Review A Perspective on the Role of Metformin in Treating [...] (ME/CFS) and Long COVID (2025) Fineberg et al

[Jonathan Edwards]

Last time I looked at the data for salt and water for POTS I was unconvinced. There is a huge bias towards getting a positive result in this sort of situation. I want to keep reviewing this because at some point hopefully there will be good data.

Medical science is very bad at salt and water mechanisms. I think people are unaware that it is relatively easy to establish facts about structure and chemistry but dynamic function is often difficult to prove.

Take the two most basic things students are taught about water balance in disease:

1. The feet swell with water in heart failure because of a rise in capillary/venular hydrostatic pressure.
2. The feet swell with water in nephrotic syndrome because of a reduced capillary/vanular oncotic pressure.

Both of these are wrong and you can be sure they are wrong from simple clinical observation of cases and arithmetic.

Giving salt and water to people with orthostatic intolerance makes superficial sense but as soon as you consider what we know about normal fluid control it makes no sense at all. The long list of unproven treatments given by the cardiologist in the video on POTS are linked by the fact that they are all supposed to raise blood pressure through water retention. People believe they work because they seem to make sense. In the absence of adequate trials there is no way of knowing whether they work. And a detailed analysis of the physiology doesn't make it very plausible.

The need is to get clinicians to be responsible and do trials. I know that you are on board with that, but it needs to be made clear that muddling along with these things without trials just delays getting things done properly.

 

[Sasha]

I want to second whoever said, 'Thanks for engaging,' @MelbME - people having good-faith discussions on these things is always clarifying and useful.

That is a very patronising view of pacing - that people can't and don't work out things for themselves, that they have to have a clinician tell them how to do it. Virtually everyone can and does work things out for themselves. Personality and circumstances can make it harder for some people to do it than others of course. Where did you get this view of pacing as something that people require instruction in?

Too often pacing advice becomes overly complicated, wrapped up in complicated formulae for which there is no good evidence, focusing on the minutiae of scheduled 15 minute rests, and removing people's agency.

At the beginning, I think a lot of people who have just got ME will struggle to accept just how much activity they have to give up in order to avoid getting worse - and they will often be under tremendous pressure from other people to keep going, such as employers and family members. It's a huge adjustment to make at a frightening and confusing time and some new PwME are likely to be in denial. I think early advice that PwME need to pace is crucial - as opposed to telling PwME exactly how they should pace.

I remember meeting a new PwME who ran her own business, which would collapse and leave her broke if she stopped working. She was beating herself up about being 'lazy'. I don't think it would be patronising for a doctor at that point to spell out that continuing to push it could be disastrous, that ME/CFS was real and serious (which is not what society tells everyone), and that the PwME ought to cut right back, with some real-life-PwME examples of what that would look like that are not based on the nonsense the clinics spout. This is the sort of S4ME factsheet that we've been talking about, and we don't consider that patronising.

I think this may be the kind of support that @Jonathan Edwards is talking about.

 

[Trish]

Well what you and I agree on is what should happen in an ideal world.

What I'm trying to say in the world we are in there is already advice being circulated on treatments or management strategies to trial.

So at what point do you attempt to try sift through that advice to find better vs worse advice in the world that exists currently in an attempt to push it towards the better? Or as an idealist do you just ignore it all?

This is an interesting discussion, and I think and important one in the context of suggested treatments such as the paper this thread is about suggests.

I think it's fine for biomedical scientists and physicians to put their head together and come up with possible drug treatments that might be helpful for ME/CFS and Long Covid, and to propose clinical trials. If there is good biomedical logic for trying metformin in ME/CFS, and experienced clinical trial doctors able to get funding to run properly set up trials, go for it.

I'll be interested to see the outcome. But we have members here on metformin for other reasons whose ME/CFS didn't change, so it's clearly not the magic bullet for everyone.
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The problem comes when such hypothesis papers are used as the basis, or justification, for doctors to go ahead and recommend the drug to their patients, and for pwME on social media to encourage their friends to try it.

As others have said, no drug is completely risk free, so there needs to be very good reason for doctors to recommend them to their patients, and if the impetus for trying the drug comes from pwME desperate to get well, doctors surely have a responsibility to point out to the pwME that there is no clinical trial evidence to support its use in that context, and to draw attention to possible side effects.
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What I'm concerned about in this discussion is your assumption that some of us are warning against doctors promoting unevidenced drugs to patients, on the assumptions that our objections are based on idealism.

For me, and I'm aware for some others, our objections to doctors giving unevidenced advice to patients is based on experience, not idealism. We are all desperate to get better, or at least to see some improvement. Some of us are bedridden, or housebound. Of course we want to be cured.

What we don't want is the constant pressure from others to keep trying every treatment going the rounds on social media and pushed by family, friends, clinicians, doubtless with the best of intentions.

