ME/CFS is a common condition that can be very debilitating. It has been recognised as a serious disease and few would dispute the impact that it can have on many of those who have the condition. Doctors assessing applicants and claimants for pensions or insurance purposes will inevitably have to consider ME/CFS on a regular basis.

Opinions remain very divided over the causes of ME/CFS, the diagnosis, the terminology that should be used, the best treatment approach and the prognosis. Opinions may be strongly held, and are in some cases politicised, with small groups of activists mobilising sections of the media to argue on subjective rather than objective grounds for a change in approach, threatening those who disagree. The basis of this disagreement appears to be largely focussed on the mainstream view that the condition is biopsychosocial rather than biomedical.

A number of these challenges have been very intemperate including death threats to researchers and treating clinicians, personal attacks on them and their families and substantial disruption to their clinical practice (Hawkes, 2011). These tactics appear to have been deployed whenever the subject has been officially debated with the result that attempts to produce clear scientifically based guidelines appear to have been impacted by personal beliefs, threats and media polarisation. There was clear concern from the medical community in relation to the attempts by the US Institute of Medicine to rationalise the debate in 2015, noting that the IOM were heavily and negatively lobbied by the ME/CFS community for undertaking the work (2015).

It is not unusual for medical assessors for pensions to experience similar issues if they do not support the application. It is important not to let such concerns influence opinions. If necessary, pensions assessors should withdraw from the process if this arises and inform the employer, pensions authority or trustees.

Some activists refuse to accept any suggestion that there may be a psychosocial component. Many patients are, however, happy to accept a psychosocial component, and recognise psychosocial issues as relevant to their symptoms and difficulties. Furthermore, some activists are opposed to any treatment aimed at improving function, including cognitive behavioural therapy (CBT) and graded exercise therapy (GET).

The current NICE guidelines have been careful to avoid reference to psychological issues or mental health issues although they do acknowledge the importance of being sensitive to ‘beliefs and values’ and how these might ‘influence their experience, understanding and choice of management’. The guidelines also acknowledge that treating clinicians may include clinical or counselling psychologists. The guidelines refer to ME/CFS as a ‘medical condition’ and do not at any point refer to it as a ‘disease’. The guidelines recommend management of pain ‘according to best practice’ and do not specify that psychological therapy for pain should not be undertaken. The guidelines state that neither GET nor CBT should be offered as a ‘cure’ for ME/CFS, but state that CBT should only be offered ‘to support people who live with ME/CFS to manage their symptoms, improve their functioning, and reduce the distress associated with having a chronic illness’.

Most disease has a primary biomedical basis, however the response of patients differs significantly, so the functional outcome in the short and long term represents a combination of the biological healing process or residual biological disease alongside the psychological and social factors. As a simple example, patients of the same age and same physical health having the same surgical procedure will return to work at differing times that depend mostly on the advice given by treating clinicians, advice from friends, family and employers, and their own tolerance of symptoms and their own desire to return to work. The functional outcome of all disease process is therefore biopsychosocial. To suggest that ME/CFS is the only condition known to man that does not have a psychosocial component is both illogical and irrational.

The opposition to GET is of particular concern. The trials for GET defined the therapy as a collaborative, negotiated and symptom-dependent therapy. Opponents defined it as mandating fixed increments of change. Some therapists may well have interpreted the guidelines as mandating fixed increments, and it is unsurprising that their approach was unsuccessful. There was particular concern when the 2021 NICE guidelines accepted the lobbyist’s viewpoint and failed to follow the normal NICE approach of synthesising trial evidence (White et al., 2023). Many patients with ME/CFS improve in function, some to normal function including high levels of competitive sport. They can only achieve this by progressively increasing activity levels to regain physical fitness. Opposition to any attempt to increase activity levels is both illogical and unhelpful.

Terminology and diagnostic criteria

The terminology used has also been challenged, with some patients preferring the term CFS, some ‘chronic fatigue syndrome’, some ‘myalgic encephalomyelitis’, some ‘ME’, some ‘ME/CFS’, some ‘CFS/ME, some ‘CFSME’ and some ‘systemic exertional intolerance disease’ (SEID). The condition was initially referred to as myalgic encephalomyelitis or encephalopathy (ME). Patients liked this label and accepted the label, however it soon became apparent that there was no evidence of any clear disease process of brain or muscles, so it was a misnomer. Attempts to change terminology have been fraught, seen by some as attempts to redefine the condition as psychological rather than physical.  

There are no clearly recognised biological markers or objective tests for the condition. Assessment has to be based on the patient’s history and their subjectively assessed symptomatology. Much is said about there being ‘no cure’ and that ‘complete and sustained recovery may be rare’. If there are no recognised biological markers or objective tests to quantify the condition, there are equally no recognised biological markers or objective tests to quantify ‘cure’ or ‘complete and sustained recovery’. The concept of their being ‘no cure’ is unscientific and inappropriate. The main issue for patients is not the presence or absence of any fatigue and pain which are very common symptoms experienced by everyone, but the severity and functional impact of their fatigue and pain. It would be much more helpful if this was the main consideration for patients and therapists. Telling a patient ‘there is no cure’ is deeply unhelpful and inappropriate; it is highly unlikely to aid recovery and engagement with therapy, and may well prevent any substantial improvement.

