Opinion CBT and graded exercise therapy studies have proven that ME/CFS and long Covid are physical diseases, yet no one is aware of that, 2024, Vink

[The text at the link is one long paragraph which is difficult to read. I have thus added in some paragraph breaks but they are not official ones]

https://www.frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2025.1495050/abstract

The cognitive behavioral model (CBmodel) (1,2) has dominated the world of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) since the 1990s. According to this model, a belief in an organic illness, known as dysfunctional beliefs, stops ME/CFS patients engaging in normal activities, resulting in avoidance behavior and deconditioning. The deconditioning then leads to further avoidance behavior and more deconditioning. According to the CBmodel, symptoms of ME/CFS are caused by deconditioning and not by an underlying illness. Cognitive behavioral therapy with graded activity (CBTplus) and graded exercise therapy (GET) were designed to reverse the dysfunctional beliefs, the avoidance behavior and the deconditioning and lead to recovery.

As many runners know, if you are a beginner and you start exercising three times a week, you can run half a marathon in 12 weeks. In a healthy sedentary person who doesn't do physical exercise or work, that will take around 12 to 24 weeks (3). Let's keep that in mind and have a look at the largest CBTplus and GET trial for ME/CFS, the PACE trial (n=641) (4), and its GET group, in particular. The 160 participants in that group were exercising five days a week for up to 30 minutes per day for 24 weeks. If there would be no underlying disease, and patients were merely deconditioned, then such an exercise regime would lead to a very substantial improvement in fitness. However, fitness did not improve (5). The same thing was seen in the CBTplus group. Consequently, an underlying disease, i.e. ME/CFS, was preventing that. It also means that patients were already exercising at their maximum when they joined the study, which disproves the assumption that patients were exercising less than they could due to dysfunctional beliefs.

Three Dutch studies (6)(7)(8) showed the following: eight months of CBTplus in adults, five months of CBTplus in adolescents and at least 16 weeks of guided self-instructions in adults, based on CBTplus, did not lead to an objective improvement of activity (actometer) (9).

A 12-week programme of GET (10), an 18-week programme combining CBTplus and GET in the more severely affected (11) and the evaluation of the efficacy of CBTplus and GET in the Belgium reference centers (12) showed no objective improvement in fitness, according to VO2peak, a timed step test, which "strongly and reliably predicts the maximal aerobic capacity VO2max" (p. ( 13)) and VO2peak or VO2max, respectively. This is not only important for ME/CFS patients, but also for those with long Covid because not only do around 60% of them fulfill ME/CFS criteria (14,15). But also, because there are at least 400 million people with long Covid according to a conservative estimate (16).

Moreover, the ReCOVer study, based on the CBmodel, found that 16 weeks of CBTplus did not lead to an objective improvement of activity (actometer) in long Covid either (17,18).In all those studies, one would have expected a (very) substantial increase in activity/fitness but this didn't happen because an underlying illness was preventing that, just like what was found by the PACE trial. Consequently, all those studies proved that ME/CFS is a physical disease and that ME/CFS patients do not suffer from dysfunctional beliefs. The ReCOVer study proved the same in long Covid.

Some people might say, but that is simply down to the fact that patients were not motivated to follow those treatments and they simply did not adhere to them. However, the above mentioned studies concluded that their treatments were effective and that implies that patients adhered to treatment. If they had not adhered to treatment, then those studies would have concluded, we cannot conclude anything about the efficacy of our treatments because patients did not adhere to it. Or, that patients did not adhere to the treatment because it was not effective and / or patients were negatively affected by it. Moreover, the aforementioned PACE trial (4) found high rates of acceptance of the treatments and of participants satisfaction; 87% (CBTplus) and 85% (GET) of participants were adequately treated, the adherence to the manual by competent therapists was very good (CBTplus) and excellent (GET), and the dropout rate was low (11%, CBTplus and 6%, GET).Additionally, the aforementioned Belgium evaluation (n=655) (12) concluded that patients had on average 41 to 62 hours of CBTplus and GET, spread over 6 to 8 months. The dropout rate was very low (only 2.8%) because patients were "generally speaking…very motivated to follow the therapy" (p. 80 ( 12)).

