No specific drug for the treatment of fatigue in palliative care

Cochrane: 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 it is frequently reported by palliative care patients. The underlying causes of fatigue are not very well understood and fatigue is difficult to treat. We searched the literature in April 2014 and found 45 randomised controlled trials for this update of the review.
We analysed data from 4696 participants who received treatment for their fatigue. The trials dealt with neurological diseases (such as multiple sclerosis (753 participants), post-polio syndrome (58) and Parkinson's disease (19)), different types of cancer (3223), HIV/AIDS (514), end-stage renal disease (56), multi-type advanced disease in hospice patients (30), amyotrophic lateral sclerosis (28) and end-stage chronic lung disease (15).
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 (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, we excluded these drugs from 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. Future trials should measure fatigue in advanced disease using comparable and standardised measures.

Authors' conclusions: 

Based on limited evidence, we cannot recommend a specific drug for the treatment of fatigue in palliative care patients. Fatigue research in palliative care seems to focus on modafinil and methylphenidate, which may be beneficial for the treatment of fatigue associated with palliative care although further research about their efficacy is needed. Dexamethasone, methylprednisolone, acetylsalicylic acid, armodafinil, amantadine and L-carnitine should be further examined. Consensus is needed regarding fatigue outcome parameters for clinical trials.