Wearden 1998.

Study characteristics
Methods	RCT, 4 parallel arms
Participants	Diagnostic criteria: Oxford Number of participants: n = 136 Gender: 97 (71%) female Age, mean (SD): 38.7 (10.8) years Earlier treatment: NS Co‐morbidity: 46 (34%) with depressive disorder according to DSM‐III‐R criteria, use of AD NS Illness duration: duration of fatigue, median (IQR) 28.0 (39.5) months Work and employment status: 114 (84%) had recently changed occupation Setting: secondary/tertiary care Country: UK
Interventions	Group 1: GET + fluoxetine (n = 33) Group 2: GET + drug placebo, 26 weeks, preferred aerobic exercise 20 min ≥ 3 times/week, up to 75% of participants' functional maximum (n = 34) Group 3: exercise placebo + fluoxetine (n = 35) Group 4: exercise placebo + drug placebo, 26 weeks, offered no specific advice but participants told to do what they felt capable of and to rest when the felt they needed to (n = 34)
Outcomes	Fatigue (FS; 14 items; ≥ 4 were used as cutoff to designate caseness) General health status (MOS, SF‐36); measure of general health status on the following 6 scales (cutoff score for poor function in parentheses): physical function (< 83.3), role or occupational function (≤ 50), social function (≤ 40), pain (≤ 50), health perception (≤ 70) and mental health (≤ 67) Anxiety or depression, HADS; cutoff of ≥ 11 designated cases) Psychiatric diagnoses (Clinical Interview Schedule + supplementary questions by psychologist) Physiological assessments (grip strength and functional work capacity) Outcomes assessed at weeks 12 and 26 (end of treatment)
Notes	Group 4 was used as treatment as usual, as participants were given no specific advice on exercise but were advised to exercise when they felt capable. We obtained supplementary HADS data from study authors for the first version of this review
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "...randomised into a treatment group by computer generated numbers, with groups of 10 to obtain roughly equal numbers"
Allocation concealment (selection bias)	Low risk	Quote: "A list of subject numbers marked with the exercise group for each number was held by the physiotherapist. Pharmacy staff dispensed medication in accordance with the subject number assigned to each subject." The initial assessment was done independently: "All patients were medically assessed by a doctor...under the supervision of a consultant physician"
Blinding (performance bias and detection bias) of participants and personnel?	High risk	Quote: "The drug treatment was double blind. The placebo to fluoxetine was a capsule of similar taste and appearance. The placebo to the exercise programme was a review of activity diaries by the physiotherapists"
Blinding (performance bias and detection bias) of outcome assessors?	High risk	Blinding not possible for self‐reported measurements (e.g. FS, SF‐36)
Incomplete outcome data (attrition bias) All outcomes	High risk	Quote: "Analysis was carried out on an intention to treat basis. When there were missing data at 12 and 26 weeks, scores on the previous assessment were substituted. No data were available on 17 patients for the week 12 assessment, functional work capacity assessments at week 0, seven at week 12 and seven at week 26" Large dropout rates in all intervention groups
Selective reporting (reporting bias)	High risk	It is clear (p 488) that investigators collected data for all 6 subscales of the MOS that they used (as well as measures for fatigue, depression and anxiety). Data from fatigue and depression (primary outcomes) are reported numerically. Data from the anxiety scale are said to show 'no significant changes' and are not reported numerically. This is also the case for 5 of the 6 subscales of the MOS, with the exception of health perceptions, which is significant and favours the intervention group. NB: Data for forced work capacity were collected by investigators but are not reported in this review
Other bias	Low risk	We do not suspect other bias