Skip to main content

Advertisement

SpringerLink
Log in

Fibromyalgia: Should the treatment paradigm be monotherapy or combination pharmacotherapy?

  • Published:
Current Pain and Headache Reports Aims and scope Submit manuscript

Abstract

Fibromyalgia (FM) is a disorder characterized by chronic widespread pain, tenderness, and associated symptoms such as fatigue, sleep disturbance, mood disorder, and cognitive dysfunction. Research on the pathophysiology of FM has focused on dysregulation of sensory processing in the central nervous system, as well as genetic and sociobiologic background factors. Abnormalities include excessive pronociceptive input and deficiency of modulatory signaling via noradrenergic and serotonergic pathways. Effective pharmacotherapy of FM includes medications that inhibit pronociceptive input and augment modulatory signaling. Several other dysregulated pathways may be involved and be potential targets for therapeutic intervention. This article reviews positive results of recent monotherapy trials of several norepinephrine and serotonin reuptake inhibitors. Although there has been little assessment of combination therapy in FM, this review outlines the basis for rational treatment using this approach (in order to most effectively treat multiple symptom domains). Controlled monotherapy trials of medications currently being approved for FM demonstrate significant effect on pain, patient global impression of change, and function. Trials are currently being developed to assess the potential additive or synergistic effects of combined central pharmacotherapy and to assess the safety and tolerability of this approach.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Wolfe F, Smythe HA, Yunus MB, et al.: The American College of Rheumatology 1990 criteria for the classification of fibromyalgia: report of the multicenter criteria committee. Arthritis Rheum 1990, 33:160–172.

    Article  PubMed  CAS  Google Scholar 

  2. Mease P: Fibromyalgia syndrome: review of clinical presentation, pathogenesis, outcome measures, and treatment. J Rheumatol 2005, 32:6–21.

    Google Scholar 

  3. Goldenberg D, Burckhardt C, Crofford L: Management of fibromyalgia syndrome. JAMA 2004, 292:2388–2395.

    Article  PubMed  CAS  Google Scholar 

  4. Smyth HA, Moldofsky H: Two contributions to understanding the “fibrositis” syndrome. Bull Rheum Dis 1978, 26:928–931.

    Google Scholar 

  5. Moldofsky H, Scarisbrick P, England R, et al.: Musculoskeletal symptoms and non-REM sleep disturbance in patients with “fibrositis syndrome” and healthy subjects. Psychosom Med 1975, 37:341–345.

    PubMed  CAS  Google Scholar 

  6. Moldofsky H, Scarisbrick P: Induction of neurasthenic musculoskeletal pain syndrome by selective sleep stage deprivation. Psychosom Med 1975, 38:35–44.

    Google Scholar 

  7. Mountz JM, Bradley LA, Modell JG, et al.: Fibromyalgia in women: abnormalities of regional cerebral blood flow in the thalamus and the caudate nucleus are associated with low pain threshold levels. Arthritis Rheum 1995, 38:926–938.

    Article  PubMed  CAS  Google Scholar 

  8. Arroyo JF, Cohen ML: Abnormal responses to electrocutaneous stimulation in fibromyalgia. J Rheumatol 1993, 20:1925–1931.

    PubMed  CAS  Google Scholar 

  9. Gracely RH, Petzke F, Wolf JM, et al.: Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. Arthritis Rheum 2002, 46:1333–1343.

    Article  PubMed  Google Scholar 

  10. Staud R: The neurobiology of chronic musculoskeletal pain (including chronic regional pain). In Fibromyalgia & Other Central Pain Syndromes. Edited by Wallace DJ, Clauw DJ. Philadelphia: Lippincott Williams & Wilkins; 2005.

    Google Scholar 

  11. Russell IJ, Orr MD, Littman B, et al.: Elevated cerebrospinal fluid levels of substance P in patients with the fibromyalgia syndrome. Arthritis Rheum 1994, 37:1593–1601.

    Article  PubMed  CAS  Google Scholar 

  12. Hsu MC, Kim S, Sundgren PC, et al.: Significant association between changes in glutamate levels and fMRI BOLD signal in the posterior insula of fibromyalgia patients. Arthritis Rheum 2007, 56:S92.

    Google Scholar 

  13. Kosek E, Hansson P: Modulatory influence on somatosensory perception from vibration and heterotopic noxious conditioning stimulation (HNCS) in fibromyalgia patients and healthy subjects. Pain 1997, 70:41–51.

    Article  PubMed  CAS  Google Scholar 

  14. Dadabhoy D, Clauw DJ: Therapy insight: fibromyalgia: a different type of pain needing a different type of treatment. Nat Clin Pract 2006, 2:364–372.

    Google Scholar 

  15. Pillemer SR, Bradley LA, Crofford LJ, et al.: The neuroscience and endocrinology of fibromyalgia. Arthritis Rheum 1997, 40:1928–1939.

