Pregabalin for the treatment of fibromyalgia syndrome: Results of a randomized, double-blind, placebo-controlled trial

Authors

  • Leslie J. Crofford,

    Corresponding author
    1. University of Michigan, Ann Arbor
    Current affiliation:
    1. Kentucky Clinic, Lexington, Kentucky
    • Room J-503, Kentucky Clinic, 740 South Limestone Street, Lexington, KY 40539
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    • Dr. Crofford has received consulting fees of less than $10,000 from Cypress Bioscience, Eli Lilly & Co., Orphan Pharmaceuticals, Pfizer, and Wyeth. Dr. Rowbotham has received consulting fees of less than $10,000 from Eli Lilly & Co. and Xenoport, owns stock in Xenoport and Neuromolecular, and was a coinvestigator on a study of gabapentin funded by Pfizer. Dr. Mease has received consulting fees of less than $10,000 from Pfizer, Cypress Bioscience, Eli Lilly & Co., and Pierre Fabre and owns stock in Cypress Bioscience. Dr. Dworkin has served on the advisory board or as a consultant for fees of less than $10,000 for Abbott Laboratories, Alpharma, AstraZeneca Pharmaceuticals, Bristol-Myers Squibb, Elan Pharmaceuticals, Eli Lilly & Co., GlaxoSmithKline, Johnson & Johnson, Merck KGaA, NeurogesX, Inc., Ortho-McNeil Pharmaceutical, and UCB Pharma; has received consulting fees of more than $10,000 from Pfizer, Allergan, Novartis, Epicept, and Endo; and owns stock in NeurogesX, Inc. Ms Corbin, Mr. Young, Ms LaMoreaux, Ms Martin, and Dr. Sharma own stock in Pfizer.

  • Michael C. Rowbotham,

    1. University of California, San Francisco
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    • Dr. Crofford has received consulting fees of less than $10,000 from Cypress Bioscience, Eli Lilly & Co., Orphan Pharmaceuticals, Pfizer, and Wyeth. Dr. Rowbotham has received consulting fees of less than $10,000 from Eli Lilly & Co. and Xenoport, owns stock in Xenoport and Neuromolecular, and was a coinvestigator on a study of gabapentin funded by Pfizer. Dr. Mease has received consulting fees of less than $10,000 from Pfizer, Cypress Bioscience, Eli Lilly & Co., and Pierre Fabre and owns stock in Cypress Bioscience. Dr. Dworkin has served on the advisory board or as a consultant for fees of less than $10,000 for Abbott Laboratories, Alpharma, AstraZeneca Pharmaceuticals, Bristol-Myers Squibb, Elan Pharmaceuticals, Eli Lilly & Co., GlaxoSmithKline, Johnson & Johnson, Merck KGaA, NeurogesX, Inc., Ortho-McNeil Pharmaceutical, and UCB Pharma; has received consulting fees of more than $10,000 from Pfizer, Allergan, Novartis, Epicept, and Endo; and owns stock in NeurogesX, Inc. Ms Corbin, Mr. Young, Ms LaMoreaux, Ms Martin, and Dr. Sharma own stock in Pfizer.

  • Philip J. Mease,

    1. Rheumatology Associates, and Swedish Medical Center, Seattle, Washington
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    • Dr. Crofford has received consulting fees of less than $10,000 from Cypress Bioscience, Eli Lilly & Co., Orphan Pharmaceuticals, Pfizer, and Wyeth. Dr. Rowbotham has received consulting fees of less than $10,000 from Eli Lilly & Co. and Xenoport, owns stock in Xenoport and Neuromolecular, and was a coinvestigator on a study of gabapentin funded by Pfizer. Dr. Mease has received consulting fees of less than $10,000 from Pfizer, Cypress Bioscience, Eli Lilly & Co., and Pierre Fabre and owns stock in Cypress Bioscience. Dr. Dworkin has served on the advisory board or as a consultant for fees of less than $10,000 for Abbott Laboratories, Alpharma, AstraZeneca Pharmaceuticals, Bristol-Myers Squibb, Elan Pharmaceuticals, Eli Lilly & Co., GlaxoSmithKline, Johnson & Johnson, Merck KGaA, NeurogesX, Inc., Ortho-McNeil Pharmaceutical, and UCB Pharma; has received consulting fees of more than $10,000 from Pfizer, Allergan, Novartis, Epicept, and Endo; and owns stock in NeurogesX, Inc. Ms Corbin, Mr. Young, Ms LaMoreaux, Ms Martin, and Dr. Sharma own stock in Pfizer.

