Underuse of Pharmacologic Therapies for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Before Specialist Evaluation, 2026, Grach et al

[Holinger]

That's the thing. People actually have spent money on blinded CoQ10 trials and some of those trials are okay in other respects too. We have a decent amount of decent evidence for that supplement, but it has been ignored in this paper.

I have clearly missed that.
I am being a bit kinder to Mayo who pre covid treated me/cfs as a conversion disorder or central sensitisation treated with cbt / get. I think everything you have to say is correct and would never go to a hospital like that now that I am in a position to be informed but they clearly moved on from damaging patients with me/CFS to baseless medical treatment.

 

[Hutan]

I am being a bit kinder to Mayo who pre covid treated me/cfs as a conversion disorder or central sensitisation treated with cbt / get.

I'm pretty sure that there are still Mayo clinics where your ME/CFS symptoms would be treated as a functional neurological disorder and you would be given CBT and GET.

See for example the website for a Mayo pediatric clinic for functional neurological disorders including 'autonomic issues' (excerpts below). I think we have a thread on a Mayo adult clinic that seems to be targeting employers and medical insurers who want to deal with chronically ill employees. That's the thing - if you don't require good evidence when deciding on appropriate treatment regimes, then you can pretty much do whatever takes your fancy. There's something for everyone (with medical insurance).

An important part of treating FND is communicating that FND is real — it's not "in a patient's head" and patients are not "faking it." This acknowledges that symptoms are involuntary and distressing and provides hope that FND is a treatable condition. Education about risk factors such as stress or trauma, which can be physical or mental, coexisting mental health disorders, and recent illnesses are important for patients and their families. Reducing medicalization and guiding patients and their families to supportive integrative care can help them understand that recovery is possible and may look different from the treatment they have received. The focus shifts to retraining the brain and the body through integration of psychological principles and therapies to redirect symptom-focused attention to the promotion of functional recovery.

"Functional neurologic disorder is a real and treatable condition. Our goal is to help patients and families understand that symptoms are involuntary and distressing — and recovery is possible. Through a multidisciplinary approach that integrates physical, occupational and recreational therapy, psychology, and education, we focus on retraining the brain and body to restore function and improve quality of life," says Amy E. Rabatin, M.D., a pediatric physiatrist at Mayo Clinic Children's.

Cognitive behavioral therapy (CBT) is foundational to FND recovery and can include concepts of relaxation, distraction, reframing, and identifying and managing stress as well as the use of strategies to recognize and mitigate symptom exacerbation. Referral to occupational therapy, physical therapy or speech therapy depends on the FND symptoms.

So, yes, very good that these particular Mayo clinicians aren't pushing a psychosomatic rehab paradigm. But, 'not doing that' is a very low bar in terms of expectations of a world leading hospital.

they clearly moved on from damaging patients with me/CFS to baseless medical treatment.

Ha, yes.

I guess the concern is that the baseless medical treatment can also damage patients in various ways, not least by distracting people for years from the urgent need for actual treatments.

 

[Holinger]

Ha, yes.

I guess the concern is that the baseless medical treatment can also damage patients in various ways, not least by distracting people for years from the urgent need for actual treatments.

If you read (which you would have) some of the ways some Fibromyalgia patients have been funnelled into a $60,000 central sensitisation course with a Dr of psychology ( it is a catastrophisation course) it is truely horrific. That sort of stuff kills people. That is what the bar was before. I am only hoping that shit is still not going on with Me/CFS. The whole thing is a very low bar. Not disputing that.

 

[Jonathan Edwards]

It is important also to note that it is true across medical conditions in general (autoimmune diseases, neurologic diseases, cardiovascular diseases, and so on) that there is no one-size fits all therapies, that a portion may benefit and a portion may have side effects.

This is a misrepresentation of the fact that shows a deep lack of understanding of the problem.

