot to do with this. Would “windows” be possible if it was a SFN problem?
One final thing – many PSSD sufferers (me included) feel no adrenaline: excitement any more – could something as basic as an epi-pen shot of adrenaline be trialled to see it can jolt our systems back into action? Probably a crazy idea but the lack of adrenaline thing is very real for many PSSD sufferers and could they be a route to remission?
Hoping for a breakthrough soon.
Best wishes,
Darren
Dr. David Healy says
Darren
Thanks for the updates. Cyproheptadine seems more helpful than most things. Its antihistamine but also antiserotonin and anticholinergic. Which bit helps the most – who knows – perhaps an interaction.
the windows effect is definitely a real thing and a hopeful thing to hang onto.
David
Darren says
Dr Healy
With apologies, one further thought from me just now…..
Like many other PSSD sufferers I’m sure, I watched the excellent Panorama programme a few weeks back (“The Anti-depressant story”). It brought out in me a mixture of anger, relief, horror amongst other emotions. Owing to the Panorama programme, the “PSSD Cat” is now out of the bag (or at least peeking out of the bag).
On that basis, is the time not NOW that we need to be putting huge pressure on Government and the big pharmaceutical companies to throw significant money, resources and efforts to find treatments or a cure as soon as possible? Do the Panorama revelations, and the suffering of so many, not merit a Select Committee hearing in Parliament asap to get the required publicity and the right pressure and focus on government and pharmaceutical companies to find a cure?
Shouldn’t we start one of those online UK GOV online petitions to get this heard and discussed in Parliament without delay?
I am certain there is ENORMOUS under-reporting of PSSD. You only need to go on to a well known social media platform and type in “PSSD” to get an idea of the scale of the number of people who are suffering terribly with this. And, given the number of people now on anti-depressants in the UK, that number is going to increase enormously in the years to come.
Ok, that’s all for now.
Thanks again.
Darren
Dr. David Healy says
D
Companies and governments knows all about this in one sense – PSSD is closely linked to dependence and withdrawal and we now have 15% of the population of most Western countries on these drugs and unable to get off them. Do companies or governments care about this? Not that I can detect.
Lots of groups have been trying to get health service input to dependence and withdrawal on antidepressants and getting nowhere. I think trying to petition etc will just be frustrating. This is not saying do nothing – the trick is to think of something to do that would really make a difference
D
Darren says
Dr Healy
I am not an expert but companies and healthcare providers (public and private) have a duty of care at law towards their consumers and patients. A duty not to cause harm and to adequately warn consumers and patients about the risks of products and treatments they are selling/ administering. Certainly there should be adequate warnings about risks which providers know, or should reasonably have known, about.
It seems to me that healthcare providers and companies are somewhat complacent if they assume a court will not see this as their problem and responsibility.
To make an analogy – “smoking kills” and similar messages are not on the side of cigarette packets to help with marketing.
Might a large legal action make a difference?
Darren
Darren says
Dr Healy
Having now read the “peripheral neourapthy” section of the NHS website, I am convinced with every fibre (excuse the pun) of my being that PSSD is peripheral neuropathy.
The numbness, shooting pains, pins and needles.. And indeed, when I was having very bad reactions to the medications I was prescribed last year, my coordination entirely went for a period of time. I also had what I felt were undoubtedly akathisia and (mild) serotonin syndrome at the time.
In my humble opinion, PSSD is almost certainly peripheral neuropathy. You are on the right track, no doubt at all in my mind.
My acupuncture etc will be targeted accordingly.
Darren
Darren says
Dr Healy
I would say sorry for the further post; but I have read your comments saying some of the best ideas and helpful information have come from people posting. Plus; I will not rest until PSSD is beaten. Both for me; and for all other sufferers.
I write, hopefully not prematurely, with some updates. In no particular order:-
1. I have been abroad on holiday these last two weeks, hence have not been able, as yet, to properly implement the strategy I outlined a few days ago I.e. acupuncture etc.
2. However, whilst on holiday I bought an (electric powered) “massage cushion”, Please bear with me on this……
3. I have used the massage cushion on my lower back/ spinal area for about 20/30 minutes per day for the last 5 days now. It is a powerful little machine with 4 moving “balls” inside it which move around and provide the massage sensation. It exerts significant pressure and the beauty of it is that you can increase the pressure the more you lean back into it.
