Mirtazapine is commonly used to treat major depressive disorder. Due to its effects on multiple neurotransmitters, it has been investigated for possible benefits in patients with fibromyalgia. The objective of this systematic review is to assess the efficacy and safety of mirtazapine in the treatment of patients with fibromyalgia. Pubmed (1946-May 2018), Embase (1947-May 2018), CENTRAL, and ClinicalTrials.gov were queried using the search term combination: fibromyalgia, pain, chronic pain, neuralgia, neuropathic pain, chronic widespread pain, or chronic pain syndrome and mirtazapine. Studies appropriate to the objective were evaluated, including three randomized, placebo-controlled trials and one open-label trial, investigating the effect of mirtazapine in patients with fibromyalgia. In patients with fibromyalgia, treatment with mirtazapine resulted in improvements in pain, sleep, and quality of life. Study durations ranged from 6 to 13 weeks and studies used varying dosing strategies for mirtazapine. Minor occurrences of somnolence, weight gain, nasopharyngitis, dry mouth, and increased appetite were reported with mirtazapine use. Based on the reviewed literature, mirtazapine appears to be a promising therapy to improve pain, sleep, and quality of life in patients with fibromyalgia. These benefits were demonstrated in patients that were treatment naïve and those that had failed previous therapies. Additional clinical evidence through larger and longer length trials would be of benefit to further define the role of mirtazapine for patients with fibromyalgia.
Pain Chronic pain Fatigue Sleep Quality of life Depression
This is a preview of subscription content, log in to check access.
All authors substantially contributed to the concept and design, acquisition of the data, or analysis and interpretation; drafting or revision of the manuscript for important intellectual content; and gave final approval for submission and publication.
No external funding was secured for this review.
Compliance with ethical standards
Conflict of interest
The authors have no conflicts of interest to disclose.
This article does not contain any studies with human participants or animals performed by any of the authors.
The authors report no financial relationships relevant to this article to disclose.
Phillips K, Clauw DJ (2013) Central pain mechanisms in the rheumatic diseases: future directions. Arthritis Rheum 65:291–302CrossRefGoogle Scholar
Kato K, Sullivan PF, Evengård B, Pedersen NL (2009) A population-based twin study of functional somatic syndromes. Psychol Med 39:497–505CrossRefGoogle Scholar
Jahan F, Nanji K, Qidwai W, Qasim R (2012) Fibromyalgia syndrome: an overview of pathophysiology, diagnosis and management. Oman Med J 27:192–195CrossRefGoogle Scholar
Wolfe F, Smythe HA, Yunus MB et al (1990) The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum 33:160–172CrossRefGoogle Scholar
Wolfe F, Clauw DJ, Fitzcharles MA et al (2011) Fibromyalgia criteria and severity scales for clinical and epidemiological studies: a modification of the ACR preliminary diagnostic criteria for fibromyalgia. J Rheumatol 38:1113–1122CrossRefGoogle Scholar
Wolfe F, Clauw DJ, Fitzcharles MA, at al (2016) Revisions to the 2010/2011 fibromyalgia diagnostic criteria. Semin Arthritis Rheum 46:319–329CrossRefGoogle Scholar
Macfarlane GJ, Kronisch C, Dean LE et al (2017) EULAR revised recommendations for the management of fibromyalgia. Ann Rheum Dis 76:318–328CrossRefGoogle Scholar
Higgins JPT, Green S (2011) Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. (updated March 2011). The Cochrane Collaboration. http://handbook.cochrane.org. Accessed 23 May 2018
Moher D, Liberati A, Tetzlaff J et al (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 151:264–269CrossRefGoogle Scholar
Jadad AR, Moore RA, Carroll D et al (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17:1–12CrossRefGoogle Scholar
Slim K, Nini E, Forestier D, Kwiatkowski F, Panis Y, Chipponi J (2003) Methodological index for non-randomized studies (minors): development and validation of a new instrument. ANZ J Surg 73:712–716CrossRefGoogle Scholar
Samborski W, Lezańska-Szpera M, Rybakowski JK (2004) Effects of antidepressant mirtazapine on fibromyalgia symptoms. Rocz Akad Med Bialymst 49:265–269PubMedGoogle Scholar
Yeephu S, Suthisisang C, Suttiruksa S, Prateepavanich P, Limampai P, Russell IJ (2013) Efficacy and safety of mirtazapine in fibromyalgia syndrome patients: a randomized placebo-controlled pilot study. Ann Pharmacother 47:921–932CrossRefGoogle Scholar
Miki K, Murakami M, Oka H, Onozawa K, Yoshida S, Osada K (2016) Efficacy of mirtazapine for the treatment of fibromyalgia without concomitant depression: a randomized, double-blind, placebo-controlled phase IIa study in Japan. Pain 157:2089–2096CrossRefGoogle Scholar
Suttiruksa S, Yeephu S, Prateepavanich P, Suthisisang C (2016) Effects of mirtazapine on quality of life of Thai patients with fibromyalgia syndrome: a double-blind, randomized, placebo-controlled trial. Asian Biomed 10:435–445Google Scholar
Verbunt JA, Pernot DH, Smeets RJ (2008) Disability and quality of life in patients with fibromyalgia. Health Qual Life Outcomes 6:8CrossRefGoogle Scholar
Theadom A, Cropley M, Humphrey KL (2007) Exploring the role of sleep and coping in quality of life in fibromyalgia. J Psychosom Res 62:145–151CrossRefGoogle Scholar
Bigatti SM, Hernandez AM, Cronan TA, Rand KL (2008) Sleep disturbances in fibromyalgia syndrome: relationship to pain and depression. Arthritis Rheum 59:961–967CrossRefGoogle Scholar