Early ReportLow-dose hydrocortisone in chronic fatigue syndrome: a randomised crossover trial
Introduction
Chronic fatigue syndrome affects up to 2·6% of people who attend primary care in the UK1 and is also encountered in many medical specialties. Patients with chronic fatigue syndrome have a poor outcome: only 3% of patients spontaneously recover at 18 months of follow-up.2
About 50% of patients with chronic fatigue syndrome have co-morbid major depression.3 However, the results from placebo-controlled trials of antidepressants differ; some studies show moderate efficacy,4 whereas others do not.5 Controlled studies suggest that graded exercise therapy6 and cognitive behavioural therapy7, 8 are effective treatments, but are relatively expensive and not widely available because of a shortage of adequately trained therapists. In addition, many patients are wary of the rationale behind these treatments. Alternative effective treatments for chronic fatigue syndrome are needed.
Studies of the hypothalamo-pituitary adrenal (HPA) axis in chronic fatigue syndrome show a mild hypocortisolism of central origin, in contrast to the hypercortisolism of major depression.9, 10, 11, 12 Given the overlap between the symptoms of Addison's disease and chronic fatigue syndrome, Demitrack and colleagues9 postulated that this hypocortisolism may be important in the mediation of central fatigue.9 There are suggestions that this underactivity of the HPA axis could result from factors that are secondary to the primary aetiology of chronic fatigue syndrome, such as sleep disturbance.13 Whatever the origin, one possibility is that low circulating cortisol could act as a biological factor that contributes to fatigue chronicity and interacts adversely with perpetuating cognitive and behavioural processes.14 Thus, a rise in cortisol concentrations might improve fatigue.
We set out to test the hypothesis that low-dose hydrocortisone therapy would improve fatigue in chronic fatigue syndrome using a randomised, double-blind, placebo-controlled, crossover design.
Section snippets
Patients
Between November, 1995, and February, 1997, we recruited patients in London and Cambridge from established clinics that specialise in chronic fatigue syndrome. The study was approved by both local ethical committees. We included patients who fulfilled both international consensus criteria for chronic fatigue syndrome.15, 16 All patients underwent medical screening that included physical examination and relevant investigation, with a minimum of urine analysis, full blood count, measurement of
Results
The trial profile shows the numbers of patients throughout the trial (figure 1). None of the 32 valid patients who started treatment dropped out. Thus, our analysis is both on an intention to treat and treatment completers basis. Our compliance assessment suggested that no patient missed more than two doses of trial medication. The mean age of the 32 patients was 35·3 (range 19–58) years and 20 were women. Nine (28%) patients had a history of psychiatric illness, whereas 19 (59%) related the
Discussion
This study shows that low-dose hydrocortisone results in significant reductions in self-rated fatigue and disability in patients with chronic fatigue syndrome. Moreover, about a third of patients had a clinically significant reduction in fatigue, most to a level at or below that of the general population, with accompanying reductions in disability.
The effect of low-dose hydrocortisone was to increase the overall 24 h cortisol output after 28 days of treatment. When taken together with the
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Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): Where will the drugs come from?
2021, Pharmacological ResearchElevated fingernail cortisol levels in major depressive episodes
2018, PsychoneuroendocrinologyCitation Excerpt :Our results, therefore, provide new evidence that indicates that this somatic symptom is linked to lowered cortisol levels, not only in other disorders which have commonly been associated with low cortisol levels, such as Chronic Fatigue Syndrome (Cleare, 2003), but also in affective disorders, such as MDE. It has been suggested that lowered cortisol may be an aetiological factor in CFS (Cleare, 2004), given that low dose cortisol replacement can alleviate the experience of fatigue (Cleare et al., 1999), which raises similar possibilities in patients with fatigue within affective disorders (Cleare, 2009). Cortisol measurement from fingernails presents a number of advantages over hair extraction, the other novel specimen recently introduced for measuring chronic cortisol levels over longer periods.
Chronic Fatigue Syndrome
2017, Principles and Practice of Pediatric Infectious DiseasesThe interface between chronic fatigue syndrome and depression: A psychobiological and neurophysiological conundrum
2017, Neurophysiologie CliniqueCitation Excerpt :Much biological research has focused on the HPA axis, with evidence of reduced cortisol output in CFS patients, which is been detectable by sequential salivary samples [14]. Cortisol replacement has been found to ameliorate symptoms of fatigue and other signs of CFS [16,46]. However, in most studies, patients with symptoms of CFS have been ill for many years; as such it is not clear whether HPA axis disturbances were present before the onset or occurred early on in the time course of CFS, nor is it clear to what extent observed HPA axis disturbances are secondary to inactivity, sleep disturbances or deconditioning or stress [15].