4. I understand this may be entirely “jumping the gun” and that this all may be temporary but, 5 days on, I have experienced some significant changes in a wide range of my symptoms (forgive some of the blunt detail but of course it is necessary)-
– my over active/ irritated bladder symptoms have disappeared;
– the acute pain in my left testicle – gone;
– the complete numbness in my penis – gone;
– I can “feel” and enjoy music again – I could not one week ago;
– I can feel some positive emotions again – less than a week ago I could not (just a sense of despair that PSSD and anhedonia would be with me forever);
– the last two nights, I have slept better than I have in a very long time;
– the last two mornings, I have woken with an erection (compared to virtually never for a very long time);
– I feel like I have some libido back (none at all a week ago);
– I feel like I have some sensation back in my genitals (none at all a week ago);
– I noticed I have some sensation back in my nipples (none at all a week ago)..
– I have noticed I have had (and felt) goosebumps on my arms these last couple days. I cannot recall the last time I felt a sensation like that.
– I actually felt some adrenaline earlier today – I cannot recall the last time I felt that.
5. As I say, I may be jumping the gun, but I do think something is going on here. Whether it is temporary or not, time will tell. But, I have had what seems like a material remission in my systems build over the last 3 or 4 days. To try and put a figure on it – I would say something like 35-40%.
6. I have a TENS/ EMS machine waiting for me when I get home, and acupuncture lined up for next week.
7. If there is something in this, what is it? I revise my theory slightly from recent posts (though these are not my theories, I’m sure I have read them all, in places, on this site and/ or others).
8. The positive experience of the last few days makes me think (though I am not in any way medically trained) that PSSD is maybe caused by two key strands: (1) a “suspension” of the proper flow of blood and key hormones (e.g. oxytocin, adrenaline etc) around the body (the “First Problem”) and/ or (2) nerve damage to the peripheral nervous system (the “Second Problem”).
9. Perhaps the First Problem causes the Second Problem? The lack of “flow” around parts of the PNS results in nerve damage and/ or loss of sensation? If that is the sequence of events, then treatment and reversal or remission of PSSD perhaps first requires the First Problem to be resolved. In solving the First Problem, proper flow of blood and hormones then allows the body to (itself) try and tackle the Second Problem.
10. For me, the existence of the “two problems” might explain why some PSSD sufferers say they sometimes get “windows” where their symptoms can (quite quickly) ease or get better for a period.
11. But if the First Problem is only resolved/ improved for a short period then the “window” is only temporary. For symptoms of PSSD to be reversed, or significantly reduced, on an ongoing basis then the First Problem needs to be resolved on an ongoing/ enduring (not temporary) basis.
12. From what I have read of acupuncture, it seems ideally placed as a good bet to solve the First Problem. Not least because it does not involve putting further pharmaceutical drugs into a body which has already clearly (in my view) been put into some sort of “state of shock” to have triggered the PSSD in the first place.
13. In the writings I have read about acupuncture it says that, whilst some patients can feel instant relief, this can sometimes be short lived; and perhaps (say) 8 or 10 sessions may be needed for lasting improvement/ lasting remission. Making the analogy to PSSD, the first acupuncture treatment often provides some relief, but it is only a “window”. To achieve lasting resolution of the First Problem, further treatments are needed until the body has managed to fully restore proper “flow” on an ongoing basis i.e. until the First Problem is properly resolved (on a lasting basis).
14. Might this logic also explain why some PSSD sufferers seemingly have the condition for multiple years – and then get better? Perhaps the body has been stuck in a “flow paralysis” (the First Problem) for all those years then somehow manages to “jump start” the flow – which then allows the healing powers of the human body to then start healing and the PSSD symptoms can start going into remission and reversal.
15. Perhaps, in some cases, the First Problem is bigger than the Second Problem. Those cases would presumably be ones where remission could be swift upon reinstating effective “flow”. Harder cases would be where the Second Problem was fairly extensive. Although I do (perhaps optimistically) read that nerves in the PNS can heal pretty well. Especially if the damage is to the sensory nerves – which would back the theory that you CAN have PSSD for years and then still make a fairly swift and extensive recovery?
