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A 3-Year, Open-Label, Flexible-Dosing Study of Milnacipran for the Treatment of Fibromyalgia

Arnold, Lesley M. MD*; Palmer, Robert H. MD; Ma, Yimin PhD

doi: 10.1097/AJP.0b013e31828440ab
Original Articles

Objectives: To evaluate the effects of long-term milnacipran treatment in fibromyalgia patients.

Methods: Patients completing a previous milnacipran study were eligible to participate in this long-term (up to 3.25 y), open-label study. After washout, dose escalation, and 8 weeks of stable-dose treatment (100 mg/d), patients received flexible doses of milnacipran (50 to 200 mg/d) for the remainder of the study. Safety evaluations included adverse events and vital signs. Clinical measures included weekly recall pain (visual analog scale [VAS]), Patient Global Disease Status (PGDS), and the Short Form-36 Health Survey (SF-36, including the Physical Component Summary [PCS] and Mental Component Summary scores). Cohort analyses were conducted to assess the effects of milnacipran over varying periods of time.

Results: Of 1227 patients entering the study, 585 (47.7%) were classified as completers, including 379 (30.9%) patients who were currently enrolled when the study was administratively terminated. Mean duration of treatment was 19 months, with 206 patients reaching the final visit and receiving 36 to 38 months of study treatment. The percentage of patients with ≥1 treatment-emergent adverse event was 88.3%, with nausea (25.9%) and headache (13.4%) being the most common events. Discontinuations due to adverse events occurred in 20.9% of patients. Potentially clinically significant increases in blood pressure or heart rate occurred in ≤1.1% of patients. Mean improvement from baseline in weekly recall VAS pain was 17.6; improvements in global status (PGDS) and physical functioning (SF-36 PCS) were also observed. In all patient cohorts, these improvements were observed by month 3 and remained relatively constant over time. At final study visit in the 3-year cohort, 70.3% of patients rated their overall fibromyalgia as “much improved” or “very much improved.”

Discussion: No new safety concerns were identified in this long-term study. Sustained symptom improvements were found in fibromyalgia patients who received up to 3.25 years of milnacipran treatment.

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*Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH

Forest Research Institute Inc., Jersey City, NJ

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Supported by Forest Laboratories Inc., (New York, NY). L.M.A. receives consulting fees from Pfizer, (New York, NY); Forest Laboratories, Grünenthal Group, (Bedminster, NJ); Daiichi Sankyo, (Parsippany, NJ); Theravance, (San Francisco, CA); and Dainippon Sumitomo Pharma (Marlborough, MA); as well as research grants (present or pending) from Pfizer, (New York, NY), Eli Lilly and Company, (Indianapolis, IN); Forest Laboratories, and Takeda Pharmaceuticals (Deerfield, IL). In the past 3 years, L.M.A. has also received consulting fees and/or grants from Cypress Bioscience, (San Diego, CA); Johnson & Johnson, (New Brunswick, NJ); AstraZeneca, (Wilmington, DE); Sanofi (formerly Sanofi-Aventis), (Bridgewater, NJ); Wyeth (currently Pfizer), (New York, NY); Boehringer Ingelheim, (Ridgefield, CT); and Novartis (East Hanover, NJ). R.H.P. and Y.M. are employees of Forest Research Institute Inc., (Jersey City, NJ); a subsidiary of Forest Laboratories Inc., and hold stock or stock options in that company.

Reprints: Lesley M. Arnold, MD, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Medical Arts Building, 222 Piedmont Avenue, Suite 8200, Mail Location 665S, Cincinnati, OH 45219 (e-mail:

Received July 2, 2012

Accepted December 20, 2012

© 2013 by Lippincott Williams & Wilkins