RxISK Research Fund and Prize

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June 27, 2022 | 48 Comments


  1. Thank you for such a comprehensive explanation of the difference between the Prize Fund and the Research Fund. Let’s hope that the ones who need to hear this ‘difference’ do read this post.
    Of course, all of us who have donated to the Prize Fund want to know that it’s kept safe and sound but we have to trust that the Rxisk Team have the interest of all sufferers uppermost in their minds when they consider its use.
    A promise is a promise – the promise was made that not a penny of the donations would be used for anything other than a cure. To suggest now that it should be used to fund any research that may or may not go anywhere near a cure is to break that promise. Should that happen, I fear that very many of us who donated out teeny tiny bit in good faith to the Prize Fund would not lift a finger to raise a penny to the new Research Fund.
    All that’s gone on reminds me of those for/ against trade unions. Vote to strike and so many will find fault – gain better pay and conditions as a result and the ones who found fault are the very ones at the front of the queue for the resulting benefits.
    We all must show which side we are on and work, as one, towards the goal. Let’s use our voices, or our pens and paper, or social media to get behind this new fund.

  2. I don’t think any of those involved in handling the Prizes are in need of using the funds for any thing other than described – (as this seems to be alluded to somewhere) and was agreed to by donors when making donations. If people are not in favour – no need to donate. But links have been given by Rxisk which can be used by anybody with an interest in finding help and helping to find that help. These links have been made publicly available and have already opened up chinks so why not get in contact? There may be information straight from the horses’ mouths the researchers mentioned would never have thought of. Many who read the blogs are savvy about networking and researching .The names on the above have already shown an interest so it’s not an automatic brush off from them for a start – which probably would happen without D H’s credentials and the evidence behind the years of work in seeking answers -against much opposition. Now is not the time to give them any ammunition to disrupt the possible beginnings of understanding this horrible situation .

    • Thanks for this Susanne.

      The most useful thing that perhaps will come out of this is that it reveals all the pent-up desperation people feel. It has always been obvious the Prize could help with this but we haven’t spelt it out enough or tried to get people to mobilize behind it.

      Most research is a waste of time. When I say we have now come across two projects – one by luisa guerrini – we means not me or anyone in rxisk. It means people out there. Tons and tons of people get in touch and over time some are clearly worth listening to because a large amount of what they say is on the mark. Not because they are academics or researchers – they’re not. And its people out there who perhaps think they can’t contribute because they don’t know what might be the right thing to research (no academic or medic knows the right thing – but they’ll never tell your that) or because they have no money who came up with luisa guerrini, prokineticin and christine heim – nothing to do with me or anyone else in rxisk.

      This led to a lot following up by me and others emailing and fixing meetings etc and at the moment it costs us so little to fund Luisa G that this also made it a good idea for the first time to think about actually doing something.

      Some of the ideas opened up by Christine Heim’s research are beautiful but less likely to tell us much about PSSD – this is going to be counter-intuitive to all those people convinced that sex is a brain thing. If this goes ahead it will take a year or more to set up because of ethics committees and will cost too much likely for anyone to afford easily. I can see business spin-offs from this one though to if anyone has deep pockets and wants to hear more – get in touch.

      If anyone else wants to transfer their funds elsewhere – tell me what the point is? Who can tell you where to put your money that would make any more sense than just burning it?

      Its a bit like people who insist we must know what pill to take to solve PSSD or withdrawal etc. We don’t. It really is a matter of sitting together until the Knight destined to find the Grail turns up. Its probably going to be a woman – not a man.

      While we wait, the Prize offers people with no money an opportunity to make a difference. It only takes one lucky person to draw the attention of one person to the prize to make a difference.
      This can give a lot of people agency or a voice. They can act like a millionaire (well 100K) without them or anyone else losing money. The person on the reddit thread with no money to donate to anything and thinking about suicide now has $100K behind him or her and a license to pester.

      Someone perhaps needs to set up a group to co-ordinate the pestering and make it count. If they can make it count, we’ll gladly sell the office in the Caribbean.


    • ‘The most useful thing that perhaps will come out of this is that it reveals all the pent up desperation people feel’.
      One of the many incredible achievements of RxISK is to achieve a much wider awareness of PSSD in both professionals, and amongst those who are prescribed SSRIs and other medications which cause such terrible suffering, and destruction of quality of life.
      Some years ago, I was able to discuss one of DH’s publications on PSSD with my then G.P.
      Despite my decades of studying and practising medicine, without RxISK, I would have remained very poorly informed about this wretched Adverse Drug Reaction to ADs and to the other drugs causing such suffering. This GP also discussed akathisia with me as a result of RxISK. Before I left that area, it was apparent that RxISK had increased both of our awareness and concern.
      Increased prescriber awareness of PSSD is the only means by which those suffering from prescription drug induced destruction of their sexuality may be recognised and understood by their doctors. The false assumption that this is a consequence of the ‘underlying mental health condition’ can now be challenged by reference to a meticulous scientific evidence base.
      The RxISK Prize; and the separately purposed Research Fund ensure a further increase in prescriber awareness as well as real hope of relief of suffering. These inspired and courageous projects could not be held by more dedicated and trusted leadership.

  3. It feels strange that someone would demand other people’s donations be shifted to a different purpose from what was intended when the donations were made.

