The monoaminergic stabiliser (−)-OSU6162 has in previous studies shown promising effects on mental fatigue after stroke and traumatic brain injury. This study investigated the safety and effectiveness of (−)-OSU6162 in patients with myalgic encephalomyelitis/chronic fatigue syndrome.

A total of 62 patients were randomly assigned to placebo or (−)-OSU6162. Primary outcomes were assessment on the mental fatigue scale (MFS) and the clinical global impression of change (CGI-C) scale. Secondary outcomes were results on the FibroFatigue scale (FF), the Beck Depression Inventory (BDI), the pain visual analogue scale and neuropsychological tests. Assessments were performed at baseline, after 1 and 2 weeks of treatment and at follow-up after 6 weeks.

MFS and CGI-C showed significant improvements for both treatment groups after treatment but not at follow-up; a similar pattern was seen for FF and BDI. However, significant differences between groups could not be demonstrated. On the other hand, correlation analyses showed a significant correlation between (−)-OSU6162 concentration and change in MFS, FF, and BDI score within the concentration interval 0.1–0.7 µM. Exploratory subgroup analyses showed a larger treatment effect with (−)-OSU6162 in improving MFS and FF symptoms in patients on antidepressant therapy compared to those without antidepressant treatment.

(−)-OSU6162 was found to be safe and well tolerated. When analysing the entire material (−)-OSU6162 was not found to differ significantly from placebo in alleviating fatigue in ME patients but was superior to placebo in counteracting fatigue in a subgroup of ME patients who received concomitant pharmacological treatment for depression.

There is evidence that patients with chronic fatigue syndrome (CFS) have mild hypocortisolism. The clinical significance of this is unclear. We aimed to determine whether hypocortisolism exerted any effect on the response of CFS to cognitive behavioural therapy (CBT).

We measured 24-h urinary free cortisol (UFC) in 84 patients with Centers for Disease Control and Prevention (CDC)-defined CFS (of whom 64 were free from psychotropic medication) who then received CBT in a specialist, tertiary out-patient clinic as part of their usual clinical care. We also measured salivary cortisol output from 0800 to 2000 h in a subsample of 56 psychotropic medication-free patients.

Overall, 39% of patients responded to CBT after 6 months of treatment. Lower 24-h UFC output was associated with a poorer response to CBT but only in psychotropic medication-free patients. A flattened diurnal profile of salivary cortisol was also associated with a poor response to CBT.

Low cortisol is of clinical relevance in CFS, as it is associated with a poorer response to CBT. Hypocortisolism could be one of several maintaining factors that interact in the persistence of CFS.

Increased rates of psychiatric disorder have previously been reported in those diagnosed with chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME), although the direction of causation in this relationship has not been established. We aimed to test the hypothesis that individuals with self-reported CFS/ME have increased levels of psychiatric disorder prior to the onset of their fatigue symptoms.

A total of 5362 participants were prospectively followed with various measures of personality, psychiatric disorder and fatigue levels collected over the first 43 years of their life. CFS/ME was identified through self-report during a semi-structured interview at age 53 years.

Thirty-four (1.1%) of the 3035 subjects assessed at age 53 years reported a diagnosis of CFS/ME. CFS/ME was more common among females, but there was no association between CFS/ME and either social class, social mobility or educational level. Those with psychiatric illness between the ages of 15 and 36 years were more likely to report CFS/ME later in life with an odds ratio (OR, adjusted for sex) of 2.65 [95% confidence interval (CI) 1.26–5.57, p=0.01]. Increased levels of psychiatric illness, in particular depression and anxiety, were present prior to the occurrence of fatigue symptoms. There was a dose–response relationship between the severity of psychiatric symptoms and the likelihood of later CFS/ME. Personality factors were not associated with a self-reported diagnosis of CFS/ME.

This temporal, dose–response relationship suggests that psychiatric disorders, or shared risk factors for psychiatric disorders, are likely to have an aetiological role in some cases of CFS/ME.

The aetiology of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is still unknown. The identification of risk factors for CFS/ME is of great importance to practitioners.

A systematic scoping review was conducted to locate studies that analysed risk factors for CFS/ME using multiple predictors. We searched for published and unpublished literature in 11 electronic databases, reference lists of retrieved articles and guideline stakeholder submissions in conjunction with the development of a forthcoming national UK guideline. Risk factors and findings were extracted in a concise tabular overview and studies synthesized narratively.

Eleven studies were identified that met inclusion criteria: two case-control studies, four cohort studies, three studies combining a cohort with a case-control study design, one case-control and twin study and one cross-sectional survey. The studies looked at a variety of demographic, medical, psychological, social and environmental factors to predict the development of CFS/ME. The existing body of evidence is characterized by factors that were analysed in several studies but without replication of a significant association in more than two studies, and by studies demonstrating significant associations of specific factors that were not assessed in other studies. None of the identified factors appear suitable for the timely identification of patients at risk of developing CFS/ME within clinical practice.

Various potential risk factors for the development of CFS/ME have been assessed but definitive evidence that appears meaningful for clinicians is lacking.