Non-pharmacological approaches to treatment

Abstract:

Chronic fatigue syndrome (CFS) as currently defined overlaps with other syndromes including chronic pain, fibromyalgia, anxiety and depression. It also resembles historical descriptions of neurasthenia. The role of psychological (cognitive) and behavioural therapies in CFS is examined.

There are both pragmatic and theoretical arguments for their application to CFS. It is pragmatic to target obvious and treatable factors including inactivity and depression. A theoretical model in which psychological, physiological and social factors interact offers a plausible rationale for such treatment but is not yet empirically proven. While there is evidence for the efficacy of this type of therapy in related syndromes, the evidence in CFS is inconclusive.

A randomized controlled trial of combined cognitive and behavioural therapy currently in progress is described. Initial results suggest that most patients receiving cognitive behaviour therapy improve, especially in terms of functional impairment. It remains to be seen whether this therapy will prove to be more effective than standard general practitioner care. In the meantime cognitive behaviour therapy offers a pragmatic and rational therapy for patients with CFS.

 

Source: Sharpe M. Non-pharmacological approaches to treatment. Ciba Found Symp. 1993;173:298-308; discussion 308-17. http://www.ncbi.nlm.nih.gov/pubmed/8491104

 

Pharmacological approaches to the therapy of chronic fatigue syndrome

Abstract:

Although a variety of pharmacological agents have been used to treat patients with chronic fatigue syndrome none has been shown to effect a complete resolution of symptoms.

Data obtained from a retrospective study and from an objective assessment of the aerobic work capacity of patients with this disorder suggest that the underlying pathophysiological abnormality is a disorder of sleep regulation. This results not only in profound fatigue and lethargy but also reduced sensory threshold for pain, disordered temperature regulation, cardiovascular abnormalities, disturbed higher cerebral function and mental depression.

Drugs which modulate sleep, such as tricyclic antidepressants, have a limited effect in improving the symptoms that CFS patients experience. We suggest that other agents which affect central nervous system neurotransmitters, particularly serotonin, may have potential in the management of this condition and need to be evaluated in large controlled clinical trials.

 

Source: McCluskey DR. Pharmacological approaches to the therapy of chronic fatigue syndrome. Ciba Found Symp. 1993;173:280-7; discussion 287-97. http://www.ncbi.nlm.nih.gov/pubmed/8491103

 

Fibromyalgia, sleep disorder and chronic fatigue syndrome

Abstract:

Various research studies show that the amalgam of disordered sleep physiology, chronic fatigue, diffuse myalgia, and cognitive and behavioural symptoms constitutes a non-restorative sleep syndrome that may follow a febrile illness, as in the chronic fatigue syndrome. Where rheumatic complaints are prominent such a constellation of disturbed sleep physiology and symptoms also characterizes the fibromyalgia disorder.

In contrast to the chronic fatigue syndrome, fibromyalgia is associated with a variety of initiating or perpetuating factors such as psychologically distressing events, primary sleep disorders (e.g. sleep apnoea, periodic limb movement disorder) and inflammatory rheumatic disease, as well as an acute febrile illness.

The chronic fatigue syndrome and fibromyalgia have similar disordered sleep physiology, namely an alpha rhythm disturbance (7.5-11 Hz) in the electroencephalogram (EEG) within non-rapid eye movement (NREM) sleep that accompanies increased nocturnal vigilance and light, unrefreshing sleep. Aspects of cytokine and cellular immune functions are shown to be related to the sleep-wake system.

The evidence suggests a reciprocal relationship of the immune and sleep-wake systems. Interference either with the immune system (e.g. by a viral agent or by cytokines such as alpha-interferon or interleukin 2) or with the sleeping-waking brain system (e.g. by sleep deprivation) has effects on the other system and will be accompanied by the symptoms of the chronic fatigue syndrome.

 

Source: Moldofsky H. Fibromyalgia, sleep disorder and chronic fatigue syndrome. Ciba Found Symp. 1993;173:262-71; discussion 272-9. http://www.ncbi.nlm.nih.gov/pubmed/8491102

 

Somatization, illness attribution and the sociocultural psychiatry of chronic fatigue syndrome

Abstract:

In addition to epidemiological and neurobiological perspectives on the relationship between chronic fatigue syndrome (CFS) and psychiatric disorders there has been increasing interest in the role of cognitive-behavioural, psychological, psychodynamic and social factors in the psychiatric aspects of this syndrome. These factors may be important in the initiation and/or maintenance of CFS and play important roles in the misdiagnosis of primary psychopathology as CFS. They may be important targets for intervention and treatment.

