Fibromyalgia

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Fibromyalgia is a disease of the muscles. It is defined as "a common nonarticular rheumatic syndrome characterized by myalgia and multiple points of focal muscle tenderness to palpation (trigger points). Muscle pain is typically aggravated by inactivity or exposure to cold. This condition is often associated with general symptoms, such as sleep disturbances, fatigue, stiffness, headaches, and occasionally depression. There is significant overlap between fibromyalgia and the chronic fatigue syndrome (fatigue syndrome, chronic). Fibromyalgia may arise as a primary or secondary disease process. It is most frequent in females aged 20 to 50 years." (From Adams et al., Principles of Neurology, 6th ed, p1494-95)".[1]

Etiology/causation

The cause is not clear; however, "patients with fibromyalgia experience pain differently from the general population".[2]

Genetics

Using self-report of "Chronic Widespread Pain" (CWP) as a surrogate marker for fibromyalgia, the Swedish Twin Registry suggests a modest genetic contribution:[3][4]

  • Monozygotic twins with CWP have a 15% chance that their twin sibling has CWP
  • Dizygotic twins with CWP have a 7% chance that their twin sibling has CWP

Abnormal sleep

Fibromyalgia is associated with alpha sleep.[5] However, it is unclear if this abnormal sleep pattern causes or follows fibromyalgia.

Vitamin D deficiency

Although initial studies suggest that low vitamin D levels may be associated with nonspecific musculoskeletal pain[6]; more recent studies make this doubtful.[7][7]

Symptoms

Symptoms from associated illnesses

Fluid retention might be associated with fibromyalgia.[8][9] This is difficult to interpret as normal patients may have a 9 pound diurnal variation in weight.[10]

Diagnosis

Differential diagnosis

A cohort study found that widespread pain significantly increased risk of subsequent diagnosis of cancer, especially breast cancer and prostate cancer.[11] The biological reason for this association is not clear.

Treatment

Clinical practice guidelines by the European League Against Rheumatism (EULAR) recommendations (parentheses contain levels of evidence and strength of recommendation) are included below.[12]
General

  1. "Full understanding of fibromyalgia requires comprehensive assessment of pain, function and psychosocial context. Fibromyalgia should be recognised as a complex and heterogeneous condition where there is abnormal pain processing and other secondary features" (IV D)
  2. "Optimal treatment requires a multidisciplinary approach with a combination of non-pharmacological and pharmacological treatment modalities tailored according to pain intensity, function, associated features such as depression, fatigue and sleep disturbance in discussion with the patient" (IV D)

Non-pharmacological management

According to the clinical practice guidelines:[12]

  1. "Heated pool treatment with or without exercise is effective in fibromyalgia" (IIa B)
  2. "Individually tailored exercise programmes, including aerobic exercise and strength training can be beneficial to some patients" with fibromyalgia" (IIb C). Subsequent to the 2008 EULAR clinical practice guidelines, a meta-analysis of randomized controlled trials found "aerobic-only training has beneficial effects on physical function and some FM symptoms. Strength-only training may improve FM symptoms, but requires further study."[13]
  3. "Cognitive behavioural therapy may be of benefit to some patients with fibromyalgia" IV D)
  4. "Other therapies such as relaxation, rehabilitation, physiotherapy and psychological support may be used depending on the needs of the individual patient (IIb C)

Pharmacological management

Medications for fibromyalgia
Study Patients Intervention Results
Amitriptyline
Üçeyler, 2008[14]
Meta-analysis		 8 trials Various doses of 10-100 mg per day Did not pool comparative outcomes
Arnold, 2000[15]
Meta-analysis		 8 trials Various doses of 5-50 mg per day Did not pool comparative outcomes
O'Malley, 2000[16]
Meta-analysis		 8 trials Various doses of 5-50 mg per day Did not isolate the effect of amitriptyline
Carette, 1994[17]
Randomized controlled trial		 97 patients 10 to 50 mg per day response at 6 months was 36% versus 19%
Hannonen, 1998[18]
Randomized controlled trial		 97 patients 25 mg or 37.5 mg per day At least minimal improvement: response at 3 months was 74% versus 49%
Duloxetine
Arnold, 2004[19]
Randomized controlled trial		 207 patients 60 mg twice a day No dichotomous results reported
Russell, 2008[20]
Randomized controlled trial		 194 patients duloxetine 60 mg 30% reduction in their pain: response at 3 months, drug = 51% and placebo = 36%
Pregabalin
Mease, 2008[21]
Randomized controlled trial		 373 patients pregabalin 450 mg 30% reduction in their pain: response at 3 months, drug = 43% and placebo = 35%
Crofford, 2005[22]
Randomized controlled trial		 263 patients pregabalin 450 mg 30% reduction in their pain: response at 2 months, drug = 48% and placebo = 27%

