A Pooled Analysis of Two Randomized, Double-Blind, Placebo-Controlled Trials of Milnacipran Monotherapy in the Treatment of Fibromyalgia


  • Disclosures: This study was supported by funding from Forest Laboratories, Inc. Dr Michael Geisser has received research grant support from Cypress Biosciences, Inc., another company involved in the development of milnacipran for the management of FM. Dr Robert Palmer is a Senior Medical Director at Forest Research Institute, a subsidiary of Forest Laboratories, Inc., and is a shareholder in that company. Dr R. Michael Gendreau is Vice President and Chief Medical Officer at Cypress Bioscience, Inc. and is a shareholder in that company. Dr Yong Wang is a full-time employee of Forest Research Institute. Dr Daniel Clauw has served as a consultant to Cypress Bioscience, Inc., Forest Laboratories, Inc., and Pierre Fabre Médicament, the company that originally developed milnacipran for clinical use. Dr Clauw has received grant support from and has previously owned stock in Cypress Bioscience, Inc.

Michael E. Geisser, PhD, University of Michigan, Department of Physical Medicine and Rehabilitation, 325 E. Eisenhower Parkway, Ann Arbor, MI 48108, U.S.A. E-mail: mgeisser@umich.edu.


Milnacipran has been shown to significantly improve the pain, global well-being, and physical function of fibromyalgia (FM), and is approved by the U.S. Food and Drug Administration for the management of this disorder. Post hoc analyses of data from two pivotal trials were conducted to further assess the clinical benefits of milnacipran, to determine the impact of baseline pain severity on treatment outcomes, and to confirm the safety and tolerability of this medication in patients with FM. Patients in these trials were randomized to placebo (n = 624), milnacipran 100 mg/day (n = 623), or milnacipran 200 mg/day (n = 837). Two different composite responder analyses were used to evaluate efficacy: a 2-measure analysis, requiring ≥ 30% improvement from baseline visual analog scale 24-hour recall pain scores and a Patient Global Impression of Change (PGIC) score of “very much improved” or “much improved”; and a 3-measure analysis, requiring a ≥ 6-point improvement from baseline in SF-36 Physical Component Summary scores in addition to the pain and PGIC criteria. Additionally, a pooled analysis of mean changes from baseline pain scores was conducted in order to evaluate the efficacy of milnacipran over the entire course of treatment. At 3 months, composite responder rates were significantly higher in the milnacipran treatment groups than in the placebo group (2- and 3-measure composite responder analyses: ≤ 0.001, both doses vs. placebo). These improvements were not dependent on baseline pain severity. Similar composite responder results were observed in patients who continued treatment for up to 6 months. Significant improvements in mean pain scores were seen with both doses of milnacipran vs. placebo as early as 1 week after treatment initiation and were sustained for up to 6 months of milnacipran treatment. The most common adverse events associated with milnacipran were nausea, headache, and constipation.