There are many different diagnostic tools available, Each diagnostic process is slightly different which can be confusing and makes research difficult (Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue et al., 2015, 2015). It is even more confusing when there are several potential choices of diagnostic category in WHO ICD10, a classification compiled in the 1980s when there was very little understanding of the biological factors underlying ME/CFS and no evidence for a neurological basis even though it is classified as a disorder of the brain.  One classification, for post-viral fatigue, applies to ‘benign myalgic encephalomyelitis’; this term has been discontinued as the term ‘benign’ is not considered appropriate.

We have now reached a point where perhaps the only thing about ME/CFS that all practitioners agree on is that the condition is not purely neurological, and the current classification of G93.3 may not be appropriate. There is, however, increasing evidence that the issue is at least in part as a result of ‘central sensitisation’ where the brain appears to be over-processing fatigue symptoms, or responding differently to physiological fatigue. In the absence of any agreement on an alternative, it may be best to stick with the current classification (Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue et al., 2015) accepting that it is just a label and this may not reflect the underlying cause, treatment or prognosis.

Many clinicians consider that they are treating patients rather than labels, so take a flexible approach to diagnosis, allowing the patient to choose the label they prefer, and focussing more on the best option for management of the condition to suit the patient. It is important to respect the label chosen by the patient. I have referred to the condition as ME/CFS as this is the label currently preferred by the ME Association.

Diagnosis generally involves assessment against a standard list of symptoms. This is in essence a questionnaire assessment. Questionnaires are used in many areas of medicine, particularly in psychiatry, and can be useful. They are, however, recognised to be subjective with limited objectivity. They are useful in research where a statistical reliability can be calculated and applied to the results. They are less useful in individual diagnosis, and clinicians are always advised not to rely entirely on questionnaire results, but also consider the history and presentation. Diagnosis should be based on clinical judgement.

It would be scientifically inappropriate to regard questionnaire assessment of ME/CFS any differently. Therefore, the fact that a patient scores as severe, or meets the most stringent criteria for ME/CFS on questionnaire does not automatically mean they have severe illness. Other factors need to be taken into account. This may explain why some patients with severe illness on questionnaire make a complete recovery while other patients with relatively mild illness show no improvement in symptoms over many years of support and therapy.

Overlap with other conditions

There are several recognised conditions where patients report severe symptoms without tests showing a clear underlying pathology. These include symptoms of chronic fatigue, chronic widespread pain (fibromyalgia syndrome), chronic back pain or neck pain, complex regional pain syndrome, chronic headaches and functional neurological disorders. Central sensitisation to symptoms of fatigue is also likely to apply to other symptoms, particularly pain, and pain is often reported alongside fatigue as a disabling symptom. A patient presenting with chronic fatigue and chronic widespread pain may receive a diagnosis of ME/CFS or fibromyalgia syndrome or both.

Many clinicians do not regard these as being separate conditions, but as part of a spectrum of symptoms and presentations, with significant overlap often seen. It is likely that therapeutic approaches for one set of symptoms will be of benefit to others, and it is unlikely that any particular therapy for one will be harmful to another. Telling patients that they have multiple conditions is not always helpful and can lead to significant health anxiety. It may be better to choose one label alone that best describes the patient’s symptoms.

It is also common to see these symptoms alongside symptoms of mental illness, particularly depression. Depression may be as a consequence of the chronic symptoms or may have been the precipitating factor for central sensitisation. Clinicians recognise the importance of treating symptoms of depression, noting that in many cases meaningful improvement in function and/or severity of symptoms often requires prior treatment of depression. Some antidepressant medications have central actions on pain and may therefore be of particular value in treating associated chronic pain conditions (such as Amitriptyline and Duloxetine).

Many medications used to treat pain or depression are noted to cause significant fatigue and cognitive dysfunction as a side effect. This applies particularly to opioids and gabapentinoids but also to many antidepressants. It is likely that many patients who report fatigue and cognitive dysfunction (often referred to as ‘brain fog’) are primarily experiencing side effects of medication prescribed for chronic pain. Adjusting medication with a holistic overview can often lead to substantial improvements in all symptoms, and substantial improvements in function. It is of particular concern that opioids and gabapentinoids are no longer considered appropriate for long-term treatment of pain, yet are often prescribed (NICE, 2021).

There is increasing evidence of overlap between symptoms of depression and biological processes that is outlined below.

The evidence base

There is now a substantial problem in relation to research into ME/CFS. Much of the research base is poor, often because studies are cross-sectional rather than longitudinal, so aetiology cannot be reliably determined. Longitudinal studies are inevitably more challenging and costly. Furthermore, researchers able to undertake longitudinal studies are usually those running clinics treating patients. As noted above, some patients are very sensitive to research outcomes and will challenge any result that does not meet with their own preconceptions. The inevitable result is that many clinicians in the best position to undertake and publish research will be very reluctant to do so.

