The effect of amantadine for the treatment of fatigue in people with multiple sclerosis

Multiple sclerosis (MS) is a chronic disease affecting young and middle-aged adults. One of the most common and disabling symptoms of MS is fatigue. Different approaches have been used to try and improve this, including energy conservation, specialised fitness training and drug treatments. Amantadine has been used to try to relieve fatigue in MS. This review found that Amantadine efficacy in reducing MS-related fatigue and its tolerability are poorly documented and more research is needed.

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 an
agreement on accurate, reliable and responsive outcome measures of fatigue; (3) perform good quality RCTs.

Read the full abstract...

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.


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 (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%.