Spoiler: My experience with experimenting

I've had ME/CFS for 36 years. I spent the first years trying everything suggested to me and everything else I could find - mostly in my case alt med nonsense like Reiki and aromatherapy and acupuncture, but I also have boxes of supplements that failed to make any difference lurking on top of my wardrobe. I also tried, to my detriment, some of the quack brain training nonsense. I was a single mother at the time, struggling to continue working part time to support my kids and could ill afford to pay for this rubbish. But I kept trying. Each time the treatment failed, I felt a failure, to myself and to my children. I even persuaded my GP to get the NHS to pay for me to go to a doctor 100km away practising a weird mixture of alt med which cost me a lot in fares and pills that made me sicker.

Others here are formerly self supporting independent adults forced back into the care of their parents, or at the mercy of professional carers, because of their serious illness, and may be subjected to whatever doctors and therapists advise their parents or GP they should try, often making them sicker.

So your apparent approval of doctors being willing to try what 'seems to work' for some patients, is not harmless, however apparently benign the drugs involved may be. It can lead to false hope, to patients feeling like failures or being accused of not wanting to get better, to being accused of unrealistic idealism, to feeling pressured by others to put ourselves through another bout of side effects and possible long term harm to prove we want to get better. It can also cost a lot of money the pwME may struggle to find.

When we reach the end of the road with treatments that have harmed us, whether it has harmed our health, or finances, or broken relationships, or lost hope and feelings of failure, some or us turn to science, not through idealism, but through bitter experience. It is a relief in a strange sort of way, for me to realise that my scientific training of my youth was right all along, and to turn back to sound science to look for answers and to step away from the endless pursuit of the next possible cure to try.
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There are other members of this forum who are willing to try anything and desperate to find a doctor who will prescribe the latest drug they have read about on social media or heard a doctor or scientist suggesting, or read about in a hypothesis paper. I do not judge patients for pursuing hope, I've been there. I wish them well.

 

[EndME]

I haven't seen anything promising from Long COVID.

The treatments I think have strongest weight of evidence amongst majority of clinicians with least risk (though without trials) are pacing for ME, LDN for Fibro, salt/water for POTS.

With all due respect, like I already mentioned above, that is simply not the case. LDN has been trialled in a large RCT for Fibromyalgia with negative results. It very much looks like to me that people are actually not concerned with looking at the evidence if this isn't even known.

You can argue about the trial not being able to pick up benefits due to x,y,z but then one has to construct an argument on how clinicians can see these benefits if they aren't apparent in the trial and that is not happening and people will actually have to look at the evidence. This just looks like the opposite with people simply not arguing logically.

 

[Kitty]

Right, but based on what I understand from others in this thread, nothing should be promoted by GPs for ME/CFS as no trial has proven that anything works yet, not even pacing.

Not at all. There are trialled treatments for symptoms like pain, nausea and poor sleep. Having ME/CFS doesn't negate those trials.

Pacing doesn't need trialling because it isn't a treatment and will not improve ME/CFS. It's a pattern of resting after reaching or surpassing an activity threshold before being active again, so as not to feel crap. Everyone does it. The only difference is the height of the threshold and the length of the recovery time in ME/CFS.

Nothing should be promoted by GPs to treat the main feature of ME/CFS—PEM—because nothing has been shown to work. It would be unethical for a GP to experiment on patients.

I'm not even sure how we've got into such a tangle over it!

 

[Evergreen]

I want to echo @EndME , @Sasha and others and say that these debates are really valuable, and thank you for sticking around.

To pick up on some of your replies to others:

So you're equating any non-trialled advice or recommendation as equal. Giving something with a high risk of harm and few reports of helping patients is equal in your opinion to trying something with low risk of harm and many reports of helping people. Is that right?

I think this is a slippery slope. What one person considers to have a high risk of harm is not what another considers to have a high risk of harm. Ditto with the frequency of reports of helping people. Depends a lot on beliefs and very little on anything resembling evidence. There are many people who would put exercise, GET and similar in the latter category. What's more, there's some trial evidence that would give at least superficial support to those beliefs, which is more than can be said for all the non-trialled stuff out there.

Treatments get trialled on patients already if they have minor side effects. Only the treatments that are seen as risky or very expensive have rapidly gone in to treatment trials for ME.

But we don't know the side effect or safety profile until something gets trialled, recommended, and then we get the post-marketing data from vast numbers of people. Individual clinicians have no chance of getting a representative picture. When patients are told that they are unlikely to get side effects, that will affect their reporting of side effects back to that clinician, and how that clinician interprets that report.

With LDN, there seems to be an assumption that there will be minimal side effects because it is used in addicts at significantly higher doses. It seems to me that a lot more side effects are reported than you'd expect based on that logic.

I'm glad there are trials happening in ME/CFS now. Given how trials in fibromyalgia are panning out, despite a lot of anecdotal hype, I'll be pleasantly surprised if it works in ME/CFS in any clinically significant way. Polo et al.'s report suggests to me that one area it's unlikely to help is pain - only 17% reported less pain. That could be less than placebo.