According to the clinical practice guidelines:[12]

  1. "Tramadol is recommended for the management of pain in fibromyalgia" (Ib A)
  2. "Simple analgesics such as paracetamol and other weak opioids can also be considered in the treatment of fibromyalgia. Corticosteroids and strong opioids are not recommended (IV D)
  3. "Antidepressants: amitriptyline, fluoxetine, duloxetine, milnacipran, moclobemide and pirlindole, reduce pain and often improve function, therefore they are recommended for the treatment of fibromyalgia" (Ib A)
  4. Tropisetron, pramipexole and pregabalin reduce pain and are recommended for the treatment of fibromyalgia" (Ib A)

Pregabalin (Lyrica) is approved for use in the United States by the Food and Drug Administration (FDA) for fibromyalgia. As compared to placebo, pregabalin benefits about 1 of every 6 people who use it if they are similar to the patients in a randomized controlled trial. In this trial, 33% of the patients who took the drug had a reduction in their pain versus 13% of the patients who took placebo.[22][21] Both trials were sponsored by Pfizer, the makers of Lyrica, which increases the likelihood of publication bias towards positive results.

Duloxetine (Cymbalta) although not currently (7/2008) approved for use in the United States by the Food and Drug Administration (FDA) for fibromyalgia. As compared to placebo, duloxetine 60 mg per day benefits about 1 of every 7 people who use it if they are similar to the patients in an randomized controlled trial. In this trial, 51% of the patients who took the drug had a 30% reduction in their pain versus 36% of the patients who took placebo (data not reported for 50% reduction).[20] This trial was sponsored by the makers of Cymbalta which increases the likelihood of publication bias towards positive results.

