Which behavioural and exercise interventions targeting fatigue show the most promise in multiple sclerosis? A systematic review with narrative synthesis and meta-analysis.

Fatigue is a common and highly debilitating symptom of multiple sclerosis (MS). This meta-analytic systematic review with detailed narrative synthesis examined randomised-controlled (RCTs) and controlled trials of behavioural and exercise interventions targeting fatigue in adults with MS to assess which treatments offer the most promise in reducing fatigue severity/impact. Medline, EMBASE and PsycInfo electronic databases, amongst others, were searched through to August 2018. Thirty-four trials (12 exercise, 16 behavioural and 6 combined; n = 2,434 participants) met inclusion criteria. Data from 31 studies (n = 1,991 participants) contributed to the meta-analysis. Risk of bias (using the Cochrane tool) and study quality (GRADE) were assessed. The pooled (SMD) end-of-treatment effects on self-reported fatigue were: exercise interventions (n = 13) -.84 (95% CI -1.20 to -.47); behavioural interventions (n = 16) -.37 (95% CI -.53 to -.22); combined interventions (n = 5) -.16 (95% CI: -.36 to .04). Heterogeneity was high overall. Study quality was very low for exercise interventions and moderate for behavioural and combined interventions. Considering health care professional time, subgroup results suggest web-based cognitive behavioural therapy for fatigue, balance and/or multicomponent exercise interventions may be the cost-efficient therapies. These need testing in large RCTs with long-term follow-up to help define an implementable fatigue management pathway in MS.