That was the major flaw in the PACE trial - they supposedly trialled pacing, but almost all of the participants would have been already pacing, they would have found some balance between activity and rest that did not result in a worsening, and so we would not expect the 'pacing' treatment arm to show any benefits. Ridiculous imposed schedules as in the APT arm is not pacing.

Agree wholeheartedly, @Hutan .

In addition, from the APT manual in the PACE trial, it looks like there was an emphasis on reducing activity. If a person doesn't need to reduce activity, then being encouraged to reduce activity might well reduce functioning. Similarly, if a person is actually able to increase activity, then being encouraged to reduce it or manage it rather than increase it would show up as inhibiting functioning on a group level.

Too often pacing advice becomes overly complicated, wrapped up in complicated formulae for which there is no good evidence, focusing on the minutiae of scheduled 15 minute rests, and removing people's agency.

Agree. Therapists getting involved has meant a lot of weird rules being introduced that patients often try hard to stick to. It can take a long time to realise, oh right, they're just making stuff up.

 

[Utsikt]

I have not been able to read every response by everyone, so I might have missed something or misunderstood someone. Please correct me if that is needed.

Well what you and I agree on is what should happen in an ideal world.

What I'm trying to say in the world we are in there is already advice being circulated on treatments or management strategies to trial.

So at what point do you attempt to try sift through that advice to find better vs worse advice in the world that exists currently in an attempt to push it towards the better? Or as an idealist do you just ignore it all?

As a scientist, I’d love to hear your opinion: who has the burden proof here?

In any sane world, it’s the person claiming that something works. If they can’t back that up, there is absolutely no reason to listen to any of their advice.

It read to me as if in Utiskt's ideal and imo highly restricted world my doctor would discourage or prevent me from trying off-label drugs if they haven't been trialled specifically for ME/CFS, but perhaps I misunderstood.

My intention was not to blanket ban medications for symptoms we know how to treat (or improve), like pain, sleep, nausea, etc.

It’s only to ban practitioners from continuously «experimenting» with off-label drugs without bothering setting up a proper trial.

Sure, LDN might be prescribed for pain or sleep, but there isn’t even any good evidence that it works there. And we all know that it’s really prescribed for «ME/CFS», they just don’t write that on the label.

Yes I agree with this. I think maybe you're missing the context of my discussion with Utsikt.

They propose that what a doctor thinks they know isn't actually true if a robust clinical trial hasn't been trialled in that patient population to prove that treatment does actually help these symptoms.

I don’t see how that’s a controversial position to take. How would these doctors know if it works? Surely you would known how easy it is to get the appearance of there being an actual effect even if it isn’t there?

Though I've found the position confusing as we seem to disagree on a few terms and it appears maybe it's not a hard and fast rule for all interventions. @Utsikt maybe you can clarify?

I tried to clarify above

 

[rvallee]

The principles of pacing are very logical.

Answering the question of should I stop now or later is a different beast. You can attempt to devise rules, but because there doesn’t appear to be any extremely consistent patterns and PEM or just general symptom worsening due to fatiguability, etc. is a scale and not binary, it’s always going to be a trade off between attempting to avoid PEM/too uncomfortable or disabling symptoms and attempting to maximise FC/QoL within a very dynamic system.

In short: Understanding that you should pace in general is logical. Doing it is a nightmare.

Which is basically the crux of the problem: a simple hard thing cannot be turned into a complex easy one. Or at least, it hasn't been done here.

Ironically, the entire rehab treatment model is based entirely on the equivalent of a magical pill: it's complex, but it's easy to do. Except, no, it's the literal opposite: it's all very simple, but as hard as knitting while wearing boxing gloves. But since it's hard, they prefer to retreat in the comfort of thinking that it's all so easy a child can do it, we're just being difficult about it.

So the logical part is turned on its head. Those who buy the fake treatment model apply it exactly as a magical pill, one that cures it all once and forever. You just gotta take it. It's so easy. Complex, but easy. When actually doing it is nearly impossible, and not because of anything having to do with us. It's basically like living under constant warfare, with random missile or drone attacks.

You can go about your daily routine for months and years without ever having a bomb fall on your head, and it has nothing whatsoever to do with that routine, or anything about it. Instead someone ordered that attack, and you just happened to be there at the wrong time. This is something the medical profession blatantly refuses to even consider, because they bought the lie that the solution is easy, and we're just stubborn and stupid about it.

 

[rvallee]

I don't think pacing is something that can be ethically trialled. What would you do - force people to keep working 40 hours a week when it makes them worse? You would find that many people eventually just could not get out of bed. That's the essence of ME/CFS - activity results in an inability to continue to be active. Pacing is basically a voluntary reduction in activity, in order to not get to the point where you have no choice but to reduce activity (and feel horrendous).

Yup. I thought about this yesterday, and I can't really imagine a way to actually trial pacing. There are too many reasons why it would not be valid, and then there's the simple fact that if the absolute perfect trial was run, independent, fully equipoised, methodologically flawless, found that pacing is better, which I'm not even sure is realistic to achieve in the form of a trial, it wouldn't matter.

