Fatigue

Key Messages

  • Fatigue is distressing, common in palliative care patients, and greatly affects quality of life. [1,2]
  • Approximately half or more of adult and paediatric patients are likely to experience fatigue
  • It is often inadequately assessed although several tools are recommended. [3]
  • Regular assessment, attention to reversible factors, and multidisciplinary approaches to treating fatigue are essential. [2,4,5]
  • Interventions involving physical exercise [2,6] and psychosocial interventions show definite promise for cancer related fatigue [4,7-9] although studies involving a defined palliative care population have not been conclusive. [9-11]
  • Guidelines for the management of cancer related fatigue are available [4,12] but do not specifically address the needs of palliative care patients, or those with non-malignant conditions. [2]
  

PubMed Searches

Fatigue
Free full text only All citations About these searches
Review Collection

Evidence Summary

Definition and Prevalence

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. [1,10,13-16] A systematic review of symptoms in adult and paediatric patients with advanced cancer indicated that over half experienced fatigue. [10,17] The prevalence of fatigue is likely to be similar or indeed higher in patients with other life-limiting diseases, including HIV-AIDS, heart disease, chronic obstructive pulmonary disease, Parkinson’s disease and renal disease. [15,16,18,19] Careful assessment is needed to ensure appropriate differentiation of fatigue and other conditions such as 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.

It is likely that the presence and intensity of fatigue may increase as patients’ disease progresses. The negative impact on quality of life of patients and their caregivers can be substantial. [13] While fatigue is distressing and common in palliative care patients it is often inadequately assessed. [1-3] Cultural issues are important in understanding the significance of fatigue for a particular person. [2]

Assessment

Simple self-report scales should be used to routinely assess fatigue. [3] In a recent review of available tools used to measure fatigue in cancer patients only four tools met the authors quality standards. [20] The Brief Fatigue Inventory (BFI), the Functional Assessment of Cancer Therapy (FACT-F), the Multidimensional Fatigue Inventory 20 (MFI-20) and the Piper Fatigue Scale (PFS) were found to have adequate psychometric properties. These tools have not been validated in the palliative care context but may be useful. 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. It is also screened in the Edmonton Symptom Assessment Scale, which has been validated in the palliative care setting. [19] Validated assessment tools are available for adolescents. Younger children can be asked if they are 'tired or not tired'. [4,5]

Treatment

Regular assessment, attention to reversible factors, and multidisciplinary approaches to treating fatigue are essential. [2,3,5] Interventions involving physical exercise (walking and multimodal exercise) [2,6] and psychosocial interventions (eg. stress management, counselling, and restorative approaches) show definite promise for cancer related fatigue [7,8] although studies of physical activity involving a defined palliative care population have not been conclusive. [9-11] Whilst guidelines for the management of cancer related fatigue are available [4] these do not specifically address the needs of palliative care patients, or those with non-malignant conditions. [2]

Practice Implications

  • 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. [21,22]
  • Validated assessment tools for measuring fatigue in cancer patients are available and may be useful in other patient groups. [20] Younger children can be asked if they are 'tired or not tired'. [4,5]
  • A multidisciplinary approach allows clinicians to identify and manage the full range of issues for patients with fatigue. Strategies [4] 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.
  • Exercise may benefit all patients and improve fatigue, but individual exercise programs are seen as the most beneficial. [23,24]
  • 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. [1,25,26]
  • Pharmacological approaches to managing fatigue are evolving. Of the psychostimulant agents, methylphenidate has been shown to be beneficial in small studies, [27-29] whilst modafinil shows promise. Progestational steroids [27] and donepezil [28] have so far not shown any benefit in trials. There is limited evidence to base recommendations on. [2]
  • Erythropoiesis stimulating agents (epoetin alfa and darbepoetin alfa) have been shown to improve cancer related fatigue in patients with chemotherapy-induced anaemia. [27] However, recent safety concerns suggest they should now only be offered to patients during myelosuppressive chemotherapy where the goal of treatment is not cure. [26,30]
  • 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. [16,19]
  • 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. [2]
  • There is little evidence for the use of psychosocial interventions to manage fatigue. [31]

Evidence Gap

  • Fatigue in palliative care patients has been identified as an important symptom for research. [2] 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. [2] 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. [13]
  • Research is required to establish validated screening and assessment tools of fatigue in palliative care.
  • 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 [28] 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.
  • New research on the benefits of melatonin in managing fatigue have not established a positive effect. [32]

 

