Payne, C., Wiffen, P. J., & Martin, S. (2012). Interventions for fatigue and weight loss in adults with advanced progressive illness. Cochrane Database of Systematic Reviews, 1, CD008427.

To determine the efficacy of interventions used in the management of fatigue and/or unintentional weight loss in adults with advanced progressive illness by reviewing the evidence contained within Cochrane reviews. This overview does not attempt to rereview the literature or provide information on outcomes not reported within the included Cochrane reviews.

The database searched was Cochrane Database of Systematic Reviews.

No keyword or subject heading was searched because it would be unreliable due to the diverse range of interventions and illnesses under review. The authors hand searched the Cochrane Database of Systematic Reviews by title for all reviews that might assess the effect of an intervention on fatigue and/or unintentional weight loss in adults with advanced progressive illness.

Studies were included if they reported interventions with fatigue and/or unintentional weight loss as the primary treatment intent.

Studies were excluded if the treatment of fatigue and/or unintentional weight loss was not a primary indication for the intervention, they were systematic reviews published outside the Cochrane Library, or if they only included children.
 

Twenty-seven systematic reviews were retrieved. Assessment of Multiple SysTemAtic Reviews (AMSTAR) was used to assess the methodological quality of each systematic review.

• The final number of systematic reviews included was 27.
• The total sample size included 302 studies with 31,833 participants.
• Adults 18 years or older with an advanced progressive illness known to have clinically significant fatigue and/or weight loss in the latter stages of illness were included. These conditions included degenerative neurological conditions, such as multiple sclerosis, Parkinson’s disease, dementia, irreversible organ failure, cancer with distant metastasis, and acquired immune deficiency syndrome (AIDS).
• The pharmacological interventions were eicosapentaenoic acid (EPA) and any drug therapy for the management of cancer-related fatigue. The nonpharmacological interventions were exercise, interventions by breast care nurses, and psychosocial interventions.

• Patients were undergoing the end of life phase of care.
• The study has clinical applicability for palliative care.

The review looked for the following outcomes:

1. Clinically significant improvements in fatigue and/or unintentional weight loss
2. Improvements in quality of life of people who have fatigue and/or unintentional weight loss
3. Withdrawals due to adverse events.

Results relative to fatigue in patients with cancer included identification of five systematic reviews (116 studies with 17,342 participants). 

Nonpharmacologic Interventions

The evidence provided some insight into interventions that may prove beneficial, such as exercise. However, recommendations could not be made for specific exercise interventions that might best manage fatigue. In a systematic review, Cruickshank et al. (2008) reviewed the effect of breast care management strategies on fatigue in women with breast cancer at any stage of their illness. No included study assessed fatigue as an independent outcome, and no conclusions could be drawn. In 2009, Goedendorp reported that for patients undergoing cancer treatment at any disease stage, there was insufficient evidence that psychosocial interventions were beneficial for fatigue management. 

Pharmacologic Interventions

Sufficient evidence was not provided for the use of EPA over placebo in patients with advanced cancer. A small but significant improvement with fatigue was found with the use of methylphenidate in 51 studies with 10,296 participants. Use of erythropoietin and darbepoetin showed evidence of an effect over standard of care or placebo for the treatment of cancer-related fatigue. However, increased safety concerns mean they are no longer recommended in practice for this use, especially if the person’s hemoglobin concentration is greater than 12 g/dL. No benefits over placebo were seen for fatigue with the use of antidepressant drug paroxetine, nor with progestational steroids.

There was a lack of robust evidence for interventions for fatigue management in the advanced stage of progressive illness related to cancer.

Extraction of data was limited to Cochrane reviews. Fatigue as an outcome indicator was not always sufficiently reported.

Exercise interventions can lead to an improvement in fatigue in patients with cancer; however, this beneficial effect requires further research for those in the advanced stage.