Category: Psychiatry/Psychology

Patients with severe ME/CFS deserve better than unproven theories

Rapid Response:

Patients with severe ME/CFS deserve better than unproven theories

Dear Editor

Miller et al argue that chronic fatigue conditions are “a dysfunctional biological response orchestrated in the brain, influenced by expectations and conditioned responses,” and as a result, even people with severe ME/CFS can recover by “reframing beliefs about illness, along with specialist rehabilitation.”

Interventions based on this model have been tested in randomised trials in people since the 1990s in people with mild to moderate symptoms. Many of the participants would not have had ME/CFS as currently diagnosed, which carries a higher risk of harm from exertion. [1-3] Even in that easier context, short-term effects have been negligible or modest, without longterm benefits. Harms were not thoroughly studied. [1-3] This does not amount to strong evidence of substantial symptomatic improvement, let alone disease modification or full recovery.

Miller et al offer no direct strong evidence to support their claim that with their approach, “even those with severe ME/CFS can recover.” They cite the experience of a unit in Leeds, based on charts of discharged patients from a quality assurance report, where no patients were rated as “not at all ill” on discharge. [4] This kind of data is not defined as research, intended to be generalisable to other patients. [5] It was a very small group, too: Only six of the patients in that report had the diagnosis ME/CFS.

The weight of the authors’ argument, then, relies on their pathophysiologic rationale, which does not account for the full range of physical impacts of the illness. They point to other literature positing similar hypotheses, but these theories remain unproven. The pathophysiology of ME/CFS remains uncertain, [1-3] and it is not even clear that there is just one type of ME/CFS with the same underlying mechanisms. [6] Heterogeneous results in studies that have attempted to establish a core part of the model – that activity level and biological impairment are related – may be related to varying diagnostic criteria. [7]

Medicine has a long history of ascribing beliefs and/or responses to stress as the cause of diseases that were not yet fully understood. It wasn’t all that long ago that asthma, rheumatoid arthritis, and peptic ulcers fell into this category. [8] It’s been proven wrong so often now, we should be highly skeptical of these theories.

Perhaps part of why psychologically-based rationales for disease can be widely accepted is because the harm this can do is underappreciated. Miller et al argued that their narrative inspires hope, and people with severe ME/CFS deserve that. But when the unproven theory can’t deliver on the claims, what then? In a study Miller et al cited, researchers found that being told the disease was psychosomatic was the most common reason for suicidal thoughts for people with ME/CFS. [9] It’s not the first study to suggest that being told they are effectively to blame for not recovering is a contributing factor to the increased risk of suicidality in people with ME/CFS. [10]

A critical part of hope for people suffering illness is being able to trust that the medical community will work objectively to find better treatments and ways to support them, rather than promote unproven theories. People with ME/CFS deserve better than being told that their minds can overcome what’s the matter with their bodies – if only they try hard enough, for long enough.

References

1. National Institute for Health and Care Excellence. Myalgic encephalomyelitis (or encephalopathy)/chronic fatigue syndrome: diagnosis and management. 29 Oct 2021. https://www.nice.org.uk/guidance/ng206

2. Chou R, McDonagh M, Griffin JC, Grusing S. Management of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): An Updated Systematic Evidence Review prepared for Centers for Disease Control and Prevention. 2022. https://stacks.cdc.gov/view/cdc/156092

3. Institute for Quality and Efficiency in Health Care (IQWiG). Current scientific knowledge on myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). 2023. https://www.iqwig.de/en/projects/n21-01.html

4. Leeds and York Partnership NHS Foundation Trust. National Inpatient Centre for Psychological Medicine: annual review 2020-21. May 2021. https://www.leedsandyorkpft.nhs.uk/our-services/wp-content/uploads/sites…

5. Health Research Authority. Defining research. October 2022. https://www.hra-decisiontools.org.uk/research/docs/DefiningResearchTable…

6. Bastos VC, Greene KA, Tabachnikova A, et al. Cerebrospinal fluid immune phenotyping reveals distinct immunotypes of myalgic encephalomyelitis/chronic fatigue syndrome. J Immunol 2025;vkaf087. doi:10.1093/jimmun/vkaf087 pmid:40373264

7. Sunnquist M, Jason LA. A reexamination of the cognitive behavioral model of chronic fatigue syndrome. J Clin Psychol 2018;74:7. doi:10.1002/jclp.22593 pmid:29457646

8. Hange D, Bengtsson C, Sundh V, Bjorkelund. The natural history of psychosomatic symptoms and their association with psychological symptoms: Observations from the Population Study of Women in Gothenburg. Eur J Gen Pract 2007;13:2. doi:10.1080/13814780701377497 pmid:17534741

