Chronic Fatigue Syndrome in Detail a Psychiatric Perspective

Chronic fatigue syndrome in detail - a psychiatric perspective.

Topics covered:

  • Introduction
    • Fatigue as a symptom
    • Fatigue as an illness
  • Clinical features
  • Classification and diagnosis
    • Chronic fatigue syndrome
    • Issues for a definition of chronic fatigue syndrome
    • The current status of chronic fatigue syndrome
    • Is chronic fatigue syndrome a useful diagnosis?
  • Epidemiology
  • Aetiology
    • Objective evidence of impairment
    • Pathophysiology
    • Psychopathology
    • Conclusions about the nature and cause of chronic fatigue syndrome
  • Course and prognosis
  • Treatment
    • Evidence
    • Management
  • Conclusions and future directions
  • Possibilities for prevention 
  • References


Fatigue as a symptom

Fatigue has been defined in a variety of ways. (1) Here, however, we are concerned with fatigue as a subjective feeling of weariness, lack of energy, and exhaustion. Fatigue should be distinguished from sleepiness and anhedonia. The feeling of fatigue is a common human experience and subjective ratings of its severity are continuously distributed in the population. Approximately 20 per cent of the general population report a symptom of significant and persistent fatigue, although relatively few of those people will regard themselves as ill and only a small minority seek a medical opinion. Even so, a complaint of fatigue is a very common clinical presentation in primary care.

Fatigue as an illness

A clinical syndrome characterized by fatigue which is disabling, exacerbated by exertion, and accompanied by other symptoms including poor concentration, irritability, and muscle pain has been recognized at least since the latter half of the last century and possibly before. During the Victorian era patients with this syndrome often received a diagnosis of neurasthenia, a condition of uncertain cause commonly ascribed to the effect of the stresses of modern life on the human nervous system. (1) As the years passed the diagnosis of neurasthenia was much less frequently made, and by the early 1900s it was falling out of common usage in Europe. (However, this diagnosis subsequently became popular in the Far East) Why did neurasthenia decline? Although it is possible that the symptom of fatigue also waned in the population, it seems more likely that patients with similar symptoms were given alternative diagnoses. These diagnoses include hypothetical disease explanations, such as chronic brucellosis and chronic Epstein–Barr virus infection, and psychiatric syndromes such as depression and anxiety.

In the last 20 years non-psychiatric physicians have again become interested in fatigue. They have increasingly recognized that the symptoms of many patients who present with chronic fatigue are not readily explained either by medical conditions such as Epstein–Barr virus infection or by obvious depression and anxiety disorders. Diagnoses used to describe this syndrome include myalgic encephalomyelitis and post-viral fatigue syndrome. However, these are unsatisfactory as they imply an unproven causal mechanism. Therefore the term chronic fatigue syndrome (CFS) was proposed as a neutral description of this condition. (2) In parallel with the increased interest in fatigue states amongst physicians, neurasthenia re-emerged in the ICD-10 psychiatric classification as a fatigue syndrome unexplained by depressive or anxiety disorder.

Clinical features

The central symptom of CFS is the symptom of fatigue. Other commonly reported symptoms include muscular pains and poor concentration.

Chronic fatigue syndrome (CFS) is a debilitating and complex disorder characterized by intense fatigue that is not improved by bed rest and that may be worsened by physical activity or mental exertion. People with CFS often function at a substantially lower level of activity than they were capable of before they became ill. The cause or causes of CFS have not been identified, and no specific diagnostic tests are available. Therefore, a CFS diagnosis requires three criteria:

  1. The individual has had severe chronic fatigue for 6 or more consecutive months that is not due to ongoing exertion or other medical conditions associated with fatigue (these other conditions need to be ruled out by a doctor after diagnostic tests have been conducted)
  2. The fatigue significantly interferes with daily activities and work
  3. The individual concurrently has 4 or more of the following 8 symptoms:
  • post-exertion malaise lasting more than 24 hours
  • unrefreshing sleep
  • significant impairment of short-term memory or concentration muscle pain
  • pain in the joints without swelling or redness
  • headaches of a new type, pattern, or severity
  • tender lymph nodes in the neck or armpit
  • a sore throat that is frequent or recurring

Case Study

A typical patient will be found in the infectious disease department of the hospital. She is 30 years old and her principal complaint is of fatigue, poor concentration, and muscle pain. These symptoms are exacerbated by physical and mental exertion, and have led to a substantial reduction in daily activities. The history is of an acute onset of symptoms after a ‘viral illness'. Appropriate enquiry reveals symptoms suggestive of depression or anxiety, but without prominent mood change. The patient believes the illness to be ‘medical' rather than ‘psychiatric'.