For conditions like autoimmune and cardiac diseases we have reliable trial based evidence of benefit for a population of patients that is mediated by some, but not others, improving. It is therefore legitimate to take clinical evidence of improvement in an individual case as evidence of a response to treatment. Nothing of this sort applies in ME/CFS. It is time that physicians and advocates got this basic concept clear. Not getting it clear will do a huge amount of harm in terms of unwanted effects of drugs and delay in getting trials done.

Doing good drug trials is not difficult. The main reason they are not done is that nobody really believes the drugs work. If they did they would do the trials tomorrow. The proof is that the UK delivery plan working group could think of nothing except naltrexone to be worth trying and that was mostly to clear the air because it was so widely recommended.

I have also reason to believe that we have useful negative data on drugs unpublished.

 

[Sasha]

I have also reason to believe that we have useful negative data on drugs unpublished.

That would be an appalling situation! I hope that whoever is in a position to do so can apply pressure to getting those results out.

 

[Jonathan Edwards]

That would be an appalling situation!

It is legitimate delay in publication but it would have been nice to have it put out as a preprint.

 

[Sasha]

It is legitimate delay in publication but it would have been nice to have it put out as a preprint.

Oh! That's much better - I thought you meant that null results were being buried. But yes, a preprint could help a lot of patients.

 

[dmh]

I have been thinking about this research and came up with some benefits and concerns but I am not a medical professional or researcher (long-time patient/caregiver/advocate). I was wondering if these are valid - I do use AI to help me make my thoughts understandable but I don't use it to make my thoughts (tbh I fight with it all the time because it tries to overwrite my voice or change my thoughts but it is still more readable than what I can do on my own). My reading is definitely impacted by severe ME/CFS (and I have associated cognitive issues so there are probably errors and I am missing stuff). Initially I had a longer list but then realized I was trying to make this study into something it wasn't. (I don't like to use a paper in advocacy without trying to understand context)

The GOOD:

• The study provides quantitative data confirming that 31.7% of patients had not tried any recommended pharmacological therapies before their specialty consultation.
• By using a large cohort from a single institutional system, the study maintains high data integrity and consistency in documentation.
• Documenting the use of medications like Low Dose Naltrexone and fludrocortisone helps normalize these off label treatments for smaller clinics (which can be useful for patients wanting to trial things who don't have specialty clinic access).
• The findings demonstrate that patients often face a significant diagnostic delay and a lack of specific treatment plans even after a diagnosis is made (which as an advocate, is something that is good to have quantified).

The CONCERNING:

• There is no data in the study showing whether the 571 patients in the specialty clinic actually improved on the specialist protocols.
• The research fails to stratify patients by severity, meaning the needs of highly disabled patients are mixed with those who have mild symptoms.
• Relying on raw Electronic Health Record data prevents the authors from distinguishing if a medication was prescribed for ME/CFS or a common comorbidity like hypertension.
• The authors acknowledge they lacked information regarding why medications were discontinued or if a patient had previously refused a drug.
• Excluding 2,086 patients with Fibromyalgia creates a sanitized dataset that does not reflect the complex reality for the majority of the community (this bugs me because I think they said there is a 70% overlap ME/CFS and FM diagnoses).
• The study attributes the lack of prescriptions to an education gap but may overlook systemic constraints like liability risks and institutional guidelines for generalists (I have gone to a bunch of doctors who actually wanted to prescribe some treatments but weren't permitted to).
• Pacing remains invisible in the data because it is a biological management strategy rather than a prescription, creating a documentation gap for the most effective management tool - I get they were looking at pharmacological treatments but that actually is actually one of the most effective treatments.
• The paper cites a 15-fold increase in incidence post-pandemic, which potentially ignores the historical 90% underdiagnosis rate that existed for decades and makes long COVID ME/CFS seem like it significantly outweighs pre-COVID ME/CFS - which could impact funding and perception. This really bothers me because we know the prevalence figures from pre-COVID were unrealistically low - the most reasonable ones are probably Data Brief #488 and KFF https://lookinside.kaiserpermanente...ovid-19-may-trigger-chronic-fatigue-syndrome/ (which only has 14% of ME/CFS triggered by COVID) and a lot of LC ME/CFS is still in the possible to go into remission stage. (LC can trigger ME/CFS but I don't think there are 15x the LC ME/CFS patients than there are ME/CFS patients from other sources).

