{
  "abstract": "Background Cancer-related fatigue (CRF) affects up to 70.7% of patients with cancer, significantly impairing quality of life and treatment adherence. Methylphenidate (MPH) and its dexmethylphenidate (D-MPH) are commonly used psychostimulants, but evidence regarding their efficacy remains inconsistent.Methods Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, we systematically searched PubMed, Cochrane Library, Embase and Web of Science from inception to June 2025. Primary outcomes were CRF improvement and safety. Meta-analysis was performed using R software (V.4.2.1) with random-effects models. Trial sequential analysis (TSA), Bayesian methods for sparse adverse event data and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment were applied.Results Nine randomised controlled trials (RCTs) involving 668 patients were included. Pooled analysis showed a slight but significant reduction in fatigue for MPH versus placebo (standardised mean difference, SMD=0.23, 95% CI 0.06 to 0.40; I²=0%). Efficacy increased at 6-week follow-up (SMD=0.30, 95% CI 0.08 to 0.52; 3 RCTs). Subgroup analysis indicated that D-MPH significantly improved CRF (SMD=0.29, 95% CI 0.01 to 0.57; 3 RCTs), while racemic MPH did not (SMD=0.19, 95% CI −0.02 to 0.41; 4 RCTs). Safety analysis revealed no significant increase in overall adverse events versus placebo, though non-significant trends towards increased mood changes (OR=3.35) and dizziness (OR=2.66) were observed. TSA indicated insufficient information size to confirm definitive efficacy (cumulative Z-curve crossed traditional boundary but not O’Brien-Fleming boundary). GRADE evidence certainty was moderate for overall MPH and D-MPH efficacy, and low for racemic MPH.Conclusions MPH demonstrates a modest improvement in CRF, with enhanced effects at 6 weeks. D-MPH shows superior therapeutic potential compared with racemic MPH. However, current evidence is insufficient to support widespread clinical application due to limitations in sample size and heterogeneity. Higher-quality RCTs are needed to confirm efficacy and safety profiles.",
  "authors": [
    {
      "affiliations": [
        "Clinical Medical College, Qinghai University Affiliated Hospital, Xining, China",
        "Qinghai University, Xining, Qinghai, China"
      ],
      "name": "Yonghao Wen"
    },
    {
      "affiliations": [
        "Clinical Medical College, Qinghai University Affiliated Hospital, Xining, China",
        "Qinghai University, Xining, Qinghai, China"
      ],
      "name": "Peng Gu"
    },
    {
      "affiliations": [
        "Department of Radiology, South China University of Technology, Guangzhou, Guangdong, China"
      ],
      "name": "Jingxin Yan"
    },
    {
      "affiliations": [
        "Qinghai University, Xining, Qinghai, China"
      ],
      "name": "Jiawu Li"
    },
    {
      "affiliations": [
        "Qinghai University Medical College, Xining, Qinghai, China"
      ],
      "name": "Genshan Li"
    },
    {
      "affiliations": [
        "Qinghai University Medical College, Xining, Qinghai, China"
      ],
      "name": "Zheng Zhang"
    },
    {
      "affiliations": [
        "Stem Cell and Regenerative Medicine Laboratory, Qinghai University Affiliated Hospital, Xining, Qinghai, China"
      ],
      "name": "Manjun Deng"
    },
    {
      "affiliations": [
        "Clinical Medical College, Qinghai University Affiliated Hospital, Xining, China",
        "Stem Cell and Regenerative Medicine Laboratory, Qinghai University Affiliated Hospital, Xining, Qinghai, China"
      ],
      "name": "Haining Fan"
    }
  ],
  "title": "Methylphenidate in improving cancer-related fatigue: efficacy and safety – systematic review and meta-analysis of randomised controlled trials with trial sequential analysis",
  "uid": "8d4382a4-4b5d-5594-ba28-3001a4f95ab0"
}