Modafinil (Provigil)
Other name: Provigil
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.
How does modafinil work?
It is thought that modafinil works by selective activation of a particular part of the brain called the hypothalamus. This area is thought to control normal sleep and wakefulness patterns. Unlike central nervous system stimulants, modafinil does not result in excessive tiredness (a 'crash' or rebound hypersomnia) as it wears off.
How do I take modafinil?
Modafinil is taken orally as tablets.
Side effects and contraindications
Modafinil is generally well tolerated with mild side effects, which can include headache, nausea, chest pain, loss of appetite and weakness. Modafinil reduces the effectiveness of contraceptive drugs so you will need to consider other birth control methods while taking the drug and for two months after stopping treatment.
Find out more
- Patient Information Leaflet – Provigil (EMC website)
- Gov.uk – Modafinil (Provigil): now restricted to narcolepsy
- Fatigue
- Living well with MS
- Treating MS symptoms
- NICE – fatigue in multiple sclerosis: modafinil
References
- Journal of Neurology, Neurosurgery and Psychiatry 2002;72(2):179-183. Summary Efficacy and safety of modafinil (Provigil) for the treatment of fatigue in multiple sclerosis: a two centre phase 2 study.
- Clinical Neurology and Neurosurgery 2010;112(1):29-31. Summary Modafinil for multiple sclerosis fatigue: does it work?
- Multiple Sclerosis Journal 2011 Aug;17(8):1002-1009. Summary HAGIL (Hamburg Vigil Study): a randomized placebo-controlled double-blind study with modafinil for treatment of fatigue in patients with multiple sclerosis.
- Journal of Neurological Sciences 2017;381:41-54. Summary The pharmacological and non-pharmacological interventions for the management of fatigue related multiple sclerosis.
- Journal of Neurological Sciences 2017;380:256-261. Summary Pharmacological treatments for fatigue in patients with multiple sclerosis: A systematic review and meta-analysis.
- Lancet Neurology 2021; 20(1): 38-48. Full article Safety and efficacy of amantadine, modafinil, and methylphenidate for fatigue in multiple sclerosis: a randomised, placebo-controlled, crossover, double-blind trial.
- Exp Neurol. 2022 Jan;347:113906. Summary Treatment of multiple sclerosis fatigue with the synthetic psychoactive drug modafinil.

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Fatigue
Fatigue is one of the most common symptoms of MS, but treatment and self management can lessen the impact of fatigue on your life.