 

[Hutan]

It is legitimate delay in publication but it would have been nice to have it put out as a preprint.

Oh! That's much better - I thought you meant that null results were being buried. But yes, a preprint could help a lot of patients.

I am sure both occur.

For example, Forestglip noted that there is a CoQ10 study registered in Clinical Trials by a Klimas team that seems to have negative results for Gulf War Illness. The evidence review draft says about this study:

Coenzyme Q10 Phase III Trial in Gulf War Illness, 2020, Klimas et al (not published)

In 2017, the Klimas team registered a trial of CoQ10 in Gulf War Illness. The double-blind placebo controlled study involved a treatment of 400 mg of CoQ10 for 2 months followed by 200 mg for 4 months. It seems that the trial was completed in 2020, but no paper has been published on the study. The results on the clinical trials registration site suggest that the study was medium sized (100 people allocated across the two treatments). The study assessed a large number of things including pain, function, cognition, sleep and depression. Differences between the treatment and placebo at 6 months were small, with no clear pattern of benefit from CoQ10. Although not published or peer-reviewed, these results seem to be good evidence that CoQ10 is not helpful for Gulf War Illness.

Forum thread here

It is possible that the authors found it hard to get a null result published and the pandemic probably made things more difficult. But, with the study completed in 2020, it seems possible that a lack of enthusiasm for getting this information out may also be contributing to the delay.

 

[Mij]

For example, Forestglip noted that there is a COQ10 study registered in Clinical Trials by a Klimas team that seems to have negative results for Gulf War Illness. The evidence review draft says about this study:

Back in 2015 a patient of Dr. Klimas shared her experience on PR and took 2400 mg.

"I'm sticking at 1800 mg for the moment, except during a PEM episode when I'm trying 2400 mg. Dr K said the 1800 mg was fine if it's working for us, but suggested we split between ubiquinol and ubiquinone".

DISCUSSION: Did I just slam the door on a PEM episode?!

Here's the background~ Daughter and I flew down to INIM late last week for our semi-annual visit. Because we are both doing much better and disability services at Miami Airport are awful (not just inefficient, but insulting, humiliating, and downright rude), we decided to walk Miami Airport...

forums.phoenixrising.me

I couldn't sleep anymore after taking 100mg for 2 months, and my COQ10 was considered 'low' after testing. I don't want that type of "energy".

 

[Hutan]

Welcome to the forum @dmh. Thank you for your post.

The study provides quantitative data confirming that 31.7% of patients had not tried any recommended pharmacological therapies before their specialty consultation.

The situation with the Mayo Clinic is quite specific. There is a high selectivity about which patients make it to the Mayo ME/CFS clinic. And, even then, as you note, the authors applied another layer of selection, removing a substantial number of patients, to create their sample. I doubt the percentage of patients who have not tried pharmacological therapies can be extrapolated with confidence beyond this particular case.

I guess we might also argue that not having tried these therapies is not a problem, if they are not helpful. Perhaps the use of some of these medications should in fact not be normalised.

The study does mention pacing as a first-line management approach, which is perhaps enough given the topic of the paper.

Thanks for the interesting comment about the contribution of Covid-19 to ME/CFS incidence and prevalence.

 

[Hutan]

Back in 2015 a patient of Dr. Klimas shared her experience on PR and took 2400 mg.

Thanks Mij. I read all of that PR thread - I think it is a really good illustration of why we need blinded trials. With the various fluctuations and all sorts of other variations that come with life, it becomes extremely hard to know if a supplement is helping at the n=1 level.

