Advertisement

Mirtazapine in Cancer-Associated Anorexia and Cachexia: A Double-Blind Placebo-Controlled Randomized Trial

      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 access
      One-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 Management
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Fearon K
        • Strasser F
        • Anker SD
        • et al.
        Definition and classification of cancer cachexia: an international consensus.
        Lancet Oncol. 2011; 12: 489-495
        • Sadeghi M
        • Keshavarz-Fathi M
        • Baracos V
        • Arends J
        • Mahmoudi M
        • Rezaei N.
        Cancer cachexia: diagnosis, assessment, and treatment.
        Crit Rev Oncol Hematol. 2018; 127: 91-104
        • Dolly A
        • Dumas JF
        • Servais S.
        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
        • Baracos VE
        • Martin L
        • Korc M
        • Guttridge DC
        • Fearon KCH.
        Cancer-associated cachexia.
        Nat Rev Dis Primers. 2018; 4: 17105
        • Roeland EJ
        • Bohlke K
        • Baracos VE
        • et al.
        Management of cancer cachexia: ASCO guideline.
        J Clin Oncol. 2020; 38: 2438-2453
        • Economos G
        • Lovell N
        • Johnston A
        • Higginson IJ
        What is the evidence for mirtazapine in treating cancer-related symptomatology? A systematic review.
        Support Care Cancer. 2020; 28: 1597-1606
        • Watanabe N
        • Omori IM
        • Nakagawa A
        • et al.
        Mirtazapine versus other antidepressive agents for depression.
        Cochrane Database Syst Rev. 2011; 12CD006528
        • Theobald DE
        • Kirsh KL
        • Holtsclaw E
        • Donaghy K
        • Passik SD
        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
        • Riechelmann RP
        • Burman D
        • Tannock IF
        • Rodin G
        • Zimmermann C
        Phase II trial of mirtazapine for cancer-related cachexia and anorexia.
        Am J Hosp Palliat Care. 2010; 27: 106-110
      1. 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.

      2. 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.

        • Oken MM
        • Creech RH
        • Tormey DC
        • Horton J
        • Davis TE
        • McFadden ET
        • Carbone PP.
        Toxicity and response criteria of the Eastern Cooperative Oncology Group.
        Am J Clin Oncol. 1982; 5: 649-655
        • Chochinov HM
        • Wilson KG
        • Enns M
        • Lander S.
        Are you depressed? Screening for depression in the terminally ill.
        Am J Psychiatry. 1997; 154: 674-676
      3. 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.

        • Terkawi AS
        • Tsang S
        • AlKahtani GJ
        • et al.
        Development and validation of Arabic version of the hospital anxiety and depression scale.
        Saudi J Anaesth. 2017; 11: S11-S18
        • National Cancer Institute (US)
        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)
        • Del Fabbro E
        • Dev R
        • Hui D
        • Palmer L
        • Bruera E.
        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
        • Mantovani G.
        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
        • Kowarik A
        • Templ M
        Imputation with the R Package VIM.
        J Statistical Software. 2016; 74: 1-6
        • R Core Team
        R: A language and environment for statistical computing.
        R Foundation for Statistical Computing, Vienna, Austria2021 (Available at:)
        • Cankurtaran ES
        • Ozalp E
        • Soygur H
        • Akbiyik DI
        • Turhan L
        • Alkis N.
        Mirtazapine improves sleep and lowers anxiety and depression in cancer patients: superiority over imipramine.
        Support Care Cancer. 2008; 16 (Accessed April, 2021): 1291-1298
        • Davis MP
        • Kirkova J
        • Lagman R
        • Walsh D
        • Karafa M.
        Intolerance to mirtazapine in advanced cancer.
        J Pain Symptom Manage. 2011; 42: e4-e7