    On the other hand, I find it incredibly sad that we’re doing this at all, that drug injury has made so many so desperate that it seems the only option is to figure it out ourselves.

    I think Mary has stated it very well, and I agree that RxISK can be trusted with the funds. (Otherwise we’d all be singing this tune, ha!) https://youtu.be/MjkMh0tKCZo

    • A good model for fundraising and research development is the Open Medicine Foundation for ME/CFS:

      They have raised millions and set up numerous research centers at prominent institutions.

      • Excellent, at least you know what plan you want to follow when you set up a fundraiser for research development. Good luck with it by the way

  4. Sorry but aren’t you contradicting yourself a bit? You’re saying the prize fund should not be dedicated to one particular research effort, for example something like Baylor which you critique, but then create a research fund to be allocated to specific projects you think are most promising.

    This doesn’t make sense.

    • It makes perfect sense

      We are very reluctant to commit money to anyone’s pet theories.
      Luisa Guerrini has solid and new data and it costs almost nothing to support her, and what she is doing should broaden out the way everyone is thinking about these issues.

      At the same time we keepthe Prize intact so people like you can chase all sorts of leads and encourage researchers to see if what they are doing might be an answer to PSSD. Nothing would give me more pleasure than to hand over the Prize to someone you had unearthed who really does understand what is going on and how to put it right – in fact not in theory.


      • What distinguishes Luisa Guerrini’s ideas from what you deride as “pet theories”? The Baylor study yielded tangible results which don’t amount to a “pet theory”. Also, you say “few people realize that paying people money to do research is like pouring water into sand.” So again, why is Luisa’s research the exception to this rule you stated which holds for research organised by other parties? Why is it legitimate to support her research efforts but not an undertaking such as Baylor?

        In respect to the prize, I think it is a great idea to generate research interest but I don’t see how a prize like this is going to achieve that aim. Have we had any indication over the past half decade since the prize fund was created that researchers have been motivated by it? If so, which undertakings have begun that have been motivated by this fund?

        • If you read the posts you’ll be able to work it out for yourself. Finding out why thalidomide causes birth defects has been a 60 year mystery. Some years back a research consortium involving Japan, the UK and L.G. had papers on the link to p53, p63, and Cereblon. This is not the full answer but is widely accepted as real step forward.

          My understanding is thalidomide is not an SSRI but lenalidomide is – and it causes identical problems and both cause suicidality, sexual dysfunction the way SSRIs – along with being anti-cancer and anti-Covid the way SSRIs are – not miracle cures for.

          So when it turns out sertraline does the same thing – this seems important to me – and costs almost nothing to fund compared to the Baylor thing which was over $1Million and yielded nothing. Not only did it yield almost nothing but the researchers sat on data that should have been in the public domain for years before hand.

          One of things the Fund brings out is that people like you could start getting in touch with researchers working on something that looks promising and you could make them aware of the conditions and the Prize.

          If you’re suffering or know someone who is, I’d have thought it would be much better for you to do that than get in the way of people who are trying to do something.


          • I’m not getting in the way of anything and I don’t understand why you seem to be taking these things personally. All I’m doing is ask questions. I frequently donate significant amounts to research, have spoken publicly about my condition, have spot a video podcast in which I talk about having PFS, and have messaged hundreds of journalists and researchers about the condition. So I don’t appreciate being told I am somehow not doing anything.

            As said, I am simply asking you questions because I think it’s important we go about things the right way given the gravity of the situation. I am open minded and would like to support as many worthwhile initiatives as possible.

            Baylor did not reveal nothing. It revealed widespread changes to the chromatin landscape and provided the most in-depth analysis of PFS to date. But again, the question I’m really asking is why is one avenue of research or initiative akin to pouring water in the sand whereas funding LG’s research is not? Isn’t this the kind of certainty you were dismissing other groups for having? “Beware people committed to a pet idea.”

            You also say “The $100K in the Prize is peanuts in terms of funding research. It won’t do much more than help fund a holiday in Stockholm for the Nobel Prize that the person, or team, who solves these problems is highly likely to get.” So then how is this a good use of the prize fund then if you consider it peanuts for accomplished researchers?

          • Erik

            Last I heard a decade back over $4 billion had been spent on mental illness genes research which has revealed nothing of any use. In contrast just before that huge outlay, a small group of doctors (2/3) put velocardiofacial syndrome on the map by just looking at people and how they responded to meds – the most solid thing that has come out of genetic research in the last 40 years.

            Big program research has a very poor track record. I moved from a lab on the West Coast of Ireland with almost no money but the freedom to follow our nose. We found out far more than the lab in Cambridge England I went to that had several Nobel Prize winners linked to it and pulled in huge grants which trapped them into doing what everyone else was doing – what was fashionable.

            PFS – a long time back – early Baylor days – I liaised with a lot of PFS folk. Very nice people but delusionally stuck on certain ideas that really have yielded nothing and I think were largely a waste of time. I don’t mind us differing on that.

            There is no right way to go about things. Research is fishing – if you know what the answer is and head down that route figuring its just a matter of demonstrating what you know to be the case – you will waste vast amounts of money and time and dash hopes. Its imaginative. And it requires the flexibility to recognise that when someone brings things to you that there might be something in this new angle.