Classification and diagnosis

Chronic fatigue syndrome

The current case definition for CFS (3) is based on an international consensus of researchers. It should be remembered that it represents nothing more than a working definition of a clinical problem, pending further understanding.

Issues for a definition of chronic fatigue syndrome

The case definition shown above has significant limitations.

  • It overlaps with other functional medical diagnoses.
  • Most patients who meet existing criteria can be given an alternative psychiatric diagnosis.
  • The homogeneity of the patient group it identifies is doubtful.
Overlap with other medically unexplained syndromes

Medically unexplained chronic fatigue is common in patients with other ‘functional' syndromes. Functional syndromes are medical diagnoses where there is no identifiable pathology such as idiopathic chronic pain, fibromyalgia, and irritable bowel syndrome. Although chronic pain syndromes are principally characterized by pain, fibromyalgia by tender points, and irritable bowel syndrome by symptoms of bowel disturbance, all these syndromes are also associated with chronic fatigue, and patients diagnosed with one of these often meet the diagnostic criteria for CFS. (1)

Overlap with psychiatric syndromes

Most patients who meet criteria for CFS also fulfil the criteria for a psychiatric diagnosis. Many patients have anxiety and depressive disorders; others merit diagnoses of somatoform disorder or neurasthenia. Therefore from the psychiatrist's perspective it is parsimonious to ask whether a diagnosis of CFS is necessary, if the patient's symptoms can equally well be described by a psychiatric diagnosis.


There is considerable evidence to support the idea that CFS is associated with depression.

  • If psychiatric patients with a depressive disorder are asked about a wide range of somatic symptoms including fatigue (which they are usually not) those reported frequently include symptoms of CFS. (4)
  • If operational criteria for depressive disorders are applied to patients with CFS a high proportion meet these, and an even higher proportion have a previous history of major depression. (5)
  • The prevalence of major depressive disorder in patients referred to hospital with CFS is substantially higher than that of patients with chronic disabling medical diseases. (6)

In practice, the diagnosis of depression can be difficult in such patients. Depressed mood is often not prominent and anhedonia can be hard to distinguish from the inability to pursue previously enjoyed activities. Furthermore, whilst there is a strong association between major depressive disorder and CFS, for as many as half of the patients seen in hospital clinics the symptoms cannot be readily subsumed under an operationally defined diagnosis of major depressive disorder.

Anxiety disorder

If depression cannot provide the whole explanation for CFS, could some patients be better described as having anxiety disorders? Although less attention has so far been devoted to this question, examination of diagnostic criteria will reveal that the typical somatic symptoms of anxiety include fatiguability and other symptoms of CFS. Furthermore, if sought, generalized anxiety disorder can often be diagnosed in patients with CFS. (7) As with depression, however, anxious mood is rarely prominent and is often related to concern about the illness.


ICD-10 differs from DSM-IV in including this category. The diagnosis requires that the patient suffers from fatigue which is exacerbated by exertion, as well as several other somatic symptoms, and does not meet the criteria for a depressive or anxiety disorder. One study found that 97 per cent of the referrals to a medical CFS clinic met the criteria for neurasthenia as defined by ICD-10. (8)

Somatoform disorders

According to DSM-IV those patients not meeting the criteria for anxiety or depressive disorders would likely be assigned to a somatoform disorder. These are a group of psychiatric syndromes characterized by medically unexplained symptoms, which are of presumed psychological origin. There are a number of subcategories.

  • Somatization disorder (Briquet's syndrome) is used to describe patients who report multiple, recurrent, medically unexplained symptoms; a minority of patients with CFS will meet the criteria for this disorder.
  • Hypochondriasis describes a syndrome in which the patient's main concern is with the possibility that they are suffering from an organic disease. Although on initial inspection this would seem to be applicable to many patients with CFS, the use of this diagnosis is problematic in the case of an illness, the cause of which is regarded as uncertain by doctors as well as patients. Furthermore, clinical experience suggests that most patients with CFS are more concerned about the symptoms and impaired functioning they are experiencing than about the precise medical diagnosis to which these symptoms are attributed. Therefore although the diagnosis of hypochondriasis has the advantage of explicitly including patients' illness beliefs and behaviour in its definition, existing diagnostic criteria do not readily fit the clinical phenomena of CFS.
  • Almost all patients with CFS not meeting the criteria for any of the above DSM disorders are likely to fall into the undemanding residual category in DSM-IV of ‘undifferentiated somatoform disorder'.


