Key points from the evidence

Key points from the evidence

The content of this evidence summary was up-to-date in April 2013. See summaries of product characteristics (SPCs), British national formulary (BNF) or the MHRA or NICE websites for up-to-date information.

Modafinil is an oral 'wakefulness-promoting' agent that is licensed in the UK for treating excessive sleepiness associated with narcolepsy with or without cataplexy.

Modafinil is not licensed for treating fatigue in multiple sclerosis (MS), and therefore this is an off-label use of this medication.

Two small placebo-controlled randomised controlled trials (RCTs) did not find any statistically significant evidence that modafinil (up to 200 mg or 400 mg daily in the respective trials) improved fatigue in adults with MS (of any disease pattern) at 8 weeks or 35 days respectively.

No serious adverse effects of modafinil were reported in either RCT; however, common adverse effects, including gastrointestinal complaints and restlessness, were observed in both.

The RCTs do not provide any evidence of the longer-term safety and efficacy of modafinil for treating fatigue in MS.

Modafinil can cause serious adverse effects including psychiatric disorders, cardiovascular symptoms, and serious skin and multi-organ hypersensitivity reactions. In January 2011, the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) concluded that the benefits of modafinil could only be considered to outweigh the risks when used to treat narcolepsy. The UK Medicines and Healthcare products Regulatory Agency (MHRA) has issued further information and advice to support the safer use of modafinil in people with narcolepsy.

Modafinil is available as 100 mg tablets at a cost of £52.60 for a 30-tablet pack, and as 200 mg tablets at a cost of £105.21 for a 30-tablet pack. The standard dose (for treating narcolepsy) is between 200 mg and 400 mg daily.

No other drugs have marketing authorisation for MS-related fatigue, although off-label use amantadine may also be considered.

About this evidence summary

'Evidence summaries: unlicensed or off-label medicines' summarise the published evidence for selected unlicensed or off-label medicines that are considered to be of significance to the NHS, where there are no clinically appropriate licensed alternatives. The summaries provide information for clinicians and patients to inform their decision-making and support the construction and updating of local formularies.

The summaries support decision-making on the use of an unlicensed or off-label medicine for an individual patient, where there are good clinical reasons for its use, usually when there is no licensed medicine for the condition requiring treatment, or the licensed medicine is not appropriate for that individual.

The strengths and weaknesses of the relevant evidence are critically reviewed within this summary, but this summary is not NICE guidance.