 

[Jonathan Edwards]

Documenting the use of medications like Low Dose Naltrexone and fludrocortisone helps normalize these off label treatments for smaller clinics (which can be useful for patients wanting to trial things who don't have specialty clinic access).

I would argue that this is a very bad thing. But documenting usage does not normalise in any legitimate sense. Patients want to trial things that they think someone has reliable evidence work. We don't have that. So normalising such things is simply a con. The logical extension is to bring back witch doctors that tell you they can exorcise your disease by spitting on your head.

 

[Utsikt]

Hi and welcome @dmh!

A few thoughts:

The GOOD:

• The study provides quantitative data confirming that 31.7% of patients had not tried any recommended pharmacological therapies before their specialty consultation.

There are no «recommended therapies» for ME/CFS, other than using well-established medications for specific symptoms (like nausea, pain, and sleep).

Documenting the use of medications like Low Dose Naltrexone and fludrocortisone helps normalize these off label treatments for smaller clinics (which can be useful for patients wanting to trial things who don't have specialty clinic access).

That’s not a good thing when we lack evidence that those treatments have a positive effect. And a positive well conducted trial would eliminate this problem.

The study attributes the lack of prescriptions to an education gap but may overlook systemic constraints like liability risks and institutional guidelines for generalists (I have gone to a bunch of doctors who actually wanted to prescribe some treatments but weren't permitted to).

The most plausible explanation is that the physicians that are unwilling to prescribe those treatments are the ones that recognise the lack of evidence and the rightfully assume that a randomly selected treatment has a higher chance of causing harm than benefits.

I had missed the claim about a 15-fold increase in ME/CFS post-covid. This is what they write:

US estimates of ME/CFS prevalence averaged 1 to 2.5 million before the COVID-19 pandemic; now, incidence rates are reported to be 15 times greater, related at least in part to long COVID.4,5

4 is this paper. The way the data was collected means that it can’t be used to estimated the total prevalence of ME/CFS.

One of the issues, recruitment bias, is highlighted by the fact that the rate of ME/CFS was much higher in the people that were recruited longer after their infection, compared to the people that were recruited very soon after their infection. So the later group are the ones that stayed sick for longer, which is not representative of the general US population. The earlier group isn’t representative either, for that matter.

5 is a paper by Jason. They recruited from LC groups, which isn’t representative and can’t be used to estimate the rate of ME/CFS in the population.

So the claim is not supported by their sources, and is probably counter productive for advocacy purposes.

 

[dmh]

I would argue that this is a very bad thing. But documenting usage does not normalise in any legitimate sense. Patients want to trial things that they think someone has reliable evidence work. We don't have that. So normalising such things is simply a con. The logical extension is to bring back witch doctors that tell you they can exorcise your disease by spitting on your head.

I don't entirely disagree - it is a fine line to walk. The problem is you do have desperate patients who will try CBT/GET/commercial SPAM programs and anything that shows up in any form of research - but you also do have patients who put a lot of effort into understanding their personal presentation and looking into medications/safety labs (which some of those treatments should not be prescribed without) and still can't get access to relatively benign options. I also think a lot of doctors/specialist/medical groups use not having clinical treatments (and I think pacing should be considered one) use the excuse that there are no treatment options to not diagnose or provide relief (We left Kaiser in 2018 because a doctor actually showed us KP's clinical guidelines saying don't diagnose ME/CFS because there are no treatments and it just upsets the patients (which is BS not knowing why you are sick is not better)). This isn't something I think is a huge step forward but I was trying to focus on potential benefits and concerns I had.

 

[Jonathan Edwards]

I don't entirely disagree - it is a fine line to walk.

I don't see any fine line. There is no justification for using treatments that have no evidence base.

but you also do have patients who put a lot of effort into understanding their personal presentation and looking into medications/safety labs (which some of those treatments should not be prescribed without) and still can't get access to relatively benign options.