The ideologues would dismiss it. The vast majority of physicians wouldn't care. None of the current guidelines or reviews would even be updated to take it into account. None of the Cochrane reviews, or "Up-to date" material would get updated. None of the government guidelines would even take it into account. Everything written about it from the pro-rehab ideological perspective would frame it just like they're doing with DecodeME: it's controversial, not groundbreaking, "we've always known", and so on. It's their playbook. It works for them. It's horrific for us, but they do very well for themselves with it.

It would literally change nothing. Evidence-based medicine just doesn't get decided based on evidence, unless either that evidence is overwhelming, and that threshold is very high, just look at how a strong majority reporting of GET being harmful is completely dismissed, or the culture demands it, wants it to appear true whether it is or not. And when the evidence is overwhelming, you pretty much don't even need any of that complexity, so it's almost all for nothing.

Clinical trials without a biological target should largely be banned, IMO. They are not a viable way to know better. If you look at everything that has been published to promote this treatment model, all the psychosocial rehabilitation and 'exploration' studies over the last 4-5 decades, and wiped them out of existence, the simple fact is that absolutely nothing would change. Everything would be the same. Nothing has been learned from those trials, not even the simple fact that they don't work at all. It's an entirely performative system where patients and outcomes are usually entirely irrelevant, simply because this process almost never comes up with anything that actually works.

 

[rvallee]

If people have pain, doctors know how to provide pain relief. If people have insomnia, doctors have some ideas on how to treat it (some of which may be good, some probably not good).

Heh, I would tone that down a bit. They can sometimes help, but they usually can't. It's kind of famous for those two.

If only, though, but the profession isn't there yet, and probably won't reach it until major transformation from AI.

 

[bobbler]

Have I said it does?

In general, there are three main causes of PEM when pacing:

1. Being forced to do more than you know you can due to circumstances outside your control.
2. Natural fluctuations that makes an average day sometimes result in PEM because you’re trying to maximise FC/QoL
3. Doing more than you know you probably should because you want to do something

It’s obviously not just about «doing», external stimuli etc. also plays a role.

Besides, logical does not mean that it has to be easy to implement. I’ve never claimed pacing is easy, and most would probably say it’s very difficult.

That doesn’t make it any less logical.

I’d add in a ‘4’ that once you hit a certain level there is the issue that activities that will be necessary at some point be it a medical thing for something else, admin thing for ME (even with help that person would need the pwme ‘input’ and some make it harder or easier), shower and many more can only be split up or adjusted so far. And the best some of us have is radical rest before and after. And the closest to spacing out to recovery fully depends again on what of those we have building up and the impact of not doing/delay vs doing.

Being ill and disabled comes with lots of extra chores and for many with me/cfs a constant undermining from most people to make things hard and to not listen to understand but parse and sabotage and think they’ve ’won/prived something’ by attrition by exhaustion. Unless protected by being fortunate with our support circle we I think do get preyed on by a certain personality type coming out in people

Anyway I think more and more about how, even if it is just increasing understanding of it in those around us (and how they can/should help/hinder) this is the one where the proper help from people changing things could make a difference and many need support with - even if it is just people getting adjustments more easily that fit them for eg calls or appts but also in that radical rest being understood as part of it too

 

[Utsikt]

I’d add in a ‘4’ that once you hit a certain level there is the issue that activities that will be necessary at some point be it a medical thing for something else, admin thing for ME (even with help that person would need the pwme ‘input’ and some make it harder or easier), shower and many more can only be split up or adjusted so far. And the best some of us have is radical rest before and after. And the closest to spacing out to recovery fully depends again on what of those we have building up and the impact of not doing/delay vs doing.

Being ill and disabled comes with lots of extra chores and for many with me/cfs a constant undermining from most people to make things hard and to not listen to understand but parse and sabotage and think they’ve ’won/prived something’ by attrition by exhaustion. Unless protected by being fortunate with our support circle we I think do get preyed on by a certain personality type coming out in people

I thought of that as a part of 1, but it’s a very good point. There are lots of things that are completely out of reach without getting PEM, regardless of how many adaptations you try to make.

 

[bobbler]

Yup. I thought about this yesterday, and I can't really imagine a way to actually trial pacing. There are too many reasons why it would not be valid, and then there's the simple fact that if the absolute perfect trial was run, independent, fully equipoised, methodologically flawless, found that pacing is better, which I'm not even sure is realistic to achieve in the form of a trial, it wouldn't matter.

The ideologues would dismiss it. The vast majority of physicians wouldn't care. None of the current guidelines or reviews would even be updated to take it into account. None of the Cochrane reviews, or "Up-to date" material would get updated. None of the government guidelines would even take it into account. Everything written about it from the pro-rehab ideological perspective would frame it just like they're doing with DecodeME: it's controversial, not groundbreaking, "we've always known", and so on. It's their playbook. It works for them. It's horrific for us, but they do very well for themselves with it.