16. I saw the acupuncturist once before coming on holiday (before I had done too much reading on PSSD). He respectfully declined to launch into a scathing criticism of the approach of modern Western medicine (drugs, drugs, drugs). However, he suggested that my liver and kidneys were likely in a “state of trauma” from all the prescription medications I had ingested into my poor body.
17. Might the cause of the “First Problem”, and the root cause of PSSD, be simply an “allergic” type reaction of the body to the relevant prescription medication(s) which have been ingested? I wonder what percentage of PSSD sufferers experienced symptoms (however mild) of akathisia, serotonin syndrome or similar? My bet would be a very high percentage. I certainly did.
18. It feels to me that PSSD, and the First Problem, arises due to the body’s (very sensible) response to the ingestion of the medications which the body has (understandably and correctly) perceived as toxic. Perhaps what the body does in response to ingestion of a toxin is that it slows down (or indeed stops) the flow of blood and other hormones around the body. Why? Presumably to slow or stop the spread of the toxin. It shuts off the “engine” and the engine (necessary to carry the flow) needs restarted. To resolve or reduce the symptoms of PSSD, we need to (properly) restart the engine (flow) – so that the feel good hormones, which none of us PSSD sufferers can feel, are freed to move around our bodies are they are supposed to. And so that the blood and hormones can set about healing any damage to nerves which have been damaged.
19. My guess is that my “engine” or “flow” shut-off last year when I had symptoms of akathisia and mild serotonin syndrome. Throughout last summer, I could not get warm – despite often wearing multiple pairs of socks – presumably this was simply because my blood and other feel good hormones were no longer effectively flowing around my body. Perhaps then, a big chunk of the problem and answer here is “flow” – it has been stopped and needs to be (effectively) restarted.
20. I feel that the approach of modern Western medicine has gotten me, and other PSSD sufferers, into this mess. I, for one, am going to look to the principles of Eastern medicine (restoring “flow”) to try and get me out of it.
I hope my symptoms will continue to ease and will keep you posted.
Darren
Dr. David Healy says
D
Good news I hope others try it. Can you give the details of the machine you used
D
Darren says
Dr Healy
Of course. It is a (wireless) “massage cushion” from “Ale-Hop”. The “rated power” is 10watts. I don’t think they are in the UK – I bought in the Canary Islands and believe they have outlets in other Spanish speaking countries. However, they do of course have a website and I believe will do online orders to wherever. It was 35 euros i think, so not expensive.
But I imagine any similar massage device could do the same job. I assume the relief and benefit is simply from increasing flow of blood and other feel good hormones around the body.
One other point whilst on – I have read many, many sorry tales on PSSD forums where people say PSSD has been triggered in them by taking one SINGLE pill of SSRI (or ashwaganda). To me, that backs the theory that PSSD must be triggered by the body going into some sort of “shock” which, in turn, stops the flow of blood and other hormones to particular parts of the body. Surely a single pill of something which is not (for most people) inherently toxic would be unlikely to cause extensive nerve damage immediately?
For my money, there is “flow paralysis” first and then nerve damage.
There’s my entirely amateur theory…..
Darren
Darren says
Dr Healy
I hope I am not jumping the gun but…… I continue to use the massage machine daily and the lessening of my PSSD and anhedonia symptoms over the course of ONE WEEK has been quite amazing.
One week ago, with my symptoms, I would have put my health at no more than 20%. I would say I am up to at least 60%.
In simple terms, I can feel that the blood and feel good hormones are now able to flow much better around my body and I think that is what is alleviating my symptoms. It feels as simple as that. I sincerely hope my recovery this last week will be maintained and continue further.
It feels to me like much of my PSSD and anhedonia symptoms have been with me due to some sort of “flow paralysis”. I think my body basically took an allergic reaction to the medications last year and has been in some form of “suspended animation” or partial “coma like state” since.
It seems to have been awaiting something to act as the “spark” to jump-start the proper flow of blood and energy again.
I am not in the realms of 100% again at this point but I shall definitely be keeping going down this route – focussing all my efforts on (non-pharmacological means of) restoring and maximising proper flow of blood and hormones around the body.
When a person takes an allergic reaction to something, sometimes an “epi-pen” is used to jolt the body and restore equilibrium. It almost feels like my body is undergoing a similar (though more gradual) resuscitation. Could an “Epi-pen” type of approach be tried to jolt PSSD blighted bodies back into life?
