Several classes of medication have been studied in the role of appetite stimulants. The best established are the progestogens - megestrol acetate and medroxyprogesterone acetate, and corticosteroids. Their mechanism of action is not well understood.
This is an active area of clinical research, and a number of other agents are also being investigated, including metoclopramide, dronabinol, EPA (fish oil), erthythropoietin, thalidomide, ghrelin, interferon, melatonin, non-steroidal anti-inflammatories, nandrolone, antidepressants such as mirtazepine, and atypical antipsychotics such as olanzapine.
What is known
There is good evidence that megestrol acetate improves appetite and weight gain in advanced cancer, but insufficient evidence that it has benefit in AIDS or other diseases causing anorexia and weight loss.  A smaller number of studies have investigated medroxyprogesterone acetate, and they also support its use in patients with cancer. 
The duration of most studies was six to twelve weeks. It was not possible to draw a conclusion about the impact on patients’ quality of life, or what dose should be used. There was a low incidence of adverse effects in these studies. [1-2]
Dexamethasone, prednisolone and methylprednisolone have all been shown to improve appetite, and some studies have also shown increases in quality of life and wellbeing. There is not enough evidence to recommend doses or duration of treatment, and it is suggested that the effects tend to diminish after four weeks, while side effects increase, although one study showed that benefits continued at eight weeks. 
Hydrazine sulphate has been shown to be ineffective in numerous studies, and should not be used as an appetite stimulant. 
Despite promising results in early studies, eicosapentaenoic acid (EPA) and cannabinoids have not gone onto produce clinically useful weight gain or improved appetite in phase III trials. [2-3]
What it means in practice
- Stimulating appetite often does not reverse cachexia. 
- Progestogens or corticosteroids can be used to improve appetite in palliative care patients. The benefits in terms of quality of life and well-being have not been established, and clinicians should assess these regularly in individual patients being treated. There are no recommendations to guide the choice of dose or the duration of treatment. 
- Choice of drug should take into account the side effect profile, cost and burden of treatment. 
- It is recommended that other agents only be used in the setting of a clinical trial. 
Finding out more
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Cachexia anorexia syndrome
- Berenstein EG, Ortiz Z. Megestrol acetate for the treatment of anorexia-cachexia syndrome. Cochrane Database Syst Rev. 2005 Apr 18;(2):CD004310.
- Yavuzsen T, Davis MP, Walsh D, Le Grand S, Lagman R. Systematic review of the treatment of cancer-associated anorexia and weight loss. J Clin Oncol. 2005 Nov 20;23(33):8500-11.
- Blum D, Omlin A, Fearon K, Baracos V, Radbruch L, Kaasa S, Strasser F; European Palliative Care Research Collaborative. Evolving classification systems for cancer cachexia: ready for clinical practice? Support Care Cancer. 2010 Mar;18(3):273-9.
- Del Fabbro E, Dalal S, Bruera E. Symptom control in palliative care--Part II: cachexia/anorexia and fatigue. J Palliat Med. 2006 Apr;9(2):409-21.
- Desport JC, Blanc-Vincent MP, Gory-Delabaere G, Bachmann P, Beal J, Benamouzig R, et al. Standards, Options and Recommendations (SOR) for the use of appetite stimulants in oncology. Work group. Federation of the French Cancer Centres (FNCLCC). Bull Cancer. 2000 Apr;87(4):315-28.
Last updated 13 December 2010