The recent RxISK post on PSSD and Thermal Thresholds led to a lot of comments about what should “we” – those with PSSD or related conditions – do. There was a looking out to FDA or other regulators, doctors or politicians to do something.
Coincidentally on davidhealy at the same time a pair of posts on antidepressant induced suicide in children, The Greatest Failure and Spectre of Dissent provoked a similar response, partly aggravated by the images that went with the posts. What do you want us to do? Tell us.
A structural response to what should be done in terms of drawing problems to the attention of FDA and other regulators, Governments and others and whether they can be of any help in PSSD or other problems is now in a post just up on dh – What To Do about Suicide.
This post deals with what readers can do if they have a particular problem or are trying to help someone with a particular problem.
The bottom line is everyone needs an Anne-Marie.
Anne-Marie dropped out of school early. Years later she was put on an SSRI which caused her to drink compulsively. She raised the issue with her doctor, the company, and others and later with AA all of whom dismissed her but she did her own research and worked on how SSRIs do this. Her conclusions mapped straight onto internal drug company conclusions that no doctors, regulators or others knew about. Her story is Here.
The breakthrough aspect of all this for me was that here was someone telling me, who has a PhD in the serotonin system and serotonin reuptake inhibition, things about serotonin and SSRIs that I didn’t know.
Faced with an Anne Marie you’d have to say – motivation is worth more than expertise. This is what the AIDS story is all about as well.
Key to the Teicher 1990 article about SSRIs inducing suicide was a set of patients telling doctors they could distinguish the suicidality induced by depression from the superficially similar suicidality caused by the drug. Perhaps they were particularly persuasive or the two doctors and one nurse were good listeners but this article changed everything – and triggered a company response – “the plural of anecdote is not data” – which is now the biggest problem everyone in medicine faces.
Anne Marie-ness is the reason to be hopeful about solving PSSD, but it will take a bunch of Anne-Maries. One of the neat things about RxISK is how many Anne Marie’s have migrated this way.
Our Anne Marie’s don’t always comment on posts but for instance the Thermal Threshold post was written by someone who has been working hard on pinpointing what kind of test might deliver a positive result that would help people get believed and would also help narrow down the target for further research.
Unless we put things on a plate for high-powered researchers they aren’t going to do anything, partly because they have their own commitments. If we put things on a plate for them, they will get the credit which is fine if that spreads the word. If they turn out to be decent people they will someday let the world also know what really happened.
When a post like Thermal Thresholds goes up, we need people to see if they can get the tests done somewhere – or even make their own kit. We only put things up that seem reasonably safe and that we’d be prepared to have done ourselves.
Even negative results will move things on.
We also need people who think the problem is in the brain or elsewhere to come up with tests that those affected might be able to get done in a clinic near them. The contributors to the various PSSD forums have done remarkable work over the years testing all the obvious drugs to see if they will reverse the problem and speculating on brain mechanisms. Getting a test that reliably picks out people with the problem is a possible next step.
One of the other Anne Maries who does comment a lot on the various posts (SS) did a lot of research on Thermal Thresholds following this post and came up with the following options – some of which may help make it easier for readers to get their thermal thresholds tested.
AD, another Anne-Marie, also did some fascinating research, in response to Thermal Thresholds. This is someone who had been in touch with RxISK before, who lives in France but comes from another country entirely, so to access complex scientific articles in English without any healthcare background is quite an achievement.
Here is the sequence. AD figured he’d pay some heed to the RxISK ideas about neuropathy in withdrawal and PSSD.
I don’t understand the great majority of what is described in these links. The reason I thought it might be interesting is because you wrote on rxisk.org, that maybe something that could be useful for protracted withdrawal issues would be to find something that activates the sodium channels.
I don’t know if a sodium channel agonist is the same as a sodium channel activator or opener, but I found these two links that talk about “dimethyl lithospermate B” that is found in a Chinese herb called Salvia miltiorrhiza or “Danshen” :
These articles turn out to be fascinating. Danshen is Red Sage which can be got – in France anyway and AD is trying it.