            Why the prize fund – because the best researchers are competitive – they are the kind of people who will place bets on which of two flies will crawl up a wall first. Most of the research community aren’t that way – its a boring job.

            This is not taking things personally but I have to say if you want me to persuade you I or RxISK are adhering to what you figure is the right way or others have told is the right way, I’m not about to do it – there are far more important things to be getting on with.


  5. The yellow bellied toad has a protein in its skin which is a prokineticin agonist called Bv8. There is a place just up the road from me that has a stock of such toads, people buy them to keep in terrariums. You could probably purchase quite a few yellow bellied toads with 100K and send them to people. I’d have a problem keeping a box of toads under control in my condition.

    My tapering off liquid Fluoxetine has made me feel quite peculiar. When I want to walk around anywhere I feel like I am off in a dream, it’s like the life has been sucked out of everything. I still cannot think as clearly as I used to. I appear to be stuck with an unnatural numbness now. I’ll continue to taper off the stuff and hope that I begin to feel more normal again.

    I think my use of daily supplements has helped, the frequency an severity of headaches has diminished possibly due to me taking 500mg Vitamin B2 each morning since February. I just wish I felt less dizzy when walking around and could focus properly without being distracted and daydreaming. I have no trouble sleeping but I stopped taking ashwagandha as I decided it might be contributing to the numbess and dizziness I have to endure during the day.

    • Justin

      This is a stunningly interesting paper. Exactly the kind of paper, Erik below and others should be reading and contacting this research group. The work hyperalgesia appears in the abstract – this essentially means just the opposite to humbing and is just what is needed in PSSD – emotional numbing etc

      It would be great if people getting working out about the RxISK Prize started chasing this group and others working on prokineticin to tell them about their condition. To be really effective it might be a good idea to form an activist group.



  6. Perhaps it’s just me but I find the level of detail in these papers quite intimidating and I feel quite stupid trying to get a handle on what is going on. I thought it might make sense to look into prokineticin agonists. I found it odd that the only one that is mentioned is this Bv8 agonist obtained from the yellow bellied toad I would have thought there would be others. I find it quite difficult to grasp how these results are discovered in the first place.

  7. Yet another shoddy misleading article published in thebmj

    ”Antidepressants can have side effects, including indigestion and feeling agitated. Side effects usually improve over time.’

    Almost half of people on long term antidepressants can stop without relapsing
    BMJ 2022; 377 doi: https://doi.org/10.1136/bmj.o1362 (Published 28 June 2022)
    Cite this as: BMJ 2022;377:o1362

    Helen Saul, editor in chief1, Deniz Gursul, research dissemination manager1, Samantha Cassidy, science writer1 , Larisa Duffy, ANTLER Trial manager2, Gemma Lewis, Sir Henry Dale Fellow2, Glyn Lewis, professor of epidemiological psychiatry2

    To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/almost-half-people-long-term-antidepressants-stop-without-relapse/

    Why was the study needed?
    More than 300 million people worldwide have depression. Most recover with the right treatment and support, but around half of those who have recovered go on to relapse.

    Antidepressants can have side effects, including indigestion and feeling agitated. Side effects usually improve over time.

    Guidance from the National Institute of Health and Care Excellence recommends that antidepressants are used as “maintenance” treatment for up to two years to prevent relapse. It also recommends cognitive behavioural therapy to change habits of thought and behaviour.

    An increasing number of people are taking antidepressants as long term maintenance. The chance of relapse is reduced by staying on the drugs for a few months after depression has cleared; however, little evidence suggests that these drugs prevent relapse when taken for longer than eight months.

    In this study, researchers explored relapse rates among people who had taken antidepressants for more than nine months.

    What did the study do?
    The study included 478 people aged 18-74 who were treated at 150 general practices in Bristol, London, Southampton, and York. Participants had all had two previous relapses of depression. They had been taking one of the four most commonly prescribed antidepressants (citalopram, sertraline, fluoxetine, or mirtazapine) for at least nine months, and were well enough to consider stopping.

    Half (238 people) continued taking their usual antidepressant (treatment group), while the others in the discontinuation group (240 people) took a placebo. These dummy pills looked identical to people’s usual pills and initially contained their normal dose of antidepressant. This dose was gradually reduced over 1-2 months until the placebo contained no antidepressant at all.

    Participants’ depressive symptoms were assessed at the start of the trial, and then again at various time points (12, 26, 39, and 52 weeks).

    What did it find?
    The study found that:

    By 52 weeks, more people on placebo relapsed (56%) than did those who continued with treatment (39%)
    More than four in 10 people (44%) on placebo did not relapse
    Most relapses occurred 12 to 26 weeks after the study started
    People in the placebo group had worse anxiety and depression scores than those in the treatment group, particularly at 12 and 26 weeks
    Discontinuing treatment cost marginally more than continuing over 12 months (because people who restart treatment have more healthcare appointments, which cost more than continuing on treatment).
    Not everyone who relapsed went back on to medication. Of 134 people in the placebo group who relapsed, most (53%) went back onto antidepressants prescribed by their doctor. But 49 people (37%) remained on placebo in the trial, and a further 14 (10%) chose not to take any medication.

    More people on placebo had withdrawal symptoms (such as sleeping problems and restlessness) than in the treatment group.

