Dear Ms Kupferschmitt,
Dear Professor Dr Köllner,
Dear Professor Dr Linden,
Dear Professor Dr Hautzinger,
Dear Members of the Relevant Subject Editorial Team at Springer Nature,
Subject: Formal Scientific Objection to Chapter 91, “Chronic Fatigue Syndrome” – Nosological Errors, Misclassification of Evidence, Causal Overreach, and Patient-Safety-Relevant Statements
As a patient organisation representing people with ME/CFS, Long COVID and Post-Vac, we are writing to you with a formal scientific objection concerning Chapter 91, “Chronic Fatigue Syndrome”, in the
Behavior Therapy Manual – Adults.
After carefully reviewing the pages available to us, pages 567–573, we do not consider this to be merely a matter of differing therapeutic schools or a controversial interpretation of an uncertain evidence base.
Rather, in our view, the chapter contains several specifically verifiable nosological and methodological errors, misclassifications within the hierarchy of evidence, insufficiently substantiated psychopathologising generalisations, causal overreach, and statements that are in substantial tension with current research on PEM and ME/CFS and may have direct implications for patient safety.
For a medical and psychotherapeutic reference book published in 2026, intended for education and professional training and capable of influencing therapeutic practice, we consider these issues to require correction.
1. Nosological category error at the very beginning of the chapter
On page 567, CFS is introduced in a manner suggesting that it is also referred to, among other terms, as ME, chronic fatigue or exhaustion syndrome, SEID, neurasthenia, somatoform disorder, or fibromyalgia.
This representation is scientifically untenable.
These are not merely different historical names for the same disease. Rather, different diagnostic concepts and distinct disease entities are presented side by side in a way that suggests diagnostic interchangeability.
ME/CFS is not fibromyalgia. ME/CFS is not neurasthenia. ME/CFS is not a somatoform disorder.
The German ICD-10-GM 2026 explicitly lists Chronic Fatigue Syndrome under G93.3- and includes Myalgic Encephalomyelitis as an inclusion term. Somatoform disorders, by contrast, are classified under F45.-. They are therefore expressly not alternative current ICD designations for the same disease.
Furthermore, ICD-10-GM 2026 explicitly differentiates between chronic fatigue with post-exertional malaise (R53.0), chronic fatigue without specification of PEM (R53.1), and Chronic Fatigue Syndrome/Myalgic Encephalomyelitis under G93.3-. R53.0 is defined as “Chronic fatigue with specification of post-exertional malaise [PEM].” Thus, the current classification specifically captures PEM without equating R53.0 with ME/CFS. This differentiation further reinforces the nosological objection to the chapter’s presentation: the current classification explicitly distinguishes categories that are conceptually conflated in the chapter.
Source: BfArM, ICD-10-GM 2026, R53.0/R53.1 and G93.3-
This is not a minor semantic issue, but a nosological category error.
It is also noteworthy that the chapter contains an internal contradiction: on page 571, it itself warns against misunderstanding CFS as a psychogenic illness or somatisation disorder. The chapter therefore initially creates precisely the diagnostic conflation against whose consequences it warns only a few pages later.
We request an explicit correction of this passage.
Source: BfArM, ICD-10-GM 2026, G93.3-
2. The blanket assertion that empirical evidence is lacking is scientifically outdated and misleading in 2026
On page 567, the chapter states that empirical evidence for the aetiological concepts associated with ME/CFS has so far been lacking.
Of course, there is still no single conclusively proven aetiology that explains every case of ME/CFS. Nor is there yet a universally established single diagnostic biomarker.
However, this is entirely different from the question of whether empirical evidence exists for pathophysiological alterations.
The evidence base has developed substantially in this respect.
There are now, among other findings, data concerning exercise-dependent muscle pathology, impaired energy production, mitochondrial alterations, hypoperfusion, microcirculation, oxygen extraction and immunometabolic changes. Appelman et al. documented severe muscle abnormalities in Long COVID patients with PEM following exertion, including larger areas of necrotic muscle fibres in 36% of the patients examined. Scheibenbogen and Wirth summarise an increasingly extensive body of experimental evidence concerning the role of skeletal muscle; Haunhorst et al. discuss microcirculation, oxygen extraction and immunometabolic responses in connection with PEM.
A scientifically accurate presentation must therefore clearly distinguish between “the definitive aetiology has not been established” and “there is no empirical evidence for biological disease mechanisms.”
The latter would simply be false in light of the current state of research.
Source: Appelman et al.,
Nature Communications 2024
Source: Scheibenbogen & Wirth, 2025
Source: Haunhorst et al.