Cross-sectional studies cannot give reliable answers about cause or prognosis, and a number of research studies have not selected appropriate controls to support their theories. Some researchers have controversial backgrounds, and their studies may not be as objective as they should. This has been the case for some fifty years, so it is unlikely to change soon.

I have included references to a number of scientific papers below. Many have flaws, as noted above, however they have all been published in recognised journals, and represent the views of some if not all doctors involved in treating ME/CFS. Some are controversial, so it is important to be circumspect and flexible when considering the findings and recommendations in all of these.

It is very important when considering patients with ME/CFS that everyone involved, patients and their families and employers, understands these limitations, and avoid taking a simplistic or dogmatic view. Most doctors involved in ME/CFS agree that there are multiple factors involved in developing the condition, and multiple factors involved in treatment and prognosis. It is important to consider all these factors if the best possible outcome is to be achieved.

Antinuclear antibodies (ANA) are often seen in blood tests from patients with ME/CFS. ANA are general markers of an immune response and are commonly found in the general population, with prevalence rates of around 20-50%, greater in women and greater in older people. Their presence is not a marker of either illness or disease as many apparently healthy, symptom-free individuals have significantly raised levels of ANA (Hayashi et al., 2008, Marin et al., 2009, Selmi et al., 2016). There is evidence for raised levels in specific auto-immune diseases such as SLE, chronic pain, and also for various occupational and environmental exposures (Cooper et al., 2006, Dirckx et al., 2015). The presence of raised ANA in patients with ME/CFS is therefore of uncertain aetiology, and it cannot be considered diagnostic. It also cannot be considered specific for infection, a marker of infection or past infection.

There are significant links between depressive disorder, and the lifestyle factors diet, sleep and exercise. These lifestyle factors have a substantial influence on neurotransmitter processes, immune-inflammatory pathways, hypothalamic-pituitary-adrenal (HPA) axis disturbances, oxidative stress and antioxidant defence systems and mitochondrial disturbances (Gardner and Boles, 2011). In addition, there is emerging evidence that medication such as paracetamol and all classes of psychotropic drugs may damage mitochondria (Neustadt and Pieczenik, 2008). Poor diet, poor sleep and lack of exercise are closely associated with all these dysfunctional outcomes which in turn are likely to influence pathways associated with depression (Lopresti et al., 2013, Morava and Kozicz, 2013, Norheim et al., 2011). Poor diet, poor sleep and lack of exercise are also closely associated with ME/CFS. There are therefore good scientific reasons why the behaviours closely associated with ME/CFS symptoms will cause dysfunction in the HPA, mitochondria, immune-inflammatory pathways and oxidative stress, and why major depressive disorder is associated with ME/CFS symptoms (Romano et al., 2015). Thus, many biochemical and physiological abnormalities seen in patients with ME/CFS may be the result of their symptoms and response to symptoms rather than the cause of their symptoms.

Patients with ME/CFS have been found to have signs of mitochondrial dysfunction (Booth et al., 2012). There is a good reason to associate fatigue with mitochondrial dysfunction, and fatigue is a hallmark symptom of known mitochondrial disease (Filler et al., 2014). Physiological stress, particularly from reactive oxygen species, can impair mitochondrial function with reduced levels of ATP and in turn lead to the symptoms of pain and fatigue (Meeus et al., 2013). Changes in lifestyle have been shown to lead to changes in mitochondrial dysfunction (Myhill et al., 2013, 2015), suggesting that the dysfunction may not be the cause of symptoms, but a product of the lifestyle associated with the symptoms. Furthermore, mitochondrial dysfunction is relatively common, and in many cases it appears asymptomatic. It is associated with sedentary lifestyle, poor diet, some medications, and lack of sleep. The overlap between ‘normal’ and patients with ME/CFS is such that it cannot be considered the cause of symptoms, or diagnostic for ME/CFS although it may well be a result of the associated symptoms and behaviours (Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue et al., 2015).

Patients with ME/CFS classically present with early fatigue, lower exercise tolerance, and post-exertional malaise all suggesting a problem with cardiorespiratory fitness and/or neuromuscular function. A major difficulty with all studies is the need to identify matched controls. Often, controls are ‘healthy’ and not selected because of matched activity levels. When researching cardiorespiratory fitness, there will inevitably be differences between those of differing activity levels, and as a result it is difficult to demonstrate that the differences seen in studies reflect an underlying difference in physiology due to a disease process or due to low activity levels. When reviewing studies into cardiorespiratory function and ME/CFS, it is important to consider selection of controls.