    Why is this important?
    The study suggests that some people who would have remained free of depression with treatment, relapse when they discontinue. But more than four in 10 are likely to remain well without treatment. These findings should inform discussions between doctors and people who have had depression. Both need to be aware of the likely benefits and harms of stopping long term treatment with antidepressants.

    Follow-up during the study identified the time points at which people might have worse anxiety or depression or be more vulnerable to relapse. Knowing in advance that these symptoms may appear—and then resolve—is helpful. For instance, many people who discontinued medication felt their mood worsening at 12 weeks, but this may have not been severe enough for them to restart treatment.

    What’s next?
    The researchers say their results should be interpreted with care because the study included only people who had had two previous relapses. The findings might not apply to people receiving treatment for their first depressive episode.

    Participants were mostly white, married, and employed, and were recruited from moderately sized general practices in urban areas. Whether the same patterns are seen in other groups (people who are younger, unemployed, or from minority ethnic groups) needs to be explored.

    Outstanding questions include:

    Does reducing the dose of antidepressant more gradually (over a longer period) have benefits?
    What is the relapse rate after 12 months?
    Since this study looked at four antidepressants, would other antidepressants that work in different ways have different relapse rates?
    It would also be useful to explore the reasons behind individual decisions to stop medication during the study

    • susanne says: re valproate
      June 22, 2022 at 5:16 pm
      As campaigners know this drug is not only used for epilepsy, She is a regular writer in thebmj so should have known this and used the opportunity to alert those who take others including antipsycholtics.

      Luckily someone more qualified than me has taken on another misleading recent article written by J W re valproate
      29 June 2022
      Alain Braillon
      retired senior consultant
      Amiens, France
      Respond to this article
      Read all responses to this article
      Transgenerational effects valproate: an enduring tragedy ignoring translational medicine!
      Re: Valproate: UK regulator looks into possible transgenerational effects Jacqui Wise. 377:doi 10.1136/bmj.o1531
      Dear Editor

      The news “UK regulator looks into possible (highlighed) transgenerational effects (of valproate)” shows how drug safety and the “first do no harm” motto are empty concepts.(1)

      Wise says about our patients’ report (2), “ the malformations and neurodevelopmental disorders in the second generation were not confirmed with medical records or professional diagnoses.”(1) However, in children whose parents had fetal valproate spectrum disorders, malformations were severe and obvious (e.g. spina bifida, craniosynostosis, cleft lip, missing digits …) as neurodevelopmental disorders, opening access to special education programs. Only 88 (47%) children had neither malformation nor developmental disorders.(2)

      Wise’s article did not question medicines regulators’ denial of animal data for so long. Transgenerational inheritance of neurodevelopmental disorders in mice was documented as early as 2010.(3) Further, no surprise: valproate is a histone deacetylase inhibitor, thus responsible for epigenetic changes. Why ignore bench research? Contributions are cheap, rapid and robust: Bingsohn and colleagues confirmed the transgenerational epigenetic side effects in invertebrates to screen for the effect of drugs on the expression of epigenetic regulatory genes as vertebrates models are limited by their long generation times and low numbers of progeny.(4)

      Last, the plan to find children with a confirmed diagnosis of fetal valproate spectrum disorder who had children themselves for a rigorous assessment misses that the present questions are about harms in: (a) children whose parents had been exposed in utero but have no obvious signs of fetal valproate spectrum disorders; (b) children and grandchildren of fathers treated by valproate as neurodevelopmental disorders are increased in the former.(5)

      Will victims continue to accumulate and suffer for a long time without screening for early treatment, a prerequisite for effectiveness in case of neurodevelopmental disorder? The denial seems global: serial registered letters with acknowledgement of receipt, the first in 2017, went unanswered by the French ministry of health.(6)

      Last, valproate is only the tip of the iceberg: many substances (medicines, environmental chemicals, air pollution and endocrine disrupting chemicals) can cause epigenetic modifications (7) and thus be responsible for major psychiatric disorders.(8)

    • the material cited in the blog is not yet published
      it has literally been done in the last few weeks

      for earlier work linked to thalidomide – googling Luisa Guerrini should get you prior papers


  8. David,

    Is Luisa Guerrini’s research done on rats or zebra fish? Why is it particularly cheap to fund her research?

    • Dan

      Rats but she can do Zebra Fish also. I think cheap at the moment because the antibodies she uses are all pretty old and not too costly. If we get into more costly antibodies then the costs will rise.

      At the moment we are looking at roughly 15K Euros for the first year – and she already has a PhD student who has been doing this work. It sounds to me like there is publishable data already.

      We will have to work out a way to let people who know something about these things see what the data looks like in the hope they can spot useful details or offer ways forward


  9. Some further clarifications since certain comments in this blog appear to be directed at me and an organization I’m affiliated with:

    1) My suggestion wasn’t for others’ contributions to be used for anything other than projects they are wholly supportive of as individuals, including the RxISK Prize. Many, if not most, of the donors would probably support RxISK’s funding of Milan’s proposal. It’s also understandable that the logistics of individually dispensing donations may not be worth the trouble.

    That’s all the suggestion was. Not a “gimme the whole pot for what I’m personally invested in,” not a critique of research, not a complaint of baiting and switching if the funds don’t immediately go to researchers.

