Protocol for the PACE trial: a randomised controlled trial of adaptive pacing, cognitive behaviour therapy, and graded exercise, as supplements to standardised specialist medical care versus standardised specialist medical care alone for patients with the chronic fatigue syndrome/myalgic encephalomyelitis or encephalopathy

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS, also called myalgic encephalomyelitis /encephalopathy or ME) is a debilitating condition with no known cause or cure. Improvement may occur with medical care and additional therapies of pacing, cognitive behavioural therapy and graded exercise therapy. The latter two therapies have been found to be efficacious in small trials, but patient organisations surveys have reported adverse effects. Although pacing has been advocated by patient organisations, it lacks empirical support. Specialist medical care is commonly provided but its efficacy when given alone is not established. This trial compares the efficacy of the additional therapies when added to specialist medical care against specialist medical care alone.

METHODS: 600 patients, who meet operationalised diagnostic criteria for CFS, will be recruited from secondary care into a randomised trial of four treatments, stratified by current co morbid depressive episode and different CFS/ME criteria. The four treatments are standardised specialist medical care either given alone, or with adaptive pacing therapy or cognitive behaviour therapy or graded exercise therapy. Supplementary therapies will involve fourteen sessions over 23 weeks and a booster session at 36 weeks. Outcome will be assessed at 12, 24, and 52 weeks after randomisation. Two primary outcomes of self-rated fatigue and physical function will assess differential effects of each treatment on these measures. Secondary outcomes include adverse events and reactions, subjective measures of symptoms, mood, sleep and function and objective measures of physical activity, fitness, cost-effectiveness and cost-utility. The primary analysis will be based on intention to treat and will use logistic regression models to compare treatments. Secondary outcomes will be analysed by repeated measures analysis of variance with a linear mixed model. All analyses will allow for stratification factors. Mediators and moderators will be explored using multiple linear and logistic regression techniques with interactive terms, with the sample split into two to allow validation of the initial models. Economic analyses will incorporate sensitivity measures.

DISCUSSION: The results of the trial will provide information about the benefits and adverse effects of these treatments, their cost-effectiveness and cost-utility, the process of clinical improvement and the predictors of efficacy.

 

Source: White PD, Sharpe MC, Chalder T, DeCesare JC, Walwyn R; PACE trial group. Protocol for the PACE trial: a randomised controlled trial of adaptive pacing, cognitive behaviour therapy, and graded exercise, as supplements to standardised specialist medical care versus standardised specialist medical care alone for patients with the chronic fatigue syndrome/myalgic encephalomyelitis or encephalopathy. BMC Neurol. 2007 Mar 8;7:6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2147058/

 

The effect of cognitive behaviour therapy for chronic fatigue syndrome on self-reported cognitive impairments and neuropsychological test performance

Abstract:

BACKGROUND: Patients with chronic fatigue syndrome (CFS) often have concentration and memory problems. Neuropsychological test performance is impaired in at least a subgroup of patients with CFS. Cognitive behavioural therapy (CBT) for CFS leads to a reduction in fatigue and disabilities.

AIM: To test the hypothesis that CBT results in a reduction of self-reported cognitive impairment and in an improved neuropsychological test performance.

METHODS: Data of two previous randomised controlled trials were used. One study compared CBT for adult patients with CFS, with two control conditions. The second study compared CBT for adolescent patients with a waiting list condition. Self-reported cognitive impairment was assessed with questionnaires. Information speed was measured with simple and choice reaction time tasks. Adults also completed the symbol digit-modalities task, a measure of complex attentional function.

RESULTS: In both studies, the level of self-reported cognitive impairment decreased significantly more after CBT than in the control conditions. Neuropsychological test performance did not improve.

CONCLUSIONS: CBT leads to a reduction in self-reported cognitive impairment, but not to improved neuropsychological test performance. The findings of this study support the idea that the distorted perception of cognitive processes is more central to CFS than actual cognitive performance.

 

Source: Knoop H, Prins JB, Stulemeijer M, van der Meer JW, Bleijenberg G. The effect of cognitive behaviour therapy for chronic fatigue syndrome on self-reported cognitive impairments and neuropsychological test performance. J Neurol Neurosurg Psychiatry. 2007 Apr;78(4):434-6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2077788/ (Full article)

 

Personality and chronic fatigue syndrome: methodological and conceptual issues

Abstract:

Among clinical psychologists, consulting physicians, scientific researchers and society in general an image has emerged of patients with chronic fatigue syndrome (CFS) as perfectionist, conscientious, hardworking, somewhat neurotic and introverted individuals with high personal standards, a great desire to be socially accepted and with a history of continuously pushing themselves past their limits.