Maximum exercise capacity is generally expressed as VO2Max, and while patients with ME/CFS generally have a lower-than-average VO2Max, the overlap between patients and controls fails to demonstrate significance. Many patients have significantly higher levels of VO2Max than inactive but healthy controls. There is evidence to suggest that post-exertional malaise relates to a dysfunctional anaerobic threshold. Retesting VO2Max at 24 hours has demonstrated a lower level in CFS patients compared with controls. While this may well explain some of the post-exertional malaise reported and could reflect a specific marker for ME/CFS, the differences seen, of around 5% in VO2Max and 11% ventilatory threshold do not explain the overall severity of the symptoms reported; there is significant overlap between values for patients and controls. Both values can be improved by regular exercise, and there is evidence that this can be achieved by patients with ME/CFS. This evidence shows that a difference in anaerobic threshold could play a part in the development and persistence of symptoms but is not the only factor and there is a lack of consistency across studies (Zambolin et al., 2022, Snell et al., 2013).

There is evidence to suggest a neurological basis, with central sensitisation representing a major factor. Studies suggest a role for immune activation or autoimmune activation leading to altered CNS function. This is of particular relevance to post-viral fatigue with prolonged immune dysfunction playing a significant part, but it does not explain the long-term symptoms or post-exertional malaise. Low fatigue tolerance is likely to be a centrally mediated issue, but without a pathological explanation (Choutka et al., 2022).

There is evidence that the gut biome plays a significant role in development and persistence of symptoms. Deficient butyrate-producing capacity associated with bacterial network disturbance is associated with symptoms and it is entirely plausible that the health of the gut plays a part. Patients with ME/CFS are likely to be relatively immunocompromised due to an inactive lifestyle and relatively sensitive to symptoms of infection, leading to a predisposition to seek treatment and be prescribed antibiotics. Frequent use of antibiotics can lead to major disruption to the natural biome (Guo et al., 2023).

Weight will inevitably affect fatigue, and most diagnostic criteria will not support a diagnosis of ME/CFS above a certain weight (Flores et al., 2013). The Fukuda criteria exclude anyone with a BMI over 45kg/m2 (Fukuda et al., 1994). This was reduced to a BMI of 40kg/m2 by the amended criteria (Reeves et al., 2003). Some criteria suggest that once diagnosed, the diagnosis remains appropriate even if the patient has increased weight above BMI 40. Nevertheless, a good functional recovery is substantially less likely in a patient living with very high obesity. The factors that predisposed to development of ME/CFS may also predispose to weight gain, and good support should be provided to help identify ways to achieve weight reduction in order to help with functional improvement.

Epidemiological studies show consistently that ME/CFS is significantly more common in women, and particularly those who have experienced childhood trauma. (Heim et al., 2009, De Venter et al., 2017, Afari et al., 2014).


A large epidemiological study in UK(Collin et al., 2017) showed very clearly that there was an unexplained 75% decline in cases of CFS over the 25 years from 1990 to 2015 with no corresponding increase in any other similar or associated condition.

Most experts are of the view that in the ‘wild’ state where there is no attempt to diagnose or treat, and most patients develop symptoms following a significant viral infection, the great majority of patients make a full recovery in a couple of years. It is possible that the process of diagnosis and intervention is harmful in at least some cases. This could explain why the incidence of ME/CFS has declined so dramatically over the twenty-five years from 1990, as GPs take the view that the best approach is to advise the patient they will recover fully, not label them as having ME/CFS and allow them to develop their own coping strategies for their symptoms. This also makes research extremely difficult, as the process of starting research with a diagnosis could automatically have a negative effect on the outcome.

Furthermore, there is a clear association between CFS and higher socioeconomic groups (Collin et al., 2017). The only explanation for this is that the condition is related to the psychosocial environment, in particular the response to patients from their family, friends and colleagues, and their ability to become less active in response to their symptoms.

There is evidence that those joining self-help groups develop worse symptoms (Sharpe et al., 1992). This also explains why patients whose family and friends reinforce illness behaviour by focussing on their symptoms, preventing them from engaging with activity and encouraging the view that they will never get better appear to have a worse prognosis than those who have a more independent approach and whose family and friends just accept them as they are.

A study looked at factors leading to persistent symptoms including chronic fatigue following COVID-19 infection. This was a very large cross-sectional study in France, and it found that the strongest factor in reporting of persistent symptoms was the belief that the person had COVID-19 rather than actually having positive serology (Matta et al., 2022). This also points to psychosocial factors rather than biological factors in the development and persistence of chronic fatigue.

The most effective therapeutic approach starts with pacing. This is supported by a substantial body of evidence and all therapeutic guidelines (Lancet, 2021).

Overall, there is no clear evidence for a purely biological cause or a purely psychological cause. The large number of factors identified, all with significant evidence that they play a part in the condition strongly indicates that the condition is multifactorial. It is likely that some individuals have a vulnerability to developing the condition through a combination of genetic physiological factors, immune function, personality traits, and life experiences. A triggering viral infection is likely to play a large part in developing the condition. Perpetuation of symptoms is likely to reflect all these factors alongside the physiological impact of low activity levels, the psychological impact of a considerable change in social interaction and work interaction and concurrent depressive illness, reinforcing behaviour by friends, family and treating clinicians and personal beliefs and behaviours.