9. König RS, Paris DH, Sollberger M, Tschopp R. Identifying the mental health burden in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients in Switzerland: A pilot study. Heliyon 2024;10:e27031. doi:10.1016/j.heliyon.2024.e27031 pmid:3843435

10. Chu L, Elliott M, Stein E, Jason LA. Identifying and managing suicidality in Myalgic Encephalitis/Chronic Fatigue Syndrome. Healthcare (Basel) 2021;9:6. doi:10.3390/healthcare9060629 pmid:34070367

Source: Hilda Bastian. BMJ 2025;389:r977 https://www.bmj.com/content/389/bmj.r977/rr-30

The impact of leading questions on ME/CFS research: bias and stigma in study design

Abstract:

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex and often misunderstood illness, characterized by post-exertional malaise, unrefreshing sleep, and cognitive impairments.

Objective: To investigate how question phrasing in ME/CFS research may influence participant attributions of fatigue/energy problems and unintentionally reinforce psychosomatic assumptions.

Methods: A total of 2248 individuals with ME/CFS from an international sample completed a survey assessing fatigue-related attributions. We analyzed how question wording influenced whether participants attributed their symptoms to physical or psychosocial causes. Particular focus was given to a fatigue attribution item that framed causes in terms of ‘personal life’ or ‘environmental factors.’

Results: Participants were significantly more likely to attribute their fatigue/energy problems to psychosocial factors when prompted with psychosocial framing. Many respondents who previously indicated physical causes as the primary source of their symptoms shifted to psychosocial explanations in response to the differently phrased item. This shift was especially pronounced among participants reporting higher levels of psychological distress.

Conclusions: Leading or biased question phrasing may distort participant responses in ME/CFS research, potentially inflating psychosomatic interpretations of the illness. Researchers should critically examine survey language to avoid introducing unintended bias that could compromise research validity and reinforce stigma.

Source: Campolattara, A. T. T., Jason, L. A., & Tuzzolino, K. C. (2025). The impact of leading questions on ME/CFS research: bias and stigma in study design. Fatigue: Biomedicine, Health & Behavior, 1–16. https://doi.org/10.1080/21641846.2025.2530338 https://www.tandfonline.com/doi/full/10.1080/21641846.2025.2530338

Unwilling or unable? Interpreting effort task performance in myalgic encephalomyelitis/chronic fatigue syndrome

Introduction:

In a recent, high-profile study of post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS), Walitt et al. (2024) assessed the performance of patients and healthy volunteers on the Effort-Expenditure for Rewards Task (EEfRT), among a host of other measures. The EEfRT is a widely used behavioral index of reward motivation and effort-based decision-making that requires repeatedly choosing between an easy task and a hard task, each involving rapid, repetitive button-pressing (Treadway et al., 2009). Walitt et al.’s study—the first to investigate effort-based decision-making in PI-ME/CFS—found that patients were less likely to choose the hard task than healthy volunteers. The authors interpreted this difference as evidence of altered “effort preference,” which they defined as “how much effort a person subjectively wants to exert” (p. 9). Walitt et al. concluded that “effort preference, not fatigue, is the defining motor behavior of this illness” (p. 10). Here we interrogate this conclusion. Were PI-ME/CFS patients less likely to choose the hard task because they wanted to exert less effort, consciously or otherwise? Or were they less able to complete the hard task, and thus chose it less often? We argue that the data support the latter interpretation.

Source: Kirvin-Quamme A, Kirke KD, Junge O, Edwards JCW, Holmes KJ. Unwilling or unable? Interpreting effort task performance in myalgic encephalomyelitis/chronic fatigue syndrome. Front Psychol. 2025 Jun 13;16:1593269. doi: 10.3389/fpsyg.2025.1593269. PMCID: PMC12202612. https://pmc.ncbi.nlm.nih.gov/articles/PMC12202612/ (Full text)

Reframing beliefs about their illness does not lead to recovery of tube-fed patients with very severe ME/CFS. Analysis of the BMJ article by Miller et al

Abstract:

The narrative which is presented by Miller et al. as new, has dominated the field of ME/CFS for the last 35 years. It has been tested by numerous studies and has been found to be ineffective and harmful, as concluded by for example NICE in 2021. Additionally, it does not lead to objective improvement and it has a negative instead of a positive effect on work and disability status.