  • I. Jon Russell,

    1. University of Texas Health Science Center, San Antonio
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  • Robert H. Dworkin,

    1. University of Rochester School of Medicine and Dentistry, Rochester, New York
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    • Dr. Crofford has received consulting fees of less than $10,000 from Cypress Bioscience, Eli Lilly & Co., Orphan Pharmaceuticals, Pfizer, and Wyeth. Dr. Rowbotham has received consulting fees of less than $10,000 from Eli Lilly & Co. and Xenoport, owns stock in Xenoport and Neuromolecular, and was a coinvestigator on a study of gabapentin funded by Pfizer. Dr. Mease has received consulting fees of less than $10,000 from Pfizer, Cypress Bioscience, Eli Lilly & Co., and Pierre Fabre and owns stock in Cypress Bioscience. Dr. Dworkin has served on the advisory board or as a consultant for fees of less than $10,000 for Abbott Laboratories, Alpharma, AstraZeneca Pharmaceuticals, Bristol-Myers Squibb, Elan Pharmaceuticals, Eli Lilly & Co., GlaxoSmithKline, Johnson & Johnson, Merck KGaA, NeurogesX, Inc., Ortho-McNeil Pharmaceutical, and UCB Pharma; has received consulting fees of more than $10,000 from Pfizer, Allergan, Novartis, Epicept, and Endo; and owns stock in NeurogesX, Inc. Ms Corbin, Mr. Young, Ms LaMoreaux, Ms Martin, and Dr. Sharma own stock in Pfizer.

  • Ann E. Corbin,

    1. Pfizer Global Research and Development, Ann Arbor, Michigan
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    • Dr. Crofford has received consulting fees of less than $10,000 from Cypress Bioscience, Eli Lilly & Co., Orphan Pharmaceuticals, Pfizer, and Wyeth. Dr. Rowbotham has received consulting fees of less than $10,000 from Eli Lilly & Co. and Xenoport, owns stock in Xenoport and Neuromolecular, and was a coinvestigator on a study of gabapentin funded by Pfizer. Dr. Mease has received consulting fees of less than $10,000 from Pfizer, Cypress Bioscience, Eli Lilly & Co., and Pierre Fabre and owns stock in Cypress Bioscience. Dr. Dworkin has served on the advisory board or as a consultant for fees of less than $10,000 for Abbott Laboratories, Alpharma, AstraZeneca Pharmaceuticals, Bristol-Myers Squibb, Elan Pharmaceuticals, Eli Lilly & Co., GlaxoSmithKline, Johnson & Johnson, Merck KGaA, NeurogesX, Inc., Ortho-McNeil Pharmaceutical, and UCB Pharma; has received consulting fees of more than $10,000 from Pfizer, Allergan, Novartis, Epicept, and Endo; and owns stock in NeurogesX, Inc. Ms Corbin, Mr. Young, Ms LaMoreaux, Ms Martin, and Dr. Sharma own stock in Pfizer.

  • James P. Young Jr.,

    1. Pfizer Global Research and Development, Ann Arbor, Michigan
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    • Dr. Crofford has received consulting fees of less than $10,000 from Cypress Bioscience, Eli Lilly & Co., Orphan Pharmaceuticals, Pfizer, and Wyeth. Dr. Rowbotham has received consulting fees of less than $10,000 from Eli Lilly & Co. and Xenoport, owns stock in Xenoport and Neuromolecular, and was a coinvestigator on a study of gabapentin funded by Pfizer. Dr. Mease has received consulting fees of less than $10,000 from Pfizer, Cypress Bioscience, Eli Lilly & Co., and Pierre Fabre and owns stock in Cypress Bioscience. Dr. Dworkin has served on the advisory board or as a consultant for fees of less than $10,000 for Abbott Laboratories, Alpharma, AstraZeneca Pharmaceuticals, Bristol-Myers Squibb, Elan Pharmaceuticals, Eli Lilly & Co., GlaxoSmithKline, Johnson & Johnson, Merck KGaA, NeurogesX, Inc., Ortho-McNeil Pharmaceutical, and UCB Pharma; has received consulting fees of more than $10,000 from Pfizer, Allergan, Novartis, Epicept, and Endo; and owns stock in NeurogesX, Inc. Ms Corbin, Mr. Young, Ms LaMoreaux, Ms Martin, and Dr. Sharma own stock in Pfizer.

  • Linda K. LaMoreaux,

    1. Pfizer Global Research and Development, Ann Arbor, Michigan
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    • Dr. Crofford has received consulting fees of less than $10,000 from Cypress Bioscience, Eli Lilly & Co., Orphan Pharmaceuticals, Pfizer, and Wyeth. Dr. Rowbotham has received consulting fees of less than $10,000 from Eli Lilly & Co. and Xenoport, owns stock in Xenoport and Neuromolecular, and was a coinvestigator on a study of gabapentin funded by Pfizer. Dr. Mease has received consulting fees of less than $10,000 from Pfizer, Cypress Bioscience, Eli Lilly & Co., and Pierre Fabre and owns stock in Cypress Bioscience. Dr. Dworkin has served on the advisory board or as a consultant for fees of less than $10,000 for Abbott Laboratories, Alpharma, AstraZeneca Pharmaceuticals, Bristol-Myers Squibb, Elan Pharmaceuticals, Eli Lilly & Co., GlaxoSmithKline, Johnson & Johnson, Merck KGaA, NeurogesX, Inc., Ortho-McNeil Pharmaceutical, and UCB Pharma; has received consulting fees of more than $10,000 from Pfizer, Allergan, Novartis, Epicept, and Endo; and owns stock in NeurogesX, Inc. Ms Corbin, Mr. Young, Ms LaMoreaux, Ms Martin, and Dr. Sharma own stock in Pfizer.

