Modafinil is a drug that promotes wakefulness and is licensed for treating people who experience excessive daytime sleepiness due to narcolepsy. Research has suggested that it may be an effective treatment for the management of multiple sclerosis fatigue in some people where daytime sleepiness is a factor in their fatigue. However following the findings of a safety review, the European Medicines Agency recommended that modafinil should now be used only for narcolepsy.
A review of research on modafinil found no strong evidence for its use in treating MS-related fatigue. Although some potential benefits of the drug were identified, these studies concluded that evidence on the effectiveness of modafinil in treating MS fatigue was weak and inconclusive.
A study published in 2021 compared three medicines (including modafinil) often prescribed for MS fatigue with placebo. The results suggest that none of the medications was more effective than placebo at reducing fatigue levels, although there was some indication that modafinil could be beneficial if daytime sleepiness is a significant contributor to fatigue levels.
Amantadine is another drug which is sometimes used to treat fatigue in MS.