Journals Library

An error has occurred in processing the XML document

An error occurred retrieving content to display, please try again.

Page not found (404)

Sorry - the page you requested could not be found.

Please choose a page from the navigation or try a website search above to find the information you need.

{{metadata.Title}}

{{metadata.Headline}}

An error has occurred in processing the XML document

{{author}}{{author}}{{($index < metadata.AuthorsAndEtalArray.length-1) ? ',' : '.'}}

An error has occurred in processing the XML document

An error has occurred in processing the XML document

{{metadata.Journal}} Volume: {{metadata.Volume}}, Issue:{{metadata.Issue}}, Published in {{metadata.PublicationDate | date:'MMMM yyyy'}}

https://dx.doi.org/{{metadata.DOI}}

Citation: {{author}}{{ (($index < metadata.AuthorsArray.length-1) && ($index <=6)) ? ', ' : '' }}{{(metadata.AuthorsArray.length <= 6) ? '.' : '' }} {{(metadata.AuthorsArray.length > 6) ? 'et al.' : ''}} {{metadata.Title}}. {{metadata.JournalShortName}} {{metadata.PublicationDate | date:'yyyy'}};{{metadata.Volume}}({{metadata.Issue}})

You might also be interested in:
{{classification.Category.Concept}}

Report Content

The full text of this issue is available as a PDF document from the Toolkit section on this page.

The full text of this issue is available as a PDF document from the Toolkit section on this page.

Abstract

BACKGROUND

Multiple sclerosis (MS) is an important problem both for people with the disease and for society. There is no cure, and alleviation of symptoms forms the cornerstone of care. Excessive fatigue that severely limits activity is experienced by at least two-thirds of the estimated 60,000 people with MS in the UK.

OBJECTIVES

(1) To identify current treatments for fatigue in MS and their evidence-base. (2) To systematically review the evidence for those treatments that have been investigated in more than one rigorous study, in order to determine their effectiveness and cost-effectiveness.

METHODS

The review was carried out in two stages: a formal scoping review (to assess the range of interventions used by people with MS), and a systematic review for treatments that had been identified as promising and that had been investigated in clinical trials (as identified in the scoping review). A systematic review of research on costs and cost-effectiveness of those interventions identified as promising was also performed. Electronic databases, including MEDLINE and EMBASE, were searched for the period 1991-June 1999 (scoping review) and 1966-December 1999 (systematic review). Reference lists from publications were also searched, and experts were contacted for any additional information not already identified.

RESULTS

Interventions identified for the treatment of fatigue in MS (1) Behavioural advice. This is the main element of initial clinical management and no rigorous research of its effectiveness was identified. (2) Drugs (amantadine, pemoline, potassium-channel blockers and antidepressants). (3) Training, rehabilitation and devices (cooling vests and electromagnetic fields). (4) Alternative therapies (bee venom, cannabis, acupuncture/acupressure and yoga). Only two drugs, amantadine and pemoline, met the criteria for full systematic review. RESULTS - EFFECTIVENESS OF AMANTADINE: One parallel and three crossover trials were found, involving a total of 236 people with MS. All studies were open to bias. All studies showed a pattern in favour of amantadine compared with placebo, but there is considerable uncertainty about the validity and clinical significance of this finding. This pattern of benefit was considerably undermined when different assumptions were used in the sensitivity analysis. RESULTS - EFFECTIVENESS OF PEMOLINE: One parallel and one crossover trial were found involving a total of 126 people with MS. Both studies were open to bias. There was no overall tendency in favour of pemoline over placebo and an excess of reports of adverse effects with pemoline. RESULTS - HEALTH ECONOMIC ANALYSIS: The drug costs of amantadine and pemoline are modest (pound 200 and pound 80 per annum, respectively). No economic evaluations were identified in the systematic review, and available data were insufficient to allow modelling of cost-effectiveness in this rapid review.

CONCLUSIONS

There is insufficient evidence to allow people with MS, clinicians or policy makers to make informed decisions on the appropriate use of the many treatments on offer. Only amantadine appears to have some proven ability to alleviate the fatigue in MS, though only a proportion of users will obtain benefit and then only some of these patients will benefit sufficiently to take the drug in the long term. CONCLUSIONS - RECOMMENDATIONS FOR RESEARCH: The frequency, severity and impact of fatigue, the poverty of available research, and the absence of any ongoing research, suggest that new research is an urgent priority. People with MS, clinicians and policy makers should work together to ensure that the evidence required is collected as quickly as possible by encouraging involvement in rigorous research. Research should not be restricted to the two drugs reviewed in depth in this report. All interventions identified in the scoping review (see above) should be considered, as should basic scientific research into the underlying mechanism of fatigue in MS.