“Concerning the Chinese herb “danshen”, I bought it and started to take it two days ago. I bought it in a crushed form. I take approximately 3 grams of it and make an infusion with hot water 2 times a day (6 grams per day)”.
But just as useful is what happened next. I wrote to Professor Suk-Ho Lee in Seoul who is the lead author on these papers. (The main use to a David Healy in all this is that he can write to people like this who pay heed because DH has academic credentials – for the moment anyway).
Professor Lee responded with a helpful and gracious response. He read the papers we sent and suggested that he didn’t think Danshen would help because it seemed to have its greatest effects on the Nav 1.5 channels which are the sodium (Na) channels in the heart which is what his group were interested in. But then he clarified for us that the brain primarily uses Nav 1.3 channels and the peripheral nerves use Nav 1.7.
This is a hugely helpful step forward both for those who figure the problem is in the brain and those who figure its in the periphery. It doesn’t mean Red Sage won’t work but it might be less effective than an agent acting more specifically on the 1.3 or 1.7 channels.
In the case of the peripheral nervous system, this brings Low Dose Naltrexone (LDN) into the frame.
“I have found some links that talk about Nav 1.7, Congenital Insensitivity to Pain and how the analgesia can be reduced (I think temporarily) with opioid antagonists. Here is a link:
In the past several people with PFS or PSSD or PGAD have tried LDN. Low Dose usually means up to 5 mg per day. My suggestion is that anyone interested in this idea try somewhere between 0.25 and 0.5 mg per day – Very low dose (VLDN).
Many people can get prescriptions for LDN from doctors these days and there is at least one pharmacy in most countries that will supply it. It is not expensive. The usual recommendations are to begin very low if you have been taking psychotropic drugs. Do not take if you are currently on psychotropic drugs. My hunch is those with PSSD, PFS or PRSD are likely to be particularly sensitive – hence the even lower dose.
If Thermal Threshold Testing and an even partial response to something like VLDN or Red Sage point to a Nav 1.7 problem, this is where researchers who can do what we can’t do are more likely to get involved. There are research centres who specialise in the genetics of Na channels and others that can investigate possible auto-immune disturbances affecting these channels.
AD did even more. He found an article on pirenzepine – an anti-cholinergic drug that seems to have nerve repair properties. Anticholinergic drugs can be anti-nicotinic or anti-muscarinic – pirenzepine is anti-muscarinic.
Over 3 years ago we published a post asking people to look into Benztropine. This is another anti-muscarinic agent that was removed from the market in many countries mysteriously a few years ago – after it was reported to have nerve repair properties that might make it a blockbuster treatment for MS.
We asked you all a bunch of questions but no-one got back to us. One person with PSSD went to extraordinary lengths to get hold of some (it’s still available in the US) and reported a benefit but he has dropped out of contact.
The pirenzepine link reinforces the idea there are possibilities in this area. It may be something other than an anti-muscarinic action that produces the benefits here. So not all anti-mucarinic drugs may help.
It could well be that even if the problem is in Nav 1.7 channels that the answer may lie in a completely different action that benztropine or pirenzepine have to some degree – perhaps not quite the right degree. There may be even better drugs out there that do whatever it is that might be helpful
This is where the work of people like Anne-Marie and AD come into the frame.
Others are contributing huge amounts. Spruce has personally contacted a very large proportion of the doctors and pharmacists in Western Australia. Heather and others affected by Ro-Accutane have done great things hounding regulators and companies. Laurie Oakley is working hard on getting support networks set up (more next week on this). These and other contributions are all needed if we are going to make a difference. Not everyone – certainly not me – has the patience or skill to spot leads in research articles outside my field of expertise.
The range of skills people have are astonishing and combined can achieve astonishing things. This can happen provided we don’t sit back and think there are experts out there who are more skilled than us or have our interests at heart.