  • Susan A. Martin,

    1. Pfizer Global Research and Development, Ann Arbor, Michigan
    Search for more papers by this author
    • Dr. Crofford has received consulting fees of less than $10,000 from Cypress Bioscience, Eli Lilly & Co., Orphan Pharmaceuticals, Pfizer, and Wyeth. Dr. Rowbotham has received consulting fees of less than $10,000 from Eli Lilly & Co. and Xenoport, owns stock in Xenoport and Neuromolecular, and was a coinvestigator on a study of gabapentin funded by Pfizer. Dr. Mease has received consulting fees of less than $10,000 from Pfizer, Cypress Bioscience, Eli Lilly & Co., and Pierre Fabre and owns stock in Cypress Bioscience. Dr. Dworkin has served on the advisory board or as a consultant for fees of less than $10,000 for Abbott Laboratories, Alpharma, AstraZeneca Pharmaceuticals, Bristol-Myers Squibb, Elan Pharmaceuticals, Eli Lilly & Co., GlaxoSmithKline, Johnson & Johnson, Merck KGaA, NeurogesX, Inc., Ortho-McNeil Pharmaceutical, and UCB Pharma; has received consulting fees of more than $10,000 from Pfizer, Allergan, Novartis, Epicept, and Endo; and owns stock in NeurogesX, Inc. Ms Corbin, Mr. Young, Ms LaMoreaux, Ms Martin, and Dr. Sharma own stock in Pfizer.

  • Uma Sharma,

    1. Pfizer Global Research and Development, Ann Arbor, Michigan
    Search for more papers by this author
    • Dr. Crofford has received consulting fees of less than $10,000 from Cypress Bioscience, Eli Lilly & Co., Orphan Pharmaceuticals, Pfizer, and Wyeth. Dr. Rowbotham has received consulting fees of less than $10,000 from Eli Lilly & Co. and Xenoport, owns stock in Xenoport and Neuromolecular, and was a coinvestigator on a study of gabapentin funded by Pfizer. Dr. Mease has received consulting fees of less than $10,000 from Pfizer, Cypress Bioscience, Eli Lilly & Co., and Pierre Fabre and owns stock in Cypress Bioscience. Dr. Dworkin has served on the advisory board or as a consultant for fees of less than $10,000 for Abbott Laboratories, Alpharma, AstraZeneca Pharmaceuticals, Bristol-Myers Squibb, Elan Pharmaceuticals, Eli Lilly & Co., GlaxoSmithKline, Johnson & Johnson, Merck KGaA, NeurogesX, Inc., Ortho-McNeil Pharmaceutical, and UCB Pharma; has received consulting fees of more than $10,000 from Pfizer, Allergan, Novartis, Epicept, and Endo; and owns stock in NeurogesX, Inc. Ms Corbin, Mr. Young, Ms LaMoreaux, Ms Martin, and Dr. Sharma own stock in Pfizer.

  • Pregabalin 1008-105 Study Group


Abstract

Objective

Fibromyalgia syndrome (FMS) is characterized by widespread musculoskeletal pain and lowered pain threshold. Other prominent symptoms include disordered sleep and fatigue. FMS affects an estimated 2% of the population, predominantly women. This trial was designed to evaluate the efficacy and safety of pregabalin, a novel α2-δ ligand, for treatment of symptoms associated with FMS.

Methods

This multicenter, double-blind, 8-week, randomized clinical trial compared the effects of placebo with those of 150, 300, and 450 mg/day pregabalin on pain, sleep, fatigue, and health-related quality of life in 529 patients with FMS. The primary outcome variable was the comparison of end point mean pain scores, derived from daily diary ratings of pain intensity, between each of the pregabalin treatment groups and the placebo group.

Results

Pregabalin at 450 mg/day significantly reduced the average severity of pain in the primary analysis compared with placebo (−0.93 on a 0–10 scale) (P ≤ 0.001), and significantly more patients in this group had ≥50% improvement in pain at the end point (29%, versus 13% in the placebo group; P = 0.003). Pregabalin at 300 and 450 mg/day was associated with significant improvements in sleep quality, fatigue, and global measures of change. Pregabalin at 450 mg/day improved several domains of health-related quality of life. Dizziness and somnolence were the most frequent adverse events. Rates of discontinuation due to adverse events were similar across all 4 treatment groups.

Conclusion

Pregabalin at 450 mg/day was efficacious for the treatment of FMS, reducing symptoms of pain, disturbed sleep, and fatigue compared with placebo. Pregabalin was well tolerated and improved global measures and health-related quality of life.

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