| Outcomes | No of Participants (studies*) Follow up | Quality of the evidence (GRADE) | Relative effect (95% CI) | Anticipated absolute effects | |
|---|---|---|---|---|---|
| Risk with Control | Risk difference with Corticosteroids (oral hydrocortisone or fludrocortisone, nasal flunisolide) versus placebo (95% CI) | ||||
|
Quality of Life: SF36 physical total Scale from: 0 to 100. |
40 (1 study) 6 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision |
The mean quality of life: sf36 physical total at 6-11 weeks in the control groups was 46.75 |
The mean quality of life: sf36 physical total at 6-11 weeks in the intervention group (fludrocortisone) was 7.54 higher (0.71 lower to 15.79 higher) | |
|
Quality of Life: SF36 energy or fatigue Scale from: 0 to 100. |
40 (1 study) 6 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision |
The mean quality of life: sf36 energy or fatigue at 6 weeks in the control groups was 18.2 |
The mean quality of life: sf36 energy or fatigue at 6 weeks in the intervention group (fludrocortisone) was 2.1 higher (7.43 lower to 11.63 higher) | |
|
Quality of Life: SF36 emotional wellbeing Scale from: 0 to 100. |
40 (1 study) 6 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision |
The mean quality of life: sf36 emotional wellbeing at 6 weeks in the control groups was 68.8 |
The mean quality of life: sf36 emotional wellbeing at 6 weeks in the intervention group (fludrocortisone) was 3.8 higher (5.29 lower to 12.89 higher) | |
|
Quality of Life: SF36 role emotional Scale from: 0 to 100. |
40 (1 study) 6 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision |
The mean quality of life: sf36 role emotional at 6 weeks in the control groups was 87.8 |
The mean quality of life: sf36 role emotional at 6 weeks in the intervention group (fludrocortisone) was 0 higher (14.96 lower to 14.96 higher) | |
|
Quality of Life: SF36 role physical Scale from: 0 to 100. |
40 (1 study) 6 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision |
The mean quality of life: sf36 role physical at 6 weeks in the control groups was 25 |
The mean quality of life: sf36 role physical at 6 weeks in the intervention group (fludrocortisone) was 11.8 lower (29.09 lower to 5.49 higher) | |
|
Quality of Life: SF36 pain Scale from: 0 to 100. |
40 (1 study) 6 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision |
The mean quality of life: sf36 pain at 6 weeks in the control groups was 50.5 |
The mean quality of life: sf36 pain at 6 weeks in the intervention group (fludrocortisone) was 0.6 lower (15.29 lower to 14.09 higher) | |
|
Quality of life: SF36 social Scale from: 0 to 100. |
40 (1 study) 6 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision |
The mean quality of life: sf36 social at 6 weeks in the control groups was 38.2 |
The mean quality of life: sf36 social at 6 weeks in the intervention group (fludrocortisone) was 1.9 higher (11.06 lower to 14.86 higher) | |
|
Quality of life: SF36 general wellbeing Scale from: 0 to 100. |
40 (1 study) 6 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision |
The mean quality of life: sf36 general wellbeing at 6 weeks in the control groups was 35.8 |
The mean quality of life: sf36 general wellbeing at 6 weeks in the intervention groups (fludrocortisone) was 3.7 lower (12.54 lower to 5.14 higher) | |
|
Fatigue: fatigue on VAS Scale from: 0 to 10. |
40 (1 study) 6 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision |
The mean fatigue: fatigue on vas at 6 weeks in the control groups was 7.5 |
The mean fatigue: fatigue on vas at 6 weeks in the intervention group (fludrocortisone) was 0 higher (1.1 lower to 1.1 higher) | |
|
Fatigue: Chronic Fatigue Syndrome Severity Rating Scale from: not reported. |
28 (1 study) 4-8 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision |
The mean [nasal] symptom scales: rhinitis severity rating at 4-8 weeks in the control group was 18.13 |
The mean symptom scales: rhinitis severity rating at 4-8 weeks in the intervention group (nasal flunisolide) was 3.17 lower (7.48 lower to 1.14 higher) | |
|
Fatigue: Profile of Mood States – fatigue Scale from: 0 to 28. |
83 (1 study) 11 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness |
The mean fatigue: profile of mood states - fatigue at 11 weeks in the control groups was 16.4 |
