Background for Fast Fact #515   Anorexia-cachexia syndrome (ACS) is a severe, multifactorial condition characterized by reduced appetite and significant loss of skeletal muscle mass and adipose tissue. It is observed in patients with advanced cancer and other life-limiting conditions at advanced stages (1). This Fast Fact discusses the pharmacologic management of ACS. Most published evidence pertains to patients with cancer or HIV/AIDS and typically measures body weight and subjective measures of appetite. Less data is available about prescribed medications for ACS related to cardiac, lung, kidney, and liver disease. See Fast Fact #386 for definitions, evaluation, and non-pharmacologic management of ACS.

Olanzapine   See Fast Fact #315. Low dose olanzapine (2.5 mg to 5 mg daily, preferably at bedtime), is the recommended pharmacologic option for cancer-related anorexia-cachexia syndrome (CACS) (2). Several studies demonstrate significant improvements in appetite within a week and weight gain within several weeks for CACS (3,4). Side effects are rare at these low doses but include somnolence and QTc prolongation. Cost depends on formulation – the orally disintegrating tablet is approximately $25/month while the tablet is about $350/month.

Dexamethasone   Several studies have shown that corticosteroids increase appetite in the short-term (weeks to short months) but have no long-term increase in body weight for CACS (5-7). Therefore, corticosteroids are usually recommended as a short-term trial for CACS, especially when prognosis is anticipated to be months or less (2). Dexamethasone is often selected because of its minimal mineralocorticoid effect (less likely to cause fluid retention and edema), ease of dosing, and low cost (about $19/month). Usual dexamethasone dose for CACS is 4 mg/day.

Dronabinol is a synthetic cannabinoid available via prescription. See Fast Fact #93 for more information. There is supporting evidence that it improves appetite for ACS secondary to HIV/AIDS; but it likely does not significantly increase body weight in this population (8). An appropriate starting dose is dronabinol 2.5 mg twice daily, which can be titrated up depending on response (8). Dizziness and dysphoria are common dose-limiting side effects (8). It has not been shown to benefit CACS (9). Cost and insurance coverage limit its use. There is some supporting data that cannabis can improve appetite (see Fast Fact #279). However, there is little evidence to guide its use for this indication and even in states where it has been decriminalized, it cannot be prescribed by clinicians nor reimbursed by insurances.

 Megestrol acetate   See Fast Fact #100. Megestrol acetate improves appetite and increases weight by 2-5 lbs in patients with CACS (10), COPD (11), and HIV/AIDS (12). The weight gained is primarily adipose tissue rather than skeletal muscle however (10,12). Like corticosteroids, it can be trialed short-term, as a second-line low-cost option, for CACS (2). Begin at 400 mg/day for two weeks and titrate to a maximum dose of 800 mg/day (13). It increases the risk of thromboembolism, which is a relative contra-indication in CACS. Other toxicities include edema, adrenal suppression, and an increased risk of death with doses above 800 mg/day (12).

Mirtazapine   See Fast Fact #314. When used as an antidepressant in the general population, it is associated with weight gain of 6 lbs (14,15). Initial studies of its use to treat CACS, at a dose of 15 mg to 30 mg/day, showed promise (16), however, more recent controlled trials show conflicting results in improving appetite or weight compared to placebo for CACS (17,18).

Other   NSAIDs may improve body weight in cancer cachexia, though evidence is mixed, and side effects limit their use (19). Omega-3-fatty acids have been investigated in CACS with inconclusive results (20).

Emerging treatment   Trials evaluating the monoclonal antibody ponsegromab show promise for increasing weight in patients with CACS (21). Further studies and discussions with regulators are required, with little known to date regarding the potential cost or insurance coverage of ponsegromab. 

Summary   Given the limited efficacy and potential side effects of many medications used to treat anorexia and cachexia, it is important to establish specific goals, expectations, and time frames, recognizing that no medication has been shown to improve overall survival. If no specific benefit is seen at the end of that time, the medication should be discontinued to avoid polypharmacy. Low dose olanzapine is felt by many to be a first-line agent for CACS. In patients unable to tolerate olanzapine, a short-term trial of megestrol acetate or dexamethasone may be offered.

