Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2007 Jan 24;2007(1):CD002818.
doi: 10.1002/14651858.CD002818.pub2.

Amantadine for fatigue in multiple sclerosis

Affiliations

Amantadine for fatigue in multiple sclerosis

E Pucci et al. Cochrane Database Syst Rev. .

Abstract

Background: Fatigue is one of the most common and disabling symptoms of people with Multiple Sclerosis (MS). The effective management of fatigue has an important impact on the patient's functioning, abilities, and quality of life. Although a number of strategies have been devised for reducing fatigue, treatment recommendations are based on a limited amount of scientific evidence. Many textbooks report amantadine as a first-choice drug for MS-related fatigue because of published randomised controlled trials (RCTs) showing some benefit.

Objectives: To determine the effectiveness and safety of amantadine in treating fatigue in people with MS.

Search strategy: We searched The Cochrane MS Group Trials Register (July 2006), The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1, 2006), MEDLINE (January 1966 to July 2006), EMBASE (January 1974 to July 2006), bibliographies of relevant articles and handsearched relevant journals. We also contacted drug companies and researchers in the field.

Selection criteria: Randomised, placebo or other drugs-controlled, double-blind trials of amantadine in MS people with fatigue.

Data collection and analysis: Three reviewers selected studies for inclusion in the review and they extracted the data reported in the original articles. We requested missing and unclear data by correspondence with the trial's principal investigator. A meta-analysis was not performed due to the inadequacy of available data and heterogeneity of outcome measures.

Main results: Out of 13 pertinent publications, 5 trials met the criteria for inclusion in this review: one study was a parallel arms study, and 4 were crossover trials. The number of randomised participants ranged between 10 and 115, and a total of 272 MS patients were studied. Overall the quality of the studies considered was poor and all trials were open to bias. All studies reported small and inconsistent improvements in fatigue, whereas the clinical relevance of these findings and the impact on patient's functioning and health related quality of life remained undetermined. The number of participants reporting side effects during amantadine therapy ranged from 10% to 57%.

Authors' conclusions: The efficacy of amantadine in reducing fatigue in people with MS is poorly documented, as well as its tolerability. It is advisable to: (1) improve knowledge on the underlying mechanisms of MS-related fatigue; (2) achieve anagreement on accurate, reliable and responsive outcome measures of fatigue; (3) perform good quality RCTs.

PubMed Disclaimer

Conflict of interest statement

None.

Update of

Similar articles

Cited by

References

References to studies included in this review

CMSRG 1987 {published data only}
    1. The Canadian MS Research Group. A randomized controlled trial of amantadine in fatigue associated with multiple sclerosis. Canadian Journal of Neurological Sciences 1987;14(3):273‐8. - PubMed
Cohen 1989 {published data only}
    1. Cohen RA, Fisher M. Amantadine treatment of fatigue associated with multiple sclerosis. Archives of Neurology 1989;46(6):676‐80. - PubMed
Krupp 1995 {published data only}
    1. Krupp LB, Coyle PK, Doscher C, Miller A, Cross AH, Jandorf L, et al. Fatigue therapy in multiple sclerosis: results of a double‐blind, randomized, parallel trial of amantadine pemoline, and placebo. Neurology 1995;45(11):1956‐61. - PubMed
Rosenberg 1988 {published data only}
    1. Rosenberg GA, Appenzeller O. Amantadine, fatigue and multiple sclerosis. Archives of Neurology 1988;45(10):1104‐6. - PubMed
Tomassini 2004 {published data only}
    1. Tomassini V, Pozzilli C, Onesti E, Pasqualetti P, Marinelli F, Pisani A, Fieschi C. Comparison of the effects of acetyl L‐carnitine and amantadine for the treatment of fatigue in multiple sclerosis: results of a pilot, randomised, double‐blind, crossover trial. Journal of the Neurological Sciences 2004;218:103‐108. - PubMed