The remaining question then is, why is no one aware of that? Or to put it differently, why did none of these studies report the above mentioned discovery? The first possible answer is because the studies were conducted by researchers who have originated and / or devoted their career to the CBmodel and the efficacy of CBTplus and / or GET for ME/CFS. As noted by Ioannidis, "investigators working in any field are likely to resist accepting that the whole field in which they have spent their careers is a 'null field.'" (p. 0700, 19).

The second possible answer is that the studies were conducted by mainly mental health experts who are not experts in exercise physiology. Consequently, they did not see what their own results showed. In a similar manner that most of us would have thrown away the mold overgrown petri dish in the research by Dr Alexander Fleming that led to the discovery of penicillin (20). It needed someone like him to understand the meaning of it.CBT and graded exercise therapy studies have proven that ME/CFS and long Covid are physical diseases. Yet no one is aware of that because many of the researchers involved in the studies have built their careers on the CBmodel and they resist accepting the true meaning of the objective outcomes of their studies because that would invalidate their model. Alternatively, the studies did not report that because most of the researchers involved are mental health experts instead of experts in exercise physiology.

Keywords: cbt, chronic fatigue syndrome, CFS, cognitive behavioural therapy, COVID-19, Long Covid, ME, ME/CFS

Received: 12 Sep 2024; Accepted: 13 Jan 2025.

 

I haven't looked too deeply at PACE. For this paper's claim that ME/CFS fitness didn't improve because of disease to be true, the fitness of the healthy controls should have substantially improved. Was that the case?

Not really clear what they're referring to. (Edit: Oh, the main claim that physical fitness didn't improve.)

The writing is very informal and it has poor grammar for a published paper.

 

I can see what they are trying to say and there is validity to the arguments but I am not sure the trials prove quite what is claimed.

I think PACE and other studies show clearly that ME/CFS is not due to unhelpful beliefs that can be addressed with either CBT or GET. But that does not prove it isn't due to beliefs that are resistant to these. I also think the use of the word 'physical' is unhelpful. Thoughts are physical too, as far as we know.

 

These titles are getting wilder.

 

Although I believe the totality of evidence relating to ME/CFS makes it much more probable that research into the biology of the condition will achieve meaningful results than psychological or behavioural investigations.

However I have to agree with @Jonathan Edwards that Vinks go beyond the evidence from the PACE and related studies in concluding that this research proves we are looking at a ‘physical disease’. Undoubtedly, as the Vinks conclude, this research proves that the psychological and behavioural interventions so far put forward do not work, so they should not be used clinically, especially given other evidence of harms. However that does not prove that all possible psychological or behavioural could never work, just the ones we have looked at so far.

It would be logically equivalent of saying that before the discovery of quinine no medicine could ever treat malaria because the medicines tried up to that point did not work.

 

Assuming “psychological” and “behavioural” are even useful categorisations. These categorisations are fundamentally descriptive, ie. based on symptoms, the symptoms being differences in psychology and behaviour.

They do not say anything about cause; we don’t have any scientific way of proving something is 100% caused by behaviour or psychology. For what leads us to change behaviour or psychology may well be physical differences. The mind is not some separate magic, it is part of the body.

Many physical diseases cause psychological and behavioural alterations. But we know the cause is physical because we’ve discovered a mechanism.

 

Most of the paper discusses trials and I am not sure how much we can know about how well the patients adhered to GET. No doubt most people who adhere to GET don't improve but actually there was one paper in the Larun review where people did get fitter - just not less ill.

I also think it is perfectly possible for frame of mind to affect the response GET - at least in theory. I have a strong impression that I did not get fit by running up and down stairs with blood samples all day as a young doctor but did very quickly restore fitness when I had three months off to laze about and do some enjoyable swimming. It is perfectly possible that unless you are in the right autonomic state training of muscles fails to occur. And mindset determines autonomic state.

I am not arguing that I believe that but I think they are over-egging their case in places - as it seems others do.

