Efficacy and safety of milnacipran 100 mg/day in patients with fibromyalgia: Results of a randomized, double-blind, placebo-controlled trial

Authors

  • Lesley M. Arnold,

    Corresponding author
    1. University of Cincinnati College of Medicine, Cincinnati, Ohio
    • Women's Health Research Program, University of Cincinnati College of Medicine, Medical Arts Building, 222 Piedmont Avenue, Suite 8200, Mail Location 665S, Cincinnati, OH 45219
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    • Dr. Arnold has received consulting fees, speaking fees, and/or honoraria from Cypress Bioscience, Wyeth, Boehringer Ingelheim, Allergan, Takeda, UCB, Theravance, AstraZeneca, and Sanofi-Aventis (less than $10,000 each) and from Eli Lilly, Pfizer, and Forest Laboratories (more than $10,000 each) and has received research support from Eli Lilly, Cypress Bioscience, Wyeth, Boehringer Ingelheim, Allergan, Forest Laboratories, and Pfizer.

  • R. Michael Gendreau,

    1. Cypress Bioscience, Inc., San Diego, California
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    • Drs. R. M. Gendreau and J. F. Gendreau own stock or stock options in Cypress Bioscience.

  • Robert H. Palmer,

    1. Forest Research Institute, Inc., Jersey City, New Jersey
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    • Drs. Palmer and Wang own stock or stock options in Forest Laboratories.

  • Judy F. Gendreau,

    1. Cypress Bioscience, Inc., San Diego, California
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    • Drs. R. M. Gendreau and J. F. Gendreau own stock or stock options in Cypress Bioscience.

  • Yong Wang

    1. Forest Research Institute, Inc., Jersey City, New Jersey
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    • Drs. Palmer and Wang own stock or stock options in Forest Laboratories.


Abstract

Objective

To assess the efficacy and safety of milnacipran at a dosage of 100 mg/day (50 mg twice daily) for monotherapy treatment of fibromyalgia.

Methods

A double-blind, placebo-controlled trial was performed to assess 1,025 patients with fibromyalgia who were randomized to receive milnacipran 100 mg/day (n = 516) or placebo (n = 509). Patients underwent 4–6 weeks of flexible dose escalation followed by 12 weeks of stable-dose treatment. Two composite responder definitions were used as primary end points to classify the response to treatment. The 2-measure composite response required achievement of ≥30% improvement from baseline in the pain score and a rating of “very much improved” or “much improved” on the Patient's Global Impression of Change (PGIC) scale. The 3-measure composite response required satisfaction of these same 2 improvement criteria for pain and global status as well as improvement in physical function on the Short Form 36 (SF-36) physical component summary (PCS) score.

Results

After 12 weeks of stable-dose treatment, a significantly greater proportion of milnacipran-treated patients compared with placebo-treated patients showed clinically meaningful improvements, as evidenced by the proportion of patients meeting the 2-measure composite responder criteria (P < 0.001 in the baseline observation carried forward [BOCF] analysis) and 3-measure composite responder criteria (P < 0.001 in the BOCF). Milnacipran-treated patients also demonstrated significantly greater improvements from baseline on multiple secondary outcomes, including 24-hour and weekly recall pain score, PGIC score, SF-36 PCS and mental component summary scores, average pain severity score on the Brief Pain Inventory, Fibromyalgia Impact Questionnaire total score (all P < 0.001 versus placebo), and Multidimensional Fatigue Inventory total score (P = 0.036 versus placebo). Milnacipran was well tolerated by most patients, with nausea being the most commonly reported adverse event (placebo-adjusted rate of 15.8%).

Conclusion

Milnacipran administered at a dosage of 100 mg/day improved pain, global status, fatigue, and physical and mental function in patients with fibromyalgia.

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