What has happened over the last 35 years is that severely ill patients have been ridiculed, gaslit and ignored by the medical profession. These patients have lost hope in the part of the medical profession which has been instrumental in doing and promoting that. They have not lost hope to recover and they are all hoping to get effective pharmacological treatments sooner rather than later as changing their mindset does not lead to recovery. And if it does, then the diagnosis of ME/CFS was simply wrong.

Source: Vink, Mark and Vink-Niese, Friso, Reframing beliefs about their illness does not lead to recovery of tube-fed patients with very severe ME/CFS. Analysis of the BMJ article by Miller et al. (June 06, 2025). No., Available at SSRN: https://ssrn.com/abstract=5284667 https://papers.ssrn.com/sol3/papers.cfm?abstract_id=5284667 (Full text available as PDF file)

Case Report: The intersection of psychiatry and medicine: diagnostic and ethical insights from case studies

Abstract:

The intersection of psychiatry and medicine presents unique diagnostic and ethical challenges, particularly for conditions involving significant brain-body interactions, such as psychosomatic, somatopsychic, and complex systemic disorders. This article explores the historical and contemporary issues in diagnosing such conditions, emphasizing the fragmentation of medical and psychiatric knowledge, biases in clinical guidelines, and the mismanagement of complex illnesses.

Diagnostic errors often arise from insufficient integration between general medicine and psychiatry, compounded by the reliance on population-based guidelines that neglect individual patient needs. Misclassification of conditions like myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), Lyme disease, and fibromyalgia as psychosomatic or psychogenic has led to stigmatization and delayed care. While these conditions are referenced as emblematic examples of misclassified and poorly understood disorders, the five clinical cases discussed in this article do not directly illustrate these diseases. Instead, they exemplify shared diagnostic and ethical dilemmas at the medicine–psychiatry interface, including uncertainty, fragmentation, and the risk of epistemic injustice.

The article critically examines terms like medically unexplained symptoms and functional disorders, highlighting their limitations and potential for misuse. Case examples underscore the consequences of diagnostic inaccuracies and the urgent need for improved approaches. Ethical considerations are also explored, emphasizing respecting patient experiences, promoting individualized care, and acknowledging the inherent uncertainties in medical diagnosis.

Advances in technologies such as brain imaging and molecular diagnostics offer hope for bridging the gap between psychiatry and medicine, enabling more accurate assessments and better patient outcomes. The article concludes by advocating comprehensive training at the medicine-psychiatry interface and a patient-centered approach that integrates clinical observation, research insights, and a nuanced understanding of mind-body dynamics.

Source: Monaco F, Vignapiano A, D’Angelo M, Raffone F, Di Stefano V, Boccia A, Longobardi A, Gruttola BD, Fornaro M, Corrivetti G, Martino I, Steardo L, Steardo L Jr. Case Report: The intersection of psychiatry and medicine: diagnostic and ethical insights from case studies. Front Psychiatry. 2025 Apr 22;16:1576179. doi: 10.3389/fpsyt.2025.1576179. PMID: 40330647; PMCID: PMC12053010. https://pmc.ncbi.nlm.nih.gov/articles/PMC12053010/ (Full text)

The PACE Trial’s GET Manual for Therapists Exposes the Fixed Incremental Nature of Graded Exercise Therapy for ME/CFS

Abstract:

The British National Institute for Health and Care Excellence (NICE) published its updated guidelines for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in October 2021. NICE concluded, after an extensive review of the literature, that graded exercise therapy (GET) is harmful and should not be used, and that cognitive behavioural therapy (CBT) is only an adjunctive and not a curative treatment. An article by White et al., which is written by 51 researchers, claims that there are eight anomalies in the review process and the interpretation of the evidence by NICE. In this article, we reviewed the evidence they used to support their claims.

Their three most important claims are that NICE redefined the disease, that CBT and GET are effective, and that fixed incremental increases are not part of GET. However, our analysis shows that the disease was not redefined by NICE. Instead, it was redefined in the 1990s by a group of doctors, including a number of authors of White et al., when they erased the main characteristic of the disease (an abnormally delayed muscle recovery after trivial exertion, which, over the years, has evolved into post-exertional malaise) and replaced it with chronic disabling severe fatigue. Their own studies show that CBT and GET do not lead to a substantial improvement of the quality-of-life scores or a reduction in CFS symptom count, nor do they lead to objective improvement.

Also, both treatments have a negative instead of a positive effect on work and disability status. Moreover, a recent systematic review, which included one of the authors of White et al., showed that ME/CFS patients remain severely disabled after treatment with CBT. Our analysis of, for example, the PACE trial’s GET manual for therapists exposes the fixed incremental nature of GET.