 

Yes

 

I don’t think that we can claim that the PACE & Co failures prove that ME is a physical disease. Just that CBT & GET are the opposite of effective treatments here.

However no need to prove that ME or LC are ‘physical’. There’s simply no justification for considering these otherwise. Whereas we’ve every reason to consider these conditions ‘physical’.

The symptoms are in line with post viral syndromes long observed. COVID-19 is an absolute killer.

Sometimes some mood changes or changes in cognitive function that may mirror depression occur or other psychiatric symptoms may be found along side the main physiological symptoms. But the former aren’t the basis for the diagnosis of ME, for which all core criteria are physiological experiences rather than anything else.

It goes against reason to present a simple sore throat following a virus as evidence of a complex psychological phenomenon. It’s not that deep it’s a sore throat. Or swollen glands, known to do this with infection don’t you know? Or it’s infection leading to some unfavourable change within the human body related to immune response to infection. That’s a thing we already know exists in this physical realm. No need to invent complex as yet unproven in fact unprovable pathways towards sickness via the unconscious mind.


As an aide, I’d like to think my mind would pep up my symptom pattern and be less pedestrian in presentation honestly. If it were really were in a cycle of endless unknowable torment, I have faith that it’s gonna be a bit more imaginative in its worldly projections. Not just do a thing, oops feel like dying do another thing feel like dying again and again. It’s too boring for a wild untapped world of psychic energy. So I don’t find such a hypothesis credible. After all doctors and other professionals have been known to be wrong about such things over and over and over….

 

Can you elaborate on both of those claims? Why and how would muscles care about your autonomic state, and why and how does mindset determine the autonomic state?

 

Muscles are totally dependent on autonomic signals for blood flow, sugar levels and oxygen (breathing depends on autonomic circuits). Mindset determines autonomic state through sympathetic and parasympathetic impulses regulating heart rate, breathing rate, eating, and all sorts.

When I say autonomic state I guess that I really mean a wider regulatory state that will include corticosteroid and other hormone levels, which again impact muscle.

Following major surgery we know that there is a negative nitrogen balance period during which it is more or less impossible to build protein components of tissues. Protein is broken down. It is not clear what mediates that over aperiodic of weeks but likely hypothalamus, which is plugged in to the autonomic system and the hormonal system. That is not mindset but mindset can influence similar systems with through consciously altering eating habits or through anxiety or depression or desire for a gold medal (which seems to have a big effect on muscle performance!).

My guess is that there are regulatory pathways we still don't really understand. One example might be the hormone leptin, which seems to get involved in all this stuff but nobody is quite sure what it's specific role is in lots of situations.

 

This is largely untrue, at least with respect to training of muscles. You are greatly overstating the effect of cognition/emotions on autonomic regulation.

 

So why has a sympathetic state traditionally been called fight, fright or flight?
How does a vasovagal faint at the sight of blood not link cognition to autonomic state?
Why do we shake when anxious?

 

There’s a difference between being able to affect the muscles, and being required for the muscle’s functioning.
The former is unquestionable, the latter not so much IMO.

 

Because people like to oversimplfy things to the point of inaccuracy.

Many people don't shake when anxious, it is separate learned behaviour and vasovagal syncope is largely is a consequence of hyperventilation. So it is cognition->behaviour->cerebral blood flow consequences->vasovagal response

I'm not sure how any of this is directly relevant to the training of muscles from exercise though.

 

I absolutely hate this stupid "fight or flight" crap and long for the day it's never said out loud again outside of weird historical "people used to say dumb shit". It's as meaningless as Asimov's 3 laws of robotics is as a framework for how to handle AI.

We also shake when we're cold. More as it gets colder. Then at some point when people are hypothermic, they actually feel hot even though they're on the verge of dying. These things don't mean much. Just old metaphors that may as well be about the moon being made of cheese. People love to oversimplify complex ideas and health is basically the last remaining important topic where woowoo dominates, even among professionals.

 

And what I was suggesting was something much more subtle and only posed as a speculation.