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Cited by 227Pain Management and Opioid UseCancer survivorship and carePalliative Care and End-of-Life Issues

Pharmacological treatments for fatigue associated with palliative care

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Mücke, Martin, Mochamat, mochamat, Cuhls, Henning, Peuckmann-Post, Vera, Minton, Ollie, Stone, Patrick, Radbruch, Lukas·2015·Cochrane Database of Systematic Reviews
DOI 10.1002/14651858.cd006788.pub3PMC PMC6483317
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Abstract

BACKGROUND: This review updates the original review, 'Pharmacological treatments for fatigue associated with palliative care' and also incorporates the review 'Drug therapy for the management of cancer-related fatigue'.In healthy individuals, fatigue is a protective response to physical or mental stress, often relieved by rest. By contrast, in palliative care patients' fatigue can be severely debilitating and is often not counteracted with rest, thereby impacting daily activity and quality of life. Fatigue frequently occurs in patients with advanced disease (e.g. cancer-related fatigue) and modalities used to treat cancer can often contribute. Further complicating issues are the multidimensionality, subjective nature and lack of a consensus definition of fatigue. The pathophysiology is not fully understood and evidence-based treatment approaches are needed. OBJECTIVES: To evaluate the efficacy of pharmacological treatments for fatigue in palliative care, with a focus on patients at an advanced stage of disease, including patients with cancer and other chronic diseases. SEARCH METHODS: For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PsycINFO and EMBASE, and a selection of cancer journals up to 28 April 2014. We searched the references of identified articles and contacted authors to obtain unreported data. To validate the search strategy we selected sentinel references. SELECTION CRITERIA: We considered randomised controlled trials (RCTs) concerning adult palliative care with a focus on pharmacological treatment of fatigue compared to placebo, application of two drugs, usual care or a non-pharmacological intervention. The primary outcome had to be non-specific fatigue (or related terms such as asthenia). We did not include studies on fatigue related to antineoplastic treatment (e.g. chemotherapy, radiotherapy, surgical intervention). We also included secondary outcomes that were assessed in fatigue-related studies (e.g. exhaustion, tiredness). DATA COLLECTION AND ANALYSIS: Two review authors (MM and MC) independently assessed trial quality and extracted data. We screened the search results and included studies if they met the selection criteria. If we identified two or more studies that investigated a specific drug with the same dose in a population with the same disease and using the same assessment instrument or scale, we conducted meta-analysis. In addition, we compared the type of drug investigated in specific populations, as well as the frequent adverse effects of fatigue treatment, by creating overview tables. MAIN RESULTS: For this update, we screened 1645 publications of which 45 met the inclusion criteria (20 additional studies to the previous reviews). In total, we analysed data from 18 drugs and 4696 participants. There was a very high degree of statistical and clinical heterogeneity in the trials and we discuss the reasons for this in the review. There were some sources of potential bias in the included studies, including a lack of description of the methods of blinding and allocation concealment, and the small size of the study populations. We included studies investigating pemoline and modafinil in participants with multiple sclerosis (MS)-associated fatigue and methylphenidate in patients suffering from advanced cancer and fatigue in meta-analysis. Treatment results pointed to weak and inconclusive evidence for the efficacy of amantadine, pemoline and modafinil in multiple sclerosis and for carnitine and donepezil in cancer-related fatigue. Methylphenidate and pemoline seem to be effective in patients with HIV, but this is based only on one study per intervention, with only a moderate number of participants in each study. Meta-analysis shows an estimated superior effect for methylphenidate in cancer-related fatigue (standardised mean difference (SMD) 0.49, 95% confidence interval (CI) 0.15 to 0.83). Therapeutic effects could not be described for dexamphetamine, paroxetine or testosterone. There were a variety of results for the secondary outcomes in some studies. Most studies had low participant numbers and were heterogeneous. In general, adverse reactions were mild and had little or no impact. AUTHORS' CONCLUSIONS: Based on limited evidence, we cannot recommend a specific drug for the treatment of fatigue in palliative care patients. Fatigue research in palliative care seems to focus on modafinil and methylphenidate, which may be beneficial for the treatment of fatigue associated with palliative care although further research about their efficacy is needed. Dexamethasone, methylprednisolone, acetylsalicylic acid, armodafinil, amantadine and L-carnitine should be further examined. Consensus is needed regarding fatigue outcome parameters for clinical trials.