3. Unsubstantiated psychopathologisation of patient behaviour
The statements on page 568 are particularly problematic.
The chapter describes some “fatigue patients” as displaying, among other things, a “combative and reproachful tone”, “dysfunctional illness behaviour”, “self-harming rest and avoidance behaviour”, increased self-monitoring, and ultimately criteria of a “hypochondriacal disorder”.
These are not neutral clinical terms.
Here, patient behaviour is framed to a considerable extent in psychopathological terms despite the fact that the core characteristic of the disease in question is an exertion-induced, frequently delayed deterioration in health status.
A patient who avoids physical exertion after repeated crashes is not thereby demonstrating “dysfunctional illness behaviour”. A patient who closely monitors their physical signals is not thereby hypervigilant or hypochondriacal. And a “combative and reproachful tone” is plainly not a diagnostic criterion for a hypochondriacal disorder.
This framing is particularly problematic in light of the experiences of people with ME/CFS concerning stigma, disbelief and loss of trust in medical institutions, which NICE explicitly documents. NICE therefore specifically calls for care that is non-judgemental, supportive and acknowledges the reality of the illness.
We therefore expressly request that the authors and editors state the robust empirical basis on which these generalised psychopathological characterisations of a group of ME/CFS patients are based.
If no corresponding evidence exists, such value-laden attributions have no place in a medical reference manual.
Source: NICE NG206 – Recommendations
4. Pacing is conceptually conflated with activation and behavioural progression
The chapter initially describes pacing correctly as energy management intended to prevent overexertion and PEM.
At the same time, however, pacing is embedded within a behavioural activation model. The chapter contains formulations such as “cautiously activating strategies”, “gradual behavioural progression”, “values-based behavioural activation”, and examples of gradually increasing activity, such as progressing from 15 to 17 minutes outside the bed.
This blurs a clinically crucial distinction.
Pacing is not graded activation therapy.
Pacing is energy management within an individual’s, often fluctuating, limits of exertion. This may allow a cautious increase in activity if it can be maintained consistently within the individual’s energy envelope. It may equally require a reduction in activity.
NICE expressly calls for flexible adjustments upwards or downwards and advises against programmes involving fixed incremental increases in activity as well as programmes based on the theory that deconditioning and avoidance of activity are perpetuating factors of the illness.
The statement that pacing is an “essential component of the behavioural therapy intervention” is likewise problematic. Pacing is not an inherently psychotherapeutic procedure. It is a disease-specific strategy for managing energy and exertion.
The chapter therefore risks semantically transforming a physiologically grounded protective strategy into a behavioural activation concept.
Source: NICE NG206 – Energy management and physical activity
5. Internal contradiction: the chapter acknowledges activation risks while simultaneously pathologising protective behaviour against precisely those risks
Another internal contradiction in the chapter is particularly serious from a patient-safety perspective.
On page 571, the chapter expressly acknowledges that a treatment concept that is too rapid and one-sidedly focused on activation can overwhelm affected individuals and, in the worst case, lead to a longer-term worsening of symptoms.
At the same time, the same chapter therapeutically emphasises “cautiously activating strategies”, “gradual behavioural progression”, “values-based behavioural activation” and a gradual increase in activity levels. Elsewhere, reductions in activity and careful self-monitoring are framed using terms such as avoidance, hypervigilance, nocebo, hypochondriacal disorder or dysfunctional illness behaviour.
This is not merely a minor terminological contradiction. On the one hand, the chapter acknowledges that exceeding exertional limits can lead to longer-term deterioration; on the other hand, it pathologises behaviours through which patients attempt to prevent precisely these consequences of overexertion.
If a specialist chapter itself acknowledges that activation may cause longer-term deterioration in ME/CFS, it must methodologically follow that PEM status, disease severity, delayed symptom deterioration, longer-term loss of function and safety endpoints constitute the central basis for all activity recommendations. A therapeutic rationale that simultaneously acknowledges these risks and psychologically problematises the protective behaviour used to avoid them is internally inconsistent and may lead to a safety-relevant misinterpretation of clinically appropriate behaviour.
In our view, this internal contradiction requires an independent editorial and scientific correction.
6. The deconditioning claim on page 569 is no longer scientifically defensible in its categorical form
On page 569, the chapter states:
“Anyone who is immobile for a longer period of time develops myalgic fatigue syndrome simply as a result.”
Such a categorical statement is no longer tenable in 2026.
