Seventy controlled studies (n=4,749) were included: 58 RCTs (n=4,176) and 12 CCTs (n=573).
The validity scores ranged from 2 to 19 for the RCTs and from 0 to 14 for the CCTs (details of the individual validity criteria were reported). The RCTs frequently had poor allocation concealment and lacked intention-to treat analyses.
Behavioural (15 RCTs, 1 CCT). Fourteen studies reported some effect of treatment and ten reported an overall effect of treatment.
One recent good-quality RCT reported a positive effect of CBT on fatigue, symptoms, physical functioning and school attendance. Most other new studies showed positive effects, but were lower quality RCTs or CCTs. The previous review reported that 3 of 4 high-quality RCTs showed positive effects. Two recent moderate-quality RCTs of GET suggested positive effects with GET on symptoms and physical functioning. The previous review reported that 2 of 3 high-quality RCTs of GET showed an overall treatment effect for this intervention.
Pharmacological (19 RCTs, 1 CCT).
Six studies reported some effect of treatment and two reported an overall effect of treatment.
One recent large RCT of galantamine hydrobromide reported no difference between treatment groups. One poor-quality RCT of hydrocortisone reported a significant treatment effect, whilst 2 recent studies of steroids reported no significant treatment difference.
The previous review reported that few RCTs showed a positive effect.
Immunological (11 RCTs, 2 CCTs).
Seven studies reported some effect of treatment and three reported an overall effect of treatment.
Two recent studies (a CCT of inosine pranobex and a low-quality RCT of staphylococcus toxoid) reported positive effects of interventions but relatively high rates of adverse effects. The previous review reported that 2 of 5 studies evaluating immunoglobulin G showed an overall effect of treatment, but some studies reported severe adverse effects.
Complementary and alternative therapies (3 RCTs, 1 CCT).
Two studies reported some effect of treatment and one reported an overall effect of treatment. One recent study of homeopathic treatment reported positive effects on one of five measures of fatigue and one of five measures of function. The previous review reported a positive effect in one small RCT of massage therapy, one poor-quality RCT of homeopathy, and one poor CCT of osteopathy.
Supplements (10 RCTs, 1 CCT).
Four studies reported some effect of treatment and three reported an overall effect of treatment.
One recent moderate quality RCT reported an overall treatment effect of acetyl-L-carnitine and propionyl-L-carnitine.
The previous review reported an overall effect of treatment in 1 of 2 good-quality RCTs evaluating fatty acids and one good-quality but small RCT of magnesium.
Other (6 CCTs).
Three studies reported some effect of treatment and one reported an overall effect of treatment for combination treatment.
Children.
Two recent studies that compared interventions that included CBT with routine care reported significant improvements in global wellness (one CCT of CBT/rehabilitation) and symptoms and school attendance (one RCT of CBT) associated with CBT interventions. One RCT on immunoglobulin G reported significant improvements in functional scores (see above for reports about adverse effects).
Severely ill patients.
There was a lack of new studies evaluating interventions in severely affected patients.