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Featured Review: Pharmacological treatments for fatigue associated with palliative care

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Is there a drug to improve tiredness, weakness, and lack of energy in advanced diseases?

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. In an advanced disease such as cancer, fatigue can be described as tiredness, weakness, or lack of energy. The underlying causes of fatigue are not very well understood and fatigue is difficult to treat.

A team of Cochrane authors based in Germany, Indonesia, and the United Kingdom worked with the Cochrane Pain, Palliative and Supportive Care Group 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.

The authors included 45 randomized controlled trials in this review, analyzing 18 drugs and including 4696 participants. There was weak evidence for the efficacy of amantadine, pemoline, and modafinil in reducing fatigue in patients with multiple sclerosis. There was also weak evidence for the efficacy of carnitine and donepezil for cancer-related fatigue. One small trial showed that people with HIV/AIDS and fatigue seemed to benefit 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. There was no information about dexamphetamine, paroxetine or testosterone. Previous studies have shown that erythropoietin and darbepoetin, drugs that improve anaemia (a shortage of red cells or haemoglobin in the blood), 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 from small studies, the evidence does not support the use of a specific drug for the treatment of fatigue in palliative care,” said Martin Mücke, a researcher at the University of Bonn in Germany and lead author of the Cochrane Review. “We encourage future trials to measure fatigue in advance diseases using comparable and standardized measures so that we better understand fatigue and possible treatments.”

Read the full Cochrane Review

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