Many patients with CFS meet the diagnostic criteria for a depressive disorder or for an anxiety disorder, although in practice the presentation is usually ‘atypical'. It is likely that patients who do not meet the criteria for either could be regarded as suffering from either neurasthenia (ICD-10) or undifferentiated somatoform disorder (DSM-IV). Therefore all patients labelled as having CFS can be given a psychiatric diagnosis. However, in many cases such diagnoses are neither adequate descriptions of the clinical syndromes, nor particularly helpful for clinical management. Certainly few patients are likely to want their illness to be reformulated in this way.

The current status of chronic fatigue syndrome

What then is the status of CFS as a diagnosis? The current broad definition simply describes a clinical presentation. A more adequate description requires that additional information be provided. As the syndrome is medically unexplained, any subdivision must be on the basis of clinical characteristics rather than disease process. Thus, one approach is to subdivide CFS according to the presence of syndromes described in existing psychiatric classifications. According to such a scheme CFS would be subclassified into CFS/depression, CFS/anxiety, and CFS without depression or anxiety disorder (i.e. narrowly defined CFS, or CFS/neurasthenia). While such a subclassification is possible, it is difficult to apply in practice because many patients do not fit comfortably into existing operational definitions of depression, anxiety, or hypochondriasis, despite often having features suggestive of these syndromes.

Is chronic fatigue syndrome a useful diagnosis?

Should the clinician ever diagnose CFS? We would say yes, but with four important caveats.

  1. CFS should be explicitly regarded as a presenting clinical syndrome, rather than a specific disease process. Whilst this is not to deny the possibility that there are specific pathophysiological processes underlying the symptoms, a balance must be struck between acceptance of this possibility and unjustified enthusiasm for each newly discovered aetiological agent.
  2. Psychiatric syndromes that have important clinical utility such as major depressive disorder should be sought, and, if present, should be included in the diagnostic statement.
  3. While the current case definition of CFS specifies only symptoms, patients' beliefs and behaviours are often a prominent part of the clinical presentation and also need to be included in any useful summary of the case.
  4. Rather than becoming side-tracked by the question of whether CFS is ‘medical' or ‘psychiatric' in nature, management is likely to be more effective if both the physician and the patient adopt an open-minded and pragmatic approach.


The epidemiology of CFS is a frequent source of confusion. Many of the current estimates of prevalence are flawed because of inadequate methodology. Several factors may influence the estimate and associations found.

  • Some studies have failed to differentiate CFS as defined by patients or their doctors, who believe that CFS (or sometimes myalgic encephalomyelitis) is the appropriate diagnosis, from CFS as defined by meeting the symptom criteria. (9) We suspect the latter outnumbers the former by perhaps ten to one. For example, only 12 per cent of primary care patients who fulfilled the complete CFS criteria used an equivalent term to refer to their illness. (10)
  • As described above it can be very difficult to differentiate CFS from depressive and anxiety disorders. Estimates that do not exclude these diagnoses are much higher than those that do. (1)
  • Recent studies demonstrate that previous reports suggesting that teachers or health-care professionals (9) are susceptible to CFS may be influenced by selection bias and treatment-seeking behaviour, and hence are not true risk factors. A similar argument applies for social class—the apparent excess of higher socio-economic classes visible in all specialist clinics is probably due to selection, referral, and attributional biases. (11)

New epidemiological studies of improved methodological rigour have begun to emerge. It is too early to give an exact picture, but it is clear that somewhere between 0.3 and 1 per cent of the general population fulfil the current criteria (3) for CFS, the figures for primary care being slightly higher. (1) CFS is thus both common and, because it is by definition associated with functional impairment, is also a public health problem worthy of note.