The mean fatigue: profile of mood states - fatigue at 11 weeks in the intervention groups (fludrocortisone) was 0.20 lower (3.47 lower to 3.07 higher) | |
|
Fatigue: Profile of Mood States – fatigue Scale from: 0 to 28. |
68 (1 study) 12 weeks |
⊕⊕⊝⊝ due to risk of bias, indirectness |
The mean fatigue: profile of mood states - fatigue at 12 weeks in the control groups was −1.8 |
The mean fatigue: profile of mood states - fatigue at 12 weeks in the intervention groups (hydrocortisone) was 1.8 lower (4.14 lower to 0.54 higher) | |
|
Fatigue: Profile of Mood States – vigour Scale from: 0 to 32. |
83 (1 study) 11 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness |
The mean fatigue: profile of mood states - vigour at 11 weeks in the control groups was 8.6 |
The mean fatigue: profile of mood states - vigour at 11 weeks in the intervention groups (fludrocortisone) was 0.2 higher (2.56 lower to 2.96 higher) | |
|
Fatigue: Profile of Mood States – vigour Scale from: 0 to 32. |
68 (1 study) 12 weeks |
⊕⊕⊝⊝ due to risk of bias, indirectness |
The mean fatigue: profile of mood states - vigour at 12 weeks in the control groups was 3.3 |
The mean fatigue: profile of mood states - vigour at 12 weeks in the intervention groups (hydrocortisone) was 0.5 higher (1.07 lower to 2.07 higher) | |
|
Fatigue: Wood Mental Fatigue Inventory Scale from: 0 to 36. |
83 (1 study) 11 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision |
The mean fatigue: wood mental fatigue inventory at 11 weeks in the control groups was 13.3 |
The mean fatigue: wood mental fatigue inventory at 11 weeks in the intervention group (fludrocortisone) was 0.8 higher (3.66 lower to 5.26 higher) | |
|
Physical function: SF36 physical function Scale from: 0 to 100. |
83 (1 study) 11 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision |
The mean physical function: sf36 physical function at 11 weeks in the control groups was 51.4 |
The mean physical function: sf36 physical function at 11 weeks in the intervention group (fludrocortisone) was 7.5 higher (3.2 lower to 18.2 higher) | |
|
Psychological status: SF36 mental health Scale from: 0 to 100. |
83 (1 study) 11 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision |
The mean psychological status: sf36 mental health at 11 weeks in the control groups was 69.8 |
The mean psychological status: sf36 mental health at 11 weeks in the intervention group (fludrocortisone) was 1.2 lower (8.92 lower to 6.52 higher) | |
| Adverse events: adverse events leading to study withdrawal |
40 (1 study) 6 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision | Peto OR 0.13 (0.01 to 2.13) | 100 per 1000 |
100 fewer per 1000 (from 250 fewer to 50 more) (with fludrocortisone) |
| Adverse events: adverse effects/adverse events |
123 (2 studies) 6-11 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness | RR 0.86 (0.63 to 1.17) | 554 per 1000 |
78 fewer per 1000 (from 205 fewer to 94 more) (with fludrocortisone) |
| Adverse events: any adverse reaction |
70 (1 study) 12 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision | RR 1.15 (0.93 to 1.43) | 771 per 1000 |
116 more per 1000 (from 54 fewer to 332 more) (with hydrocortisone) |
|
Psychological status: Beck Depression Inventory Scale from: 0 to 63. |
83 (1 study) 11 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision |
The mean psychological status: beck depression inventory at 11 weeks in the control groups was 10.8 |
The mean psychological status: beck depression inventory at 11 weeks in the intervention groups (fludrocortisone) was 0.4 lower (3.43 lower to 2.63 higher) | |
|
Psychological status: Beck Depression Inventory Scale from: 0 to 63. |
68 (1 study) 12 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision |
The mean psychological status: beck depression inventory at 12 weeks in the control groups was −0.4 |
The mean psychological status: beck depression inventory at 12 weeks in the intervention groups (hydrocortisone) was 1.7 lower (3.90 lower to 0.5 higher) | |
|
Psychological status: Profile of Mood States – anger Scale from: 0 to 48. |
68 (1 study) 12 weeks |
⊕⊕⊝⊝ due to risk of bias, indirectness |
The mean psychological status: profile of mood states - anger, at 12 weeks in the control groups was −0.8 |