    If there was never any intention for the prize fund to serve a dual function as a type of escrow for post-drug investigations, then it never should have been portrayed as such. Period. No time-limit on it acting as a carrot on a stick was imposed/provided and, in the meantime, it must have depreciated in value significantly since its inception and has been rolled-over to a $200k contribution goal. It appears the answer to “when” is “eternity” and it’s hard to believe anyone against using it for research would have risked donating if they thoroughly read the initial proposal published on RxiSK.

    2) RxISK or Dr. Healy may have been approached prospectively about a multi-drug, whole-genome sequencing, project to be undertaken by professional geneticists independently of any hypothesis except that we are intrinsically predisposed to these syndromes and that these syndromes are not typical/common adverse drug reactions. That failed to manifest, largely due to the costs involved. I can’t recall a request for partial funding for this proposal being sent, or find any record of a request being sent, but can honestly admit approaching Healy/RxISK about funding was definitely discussed by those involved in relation to this, if only briefly.

    3) The upcoming PFS research at the Institute for Human Genetics is based on Baylor’s (million-dollar???) finding of significantly and expansively altered gene expression in the genital skin of patients, with consideration of the entire breadth of reported symptoms, including observations of altered penile vasculature. Is this dependent on the underlying pathology, or merely coincidental? Any allusions to this research initiative being undertaken as some type of amateur science project are unfounded.

    I don’t really care that much if RxISK/DBM holds my small percentage of contributions to the Prize forever. If that’s what they want to do with it, it can be considered a gift for hosting discussion of post-Accutane sexual/reproductive symptoms when no one else would and for filing the citizen’s petition with the FDA. It was truly appreciated.

    The contributor(s) of the $30 should be offered refund(s) if they insist and past donors notified that the terms have changed if the RxISK prize will never be used for research.

    • Bill

      I don’t know what organization you are affiliated with so there is nothing aimed at you or it.

      I think the finally published Baylor epigenetic stuff is useful This may have only appeared because so many people kicked up a stink and which partly seems to have appeared becuase for ages the team behind it were as I understand it trying to twist it to fit the ideas they had to begin with – and it didn’t fit and they didn’t want or at least didn’t rush to publish.

      I thought it was fascinating because the things that seems to leap out from it are things to do with skin etc that fit well with my hunches about what it going on. I have tried to get people I know who know something about genetics and epigenetics to look at it with that in mind. There are other epigenetic screens done by Antonei Csoka and colleagues and for isotretinoin – someone should be putting all these together and looking for commonalities. Anyone who knows someone who could do this – and it could be done in spare time – could point to the rxisk prize as encouragement – early spadework wouldn’t get the prize but might take someone down a fruitful avenue.

      I think you are mischaracterising the rxisk prize – you’ve pulled out a few words and said hey there you see. If you look at the totality of all the posts, they dont support the interpretation you are offering. And particularly don’t support by offering a very visible proof to people who are being scammed that some of the people trying to gouge money out those affected with these conditions should not be believed and here’s the evidence for that – they haven’t gone near trying to collect the Prize. Things like were stated very early on as reasons for the Prize.

      As you mention – we spent a lot of time into getting a petition into FDA about the sexual effects of isotretinoin. What that seemed to show was that those affected by isotretinoin for some reason have not been able to a achieve a focus that would make them effective. There are some hugely effective people like Sam Ward but the group is split between those focussed on suicide and those on sex or othre things, those wanting the drug removed from the market and those who want warnings. Maybe you have some thoughts on why this is.

      We have encouraged Luisa Guerrini to test isotretinoin and finasteride as well and isotretinoin at least has the same effects as SSRIs and thalidomide. It has always seemed to me that we would be on more solid ground if we can find effects these very different drugs share.


      • David, excuse me but this is incredibly frustrating. You now say
        “I think the finally published Baylor epigenetic stuff is useful”. In your post you say “the study at Baylor University in Texas – nothing at present useful came from it.”

        These are the kind of contradictory statements which I take issue with. In the same way you say certain research avenues are “pet theories” whereas others are not, in the context of you saying be wary of those who are certain about things.

        • Erik

          Sorry these exchanges have distressed you so much and the distress this response is going to cause

          Coming back to Baylor – you make my point that breakthroughs happen by accident and only if people can spot the accident and are not fixated on the orthodox narrative. After a lot of anger and pressure, as I understand it, Baylor were forced to publish their epigenetic findings which they had been sitting on for years because they didn’t fit the orthodox narrative. Given they had been handed well over a Million dollars to do the work, this was scandalous on their part.

          When the findings came to light there were a few things to note. One is that one drug finasteride can cause 3500 changes – there is no drug that does one thing. The strongest changes are in the areas of skin and related changes.

          There is a French aphorism about research and serendipity (accident combined with prepared mind) that research is like looking for a needle in a haystack and finding the farmer’s daughter. In this case you have her skin and things like that coming into view.

          I’d like it if the next comment you make here shows evidence of having chased skin people – did you know that skin has all the major senses built into it – even vision. For my money the ensuring sexual defects are sensory problems and skin is a great place to look. There is a simple book by David Linden called Touch that might get you started on this.