Darren
Chad says
Hey Darren,
Any more progress to report?
Sturm says
Hi,
I actually tried ECT to try to cure my PSSD (I’ve had it now for a bit over a year, but was on SSRIs and SNRIs for a decade, between 12-22). Even unilateral ECT very quickly caused my emotional blunting and severe anhedonia to disappear. I had a second course of ECT too (bitemporal / bilateral), I am still doing it, it and I believe it is causing additional improvements in most sexual symptoms, as well as my akathisia (a symptom I also associate with my PSSD). I do want to try really low dose Cogentin though as I am still attempting ECT.
I have heard of someone else with a condition mimicking PSSD, which ECT was able to cure. I also met with his psychiatrist and he actually did say that he had PSSD patients previously who were able to reverse their condition via frequent enough ECT.
I did post this yesterday as well, but there is a bloke in Australia named Joshua Leisk who claims PSSD is actually an SSRI-induced form of CFS/ME and that his protocol should likewise be able to reverse it.
Dr. David Healy says
This is fascinating and unsettling. ECT as a treatment works on the motor system primarily to bring about changes in conditions that are largely motor conditions. PSSD and emotional anhedonia along with protracted withdrawal seem more like sensory system problems – so it is not immediately clear ECT should help.
A number of things have made temporary differences in PSSD – treatments tried and often on stopping give a window of apparent recovery. In the case of ECT – there is the anaesthetic which may be important and if it is, then ECT given in one clinic might help but given in others might not because they use a different anaesthetic.
But another factor is cholinergic antagonists like suxamethonium are given to temporarily paralyse muscles so there will be no physical convulsion or a heavily damped down one. Given recent interest in the effects of cholinergic drugs in peripheral neuropathies this might bring the ECT and peripheral neuropathies closer together.
Turning to ECT is a very drastic move and speaks strongly to the desperation people who have PSSD experience. It is good that some people try things like this, which to most people will look quite scary. And reports of benefits are great to get given the risks taken but following this comment up needs a bit of thought.
Anyone thinking about ECT on the basis of this comment needs to start figuring if they really need the convulsion or whether there is an anaesthetist they can approach who might be willing to try a brief anaesthetic and/or exposure to suxamethonium – or perhaps rocuronium which is longer lasting
David H
Max says
Hi Darren,
This is most interesting. Any more progress to report as it pertains to your symptoms and use of the massage cushion?
M
Sturm says
Hi,
You do mention that it doesn’t make immediate sense that bilateral ECT (given M/W/F) could cure PSSD.
The anhedonia that I used to have as one of the (many) symptoms of my PSSD very quickly actually disappeared due to ECT. It only took a few sessions of unilateral ECT given three times a week and it did go away extraordinarily fast. I’ve only ever been given Methohexital (the most common GA used for ECT, as I’m positive you know). I would definitely be interested in trying Ketamine as an anaesthetic though. If ECT could quickly rid of the anhedonia I experienced as a PSSD symptom, do you have any explanation for that? Maybe ECT indeed could work for all of this. I also am quite interested in taking Benzatropine. You say the lowest dose I could get would be recommendable?
As I already mentioned, Joshua Leisk’s theory is also pretty interesting. According to him, some people with CFS/ME also get sexual symptoms such as genital numbness and muted orgasms that are likewise found in PSSD, PFS, and PAS.
Dr. David Healy says
Which is why I suggested check out suxamethonium or whatever neuromuscular blocker you are being given. You really should do an experiment which is ask your doctors to get the anesthetic team to give you methohexital and suxamethonium without giving you ECT and see what the effects are. You will need to have methohexital with Sux in order to avoid being awake for what would otherwise be the scariest experience of your life.
Ketamine makes SSRI withdrawal and PSSD worse – which also suggests it may be the suxamethonium that is producing the benefit in your case
D
Timo says
Is the statement that ketamine exacerbates SSRI withdrawal and PSSD your general observation or was it only referring to the writer of the comment? I can no longer tolerate any antidepressants and am currently considering a trial of ketamine with my psychiatrist. Unfortunately, I can’t find much information about this on your blog. I am worried that my atopy, allergies and possible mast cell issues will worsen by taking Ketamine.
