Efficacy and safety of non-pharmacological interventions for fatigue in Parkinson’s disease: protocol for a systematic review and network meta-analysis

Fatigue is a prevalent and disabling non-motor symptom in Parkinson’s disease (PD), significantly impairing patients’ quality of life. Non-invasive, non-pharmacological interventions, including acupuncture, Tai Chi, and transcranial magnetic stimulation, have gained attention for their favorable safety profiles and cost-effectiveness. However, current evidence is limited by significant heterogeneity in intervention protocols, diverse fatigue measurement scales, and varying methodological quality of existing trials. This study aims to rigorously evaluate the efficacy and safety of non-pharmacological interventions for PD fatigue through a systematic review and network meta-analysis (NMA), providing an evidence-based foundation for clinical practice. A comprehensive systematic search will be conducted across eight electronic databases (PubMed, Web of Science, Cochrane Library, Embase, SinoMed, VIP, CNKI, and WanFang) and two clinical trial registries (ClinicalTrials.gov and ChiCTR) from inception to April 20, 2026. Eligible randomized controlled trials (RCTs) comparing non-invasive, single-modality non-pharmacological interventions against inactive controls or active pharmacotherapy will be included. To ensure transitivity and clinical interpretability, the primary outcome will be strictly restricted to the change in Fatigue Severity Scale (FSS) scores, utilizing mean differences. Secondary outcomes will include other fatigue scales, motor symptoms, and quality of life, and systematically categorized adverse events (serious vs. non-serious). Risk of bias will be assessed using the Cochrane ROB2 tool. Pairwise meta-analysis will be conducted using RevMan v5.4 software, and STATA 18.0 will be utilized for NMA, with intervention rankings generated only for nodes meeting a predefined threshold of at least three studies. Evidence certainty will be evaluated using an NMA-specific GRADE framework. This protocol outlines a rigorous methodology to synthesize current evidence on the efficacy and safety of non-pharmacological interventions for PD fatigue. The findings are anticipated to inform patient-centered clinical guidelines and highlight critical research gaps. PROSPERO CRD420251017727.