The use of modafinil for the treatment of fatigue in multiple sclerosis: A systematic review and meta-analysis of controlled clinical trials.

Introduction: Multiple sclerosis (MS) is a debilitating neurological condition affecting nearly one million people across the United States. Among the most prominent symptoms of the condition are excessive fatigue and daytime sleepiness. Numerous clinical trials have investigated the efficacy of modafinil in addressing fatigue among these patients.

Objective: The objective of the present study is to assess the safety and efficacy of modafinil for the treatment of fatigue in MS.

Methodology: An electronic search of PUBMED, ScienceDirect, and Cochrane Central was conducted for articles published from inception to December 2023 using search terms such as "modafinil," "fatigue," and "MS."

Results: Seven studies were included in our analysis. Modafinil leads to a meaningful reduction in fatigue when compared with placebo, as measured by Modified Fatigue Impact Scale [mean difference (MD) = -4.42 [-8.01, -.84]; I= 45%; p = .02] and Epworth Sleepiness Scale [MD = -.87 [-1.64, -.10]; I= 0%; p = .03]. Modafinil also demonstrated a greater risk of precipitating adverse events (e.g., insomnia, gastrointestinal symptoms) when compared with placebo [RR = 1.30 [1.03, 1.66]; I= 0%; p = .03]. In quality-of-life assessments, modafinil was associated with overall improvement in well-being [standardized mean difference = .18 [.01, .35]; I= 56%; p = .04].

Conclusion: The data indicates that modafinil confers a therapeutic benefit when treating fatigue in patients with MS and improves overall quality of life; however, there is a risk of precipitating adverse events. Ultimately, higher quality of evidence may be required to better inform clinical management.