  1. Mücke M; Mochamat, Cuhls H, Peuckmann-Post V, Minton O, Stone P, Radbruch L. Pharmacological treatments for fatigue associated with palliative care. Cochrane Database Syst Rev. 2015 May 30;5:CD006788.
  2. Radbruch L, Strasser F, Elsner F, Gonçalves JF, Løge J, Kaasa S, et al. Fatigue in palliative care patients -- an EAPC approach. Palliat Med. 2008 Jan;22(1):13-32.
  3. 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.
  4. National Comprehenive Cancer Network (NCCN). Cancer-Related Fatigue. NCCN Clinical Practice Guidelines in Oncology. 2010 [cited 2010 June 28]; v.1.2010 [Available: www.nccn.org]
  5. Ullrich CK, Dussel V, Orellana L, Kang TI, Rosenberg AR, Feudtner C, et al. Self-reported fatigue in children with advanced cancer: Results of the PediQUEST study. Cancer. 2018 Sep 15;124(18):3776-3783. doi: 10.1002/cncr.31639. Epub 2018 Oct 6.
  6. Cramp F, Byron-Daniel J. Exercise for the management of cancer-related fatigue in adults. Cochrane Database Syst Rev. 2012 Nov 14; 11:CD006145.
  7. 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.
  8. 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.
  9. 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.
  10. Bhardwaj T, Koffman J. Non-pharmacological interventions for management of fatigue among children with cancer: systematic review of existing practices and their effectiveness. BMJ Support Palliat Care. 2017 Dec;7(4):404-414. doi: 10.1136/bmjspcare-2016-001132. Epub 2017 Jul 31.
  11. Heywood R, McCarthy AL, Skinner TL. Efficacy of Exercise Interventions in Patients With Advanced Cancer: A Systematic Review. Arch Phys Med Rehabil. 2018 Dec;99(12):2595-2620. doi: 10.1016/j.apmr.2018.04.008. Epub 2018 May 5.
  12. National Cancer Institute. Fatigue (PDQ®). Bethesda, MD: National Cancer Institute. [Cited 2015 June 16].
  13. 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.
  14. 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.
  15. 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.
  16. Siciliano M, Trojano L, Santangelo G, De Micco R, Tedeschi G, Tessitore A. Fatigue in Parkinson's disease: A systematic review and meta-analysis. Mov Disord. 2018 Nov;33(11):1712-1723. doi: 10.1002/mds.27461. Epub 2018 Sep 28.
  17. 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. 
  18. 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.
  19. Chen YW, Camp PG, Coxson HO, Road JD, Guenette JA, Hunt MA, et al. A Comparison of Pain, Fatigue, Dyspnea and their Impact on Quality of Life in Pulmonary Rehabilitation Participants with Chronic Obstructive Pulmonary Disease. COPD. 2018 Feb;15(1):65-72. doi: 10.1080/15412555.2017.1401990. Epub 2017 Dec 11.
  20. Al Maqbali M, Hughes C, Gracey J, Rankin J, Dunwoody L, Hacker E. Quality assessment criteria: psychometric properties of measurement tools for cancer related fatigue. Acta Oncol. 2019 Sep;58(9):1286-1297. doi: 10.1080/0284186X.2019.1622773. Epub 2019 Jun 17.
  21. Jacobsen PB. Assessment of fatigue in cancer patients. J Natl Cancer Inst Monogr. 2004;(32):93-7.
  22. 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.
  23. Buffart LM, Sweegers MG, May AM, Chinapaw MJ, van Vulpen JK, Newton RU, et al. Targeting Exercise Interventions to Patients With Cancer in Need: An Individual Patient Data Meta-Analysis. J Natl Cancer Inst. 2018 Nov 1;110(11):1190-1200. doi: 10.1093/jnci/djy161.
  24. Gebruers N, Camberlin M, Theunissen F, Tjalma W, Verbelen H, Van Soom T, et al. The effect of training interventions on physical performance, quality of life, and fatigue in patients receiving breast cancer treatment: a systematic review. Support Care Cancer. 2019 Jan;27(1):109-122. doi: 10.1007/s00520-018-4490-9. Epub 2018 Oct 9.
  25. Carroll JK, Kohli S, Mustian KM, Roscoe JA, Morrow GR. Pharmacologic treatment of cancer-related fatigue. Oncologist. 2007;12 Suppl 1:43-51.
  26. Tomlinson D, Robinson PD, Oberoi S, Cataudella D, Culos-Reed N, Davis H, et al. Pharmacologic interventions for fatigue in cancer and transplantation: a meta-analysis. Curr Oncol. 2018 Apr;25(2):e152-e167. doi: 10.3747/co.25.3883. Epub 2018 Apr 30.
  27. 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.
  28. Harris JD. Fatigue in chronically ill patients. Curr Opin Support Palliat Care. 2008 Sep;2(3):180-6.
  29. 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.
  30. National Comprehenive Cancer Network (NCCN). Cancer - and Treatment-related Anemia. NCCN Clinical Practice Guidelines in Oncology. 2008 [cited 2010 June 28]; v.1.2011 [Available: www.nccn.org]
  31. Poort H, Peters M, Bleijenberg G, Gielissen MF, Goedendorp MM, Jacobsen P, Verhagen S, Knoop H. Psychosocial interventions for fatigue during cancer treatment with palliative intent. Cochrane Database Syst Rev. 2017 Jul 14;(7):CD012030. doi: 10.1002/14651858.CD012030.pub2.
  32. Lund Rasmussen C, Klee Olsen M, Thit Johnsen A, Petersen MA, Lindholm H, Andersen L, et al. Effects of melatonin on physical fatigue and other symptoms in patients with advanced cancer receiving palliative care: A double-blind placebo-controlled crossover trial. Cancer. 2015 Oct 15;121(20):3727-36. doi: 10.1002/cncr.29563. Epub 2015 Jul 15.

Overview Articles

Guidelines

Link to Prescribing Information

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

Last updated 08 November 2019