          What I’d love to hear from you is any progress you make with epigenetic folk, skin folk and pharmacologists. The key thing no one is talking about, the thing that will win a Nobel Prize is pharmacological and its not what receptor does finasteride or isotretinoin or SSRIs work on but why do certain systems seize up. Why do certain receptor changes remain locked in place for months or years. No pharmacologist I ask about this has any answers – hence the Nobel Prize.

          So rather than you try to understand me, or having to cope with the idea that solving problems like this needs several different thinking styles of which some might be more useful at one point and the fixity and focus you are bringing to things might be more useful later, it would be great to hear that you have, perhaps using the RxISK Prize as a calling card, engaged some of these other folk and found some leads.

          For the record one of the reasons Luisa Guerrini’s work seems interesting to me is that the mechanisms she is working on might explain why things get locked in place. She is not working on one of the 3500 epigenetic changes these drugs can produce but on possibly one of the relatively few mechanisms that give rise to epigenetic changes.

          I look forward to hearing about some promising leads, you’ve stumbled across in the haystack and hope you are not too focussed on needles.


          • I’m not distressed just frustrated as I had hoped you could be more humble and straight forward in your responses. Especially when dealing with such a serious topic.

            Your statements are openly contradictory and are not logical. This is not good when deriding the efforts of others.

            You say we should look at skin, which is precisely what Baylor investigated. You say “I think the finally published Baylor epigenetic stuff is useful”. In your previous post you say “the study at Baylor University in Texas – nothing at present useful came from it.”

            You then say “Now if you are anyone else is going to help people with PFS forward you will look closely at the results (from Baylor) and see what can be done to get people who might know something about the main findings to take an interest in what is there.”

            Why would we pursue the findings of a study you said produced nothing useful? Which is it? Useful or not useful?

            Please stop being so all over the place and be more precise with statements when talking about the efforts of others.

        • @eric … look to Obi Wan Kenobi “Only a Sith deals in absolutes.”
          In that phrase lies the answer

  10. The article is too long to copy it all but the whole is accessible on thebmj website. Thanks to the journalist and all those who worked on publishing this.
    From FDA to MHRA: are drug regulators for hire?
    BMJ 2022; 377 doi: https://doi.org/10.1136/bmj.o1538 (Published 29 June 2022)
    Cite this as: BMJ 2022;377:o1538

    Maryanne Demasi, investigative journalist
    Author affiliations
    Patients and doctors expect drug regulators to provide an unbiased, rigorous assessment of investigational medicines before they hit the market. But do they have sufficient independence from the companies they are meant to regulate? Maryanne Demasi investigates

    Over the past decades, regulatory agencies have seen large proportions of their budgets funded by the industry they are sworn to regulate.

    Industry fees…….

    Table 1 How the regulators compare……….
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    Transparency, conflicts of interest, and data……….

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    Reform …………

  11. I was wondering about what you think about this paper? https://www.pssdforum.org/viewtopic.php?t=5075
    Irisin is also released by exercise. I have been ridiculously sedentary as of late, and my post ssri brain fog and impotence gets a lot worse of it.Sexual anhedonia is barely affected at all no matter how regularly i exercise,though emotional anhedonia and ability to feel peace of mind improves a bit if i exercise regularly and are social, etc .Maybe these improvements are all related to testosterone catecholamines and bdnf. But the difference cognitively is very significant, proves exercise matters a lot but i suppose we already knew that. I wonder if irisin injections will also work in humans has this been tried?

  12. ‘This $ Million funded a study in Baylor University in Texas which did not produce the results the PFSers were sure it would – nothing at present useful came from it.’

    What does this mean? The study presented the analysis it was designed to present. It was never going to provide actionable insights towards treatment, but instead proved definitively that something is going very wrong within PFS bodies— tying biological data with the devastating multi system symptoms that patients experience. This information has been used to direct the next stage of research, to see if these changes are driven by Androgen Receptor dysregulation, a master regulator of the epigenome. The PFS community understand this is going to be a marathon, not a sprint.

    With regards to the time it took to publish. This is likely because of institutional pressure from the drug manufacturing company as the article went through peer review— we all know that the pharmaceutical companies would rather this problem didn’t exist in a subset of individuals.

    I was keen to support Rxisk, but these kind of unprofessional comments really do our community no favours and needlessly foster a divisive atmosphere. That’s without even mentioning the bizarrely misandrist comment about PFS sufferers all being men. FWIW that’s not true. A small number of women have reported PFS-like symptoms from antiandrogenic symptoms, erasing their experience is disrespectful to say the least.

    • David

      I see you were keen to support rxisk – but somehow never have. You have the Baylor thing wrong. A lot of pressure had to be put on Baylor to publish by people within the PFS community, by me and others. The blockage did not come from Merck.

      The Baylor data points in entirely different directions to what the people who put money into the project expected. Now if you are anyone else is going to help people with PFS forward you will look closely at the results and see what can be done to get people who might know something about the main findings to take an interest in what is there. This would likely be more useful than contributing any money to anyone, especially perhaps the PFS Foundation who have a track record of putting over a million dollars into the Baylor study and only produced an accidental finding.

      Comments like the one you’ve sent in are a dime and dozen and get no-one anywhere.


      • I have supported Rxisk in the past, under my real name and email, as opposed to the alias I am using here. I will likely continue to donate, as all sensible investigation into these conditions is desperately needed

        Awor, the most prominent member of the PFS community at the time, and codesigner of the Baylor study, cited blockages in the peer review process. I don’t understand why you would present this otherwise.

