Background: Modafinil is a wakefulness-promoting drug used to treat narcolepsy, obstructive sleep apnoea, and shift-work sleep disorder. Modafinil has also been used for the treatment of fatigue and excessive sleepiness in other neurological disorders including multiple sclerosis, psychiatric disorders, and for cognitive enhancement. Recent preclinical studies suggest a potential neuroprotective effect of modafinil in neurodegenerative diseases. Therefore, we investigated its neuroprotective potential in multiple sclerosis.
Objective: To retrospectively assess disease progression in a group of MS patients that had received treatment with modafinil, and a matched group that received no treatment with modafinil.
Methods: We assessed the expanded disability status scale (EDSS) score change, over at least three years, in 30 patients with MS treated with modafinil, and in 90 patients who did not receive modafinil. The two groups were matched for initial EDSS, age, sex, type of disease, disease duration, duration of follow-up, and concomitant disease modifying therapies.
Results: In relapsing-remitting (RR) patients treated with modafinil there was no significant EDSS change over the follow-up period. In RR patients not treated with modafinil, the mean EDSS increased significantly (0.94; p=0.0001) over the follow-up period. Independent of modafinil treatment status, our model indicated an additional mean EDSS increase of 1.1 point (p=0.0002) for progressive patients i.e. mean EDSS change was 1.1 point for modafinil treated, and 1.1+0.94=2.04 points for modafinil-untreated patients.
Conclusion: Our results support the hypothesis that modafinil has neuroprotective potential, and may play a role in the treatment of multiple sclerosis. A prospective study will need to confirm this finding.
Modafinil is a drug which really has a undefined mechanism of action that has been used off-label to allay symptoms of the neurological fatigue. The study suggests that progression of EDSS is slower in people with MS
on modafinil for 3 years or more and that the effect is more pronounced
at lower EDSS levels i.e. less disability, but was not dependent on disease modifying treatment. Modafinil is not without its side effects are therefore we need to see this this data can be repeated in a proper clinical study.
This also suggests that we need combination therapies in RRMS neuroprotectives and anti-inflammatories just as we have suggested will be important in progressiveMS