Long-term outcomes and prognosis

Few studies have followed the outcomes of patients with ME/CFS, and there is significant controversy over some results. Measuring outcomes objectively when there is no objective diagnostic test other than assessment of subjective symptoms is inevitably challenging. There are, however, a number of studies showing that some patients make full or good recoveries. Studies have also been done in patients with fibromyalgia who often have fatigue that meets the diagnostic criteria for ME/CFS, and who are considered by some to have the same underlying condition. Studies considering only symptom improvement generally find a relatively small number reporting complete resolution of symptoms. Many more are reported to improve. When functional status and change are reported, the outcomes are significantly different. A substantial majority of patients presenting with fibromyalgia syndrome or with a long history of the condition are in employment, and many patients with ME/CFS are able to engage with employment. (Walitt et al., 2011, Cairns and Hotopf, 2005, Deale et al., 2001, Marlin et al., 1998, Nisenbaum et al., 2003, Joyce et al., 1997, Andersen et al., 2004, Hill et al., 1999, Vercoulen et al., 1996, Stevelink et al., 2022, Stevelink et al., 2019).

It should be noted that patients with ME/CFS may well change employment to one that his less physically or cognitively demanding, or with fewer hours or greater flexibility. It should also be noted that some patients will follow a relapsing remitting course, with periods of perhaps several years in employment, then a period when they are unable to work of between a few months and several years, and then another period of several years in employment. This pattern may repeat throughout their working life.

Most studies looking at long-term outcomes have relatively short follow-up periods, usually less than five years. It is extremely difficult to undertake a longer study. It is common to see patients with a past history of ME/CFS returning to employment, often many years after initial diagnosis, and their employment history often shows a cyclical pattern of employment, illness and re-employment, with periods of several years when they are unwell and several years when they are capable of employment, some full time in relatively challenging roles. Some make a complete functional recovery that can include a return to international competitive sport (Hemmings, 2024). Results from studies that took place over a few years are often used as evidence that patients can never recover and should be considered permanently incapable of working for periods of perhaps twenty or thirty years. Such an extrapolation is clearly unsupported by the evidence and inappropriate particularly for a condition that is likely to have a significant psychosocial aetiology; it can reinforce negative perceptions and therefore significantly affect long-term outcome.

Overall, the evidence indicates a complex interaction of biological, physiological, pathological and psychosocial factors in the development and persistence of ME/CFS. It is likely that patients have a predisposition to developing the condition, that this relates to physiology, immunology, and personality traits, and persistence relates also to pathology, activity levels and psychosocial factors. The variability in outcomes indicates that it is inappropriate to consider the condition as one simple process with all patients likely to follow the same course, but each patient is different. A formulation of the aetiology of their condition requires a careful review of all the factors, and any prognosis must consider biological and psychosocial factors. It is wrong to assume all patients can get better, and equally wrong to assume none can get better. It is unhelpful to apply a binary measure of outcome. The goal should be functional improvement, recognising that all individuals seek to achieve a balance between functional capacity and symptoms, and there will be a difference between what they could achieve and what they choose to achieve.

The evidence overall indicates that while a complete recovery with no symptoms of fatigue or pain is relatively unlikely, the majority of patients will report significant functional improvements over the long term. There is no overall reason why most patients cannot work at any stage in future, although many will benefit from a reduction in physical demands, a reduction in psychological demands, a reduction in hours and a flexible approach. A return to a particularly demanding role such as the armed forces, police or firefighting may well be less likely, but a redeployment to a more suitable role will help with both psychological and physical rehabilitation. Some will not believe they can return to work. Some will not be able to return to work. Some will choose not to return to work. There is no objectively reliable way to easily differentiate between these three groups, particularly in the short term.

Pensions assessments

When assessing applicants for pensions with a history of ME/CFS, it is particularly important to understand the evidence base, and apply it carefully and logically. I have summarised the various strands of evidence from the literature. Pensions assessors need to develop a thorough understanding through their own research in order to pull the various strands of evidence together and develop both a formulation of the reason(s) why the applicant has developed the condition and their most likely prognosis. It should also be noted that for a condition where activists are clearly opposed to any therapy likely to improve function, there will be pensions applicants who adopt this approach. Statistical analysis alone is unlikely to be helpful when patients refuse to engage with therapy.

Many will also be in the process of seeking and accessing benefits to support them, and in order to do so they have to put often considerable effort into proving how ill they are. It is unreasonable to expect someone in this situation to also put considerable effort into trying to engage with therapy and improve function. We recognise this as a problem across medicine when patients are making claims or seeking benefits. Therapists in other areas will often delay the start of therapy until the claim process is complete in order to enable the patient to focus on the therapy and recognise therapeutic gains as a positive step. Some of those involved in treatment for ME/CFS may have their own beliefs related to causation and prognosis that may well not align with the general scientific view and the overall evidence, and it is important to consider all reports including specialist reports carefully and critically.

