Pharmacological, Non-pharmacological, and Neuromodulatory Interventions for Multiple Sclerosis-related Fatigue: An Overview of Reviews and Meta-review of Therapeutic Efficacy
Yousef Hawas1, Mohamed Abouzid2, Abdallah Ashraf Hamad3, Mohamed El-Moslemani4, Habiba Tariq Saeed1, Esraa Salama5, Mohammad Al Diab Al Azzawi6, Dalia Kamal Ewis7, Abdelfattah Arafa4, Asmaa Zakria Alnajjar8, Ahmed Abo Elnaga9, Mohamed Khalil1, Yasmin Negida10
1Faculty of Medicine, Tanta University, Tanta, Egypt, 2Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, Poznan, Poland, 3Faculty of Medicine, Menoufia University, Menoufia, Egypt, 4Faculty of Medicine, Al-Azhar University, Damietta, Egypt, 5Faculty of Medicine, Benha University, Benha, Egypt, 6Faculty of Medicine, The National Ribat University, Khartoum, Sudan, 7Faculty of Medicine, Beni Suef University, Beni Suef, Egypt, 8Faculty of Medicine, Al-Azhar University, Gaza Palestine, 9Faculty of medicine, Mansoura university, Mansoura, Egypt, 10Faculty of medicine Zagazig university
Objective:
This study aimed to synthesize and appraise the current evidence for all interventions targeting MS-related fatigue and to highlight the most reliable treatment options
Background:
Multiple sclerosis (MS) is an autoimmune-mediated disorder of the central nervous system characterized by inflammation, demyelination, and neurodegeneration. Fatigue is one of the most frequently reported and debilitating symptoms of MS, significantly impairing quality of life.
Design/Methods:
PubMed, Web of Science, Scopus, Epistemonikos, and the Cochrane Database of Systematic Reviews were searched. Methodological quality was graded with AMSTAR-2. Systematic reviews with meta-analyses were included.
Results:
46 systematic reviews with meta-analyses covering 287 RCTs 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 behavioural therapy (CBT) and mindfulness/acceptance therapies yielded small to moderate improvements, while energy-conservation education showed a modest benefit. Cooling garments (–2.26) and massage (–1.62) showed significant effects, though based on a few heterogeneous trials. Vitamin D supplementation yielded a small effect (–0.18), whereas other drugs were ineffective. Among neuromodulation approaches, transcranial direct current stimulation (tDCS) demonstrated a significant short-term impact (–1.02) that disappeared at follow-up, while repetitive transcranial magnetic stimulation (rTMS) and pulsed electromagnetic field (PEMF) produced a modest benefit (–0.65).
Conclusions:
Structured exercise supported by CBT or mindfulness offers the most dependable and clinically meaningful relief from MS-related fatigue. Cooling garments and massage may provide rapid but short-lived relief. Vitamin D repletion is prudent for general health, yet unlikely to substantially reduce fatigue, and current pharmacologic agents lack convincing efficacy. Neuromodulation can be considered an adjunct, but the benefits are transient and of low evidence quality. Future RCTs should adopt longer follow-up, harmonized fatigue outcomes, and direct head-to-head comparisons; an updated network meta-analysis is warranted.
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