Fatigue

Key messages

  • Fatigue is distressing, common in palliative care patients, and greatly affects quality of life. [1] It is often inadequately assessed. [2] Cultural issues are important in understanding the significance of fatigue for a particular person. [1]
  • Simple self-report scales should be used to routinely assess fatigue. [2] Regular assessment, attention to reversible factors, and multidisciplinary approaches to treating fatigue are essential. [1,3]
  • Interventions involving physical exercise (walking and multimodal exercise) [1,4] and psychosocial interventions (eg, stress management, counselling, and restorative approaches) show definite promise for cancer related fatigue [3, 5-6] although studies of physical activity involving a defined palliative care population have not been conclusive. [7]
  • Pharmacological approaches to managing fatigue are evolving. Of the psychostimulant agents, methylphenidate has been shown to be beneficial in small studies, [8-10] whilst modafinil shows promise. Progestational steroids [8] and donepezil [9] have so far not shown any benefit in trials.
  • Whilst guidelines for the management of cancer related fatigue are available [3,11] these do not specifically address the needs of palliative care patients, or those with non-malignant conditions. [1]

Background

Fatigue, defined as a persistent sense of tiredness which is not relieved by sleep or rest, is an extremely common problem amongst palliative care patients and causes significant distress. [12-14] A systematic review of symptoms in patients with advanced cancer indicated that over half experienced fatigue. [15] It is likely that the presence and intensity of these symptoms increases as patients’ disease progresses. The negative impact on quality of life of patients and their caregivers is substantial. [12] The prevalence of fatigue is likely to be similar or indeed higher in patients with other progressive chronic diseases, including HIV-AIDS, heart disease, chronic obstructive pulmonary disease, and renal disease. [14,16] Careful assessment is needed to ensure appropriate differentiation of fatigue and depression.

Factors which may contribute to fatigue in palliative care patients, some of which can be treated or modified, include:

  • Anaemia
  • Cachexia and nutritional deficiencies
  • Dyspnoea
  • Hypothyroidism, hypogonadism, adrenal insufficiency
  • Metabolic disorders
  • Reduced activity and deconditioning
  • Pain
  • Depression or emotional distress
  • Insomnia
  • Chemotherapy and radiotherapy
  • Adverse effects of medications

Active research areas / controversies

  • Fatigue in palliative care patients has been identified as an important symptom for research. [1] The experience of fatigue amongst people with advanced progressive diseases may be different to cancer treatment related fatigue. Evidence from studies of cancer treatment related fatigue should be assessed for its relevance to individuals in palliative care.
  • Cultural issues in assessment and treatment of fatigue have been recognised as important, with many European languages having no word for fatigue. [1] Other issues being studied include: mechanisms and causes, prevalence patterns, and outcomes of cancer related fatigue, and the social and economic impact on both patients and caregivers. There appears to be an overlap between fatigue and problems of psychological distress, reduced functional ability and pain; the causal links between these problems have not yet been clarified. [12]
  • N of 1 randomised trials of methylphenidate are currently underway to identify those patients who are most likely to benefit, and to clarify the benefit versus the burden of treatment. Bupropion, androgen replacement therapy and L-carnitine [9] are also being studied as potential pharmacological agents for treating fatigue in palliative care patients, and show promise.
  • Trials are underway to clarify the risks associated with use of erythropoiesis stimulating agents (epoetin alfa and darbepoetin alfa) in cancer related fatigue associated with anaemia.

What is known

Fatigue is a multidimensional problem that causes a combination of physical, emotional and cognitive difficulties. [1-2]

Implications for practice

  • Fatigue should be recognised as a major problem for palliative care patients, and should therefore be routinely asked about. Fatigue is one of the symptoms screened for by the Symptom Assessment Scale in the PCOC dataset, which is used by many palliative care services in Australia. Other more detailed assessment tools are also available. [17-18]
  • Validated assessment tools are available for adolescents. Younger children can be asked if they are 'tired or not tired'. [3]
  • A multidisciplinary approach allows clinicians to identify and manage the full range of issues for patients with fatigue. Strategies [3] may include:
    • Activity enhancement / exercise
    • Energy conservation and provision of aids and equipment
    • Nutritional assessment and support
    • Psychosocial support
    • Distraction and concentration techniques
    • Addressing sleeping problems.
  • There is little evidence from placebo control studies to guide pharmacological management of fatigue. Low dose methylphenidate appears to be potentially effective, based on small studies. Treatment of depression with antidepressants has not so far been shown to improve fatigue in randomised control trials. [19]
  • Erythropoiesis stimulating agents (epoetin alfa and darbepoetin alfa) have been shown to improve cancer related fatigue in patients with chemotherapy-induced anaemia. [8] However, recent safety concerns suggest they should now only be offered to patients during myelosuppressive chemotherapy where the goal of treatment is not cure. [20]
  • Research on management of this symptom has mainly studied cancer related fatigue and HIV / AIDS. There is little specific evidence regarding the management of fatigue in other advanced non-malignant conditions.
  • Fatigue may be protective of the individual who is very close to death. Active treatment of fatigue, and encouragement to increase physical activity, are most often inappropriate at that point. [1]
  

