Authors' objectives:

The aim of this study was to assess the effectiveness of all available interventions which have been evaluated for use in the treatment or management of adults and children with chronic fatigue syndrome (CFS)/Myalgic Encephalomyelitis (ME).

Authors' results and conclusions: Behavioural Both cognitive behavioural therapy (CBT) and graded exercise therapy (GET) showed positive results. Three of the four RCTs evaluating CBT found a positive overall effect of the intervention and these studies also scored highly on validity assessment. One RCT which also included immunologic therapy and one controlled trial of modified CBT did not find overall beneficial effects of CBT. These two studies scored lower on the validity assessment, and the controlled trial presented within group differences rather than between group differences. The studies evaluating CBT did not report any adverse effects of the intervention although in one RCT two participants dropped out of the CBT group because they felt a deterioration in their symptoms was due to the intervention. A second RCT reported drop-out rates of around 20-35% in all three intervention groups, with the highest rates in the CBT group, but reasons for drop-outs were not reported. All three RCTs of GET were of high quality and two found an overall beneficial effect of the intervention compared to the control groups. The third, which also investigated Dialyzable Leukocyte Extract (DLE), found a beneficial effect of CBT compared with DLE for one of the outcomes investigated. The studies did not report any adverse effects of GET although two studies did report study withdrawals that may have been related to adverse effects of the intervention. Immunological Five RCTs investigated the effects of immunoglobulin G; four found some positive effect, two of which found an overall beneficial effect, and the fifth and largest found no effect of treatment. Some severe adverse effects were found in the studies of immunoglobulin G. Two participants had to withdraw from immunoglobulin G treatment due to severe constitutional symptom reactions and one person withdrew due to mild but transient liver failure. Phlebitis has also been noted with immunoglobulin infusions. It should be noted that immunoglobulins and leukocyte extract are blood products and there are known risks associated with their use, such as the possible transfer of infectious diseases. An overall beneficial effect of ampligen was found in one RCT. One RCT assessed the combined effect of leukocyte extract and cognitive behavioural therapy and although no effect of leukocyte extract on its own was found a beneficial effect on one of the outcomes investigated in the group receiving both leukocyte extract and CBT was reported. One RCT evaluated the antihistamine terfenadine and found no beneficial effects. Antiviral Two RCTs evaluated interferon, one of which found an overall beneficial effect. The other presented only within group differences and so no conclusion regarding the effects of treatment can be drawn. No significant effects were found in a small RCT of ganciclovir, or in a controlled trial of vaccination with staphylococcus toxoid. The trial of gancilovir was ended prematurely due to adverse events in the intervention group. The effect of aciclovir was assessed in one small RCT and a negative effect was reported for some of the outcomes investigated. Three people had to withdraw from aciclovir treatment due to reversible renal failure. Pharmacological Very few of the RCTs showed an overall beneficial effect. Antidepressants Two poor quality RCTs of phenelzine and fluoxetine, and a good quality RCT of moclobemide reported no effects of treatment either on symptoms of depression or on any of the other outcome measures reported. A good quality RCT of fluoxetine combined with graded exercise therapy also showed no effect on depression or other measured outcomes. One controlled trial of selegiline reported some positive effects of treatment but found no overall effect. Corticosteroids Four reasonable quality RCTs assessed the effects of steroid treatment. Two RCTs of fludrocortisone reported no effect of treatment, two of hydrocortisone found some beneficial effect of treatment. Anticholinergic agents A poor quality RCT of sulbutiamine reported no effect of treatment. One trial which assessed galanthamine hydrobromide, presented results as within group differences and no conclusion regarding the effect of treatment can be drawn from this trial. Other pharmacological agents One trial which assessed the growth hormone Genotropin presented results as within group differences and no conclusion regarding the effect of treatment can be drawn from this trial. One poor quality RCT showed an overall beneficial effect of oral nicotinamide adenine dinucleotide (NADH). Adverse events serious enough to cause people to withdraw from the study occurred with fludrocortisone, moclobemide, sulbutiamine, galanthamine hydrobromide, phenelzine and fluoxetine. Supplements Two good quality RCTs of essential fatty acids reported some beneficial effects of the intervention and one also found an overall beneficial effect. Magnesium supplements were found to have an overall beneficial effect in one good quality, but small RCT. One poor quality RCT and one controlled trial evaluated general supplements. The controlled trial reported no significant effect of treatment, but the RCT reported an overall beneficial effect. One poor quality RCT of liver extract reported no beneficial effects. The RCT of magnesium supplements reported that two participants left the intervention group after experiencing a generalised rash and the other studies did not report adverse effects. Complementary/alternative Alternative therapies were evaluated in three poor quality RCTs and one controlled trial. An overall beneficial effect of massage therapy was found in one small RCT. Two RCTs assessed the effectiveness of homeopathy; one found a positive effect and the second reported overall beneficial effects. A very poor controlled trial of osteopathy found overall beneficial effects. There were no reports of adverse events from the interventions in any of these studies. Other A good quality RCT reported overall beneficial effects of treatment with a combination of drugs depending on the specific symptoms of each patient. An overall beneficial effect was found in two controlled trials of two different multi-treatment approaches, one of which included CBT and one of which was based on providing information and advice. However, the methodological quality of both these studies was very poor. A controlled trial of a buddy/mentor programme found a beneficial effect for one of the seven outcomes investigated; this study scored poorly on the validity assessment and only included 12 participants.

Authors' recommendations: Overall the interventions demonstrated mixed results in terms of effectiveness. All conclusions about effectiveness should be considered together with any methodological inadequacies of the studies. Interventions for which there is evidence of effectiveness from RCTs include cognitive behavioural therapy and graded exercise therapy. In some of the included studies, bed or wheelchair restricted patients have been excluded and only one study included young people under 18 years of age, which raises questions about the applicability of findings to all people with CFS/ME. Further research is needed into (i) how subgroups of patients may respond differently to treatments and (ii) the potential additive or combined effects of treatments where more than one therapy is used. The large number of outcome measures used makes standardisation of outcomes a priority for future research. Future research needs to combine scientific rigour with patient acceptability and good quality research is needed to evaluate the effectiveness of a range of interventions including pacing, ideally in comparison with CBT and GET.

Authors' methods: Systematic review

Project Status: Completed

URL for project: http://www.york.ac.uk/inst/crd/CRD_Reports/crdreport22.pdf

Year Published: 2002

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: England

Organisation Name: University of York

Contact Address: University of York, York, Y01 5DD, United Kingdom. Tel: +44 1904 321040, Fax: +44 1904 321041,

Contact Name: crd@york.ac.uk

Contact Email: crd@york.ac.uk

Copyright: Centre for Reviews and Dissemination