The aim of this article is to (a) give a concise review of the main recent studies on personality and CFS, (b) address the major methodological problems in the study of personality in CFS and (c) discuss some of the conceptual assumptions that seem to limit the research on personality and CFS.

The results of the reviewed studies range from no evidence of major differences between the personalities of patients with CFS and controls, to evidence of severe psychopathology and personality disorder in patients with CFS. Although personality seems to play a role in CFS, it is difficult to draw general conclusions on the relation between personality and CFS. It is argued that this is partially due to the diversity and heterogeneity in study methods, patient populations, control groups and CFS case definitions.

Personality should be regarded as an important factor to be studied in CFS. However, additional studies are needed, not focusing exclusively on personality disorder, or personality considered on a general trait level. In recent developments in personality research, the continually evolving life narrative that makes sense of, and gives direction to, an individual’s life is also regarded as an important aspect of personality. New insights into personality and CFS might be gained by systematically studying the self-narratives of patients with the syndrome.

 

Source: van Geelen SM, Sinnema G, Hermans HJ, Kuis W. Personality and chronic fatigue syndrome: methodological and conceptual issues. Clin Psychol Rev. 2007 Dec;27(8):885-903. Epub 2007 Jan 27. https://www.ncbi.nlm.nih.gov/pubmed/17350740

 

Incidence, prognosis, and risk factors for fatigue and chronic fatigue syndrome in adolescents: a prospective community study

Abstract:

OBJECTIVE: The objective of this study was to describe the incidence, prevalence, risk factors, and prognosis of fatigue, chronic fatigue, and chronic fatigue syndrome in 11- to 15-year-olds.

METHODS: A random general population sample (n = 842) of British adolescents and their parents were assessed at baseline and 4 to 6 months later. The main outcomes were fatigue, chronic fatigue, and chronic fatigue syndrome, operationally defined.

RESULTS: The incidence over 4 to 6 months was 30.3% for fatigue, 1.1% for chronic fatigue, and 0.5% for chronic fatigue syndrome. The point prevalence was 34.1% and 38.1% for fatigue, 0.4% and 1.1% for chronic fatigue, and 0.1% and 0.5% for chronic fatigue syndrome at time 1 and time 2, respectively. Of participants who were fatigued at time 1, 53% remained fatigued at time 2. The 3 cases of chronic fatigue and 1 case of chronic fatigue syndrome at time 1 had recovered by time 2. Higher risk for development of chronic fatigue at time 2 was associated with time 1 anxiety or depression, conduct disorder, and maternal distress; in multivariate analysis, baseline anxiety or depression remained a significant predictor of chronic fatigue. Increased risk for development of fatigue at time 2 was associated with time 1 anxiety or depression, conduct disorder, and older age; in multivariate analyses, these factors and female gender all were significant predictors of fatigue.

CONCLUSIONS: The incidence rates for chronic fatigue and chronic fatigue syndrome in this adolescent sample were relatively high, but the prognosis for these conditions was good. This prospective study provides evidence for an association between emotional/behavioral problems and subsequent onset of fatigue/chronic fatigue.

 

Source: Rimes KA, Goodman R, Hotopf M, Wessely S, Meltzer H, Chalder T. Incidence, prognosis, and risk factors for fatigue and chronic fatigue syndrome in adolescents: a prospective community study. Pediatrics. 2007 Mar;119(3):e603-9. https://www.ncbi.nlm.nih.gov/pubmed/17332180

 

An ‘overwhelming illness’: women’s experiences of learning to live with chronic fatigue syndrome/myalgic encephalomyelitis

Abstract:

The processes through which people learn to live with CFS/ME are poorly understood and have not been rigorously explored within the literature. Semi-structured interviews were conducted with eight women and analysed using interpretative phenomenological analysis. Participants initially described being ‘overwhelmed’ by CFS/ME. Attempts at seeking help were unsatisfactory and participants described feeling let down and disbelieved.

Participants reacted to this by identifying types of ‘self-help’ and assertively taking more responsibility for their illness and its treatment. Acquiring social support and greater knowledge were key mediating factors in the emergence of control and acceptance. The relevance of the themes to existing research and the implications for clinical practice are considered.

 

Source: Edwards CR, Thompson AR, Blair A. An ‘overwhelming illness’: women’s experiences of learning to live with chronic fatigue syndrome/myalgic encephalomyelitis. J Health Psychol. 2007 Mar;12(2):203-14. https://www.ncbi.nlm.nih.gov/pubmed/17284485

 

Alexithymia in chronic fatigue syndrome: associations with momentary, recall, and retrospective measures of somatic complaints and emotions

Abstract:

OBJECTIVE: The relationship between alexithymia and real-time momentary symptom assessments has not been reported. This cross-sectional study hypothesized that alexithymia would be a predictor of somatic symptoms using three different types of symptom measurement (momentary, recall, and retrospective) in the medically unexplained illness of chronic fatigue syndrome (CFS). In addition, it was hypothesized that negative affect would be a significant mediator of the relationship between alexithymia and somatic symptoms. Finally, the relation of alexithymia to physical illness attribution (a CFS illness predictor) was explored.