It would literally change nothing. Evidence-based medicine just doesn't get decided based on evidence, unless either that evidence is overwhelming, and that threshold is very high, just look at how a strong majority reporting of GET being harmful is completely dismissed, or the culture demands it, wants it to appear true whether it is or not. And when the evidence is overwhelming, you pretty much don't even need any of that complexity, so it's almost all for nothing.

Clinical trials without a biological target should largely be banned, IMO. They are not a viable way to know better. If you look at everything that has been published to promote this treatment model, all the psychosocial rehabilitation and 'exploration' studies over the last 4-5 decades, and wiped them out of existence, the simple fact is that absolutely nothing would change. Everything would be the same. Nothing has been learned from those trials, not even the simple fact that they don't work at all. It's an entirely performative system where patients and outcomes are usually entirely irrelevant, simply because this process almost never comes up with anything that actually works.

I agree

But many of us are trapped in the default none the less anyway because of how people work. Somehow if it isn’t proven then they’ll be stuck working until they collapse


I’d have at least felt my life had been worth something if someone with integrity and enough skill to do it right had been noting what I had to go through did to my health instead of me having to do it anyway and it wasn’t and people write some nonsense narrative so they still weren’t wrong and what really happened didn’t exist.

The consequences happen anyway it’s just in the current set up they are denied and/or suggested to be something else or ‘not from what they believed’ etc

But yes it would be unethical to do anything other than what the natural environment does to people and letting them use whatever they found best to cope/manage - which yes might be eccentric that they work on no sleep then catch up on their week off (that’s not ‘bad management’ that’s the only option available to them given the other restrictions) and that would give enough variety anyway in whether the minutiae matter or as I suspect it’s as simple as : if you force someone into a load that’s four times their threshold each week they will get worse and stop blaming ‘how’ they get thru that instead of them ‘having to get through that’s being the cause of both.

I think too many sadly get distracted and obsessed with the patterns of doing rather than just comparing if someone milder reduced to two days with help then things are ok and no one stuck with full time and those around not ‘getting it’ comes out well long term and torturing them with enforced meditation or telling them to choose certain days to shower rather than following their body is just cruel on top of it.

So that type of research design too many want, micro managing and looking at ‘amount’ in arbitrary ways rather than just using whatever tools we have to measure without interfering is where the ethics becomes an issue.

As would the issue of who gets the data and if anyone is up to the job of being trusted to do things right when it comes to interpreting the data anyway


It’s an important one of course even for things like this. Because someone could try a drug but also be stuck in a situation that will cause a long term trajectory anyway - and a drug could actually improve them by increasing their threshold but not quite enough that given their commitments they don’t get slightly worse , just that not being as bad as they would have without it.

The best we have currently even with trials is numbers of people and hoping controls vs subjects have similar amounts of people in different levels of situation vs severity.

But , if it wasn’t for needing to keep this up for eg 2yrs because it being a longer term knock on, it would be useful to have a sense of this one not just for keeping us more well and safe but also for when we are measuring eg drug treatments to know /be able to measure what an even-keel situation is.

 

[Hutan]

This is from the latest version of the Helsinki Declaration (that being a very influential statement on health research involving humans from the World Medical Council:

*****

Unproven Interventions in Clinical Practice​

When an unproven intervention is utilized in an attempt to restore health or alleviate suffering for an individual patient because approved options are inadequate or ineffective and enrollment in a clinical trial is not possible, it should subsequently be made the object of research designed to evaluate safety and efficacy. Physicians participating in such interventions must first seek expert advice, weigh possible risks, burdens, and benefits, and obtain informed consent. They must also record and share data when appropriate and avoid compromising clinical trials. These interventions must never be undertaken to circumvent the protections for research participants set forth in this Declaration.
********

Doctors who continue to prescribe unproven interventions, making no effort to promote good quality trials, are not complying with the Helsinki Declaration. That is pretty clear.

It might also be argued that people who promote unproven interventions in clinical guidelines when there is no prospect of a trial are not complying with the Helsinki Declaration.

 

[bobbler]

Heh, I would tone that down a bit. They can sometimes help, but they usually can't. It's kind of famous for those two.

If only, though, but the profession isn't there yet, and probably won't reach it until major transformation from AI.

There’s perhaps where we are all seeming at cross-purposes but really aren’t.

Fir people with our label then as you said particularly for those two issues (pain, sleep) then due to the ‘functional lies’ even if the norms for normal people, such as pain management that isn't psych re-education, might help (or just need to be adjusted if sensitive dosage wise etc) due to the label as a group we are much more likely to get only offered the useless alternatives assuming it just needs a bit of distraction and to stop thinking about the pain or behave better etc.