The mean psychological status: profile of mood states - anger, at 12 weeks in the intervention group (hydrocortisone) was 0.8 lower (2.63 lower to 1.03 higher) | |
|
Psychological status: Profile of Mood States – anxiety Scale from: 0 to 36. |
68 (1 study) 12 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision |
The mean psychological status: profile of mood states - anxiety, at 12 weeks in the control groups was −2.1 |
The mean psychological status: profile of mood states - anxiety, at 12 weeks in the intervention group (hydrocortisone) was 1.3 higher (0.17 lower to 2.77 higher) | |
|
Psychological status: Profile of Mood States – confusion Scale from: 0 to 28. |
68 (1 study) 12 weeks |
⊕⊕⊝⊝ due to risk of bias, indirectness |
The mean psychological status: profile of mood states - confusion, at 12 weeks in the control groups was −1.4 |
The mean psychological status: profile of mood states - confusion, at 12 weeks in the intervention group (hydrocortisone) was 0.3 higher (1.18 lower to 1.78 higher) | |
|
Psychological status: Profile of Mood States – depression Scale from: 0 to 60. |
68 (1 study) 12 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision |
The mean psychological status: profile of mood states - depression, at 12 weeks in the control groups was 0 |
The mean psychological status: profile of mood states - depression, at 12 weeks in the intervention group (hydrocortisone) was 1.6 lower (3.61 lower to 0.41 higher) | |
|
Psychological status: Symptom checklist-90-R general sensitivity index Scale from: not reported. |
68 (1 study) 12 weeks |
⊕⊕⊝⊝ due to risk of bias, indirectness |
The mean psychological status: symptom checklist-90-r general sensitivity index at 12 weeks in the control groups was −0.1 |
The mean psychological status: symptom checklist-90-r general sensitivity index at 12 weeks in the intervention group (hydrocortisone) was 0 higher (0.1 lower to 0.1 higher) | |
|
Psychological status: Symptom checklist-90-R positive symptom distress index Scale from: not reported. |
68 (1 study) 12 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision |
The mean psychological status: symptom checklist-90-r positive symptom distress index at 12 weeks in the control groups was −0.1 |
The mean psychological status: symptom checklist-90-r positive symptom distress index at 12 weeks in the intervention group (hydrocortisone) was 0.1 higher (0.04 lower to 0.24 higher) | |
|
Psychological status: Symptom checklist-90-R positive symptom total Scale from: not reported. |
68 (1 study) 12 weeks |
⊕⊕⊝⊝ due to risk of bias, indirectness |
The mean psychological status: symptom checklist-90-r positive symptom total at 12 weeks in the control groups was −2.4 |
The mean psychological status: symptom checklist-90-r positive symptom total at 12 weeks in the intervention group (hydrocortisone) was 0.2 lower (5.5 lower to 5.1 higher) | |
|
Psychological status: Hamilton Depression Rating Scale Scale from: not reported. |
65 (1 study) 12 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision |
The mean psychological status: hamilton depression rating scale at 12 weeks in the control groups was 0.1 |
The mean psychological status: hamilton depression rating scale at 12 weeks in the intervention group (hydrocortisone) was 0.9 lower (2.55 lower to 0.75 higher) | |
|
Psychological status: Positive and negative effect scale (PANAS) positive affect Scale from: 10 to 50. |
40 (1 study) 6 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision |
The mean psychological status: positive and negative effect scale (panas) positive affect at 6 weeks in the control groups was 21.7 |
The mean psychological status: positive and negative effect scale (panas) positive affect at 6 weeks in the intervention group (fludrocortisone) was 1 higher (3.67 lower to 5.67 higher) | |
|
Activity levels: activity scale Scale from: not reported. |
68 (1 study) 12 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision |
The mean activity levels: activity scale at 12 weeks in the control groups was 0.7 |
The mean activity levels: activity scale at 12 weeks in the intervention group (hydrocortisone) was 0.4 lower (1 lower to 0.2 higher) | |
|
Activity levels: distance before exhausted (ordinal scale) Scale from: 1 to 5. |
