Effects of Occupational Therapy Interventions on Occupational Performance and Physical and Cognitive Fatigue in Adults with Multiple Sclerosis: A Systematic Review of Randomized Controlled Trials

Background/Objectives: Multiple sclerosis (MS) frequently limits participation in daily occupations and is associated with disabling fatigue. However, the effects of occupational therapy (OT) remain uncertain because available trials have evaluated heterogeneous interventions and outcomes. This systematic review synthesized evidence from randomized controlled trials (RCTs) on occupational performance and physical and cognitive fatigue in adults with MS. Materials and Methods: Seven bibliographic databases were searched from inception to 10 August 2026: MEDLINE via PubMed, Scopus, the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Library, Web of Science Core Collection, APA PsycINFO via EBSCOhost, CINAHL Complete via EBSCOhost, and ProQuest Central. Two independent reviewers performed study selection, data extraction, and risk-of-bias assessment using RoB 2. Certainty of evidence was evaluated using GRADE. Given the clinical and methodological heterogeneity, findings were synthesized narratively following the Synthesis Without Meta-Analysis guideline. The protocol was registered in PROSPERO (CRD420251115448). Results: Seven RCTs involving 488 randomized participants were included. Findings for occupational performance were inconsistent: one small waitlist-controlled trial reported large short-term benefits from occupational performance coaching, whereas an active-comparator trial found improvements in both groups without clear superiority. Other findings showed no comparative benefit or provided only indirect evidence. Fatigue findings were similarly inconsistent: one 20-participant pilot trial favored a sleep-targeted OT intervention, two trials found no comparative benefit, and one large trial transiently favored usual-care OT. The certainty of evidence was very low for both outcomes. Conclusions: The available evidence does not consistently establish that OT interventions improve occupational performance or reduce physical and cognitive fatigue in adults with MS. Larger, adequately powered RCTs using clearly defined OT interventions, standardized outcomes, and longer follow-up periods are required.