Appetite Stimulants

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 evidence that megestrol acetate (MA) improves appetite (NNT = 4) and has a small effect on weight gain (NNT = 12) in advanced cancer, AIDS, and some other conditions, with the effect increasing at higher doses. [1] These benefits were seen when compared with placebo, but not in studies where it was compared with other drugs. Megestrol acetate has not been shown to improve quality of has a range if adverse effects. Thromboembolic complications resulted in death in one in 23 patients taking this medication.

A smaller number of studies have investigated medroxyprogesterone acetate (MPA). [2]
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. 

Dexamethasone, prednisolone and methylprednisolone have all been shown to improve appetite in patients with cancer, 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 last four to eight weeks, while side effects increase with duration of treatment. [2,3] 

Hydrazine sulphate has been shown to be ineffective in numerous studies, and should not be used as an appetite stimulant. [2] 

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. [2,4] Side effects of EPA are mild but they affect quality of life, limiting its acceptability to patients. [5]

A systematic review of use of thalidomide to treat cachexia found few high quality studies, and no recommendation could be made based on the available evidence. [6]

Non-steroidal anti-inflammatory drugs have been investigated as a possible treatment for cachexia, based on their potential to modulate the pro-inflammatory components of the cachexia anorexia syndrome. Two systematic reviews have evaluated the literature on use of non-steroidal anti-inflammatory drugs, and suggest that whilst some improvements in weight and physical performance have been shown, the evidence is of poor quality and NSAIDs cannot be recommended to treat cachexia except in clinical trials at this stage. [7,8]

What it means in practice

  • Stimulating appetite often does not reverse cachexia. [9]
  • 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. [2]
  • Choice of drug should take into account the side effect profile, cost and burden of treatment. [1,9] 
  • It is recommended that other agents only be used in the setting of a clinical trial. [10]
  1. Ruiz Garcia V, López-Briz E, Carbonell Sanchis R, Gonzalvez Perales JL, Bort-Marti S. Megestrol acetate for treatment of anorexia-cachexia syndrome. Cochrane Database Syst Rev. 2013 Mar 28;3:CD004310.
  2. 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.
  3. Miller S, McNutt L, McCann MA, McCorry N. Use of corticosteroids for anorexia in palliative medicine: a systematic review. J Palliat Med. 2014 Apr;17(4):482-5.
  4. Blum D, Omlin A, Fearon K, Baracos V, Radbruch L, Kaasa S, et al. Evolving classification systems for cancer cachexia: ready for clinical practice? Support Care Cancer. 2010 Mar;18(3):273-9.
  5. Ries A, Trottenberg P, Elsner F, Stiel S, Haugen D, Kaasa S, et al. A systematic review on the role of fish oil for the treatment of cachexia in advanced cancer: an EPCRC cachexia guidelines project. Palliat Med. 2012 Jun;26(4):294-304. Epub 2011 Aug 24.
  6. Reid J, Mills M, Cantwell M, Cardwell CR, Murray LJ, Donnelly M. Thalidomide for managing cancer cachexia. Cochrane Database Syst Rev. 2012 Apr18;4:CD008664.
  7. Solheim TS, Fearon KC, Blum D, Kaasa S. Non-steroidal anti-inflammatory treatment in cancer cachexia: a systematic literature review. Acta Oncol. 2013 Jan;52(1):6-17. Epub 2012 Oct 1.
  8. Reid J, Hughes CM, Murray LJ, Parsons C, Cantwell MM. Non-steroidal anti-inflammatory drugs for the treatment of cancer cachexia: a systematic review. Palliat Med. 2013 Apr;27(4):295-303. Epub 2012 Mar 26.
  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. [No Abstract Available]
  10. 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.

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Last updated 17 January 2017