    Article  PubMed  CAS  Google Scholar 

  16. Wood PB, Schweinhardt P, Jaeger E, et al.: Fibromyalgia patients show an abnormal dopamine response to pain. Eur J Neurosci 2007, 25:3576–3582.

    Article  PubMed  Google Scholar 

  17. Geenen R, Jacobs JW, Bijlsma JW: Evaluation and management of endocrine dysfunction in fibromyalgia. Rheum Dis Clin North Am 2002, 28:389–404.

    Article  PubMed  Google Scholar 

  18. Mease PJ, Clauw DJ, Arnold LM, et al.: Fibromyalgia syndrome. J Rheumatol 2005, 32:2270–2277.

    PubMed  Google Scholar 

  19. Mease P, Arnold LM, Bennett R, et al.: Fibromyalgia syndrome. J Rheumatol 2007, 34:1415–1452.

    PubMed  Google Scholar 

  20. Mease PJ, Arnold LM, Crofford LJ, et al.: Identifying the clinical domains of fibromyalgia: contributions from clinical and patients delphi exercises. Arthritis Care Res 2008, 59:952–960.

    Article  Google Scholar 

  21. Bennett RM, Jones J, Turk DC, et al.: An internet survey of 2,596 people with fibromyalgia. BMC Musculoskelet Disord 2007, 9:27–38.

    Article  Google Scholar 

  22. Arnold LM: New therapies in fibromyalgia. Arthritis Res Ther 2006, 8:212–232.

    Article  PubMed  Google Scholar 

  23. Carette S, Bell MJ, Reynolds WJ, et al.: Comparison of amitriptyline, cyclobenzaprine, and placebo in the treatment of fibromyalgia. A randomised, double blind clinical trial. Arthritis Rheum 1994, 37:32–40.

    Article  PubMed  CAS  Google Scholar 

  24. Arnold LM, Keck PE Jr, Welge JA: Antidepressant treatment of fibromyalgia. A meta-analysis and review. Psychosomatics 2000, 41:104–113.

    Article  PubMed  CAS  Google Scholar 

  25. Rossy LA, Buckelew SP, Dorr N, et al.: A meta-analysis of fibromyalgia treatment interventions. Ann Behav Med 1999, 21:180–191.

    Article  PubMed  CAS  Google Scholar 

  26. Wolfe F, Cathey MA, Hawley DJ: A double-blind placebo controlled trial of fluoxetine in fibromyalgia. Scand J Rheumatol 1994, 23:255–259.

    Article  PubMed  CAS  Google Scholar 

  27. Arnold LM, Hess EV, Hudson JI, et al.: A randomized, placebo-controlled, double-blind, flexible-dose study of fluoxetine in the treatment of women with fibromyalgia. Am J Med 2002, 112:191–197.

    Article  PubMed  CAS  Google Scholar 

  28. Arnold LM, Rosen A, Pritchett YL, et al.: Duloxetine in the treatment of fibromyalgia in women: results from two clinical trials. Pain 2005, 119:5–15.

    Article  PubMed  CAS  Google Scholar 

  29. Russell IJ, Mease P, Smith T, et al.: The safety and efficacy of duloxetine for the treatment of fibromyalgia in patients with or without major depressive disorder: results from a 6-month randomized, double-blind, placebo-controlled, fixed-dose trial. J Musculoskelet Pain 2007, 15:8.

    Google Scholar 

  30. Chappell AS, Littlejohn G, Kajdasz D, et al.: A 1-year safety and efficacy study of duloxetine in patients with fibromyalgia. Ann Rheum Dis 2008, 67:253.

    Google Scholar 

  31. Gendreau RM, Thorn MD, Gendreau JF, et al.: Efficacy of milnacipran in patients with fibromyalgia. J Rheumatol 2005, 32:1975–1985.

    PubMed  CAS  Google Scholar 

  32. Clauw DJ, Mease PJ, Palmer RH, et al.: Milnacipran for the treatment of fibromyalgia syndrome: a 15-week, randomized, double-blind, placebo-controlled trial. Ann Rheum Dis 2008, 67:252.

    Google Scholar 

  33. Mease P, Clauw DJ, Palmer RH, et al.: Milnacipran efficacy and safety in the treatment of fibromyalgia syndrome. Ann Rheum Dis 2008, 67:256.

    Article  Google Scholar 

  34. Crofford L, Rowbotham M, Mease P, et al.: Pregabalin for the treatment of fibromyalgia syndrome: results of a randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2005, 52:1264–1273.

    Article  PubMed  CAS  Google Scholar 

  35. Mease PJ, Russell IJ, Arnold LM, et al.: A randomized, double-blind, placebo-controlled, phase III trial of pregabalin in the treatment of patients with fibromyalgia. J Rheumatol 2008, 35:502–514.

    PubMed  CAS  Google Scholar 

  36. Arnold LM, Leon T, Whalen E, et al.: Treatment with pregabalin is associated with improvement in pain regardless of the presence of baseline symptoms of anxiety or depression: findings from 3 randomized clinical trials. Ann Rheum Dis 2008, 67:249.