This paper examines the relevance of the following issues for better understanding the relationship between CFS and the results of psychiatric studies: (1) the concepts of somatization and abnormal illness behaviour; (2) the role of patients’ illness attributions; (3) psychological and psychodynamic constructs such as depressive vulnerability occurring in individuals dependent upon achievement for the maintenance of self-esteem and euthymic mood, perfectionism, and helplessness; (4) the role of personality characteristics and styles; (5) the potential iatrogenic role of the health care system in producing disability in individuals with a diagnosis of CFS; (6) the role of the media and other sociocultural forces in the patient’s choice of the CFS label; and (7) the impact of the CFS label on the patient. The importance of differentiating between initiating and maintaining or perpetuating factors is emphasized.

 

Source: Abbey SE. Somatization, illness attribution and the sociocultural psychiatry of chronic fatigue syndrome. Ciba Found Symp. 1993;173:238-52; discussion 252-61. http://www.ncbi.nlm.nih.gov/pubmed/8491101

 

Chronic fatigue and chronic fatigue syndrome: clinical epidemiology and aetiological classification

Abstract:

To determine the medical and psychiatric diagnoses that have an aetiological role in chronic fatigue we conducted a prospective study of 405 (65% women) patients who presented for evaluation with this chief complaint to an academic medical centre.

The average age was 38.1 years and the average duration of fatigue at entry in the study was 6.9 years. All patients were given comprehensive physical and laboratory evaluations and were administered a highly structured psychiatric interview. Psychiatric diagnoses explaining the chronic fatigue were identified in 74% of patients and physical disorders were diagnosed in 7% of patients.

The most common psychiatric conditions in this series were major depression, diagnosed in 58% of patients, panic disorder, diagnosed in 14% of patients, and somatization disorder, diagnosed in 10% of patients. Primary sleep disorders, diagnosed in 2% patients, and chronic infections, confirmed in 1.6% patients, explained the majority of cases whose chronic fatigue was attributed to a physical disorder.

Thirty per cent of patients met the criteria used to define the chronic fatigue syndrome (CFS). Compared with age- and gender-matched control subjects with chronic fatigue, CFS patients had a similarly high prevalence of current psychiatric disorders (78% versus 82%), but were significantly more likely to have somatization disorder (28% versus 5%) and to attribute their illness to a viral infection (70% versus 33%).

We conclude that most patients with a chief complaint of chronic fatigue, including those exhibiting the features of CFS, suffer from standard mood, anxiety and/or somatoform disorders. Careful research is still needed to determine whether CFS is a distinct entity or a variant of these psychiatric illness.

 

Source: Manu P, Lane TJ, Matthews DA. Chronic fatigue and chronic fatigue syndrome: clinical epidemiology and aetiological classification. Ciba Found Symp. 1993;173:23-31; discussion 31-42. http://www.ncbi.nlm.nih.gov/pubmed/8491100

 

The neuropsychiatry of chronic fatigue syndrome

Abstract:

This paper explores the relationship between chronic fatigue syndrome (CFS) and psychiatric disorder, with special reference to neuropsychiatry, Topics reviewed include (1) epidemiological evidence of central disorder in CFS; (2) evidence from longitudinal studies of an interaction between vulnerability to CFS and psychiatric disorder; and (3) evidence from neuroimaging, neuropsychology, neurophysiology and neuroendocrinology of disordered CNS function in CFS. The most impressive evidence of CNS disturbance comes from neuroendocrinological studies, which suggest a role of hypothalamic disorder as a final common pathway for CFS. It is concluded that the equal and opposite tendencies of psychiatry to be ‘brainless’ and neurology to be ‘mindless’ have led to needless controversy over the nature of CFS. Now that the contributions of psychiatric disorder to CFS, and of neurobiological dysfunction to psychiatric disorder, are both established, it will be possible to make real advances in understanding the nature of CFS.

 

Source: Wessely S. The neuropsychiatry of chronic fatigue syndrome. Ciba Found Symp. 1993;173:212-29; discussion 229-37. http://www.ncbi.nlm.nih.gov/pubmed/8491099

 

Immunity and the pathophysiology of chronic fatigue syndrome

Abstract:

The pathophysiology of chronic fatigue syndrome (CFS) remains unknown. The syndrome often follows a recognized or presumed infection and the disorder may therefore result from a disordered immune response to a precipitating infection or antigenic challenge.

Abnormalities of both humoral and cellular immunity have been demonstrated in a substantial proportion of patients with CFS. The most consistent findings are of impaired lymphocyte responses to mitogen and reduced natural killer cell cytotoxicity. Cutaneous anergy and immunoglobulin G subclass deficiencies have also been found.

Further studies are needed examining cytokine levels in serum and cerebrospinal fluid, and cytokine production in vitro in patients with CFS. Interpretation of the findings of published studies of immunity is limited by probable heterogeneity in the patient groups studied, and by the lack of standardization and reproducibility in the assays used.