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  • Evidence-based interventions for managing fatigue in metastatic breast cancer and other advanced cancer populations are lacking.

    “Evidence-based interventions for managing fatigue in MBC and other advanced cancer populations are lacking [7–9].”

    From Protocol of a randomized trial of acceptance and commitment therapy for fatigue interference in metastatic breast cancer (2020) · cites this paper as [7]

    The Authors’ conclusions (Implications for practice; page unavailable) say evidence is too weak to support a specific drug for fatigue in palliative care patients, including those with cancer. The review addresses pharmacological treatments, not interventions generally, and does not establish the claim specifically for metastatic breast cancer. (LLM, conf=0.86)

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  • A Cochrane meta-analysis found the evidence for pharmacologic fatigue interventions in advanced cancer and palliative care inconclusive and noted small, heterogeneous samples.

    “A Cochrane meta-analysis of pharmacologic interventions for fatigue in advanced cancer and other palliative care patients characterized the evidence as inconclusive and highlighted the small, heterogeneous samples in many studies [7].”

    From Protocol of a randomized trial of acceptance and commitment therapy for fatigue interference in metastatic breast cancer (2020) · cites this paper as [7]

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3 of the 153 references couldn’t be matched to a known paper.

Research works printed but not linked: 2

  1. Radbruch L, Strasser F, Elsner F, Goncalves JF, Loge J, Kaasa S, et al. Fatigue in palliative care patients -- an EAPC approach. Palliative Medicine 2008;22(1):13-32. [PMID: ] [DOI] [PubMed] [Google Scholar]
  2. Review Manager. Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.

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Authors
Mücke, M., Mochamat, M., Cuhls, H., Peuckmann-Post, V., Minton, O., Stone, P., & Radbruch, L.
Affiliations
  • University Hospital Bonn (DE)
  • Diponegoro University (ID)
  • Palliative Medicine; Medical Faculty RWTH Aachen University; Aachen Germany
  • St George's, University of London (GB)
  • University College London (GB)
ORCID
Venue
Cochrane Database of Systematic Reviews
Publisher
Wiley
Published
2015-05-30
Volume
2020
Issue
4
Pages
CD006788-CD006788
ISSN
  • 1361-6137 (ISSN-L)
  • 1465-1858
DOI
10.1002/14651858.cd006788.pub3
PMC
PMC6483317
OpenAlex
W1525436179
Cited by
227
References
153
Citations by year
2026: 2 · 2025: 8 · 2024: 8 · 2023: 11 · 2022: 19 · 2021: 31 · 2020: 20 · 2019: 9 · 2018: 15 · 2017: 30 · 2016: 18 · 2015: 13 · 2014: 11 · 2013: 12 · 2012: 11
FWCI
5.15
Type
journal article
Language
en
Open access
Locations
  • Cochrane Database of Systematic Reviews (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • RWTH Publications (RWTH Aachen) (submittedVersion)
Funders
Marie Curie (MCCC-FCO-11-U)
Topics
  • Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Opioid Use
  • Health Sciences › Medicine › Oncology › Cancer survivorship and care
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Palliative Care and End-of-Life Issues
Keywords
fatigue, palliative care, pharmacotherapy, cancer-related fatigue, advanced disease, drug efficacy, adverse effects, quality of life, quality of life interventions, non-pharmacological treatment, chronic disease, end-of-life care, palliative sedation, palliative radiotherapy, palliative chemotherapy, palliative surgery, palliative care nursing, palliative social work
MeSH terms
Modafinil, Adult, Amantadine, Central Nervous System Stimulants, Benzhydryl Compounds, Carnitine, Chronic Disease, Fatigue, Humans, Kidney Failure, Chronic, Methylphenidate, Multiple Sclerosis, Neoplasms, Palliative Care, Pemoline, Randomized Controlled Trials as Topic

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