Dr. David Healy says
I gave it to 6 people with PSSD and or protracted withdrawal and it helped none and made some worse
D
Sturm says
I also want to additionally add that, actually, Anti-NMDAR Encephalitis has been reversed in multiple cases by frequent enough bilateral ECT. Afaik, there is no explanation for how it is able to relatively commonly do this, yet it does. Chronic and Tardive Akathisia have likewise been somewhat often reported to be reversed completely by ECT.
Dr. David Healy says
ECT works in this case because it is treating catatonic – motor – features
D
Fiona Petty says
I had horrendous reaction to Pfizer covid jab including visit to A and E with megraine of the most severe kind. Since then dizziness getting worse and worse and finally diagnosed with PSSD after 2 years. Head MRI and ear and neck tomorrow. I walk with a stick and exercise regularly intensively and yoga and now have some rehab exercises to do. I feel like blood is not flowing properly to my head so I find these articles interesting.
Tim says
Now, when half a year has passed since this post, is there any information about the results of treatment trials with benztropine?
Dr. David Healy says
Tim
Good question. Benztropine got mentioned 5 months back but it was really much more recent that I began suggesting activelty to people to try it – it was mid September. It was only after a series of posts on anticholinergic drugs that I began to get enquiries like – I can’t get benztropine in my country – what can I take instead.
After anyone gets benztropine or a related drug it will take 3 to 6 months taking it for anyone to be able to let any of us know if it has made any difference. The pirenzepine trial run by WinSanTor report sensations – tingling etc – not always normal sensation – increasing after a few months with some people after 6 months reporting being more like normal.
This was a trial. RxISK is not running a trial – we depend on people who get hold of one of these drugs to keep us updated on what they notice – and the plan at this end is to make any observations available. I know one man reported having to stop for unrelated reasons – he had another condition that needed treating.
I have plans to run another post on linked issues soon but there is a lot going on at the moment which is getting in the way of putting up what will be a relatively complex post
But to come back to your main point – we do need reports back from people – good or bad anything you can do on Reddit or any other forum to get people reporting would be help us all take stock
David
Window says
Hey. I have suffered from pssd for over ten years. (isotretinoin, ssri, snri..). My symptoms got worse and more extensive both during use and when stopping. I think the most important thing in research would be to take into account the “windows” experienced by patients. I myself am one of those who are able to get windows mainly only when stopping ssri or some other medicine that affects the brain. For example, on the fourth day after stopping the medication, for about one evening, sexuality (libido, sense of touch, ability to orgasm, relaxation) / social feelings / affective empathy function as before the medication. Different drugs temporarily activate the functions they damaged in the brain when they are removed. It depends on the drug and the dose, whether it helps 100% or less and only one of the damaged functions or all. I have understood that some people also get such generally short-term or temporary benefits when starting or using different medicines or natural products. Also, e.g. in connection with long supervision. But how to make this broken mechanism work permanently or long term. And safely without risks of new drug side effects or worsening of the condition? I personally link most of my symptoms to the fact that oxytocin is either not secreted as a result of the broken function of the ssri or it doesn’t work/get there. Oxytocin is strongly related to presence, pleasure, relaxation, recovery, affection, social feelings, orgasm, caregiving, love, social connection… the very things I lost as a result of ssri. It’s certainly not the only neurotransmitter or hormone that has changed, certainly also at least serotonin and dopamine, but oxytocin is probably the most essential for me. I think this proves that the possible neuropathy is of cerebral origin, and not permanent. And social anhedonia is also medicated because sometimes the feelings can return during the windows as well. As a young woman who got sick myself, I only noticed the lack of touch for sure at the very end, when it got really bad. After the last trial and termination, the sexual stimulation caused a really strong anesthetic spike-like effect. From what I’ve read of people’s experiences, for some this symptom is not even noticeable or it gets better first even if all other symptoms of libido/emotional life remain. In my opinion, drug damage should be approached as a syndrome, and not one symptom above. It would be important for everyone to get an explanation and a certificate for their injuries. There is something common in the background, even if for different people the Domino phenomenon goes in different directions, one or more. Sorry for my bad English, I used a translator.
Darman says
Dear Dr Healy
Regarding Benztropine, what is a very low dose as you suggested?