The pattern of abnormalities reported in immunological testing in patients with CFS is consistent with the changes seen during the resolving phases of acute viral infection. These data provide circumstantial support for the hypothesis that CFS results from a disordered immune response to an infection. Longitudinal studies of immunity in patients developing CFS after defined infectious illnesses will provide the best means of further examining this hypothesis.

 

Source: Lloyd AR, Wakefield D, Hickie I. Immunity and the pathophysiology of chronic fatigue syndrome. Ciba Found Symp. 1993;173:176-87; discussion 187-92. http://www.ncbi.nlm.nih.gov/pubmed/8491097

 

Muscle histopathology and physiology in chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is characterized by fatigue at rest which is made worse by exercise. Previous biopsy studies on small numbers of CFS patients have shown a range of morphological changes to which have been attributed fatigue and myalgia.

We have now studied 108 patients with CFS or muscle pain and 22 normal volunteers by light and electron microscopy. There was no consistent correlation between symptoms and changes in fibre type prevalence, fibre size, degenerative or regenerative features, glycogen depletion, or mitochondrial abnormalities. Physiological contractile properties of quadriceps (maximal isometric force generation, frequency: force characteristics and relaxation rate) were also examined before and for up to 48 hours after a symptom-limited incremental cycle ergometer exercise test in 12 CFS patients and 12 normal volunteers.

Voluntary and stimulated force characteristics were normal at rest and during recovery. Exercise duration was similar in the two groups although CFS patients had higher perceived exertion scores in relation to heart rate during exercise, indicating a reduced effort sensation threshold. On physiological and pathological grounds it is clear that CFS is not a myopathy. Psychological/psychiatric factors appear to be of greater importance in this condition.

 

Source: Edwards RH1, Gibson H, Clague JE, Helliwell T. Muscle histopathology and physiology in chronic fatigue syndrome. Ciba Found Symp. 1993;173:102-17; discussion 117-31. http://www.ncbi.nlm.nih.gov/pubmed/8491096

 

Hypothesis: the nasal fatigue reflex

Abstract:

Natural selection results in adaptations. I suggest that unexplained fatigue may be an adaptive response to nasal impairment.

For macrosmatic animals, intact olfaction is necessary to detect predators. In such animals, any reflex (e.g., fatigue) triggered by nasal dysfunction that limited exposure would offer great survival advantage. The “fatigued” animal would remain in its protected environment, unexposed to hungry carnivores, while the nose healed.

In humans, clinical syndromes associated with unexplained fatigue (chronic fatigue syndrome, tension fatigue syndrome, allergic fatigue, neurasthenia, etc.) are characterized by symptoms that, in part, are nasal in origin.

The older medical literature does describe the resolution of fatigue in neurasthenia after nasal treatments. Nasal reflexes in animals do cause significant systemic effects, including an inhibition of muscle action potentials that is, perhaps, analogous to the “heavy-limbed” sensation of those with fatigue.

Furthermore, reflexes similar to the one proposed do exist in humans: the diving reflex presumably served our amphibian ancestors well as an oxygen conserving technique with submersion, but serves no known useful function now. Other human nasopharyngeal reflexes with profound cardiovascular and systemic effects are well described but only occasionally studied. The proposed nasal fatigue reflex should be examined as a possible ancient adaptive response to nasal malfunction.

 

Source: Chester AC. Hypothesis: the nasal fatigue reflex. Integr Physiol Behav Sci. 1993 Jan-Mar;28(1):76-83. http://www.ncbi.nlm.nih.gov/pubmed/8476744

 

Development of a fatigue scale

Abstract:

A self-rating scale was developed to measure the severity of fatigue. Two-hundred and seventy-four new registrations on a general practice list completed a 14-item fatigue scale. In addition, 100 consecutive attenders to a general practice completed the fatigue scale and the fatigue item of the revised Clinical Interview Schedule (CIS-R). These were compared by the application of Relative Operating Characteristic (ROC) analysis. Tests of internal consistency and principal components analyses were performed on both sets of data. The scale was found to be both reliable and valid. There was a high degree of internal consistency, and the principal components analysis supported the notion of a two-factor solution (physical and mental fatigue). The validation coefficients for the fatigue scale, using an arbitrary cut off score of 3/4 and the item on the CIS-R were: sensitivity 75.5 and specificity 74.5.

 

Source: Chalder T, Berelowitz G, Pawlikowska T, Watts L, Wessely S, Wright D, Wallace EP. Development of a fatigue scale. J Psychosom Res. 1993;37(2):147-53. http://www.ncbi.nlm.nih.gov/pubmed/8463991