Abstract
Context
Few pharmacological interventions are available for cancer-associated anorexia and
cachexia. Mirtazapine has been suggested for use in cancer-associated anorexia and
cachexia.
Objectives
This study was conducted to assess the efficacy and tolerability of mirtazapine in
cancer-associated anorexia and cachexia.
Methods
A double-blind placebo-controlled randomized trial. The study included 120 incurable
solid tumour patients with anorexia (appetite loss ≥4 on 0 – 10 scale, 10 = maximum
appetite loss), cachexia (>5% body weight loss over 6 months or >2% plus body mass
index <20) and depression score ≤3 on 0-6 scale (6 = extreme feelings of depression).
Patients were 1:1 randomized to receive mirtazapine 15mg daily at night for 8 weeks
or placebo. The primary endpoint was change in appetite from baseline to day 28. Other
outcomes included changes in quality-of-life, fatigue, depressive symptoms, body weight,
lean body mass, handgrip strength, inflammatory markers, adverse events and survival.
Results
48 (80%) patients in the mirtazapine arm and 52 (87%) in the placebo were assessable
for the 1ry endpoint. Appetite score increased significantly with mirtazapine as well
as with placebo (P < 0.0001 each). The increase in appetite score did not differ significantly between
the two arms in the per-protocol and intention-to-treat analysis (P = 0.472 and 0.462, respectively). Mirtazapine was associated with significantly less
increase in depressive symptoms and higher prevalence of somnolence. The change in
other outcomes did not differ significantly between mirtazapine and placebo.
Conclusion
Mirtazapine 15mg at night for 28 days is no better than placebo in improving the appetite
of incurable solid tumor patients with cancer-associated anorexia and cachexia.
Key Words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of Pain and Symptom ManagementAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Definition and classification of cancer cachexia: an international consensus.Lancet Oncol. 2011; 12: 489-495
- Cancer cachexia: diagnosis, assessment, and treatment.Crit Rev Oncol Hematol. 2018; 127: 91-104
- Cancer cachexia and skeletal muscle atrophy in clinical studies: what do we really know?.J Cachexia Sarcopenia Muscle. 2020; https://doi.org/10.1002/jcsm.12633
- Cancer-associated cachexia.Nat Rev Dis Primers. 2018; 4: 17105
- Management of cancer cachexia: ASCO guideline.J Clin Oncol. 2020; 38: 2438-2453
- What is the evidence for mirtazapine in treating cancer-related symptomatology? A systematic review.Support Care Cancer. 2020; 28: 1597-1606
- Mirtazapine versus other antidepressive agents for depression.Cochrane Database Syst Rev. 2011; 12CD006528
- An open-label, crossover trial of mirtazapine (15 and 30 mg) in cancer patients with pain and other distressing symptoms.J Pain Symptom Manage. 2002; 23: 442-447
- Phase II trial of mirtazapine for cancer-related cachexia and anorexia.Am J Hosp Palliat Care. 2010; 27: 106-110
National Comprehensive Cancer Network. Palliative care (Version 1. 2020). PA: National Comprehensive Cancer Network, 2020. Available at: https://www.nccn.org/professionals/physician_gls/pdf/palliative.pdf. Accessed September 10, 2020.
Edmonton Canada: Alberta Health Services, 2015. Symptom assessment system, revised version (ESAS-R) - Arabic. Available at: https://www.cancercareontario.ca/sites/ccocancercare/files/assets/CCOESAS-Arabic.pdf. Accessed August, 2017.
- Toxicity and response criteria of the Eastern Cooperative Oncology Group.Am J Clin Oncol. 1982; 5: 649-655
- Are you depressed? Screening for depression in the terminally ill.Am J Psychiatry. 1997; 154: 674-676
Ribaudo JM, Cella D, Hahn EA, et al. Re-validation and shortening of the Functional Assessment of Anorexia/Cachexia Therapy (FAACT) questionnaire. Qual Life Res. 2000;9(10):1137–46.
- Development and validation of Arabic version of the hospital anxiety and depression scale.Saudi J Anaesth. 2017; 11: S11-S18
- Common Terminology Criteria for Adverse Events (CTCAE) v4.03.U.S. Department of Health and Human Services, Bethesda, MD.2010 (Available at:) (Accessed August, 2017)
- Effects of melatonin on appetite and other symptoms in patients with advanced cancer and cachexia: a double-blind placebo-controlled trial.J Clin Oncol. 2013; 31: 1271-1276
- Randomised phase III clinical trial of 5 different arms of treatment on 332 patients with cancer cachexia.Eur Rev Med Pharmacol Sci. 2010; 14: 292-301
- Imputation with the R Package VIM.J Statistical Software. 2016; 74: 1-6
- R: A language and environment for statistical computing.R Foundation for Statistical Computing, Vienna, Austria2021 (Available at:)
- Mirtazapine improves sleep and lowers anxiety and depression in cancer patients: superiority over imipramine.Support Care Cancer. 2008; 16 (Accessed April, 2021): 1291-1298
- Intolerance to mirtazapine in advanced cancer.J Pain Symptom Manage. 2011; 42: e4-e7
Article info
Publication history
Published online: May 26, 2021
Accepted:
May 20,
2021
Identification
Copyright
© 2021 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.