A considerable amount of research has been devoted to investigating the nature and causes of CFS without arriving at firm conclusions. Unfortunately, most of these studies have suffered from methodological shortcomings, principally in patient selection. Patients have often been recruited from tertiary care clinics, using various diagnostic criteria, which have been inconsistently applied. Only a minority of studies have included comparison groups of patients with diagnoses of depression or anxiety disorders. Furthermore, because most studies have used a case–control design, it is often impossible to know whether the findings they report are causes or consequences of the illness (for instance, as the result of reduced activity or sleep disturbance).

Objective evidence of impairment

Exercise capacity and muscle function

Exercise testing has confirmed poor performance and also abnormal physiological responses to exercise. While the majority of studies have concluded that muscle function is normal, there is some evidence that many patients suffer from physiological deconditioning secondary to inactivity. (12) The ability to exercise is also reduced in patients suffering from depression, although other, as yet undefined, pathophysiological processes may be operating in a subgroup of patients with CFS. 

Cognitive functioning

Although some studies have found no objective impairment of cognitive functioning, others have suggested subtle deficits in information processing. However, similar deficits have been found in patients suffering from depression, and the specificity of this observation remains uncertain. (13)


Clinical observations of patients with CFS have led to the investigation of a number of hypotheses about the underlying pathophysiological mechanisms.

Cardiovascular and respiratory abnormalities

Several investigators have reported abnormalities in the cardiorespiratory systems that may underpin the exercise intolerance. Hyperventilation has been suggested as a mechanism of symptom production, but only a minority appear to have biochemically confirmed hyperventilation. Low blood pressure has long been associated with the symptom of fatigue, and in some parts of Europe unexplained fatigue is confidently ascribed to this. Postural hypotension has recently been noted in patients with CFS, (14) and whilst this may be a cause of fatigue it may also be a consequence of inactivity. Finally, various abnormalities in cardiac function have also been reported but are of uncertain significance.


Perhaps because patients commonly describe their illness as beginning with ‘flu-like symptoms', many investigators have sought objective evidence of an initiating or ongoing viral infection.

Viral infection can probably initiate CFS. A prospective follow-up of people with positive evidence of acute Epstein–Barr infection did find that some patients went on to develop a fatigue syndrome. (15) Other infectious agents that may trigger CFS include Q fever and viral meningitis. However, a much larger prospective study in primary care found no association at all between self-reported viral infections and subsequent fatigue. (16) So if viruses do play a role in precipitating CFS, it would appear that it is only when certain types of viruses infect vulnerable persons.

If CFS can be precipitated by viral infection does persistence of the virus cause the ongoing symptoms? On current evidence the answer to this question seems to be that it is not. (1)

Immune dysfunction

The evidence for an association between immunological abnormalities and CFS is more consistent than that for infective agents, with several studies suggesting abnormalities in lymphocyte numbers and function. (17) However, similar changes can be found in patients with depressive disorders, and, although some studies have attempted to control for emotional disorder, both the specificity and causal importance of these observations remain unclear.

Sleep abnormalities

Unrefreshing sleep is an almost ubiquitous complaint of people suffering from CFS. While studies have identified major sleep disorders such as sleep apnoea and narcolepsy in a minority of patients, simple disruption of slow-wave sleep is a much more common observation. (18) While inefficient sleep could contribute to the daytime fatigue reported in both conditions, its specificity and aetiological role are uncertain.

Neuroendocrine abnormalities

The prominent fatigue of Addison's disease has led to several researchers suggesting the hypothesis that adrenal function is also impaired in patients with CFS. In support of this suggestion there is some evidence that patients with chronic fatigue and fibromyalgia have both low levels of cortisol and an abnormal adrenal response to stress and exertion. (19) These findings require replication. If they prove to be robust, they may not only suggest a mechanism of symptom production in CFS but also represent a definite biological difference between CFS and depressive disorders, in which cortisol levels are typically elevated.

Neurotransmitter abnormalities

Recent studies of patients with CFS have found evidence of abnormal functioning of cerebral serotonergic systems, which differ from those found in patients with depression. (20) Like the abnormalities in adrenal function these findings are preliminary but of considerable potential interest.