It is particularly important to look at past employment history, and past medical experiences; these often provide a good indicator of the likely future prognosis. It is also important to compare reported symptoms and function with observed behaviour. If there is a clear disconnect between reported function and observed function, for example if someone claims they can cycle for 50km every day but are so fatigued and weak they are unable to walk, this would not support the view that they are consistent and reliable in their history and presentation, and it would be difficult to justify an opinion that they are permanently incapable of any work. Taking a full social history including all daily activities may demonstrate a consistent picture supporting their reported disability or an inconsistent picture that suggests that their presentation is unreliable.

Any assessment for pensions will need to consider the history of the condition over the long term, all factors likely to have influenced the course of the illness, and beliefs and behaviours that are likely to influence prognosis. It is also important to consider other chronic diseases and the relationship between the various conditions. The assessor will need to consider whether the current presentation is most likely to reflect a period of relapse with an expected period of remission, following a pattern throughout life. Is the pattern of relapse and remission a progressive one, and have they reached a point where some improvement is likely but insufficient to support a return to any work? It is important to consider what therapy has been provided and how the applicant has responded. Past and current psychosocial events and influences must be considered. The likely course of co-existing chronic diseases should be considered, and the likely future impact of psychosocial circumstances and events. Most importantly, the timeline to normal pension age is of critical importance. If the applicant is only months or a few years away from normal pension age, the likelihood of substantial improvement may be less than for someone who has thirty or even forty years to go before normal pension age.

There is no evidence that can enable a simple algorithmic approach to pensions assessments. All factors must be considered, and any opinion needs to be justified, considering past history, patterns of illness, severity of current symptoms, personal circumstances and beliefs and likely changes to circumstances as well as symptoms. The impact of co-existing morbidity must also be considered. The expectation is that some applications for pensions due to ME/CFS will be supported while others will not.


2015. What's in a name? Systemic exertion intolerance disease. Lancet, 385, 663.

AFARI, N., AHUMADA, S. M., WRIGHT, L. J., MOSTOUFI, S., GOLNARI, G., REIS, V. & CUNEO, J. G. 2014. Psychological trauma and functional somatic syndromes: a systematic review and meta-analysis. Psychosom Med, 76, 2-11.

ANDERSEN, M. M., PERMIN, H. & ALBRECHT, F. 2004. Illness and disability in Danish Chronic Fatigue Syndrome patients at diagnosis and 5-year follow-up. J Psychosom Res, 56, 217-29.

BOOTH, N. E., MYHILL, S. & MCLAREN-HOWARD, J. 2012. Mitochondrial dysfunction and the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Int J Clin Exp Med, 5, 208-20.

CAIRNS, R. & HOTOPF, M. 2005. A systematic review describing the prognosis of chronic fatigue syndrome. Occup Med (Lond), 55, 20-31.

CHOUTKA, J., JANSARI, V., HORNIG, M. & IWASAKI, A. 2022. Unexplained post-acute infection syndromes. Nat Med, 28, 911-923.

COLLIN, S. M., BAKKEN, I. J., NAZARETH, I., CRAWLEY, E. & WHITE, P. D. 2017. Trends in the incidence of chronic fatigue syndrome and fibromyalgia in the UK, 2001-2013: a Clinical Practice Research Datalink study. J R Soc Med, 110, 231-244.

COMMITTEE ON THE DIAGNOSTIC CRITERIA FOR MYALGIC ENCEPHALOMYELITIS/CHRONIC FATIGUE, S., BOARD ON THE HEALTH OF SELECT, P. & INSTITUTE OF, M. 2015. The National Academies Collection: Reports funded by National Institutes of Health. Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness. Washington (DC): National Academies Press (US)

Copyright 2015 by the National Academy of Sciences. All rights reserved.

COOPER, G. S., PARKS, C. G., SCHUR, P. S. & FRASER, P. A. 2006. Occupational and environmental associations with antinuclear antibodies in a general population sample. J Toxicol Environ Health A, 69, 2063-9.

DE VENTER, M., ILLEGEMS, J., VAN ROYEN, R., MOORKENS, G., SABBE, B. G. C. & VAN DEN EEDE, F. 2017. Differential effects of childhood trauma subtypes on fatigue and physical functioning in chronic fatigue syndrome. Compr Psychiatry, 78, 76-82.

DEALE, A., HUSAIN, K., CHALDER, T. & WESSELY, S. 2001. Long-term outcome of cognitive behavior therapy versus relaxation therapy for chronic fatigue syndrome: a 5-year follow-up study. Am J Psychiatry, 158, 2038-42.

DIRCKX, M., SCHREURS, M. W., DE MOS, M., STRONKS, D. L. & HUYGEN, F. J. 2015. The prevalence of autoantibodies in complex regional pain syndrome type I. Mediators Inflamm, 2015, 718201.

FILLER, K., LYON, D., BENNETT, J., MCCAIN, N., ELSWICK, R., LUKKAHATAI, N. & SALIGAN, L. N. 2014. Association of Mitochondrial Dysfunction and Fatigue: A Review of the Literature. BBA Clin, 1, 12-23.