There are no 'benign options'. Even some over the counter drugs can have lethal side effects. And if there is no evidence for efficacy what is the point anyway? We can be 95% sure that most of these drugs don't work for ME/CFS. Doctors always cling to a group of drugs they can dish out when there aren't any proven ones. I spent years doing that in the 1970s and 1980s. If you really want safe options why ot go to a hoemopath who dishes out empty tablets?

excuse that there are no treatment options to not diagnose or provide relief (We left Kaiser in 2018 because a doctor actually showed us KP's clinical guidelines saying don't diagnose ME/CFS because there are no treatments and it just upsets the patients (which is BS not knowing why you are sick is not better))

But hang on. If there are no useful treatments you are not i a position to 'provide relief' with medicines and ought to be honest about it. Doctors cannot provide relief for ME/CFS at present. We need to face up to that. And the argument that you should not diagnose isn't so crazy because we don't know why people with ME/CFS are sick. ME/CFS is not an explanation and should not be taken as indicating that a doctor has some knowledge of your illness. Us doctors know nothing about the illness - not even whether all the people with the diagnosis have the same illness.

I never used the term ME/CFS when I was practicing. I tried to explain to patients that I and other doctors recognised their sort of problem but that we knew almost nothing about it. If 'ME/CFS' is being used as a label to imply knowledge then that is phoney. I realise that a lot of people with ME/CFS find that hard to accept but the longer doctors pretend they know things when they don't the longer they will go on being ignorant.

 

[Hutan]

If 'ME/CFS' is being used as a label to imply knowledge then that is phoney. I realise that a lot of people with ME/CFS find that hard to accept but the longer doctors pretend they know things when they don't the longer they will go on being ignorant.

I think the label just means that the person has a collection of symptoms compatible with ME/CFS definitions and has had those symptoms for some months. The label means, by definition, that the person has PEM, as imperfect and imprecise as that term is. And that does imply some knowledge about the effect of exertion. That knowledge is useful for management.

I think there are quite a few diseases with no treatments, and I doubt the argument is often made that people should not be diagnosed with those, if they seek a diagnosis. I think the path towards finding useful treatments does require that people are grouped and labelled.

 

[Jonathan Edwards]

I think there are quite a few diseases with no treatments, and I doubt the argument is often made that people should not be diagnosed with those, if they seek a diagnosis.

I agree but the diagnosis should not be made to give the implication that there is an understanding of what is wrong. The argument is very complex but I don't think any of this justifies the idea that ungrounded treatments should be 'normalised' so that doctors can pretend they know what they don't.

It's a bit like the argument that one should not cast doubt of CPET measuring PEM because people need proof of PEM to get disability payments. The more phoney arguments are used the slower any change will be.

 

[Jonathan Edwards]

And that does imply some knowledge about the effect of exertion.

And actually I think this is pretty circular. If someone has PEM they know they have it, because we only know because they say so. So if ME/CFS is a persistent disabling condition with worsening after exertion, the person can say 'well yes, I know that'. We do know a bit about the statistics of prognosis but one can know those for a clinical picture without needing a diagnostic label and we often do. Prognosis often depends on a complex stratified analysis of the clinical presentation rather than what Sir Anthony Dawson used to call 'Procrustean diagnoses'.

And reading here I get the impression that PEM is an extremely variable category, such that it may be unwise to extrapolate from one case to another. We can advise people that others' experience is that pushing through is, in the long term, a bad idea. But if that gets enshrined in some stereotyped concept of PEM, bogus theorising and ungrounded treatments tend to rapidly follow. So we end up with these complicated recipes for energy management that just wear people out writing diaries for.

I am getting a bit irritated by people giving seminars and discussing policy at meetings talking about 'pem' as a word the rhymes with 'them'. It seems a relatively new habit. My suspicion is that folklorisation will tend to rapidly follow, just like 'nets' for neutrophil DNA extrusions.