Brain imaging

Finally, a variety of techniques have been used to examine both the function and structure of the brain in patients with CFS. Cerebral perfusion studies have shown abnormalities, although similar, if not identical, abnormalities are also found in patients with depression. Possible white-matter changes reported on magnetic resonance scans are more controversial, and are harder to interpret. (21)


Despite a considerable research effort, so far no single pathophysiological process has been conclusively identified as causal of CFS. There is some evidence for a loss of physical fitness and possibly for abnormalities of neuroendocrine function. Viral infection may play a role as precipitating agent, although its importance as a perpetuating factor is far less certain. Immunological abnormalities are common but of uncertain specificity. The current attention on neuroendocrine function takes the focus of investigation closer to those features known to be associated with depressive states. However, recent and intriguing observations suggest that the changes in neurotransmitter and neuroendocrine function in patients with CFS may differ from those commonly observed in patients diagnosed with depressive disorder. Further studies are needed to confirm these abnormalities and to clarify whether they are causal or merely epiphenomena.


The initial psychiatric hypothesis to explain CFS was that it was identical to depressive disorder. This hypothesis relegated CFS to the status of mere misdiagnosis. However, this view was clearly an oversimplification, and more complex explanations are required.


A process referred to as ‘somatization' is commonly invoked as an additional process to explain why patients with emotional disturbances such as depression present with somatic complaints like fatigue and not with low mood. The term somatization implies that ‘mental' processes are causing ‘somatic' symptoms, and it is therefore essentially dualistic. The hypothesis that the somatic symptoms of CFS are readily understandable as part of an emotional disturbance is a parsimonious alternative to some of the more elaborate pathophysiological mechanisms outlined above. However, there is no ‘marker' for somatization and its operation is difficult to prove. Therefore tests of this hypothesis require that observable aspects of this process are present in patients diagnosed as suffering from CFS.


One of the components of somatization that can be measured is the patients' understanding of, and beliefs about, their illness. Systematic studies have confirmed that patients attending specialist clinics with CFS typically attribute their illness to organic disease even when no evidence of this can be found by their physicians. Perhaps more importantly, they may strongly resist psychological and psychiatric explanations for their symptoms. (22) Whether these patients are biased in their views about illness or simply wiser than their physicians is unclear. However, strong and exclusively physical disease attributions may be a marker for an important illness-perpetuating process in CFS as they predict a poorer clinical outcome. (23)

Perceptual processes

Patients with CFS report a greater sense of effort in response to both psychological and physical demands than is explicable from the objectively measurable impairments. (24) This observation raises the possibility that they are especially sensitive to bodily sensations, that is they ‘amplify' them. It is possible that as in panic disorder, the patients' beliefs about their symptoms may lead them to focus attention on to bodily sensations. Although a plausible hypothesis, there is so far little evidence that this process is important in patients with CFS. The notion of a central disorder of the sense of effort merits further exploration.

Coping behaviour

A tendency to avoid activities that exacerbate symptoms has been shown to occur in patients with CFS. Activities avoided include not only physical activity but also the ingestion of certain foods, drugs, and alcohol. (25) Such avoidance is associated with persistent disability, and has been suggested as the mechanism by which disease attributions for symptoms predicts poor outcome.

Personality characteristics

Both studies and clinical experience suggest that many persons with CFS have a tendency towards hard driving, perfectionist, or obsessive– compulsive personalities, and overactive lifestyles. (26) Such persons may be both predisposed to becoming emotionally exhausted, and biased towards presenting emotional distress in a somatic form.

Stigma, misinformation, and communication

Patients with the aforementioned personality type may be more susceptible to those social pressures that lead to chronic fatigue, by being more fearful of the social stigma attached to a ‘psychiatric' explanation for their distress. Another potentially important social factor is the availability of misleading information about the illness. Both self-help books and the media have tended to emphasize ‘medical' explanations for the symptoms of CFS at the expense of more psychiatric or psychological conceptualizations. It has also been suggested that CFS may serve a culturally defined function of social communication, allowing a socially acceptable and hence ‘non-psychiatric' expression of distress and protest about intolerable occupational and personal pressures. Much the same has been said of neurasthenia in the People's Republic of China.


Psychopathological explanations of CFS are clinically plausible and have enjoyed some degree of empirical support. In particular, a strong and exclusive medical disease attribution has been found to be a strong predictor of poor prognosis. (23) Social factors may also be important in shaping the illness.