    Google Scholar 

  37. Arnold LM, Russell IJ, Diri EW, et al.: A 14-week, randomized, double-blind, placebo-controlled, durability of effect study of pregabalin for pain associated with fibromyalgia. J Pain 2008 (Epub ahead of print).

  38. Crofford LJ, Mease PJ, Simpson SL, et al.: Fibromyalgia relapse evaluation and efficacy for durability of meaningful relief (FREEDOM): a 6-month, double-blind, placebo-controlled trial with pregabalin. Pain 2008, 136:419–431.

    Article  PubMed  CAS  Google Scholar 

  39. Farrar JT, Young JP Jr, LaMoreaux L, et al.: Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain 2001, 94:149–158.

    Article  PubMed  CAS  Google Scholar 

  40. Gendreau RM, Williams DA, Palmer RH, et al.: Composite responder endpoints for fibromyalgia trails: experience with milnacipran. Arthritis Rheum 2007, 56:S603.

    Google Scholar 

  41. Russell AS: Effect of gamma-hydroxybutyrate on pain, fatigue, and alpha sleep anomaly in patients with fibromyalgia. J Rheumatol 1999, 26:2712.

    PubMed  CAS  Google Scholar 

  42. Russell IJ, Bennett RM, Michalek JE: Sodium oxybate relieves pain and improves sleep in fibromyalgia syndrome [FMS]: a randomized, double-blind, placebo-controlled, multi-center clinical trial. Presented at the ACR/ARHP Scientific Meeting. San Diego, USA; November 12–17, 2005.

  43. Moldofsky H, Alvarez-Horine S: Effects of sodium oxybate on sleep physiology and sleep-related symptoms in fibromyalgia. Ann Rheum Dis 2008, 67:256.

    Article  Google Scholar 

  44. Wolfe F, Anderson J, Harkness D, et al.: A prospective, longitudinal, multicenter study of service utilization and costs in fibromyalgia. Arthritis Rheum 1997, 40:1560–1570.

    Article  PubMed  CAS  Google Scholar 

  45. Sorensen J, Bengtsson A, Backman E, et al.: Pain analysis in patients with fibromyalgia. Effects of intravenous morphine, lidocaine, and ketamine. Scand J Rheumatol 1995, 24:360–365.

    Article  PubMed  CAS  Google Scholar 

  46. Russell I, Kamin M, Bennett RM, et al.: Efficacy of tramadol in treatment of pain in fibromyalgia. J Clin Rheumatol 2000, 6:250–257.

    Article  Google Scholar 

  47. Bennett RM, Kamin M, Karim R, et al.: Tramadol and acetaminophen combination tablets in the treatment of fibromyalgia pain: a double-blind, randomized, placebo-controlled study. Am J Med 2003, 114:537–545.

    Article  PubMed  CAS  Google Scholar 

  48. Goldenberg DL, Felson DT, Dinerman H: A randomized, controlled trial of amitriptyline and naproxen in the treatment of patients with fibromyalgia. Arthritis Rheum 1986, 29:1371–1377.

    Article  PubMed  CAS  Google Scholar 

  49. Fregni F, Gimenes R, Valle AC, et al.: A randomized, sham-controlled, proof of principle study of transcranial direct current stimulation for the treatment of pain in fibromyalgia. Arthritis Rheum 2006, 54:3988–3998.

    Article  PubMed  Google Scholar 

  50. Sampson SM, Rome JD, Rummans TA: Slow-frequency rTMS reduced fibromyalgia pain. Pain Med 2006, 7:115–118.

    Article  PubMed  Google Scholar 

  51. Thomas AW, Graham K, Prato FS, et al.: A randomized, double-blind, placebo-controlled clinical trial using a low-frequency magnetic field in the treatment of musculoskeletal chronic pain. Pain Res Manage 2007, 12:249–258.

    Google Scholar 

  52. Boyer EW, Shannon M: The serotonin syndrome. N Engl J Med 2005, 352:112–120.

    Article  Google Scholar 

  53. Holman AJ, Myers RR: A randomized, double-blind, placebo-controlled trial of pramipexole, a dopamine agonist, in patients with fibromyalgia receiving concomitant medications. Arthritis Rheum 2005, 52:2495–2505.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Seattle Rheumatology Associates, Swedish Medical Center, 1101 Madison Street, Suite 1000, Seattle, WA, 98104, USA

    Philip J. Mease

Authors
  1. Philip J. Mease
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kristin Seymour
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Philip J. Mease.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mease, P.J., Seymour, K. Fibromyalgia: Should the treatment paradigm be monotherapy or combination pharmacotherapy?. Current Science Inc 12, 399–405 (2008). https://doi.org/10.1007/s11916-008-0068-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11916-008-0068-4

Keywords

Search

Navigation