40 (1 study) 6 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision |
The mean activity levels: distance before exhausted (ordinal scale) at 6 weeks in the control groups was 2.7 |
The mean activity levels: distance before exhausted (ordinal scale) at 6 weeks in the intervention group (fludrocortisone) was 0 higher (0.72 lower to 0.72 higher) | |
|
Activity levels: Duke Activity Status Index Scale from: 0 to 58.2. |
83 (1 study) 11 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision |
The mean activity levels: duke activity status index at 11 weeks in the control groups was 6.7 |
The mean activity levels: duke activity status index at 11 weeks in the intervention group (fludrocortisone) was 2.5 higher (1.49 lower to 6.49 higher) | |
| Cognitive function: Reaction time (secs) |
40 (1 study) 6 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision |
The mean cognitive function: reaction time (secs) at 6 weeks in the control groups was 0.36 |
The mean cognitive function: reaction time (secs) at 6 weeks in the intervention group (fludrocortisone) was 0.01 lower (0.06 lower to 0.04 higher) | |
|
Cognitive function: inability to concentrate on VAS Scale from: 0 to 10. |
40 (1 study) 6 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision |
The mean cognitive function: inability to concentrate on vas at 6 weeks in the control groups was 5.8 |
The mean cognitive function: inability to concentrate on vas at 6 weeks in the intervention group (fludrocortisone) was 0.6 lower (2.18 lower to 0.98 higher) | |
|
Cognitive function: forgetfulness on VAS Scale from: 0 to 10. |
40 (1 study) 6 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision |
The mean cognitive function: forgetfulness on vas at 6 weeks in the control groups was 5.6 |
The mean cognitive function: forgetfulness on vas at 6 weeks in the intervention group (fludrocortisone) was 0.9 lower (2.45 lower to 0.65 higher) | |
|
Cognitive function: confusion on VAS Scale from: 0 to 10. |
40 (1 study) 6 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision |
The mean cognitive function: confusion on vas at 6 weeks in the control groups was 4.4 |
The mean cognitive function: confusion on vas at 6 weeks in the intervention group (fludrocortisone) was 0.1 lower (1.68 lower to 1.48 higher) | |
|
Pain: muscle pain on VAS Scale from: 0 to 10. |
40 (1 study) 6 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision |
The mean pain: muscle pain on vas at 6 weeks in the control groups was 5.9 |
The mean pain: muscle pain on vas at 6 weeks in the intervention group (fludrocortisone) was 0.1 lower (1.82 lower to 1.62 higher) | |
|
Pain: joint pain on VAS Scale from: 0 to 10. |
40 (1 study) 6 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision |
The mean pain: joint pain on vas at 6 weeks in the control groups was 5.1 |
The mean pain: joint pain on vas at 6 weeks in the intervention group (fludrocortisone) was 0.3 lower (2.39 lower to 1.79 higher) | |
|
Sleep quality: unrefreshing sleep on VAS Scale from: 0 to 10. |
40 (1 study) 6 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision |
The mean sleep quality: unrefreshing sleep on vas at 6 weeks in the control groups was 8.2 |
The mean sleep quality: unrefreshing sleep on vas at 6 weeks in the intervention group (fludrocortisone) was 0.5 lower (1.68 lower to 0.68 higher) | |
|
Sleep quality: Functional Outcomes of Sleep Questionnaire Scale from: not reported. |
28 (1 study) 4-8 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision |
The mean [nasal] sleep quality: functional outcomes of sleep questionnaire at 4-8 weeks in the control group was 12.4 |
The mean [nasal] sleep quality: functional outcomes of sleep questionnaire at 4-8 weeks in the intervention group (nasal flunisolide) was 0.89 higher (0.99 lower to 2.77 higher) | |
|
Sleep quality: Epworth Sleepiness Scale Scale from: 0 to 24. |
28 (1 study) 4-8 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision |
The mean [nasal] sleep quality: epworth sleepiness scale at 4-8 weeks in the control group was 11.66 |
The mean [nasal] sleep quality: epworth sleepiness scale at 4-8 weeks in the intervention group (nasal flunisolide) was 3.18 lower (6.57 lower to 0.21 higher) | |
| Exercise performance measure: Treadmill time (mins) |