PubMed Searches

Fatigue
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Review Collection
  1. Radbruch L, Strasser F, Elsner F, Gonçalves JF, Løge J, Kaasa S, Nauck F, Stone P; Research Steering Committee of the European Association for Palliative Care (EAPC). Fatigue in palliative care patients -- an EAPC approach. Palliat Med. 2008 Jan;22(1):13-32.
  2. National Institutes of Health. Symptom management in cancer: pain, depression and fatigue: State-of-the-Science Conference Statement. J Pain Palliat Care Pharmacother. 2003;17(1):77-97.
  3. NCCN. Cancer-Related Fatigue. NCCN Clinical Practice Guidelines in Oncology. 2010 [cited 2010 June 28]; v.1.2010 [Available: www.nccn.org]
  4. Cramp F, Daniel J. Exercise for the management of cancer-related fatigue in adults. Cochrane Database Syst Rev. 2008 Apr 16;(2):CD006145.
  5. Jacobsen PB, Donovan KA, Vadaparampil ST, Small BJ. Systematic review and meta-analysis of psychological and activity-based interventions for cancer-related fatigue. Health Psychol. 2007 Nov;26(6):660-7.
  6. Kangas M, Bovbjerg DH, Montgomery GH. Cancer-related fatigue: A systematic and meta-analytic review of non-pharmacological therapies for cancer patients. Psychol Bull. 2008 Sep;134(5):700-41.
  7. Lowe SS, Watanabe SM, Courneya KS. Physical activity as a supportive care intervention in palliative cancer patients: a systematic review. J Support Oncol. 2009 Jan-Feb;7(1):27-34.
  8. Minton O, Stone P, Richardson A, Sharpe M, Hotopf M. Drug therapy for the management of cancer related fatigue.Cochrane Database Syst Rev. 2008 Jan 23;(1):CD006704.
  9. Harris JD. Fatigue in chronically ill patients. Curr Opin Support Palliat Care. 2008 Sep;2(3):180-6.
  10. Hardy SE. Methylphenidate for the treatment of depressive symptoms, including fatigue and apathy, in medically ill older patients and terminally ill adults. Am J Geriatric Pharmacother. 2009 Feb;7(1):34-59.
  11. National Cancer Institute. Fatigue (PDQ®). Bethesda, MD: National Cancer Institute. [Cited 2015 June 16].
  12. Curt G, Breitbart W, Cella D, Groopman JE, Horning SJ, Itri LM, et al. Impact of cancer-related fatigue on the lives of patients: New findings from the Fatigue Coalition. Oncologist. 2000;5(5):353-60.
  13. Eddy L, Cruz M. The relationship between fatigue and quality of life in children with chronic health problems: a systematic review. J Spec Pediatr Nurs. 2007 Apr;12(2):102-14.
  14. Murtagh FE, Addington-Hall J, Higginson IJ. The prevalence of symptoms in end-stage renal disease: a systematic review.Adv Chronic Kidney Dis. 2007 Jan;14(1):82-99.
  15. Teunissen SC, Wesker W, Kruitwagen C, de Haes HC, Voest EE, de Graeff A. Symptom prevalence in patients with incurable cancer: a systematic review. J Pain Symptom Manage. 2007 Jul;34(1):94-104. Epub 2007 May 23. 
  16. Solano JP, Gomes B, Higginson IJ. A comparison of symptom prevalence in far advanced cancer, AIDS, heart disease, chronic obstructive pulmonary disease, and renal disease. J Pain Symptom Manage. 2006 Jan;31(1):58-69.
  17. Jacobsen PB. Assessment of fatigue in cancer patients. J Natl Cancer Inst Monogr. 2004;(32):93-7.
  18. Whitehead L. The measurement of fatigue in chronic illness: a systematic review of unidimensional and multidimensional fatigue measures. J Pain Symptom Manage. 2009 Jan;37(1):107-28.
  19. Carroll JK, Kohli S, Mustian KM, Roscoe JA, Morrow GR. Pharmacologic treatment of cancer-related fatigue. Oncologist. 2007;12 Suppl 1:43-51.
  20. NCCN. Cancer - and Treatment-related Anemia. NCCN Clinical Practice Guidelines in Oncology. 2008 [cited 2010 June 28]; v.1.2011 [Available: www.nccn.org]

Guidelines

Link to prescribing information

NB Prescribing information may not yet have been updated to include the most recent evidence.

Overview articles

Last updated 18 January 2017