References to studies excluded from this review

Chiba 1992 {published data only}
    1. Chiba S, Ito M, Matsumoto H. Amantadine treatment for refractory pain and fatigue in patients with multiple sclerosis. Canadian Journal of Neurological Sciences 1992;19(2):309. - PubMed
Geisler 1996 {published data only}
    1. Geisler MW, Sliwinski M, Coyle PK, Masur DM, Doscher C, Krupp LB. The effects of amantadine and pemoline on cognitie functioning in multiple sclerosis. Archives of Neurology 1996;53(2):185‐8. - PubMed
Kemp 1993 {published data only}
    1. Kemp Ba, Gora ML. Amantadine and Fatigue of Multiple Sclerosis. The Annals of Pharmacotherapy 1993;27(7‐8):893‐5. - PubMed
Maciejek 1989 {published data only}
    1. Maciejek Z. Changes in visual ovoked potentials in patients with multiple sclerosis treated with isoprinosine and amantadine. Archivum Immunologiae et Therapiae Experimentalis 1989;37(5‐6):621‐8. - PubMed
Murray 1985 {published data only}
    1. Murray TJ. Amantadine therapy for fatigue in multiple sclerosis. Canadian Journal of Neurological Sciences 1985;15(3):251‐4. - PubMed
Plaut 1987 {published data only}
    1. Plaut GS. Effectiveness of amantadine in reducing relapses in multiple sclerosis. Journal of the Royal Society of Medicine 1987;80(2):91‐3. - PMC - PubMed
Sailer 1996 {published data only}
    1. Sailer M, Smid HOGM, Schoenfeld A, Hauser U, Heinze Hj. Effect of amantadine on cognitive processes in multiple sclerosis with fatigue: A double‐blind placebo controlled cross‐over study. European Journal of Neurology 1996;3 Suppl (4):61‐2.
Sailer 2000 {published data only}
    1. Sailer M, Heinze Hi, Schoenfeld MA, Hauser U, Smid HG. Amantidine influences cognitive processing in patients with multiple sclerosis. Pharmacopsychiatry 2000;33(1):28‐37. - PubMed