And even when the issue causing pain is a diagnosed, structural show in a test thing known to cause agony in all … then then ‘label’ combined with someone of a certain personality type or belief having power or influence over whether the normal just gets followed means a lot of other nonsense stuff either gets prescribed instead or used as a question mark to delay giving those basics. Or indeed if the 'first line' is something that will contraindicate for me/cfs such as exercise and really an approach using things that are used for others (maybe alongside it or after they tried it etc) less commonly might be worth seeing if it works etc.

And being in pain for weeks, months, years - or other things that might have a fix - longer than necessary or would happen for a deserving patient and combined with the added work, stress and hurt of that obstructive behaviour isn’t good for me/cfs.

And as we get iller some of the things/extras that might have been small or are small to well people (like ‘we don’t give out skin creams or hayfever /sinus stuff type level) collect and play a significant draw on our energy if only in our ever-lengthening thing daily routine of chores

There is probably a level further on this ‘middle ground’ stuff too but too tired to dare dipping my toe into getting the wording precisely in that one!

 

[Hutan]

On the guideline:

I think I already said this early but I'm not talking about guidelines here or at any point during this thread.

I don't know why you keep bringing it up? Perhaps you missed it when I replied to you at beginning of thread.

They have details on this process publicly somewhere. But I'm also not able to discuss the advice or outcomes in any specifics.

I know it clearly matters a great deal to you and I'm sure you'd love to be able to write the guidelines yourself. I also hope for a good outcome.

The reason we are talking about guidelines is because you are on the committee deciding the Australian clinical guideline for ME/CFS. Yes, the guideline matters to me; I'm sure I'm not the only one it matters to. That guideline will be very influential in the care of people with ME/CFS in Australia and elsewhere. It is therefore of interest to us what you know and believe about clinical care of people with ME/CFS. It is reasonable for us to ask you and others on the committee about what you believe, and I don't think anyone on the committee has a good reason not to be clear with the ME/CFS community about the detail of what they are going into the process advocating for.

You say that you hope for a good outcome. And I'm saying that the members of the committee need to do more than hope. You need to be fully informed. I very much appreciate that you are still here, engaging in the conversation. I hope that some of the things we write will help you advocate for a good outcome.

Yes, I'm frustrated not to be part of the guideline process. And I'm very fearful that it will produce harmful nonsense. The Chair of the committee is a GP who published a chapter on CFS in a 2014 book called Clinical Naturopathy. The chapter includes a lot of poorly evidenced claims e.g.

Very recent research has revealed that childhood trauma—abuse of sexual or emotional type—may predispose an individual to developing CFS in the presence of other initiating factors.34 Neuroendocrine dysfunction, as discussed in Chapter 18 on stress and fatigue, explains how the combination of these factors develop as a potential risk for CFS.35

Pre-disposing factors: post-traumatic stress disorder; trauma/abuse

Predictive risk factors for developing CFS: older age, female, low or middle rather than high educational level, the presence of an anxiety disorder, mood disorder, emotional instability....

He recommends acupuncture, ginger, turmeric, magnesium, vitamin C injections, countless unproven things actually. Also exercise:

Negotiation of a balanced and achievable exercise plan with the patient (after a medical check-up) is advised. This may involve a graded exercise program supervised by a qualified health professional such as an exercise physiologist or equivalent. Two reviews64,65 of research show that after three months of exercise intervention, physical function improved and less fatigue was experienced by those who participated. However, improved responses were seen when education was combined with exercise therapy but not when antidepressants were also used in combination.64 Additionally, exercise may be less palatable to some groups of patients than other interventions.64

We probably need a thread on Dr Deed. I don't know him, perhaps he is really is fine, perhaps he has changed his mind on all of that, but he was willing to send those unproven ideas out into the world, into the hearts and minds of naturopaths with a zeal to help people with CFS and he did not seem to have the capacity to adequately assess evidence. Perhaps you can understand now why I feel that we are pretty screwed? There are others on the committee that I have significant concerns about e.g. Dr Sarah Knight, your co-researcher with her BPS leanings and use of surveys diagnosing psychological pathologies that are completely unsuited to people with chronic illness.

The composition of the committee seems almost to have been designed to come up with a list of unproven interventions that essentially are a sop to people with ME/CFS - 'look, here are all these things you can do to be well!', instead of acknowledging that there are no disease modifying treatments, and supportive care is all that the medical profession can offer.

So, when I see you seeming to be an advocate for unproven treatments, and seeming to be in favour of clinicians medicalising pacing and seeing it as a treatment to be provided by clinicians, I get even more concerned about how many committee members we can really rely on to push for a sensible useful guideline, and am even more concerned about what harm the new guideline may inflict on us.


On unproven treatments:

I think we agree ideally but I'm saying in real practice you have GPs prescribing all sorts of medications and interventions to patients that haven't been trialled in that population.

That GPs are prescribing all sorts of unproven interventions is a problem. We have GPs promoting hypnosis, homeopathy, the lightning process, many other unevidenced things that the individual doctor is utterly convinced are helpful to some people. Things need to be better. Surely the NHMRC is one institution that should, if not tackle that problem, then at least not contribute to making things worse, by giving those interventions the credibility of NHMRC endorsement?