METHODS: Participants were 111 adults with CFS. Alexithymia was assessed with the Toronto Alexithymia Scale. Momentary ratings of current symptoms and affect were recorded in electronic diaries carried for 3 weeks. Weekly recall of these momentary reports was also recorded. Retrospective measures included 6-month ratings of fatigue and pain, the Fatigue Severity Scale, the Brief Pain Inventory-Short Form, a CFS symptom measure, the Beck Depression Inventory-II, the Beck Anxiety Inventory, and an illness attribution rating.

RESULTS: Partial correlations, controlling for age and sex, yielded no significant associations between general or specific forms of alexithymia and momentary ratings of fatigue or pain. On the other hand, a significant association, partially mediated by anxiety scores, was found between a specific form of alexithymia and a retrospective pain measure. Finally, physical illness attribution was not significantly associated with alexithymia.

CONCLUSION: Based on assessments of real-time and retrospectively measured symptoms, these data provided only modest support for the alexithymia construct as a predictor of somatic symptoms in people with CFS.

 

Source: Friedberg F, Quick J. Alexithymia in chronic fatigue syndrome: associations with momentary, recall, and retrospective measures of somatic complaints and emotions. Psychosom Med. 2007 Jan;69(1):54-60. https://www.ncbi.nlm.nih.gov/pubmed/17244849

 

A case control study of premorbid and currently reported physical activity levels in chronic fatigue syndrome

Abstract:

BACKGROUND: Patients with chronic fatigue syndrome typically report high levels of physical activity before becoming ill. Few studies have examined premorbid and current activity levels in chronically fatigued patients.

METHODS: In a case-control study, 33 patients with chronic, unexplained, disabling fatigue attending a university-based clinic specializing in fatigue were compared to 33 healthy, age- and sex-matched controls. Patients rated their activity levels before their illness and currently, using scales designed for this purpose. Controls reported their level of activity of 2 years previously and currently. Chi-square analyses, Student’s t tests, and Wilcoxon signed rank tests were used in pair matched analyses.

RESULTS: Compared to healthy controls, patients with chronic, unexplained fatigue rated themselves as more active before their illness (p < or = 0.001) and less active currently (p < or = 0.001). The patients also reported they currently stood or walked less than the controls (median [inter-quartile range] = 4 2345 versus 9 [7.5-12] hours, p < or = 0.001), and spent more time reclining (median [inter-quartile range] = 12 10111213141516 versus 8 [8-9.5] hours, p < or = 0.001). These differences remained significant for the subset of patients who met strict criteria for chronic fatigue syndrome or fibromyalgia.

CONCLUSION: Patients with chronic, unexplained, disabling fatigue reported being more active before becoming ill than healthy controls. This finding could be explained by greater premorbid activity levels that could predispose to illness, or by an overestimation of previous activity. Either possibility could influence patients’ perceptions of their current activity levels and their judgments of recovery. Perceived activity should be addressed as part of management of the illness.

 

Source: Smith WR, White PD, Buchwald D. A case control study of premorbid and currently reported physical activity levels in chronic fatigue syndrome. BMC Psychiatry. 2006 Nov 13;6:53. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1647270/ (Full article)

 

Premorbid predictors of chronic fatigue

Abstract:

CONTEXT: Chronic fatigue syndrome is a disabling problem characterized by persistent fatigue lasting at least 6 months with a number of ancillary symptoms. Although the etiology of chronic fatiguing illness is unknown, some evidence suggests that stress may confer increased risk for development of the disorder. Moreover, subjects with chronic fatiguing illness may have distinctive personality traits, although this finding could reflect confounding by other mechanisms.

OBJECTIVE: To assess the prospective association of premorbid self-reported stress and personality with chronic fatigue-like illness.

DESIGN: Prospective nested case-control study in a population-based sample.

SETTING: General community.

PARTICIPANTS: From the Swedish Twin Registry, 19,192 twins born between January 1, 1935, and December 31, 1958.

MAIN OUTCOME MEASURES: Information about current chronic fatiguing illnesses was obtained from computer-assisted telephone interviews conducted between 1998 and 2002. Self-reported stress (based on a single question) and personality scales (emotional instability and extraversion in the Eysenck Personality Inventory) were measured from 1972 to 1973 by a mailed questionnaire. Relative risks were estimated with case-control analyses (matched for age and sex) and co-twin control analyses (comparing discordant pairs).

