UK: Researchers have found in a new study that methylphenidate did not significantly reducefatigueseverity in patients with advancedcancerafter 6 (± 2) weeks of treatment. However, it was found to be safe and well-tolerated. The phase III, double-blind, placebo-controlled trial, published inHealth Technology Assessmentand led by Dr. Patrick Stone and colleagues from the Marie Curie Palliative Care Research Department, University College London, aimed to assess whether methylphenidate could offer clinical benefit for cancer-related fatigue inpalliative carepatients. This large-scale study involved 162 adults with advanced cancer and moderate-to-severe fatigue, recruited from 17 palliative care services across England between June 2018 and April 2023. Patients were randomly assigned to receive either methylphenidate or a placebo, with the medication dose gradually increased over six weeks, depending on individual response and side effects. The primary objective was to evaluate changes in fatigue levels after six weeks, using the Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F) scale. The following were the key findings of the study: Despite previous meta-analyses suggesting that methylphenidate may benefit cancer-related fatigue, this rigorous trial did not confirm a meaningful therapeutic effect. Researchers highlighted the highly selective nature of the participant group due to extensive exclusion criteria and noted that the chosen threshold for clinical significance may be open to debate. Given the findings, the authors concluded that methylphenidate should not be recommended for managing fatigue in patients with advanced cancer receiving palliative care. However, they acknowledged the potential for further research into its use in other populations or for different indications. "Cancer-related fatigue remains a challenging symptom to treat, and while methylphenidate was shown to be safe, its effectiveness in this context appears limited based on current evidence," they wrote. Stone P, Minton O, Richardson A, Buckle P, Enayat ZE, Marston L, Freemantle N. Methylphenidate versus placebo for fatigue in patients with advanced cancer: the MePFAC randomised controlled trial. Health Technol Assess 2025;29(36). https://doi.org/10.3310/GJPS6321