Review Does the effect of CBT for CFS (ME/CFS) vary by patient characteristics? A systematic review and individual patient data meta-analysis, 2023, Knoop

Free fulltext:
https://www.cambridge.org/core/jour...metaanalysis/63F43CD7337CA7D005FA5FFE074A341F

Does the effect of cognitive behavior therapy for chronic fatigue syndrome (ME/CFS) vary by patient characteristics? A systematic review and individual patient data meta-analysis
Published online by Cambridge University Press: 06 November 2023

T. A. Kuut[Opens in a new window],
L. M. Buffart,
A. M. J. Braamse,
I. Csorba,
G. Bleijenberg,
P. Nieuwkerk,
R. Moss-Morris,
F. Müller and
H. Knoop

Abstract

Debate is ongoing on the efficacy of cognitive behavior therapy (CBT) for myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS).

With an individual patient data (IPD) meta-analysis we investigated whether the effect of CBT varied by patient characteristics.

These included post-exertional malaise (PEM), a central feature of ME/CFS according to many.

We searched for randomized controlled trials similar with respect to comparison condition, outcomes and treatment-protocol.

Moderation on fatigue severity (Checklist Individual Strength, subscale fatigue severity), functional impairment (Sickness Impact Profile-8) and physical functioning (Short Form-36, subscale physical functioning) was investigated using linear mixed model analyses and interaction tests.

PROSPERO (CRD42022358245).

Data from eight trials (n = 1298 patients) were pooled.

CBT showed beneficial effects on fatigue severity (β = −11.46, 95% CI −15.13 to −7.79); p < 0.001, functional impairment (β = −448.40, 95% CI −625.58 to −271.23); p < 0.001; and physical functioning (β = 9.64, 95% CI 3.30 to 15.98); p < 0.001.

The effect of CBT on fatigue severity varied by age (pinteraction = 0.003), functional impairment (pinteraction = 0.045) and physical activity pattern (pinteraction = 0.027).

Patients who were younger, reported less functional impairments and had a fluctuating activity pattern benefitted more.

The effect on physical functioning varied by self-efficacy (pinteraction = 0.025), with patients with higher self-efficacy benefitting most.

No other moderators were found. It can be concluded from this study that CBT for ME/CFS can lead to significant reductions of fatigue, functional impairment, and physical limitations.

There is no indication patients meeting different case definitions or reporting additional symptoms benefit less from CBT.

Our findings do not support recent guidelines in which evidence from studies not mandating PEM was downgraded.

 

https://www.eurekalert.org/news-releases/1006784

NEWS RELEASE 6-NOV-2023
Cognitive Behavioral Therapy beneficial for patients with ME/CFS

Research from Amsterdam UMC shows that patients with Post-Exertional Malaise can also benefit from CBT

Peer-Reviewed Publication
AMSTERDAM UNIVERSITY MEDICAL CENTERS



Researchers from Amsterdam UMC and King's College London have shown that Cognitive Behavioural Therapy (CBT) is beneficial for those with ME/CFS. They analysed data from trials involving almost 1300 patients and found that CBT led to a reduction in fatigue and physical limitations. These results are published today in Psychological Medicine.

“We found CBT led to a clinically relevant reduction in fatigue and functional impairment as well as an increase in physical functioning. These results give a clear picture that CBT can be beneficial for a substantial number of patients. About half were no longer severely fatigued after treatment,” says Professor Hans Knoop, Clinical Psychologist at Amsterdam UMC and leader of the research group.

Who Benefits?

It is often assumed that patients who experience an increase of symptoms following exertion, also known as post-exertional malaise (PEM), do not profit from CBT or, even, that CBT makes their symptoms worse. The researchers tried to determine for which patients CBT was beneficial. They found that patients could profit from CBT irrespective of which symptoms they experienced or how ME/CFS was diagnosed.

There were differences between patients in the extent they benefitted from CBT: Younger patients, patients with less functional impairment and patients who were still relatively active profited more from CBT.

“Reporting more functional impairments and being physical inactive may indicate more severe disease and this subgroup of patients probably needs additional or more intensive treatment,” says Tanja Kuut, clinical psychologist at Amsterdam UMC and lead author of this study.

