Methylphenidate Safe but Ineffective for Cancer-Related Fatigue: Study
UK: Researchers have found in a new study that methylphenidate did not significantly reduce fatigue severity in patients with advanced cancer after 6 (± 2) weeks of treatment. However, it was found to be safe and well-tolerated.
The phase III, double-blind, placebo-controlled trial, published in Health Technology Assessment and 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 in palliative care patients. 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:
- Patients receiving methylphenidate showed slightly better fatigue scores compared to the placebo group, but the difference was neither statistically nor clinically significant.
- At six weeks, the mean fatigue score improvement in the methylphenidate group was 1.97 points higher, which did not meet the 5-point threshold for clinical significance.
- Over the full study period, the average improvement in fatigue was nominally significant (Diff 2.20), yet still fell short of clinical relevance.
- Secondary outcomes, such as quality of life, physical symptoms, and activities of daily living, showed no significant differences between the two groups.
- A small but statistically significant reduction in depression scores was observed in the methylphenidate group.
- Serious adverse events were reported at similar rates in both groups, with no unexpected reactions.
- There was no increased risk of death among participants receiving methylphenidate.
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.
Reference:
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
