Milnacipran for the treatment of fibromyalgia in adults: A 15-week, multicenter, randomized, double-blind, placebo-controlled, multiple-dose clinical trial

• Published in: Clinical therapeutics 2008-11, Vol.30 (11), p.1988-2004
• Main Authors: Clauw, Daniel J., MD, Mease, Philip, MD, Palmer, Robert H., MD, Gendreau, R. Michael, MD, PhD, Wang, Yong, PhD
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antidepressants; Arthritis; Biological and medical sciences; Capsules; Chronic fatigue syndrome; Chronic pain; Constipation - chemically induced; Cyclopropanes - adverse effects; Cyclopropanes - therapeutic use; Diseases of the osteoarticular system; Dizziness - chemically induced; Dopamine; Dose-Response Relationship, Drug; Double-Blind Method; fatigue; Fatigue - drug therapy; Female; Fibromyalgia; Fibromyalgia - diagnosis; Fibromyalgia - drug therapy; Fibromyalgia - physiopathology; Humans; Internal Medicine; Male; Medical Education; Medical sciences; Middle Aged; milnacipran; Miscellaneous. Osteoarticular involvement in other diseases; pain; Pain - drug therapy; Pain - physiopathology; Pain Measurement - methods; Patient Satisfaction - statistics & numerical data; Pharmacology. Drug treatments; physical function; Placebos; Psychiatry; Psychopharmacology; Quantitative psychology; Questionnaires; Rheumatology; Serotonin Uptake Inhibitors - adverse effects; Serotonin Uptake Inhibitors - therapeutic use; Time Factors; Treatment Outcome; Vomiting - chemically induced
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/j.clinthera.2008.11.009

Abstract Background: Preclinical and clinical studies have suggested that milnacipran, a dual norepinephrine-serotonin reuptake inhibitor, may be efficacious in the treatment of fibromyalgia (FM). Objective: This study was conducted to evaluate the efficacy and tolerability of milnacipran in treating the multiple domains of FM. Methods: This was a multicenter, double-blind, placebo-controlled trial. Adult patients (age 18–70 years) who met 1990 American College of Rheumatology criteria for FM were randomized to receive milnacipran 100 mg/d, milnacipran 200 mg/d, or placebo for 15 weeks. Because this was a pivotal registration trial, the primary end points were chosen to investigate efficacy for 2 potential indications: the treatment of FM and the treatment of FM pain. Thus, the 2 primary efficacy end points were rates of FM composite responders and FM pain composite responders. FM composite responders were defined as patients concurrently experiencing clinically meaningful improvements in the following 3 domain criteria: pain (≥30% improvement, as recorded in an electronic diary); patients' global status (a rating of very much improved or much improved on the Patient Global Impression of Change [PGIC] scale); and physical function (a ≥6-point improvement on the 36-item Short-Form Health Survey [SF-36] Physical Component Summary score). FM pain composite responders were defined as those who met the pain and PGIC criteria. Adverse events reported by patients or observed by investigators were recorded throughout the trial. Results: Of 2270 patients screened, 1196 were randomized to receive milnacipran 100 mg/d (n = 399), milnacipran 200 mg/d (n = 396), or placebo (n = 401). The majority of patients were female (96.2%) and white (93.5%). The population had a mean age of 50.2 years, a mean baseline weight of 180.8 pounds, and a mean baseline body mass index of 30.6 kg/m2 . Compared with placebo, significantly greater proportions of milnacipran-treated patients were FM composite responders (100 mg/d: P = 0.01; 200 mg/d: P = 0.02) and FM pain composite responders (100 mg/d: P = 0.03; 200 mg/d: P = 0.004). Milnacipran was associated with significant improvements in pain after 1 week of treatment (100 mg/d: P = 0.004; 200 mg/d: P = 0.04), as well as significant improvements in multiple secondary efficacy end points, including global status (PGIC: P