        The PFS foundation no longer seem to have scientific understanding and advancement towards therapeutics as their main objective, which is why the PFS Network has been founded. If the Baylor study results pointed in the opposite direction, then the world renowned AR experts at Kiel would not be giving their time and working at cost to try and uncover the pathomechanism. I’m fairly confident you know all of this already, which makes me confused why you present otherwise. The moment one of these diseases is officially recognised, which is unlikely to precede real scientific understanding, will surely be a watershed moment for all of our post drug communities.

        Are you going to ignore the misandrist comment in the original blog post, and erase women with PFS’s experiences?

        • David

          These results were unlikely to have been blocked by Merck, no matter what you were told. I liaised closely with people well placed in the PFS community to know what was happening and this was never offered as an explanation. Why would Merck block something that was essentially good for them?

          Finding 3500 epigenetic changes on finasteride just shows finasteride is a drug – all drugs do things like this. It doesn’t prove an illness. You could say its a poisoning but all drugs are poisons from which we hope to bring good.

          If you want to give Merck problems start chasing the skin leads which by the sounds of it puzzled the Baylor folk and held up publication while they tried to work out was there a way to make this tally with their original story.

          Here’s a thought – if you want to get the Kiel people to work faster and share any results – let them know about the RxISK Prize – its not confined to PSSD. But I doubt they are going to be able to claim it if they don’t broaden their focus to include SSRIs and Isotretinoin – let me rephrase this just be sure you know what is being said – it is unlikely that any claims they make about what goes on in PFS are likely to hold water if they don’t hold for SSRIs and Isotretinoin also. This is why we have encouraged Luisa Guerrini to include finasteride and isotretinoin in her assay systems also.

          I’m not surprised if the PFS Foundation are leery about pumping big money into research given their Baylor experience.

          Misandrist – hostility toward men? Not sure what you mean – a resistance to people like Riccardo Menozzi getting in touch and demanding we hand over all Prize Money – that we PFSers know how to do research. Or do you mean excluding women taking finasteride which doesn’t sound misandrist. There are women transitioning who are taking it and others but the numbers are relatively small and no women with convincing PFS have reported this to us.


  13. Erik/David/Bill – and others

    Let me try one more time. This time let me put it this way – it seems the thinking of most PFS folk is controlled by Merck just as the thinking of most PSSD folk is controlled by Lilly, Pfizer and GSK.

    How so? Well in the case of PSSD, people naturally have thought the effect is happening at 5HT or closely related dopamine receptors and in the brain. This is because of company marketing, which focusses on brains and serotonin.

    But the antidepressant effect companies want to make money out of isn’t the commonest or strongest thing these drugs do. Sure they act at serotonin sites but there is more of this in the rest of the body including skin and only a tiny fraction in the brain and these drugs are all antihistamines also.

    The commonest and strongest and clearest and quickest thing these drugs do is affect sexual function. Why or how – no-one at the moment knows. Companies don’t want you to look at this – and no-one does – ‘we’ keep looking at brains and serotonin even though this cannot tell us why some effects become permanent.

    With Finasteride, the effect Merck want you to look at is hormones and 5-ARI – this is their marketing and researchers dutifully focus on this. The Baylor study suggests this is not the commonest or strongest effect this drug has. The Baylor study points toward — skin not brains. (Isotretinoin points to skin not brains).

    Sure an action on 5-ARI will tell us something about why this drug does the thing that Merck want to make money out of but that is not the same as what the drug does and seems unlikely to have much to do with why this drug produces permanent effects.

    Why is that PSSD or isotretinoin folk are not looking at 5-ARI and finasteride folk are not looking at serotonin? Because company marketing has blinkered them.

    Given the common clinical picture across 3 drug groups, the problem has to lie elsewhere and especially the important part of the problem which is why do these effects endure.

    If I were Merck I would fund the eminent AR researchers in Kiel and get them to keep looking at this till the cows come home. Ditto with serotonin, PSSD and Lilly or Pfizer.


    • Hi David,

      Thanks for getting this set up. Can I just ask, as a layman with little scientific understanding, I am curious how changes within the skin could cause brain fog and zero libido? These are my only problems with this condition, I don’t have any sensitivity issues like a lot report, but my problems presented very shortly after my accutane course. Another ‘symptom’ I have is a complete halt to my hair loss (not something that ever bothered me, but it’s been stopped in it’s tracks since accutane.) You will be far better versed in all the science than me, but I am struggling to understand how the skin could be implicated rather than the hormones in my situation.

      Thank you in advance, for your response to this and all that you do for us!


      • Peter

        A few posts back on RxISK, there is a post on brain fog that might answer the brain fog bit.

        There are also posts on RXISK about skin and libido. With PSSD and accutane and PFS, but maybe most clearly with PSSD, genital numbness and muted orgasm comes first – something that happens on a low dose of an SSRI within about 15 minutes of the first pill. So we have a clear skin effect. What’s the brain there for? Well it detects things like this. Genital sensations are tuned down and not as arousing and if that’s the way you are chronically – libido then falls. It doesn’t drop early on.

        This all fits with the James-Lange theory of the emotions. Our emotions happen in our body – and the role of the brain is to make sense of what is going on in the body.

