Diverse mechanisms and treatment strategies to confront fatigue in multiple sclerosis: A systematic review [version 1; peer review: 2 not approved]

Background: Firm conclusions about the applicability of treatment methods other than pharmacotherapy in treating fatigue in multiple sclerosis (MS) remain elusive. Our objective is to synthesize and review the epidemiological literature systematically and find an effective therapeutic plan for fatigue. The effect of individual treatment and combined treatment strategies are studied. Methods: An electronic database search included EBSCO, PubMed, SCIENCE DIRECT and Scopus from January 1, 2013, to September 30, 2018. Search terms used are "Fatigue AND Multiple sclerosis AND therapy". The articles included in the study are open access, published in last five years, not restricted to region and language. The search included randomized controlled trials (RCTs), observational studies, and systematic reviews. Results: We included 13 systematic reviews, 10 RCTs and 7 observational studies. A Cochrane review on 3206 patients showed exercise therapy to have a positive effect on fatigue in RRMS patients. The EPOC trial showed switching interferon therapy or glatiramer to fingolimod showed improved fatigue levels. The FACETS trial showed incorporating behavioral therapy to ongoing recommended therapy is beneficial. Few observational studies demonstrated that fatigue is influenced by pain, mood problems, and depression. Conclusions: The diverse pathology of fatigue related to MS is important in understanding and quantifying the role of each causal factor. Evidence reveals a positive effect on fatigue levels of RRMS patients with regular CBT and exercise-based combination therapy. Progressive forms of the disease have the worst prognosis. Individually aerobic exercises, behavioral therapy and pharmacotherapy have positive effects. A modified amalgamation of the same is a better hope for MS patients.