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

Rammohan KW, et al.
Efficacy and safety of modafinil (Provigil) for the treatment of fatigue in multiple sclerosis: a two centre phase 2 study.
Journal of Neurology, Neurosurgery and Psychiatry 2002;72(2):179-183.
Summary (link is external)
Littleton ET, et al.
Modafinil for multiple sclerosis fatigue: does it work?
Clinical Neurology and Neurosurgery 2010;112(1):29-31.
Summary (link is external)
Möller F, et al.
HAGIL (Hamburg Vigil Study): a randomized placebo-controlled double-blind study with modafinil for treatment of fatigue in patients with multiple sclerosis.
Multiple Sclerosis Journal 2011 Aug;17(8):1002-1009.
Summary (link is external)
Miller P, et al.
The pharmacological and non-pharmacological interventions for the management of fatigue related multiple sclerosis.
Journal of Neurological Sciences 2017;381:41-54.
Summary (link is external)
Yang TT, et al.
Pharmacological treatments for fatigue in patients with multiple sclerosis: A systematic review and meta-analysis.
Journal of Neurological Sciences 2017;380:256-261.
Summary (link is external)
Nourbakhsh B, Revirajan N, Morris B, et al.
Safety and efficacy of amantadine, modafinil, and methylphenidate for fatigue in multiple sclerosis: a randomised, placebo-controlled, crossover, double-blind trial.
Lancet Neurology 2021; 20(1): 38-48.
Full article (link is external)
Cocco E, Fadda P.
Treatment of multiple sclerosis fatigue with the synthetic psychoactive drug modafinil.
Exp Neurol. 2022 Jan;347:113906.
Summary (link is external)
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