Fatigue severity remains stable over time and independently associated with orthostatic symptoms in chronic fatigue syndrome: a longitudinal study


Jones DE, Gray J, Frith J, Newton JL


UK NIHR Biomedical Centre in Ageing, Institute of Cellular Medicine, Institute for Ageing and Health, Newcastle University, Newcastle, UK


To examine fatigue variability over time in chronic fatigue syndrome (CFS) and the effect of other symptoms on its predictability.


Longitudinal cohort study of patients with CFS (Fukuda criteria).


Specialist CFS clinical service.


Phase 1: 100 patients who participated in a study of CFS symptoms in 2005 were revisited in 2009. Phase 2: 25 patients completed fatigue diaries to address intra- and inter-day variability in perceived fatigue.

Main outcome measures

Phase 1: subjects completed fatigue impact scale (FIS), Epworth sleepiness scale (ESS), orthostatic grading scale (OGS) and hospital anxiety and depression scale (HADS). Changes in variables represented the differences between 2005 and 2009. Phase 2: subjects rated fatigue on a scale of 0 (no fatigue) to 10 (severe fatigue) four times a day for 5 weeks.


Symptom assessment tools were available in both 2005 and 2009 for 74% of patients. FIS and HADS depression (HAD-D) and anxiety (HAD-A) scores significantly improved during follow-up whereas ESS and OGS remained stable. FIS improved in 29/74 (39%) subjects, and by ≥ 10 points in 19 (26%). FIS worsened by ≥ 10 points in 33/74 (45%) subjects. On multivariate analysis, independent predictors of current fatigue (FIS in 2009) were FIS in 2005, HAD-D in 2009, OGS in 2009 and change in HAD-A. Reported fatigue was stable from week to week and from day to day. Patients reported higher fatigue in the morning (mean±SD; 6.4±2), becoming significantly lower at lunchtime (6.2±2; P<0.05) and increasing again to 7±2 at bedtime.


Current fatigue is independently associated with current autonomic symptom burden, current depression and change in anxiety during follow-up. These findings have implications for targeted symptom management in CFS.


Journal of Internal Medicine, 2011 Feb; 269(2): 182–8

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