Additional references

Anonymous 1998
    1. Multiple Sclerosis Council for Clinical Practice Guidelines. Fatigue and Multiple Sclerosis. Evidence‐Based Management Strategies for Fatigue in Multiple Sclerosis. Clinical Practice Guidelines. Multiple Sclerosis Council for Clinical Practice Guidelines, 1998.
Beck 1961
    1. Beck AT, Ward CH, Medelson M, Mock JE, Mohr DC, Erbaugh JK. An inventory for measuring depression. Archives of General Psychiatry 1961;4:567‐71. - PubMed
Bertolone 1993
    1. Bertolone K, Coyle PK, Krupp LB, Doscher CA. Cytokine correlates of fatigue in multiple sclerosis. Neurology 1993;43(4 Suppl 2):A356.
Branas 2000
    1. Branas P, Jordan R, Fry‐Smith A, Burls A, C Hyde. Treatments for fatigue in multiple sclerosis: a rapid and systematic review. Health Technology Assessment 2000;4(27):1‐61. - PubMed
Bryson 1980
    1. Bryson YJ, Monahan C, Pollack M, Shields WD. A prospective double‐blind study of side effects associated with the administration of amantadine for influenza A virus prophylaxis. Journal of Infectious Diseases 1980;141:543‐7. - PubMed
Crosby 2003a
    1. Crosby N, Deane KHO, Clarke CE. Amantadine for diskynesia in Parkinson's disease. Cochrane Database of Systematic Reviews 2003, Issue 2. [DOI: 10.1002/14651858.CD003467] - DOI - PMC - PubMed
Crosby 2003b
    1. Crosby N, Deane KHO, Clarke CE. Amantadine in Parkinson's disease.. Cochrane Database of Systematic Reviews 2003, Issue 1. [DOI: 10.1002/14651858.CD003468] - DOI - PMC - PubMed
Curtin 2002 A
    1. Curtin F, Altman DG, Elbourne D. Meta‐analysis combining parallel and cross‐over clinical trials. I: Continuous outcomes. Statistics in Medicine 2002;21(15):2131‐44. - PubMed
Curtin 2002 B
    1. Curtin F, Elbourne D, Altman DG. Meta‐analysis combining parallel and cross‐over clinical trials. II: Binary outcomes. Statistics in Medicine 2002;21(15):2145‐59. - PubMed
Dolin 1982
    1. Dolin R, Reichman RC, Madore HP, Maynard R, Linton PN, Webber‐Jones J. A controlled trial of amantadine and rimantadine in the prophylaxis of influenza A infection. New England Journal of Medicine 1982;307:580‐4. - PubMed
Fischer 1999
    1. Fischer JS, Rudick, Cutter GR, Reingold SC. The Multiple Sclerosis Functional Composite measure (MSFC): an integrated approach to MS clinical outcome assessment. Multiple Sclerosis 1999;5(4):244‐50. - PubMed
Fisk 1994
    1. Fisk JD, Ritvo PG, Ross L, Haase DA, Marrie TJ, Schlech WF. Measuring the functional impact of fatigue: initial validation of the Fatigue Impact Scale. Clinical Infectious Diseases 1994;18(Suppl.1):S79‐83. - PubMed
Flensner 2005
    1. Flensner G, Ek AC, Soderhamn O. Reliability and validity of the Swedish version of the Fatigue Impact Scale (FIS). Scandinavian Journal of Occupational Therapy 2005;12:170‐80. - PubMed
Hauser 1983
    1. Hauser SL, Dawson DM, Lehrich JR, Bela MF, KevyV, Propper RD, et al. Intensive immunosuppression in progressive multiple sclerosis. New England Journal of Medicine 1983;308(4):173‐80. - PubMed
Hauser 2003
    1. Hauser W, Almouhtasseb R, Muthny FA, Grandt D. Validation of a German Version of the Fatigue Impact Scale FIS‐D [Validierung der deutschen Version der Fatigue Impact Scale FIS‐D]. Zeitschrift für Gastoenterologie 2003;41:973‐82. - PubMed
Hayden 1996
    1. Hayden F. Antimicrobial Agents. In: Hardman JG, Limbird LE, Molinoff PB, Ruddon RW editor(s). Goodman & Gillman's: The pharmacological basis of therapeutics. Ninth. New York: Mc Graw Hill, 1996:1191‐223.
Higgins 2005
    1. Higgins JPT, Green S, editors. Formulating the problem. Cochrane Handbook for Systematic Reviews of Interventions 4.2.5 [updated May 2005], Section 4. www.cochrane.org/resources/handbook/hbook.htm. Chichester, UK: John Wiley & Sons, Ltd., (accessed 2005).
Jadad 1996
    1. Jadad AR, Moore RA, Carroll D. Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. Assessing the quality of reports of Randomised Clinical Trials: is blinding necessary?. Controlled Clinical Trials 1996;17(1):1‐12. - PubMed
