Fatigue and Sleepiness in Multiple Sclerosis and Their Response to Short-Term Treatment With Modafinil

Background: Patients with multiple sclerosis (pwMS) often experience significant fatigue. Simultaneously, previous studies show that pwMS frequently suffer from sleepiness and sleep problems. We aimed to contribute to the understanding of correlations between sleep and sleepiness/fatigue in pwMS to better identify responders to the wake-inducing drug, modafinil.

Methods: This open-label, two-centre study included 26 pwMS suffering from daytime tiredness. Sleepiness, fatigue, and sleep were evaluated by questionnaires (Epworth Sleepiness Scale [ESS], Modified Fatigue Impact Scale [MFIS]/Multidimensional Fatigue Inventory [MFI-20], and Pittsburgh), daily sleep diary, and a wrist-worn actigraph before and after 3-week modafinil treatment.

Results: One-third of the pwMS fulfilled the criteria of excessive daytime sleepiness (EDS, defined as ESS ≥ 10). Eighty-two percent (MFIS) of the patients were fatigued, and a high proportion (96%) of the pwMS were poor sleepers. Sleepiness (ESS) was inverse correlated to the subjective sleep quality. Actigraph data did not relate to subjective sleep, but total sleep time (TST) and higher sleep efficacy (SE) estimated by actigraph were positively correlated to the degree of fatigue. Modafinil had a positive effect on EDS.

Discussion: In the present study, we found that the tired multiple sclerosis (MS) patient may suffer from both EDS and fatigue. We found an inverse correlation between EDS and subjective sleep quality. On the contrary, fatigue was positively correlated with longer TST and higher SE, estimated by actigraph. Sleepiness and fatigue did not correlate, and thus, it is highly relevant to distinguish these two symptoms. Modafinil only showed an effect on fatigue when the patient also suffered from EDS, which could suggest that ESS is a possible screening tool for responders to modafinil treatment.

Conclusion: Sleepiness and fatigue do not seem to correlate in pwMS, and we recommend screening tools for sleepiness as well as sleep quality before initiating modafinil treatment to identify potential responders to the treatment.