On pacing:

I think some in the thread say Pacing isn't a treatment strategy either, it's logical and intuitive. In that case it shouldn't be recommended by GPs either as people already just do it. I think Hutan even suggested it's patronizing to try train people to pace as a treatment strategy.

I liked the description of pacing as 'just coping'. That seems to me to sum things up. I liked the comments that people have made that doctors should talk to people about pacing, adjusting activity in order to maximise quality of life, but that clinicians probably won't need to go into detail about how people do it. Ideas about the detail of pacing are more likely to come from social media discussions, patient support group discussions and patient support group literature. It is true that I really don't think people can be 'trained' to pace, and I don't see pacing as a treatment.

I mentioned above, clinicians have a role in facilitating pacing, by writing letters to the school or employer supporting accommodations, by helping the patient to get practical and financial support, by encouraging their patients to pay attention to their body and to make the very hard decisions about giving some activities up. As much as anything, having the clinician treat ME/CFS as a real and serious health condition creates the environment where the patient can take steps to adjust their life to the new circumstances.

 

[MelbME]

I have not been able to read every response by everyone, so I might have missed something or misunderstood someone. Please correct me if that is needed.

As a scientist, I’d love to hear your opinion: who has the burden proof here?

In any sane world, it’s the person claiming that something works. If they can’t back that up, there is absolutely no reason to listen to any of their advice.

My intention was not to blanket ban medications for symptoms we know how to treat (or improve), like pain, sleep, nausea, etc.

It’s only to ban practitioners from continuously «experimenting» with off-label drugs without bothering setting up a proper trial.

Sure, LDN might be prescribed for pain or sleep, but there isn’t even any good evidence that it works there. And we all know that it’s really prescribed for «ME/CFS», they just don’t write that on the label.

I don’t see how that’s a controversial position to take. How would these doctors know if it works? Surely you would known how easy it is to get the appearance of there being an actual effect even if it isn’t there?

I tried to clarify above

I agree with you regarding burden of proof. Not saying your take on controversial at all, I'm being controversial because I have these questions on what can be done for what I fear is a wild West of treatments in the absence of approved ones.

If we were in a situation where there were some successful trialled treatment options for ME/CFS then this wouldn't even be a conversation.

It is actually confusing to follow a conversation here because I think I'm having a back and forth with you but others jump on to pick out words or statements to discuss as well and I'm not really keeping up with everything. It's a bit difficult to stay on track. But its important for me to get your thoughts on this one:

1) do we consider pacing an intervention? I think this depends on how you see it. If it's simply to fit to your functional capacity that's naturally guided but what you can and can't do then that's not an intervention. But if a GPs general advice is diet and exercise to improve health then pacing is a little at odds with that (and one could argue this advice is also intuitive). It's even more at odds if the GP was to suggest an active pacing strategy where you continue to limit exertion on days when you feel you have a lot more energy. At that point is it an intervention? I think it is.

 

[bobbler]

I agree with you regarding burden of proof. Not saying your take on controversial at all, I'm being controversial because I have these questions on what can be done for what I fear is a wild West of treatments in the absence of approved ones.

If we were in a situation where there were some successful trialled treatment options for ME/CFS then this wouldn't even be a conversation.

It is actually confusing to follow a conversation here because I think I'm having a back and forth with you but others jump on to pick out words or statements to discuss as well and I'm not really keeping up with everything. It's a bit difficult to stay on track. But its important for me to get your thoughts on this one:

1) do we consider pacing an intervention? I think this depends on how you see it. If it's simply to fit to your functional capacity that's naturally guided but what you can and can't do then that's not an intervention. But if a GPs general advice is diet and exercise to improve health then pacing is a little at odds with that (and one could argue this advice is also intuitive). It's even more at odds if the GP was to suggest an active pacing strategy where you continue to limit exertion on days when you feel you have a lot more energy. At that point is it an intervention? I think it is.

I'm sorry to butt in given your first paras but I really appreciate that last para.

I think I'm starting to realise there is something unarticulated that is to do with how what might be the 'norms' of what used to be recommended or included in standard medical care have changed over the years towards what unfortunately for pwme is on the very ground we got to discover for the last few decades isn't what works for us: exercise and mindset change assuming the 'fatigue' is of the type that is 'in the mind and improves with a walk round the block'.

So there is something to be put that says where this 'what someone without a label meaning some people just assumed anything they had was in their mind would perhaps have been treated with or seen as common sense in the past' now is ironically getting moved towards the 'old school cfs/todays' fatigue/chronic fatigue/MUS guidelines'.

Just at the point where if there were justice in the world eg in the UK with the new guidelines coming in then that old chestnut would have meant we finally got all that wiped from our record and people's approach to us and treated like others had been where we also had pain or another issue that needed to be investigated. But with the only condition being that people took seriously when we said we had impact from exertion so the options involving that needed to be avoided and second-line therapies instead tried.