Findings contradict guidelines
In 2021, NICE, the British National Institute of Clinical Excellence, published new guidelines for ME/CFS. They not only proposed to use a new case definition for ME/CFS but concluded that CBT may merely support patients in managing symptoms but cannot be seen as a treatment that can reduce symptoms and help recovery. This conclusion was partly based on the lack of evidence of the efficacy of CBT when certain (new) case definitions of ME/CFS were used to diagnose it or when PEM was reported by patients.

The findings of the new study show that CBT can also be effective for patients with PEM and those diagnosed using the new case definitions. In the eyes of Knoop and Kuut, this is encouraging news for patients, and it provides guidance for healthcare providers who were uncertain which patients they should refer to CBT.



JOURNAL
Psychological Medicine

METHOD OF RESEARCH
Meta-analysis

SUBJECT OF RESEARCH
Not applicable

ARTICLE TITLE
Does the effect of cognitive behaviour therapy for chronic fatigue syndrome (ME/CFS) vary by patient characteristics?: a systematic review and individual patient data meta-analysis

ARTICLE PUBLICATION DATE
6-Nov-2023

 

Published in Psychological Medicine, whose editorial board can be seen here, https://www.cambridge.org/core/jour...nformation/about-this-journal/editorial-board

Familiar names include Matthew Hotopf, Michael Sharpe and S. Wessely

 

I've not has the time to look, but I'm guessing that there is a lack of objective measures being assessed?

 

How was it put again? Oh, yes, patient-hating charlatans.

 

This seems to be a meta-analysis of Dutch CBT trials, since the Dutch CBT protocol had to be followed for a trial to be included. In this case, most if not all of these trials did not evaluate PEM or did not evaluate it correctly.

 

Thirty years of trials and no evidence of lasting benefit. There should be thousands of people out there who have recovered complete health in that time if it worked.

I am beyond angry at money still being wasted on these studies and so called researchers making money from our suffering and broken lives. They have to know it is fake.

 

Is the conclusion that if studies selected on the basis of PEM failed to show any reliable evidence of effect and effect is not dependent on whether people have PEM that the absence of reliable evidence can be extended to all cases?

Has this guy Knoop absolutely no idea of what he is doing?
(Sorry, we answered that before.)

 

All of the 8 included studies were from the same research team (the Dutch research team of Knoop/Belijenberg). The review states: "All studies were from our own research group. No additional RCTs from other researchers fulfilling our eligibility criteria were found."

So this is pretty much a review of their own studies. It's still interesting though to see the results of these studies combined using the raw data. The main effect for fatigue is notably large (cohen's D of 0.84).

They say the effect for fatigue was larger in adolescents and patients with less functional impairment. Improvements in physical functioning were much smaller in those with low self-efficacy. If one looks at the full results of the moderation analysis, however, in table 4, what stands out is that pretty much nothing had a clear influence on the treatment effect (except perhaps for age on the effect of fatigue).

So all the factors in their cognitive-behavioral model: self-efficacy, focus on bodily symptoms, catastrophizing, sleep problems and sleep-wake pattern, and physical activity pattern, did not have the influence on the treatment as expected.

It is sometimes stated in the ME/CFS community that CBT might work for the lesser-ill patients with fatigue and depression but not for the more severely affected with true ME/CFS. For the patients that were in these trials, however, there were remarkably little difference in treatment effect between different levels of severity. Functional impairment, depression, number of symptoms: it all had little effect on the size of the treatment effects, suggesting that the reports were not due to a subgroup of patients that is less ill.

The authors also say that they checked for PEM and the new NICE and IOM criteria and found that these had no influence on the treatment effect. But they did so retrospectively and incompletely. PEM was probably assessed with one question that is part of the Fukuda-criteria assement and it appears that the authors simply ignored Orthostatic intolerance even though it is part of the IOM. They write: "Another limitation pertains to our operationalization of the SEID diagnosis without orthostatic intolerance, which was not assessed."

 

All of the RCTs are from the same Dutch group (bolding mine in the quote below) and date from before 2015 except for one, so PEM was evaluated retrospectively. They all compared CBT to usual care or waiting list.

The results of one of the more recent trial (2015) are not published; as for the others, the authors rated four of them as “having some concerns” with respect to bias and three at high risk of bias:

 

These are the studies included in their analysis - they say that all used "CDC" criteria (which confusingly they reference as Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution, 2003, Reeves et all).

Click to expand.