Abstract

BACKGROUND

Multiple sclerosis (MS) is an important problem both for people with the disease and for society. There is no cure, and alleviation of symptoms forms the cornerstone of care. Excessive fatigue that severely limits activity is experienced by at least two-thirds of the estimated 60,000 people with MS in the UK.

OBJECTIVES

(1) To identify current treatments for fatigue in MS and their evidence-base. (2) To systematically review the evidence for those treatments that have been investigated in more than one rigorous study, in order to determine their effectiveness and cost-effectiveness.

METHODS

The review was carried out in two stages: a formal scoping review (to assess the range of interventions used by people with MS), and a systematic review for treatments that had been identified as promising and that had been investigated in clinical trials (as identified in the scoping review). A systematic review of research on costs and cost-effectiveness of those interventions identified as promising was also performed. Electronic databases, including MEDLINE and EMBASE, were searched for the period 1991-June 1999 (scoping review) and 1966-December 1999 (systematic review). Reference lists from publications were also searched, and experts were contacted for any additional information not already identified.

RESULTS

Interventions identified for the treatment of fatigue in MS (1) Behavioural advice. This is the main element of initial clinical management and no rigorous research of its effectiveness was identified. (2) Drugs (amantadine, pemoline, potassium-channel blockers and antidepressants). (3) Training, rehabilitation and devices (cooling vests and electromagnetic fields). (4) Alternative therapies (bee venom, cannabis, acupuncture/acupressure and yoga). Only two drugs, amantadine and pemoline, met the criteria for full systematic review. RESULTS - EFFECTIVENESS OF AMANTADINE: One parallel and three crossover trials were found, involving a total of 236 people with MS. All studies were open to bias. All studies showed a pattern in favour of amantadine compared with placebo, but there is considerable uncertainty about the validity and clinical significance of this finding. This pattern of benefit was considerably undermined when different assumptions were used in the sensitivity analysis. RESULTS - EFFECTIVENESS OF PEMOLINE: One parallel and one crossover trial were found involving a total of 126 people with MS. Both studies were open to bias. There was no overall tendency in favour of pemoline over placebo and an excess of reports of adverse effects with pemoline. RESULTS - HEALTH ECONOMIC ANALYSIS: The drug costs of amantadine and pemoline are modest (pound 200 and pound 80 per annum, respectively). No economic evaluations were identified in the systematic review, and available data were insufficient to allow modelling of cost-effectiveness in this rapid review.

CONCLUSIONS

There is insufficient evidence to allow people with MS, clinicians or policy makers to make informed decisions on the appropriate use of the many treatments on offer. Only amantadine appears to have some proven ability to alleviate the fatigue in MS, though only a proportion of users will obtain benefit and then only some of these patients will benefit sufficiently to take the drug in the long term. CONCLUSIONS - RECOMMENDATIONS FOR RESEARCH: The frequency, severity and impact of fatigue, the poverty of available research, and the absence of any ongoing research, suggest that new research is an urgent priority. People with MS, clinicians and policy makers should work together to ensure that the evidence required is collected as quickly as possible by encouraging involvement in rigorous research. Research should not be restricted to the two drugs reviewed in depth in this report. All interventions identified in the scoping review (see above) should be considered, as should basic scientific research into the underlying mechanism of fatigue in MS.

If you would like to receive a notification when this project publishes in the NIHR Journals Library, please submit your email address below.

An error has occurred in processing the XML document

 

Responses to this report

 

No responses have been published.

If you would like to submit a response to this publication, please do so using the form below.

Comments submitted to the NIHR Journals Library are electronic letters to the editor. They enable our readers to debate issues raised in research reports published in the Journals Library. We aim to post within 2 working days all responses that contribute substantially to the topic investigated, as determined by the Editors.

Your name and affiliations will be published with your comment.

Once published, you will not have the right to remove or edit your response. The Editors may add, remove, or edit comments at their absolute discretion.

By submitting your response, you are stating that you agree to the terms & conditions