Jefferson 2006a
    1. Jefferson T, Demicheli V, Pietrantonj C, Rivetti D. Amantadine and rimantadine for influenza A in adults. Cochrane Database of Systematic Reviews 2006, Issue 2. [DOI: 10.1002/14651858.CD001169.pub3] - DOI - PMC - PubMed
Jefferson 2006b
    1. Jefferson T, Demicheli V, Rivetti D, Jones M, Pietrantonj C, Rivetti A. Antivirals for influenza in healthy adults: systematic review. Lancet 2006;367:303‐13. - PubMed
Kamps 2006
    1. Kamps BS, Hoffmann C, Preiser W. Influenza Report 2006. www.InfluenzaReport.com [accessed 01 May 2006].
Kos 2005
    1. Kos D, Kerckhofs E, Carrea I, Verza R, Ramos M, Jansa J. Evaluation of the Modified Fatigue Impact Scale in four different European countries. Evaluation of the Modified Fatigue Impact Scale in four different European countries. Multiple Sclerosis 2005;11:76‐80. - PubMed
Krupp 1997
    1. Krupp LB. Mechanism, measurement, and management of fatigue in multiple sclerosis. In: Thompson A, et al. editor(s). Multiple Sclerosis. Martin Dunitz, 1997.
Krupp1989
    1. Krupp LB, LaRocca NG, Muir‐Nash J, Steinberg AD. The fatigue severity scale: application to patients with Multiple Sclerosis and Systemic Lupus Erythematosus. Archives of Neurology 1989;46(10):1121‐3. - PubMed
Kurtzke 1983
    1. Kurtzke JF. Rating neurologic impairment in Multiple Sclerosis: An Expanded Disability Status Scale (EDSS). Neurology 1983;33(11):1444‐52. - PubMed
Lim 2005
    1. Lim JK, Wooten D, Siegel R, Cheung RC. Amantadine in treatment of chronic hepatitis C virus infection?. Journal of Viral Hepatitis 2005;12:445‐55. - PMC - PubMed
Mathiowetz 2003
    1. Mathiowetz V. Test‐retest reliability and convergent validity of the Fatigue Impact Scale for persons with multiple sclerosis. American Journal of Occupational Therapy 2003;57:389‐95. - PubMed
McDonald 2001
    1. McDonald WI, Compston A, Edan G, Goodkin, Hartung HP, Lublin FD, et al. Recommended Diagnostic Criteria for Multiple Sclerosis: Guidelines from the International Panel on the Diagnosis of Multiple Sclerosis. Annals of Neurology 2001;50(1):121‐7. - PubMed
Pittion‐Vouyovitch06
    1. Pittion‐Vouyovitch S, Debouverie M, Guillemin F, Vandenberghe N, Anxionnat R, Vespignani H. Fatigue in multiple sclerosis is related to disability, depression and quality of life [Fatigue in multiple sclerosis is related to disability, depression and quality of life]. Journal Neurological Sciences 2006;243:39‐45. - PubMed
Poser 1983
    1. Poser CM, Paty DW, Scheinberg L, Donald WI, Davis FA, Ebers GC, et al. New diagnostic criteria for Multiple Sclerosis: guide‐lines for research protocols. Annals of Neurology 1983;13(3):227‐31. - PubMed
Radloff 1977
    1. Radloff LS. The CES‐D Scale: a self‐report depression scale for research in the general population. Applied Psychological Measures 1977;1:385‐401.
Schumacher 1965
    1. Schumacher GA, Beebe G, Kibler RF, kurland LT, Kurtzke JF, McDowell F, et al. Problems of experimental trials of therapy in Multiple Sclerosis: Report by the panel of the evaluetion of experimental trials in Multiple Sclerosis. Annals of the New York Academy of Sciences 1965;122:552‐68. - PubMed
Schwab 1972
    1. Schwab RS, Poskanzer DC, England AC, Young RR. Amantadine in Parkinson's disease. Review of more than two years experience. JAMA: the Journal of the American Medical Association 1972;222(7):792‐5. - PubMed
Schwartz 1993
    1. Schwartz J, Jandorf L, Krupp LD. The measurment of fatigue: a new scale. Journal of Psychosomatic Research 1993;37(7):753‐62. - PubMed
Stoof 1992
    1. Stoof JC, Booij J, Drukarch B. Amantadine as N‐methyl‐D‐aspartic acid receptor antagonist: new possibilities for therapeutic applications?. Clinical Neurology and Neurosurgery 1992;94 Suppl:4‐6. - PubMed
Tempelaar 1989
    1. Tempelaar R, Haes JC, Ruiter JH, Bakker D, Heuvel WJ, Nieuwenhuijzen MG. The social experiences of cancer patients under treatment: a comparative study. Social Science & Medicine 1989;29:635‐42. - PubMed

Publication types

MeSH terms