Conclusions about the nature and cause of chronic fatigue syndrome

Research into the cause of CFS has been hindered by poor methodology. Nonetheless, and perhaps surprisingly, some replicable findings have been obtained. In particular, there is evidence of a measurable impairment of physical function and perhaps of cognitive function. Pathophysiological abnormalities so far identified have not been substantial, but do include some tantalizing indications of immune, neurotransmitter, and endocrine dysfunction. Psychopathological enquiries have revealed convincing evidence of an association with depression and anxiety syndromes, and also a tendency by patients to attribute their symptoms to ‘medical' rather than ‘psychiatric' illness. It now seems clear that rather than regarding pathophysiological and psychopathological studies as separate and competing approaches to the problem, it will be more useful to consider a model of CFS that combines multiple aetiological factors. 

According to this integrated scheme causal factors are divided into those that predispose to the illness, those that precipitate it, and those that perpetuate established illness. Predisposing factors include previous episodes of major depressive disorder, and perhaps also certain personality characteristics, particularly achievement orientation and perfectionism associated with chronic stress, especially occupational stress. The precipitation of CFS by a viral infection is clinically plausible and proven in certain circumstances, whilst life stresses also seem to be important. Perpetuating factors may include neuroendocrine dysfunction, emotional disorder, and physical disease attributions, as well as coping by avoidance, chronic unresolved personal and occupational difficulties and conflicts, and misinformation about the illness.

Course and prognosis

Anecdotal reports of the prognosis of CFS make gloomy reading. What is more, systematic studies are hardly more encouraging, suggesting that the commonest outcome of those attending a specialist CFS clinic is continuing ill health, up to and beyond 5 years. (23) However, these observations need elaboration.

  • The rather dispiriting prognostic studies all refer to patients seen in specialist centres. Nearly all had several years of illness prior to referral, and it is unsurprising to find that chronicity predicts chronicity. Primary care and community samples and patients appear to have a better outcome.
  • Patients seen in specialist clinics often have strong views about illness aetiology and illness management that may negatively influence their acceptance of and adherence to potentially effective treatment.
  • The current generation of outcome studies refer to the situation without treatment, perhaps because many suggested either that no treatment was possible or, alternatively, promoted ineffective treatments. Later sections of this chapter suggest that this view needs to be revisited.



Drug treatment

Many pharmacological treatments have been suggested for patients with CFS. To date, none are of proven efficacy and several are potentially harmful. The evidence for antidepressant agents is mixed. One large trial found no response to fluoxetine. (27) Another found minor benefit. (28)

We still recommend that a trial of treatment with antidepressant drugs should be considered, especially if the clinical picture is suggestive of depressive disorder. Of available agents none is clearly superior for this patient group, although clinical experience suggests that the selective serotonin-reuptake inhibitor antidepressants may be better tolerated. The clinical similarities of CFS with ‘atypical' depression may suggest a role for monoamine oxidase inhibitors, but this is not established.

We have already remarked that, unlike major depression, some CFS patients without overt mood disorder show a pattern of reduced cortisol activity. Recently, two trials have used cortisol replacement as a possible therapy. (29,30) The results of these studies suggest that hydrocortisone does cause a symptomatic improvement measured against placebo, and can be achieved using doses sufficiently low to reduce the risk of adrenal suppression. Nevertheless, the evidence remains insufficient, set against the risk of side-effects, to recommend this for routine clinical use at present.

Behaviour therapy

In both fibromyalgia and CFS a modest amount of evidence suggests that graded increases in physical activity are helpful in improving function and relieving symptoms. (31) However, in unselected patients adherence to the treatment regimen is problematic. (28)

Cognitive–behaviour therapy

This article will comment on several published randomized trials of cognitive–behaviour therapy for patients with CFS. 