Why the authors are not aware of that is unclear because eight of them were involved in the PACE trial. Three of them were centre leaders and its principal investigators, four others were also centre leaders, and another one was one of the three independent safety assessors of the trial. Moreover, many of these eight authors wrote, or were involved in writing, this manual.

In conclusion, our analysis shows that the arguments that are used to claim that there are eight anomalies in the review process and the interpretation of the evidence by NICE are anomalous and highlight the absence of evidence for the claims that are made. Furthermore, our analysis not only exposes the fixed incremental nature of GET, but also of CBT for ME/CFS.

Source:Vink M, Partyka-Vink K. The PACE Trial’s GET Manual for Therapists Exposes the Fixed Incremental Nature of Graded Exercise Therapy for ME/CFS. Life (Basel). 2025 Apr 2;15(4):584. doi: 10.3390/life15040584. PMID: 40283139. https://www.mdpi.com/2075-1729/15/4/584 (Full text)

Response to treatment in the Multiple Symptoms Study 3 trial

Letter:
Chistopher Burton and colleagues conducted an unblinded trial of a consultative intervention for 354 people with persistent physical symptoms but no identifiable “organic” cause. Patient Health Questionnaire-15 (PHQ-15) score, which is a brief, subjective, self-administered screen of severity of somatic complaints, was the primary outcome. This kind of trial design can be expected to produce modest positive outcomes, via expectation bias alone. No real-life, objective assessment of functioning was conducted.
The intervention involved up to four sessions with a general practitioner, offering patients “rational explanations” for their symptoms in the absence of known, falsifiable causes and helping patients to develop strategies for managing symptoms. Although the “rational explanations” are not described, they presumably did not include “organic” diseases or conditions.
Scores on the PHQ-15 range from 0 to 30. Recruited patients had scores from 10 to 20, indicating moderate severity. At the end of the study, the adjusted between-group difference of –1·82 did not reach the minimal clinically important difference of 2·3. The change is well within what would be expected from bias alone. The results therefore confirmed that the intervention was of limited, if any, practical benefit. However, the paper presents the findings as though they had shown the opposite.
Instead of the “rational explanations” promoted by the investigators, more straightforward and honest explanations—for example, we do not know what is causing symptoms—could easily have produced similar results. Patients desire resolution of symptoms and recovery of functions. The trial did not achieve this result. Post-intervention, participants continue to have an impaired quality of life and poor experiences of health care.
DT holds an academic position at the Center for Global Public Health at UC Berkeley, which is largely supported by crowdfunded donations directly to the university, many of them from patients with myalgic encephalomyelitis or chronic fatigue syndrome and related conditions that fall under the heading of persistent physical symptoms. JSC declares no competing interests.
Source: Joan S Crawford and David Tuller. Response to treatment in the Multiple Symptoms Study 3 trial.  The Lancet, Volume 405, Issue 10485, 1145 – 1146  https://link.springer.com/article/10.1007/s00421-025-05759-5 (Full text)

“I still can’t forget those words”: mixed methods study of the persisting impact on patients reporting psychosomatic and psychiatric misdiagnoses

Abstract:

Objectives: This research aimed to improve understanding of persisting impacts of patient-reported psychosomatic and psychiatric misdiagnoses on patients with systemic autoimmune rheumatic diseases (SARDs).
Methods: Mixed methods data from two SARDs cohorts were analysed (N = 1,543 and N = 1,853). Validated instruments and patient-designed questions were used to measure self-reported depression, anxiety and mental wellbeing, in addition to medical relationships and healthcare behaviours. Comparative tests were used to evaluate differences between patients reporting a psychosomatic and/or psychiatric misdiagnoses and other patients.
Results: Persisting adverse outcomes of perceived psychosomatic and psychiatric misdiagnoses were identified in multiple domains. This included >80% of patients reporting that it had damaged their self-worth, and 72% reporting that it still upset them. Patients reporting psychosomatic and/or psychiatric misdiagnoses had significantly lower mental wellbeing, and higher depression and anxiety levels (all p< 0.001), and lower levels of satisfaction with every aspect of medical care, compared with patients reporting no psychosomatic or psychiatric misdiagnoses. Psychosomatic and psychiatric misdiagnoses had varying associations with healthcare behaviours, including a significantly higher likelihood of under-reporting symptoms (p< 0.001) and healthcare avoidance (p= 0.012), but not with medication adherence (p= 0.2). Thematic analysis of qualitative data revealed that symptom under-reporting and healthcare avoidance often resulted from distrust and fear that symptoms would be disbelieved and misattributed again.
Conclusion: Patient-reported psychosomatic and psychiatric (mis)diagnoses are associated with persisting adverse impacts in multiple domains including mental health, medical relationships, self-worth, and some healthcare behaviours. Health services and clinicians should consider these potential adverse impacts on patients and offer support to reduce any persisting negative impacts.