FLORES, S., BROWN, A., ADEOYE, S., JASON, L. A. & EVANS, M. 2013. Examining the impact of obesity on individuals with chronic fatigue syndrome. Workplace Health Saf, 61, 299-307.

FUKUDA, K., STRAUS, S. E., HICKIE, I., SHARPE, M. C., DOBBINS, J. G. & KOMAROFF, A. 1994. The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med, 121, 953-9.

GARDNER, A. & BOLES, R. G. 2011. Beyond the serotonin hypothesis: mitochondria, inflammation and neurodegeneration in major depression and affective spectrum disorders. Prog Neuropsychopharmacol Biol Psychiatry, 35, 730-43.

GUO, C., CHE, X., BRIESE, T., RANJAN, A., ALLICOCK, O., YATES, R. A., CHENG, A., MARCH, D., HORNIG, M., KOMAROFF, A. L., LEVINE, S., BATEMAN, L., VERNON, S. D., KLIMAS, N. G., MONTOYA, J. G., PETERSON, D. L., LIPKIN, W. I. & WILLIAMS, B. L. 2023. Deficient butyrate-producing capacity in the gut microbiome is associated with bacterial network disturbances and fatigue symptoms in ME/CFS. Cell Host Microbe, 31, 288-304.e8.

HAWKES, N. 2011. Dangers of research into chronic fatigue syndrome. BMJ, 342, d3780.

HAYASHI, N., KOSHIBA, M., NISHIMURA, K., SUGIYAMA, D., NAKAMURA, T., MORINOBU, S., KAWANO, S. & KUMAGAI, S. 2008. Prevalence of disease-specific antinuclear antibodies in general population: estimates from annual physical examinations of residents of a small town over a 5-year period. Mod Rheumatol, 18, 153-60.

HEIM, C., NATER, U. M., MALONEY, E., BONEVA, R., JONES, J. F. & REEVES, W. C. 2009. Childhood trauma and risk for chronic fatigue syndrome: association with neuroendocrine dysfunction. Arch Gen Psychiatry, 66, 72-80.

HEMMINGS, A. 2024. Anna's story [Online]. Available: [Accessed].

HILL, N. F., TIERSKY, L. A., SCAVALLA, V. R., LAVIETES, M. & NATELSON, B. H. 1999. Natural history of severe chronic fatigue syndrome. Arch Phys Med Rehabil, 80, 1090-4.

JOYCE, J., HOTOPF, M. & WESSELY, S. 1997. The prognosis of chronic fatigue and chronic fatigue syndrome: a systematic review. Qjm, 90, 223-33.

LANCET 2021. National Institute for Health and Care Excellence: Guidelines. Myalgic encephalomyelitis (or encephalopathy)/chronic fatigue syndrome: diagnosis and management. London: National Institute for Health and Care Excellence (NICE)

Copyright © NICE 2021.

LOPRESTI, A. L., HOOD, S. D. & DRUMMOND, P. D. 2013. A review of lifestyle factors that contribute to important pathways associated with major depression: diet, sleep and exercise. J Affect Disord, 148, 12-27.

MARIN, G. G., CARDIEL, M. H., CORNEJO, H. & VIVEROS, M. E. 2009. Prevalence of antinuclear antibodies in 3 groups of healthy individuals: blood donors, hospital personnel, and relatives of patients with autoimmune diseases. J Clin Rheumatol, 15, 325-9.

MARLIN, R. G., ANCHEL, H., GIBSON, J. C., GOLDBERG, W. M. & SWINTON, M. 1998. An evaluation of multidisciplinary intervention for chronic fatigue syndrome with long-term follow-up, and a comparison with untreated controls. The American Journal of Medicine, 105, 110S.

MATTA, J., WIERNIK, E., ROBINEAU, O., CARRAT, F., TOUVIER, M., SEVERI, G., DE LAMBALLERIE, X., BLANCHÉ, H., DELEUZE, J. F., GOURAUD, C., HOERTEL, N., RANQUE, B., GOLDBERG, M., ZINS, M. & LEMOGNE, C. 2022. Association of Self-reported COVID-19 Infection and SARS-CoV-2 Serology Test Results With Persistent Physical Symptoms Among French Adults During the COVID-19 Pandemic. JAMA Intern Med, 182, 19-25.

MEEUS, M., NIJS, J., HERMANS, L., GOUBERT, D. & CALDERS, P. 2013. The role of mitochondrial dysfunctions due to oxidative and nitrosative stress in the chronic pain or chronic fatigue syndromes and fibromyalgia patients: peripheral and central mechanisms as therapeutic targets? Expert Opin Ther Targets, 17, 1081-9.

MORAVA, E. & KOZICZ, T. 2013. Mitochondria and the economy of stress (mal)adaptation. Neurosci Biobehav Rev, 37, 668-80.

MYHILL, S., BOOTH, N. E. & MCLAREN-HOWARD, J. 2013. Targeting mitochondrial dysfunction in the treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) - a clinical audit. Int J Clin Exp Med, 6, 1-15.