They then claim that 1157 of the 1258 total number of patients had PEM, without explaining how they determined this.

Click to expand.


Taking one study used, Cognitive behaviour therapy for adolescents with chronic fatigue syndrome: randomised controlled trial, 2005, Stulemeijer et al. I can find no reference to PEM in any form, not even of fatigue following exertion.

Just to be sure, I checked , Efficacy of web-based cognitive–behavioural therapy for chronic fatigue syndrome: randomised controlled trial, 2018, Janse et al. Again, no mention at all of PEM in any form in the text.

I'm in agreement with cassava above, there seems to be no basis for the claim that these participants had PEM.

 

So it's OK after all to pick and choose?

Has it not occurred to them that next time any regulatory body with patient representatives sits down to consider some guidelines that faced with papers like this the representatives will be entitled to ask 'with crap like this from these researchers why on earth should anything by them be taken seriously?' The techies might even twig that benefit of the doubt was not entirely necessary.

 

The reference to Reeves 2003 possibly means that the trials from 2005 onwards used the revised “empirical definition”, which does not require PEM. They only require four or more symptoms from the Fukuda criteria as well as scoring higher than a certain threshold on the Multidimensional Fatigue Inventory, the physical function subscale of the SF-36 and the CDC’s CFS symptom inventory.

Of note, a study by Leonard Jason’s group found that 38% of patients who had major depressive disorder were misdiagnosed as having CFS according to the Reeves criteria. https://journals.sagepub.com/doi/10.1177/1044207308325995

 

This is from memory, but I think the 2003 paper only clarified some ambiguities in the Fukuda criteria and recommended some questionnaires to use. The thresholds were defined later, so reference to this 2003 study does not mean the empirical definition, I think.

The supplementary material states:

"Symptoms were assessed by a questionnaire assessing nine accompanying symptoms of the Centers for Disease Control and Prevention (CDC) criteria for ME/CFS (Fukuda et al., 1994; Reeves et al., 2003). (1) Post-exertional malaise (PEM): “increase of symptoms following exertion”; (2) unrefreshing sleep;
​

So PEM was likely assessed with the single question: "do you have an increase of symptoms following exertion?" which isn't very specific.

 

In the supplementary materials they give an overview of their assessment. Lack of blinding + subjective outcome measures did not lead to high risk of bias rating. The studies that received a high risk of bias rating did so because they had missing outcome data.

 

So, if I'm getting this right, the IOM (now National Academy of Medicine), CDC, IQWIG and NICE, among others, all found that almost all of the biopsychosocial evidence for CFS is of low quality and highly biased, and a bunch of highly biased quacks who produced much of this evidence publish yet another low-quality highly-biased review of a few cherry-picked low-quality highly-biased studies, publish it in what is basically a highly-biased and -conflicted journal and think it somehow overturns multiple prior independent analyses that the evidence amounts to nothing?

On top of, of course, widespread recognition that it's completely failed to address Long Covid, an issue that meets all their criteria, and recognition that there are no treatments for CFS. After years of insisting that criticism of this model of CBT is invalid since it's used to help patients with other diseases manage their condition better, which they here dismiss, insisting that it's a curative treatment model, which is not at all the case e.g. for cancer, which they often use as an example.

Even though their own findings are entirely consistent with there being no effect, since the "effect" they tortured out of unreliable data basically follows illness severity and impact, and have no objective evidence of benefits. Which basically all shows that this entire methodology is useless, as it cannot tell the difference between, well, anything, frankly.

Medicine has the unique distinction of being the only scientific discipline to actually regress. And not by a little. And showing fanaticism and inability to learn and adapt to or follow evidence. All while showing contempt and hostility to patients suffering from a complete loss of function and quality of life. This is all very disturbing. It's not surprising that no progress has been made here, this is not a way to solve problems.

 

On second thought, since all but one of the studies used the Fukuda criteria with the four or greater symptom criterion, the authors can simply claim that the participants did have PEM at the time that they were recruited (and not retrospectively) based on their clinical assessment, i.e. whether they responded that they experienced “postexertional malaise lasting more than 24 hours”. The question, then, is whether this truly represented a ME/CFS crash or was confused with the kind of post-exertional fatigue that can be seen in other health conditions.

 

Indeed. This goes to show that a risk of bias assessment should not be carried out by the same group of investigators that conducted the studies…