Source: Melanie Sloan, Michael Bosley, Caroline Gordon, Thomas A Pollak, Farhana Mann, Efthalia Massou, Stephen Morris, Lynn Holloway, Rupert Harwood, Kate Middleton, Wendy Diment, James Brimicombe, Elliott Lever, Lucy Calderwood, Ellie Dalby, Elaine Dunbar, David D’Cruz, Felix Naughton, “I still can’t forget those words”: mixed methods study of the persisting impact on patients reporting psychosomatic and psychiatric misdiagnoses, Rheumatology, 2025;, keaf115, https://doi.org/10.1093/rheumatology/keaf115 https://academic.oup.com/rheumatology/advance-article/doi/10.1093/rheumatology/keaf115/8042899 (Full text available as PDF file)

Relationship between major depressive disorder and myalgic encephalomyelitis/chronic fatigue syndrome: a two-sample mendelian randomization study analysis

Abstract:

Major depressive disorder (MDD) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) frequently occur together; yet their causal relationship remains unclear. To investigate the potential genetic causal link between these conditions, we conducted a two-sample Mendelian randomization (MR) analysis.

Summary data from Genome-Wide Association Studies (GWAS) for MDD were sourced from the UK Biobank and the Psychiatric Genomics Consortium, while GWAS data for ME/CFS were retrieved from the UK Biobank. Inverse-variance weighting (IVW), the MR-Egger method, and weighted median, simple and weighted modes were used to perform the MR analysis. In addition, Cochrane’s Q-test was used to detect heterogeneity among the MR results. Horizontal pleiotropy was detected using the MR-Egger intercept and the MR pleiotropy residual sum and outlier (MR-PRESSO) tests. Leave-one-out analysis was performed to investigate the sensitivity of the association between MDD and ME/CFS.

The results of the MR analysis revealed no causal relationship between MDD and ME/CFS. The pleiotropy test revealed that causality bias was improbable, and no evidence of heterogeneity was found among the genetic variants. Finally, the leave-one-out test confirmed the stability and robustness of our findings.

Source: Song, W., Hou, X., Wu, M. et al. Relationship between major depressive disorder and myalgic encephalomyelitis/chronic fatigue syndrome: a two-sample mendelian randomization study analysis. Sci Rep 15, 1155 (2025). https://doi.org/10.1038/s41598-025-85217-6 https://www.nature.com/articles/s41598-025-85217-6 (Full text)

Re-visiting professional ethics in psychotherapy: reflections on the use of talking therapies as a supportive adjunct for myalgic encephalomyelitis/chronic fatigue syndrome and ‘medically unexplained symptoms’

Abstract:

Following years of debate over the effectiveness of cognitive behavioural therapy for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), public health bodies in the UK and beyond have determined that no psychotherapy is clinically proven for this patient group. In the field of ME/CFS and the wider arena of ‘medically unexplained symptoms’ (MUS), patient survey data and qualitative research capturing patient experiences and psychotherapist attitudes suggest that therapeutic practice may sometimes fall short of required ethical standards. This raises questions about how psychotherapists can safely support, as opposed to treat, people with these debilitating conditions.

We consider four ethical principles that feature throughout psychotherapists’ codes of practice, those of respect, competence, responsibility and integrity, and discuss examples of good and poor practice in this arena as evinced by recent empirical literature.

Following this, we offer a variety of suggestions to help strengthen ethical psychotherapy practice with patients with ME/CFS and other MUS. In terms of practitioner education, we recommend greater emphasis on humility, reflexivity and disability-affirming practices, exploration of personal as well professional ethics, and integration of patient expertise-by-experience, accompanied with the latest evidence, into foundational and ongoing training.

In terms of ongoing practice, we suggest consideration of formalised patient-focused feedback systems and greater transparency vis-à-vis patient access to clinical notes. Finally, we underline the importance of elevating patients from mere subjects to co-producers of psychotherapy research.

Source: Hunt J, Blease C. Re-visiting professional ethics in psychotherapy: reflections on the use of talking therapies as a supportive adjunct for myalgic encephalomyelitis/chronic fatigue syndrome and ‘medically unexplained symptoms’. J Med Ethics. 2024 Dec 31:jme-2023-109627. doi: 10.1136/jme-2023-109627. Epub ahead of print. PMID: 39740979. https://jme.bmj.com/content/early/2024/12/31/jme-2023-109627 (Full text)