Dr. David Healy says
D
There is an update to this. I now think the best bet is Oxybutynin either 5 mg or 10 mg extended release one pill in the morning – perhaps lower dose to start with to ensure lesser side effects.
There is a Gel form – Gelnique – that I believe can be rubbed into genitals.
I was being over-cautious with the earlier benztropine proposal
D
Darman says
many thanks for your reply Doctor. I will look into this.
Darman says
I have been taking 5mg every morning for over 1 month now. No change so far but I will continue.
Dr. David Healy says
Thanks for reporting this. If you are having no adverse effects it might be worth increasing the dose to 10 mg. Great if you can keep us updated on any changes for good or bad and hopefully you can make it beyond 3 months which might be when the first signs of a difference will become more obvious
David
Darman says
Hello Dr Healy.
I have completed three months now but with no positive signs. Not sure if I should continue. Do you offer any private consultations?
Dr. David Healy says
Darman
Again thanks for the update Private consultations with me aren’t the answer here in that neither I nor anyone else has the answer. It’s much more a case of you and others who are trying things who will need to be consulted about exactly what effects Drug X or Treatment Y has had so that the rest of us can work if what you have found will generalize to anyone else.
Re moving forward I still think anticholinergic drugs are currently our best bet. Three months is the minimum time I would have expected any benefit to show especially at as a low dose as you started at. The problems can happen much earlier but from this report you don’t at present seem to have any. Six months would be a more definitive test – this is the duration WinSanTor have been using for their pirenzepine paste trial.
This is your call but I think if it were me I would ensure I’m on a higher dose (5 mg morning and afternoon) or switch to oxybutynin 10 mg in the morning – this has one advantage in that it also comes as a Gel so it can be applied to genitals directly. It is applied to the genito-urinary skin and mucose area in women who have bladder problems (this is the reason a Gel was produced). Testing to see if direct application to an area where the nerves don’t seem to be working makes some sense and even with internal bladder problems the Gel seems to ensure some of the drug gets into the body more generally
David
Darman says
Thank you for your reply and thoughts doctor. I will continue for now however I’m not convinced, in my case at least, that this has anything to do with nerve damage. It feels far more of a mental issue to me.
Dr. David Healy says
D
Everyone feels their brain is the problem – its almost certainly not. Too many of you are functioning amazingly well researching things etc for this to be the case.
I have a Mad in America Seminar in two weeks time where I will explain why it feels very like the brain rather than anywhere else is where the problem is – misleadingly feels that way
David
Darman says
Thank you. Dr Healy.
I will persevere and report back..
Darman
Ricardo says
Recently there’s a claim of some famous youtube “biohacker” having fully cured from PSSD (post Lion’s mane, which he identified as the same). As science still hasn’t solved the problem we shouldn’t discart anything, especially cases of recovery.
Basically his approach, more in line (in fact) with Melcangi’s, focuses totally on endocrine processes. Many of the endocrine processes halted by 5-alpha reductase inhibition turn out out to be neurological (along the cascade of hormone/steroid transformation and synthesis blocked by 5-ar inhibition).
– He claims DHB (dihydroboldenone) gave him back full emotions, even though that was transcient and the drug liver-toxic.
– DHT gel (not so surprisingly) having got him back “bull” side penis.
– Allopregnanolone drops also helped a big lot.
– The main recovery factor having been an extremely dangerous drug for épilepsie known for (says him) to switch or édit genes (sodium valporate).
– The above mentioned steroid having been taken concurrent’y to valporate to make their effects permanent (says he…).
Another approach validated by Melcangi is the fashionable idea of the gut-brain axis. Plenty of anecdotal reports claim either cure, if only embetterment from FMT (Fecal Microbiita Transplantation) and pre-probiotics (soon psychobiotics…). These microbiota modifications are also popular for what concerns ME/CFS/ Long Covid.
In the position we are we shouldn’t discart anything, we should even promote this brave sufferers who tried things, many successfully.
The gut-brain-axis angle of the problem is the less invasive of all, far less invasive than taking g medicine. The steroid replacement approach makes obvious sense, it SCREAMS sense. DHT is what the organism was deprived in the first place with PFS.
I’m not sure solutions are out of hand, far from it.