So by the time anything being looked at now is implemented then is the 'norm' going to end up being that if someone has trouble with sleep or pain they are sent off to CBT - which is what we know doesn't work when it is someone who has ME/CFS and their load vs threshold is one underlying issue potentially combined with something else (causing the pain or sleep issues and support that isn't psych or exercise could at least help with the vicious cycle of that draining the battery on the ME/CFS and as that gets worse then pain and sleep does etc).

Which means that even if the advice sounds like standard advice, by the time it comes in then it is to those in the medical system actually different or counter-intuitive or 'needing an exception/adjustment' to what they are at that point giving out as standard 'care/advice' to those without ME who walk in talking about the types of symptoms we might need help with eg sleep being sent off for exercise and sleep hygiene (makes me worse, as normally my sleep is messed around from PEM and needs to cycle thru with a hypersleep somewhere in the middle, so trying to force someone they can only sleep at certain times causes massive deterioration within about 4weeks).

It is weird when we have to call what could just be 'common sense/empathy' to many an intervention because of the tidal-flow of a system without these things being spelled out. But my experience that if it isn't this then something else needs to be put in place that does the same job, because that's what some of us battle at each conversation about everything.

 

[Trish]

1) do we consider pacing an intervention? I think this depends on how you see it. If it's simply to fit to your functional capacity that's naturally guided but what you can and can't do then that's not an intervention. But if a GPs general advice is diet and exercise to improve health then pacing is a little at odds with that (and one could argue this advice is also intuitive). It's even more at odds if the GP was to suggest an active pacing strategy where you continue to limit exertion on days when you feel you have a lot more energy. At that point is it an intervention? I think it is.

I think it's an intervention only in the broad same sense as my adjusting my life and environment to avoid getting asthma attacks from things I'm allergic to, and to avoid things that trigger my migraine attacks. The GP's role might be to help me identify the triggers of these reactions if I ask for help doing so, but not to micromanage my life.

Similarly the GP's role is to check whether pwME understand and have learned to recognise their episodes of PEM, and to give general advice about adjusting lifestyle and environment to avoid episodes of PEM where possible by reducing exertion and resting more. Just the simple information that you can't exercise your way to recovery is really important. It's not treatment, but it is important information.

 

[Utsikt]

I'm being controversial because I have these questions on what can be done for what I fear is a wild West of treatments in the absence of approved ones.

This might be a language thing of me not understanding «what can be done», but we just have to completely move away from the unevidenced treatments, and explain 1) why the evidence isn’t good enough, and 2) why the «it works for some» argument isn’t valid (this is the one most laypeople struggle with in my experience).

It's a bit difficult to stay on track.

Completely agree.

1) do we consider pacing an intervention?

No.

But how do you define «intervention»? (See below)

But if a GPs general advice is diet and exercise to improve health then pacing is a little at odds with that (and one could argue this advice is also intuitive).

I couldn’t care less what the «general advice» is, to be honest. Encouraging diet and exercise is by itself an «intervention» by every reasonable definition of the word. I don’t think intuition has anything to do with the question, and the intuition would depend on your world view, where it appears that most have fallen pray to the exercise/rehab propaganda that is deeply intertwined with certain political ideas that view ill health as a personal failure.

If you went back a few decades, convalescence would be the intuitive answer.

It's even more at odds if the GP was to suggest an active pacing strategy where you continue to limit exertion on days when you feel you have a lot more energy. At that point is it an intervention? I think it is.

I think this might be based on a misconception about what PEM is and how it can occur. PEM is often delayed, and it can be caused by exertion that doesn’t use up you «energy» that day (with energy defined as «not feeling acutely unwell»).

You’ll also hear frequent accounts of what is often perceived/described as adrenaline surges or people actually feeling better while doing something (especially things they enjoy), only for them to crash brutally a day or two after.

So pacing is still just «try to avoid being more unwell than needed», but maximising for long term avoidance of unwellness and maintenance of FC and QoL, and not just the immediate here and now.

But if we go back to the question about what an intervention is, my layman understand is that in a medical context, an interventions is something that is done with the explicit goal of improving the condition.

Pacing is not disease modifying. It’s just adapting to the disease according to logic.

If you take «intervention» to mean «interfering», then pacing is an intervention. But so would literally everything else be, so you kind of have to draw the line somewhere. So I draw it at the purpose of the interference, so to speak.

Regardless of if it’s an intervention or not, pacing would still be the logical default if you follow the Hippocratic oath of first do no harm. So the burden of proof would only apply to interference or interventions that deviates from pacing (like CBT, GET or pacing up), and obviously anything else that claims to be disease modifying.

The nifty thing with pacing is also that it’s defined in terms of what you attempt to maximise for, not in terms of what you do exactly.

So any deviations from pacing would have to argue for why you shouldn’t maximise FC&QoL and minimise unwellness, or why doing X would result in a better outcome.