        But we are all biased to see reduced brain activity as the cause rather than the consequence. The brain might be the cause but we need to keep in mind – as it were – that our skin may be much more brainy than we usually think,

        The other point is pharmacological. Which is some receptor or enzyme is twisting out of shape and staying twisted and we need to track that down.


  14. How confident are the rxisk team that this will produce understanding of pssd or a cure.When you wrote “This research cannot fail. It seems bound to shed light on some of the most enduring mysteries in pharmacology.”:that seemed to be a very strong statement, almost like a promise!

    • This work is almost certain to break new ground and get more people looking more closely at these issues. That is not the same as a cure for PSSD, PFS or PRSD but it is very different to the old grounds people have been tramping over looking for a cure for PSSD and PFS and PRSD for decades.

      An proper understanding of what causes some systems to lock up will transform pharmacology – we have no idea how this happens at the moment even though another condition – tardive dyskinesia – in which this happens has been known about for 60 years.

      Whether this new work unlocks the mystery or is a false dawn I can’t say but it at the least I hope it will be the rock that slips and triggers an avalanche which will then uncover what we need


  15. I think this looks to be a good iniative. Can only hope this will indeed lead to a better understanding but I can understand that there is no guarantee whatsoever. However if nothing is done or tried nothing changes either so we’ll have to wait and see.

    Kinda sad that the money and the iniative has to happen this way. I mean to say these are issues which are known in a way for some time and I can understand that certain pharma companies don’t want to spend research and money on it because that would mean they’d have to admit their drugs are causing this and/or other issues.

    On the other hand in a naive way I expected competitors or different fields to have jumped on this before but alas.

    In conclusion thanks again for the continued attention you are bringing to this and other issues.

  16. Has the role of electricity been ruled out as a possible cause?

    This may not be directly relevant is interesting
    American Society of Nephrology

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    Clinical Epidemiology
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    Comparative Cardiac Safety of Selective Serotonin Reuptake Inhibitors among Individuals Receiving Maintenance Hemodialysis
    Magdalene M. Assimon, M. Alan Brookhart and Jennifer E. Flythe
    JASN April 2019, 30 (4) 611-623; DOI: https://doi.org/10.1681/ASN.2018101032
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    Significance Statement
    Patients on hemodialysis may be particularly susceptible to the lethal cardiac consequences of drug-induced QT prolongation because they generally have a substantial cardiovascular disease burden and high level of polypharmacy, and are recurrently exposed to electrolyte shifts during dialysis. Electrophysiologic data indicate that among selective serotonin reuptake inhibitors (SSRIs), citalopram and escitalopram prolong the QT interval to the greatest extent. In a cohort of 65,654 hemodialysis patients, individuals receiving SSRIs with higher (citalopram, escitalopram) versus lower (fluoxetine, fluvoxamine, paroxetine, sertraline) potential to prolong the QT interval had a higher risk of sudden cardiac death. This risk was more pronounced among elderly individuals, females, those with conduction disorders, and those taking other non-SSRI QT-prolonging medications. When prescribing SSRIs to patients on hemodialysis, clinicians should consider the QT-prolonging potential of these agents.

    all these so called ‘simple’creatures function as well as reproduce without brains

    How can animals function without a brain

    A brain is basically what results when a large group of nerve cells called neurons form one large cluster. Acting together, these neurons control the bodily functions of an animal. So how can any animal survive without a brain?
    Jellyfish, for example, have a system of nerve cells, known as a neural net, throughout their bodies. And as David has pointed out the octupus ‘brain’ is essentially it’s skin.

    It is thought that we all evolve from the same beginnings so it wouldn’t be surprising if the skin is still vitally involved

  17. I think it is predominately a ‘skin’ organ issue. Shortly after being prescribed Sertraline in 2004,i lost genital sensation, there was also reduced sensation in my nipples and feet. My female GP told me to get relationship Counselling as quote ‘The most important organ in our sex lives is the brain’.
    No amount of relationship counselling or date nights changed the genital numbness. It felt like a battery or switch had been removed. If the remote, has no batteries, or the plug is switched off the TV is not going to work, the Kettle is not going to boil no matter how much our brain, mind wills it.

    A few months ago I came across an article in I think The Huff post which was asking women when they first remember having an orgasm. I was quite surprised to see some of them saying when they were 4,8,9.. I maybe did not realise prebuscent girls can orgasm(This was as a result of skin arousal, not visual stimulation)
    I have worked with abuse, and rape survivors both male and female adults, and child abuse survivors. Something that is rarely talked about, although it may be in Therapy services is how the body can produce an involuntary orgasm despite the brain, mind feeling ‘traumatised:This can cause confusion and guilt, many will never talk about this.
    Likewise if women have PSSD, or SSD why would they consent to sex (Rape trial consent issues?)

    • I don’t know if it’s skin related or brain related. My only experience was that during my partial recovery for 1-2 weeks my skin numbness was reversed at the same time my blank mindedness went away and pleasure senses was coming back. so it somehow was getting better at the same time.

  18. Once upon a time nobody knew it would possible to measure the speed of light. Maybe something akin to the immeasurable speed just yet, of the connection between emotion and physical body

  19. This sounds like a good argument for us to use donations to increase the size of the Prize instead of funding individual speculative research projects

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