  • The first systematic modern evaluation of cognitive–behaviour therapy for CFS was an uncontrolled evaluation based on a simple cognitive–behavioural model.It was important because, although there was a high rate of patient refusal, many achieved a marked improvement that was sustained at long-term follow-up—a result that challenged the prevailing idea that nothing could be done for such patients.
  • The first randomized trial of cognitive–behaviour therapy for CFS compared a brief rehabilitative behavioural therapy with standard medical care. The therapy in this study lasted for only six sessions while the average duration of a patient's illness was 5.5 years. The effect of therapy may also have been unintentionally diluted by the study methodology, which attempted to evaluate immunotherapy as well as cognitive–behaviour therapy in a factorial design. No difference was found in the effect of the treatments on disability at the 3-month final follow-up evaluation. (32)
  • A further randomized trial of intensive rehabilitative, cognitive– behaviour therapy compared with standard medical care (33) found a far greater improvement in disability than in patients who had received only medical care. This superiority of cognitive–behaviour therapy was also reflected in a greater improvement on subjective ratings of general state, fatigue, and depression. A notable observation was a slow improvement in disability, which continued during the follow-up period. At the final (12-month) evaluation approximately three-quarters of patients who received cognitive–behaviour therapy attained normal daily functioning, compared with only one-quarter of those given medical care alone.
  • A more recent study to be completed was conducted at King's College Hospital, London (34) by the same group who conducted the original case series. The cognitive–behaviour therapy evaluated was similar to that used in the Oxford trial, although with more emphasis on early behavioural change. This study also differed by comparing cognitive–behaviour therapy with relaxation therapy, rather than simple medical care. The patients in each treatment condition received therapy for a similar amount of time, thereby controlling for non-specific effects. The results of this study were remarkably similar to those obtained in Oxford.

Whilst the results of further similar studies are awaited, a systematic review has concluded that cognitive–behaviour therapy offers a potentially useful approach to the rehabilitation of patients with CFS. (35) However, the general applicability of cognitive–behaviour therapy is limited by the requirement for skilled therapists, and it does not help all patients.


Assessing the patient

A combined medical and psychiatric assessment is required in every case of suspected CFS, (36) and this is summarized in Table 4.

Table 4 Management of CFS


  • Accept patient's complaints as genuine
  • Educate about multifactorial nature
  • Encourage self-help and normal activity


  • Consider antidepressant drugs
  • Avoid polypharmacy
  • Use experimental drugs only in trials


  • Gradual increase in exercise
  • Cognitive behaviour therapy
  • Other psychotherapies if acceptable and indicated

Excluding organic disease

A small minority of those patients who present with severe chronic fatigue will be found to have occult organic disease. How frequently organic disease is found will depend on how thorough an assessment the patient has already received. Even if disease is not evident at assessment, it is wise to remain vigilant to this possibility and to reinvestigate if new clinical signs appear.

Identifying psychiatric syndromes

All patients should have a psychiatric history taken and their mental state examined. The assessment should seek evidence of major depression, anxiety, and panic disorder, and also evaluate any suicidal intent. The psychiatric assessment should be systematic, as hidden distress is common and casual estimates of the patient's degree of distress may be misleading.

Additional patient characteristics

An adequate individual patient assessment must identify all the important obstacles to recovery. It often needs to go beyond diagnosis to include a systematic individualized description of each case. The aspects to be considered in the systematic description include the individual's beliefs about their illness, their coping behaviour, emotional state, and physiological condition as well as interpersonal and occupational problems and the family's understanding of the illness.

Making the diagnosis

The choice of diagnosis should be pragmatic; there is little merit in giving a diagnosis of CFS if the patient's symptoms are clearly those of depression or anxiety, and they are accepting of this diagnosis. In other cases, a diagnosis of CFS may be the most appropriate; it offers the patient a coherent label for their symptoms and will therefore lessen the risk that they will embark on a fruitless search for a ‘better' explanation. The label CFS also avoids the misleading connotations of ‘pseudodisease' labels such as chronic Epstein–Barr virus infection or myalgic encephalomyelitis. Above all, it is most important that neither the physician nor the patient stops at this diagnosis, but goes on to explain what it does and does not mean. (37)

Case formulation

A multidimensional description of the patient's illness provides a comprehensive picture of the factors that may be relevant to the patient's illness and is an important supplement to diagnosis. Its use can be illustrated by returning to the case example described above.

Case Study

Assessment of the patient described at the beginning of this review revealed that she believed that her symptoms were caused by an ongoing virus infection and that she should beware of exacerbating them. She consequently avoided activity and had been profoundly inactive for over a year, often lying in bed and sleeping for long periods. Therefore she was likely to be physiologically deconditioned. She was frustrated with her inability to do things and sometimes felt low in mood about her predicament. Her previous job had been very stressful, but since becoming ill she had been unable to work. She had now lost her job and was cared for by her mother who also believed she had a permanent disability. Her doctor said that the best thing was rest. 

General care

Treatment is summarized in Table 4. The five basic steps essential to the care of patients with CFS are as follows.

