Measurements and management of multiple sclerosis-related fatigue: an umbrella review and meta-analysis.
Abstract
Purpose
This study aims to synthesize and appraise systematic reviews with meta-analyses that assessed pharmacological, non-pharmacological, and neuromodulatory interventions for MS-related fatigue. MATERIAL AND
Methods
PubMed, WOS, Scopus, Epistemonikos, and the Cochrane Database of Systematic Reviews were searched till Nov 2025. Effect sizes are reported as standardized mean differences (SMDs) with 95% confidence intervals (CIs). Methodological quality was graded with AMSTAR-2. An exploratory meta-meta-analysis was also performed.
Results
Forty-six systematic reviews with meta-analyses covering 287 primary studies were included. Exercise provided the most consistent benefit: aerobic training produced a modest but reliable reduction in fatigue (SMD -0.32), while resistance exercise (-1.09) and yoga/mind-body formats (-0.70) showed larger but more heterogeneous effects. Cognitive behavioral therapy (CBT) and mindfulness/acceptance therapies yielded small to moderate improvements, while energy-conservation education showed a modest benefit. Vitamin D supplementation yielded a small effect (-0.18). Among neuromodulation approaches, transcranial direct current stimulation demonstrated a significant short-term impact (-1.02).
Conclusion
Structured exercise supported by CBT or mindfulness offers the most clinically meaningful relief from MS-related fatigue. Future RCTs should adopt longer follow-up, and use standardized outcome fatigue scales. These conclusions should be interpreted considering the generally low methodological quality of the included reviews.