A double-blind, multicenter trial comparing duloxetine with placebo in the treatment of fibromyalgia patients with or without major depressive disorder

Authors

  • Lesley M. Arnold,

    Corresponding author
    1. University of Cincinnati College of Medicine, Cincinnati, Ohio
    • University of Cincinnati Medical Arts Building, Suite 8200, 222 Piedmont Avenue, Cincinnati, OH 45219
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    • Drs. Crofford and Arnold have received consulting fees or honoraria in the last 2 years from Eli Lilly and Company (Dr. Crawford <$10,000, Dr. Arnold >$10,000).

  • Yili Lu,

    1. Eli Lilly and Company, Indianapolis, Indiana
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  • Leslie J. Crofford,

    1. University of Michigan, Ann Arbor
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    • Drs. Crofford and Arnold have received consulting fees or honoraria in the last 2 years from Eli Lilly and Company (Dr. Crawford <$10,000, Dr. Arnold >$10,000).

  • Madelaine Wohlreich,

    1. Eli Lilly and Company, Indianapolis, Indiana
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  • Michael J. Detke,

    1. Indiana University Medical School and Eli Lilly and Company, Indianapolis, Indiana, McLean Hospital, Belmont, Massachusetts, and Harvard Medical School, Boston, Massachusetts
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  • Smriti Iyengar,

    1. Eli Lilly and Company, Indianapolis, Indiana
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  • David J. Goldstein

    1. Indiana University Medical School and PRN Consulting, Indianapolis, Indiana
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    • In addition to the authors employed by Eli Lilly and Company listed above, Dr. Goldstein's wife is employed by Eli Lilly and Company.


Abstract

Objective

To assess the efficacy and safety of duloxetine, a serotonin and norepinephrine reuptake inhibitor, in subjects with primary fibromyalgia, with or without current major depressive disorder.

Methods

This study was a randomized, double-blind, placebo-controlled trial conducted in 18 outpatient research centers in the US. A total of 207 subjects meeting the American College of Rheumatology criteria for primary fibromyalgia were enrolled (89% female, 87% white, mean age 49 years, 38% with current major depressive disorder). After single-blind placebo treatment for 1 week, subjects were randomly assigned to receive duloxetine 60 mg twice a day (n = 104) or placebo (n = 103) for 12 weeks. Co–primary outcome measures were the Fibromyalgia Impact Questionnaire (FIQ) total score (score range 0–80, with 0 indicating no impact) and FIQ pain score (score range 0–10). Secondary outcome measures included mean tender point pain threshold, number of tender points, FIQ fatigue, tiredness on awakening, and stiffness scores, Clinical Global Impression of Severity (CGI-Severity) scale, Patient Global Impression of Improvement (PGI-Improvement) scale, Brief Pain Inventory (short form), Medical Outcomes Study Short Form 36, Quality of Life in Depression Scale, and Sheehan Disability Scale.

Results

Compared with placebo-treated subjects, duloxetine-treated subjects improved significantly more (P = 0.027) on the FIQ total score, with a treatment difference of −5.53 (95% confidence interval −10.43, −0.63), but not significantly more on the FIQ pain score (P = 0.130). Compared with placebo-treated subjects, duloxetine-treated subjects had significantly greater reductions in Brief Pain Inventory average pain severity score (P = 0.008), Brief Pain Inventory average interference from pain score (P = 0.004), number of tender points (P = 0.002), and FIQ stiffness score (P = 0.048), and had significantly greater improvement in mean tender point pain threshold (P = 0.002), CGI-Severity (P = 0.048), PGI-Improvement (P = 0.033), and several quality-of-life measures. Duloxetine treatment improved fibromyalgia symptoms and pain severity regardless of baseline status of major depressive disorder. Compared with placebo-treated female subjects (n = 92), duloxetine-treated female subjects (n = 92) demonstrated significantly greater improvement on most efficacy measures, while duloxetine-treated male subjects (n = 12) failed to improve significantly on any efficacy measure. The treatment effect on significant pain reduction in female subjects was independent of the effect on mood or anxiety. Duloxetine was safely administered and well tolerated.

Conclusion

In this randomized, controlled, 12-week trial (with a 1-week placebo lead-in phase), duloxetine was an effective and safe treatment for many of the symptoms associated with fibromyalgia in subjects with or without major depressive disorder, particularly for women, who had significant improvement across most outcome measures.

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