RESULTS: Higher emotional instability and self-reported stress in the premorbid period were associated with higher risk for chronic fatigue-like illness in matched case-control analyses (odds ratios, 1.72 and 1.64, respectively). In co-twin control analyses, relative risk of emotional instability decreased to 1.02 whereas that of stress increased considerably to 5.81. There was no association between extraversion and fatigue.

CONCLUSIONS: Elevated premorbid stress is a significant risk factor for chronic fatigue-like illness, the effect of which may be buffered by genetic influences. Emotional instability assessed 25 years earlier is associated with chronic fatigue through genetic mechanisms contributing to both personality style and expression of the disorder. These findings suggest plausible mechanisms for chronic fatiguing illness.

 

Source: Kato K, Sullivan PF, Evengård B, Pedersen NL. Premorbid predictors of chronic fatigue. Arch Gen Psychiatry. 2006 Nov;63(11):1267-72. https://www.ncbi.nlm.nih.gov/pubmed/17088507

 

Early adverse experience and risk for chronic fatigue syndrome: results from a population-based study

Abstract:

CONTEXT: Chronic fatigue syndrome (CFS) is an important public health problem. The causes of CFS are unknown and effective prevention strategies remain elusive. A growing literature suggests that early adverse experience increases the risk for a range of negative health outcomes, including fatiguing illnesses. Identification of developmental risk factors for CFS is critical to inform pathophysiological research and devise targets for primary prevention.

OBJECTIVE: To examine the relationship between early adverse experience and risk for CFS in a population-based sample of clinically confirmed CFS cases and nonfatigued control subjects.

DESIGN, SETTING, AND PARTICIPANTS: A case-control study of 43 cases with current CFS and 60 nonfatigued controls identified from a general population sample of 56 146 adult residents from Wichita, Kan.

MAIN OUTCOME MEASURES: Self-reported childhood trauma (sexual, physical, and emotional abuse and emotional and physical neglect) and psychopathology (depression, anxiety, and posttraumatic stress disorder) by CFS status.

RESULTS: The CFS cases reported significantly higher levels of childhood trauma and psychopathology compared with the controls. Exposure to childhood trauma was associated with a 3- to 8-fold increased risk for CFS across different trauma types. There was a graded relationship between the degree of trauma exposure and CFS risk. Childhood trauma was associated with greater CFS symptom severity and with symptoms of depression, anxiety, and posttraumatic stress disorder. The risk for CFS conveyed by childhood trauma increased with the presence of concurrent psychopathology.

CONCLUSIONS: This study provides evidence of increased levels of multiple types of childhood trauma in a population-based sample of clinically confirmed CFS cases compared with nonfatigued controls. Our results suggest that childhood trauma is an important risk factor for CFS. This risk was in part associated with altered emotional state. Studies scrutinizing the psychological and neurobiological mechanisms that translate childhood adversity into CFS risk may provide direct targets for the early prevention of CFS.

 

Source: Heim C, Wagner D, Maloney E, Papanicolaou DA, Solomon L, Jones JF, Unger ER, Reeves WC. Early adverse experience and risk for chronic fatigue syndrome: results from a population-based study. Arch Gen Psychiatry. 2006 Nov;63(11):1258-66. https://www.ncbi.nlm.nih.gov/pubmed/17088506

 

Long-term efficacy of cognitive-behavioral therapy by general practitioners for fatigue: a 4-year follow-up study

Abstract:

OBJECTIVE: In an earlier study, we found that cognitive-behavioral therapy (CBT) delivered by general practitioners (GPs) for fatigue among employees on sick leave was not effective after 12 months. In this study we aim to assess the long-term efficacy of CBT by GPs for fatigue. It was hypothesized that the intervention could prevent deterioration as well as relapse of fatigue complaints and relapse into absenteeism in the long term.

METHODS: Patients who participated in the original randomized controlled trial were followed up 4 years later. Fatigue and absenteeism were the main outcomes.

RESULTS: Fatigue and absenteeism were high in the intervention and control groups at the 4-year follow-up. There was no significant difference between the intervention group and the control group on fatigue and absenteeism. The intervention group however tended toward less-favorable outcomes as compared with the control group.

CONCLUSIONS: Like that of chronic fatigue syndrome, the prognosis of less-advanced fatigue is rather poor. CBT delivered by GPs is not effective in the long term.

 

Source: Leone SS, Huibers MJ, Kant I, van Amelsvoort LG, van Schayck CP, Bleijenberg G, Knottnerus JA. Long-term efficacy of cognitive-behavioral therapy by general practitioners for fatigue: a 4-year follow-up study. J Psychosom Res. 2006 Nov;61(5):601-7. https://www.ncbi.nlm.nih.gov/pubmed/17084137