NEUSTADT, J. & PIECZENIK, S. R. 2008. Medication-induced mitochondrial damage and disease. Mol Nutr Food Res, 52, 780-8.

NICE 2021. Chronic pain in over 16s: assessment and management. NG 206. National Institute for Health and Care Excellence.

NISENBAUM, R., JONES, J. F., UNGER, E. R., REYES, M. & REEVES, W. C. 2003. A population-based study of the clinical course of chronic fatigue syndrome. Health Qual Life Outcomes, 1, 49.

NORHEIM, K. B., JONSSON, G. & OMDAL, R. 2011. Biological mechanisms of chronic fatigue. Rheumatology (Oxford), 50, 1009-18.

REEVES, W. C., LLOYD, A., VERNON, S. D., KLIMAS, N., JASON, L. A., BLEIJENBERG, G., EVENGARD, B., WHITE, P. D., NISENBAUM, R. & UNGER, E. R. 2003. Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution. BMC Health Serv Res, 3, 25.

ROMANO, G. F., TOMASSI, S., RUSSELL, A., MONDELLI, V. & PARIANTE, C. M. 2015. Fibromyalgia and chronic fatigue: the underlying biology and related theoretical issues. Adv Psychosom Med, 34, 61-77.

SELMI, C., CERIBELLI, A., GENERALI, E., SCIRE, C. A., ALBORGHETTI, F., COLLOREDO, G., PORRATI, L., ACHENZA, M. I., DE SANTIS, M., CAVACIOCCHI, F., MASSAROTTI, M., ISAILOVIC, N., PALEARI, V., INVERNIZZI, P., MATTHIAS, T., ZUCCHI, A. & MERONI, P. L. 2016. Serum antinuclear and extractable nuclear antigen antibody prevalence and associated morbidity and mortality in the general population over 15years. Autoimmun Rev, 15, 162-6.

SHARPE, M., HAWTON, K., SEAGROATT, V. & PASVOL, G. 1992. Follow up of patients presenting with fatigue to an infectious diseases clinic. Bmj, 305, 147-52.

SNELL, C. R., STEVENS, S. R., DAVENPORT, T. E. & VAN NESS, J. M. 2013. Discriminative validity of metabolic and workload measurements for identifying people with chronic fatigue syndrome. Phys Ther, 93, 1484-92.

STEVELINK, S. A. M., FEAR, N. T., HOTOPF, M. & CHALDER, T. 2019. Factors associated with work status in chronic fatigue syndrome. Occup Med (Lond).

STEVELINK, S. A. M., MARK, K. M., FEAR, N. T., HOTOPF, M. & CHALDER, T. 2022. Chronic fatigue syndrome and occupational status: a retrospective longitudinal study. Occup Med (Lond), 72, 177-183.

VERCOULEN, J. H., SWANINK, C. M., FENNIS, J. F., GALAMA, J. M., VAN DER MEER, J. W. & BLEIJENBERG, G. 1996. Prognosis in chronic fatigue syndrome: a prospective study on the natural course. J Neurol Neurosurg Psychiatry, 60, 489-94.

WALITT, B., FITZCHARLES, M. A., HASSETT, A. L., KATZ, R. S., HAUSER, W. & WOLFE, F. 2011. The longitudinal outcome of fibromyalgia: a study of 1555 patients. J Rheumatol, 38, 2238-46.

WHITE, P., ABBEY, S., ANGUS, B., BALL, H. A., BUCHWALD, D. S., BURNESS, C., CARSON, A. J., CHALDER, T., CLAUW, D. J., COEBERGH, J., DAVID, A. S., DWORETZKY, B. A., EDWARDS, M. J., ESPAY, A. J., ETHERINGTON, J., FINK, P., FLOTTORP, S., GARCIN, B., GARNER, P., GLASZIOU, P., HAMILTON, W., HENNINGSEN, P., HOERITZAUER, I., HUSAIN, M., HUYS, A. M. L., KNOOP, H., KROENKE, K., LEHN, A., LEVENSON, J. L., LITTLE, P., LLOYD, A., MADAN, I., VAN DER MEER, J. W. M., MILLER, A., MURPHY, M., NAZARETH, I., PEREZ, D. L., PHILLIPS, W., REUBER, M., RIEF, W., SANTHOUSE, A., SERRANOVA, T., SHARPE, M., STANTON, B., STEWART, D. E., STONE, J., TINAZZI, M., WADE, D. T., WESSELY, S. C., WYLLER, V. & ZEMAN, A. 2023. Anomalies in the review process and interpretation of the evidence in the NICE guideline for chronic fatigue syndrome and myalgic encephalomyelitis. J Neurol Neurosurg Psychiatry, 94, 1056-1063.

ZAMBOLIN, F., DURO-OCANA, P., FAISAL, A., BAGLEY, L., GREGORY, W. J., JONES, A. W. & MCPHEE, J. S. 2022. Fibromyalgia and Chronic Fatigue Syndromes: A systematic review and meta-analysis of cardiorespiratory fitness and neuromuscular function compared with healthy individuals. PLoS One, 17, e0276009.