Anorexia-Cachexia Syndrome — or ACS — is a severe, multifactorial condition seen in advanced cancer and other life-limiting illnesses. It leads to loss of appetite, muscle wasting, and fat loss.
There are different reasons for weight loss: cancer, heart disease , lung disease, kidney and liver disease, brain(depression), hyperthyroidism are just some examples.
Overview
Let’s explore the medications used to manage Anorexia Cachexia Syndrome (ACS). We will not be discussing bulimia and anorexia nervosa here.
It’s important to note that no medication has been proven to improve overall survival in ACS. The primary goals are comfort, strength, and quality of life. If a dietitian consults on supplements and those fail, we may consider medication depending on the underlying cause.
Olanzapine
Labelled as an antipsychotic but often used in chemotherapy induced nausea and vomiting has been shown to cause weight gain. Low-dose olanzapine, 2.5 to 5 mg daily, especially at bedtime, is often first-line for cancer-related ACS. It can improve appetite within a week and weight in a few weeks.
- Adverse effects include possible drowsiness, QTc changes such as QTc prolongation and can cause hyperglycemia.
Dexamethasone
Dexamethasone boosts appetite short-term but doesn’t maintain weight long-term. It’s best for patients with limited prognosis — often a short trial at 4 mg per day.
- Steroids however can cause Fluid retention, fatigue, hyperglycemia and adrenal insufficiency long -term.
Dronabinol & Cannabis
Dronabinol, a synthetic cannabinoid, may help appetite in HIV/AIDS but shows little weight gain in cancer. Dizziness and mood changes are common. Cannabis has limited data and can’t be prescribed in many regions due to issues around regulation and travel restrictions.
Adverse effects include: Dizziness / Dysphoria/Impaired driving
Contraindicated in those under 26 or pregnant or with unstable cardiac disease
It is not approved for CACS (Cancer Anorexia Cachexia Syndrome)
Megestrol Acetate
Megestrol acetate increases appetite and weight — mostly fat, not muscle. Start at 400 mg per day, up to 800 mg. But beware: higher doses increase risk of blood clots (think pulmonary embolism and DVT) and fluid retention.
- Adverse Effects : Clots, Edema, Adrenal suppression
Mirtazapine
Mirtazapine, an antidepressant, can cause modest weight gain but results are mixed in cancer cachexia. Typical dose: 15–30 mg at night . Mirtazepine has shown mixed results in appetite studies.
Other / Emerging
NSAIDs ,androgens and Omega-3 fatty acids have mixed or inconclusive results. Early studies of ponsegromab — a monoclonal antibody — show promise, but it’s still under investigation.
More research needed on the above .
Summary
In summary:
Treat the underlying condition (rule out depression, hyperthyroidism etc)
- No drug reverses ACS completely.
- Set clear goals and review benefits within weeks.
- Stop medications if no response.
- Low-dose olanzapine is a reasonable first choice.
- Dexamethasone or megestrol can be short-term options when needed.
Focus on: Clear goals 
, Short trials , Avoid polypharmacy
Disclaimer
This educational blog is for informational purposes only and does not replace medical advice. Treatment decisions should be individualized by qualified healthcare professionals.
References
1. Groarke JD, Crawford J, Collins SM, et al. Ponsegromab for the Treatment of Cancer Cachexia. N Engl J Med. 2024;391(24):2291-2303.
2. 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
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. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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
11. Roeland EJ, Bohlke K, Baracos VE, et al. Cancer Cachexia: ASCO Guideline Rapid Recommendation Update. J Clin Oncol 2023;41(25):4178–4179.
12. Moertel CG, Schutt AJ, Reitemeier RJ, et al. Corticosteroid therapy of preterminal gastrointestinal cancer. Cancer. 1974 Jun;33(6):1607–9.
13. 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.
14. 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.
15. 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.
16. Watanabe N, Omori IM, Nakagawa A, et al. Mirtazapine versus other antidepressive agents for depression. Cochrane Database Syst Rev. 2011;(12):CD006528.
17. 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.
18. 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.
19. 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].