Efficacy of Milnacipran in Patients with Fibromyalgia

R. MICHAEL GENDREAU, MICHAEL D. THORN, JUDY F. GENDREAU, JAY D. KRANZLER, SAULO RIBEIRO, RICHARD H. GRACELY, DAVID A. WILLIAMS, PHILIP J. MEASE, SAMUEL A. McLEAN, and DANIEL J. CLAUW

ABSTRACT.

Objective. Fibromyalgia (FM) is a common musculoskeletal condition characterized by widespread pain, tenderness, and a variety of other somatic symptoms. Current treatments are modestly effective. Arguably, the best studied and most effective compounds are tricyclic antidepressants (TCA). Milnacipran, a nontricyclic compound that inhibits the reuptake of both serotonin and norepinephrine, may provide many of the beneficial effects of TCA with a superior side effect profile.

Methods. One hundred twenty-five patients with FM were randomly assigned in a 3:3:2 ratio to receive milnacipran twice daily, milnacipran once daily, or placebo for 3 months in a double-blind dose-escalation trial; 92% of twice-daily and 81% of once-daily participants achieved dose escalation to the target milnacipran dose of 200 mg.

Results. The primary endpoint was reduction of pain. Both the once- and twice-daily groups showed statistically significant improvements in pain, as well as improvements in global well being, fatigue, and other domains. Response rates for patients receiving milnacipran were equal in patients with and without comorbid depression, but placebo response rates were considerably higher in depressed patients, leading to significantly greater overall efficacy in the nondepressed group.

Conclusion. In this Phase II study, milnacipran led to statistically significant improvements in pain and other symptoms of FM. The effect sizes were equal to those previously found with TCA, and the drug was generally well tolerated. (J Rheumatol 2005;32:1975-85)

Key Indexing Terms:

FIBROMYALGIA
PAIN
MILNACIPRAN
ANTIDEPRESSANT
ANALGESIC

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From Cypress Biosciences, San Diego, California; and the Chronic Pain and Fatigue Research Center, Division of Rheumatology, Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA.

Supported by Cypress Biosciences, San Diego, California. Drs. M. Gendreau, J. Gendreau, and J. Kranzler are employees of Cypress Biosciences. Drs. Clauw, Gracely, and Williams are paid consultants for and shareholders in Cypress Biosciences. Drs. Mease and Thorn are consultants for Cypress Biosciences.

R.M. Gendreau, MD, PhD; J.F. Gendreau, MD; J.D. Kranzler, MD, PhD, Cypress Biosciences; M.D. Thorn, DrPH, Statistical Resources, Inc., Chapel Hill, NC; S. Ribeiro, MD, Department of Psychiatry, University of Michigan; R.H. Gracely, PhD, Chronic Pain and Fatigue Research Center, University of Michigan; D.A. Williams, PhD, Chronic Pain and Fatigue Research Center, Division of Rheumatology, Department of Medicine, University of Michigan; P.J. Mease, MD, Seattle Rheumatology Associates, Seattle, WA; S.A. McLean, MD, Chronic Pain and Fatigue Research Center, Department of Emergency Medicine, University of Michigan; D.J. Clauw, MD, Chronic Pain and Fatigue Research Center, Division of Rheumatology, Department of Medicine, University of Michigan.

Address reprint requests to Dr. R.M. Gendreau, Cypress Biosciences, 4350 Executive Drive, Suite 325, San Diego, CA 92121. E-mail: mgendreau1@cypressbio.com

Accepted for publication May 30, 2005.

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