title: Efficacy of mirtazapine for the treatment of fibromyalgia without concomitant depression: a randomized, double-blind, placebo-controlled phase IIa study in Japan.
abstract: To evaluate the efficacy and safety of mirtazapine in Japanese patients with fibromyalgia (FM), a parallel-group, randomized, double-blind, placebo-controlled phase IIa study was conducted at 57 sites between November 2012 and February 2014. Patients aged 20 to 64 years who met the American College of Rheumatology 1990 diagnostic FM criteria and had stably high pain scores during a placebo run-in period were randomly assigned (1:1) by a computer-generated allocation sequence (block size 4) to receive mirtazapine orally (15 mg/d for 1 week and then 30 mg/d) or matching placebo for 12 weeks. The primary endpoint was change in mean numerical rating scale (NRS) pain score from baseline to endpoint (week 12 or early discontinuation). Of the 430 patients randomized (n = 215 each group), 422 (n = 211 each group) were analyzed for the primary endpoint. At the study endpoint, mirtazapine caused a significantly greater reduction in the mean NRS pain score compared with placebo (difference, 0.44; 95% confidence interval, -0.72 to -0.17; P = 0.0018). The reduction by mirtazapine remained significantly greater compared with placebo from week 6 onward. More patients treated with mirtazapine had their NRS pain score reduced by ≥30% from baseline (45.5% vs 30.8%). Mirtazapine also improved pain-related quality of life assessed by the Japanese version of the Fibromyalgia Impact Questionnaire and the Short-Form 36 Questionnaire. Adverse events were more common with mirtazapine than placebo (68.8% vs 56.7%), including somnolence (32.1% vs 7.4%), weight gain (17.7% vs 0.9%), and increased appetite (11.6% vs 3.3%). In conclusion, mirtazapine was an effective and safe treatment for Japanese patients with FM.
authors.affiliation: Department of Pain Medicine, Osaka University Graduate School of Medicine, Suita, Japan; Center for pain management, Hayaishi Hospital. Osaka, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Miki
authors.affiliation: Department of Psychosomatic Medicine, Nihon University Hospital, Tokyo, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Murakami
authors.affiliation: Department of Rheumatology, Hachioji Medical Center, Tokyo Medical University, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Oka
authors.affiliation: Clinical Research Planning Department, Meiji Seika Pharma Co, Ltd, Tokyo, Japan.
authors.forename: Kaname
authors.initials: K
authors.lastname: Onozawa
authors.affiliation: Clinical Research Planning Department, Meiji Seika Pharma Co, Ltd, Tokyo, Japan.
authors.forename: Sadahiro
authors.initials: S
authors.lastname: Yoshida
authors.affiliation: Department of Neuropsychiatry, St. Marianna University School of Medicine, Miyamae-ku, Kawasaki, Japan, M. Murakami is now with the Sanno Hospital, International University of Health and Welfare, Tokyo, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Osada
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy* / Q000209:etiology; D004311:Double-Blind Method; D005260:Female; D005356:Fibromyalgia / Q000150:complications* / Q000188:drug therapy* / Q000523:psychology; D006801:Humans; D007564:Japan; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008875:Middle Aged; D000078785:Mirtazapine; D010147:Pain Measurement; D011569:Psychiatric Status Rating Scales; D011788:Quality of Life / Q000523:psychology; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D000929:Antidepressive Agents, Tricyclic; D008803:Mianserin; D000078785:Mirtazapine