It’s the Wizard of Oz story. See Die RxISKing it One and Two.
What a fantastic post – so uplifting despite the fact that there are no answers there yet. I feel that this is exactly what we need – to know what has been happening, out of our sights, in the name of ‘progress’.
It is so easy to feel that our attempts are in vain. That we’ve tried to do all in our powers to raise awareness and donations and still see very little progress. I certainly now feel revitalised to push things even further – knowing that there are so many other worthwhile attempts in the research area going on too.
There is a goal:
The Intolerance of Deception
It doesn’t take much to inspire, a word or two, is sometimes all it needs and someone like Anne-Marie is very impressive. So much so, that the blog is still live with comments with alcohol and drugs…one of my doctors notes suggested that I had more than one glass of wine…aka Seroxat ..
So, let the Talent flow for the intolerance of deception and celebrate the Heather’s and Mary’s, the Anne-Marie’s, the Laurie’s, et al, for their unrelenting dedication ..
Those who can and write well in English could contact researchers by taking their names from neurologic and epigenetic studies found on pubmed. You can try to get them interested in the problem of PSSD, warning that it is supposed, among others, a hypothesis of epigenetic changes at the base, you can ask them what kind of study could approach the understanding of post-SSRI sexual dysfunction. Examples of studies that revolve around SSRIs, serotonin, epigenetics, gene expression https://www.ncbi.nlm.nih.gov/pubmed/29104538, http://www.mdpi.com/1422-0067/19/6/1788/htm …
The same can be done by contacting researchers who have already undertaken to study small fibers in the genitals.
I have sent a lot of emails in the last few years, but unfortunately only a few times I got an answer, maybe also because I do not express myself well in English (I’m an italian woman) and I can not be convincing who is already very busy doing something else…
I would like if there was a protected group of users busy contacting researchers and doing their own research, to keep up to date together step by step, in addition to pssdforum, does it exist?
On the wake of sodium channels: https://en.wikipedia.org/wiki/Sodium_channel#Alpha_subunits
– Potent Modulation of the Voltage-Gated Sodium Channel Nav1.7 by OD1, a Toxin from the Scorpion Odonthobuthus doriae
“The present study shows that the scorpion toxin OD1 is a potent modulator of Nav1.7. Low nanomolar concentrations of this toxin impair the steady-state fast inactivation process, enhance the recovery from fast inactivation, increase the peak Na+ current, and give rise to a substantial persistent Na+ current.”
– Mapping protein interactions of sodium channel NaV1.7 using epitope‐tagged gene‐targeted mice
– Analgesic Effects of GpTx-1, PF-04856264 and CNV1014802 in a Mouse Model of NaV1.7-Mediated Pain
– Voltage-gated sodium channel mutations and painful neuropathy: Nav1.9 joins the family
– Third Sodium Channel Implicated in Painful Small-Fiber Neuropathy
Mutations in Nav1.9 render pain neurons hyperexcitable
– Reduced Nav1.6 Sodium Channel Activity in Mice Increases In Vivo Sensitivity to Volatile Anesthetics
I have not found anything special by searching on Google keywords: sodium channel genital, or sodium channel sexual.
It is mainly about neuropathic pain. Maybe the opposite of pain is anesthesia (like genital anesthesia), but I’m not sure it’s the key to PSSD: I no longer have arousal and sexual pleasure, yet I do not feel pain and I do not even feel anesthesia to touch, but “sexual anesthesia”… I feel that in my case the problem does not start from genital anesthesia, but from the fact that there is no excitatory response and genital congestion.
There is much to investigate with ion channels.
One thing that could be interesting is that the genes that code each channel can have mutations / variations in some individuals; for example, SCN11A is the gene that encodes nav 1.9: “They found eight heterozygous SCN11A variants in 12 patients. Two of these variants, I381T (located in domain I, transmembrane segment 6-D1/S6, present in two patients) and L1158P (DIII/S4, present in two patients)..”