40 (1 study) 6 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision |
The mean exercise performance measure: treadmill time (mins) at 6 weeks in the control groups was 20.2 |
The mean exercise performance measure: treadmill time (mins) at 6 weeks in the intervention group (fludrocortisone) was 2.6 higher (3.85 lower to 9.05 higher) | |
|
Symptom scales: Wellness scale Scale from: 0 to 100. |
83 (1 study) 11 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision |
The mean symptom scales: wellness scale at 11 weeks in the control groups was 2.7 |
The mean symptom scales: wellness scale at 11 weeks in the intervention groups (fludrocortisone) was 1.1 higher (3.58 lower to 5.78 higher) | |
|
Symptom scales: Wellness scale Scale from: 0 to 100. |
65 (1 study) 12 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision |
The mean symptom scales: wellness scale at 112 weeks in the control groups was 1.7 |
The mean symptom scales: wellness scale at 12 weeks in the intervention groups (hydrocortisone) was 4.6 higher (0.5 lower to 9.70 higher) | |
|
Symptom scales: Sickness Impact Profile Scale from : 0 to 68. |
67 (1 study) 12 weeks |
⊕⊕⊝⊝ due to risk of bias, indirectness |
The mean symptom scales: sickness impact profile at 12 weeks in the control groups was −2.2 |
The mean symptom scales: sickness impact profile at 12 weeks in the intervention group (hydrocortisone) was 0.3 lower (3.46 lower to 2.86 higher) | |
|
Symptom scales: headaches on VAS Scale from: 0 to 10. |
40 (1 study) 6 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision |
The mean symptom scales: headaches on vas at 6 weeks in the control groups was 6 |
The mean symptom scales: headaches on vas at 6 weeks in the intervention group (fludrocortisone) was 0 higher (1.55 lower to 1.55 higher) | |
|
Symptom scales: painful lymph nodes on VAS Scale from: 0 to 10. |
40 (1 study) 6 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision |
The mean symptom scales: painful lymph nodes on vas at 6 weeks in the control groups was 3.7 |
The mean symptom scales: painful lymph nodes on vas at 6 weeks in the intervention group (fludrocortisone) was 0.2 lower (2.31 lower to 1.91 higher) | |
|
Symptom scales: sore throat on VAS Scale from: 0 to 10. |
40 (1 study) 6 weeks |
⊕⊝⊝⊝ due to risk of bias, indirectness, imprecision |
The mean symptom scales: sore throat on vas at 6 weeks in the control groups was 3.3 |
The mean symptom scales: sore throat on vas at 6 weeks in the intervention group (fludrocortisone) was 0.2 lower (1.8 lower to 1.4 higher) | |
Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias
The majority of the evidence included an indirect population (downgraded by one increment) : downgraded if the ME/CFS diagnostic criteria used did not include PEM as a compulsory feature [original analysis]; percentage of participants with PEM unclear [PEM reanalysis – see Appendix G for additional details]
Downgraded by 1 increment if the confidence interval crossed one MID or by 2 increments if the confidence interval crossed both MIDs
The majority of the evidence included an indirect population (downgraded by one increment) or a very indirect population (downgraded by two increments): 1) downgraded if the ME/CFS diagnostic criteria used did not include PEM as a compulsory feature [original analysis]; percentage of participants with PEM unclear [PEM reanalysis – see Appendix G for additional details]. 2) Additionally downgraded due to all participants having rhinitis (Kakumanu 2003)
The majority of the evidence included an indirect population (downgraded by one increment) or a very indirect population (downgraded by two increments): 1) downgraded if the ME/CFS diagnostic criteria used did not include PEM as a compulsory feature [original analysis]; percentage of participants with PEM unclear [PEM reanalysis – see Appendix G for additional details]. 2) Additionally downgraded due the majority of evidence coming from a study where all participants had neurally-mediated hypotension (Rowe 2001)
Studies included for corticosteroids: hydrocortisone – Mckenzie 1998; fludrocortisone – Peterson 1998, Rowe 2001; nasal flunisolide – Kakumanu 2003
From: Pharmacological interventions
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