Pharmacological treatments for fatigue associated with palliative care

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, thereby impacting daily activity and quality of life, often with rest not counteracting fatigue. Fatigue frequently occurs in patients with advanced disease and modalities treating cancer often contribute or cause fatigue. Further complicating issues are its multidimensionality, subjective nature, and lack of a consensus definition of fatigue. Pathophysiology is not fully understood and evidence-based treatment approaches are needed.

The objective was to determine efficacy of pharmacological treatments on non-specific fatigue in palliative care. The focus was on patients at an advanced stage of disease, including cancer and other chronic diseases associated with fatigue, aiming to relieve fatigue. Studies aiming at curative treatment (e.g. surgical intervention for early breast cancer) were not included.

We searched EMBASE; Psych Lit, CENTRAL and MEDLINE to June 2009.

We considered randomised controlled trials (RCTs) concerning adult palliative care with focus on pharmacological treatment of fatigue. The primary outcome had to be non-specific fatigue (or related terms such as asthenia).

Results were screened and included if they met the selection criteria. If two or more studies were identified that investigated a specific drug in a population with the same disease, meta-analysis was conducted. In addition, comparison of type of drug investigated in a specific population as well as comparison of frequent adverse effects of fatigue treatment was done by creating overview tables.

More than 2000 publications were screened, and 22 met inclusion criteria. In total, data from 11 drugs and 1632 participants were analysed. Studies investigating amantadine, pemoline, and modafinil in participants with Multiple Sclerosis (MS)-associated fatigue and methylphenidate in patients suffering from advanced cancer and fatigue could be used for meta-analysis. Amantadine in MS and methylphenidate in cancer patients showed a superior effect. Most studies had low participant numbers and were heterogenous.

Based on limited evidence, we cannot recommend a specific drug for treatment of fatigue in palliative care patients. Surprisingly, corticosteroids have not been a research focus for fatigue treatment, although these drugs are frequently used. Recent fatigue research seems to focus on modafinil, which may be beneficial although there is no evidence currently. Amantadine and methylphenidate should be further examined. Consensus regarding fatigue assessment in advanced disease is needed.