We performed a systematic review and meta-analysis of MS fatigue treatments. A comprehensive literature search identified potential articles published from 1987 forward. Clinicaltrials.gov and PCORI’s website were searched to identify ongoing research. For randomized controlled trials (RCTs), we performed meta-analysis of efficacy for fatigue and QOL; adverse effect information was also extracted. Strength of evidence (SOE) was appraised using modified criteria from the AHRQ evidence-based practice system. We created 3 evidence maps using HTML, SVG and JavaScript.

282 studies met inclusion criteria. All studies (categorized by design and intervention type) were summarized in Map 1. Map 2 summarizes evidence from 45 RCTs comparing treatments to inactive control. Four interventions (aquatic exercise, combination exercise, supervised aerobic exercise, fatigue self-management) improved both fatigue and QOL. Aquatic exercise reduced fatigue the most (Hedges g=1.66, moderate SOE).  Only 1 pharmacologic intervention (paroxetine) improved fatigue, but had insufficient evidence regarding QOL. Map 3 summarizes evidence from 15 RCTs comparing 2 or more active treatments. Sertraline, cognitive behavioral therapy and balance training demonstrated efficacy for fatigue (low to moderate SOE).

Absence of sufficient evidence for amantadine, modafinil, and methylphenidate was striking given common clinical use and potential for adverse effects. Our findings suggest increased focus on exercise and behavioral/educational interventions is warranted.

Interactive visual evidence maps translate evidence-based medicine into a usable tool which can support informed, shared decision-making for policymakers, clinicians, and patients.