Charlton, Slaghekke, Appelman et al. specifically investigated whether the characteristic physical changes observed in Long COVID and ME/CFS can be explained by inactivity or deconditioning.
Patients with Long COVID and ME/CFS were compared with healthy individuals following 60 days of strict bed rest.
The results showed substantial differences in the physiological and muscular changes. Bed rest caused a different form of muscle atrophy, whereas Long COVID and ME/CFS patients showed, among other things, a different muscle fibre composition and different relationships between mitochondrial function and exercise capacity.
The authors conclude that physical inactivity alone is insufficient to explain reduced exercise capacity and skeletal muscle alterations in Long COVID and ME/CFS.
Particularly noteworthy is the fact that this study did not investigate merely an indirect association, but directly tested the deconditioning hypothesis using an extreme inactivity model—60 days of bed rest.
The formulation in the chapter is therefore not merely “open to discussion”. In its sweeping form, it has been superseded by current experimental comparative data.
Source: Charlton, Slaghekke, Appelman et al.,
Nature Communications 2026
7. The Cochrane review is presented as “good evidence”, although its own limitations do not support such a generalisation
On page 572, the chapter states that there is “good evidence” for disorder-specific exercise therapy, citing the 2024 Cochrane review by Larun et al. as a central source.
This presentation is incomplete and substantially overstates the evidentiary strength of the review.
Cochrane itself states that, in the short term, exercise therapy probably has an effect on fatigue compared with more passive controls. For long-term effects, however, the evidence is very uncertain. The evidence concerning the risk of serious adverse effects is also very uncertain.
Of particular importance, the included studies used the Oxford criteria or CDC-1994 criteria. Cochrane expressly notes that individuals diagnosed according to other criteria may experience different treatment effects.
An additional issue is even more problematic: the review cited as the “current 2024 Cochrane review” is based on a systematic literature search that essentially extended only through May 2014.
A publication date of 2024 must not be confused with an evidence search conducted through 2024.
To cite a review with a search base approximately ten years old, older case definitions, uncertain long-term effects and very uncertain evidence concerning serious adverse effects as “good evidence” for exercise therapy in a contemporary ME/CFS population defined by PEM is not methodologically appropriate.
Source: Cochrane Review CD003200 –
Exercise therapy for chronic fatigue syndrome
8. Objective evidence-classification error: a quasi-experimental study is cited as evidence from “randomised studies”
On page 572, the chapter states that, in Post-COVID, evidence from “randomised studies” for the efficacy of CBT combined with exercise therapy is increasingly available. Among the cited sources are Frisk et al. 2023 and Nerli et al. 2024.
Frisk et al. already states in its title: “A safe and effective micro-choice based rehabilitation for patients with long COVID: results from a quasi-experimental study”.
The study was explicitly quasi-experimental, not randomised.
This is not a matter of interpretation. It is an objectively incorrect classification of the level of evidence.
Nerli et al. was indeed a randomised clinical trial. However, it specifically investigated patients with mild to moderate Post-COVID disease. The authors themselves point out that it remains necessary to determine which subgroups the intervention is relevant for.
This does not support a general statement concerning efficacy in ME/CFS, pronounced PEM or severe disease.
We expect a scientific reference manual to classify study designs correctly.
Source: Frisk et al.,
Scientific Reports 2023
Source: Nerli et al.,
JAMA Network Open 2024
9. CBT is placed within a disease-related treatment framework even though current guidelines explicitly draw a different boundary
The chapter presents CBT as a treatment for CFS and discusses “behavioural activation”, illness acceptance, activity patterns and illness behaviour.
The current guideline position is substantially clearer:
NICE expressly states that CBT is not a cure for ME/CFS.
It may be offered to people with ME/CFS if they wish to receive support in managing symptoms, maintaining or improving functioning, and coping with the impact of living with a chronic illness.
NICE also explicitly states that CBT for ME/CFS should not be based on the assumption that abnormal illness beliefs and behaviours are the underlying cause of the illness.
Of course, studies and meta-analyses exist that report improvements in subjective fatigue and functional measures under CBT, including Kuut et al. 2024. This does not, however, justify a causal psychological model of the disease or the presentation of CBT as a disease-modifying treatment.
In addition, the randomised controlled PsyLoCo trial published in July 2026 found no significant superiority of the manualised psychotherapeutic group intervention over treatment as usual—neither in somatic symptom burden nor in depression or anxiety. The study was small and exploratory and should therefore not be overinterpreted; nevertheless, it does contradict any assumption that the efficacy of psychotherapeutic treatment in Post-COVID can simply be taken for granted.
