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Cancer-related fatigue—pharmacological interventions: systematic review and network meta-analysis
  1. Ronald Chow1,2,
  2. Eduardo Bruera3,
  3. Michael Sanatani2,
  4. Leonard Chiu4,
  5. Elizabeth Prsic1,
  6. Gabriel Boldt2 and
  7. Michael Lock2
  1. 1 Yale New Haven Hospital, Yale School of Medicine, New Haven, Connecticut, USA
  2. 2 London Health Sciences Centre, Schulich School of Medicine & Dentistry, London, Ontario, Canada
  3. 3 The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  4. 4 Columbia Vagelos College of Physicians and Surgeons, New York, New York, USA
  1. Correspondence to Ronald Chow, Yale University, New Haven, CT, USA; ronald.chow{at}


Introduction Cancer-related fatigue (CRF) is a very common symptom in patients with cancer, and one of the five areas of highest priority in cancer research. There is currently no consensus on pharmacologic interventions for treating CRF. The aim of this systematic review is to provide more clarity on which pharmacologic interventions may be most promising, for future clinical trials. The network meta-analysis provides the ability to compare multiple agents when no direct head-to-head trials of all agents have been performed.

Methods Medline (PubMed), EMBASE and Cochrane Central Register of Controlled Trials were searched up until 5 March 2021. Studies were included if they reported on a pharmacologic intervention for CRF. Standardised mean differences and corresponding 95% CIs were computed using a random-effects maximum-likelihood model.

Results This review reports on 18 studies and 2604 patients, the most comprehensive review of pharmacologic interventions for CRF at the time of this publication. Methylphenidate, modafinil and paroxetine were superior to placebo. Methylphenidate and modafinil were equivalent to one another. Paroxetine was superior to modafinil.

Conclusion Paroxetine should be further studied in future trials. As well, more safety data are needed on pharmacologic interventions.

  • fatigue
  • pharmacology

Data availability statement

No data are available. Systematic review; data are available in published papers or via contact with authors.

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Data availability statement

No data are available. Systematic review; data are available in published papers or via contact with authors.

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  • Contributors All authors contributed significantly.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.