References  

1. Daley SF, Ali MA, Ohnuma T, et al. Anorexia and Cachexia. In: StatPearls. Treasure Island (FL): StatPearls Publishing; January 19, 2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430977/ [Last accessed: 6/23/2025].
2. Roeland EJ, Bohlke K, Baracos VE, et al. Cancer Cachexia: ASCO Guideline Rapid Recommendation Update. J Clin Oncol 2023;41(25):4178–4179.
3. Sandhya L, Devi Sreenivasan N, Goenka L, et al. Randomized Double-Blind Placebo-Controlled Study of Olanzapine for Chemotherapy-Related Anorexia in Patients With Locally Advanced or Metastatic Gastric, Hepatopancreaticobiliary, and Lung Cancer. J Clin Oncol. 2023;41(14):2617-2627.
4. Navari RM, Pywell CM, Le-Rademacher JG, et al. Olanzapine for the Treatment of Advanced Cancer-Related Chronic Nausea and/or Vomiting: A Randomized Pilot Trial. JAMA Oncol. 2020;6(6):895-899.
5. Moertel CG, Schutt AJ, Reitemeier RJ, et al. Corticosteroid therapy of preterminal gastrointestinal cancer. Cancer. 1974 Jun;33(6):1607–9.
6. Bruera E, Roca E, Cedaro L, et al. Action of oral methylprednisolone in terminal cancer patients: a prospective randomized double-blind study. Cancer Treat Rep. 1985;69(7-8):751-754.
7. Yavuzsen T, Davis MP, Walsh D, et al. Systematic review of the treatment of cancer-associated anorexia and weight loss. J Clin Oncol. 2005;23(33):8500-8511.
8. Beal JE, Olson R, Laubenstein L, et al. Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS. J Pain Symptom Manage. 1995;10(2):89-97.
9. Jatoi A, Windschitl HE, Loprinzi CL, et al. Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: a North Central Cancer Treatment Group study. J Clin Oncol. 2002;20(2):567-573.
10. Loprinzi CL, Schaid DJ, Dose AM, et al. Body-composition changes in patients who gain weight while receiving megestrol acetate. J Clin Oncol. 1993;11(1):152-154.
11. Weisberg J, Wanger J, Olson J, et al. Megestrol acetate stimulates weight gain and ventilation in underweight COPD patients. Chest. 2002;121(4):1070-1078.
12. Ruiz Garcia V, López-Briz E, Carbonell Sanchis R, et al. Megestrol acetate for treatment of anorexia-cachexia syndrome. Cochrane Database Syst Rev 2013;2013(3):Cd004310.
13. Loprinzi CL, Michalak JC, Schaid DJ, et al. Phase III evaluation of four doses of megestrol acetate as therapy for patients with cancer anorexia and/or cachexia. J Clin Oncol. 1993;11(4):762-767.
14. Watanabe N, Omori IM, Nakagawa A, et al. Mirtazapine versus other antidepressive agents for depression. Cochrane Database Syst Rev. 2011;(12):CD006528.
15. Laimer M, Kramer-Reinstadler K, Rauchenzauner M, et al. Effect of mirtazapine treatment on body composition and metabolism. J Clin Psychiatry. 2006;67(3):421-424.
16. Riechelmann RP, Burman D, Tannock IF, et al. Phase II trial of mirtazapine for cancer-related cachexia and anorexia. Am J Hosp Palliat Care. 2010;27(2):106-110.
17. Hunter CN, Abdel-Aal HH, Elsherief WA, et al. Mirtazapine in Cancer-Associated Anorexia and Cachexia: A Double-Blind Placebo-Controlled Randomized Trial. J Pain Symptom Manage. 2021;62(6):1207-1215.
18. Arrieta O, Cárdenas-Fernández D, Rodriguez-Mayoral O, et al. Mirtazapine as Appetite Stimulant in Patients With Non-Small Cell Lung Cancer and Anorexia: A Randomized Clinical Trial. JAMA Oncol. 2024;10(3):305-314.
19. Solheim TS, Fearon KC, Blum D, et al. Non-steroidal anti-inflammatory treatment in cancer cachexia: a systematic literature review. Acta Oncol. 2013;52(1):6-17. 
20. Ma YJ, Yu J, Xiao J, et al. The consumption of omega-3 polyunsaturated fatty acids improves clinical outcomes and prognosis in pancreatic cancer patients: a systematic evaluation. Nutr Cancer. 2015;67(1):112-118. 
21. Groarke JD, Crawford J, Collins SM, et al. Ponsegromab for the Treatment of Cancer Cachexia. N Engl J Med. 2024;391(24):2291-2303.

Authors Affiliations: 1. Icahn School of Medicine at Mount Sinai, New York, NY. 2. The Mount Sinai Hospital, New York, NY.
Conflicts of Interest: No conflicts of interest to be disclosed
Version History: first electronically published in July 2025; originally edited by Sean Marks MD.