Who develops PSSD could perhaps have in common the variant of a gene that controls a type of ion channel (sodium, calcium, potassium); who develops PGAD could have a different gene mutation in common, etc.
The comparison of genome analysis of who has pssd can highlight this mutation?
sorry for my english and any mistakes.
Sorry, I know this is off tangent, but something L has written about sodium and potassium has rung reminder bells for me and I just wanted to add this:-
In 1950 my father was diagnosed as having manic depression ( following several cyclic manic events since 1940 when he had a 7 hour operation in Manchester, the second ever done in the world, for pericardiectomy, which involved, I understand, lifting the heart out of the body to remove a calcified layer round it which was squeezing it to death). Without this experimental operation, his death was assured anyway. He survived, against all odds, 72 years and did amazing work in the field of design engineering.
Back in 1950 they hadn’t latched onto the ‘serotonin famine in the brain’ stuff, but my mother was told that his manic depression resulted from ‘an imbalance of sodium and potassium in the brain’. Could this be connected with what L is writing here?
As a young child, my father had had a passion for eating salt by the handful. He found be found hiding under the table with the salt cellar, guzzling salt. Could this account for the calcium build up round his heart and the later apparent ‘brain imbalance’. Could a sodium/potassium imbalance be happening to many people now taking SSRIs etc so that many more manic depression diagnoses are being made nowadays, when in the 1940s and 1950s it was relatively rare?
This was a 1960s idea based on what was then known about lithium. Its not entirely unrelated to what antidepressants also do but without knowing what the basis for PSSD is and the genital anesthesia that all SSRIs cause within minutes of the first dose, it’s difficult to know what the links between this and the 1960s ideas – which the 1960s dudes dropped soon after – are
Tarang Sharma and colleagues -Thanks so very much for giving hope that some of the younger cohort are not swallowing the lies put out by the colleges and regulators – with the help of the media and even some ‘user’ organisations. These should be reading your thesis and spreading the message. Will copy it to as many as I can . We don’t want just some young people and adults to be saved we need all to be safe from harm and it can’t just be up to the personal bias of individual prescribers . The harms can include also that the symptoms lead to incarceration, increased drugging damaging comments being recorded on files as well as the particular adverse effects of the drugs you document. I am wondering why the cut off for for describing children and adolescents is 24 yrs? That range would usually include adults?
After reading such a document I would hope though that no even adult would take the drugs at the very least without the prescriber giving proof of having read the lack of/evidence and therefore being able to warn of the risk – and it is still not clear who will be at risk and how great the risk would be individually.In fact as they are so dangerous I would prefer them to be banned altogether as there are ,as explained on the blog elsewhere, other less dangerous drugs, if drugs are the desired choice to the person and other acceptable options have been tried.. I would respectfully disagree with Tarang and colleagues that ‘prescribing for children Could be negligent’ but maybe that’s a requirement of what can be publishe She/they give the evidence that it Should be negligent. DH has pointed out on the blog elsewhere that a legal case is not really feasible, but medics are still worried if cases are referred to the GMC (even if that org is not trusted or respected either, see their blustering re the Gosport scandal, just one of many ‘failures’) ) maybe that would be a route worth trying again?.
I think 24 is the age when its assumed that the brain has reached maturity ie fully developed.
Thanks Mary R. I was wondering if there were legal reasons – It is a very crude assumption though isn’t it…
The legal issue has nothing to do with a maturing brain. The clinical trials have shown no benefit to these drugs in people 25 or under against which the risks could be offset. The risks are exactly the same in people over 25 but the clinical trials one way or the other appear to have shown some benefit and because of this regulators have decided that warnings would put people off getting this benefit and therefore they won’t warn.
D I noticed we are nearly at the $50,000 mark for the prize – it’s shot up since i last looked. Are we still going for the $100,000?
Lets get to $50 K first