Treatment of multiple sclerosis fatigue with the synthetic psychoactive drug modafinil

Multiple sclerosis (MS) is a complex disorder characterized by a broad spectrum of symptoms that evolve throughout the disease. Symptoms can be categorized as visible and invisible based on external sight recognition. However, although others poorly recognize it, invisible symptoms such as mood dysfunction, neuropathic pain, or fatigue can significantly affect activities of daily living and the quality of life of people with MS (PwMS). PwMS frequently complain of fatigue, which has physical or cognitive manifestations. Fatigue in MS does not improve or resolve with rest, and it is disproportionate with respect to the exerted effort. Fatigue management in MS is challenging, and a few pharmacological approaches have been successfully proposed. Among them, the drug modafinil has attracted attention because of its properties as a synthetic psychoactive drug. In this review, we focus on the evidence available to date, supporting the use of modafinil in MS fatigue. However, despite the availability of some trials evaluating the effects of modafinil on fatigue, their contrasting results failed to support its usefulness in fatigue management in MS.