A Cochrane review ¹ included 5 studies (1 parallel arms, 4 crossover trials) with a total of 272 subjects. Quality of the studies was generally 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%.

Comment: The quality of evidence is downgraded by imprecise results (limited study size for each comparison), by limitations in study quality and by inconsistency (variability in results across studies).