  1. Acknowledge the reality of the patient's symptoms and disability associated with them.
  2. Provide appropriate education about the nature of the syndrome to both the patient and his or her family, whilst avoiding unproductive argument.
  3. Treat identifiable depression and anxiety disorder.
  4. Encourage a return to normal functioning by overcoming avoidance and regaining the capacity for physical activity.
  5. Help the patient to overcome occupational and interpersonal obstacles while maintaining their self-esteem.
Pharmacological treatments

Patients are often reluctant to take antidepressants and careful explanation and follow-up are required. Other pharmacological agents should only be used with care and preferably only as part of randomized controlled trials.

Exercise therapy

This should be considered for patients who are physically inactive. However, the simplistic application of exercise regimens, particularly if given without explanation and follow-up, is unlikely to be helpful, and may be harmful by damaging the patient's confidence.


Psychosocial difficulties may be targeted using psychotherapy. Reluctance to consider the role of psychological factors in CFS and related syndromes makes the application of psychotherapy potentially difficult, but not impossible.

Potential problems

Several issues may complicate the management of patients with CFS. These include the following.

Strong illness beliefs

Difficulties are most likely to arise when patient and physician hold differing beliefs about the nature and management of the illness. This problem can often be overcome by the physician acknowledging the patient's beliefs without necessarily agreeing with them. If the patient's family, friends, or acquaintances suggest or encourage views that the physician regards as unhelpful the problem is more difficult and a meeting with the other parties may be necessary.

Alternative therapies

Patients with CFS often turn to alternative medicine. Some complementary therapies may be continued in parallel with rehabilitative management. However, if they interfere with that treatment, the need to pursue one approach at a time should be explained to the patient, who should be encouraged to defer their use of the competing therapy until the current management plan has been completed.

Official reports

Perhaps the greatest source of difficulty is encountered when patients ask the physician to write reports on their behalf, saying that they suffer from permanent disability. On the one hand the physician wants to help the patient, but on the other wants to avoid a self-fulfilling prophecy. This dilemma has no easy solution, but it seems important not to confirm a negative prognosis until potentially effective treatments have been tried.

Poor prognosis patients

For patients who have been identified as having a poor prognosis because of a long history of severely impaired functioning, or poor response to treatment, regular (albeit infrequent) long-term follow-up is, at the least, likely to limit iatrogenic harm from unnecessary investigations and ineffective treatments. It may also actually improve the patient's functioning in the longer term.

Conclusions and future directions

Chronic fatigue syndrome is best regarded as a descriptive term for a type of clinical presentation. The group of patients it defines is almost certainly aetiologically heterogeneous and needs to be subclassified. While psychiatric diagnosis provides one approach to subclassification, the current diagnostic systems have significant limitations, and a multidimensional description of the patient's characteristics may be more clinically useful.

The illness defined by the term chronic fatigue syndrome is important because it represents potentially treatable disability and suffering. It is also important because the clinical problems it gives rise to demand that we address shortcomings in our present approach to medically unexplained illness. Whatever is ultimately discovered about the causes of CFS, the attention it is receiving offers a golden opportunity to reappraise our understanding and classification of human illness and to re-examine our current organization of medical care.

Possibilities for prevention

We do not know how to prevent CFS, but its development can be modified. The most important place for such intervention may be the transition from a transient fatigue state to chronic disability. Although most of us have been exposed to Epstein–Barr virus infection by the time we reach 30 years of age, few go on to develop CFS. Encouraging modest amounts of activity in the weeks after an acute infection has been shown to be effective in reducing the duration of symptoms. Any attempt at maintaining activity and preventing a slide into a vicious circle of symptoms, reduced activity, demoralization, disability, and depression might therefore offer an opportunity for prevention.

There is a second area for intervention—medical and lay attitudes to symptoms and distress. The media have a part to play in promoting awareness of the dangers of simplistic inaccurate depictions of illness as either physical or psychological, which does a grave disservice to those complex illnesses than cannot be so easily pigeon-holed. Likewise, doctors must be acutely aware of the dangers of disconfirmation of a patient's subjective suffering by ill-considered remarks, and a sadly all too pervasive attitude that elevates physical above psychological suffering. Finally, we believe that a good and well-informed doctor– patient relationship is probably the best preventive strategy to reduce the incidence of prolonged fatigue syndromes. 


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