Pharmacological treatments for fatigue associated with palliative care

Dr Martin Mücke, Physician, Department of Palliative Medicine and Department of General Practice and Family Medicine, University Hospital of Bonn, Bonn, Germany. Dr Mochamat, Physician, Department of Anesthesiology and Intensive Care, University of Diponegoro / Kariadi Hospital, Semarang, Indonesia and Prof Dr. Lukas Radbruch, Head of Department, Department of Palliative Medicine, University Hospital of Bonn, Germany.

Dr Martin Mücke

Patrick, a 65-year-old man with prostate carcinoma, was admitted to our palliative care unit for symptom control. Patrick told us, “I’m not sure whether it’s worth it to feel like this every day. I’d like to die. I was used to taking a walk every day, that was quality of life; but now, I can’t do that. I can’t even manage visits from my friends and some days I don’t even get out of bed. I feel like I just don’t have enough energy.” This is a typical statement of palliative patients suffering from fatigue and Patrick is not alone in his battle with fatigue. Cancer-related fatigue is one of the most commonly reported cancer-related symptoms, occurring in more than 90 % of patients with this disease.

Dr Mochamat

In an advanced disease such as cancer, fatigue can be described as tiredness, weakness or lack of energy. Fatigue can affect daily activity and quality of life and is frequently reported by palliative care patients. Fatigue is a protective response to physical or mental stress, often relieved by rest in healthy individuals. By contrast, in palliative care patients fatigue can be severely debilitating and is often not counteracted with rest, thereby impacting on daily activity and quality of life. The underlying causes of fatigue are not very well understood and fatigue is difficult to treat.

Prof Dr Lukas Radbruch

In collaboration with the Cochrane Pain, Palliative and Supportive Care Group, a team of authors from Germany, Indonesia and the United Kingdom, conducted a systematic review to evaluate the efficacy of pharmacological treatments for fatigue in palliative care. The review focused on patients at an advanced stage of disease, including those with cancer and other chronic diseases.

The team searched the literature in the electronic databases of Register of Controlled Trials, MEDLINE, EMBASE and PsycINFO, and other resources up to April 2014 and found 45 randomised controlled trials for this update of the review. The authors analysed data from 18 drugs and 4,696 participants who received treatment for their fatigue. The trials dealt with neurological diseases (such as multiple sclerosis, post-polio syndrome and Parkinson’s disease), different types of cancer, HIV/AIDS, end-stage renal disease, multi-type advanced disease in hospice patients, amyotrophic lateral sclerosis and end-stage chronic lung disease.

Amantadine was shown to be effective in reducing fatigue in patients with multiple sclerosis. Participants with HIV/AIDS and fatigue benefited from treatment with methylphenidate or pemoline. There was some low-quality evidence from small trials that methylphenidate, a stimulant drug that improves concentration, is effective for the management of cancer-related fatigue. Previous studies have shown that erythropoietin and darbepoetin, drugs that improve anaemia (lack of iron), are also effective for cancer-related fatigue. However, due to safety concerns and side effects shown by more recent studies, erythropoietin and darbepoetin should no longer be used. Therefore, these drugs were not included in this review update. Overall, most side effects of the investigated drugs seemed to be mild.

Based on limited evidence, the authors still cannot recommend a specific drug for the treatment of fatigue in palliative care. Future trials should measure fatigue in advanced disease using comparable and standardised validated outcome instruments.

We do hope that this will give us some tools and interventions to help patients like Patrick!

Read the full Cochrane Review
This post relates to the longer article by Mücke M, Mochamat,  Cuhls H, Peuckmann-Post V, Minton O, Stone P, Radbruch L. Pharmacological treatments for fatigue associated with palliative care. Cochrane Database of Systematic Reviews 2015, Issue 5. Art. No.: CD006788. DOI: 10.1002/14651858.CD006788.pub3. Read the full Cochrane Review here.