References

  1. ↑ National Library of Medicine. Fibromyalgia. Retrieved on 2007-11-13.
  2. ↑ Abeles AM, Pillinger MH, Solitar BM, Abeles M (2007). "Narrative review: the pathophysiology of fibromyalgia". Ann. Intern. Med. 146 (10): 726–34. PMID 17502633. [e]
  3. ↑ Kato K, Sullivan P, Evengård B, Pedersen N (2006). "Importance of genetic influences on chronic widespread pain". Arthritis Rheum. 54 (5): 1682-6. DOI:10.1002/art.21798. PMID 16646040. Research Blogging.
  4. ↑ Kato K, Sullivan P, Evengård B, Pedersen N (2006). "Chronic widespread pain and its comorbidities: a population-based study". Arch. Intern. Med. 166 (15): 1649-54. PMID 16908799.
  5. ↑ Roizenblatt S, Moldofsky H, Benedito-Silva AA, Tufik S (2001). "Alpha sleep characteristics in fibromyalgia". Arthritis Rheum. 44 (1): 222–30. DOI:<222::AID-ANR29>3.0.CO;2-K 10.1002/1529-0131(200101)44:1<222::AID-ANR29>3.0.CO;2-K. PMID 11212164. <222::AID-ANR29>3.0.CO;2-K Research Blogging.
  6. ↑ Plotnikoff GA, Quigley JM (2003). "Prevalence of severe hypovitaminosis D in patients with persistent, nonspecific musculoskeletal pain". Mayo Clin. Proc. 78 (12): 1463–70. PMID 14661675. [e]
  7. ↑ 7.0 7.1 Warner AE, Arnspiger SA (February 2008). "Diffuse musculoskeletal pain is not associated with low vitamin D levels or improved by treatment with vitamin D". J Clin Rheumatol 14 (1): 12–6. DOI:10.1097/RHU.0b013e31816356a9. PMID 18431091. Research Blogging.
  8. ↑ Deodhar AA, Fisher RA, Blacker CV, Woolf AD (June 1994). "Fluid retention syndrome and fibromyalgia". Br. J. Rheumatol. 33 (6): 576–82. PMID 8205408. [e]
  9. ↑ Dunnigan MG, Henderson JB, Hole D, Pelosi AJ (November 2004). "Unexplained swelling symptoms in women (idiopathic oedema) comprise one component of a common polysymptomatic syndrome". QJM 97 (11): 755–64. DOI:10.1093/qjmed/hch126. PMID 15496531. Research Blogging.
  10. ↑ Denning DW, Dunnigan MG, Tillman J, Davis JA, Forrest CA (May 1990). "The relationship between 'normal' fluid retention in women and idiopathic oedema". Postgrad Med J 66 (775): 363–6. PMID 2371185. [e]
  11. ↑ McBeth J, Silman AJ, Macfarlane GJ (2003). "Association of widespread body pain with an increased risk of cancer and reduced cancer survival: a prospective, population-based study". Arthritis Rheum. 48 (6): 1686–92. DOI:10.1002/art.10973. PMID 12794837. Research Blogging.
  12. ↑ 12.0 12.1 12.2 Carville SF, Arendt-Nielsen S, Bliddal H, et al (2008). "EULAR evidence-based recommendations for the management of fibromyalgia syndrome". Ann. Rheum. Dis. 67 (4): 536-41. DOI:10.1136/ard.2007.071522. PMID 17644548. Research Blogging.
  13. ↑ Busch AJ, Schachter CL, Overend TJ, Peloso PM, Barber KA (June 2008). "Exercise for fibromyalgia: a systematic review". J. Rheumatol. 35 (6): 1130–44. PMID 18464301. [e]
  14. ↑ Uçeyler N, Häuser W, Sommer C (September 2008). "A systematic review on the effectiveness of treatment with antidepressants in fibromyalgia syndrome". Arthritis and rheumatism 59 (9): 1279–98. DOI:10.1002/art.24000. PMID 18759260. Research Blogging.
  15. ↑ Arnold LM, Keck PE, Welge JA (2000). "Antidepressant treatment of fibromyalgia. A meta-analysis and review". Psychosomatics 41 (2): 104–13. PMID 10749947. [e]
  16. ↑ O'Malley PG, Balden E, Tomkins G, Santoro J, Kroenke K, Jackson JL (September 2000). "Treatment of fibromyalgia with antidepressants: a meta-analysis". Journal of general internal medicine : official journal of the Society for Research and Education in Primary Care Internal Medicine 15 (9): 659–66. PMID 11029681. PMC 1495596. [e]
  17. ↑ Carette S, Bell MJ, Reynolds WJ, et al (January 1994). "Comparison of amitriptyline, cyclobenzaprine, and placebo in the treatment of fibromyalgia. A randomized, double-blind clinical trial". Arthritis and rheumatism 37 (1): 32–40. PMID 8129762. [e]
  18. ↑ Hannonen P, Malminiemi K, Yli-Kerttula U, Isomeri R, Roponen P (December 1998). "A randomized, double-blind, placebo-controlled study of moclobemide and amitriptyline in the treatment of fibromyalgia in females without psychiatric disorder". British journal of rheumatology 37 (12): 1279–86. PMID 9973149. [e]
  19. ↑ Arnold LM, Lu Y, Crofford LJ, et al (September 2004). "A double-blind, multicenter trial comparing duloxetine with placebo in the treatment of fibromyalgia patients with or without major depressive disorder". Arthritis and rheumatism 50 (9): 2974–84. DOI:10.1002/art.20485. PMID 15457467. Research Blogging.
  20. ↑ 20.0 20.1 Russell IJ, Mease PJ, Smith TR, et al (June 2008). "Efficacy and safety of duloxetine for treatment of fibromyalgia in patients with or without major depressive disorder: Results from a 6-month, randomized, double-blind, placebo-controlled, fixed-dose trial". Pain 136 (3): 432–44. DOI:10.1016/j.pain.2008.02.024. PMID 18395345. Research Blogging. Clinical trial registration number NCT00190866 Cite error: Invalid <ref> tag; name "pmid18395345" defined multiple times with different content
  21. ↑ 21.0 21.1 Mease PJ, Russell IJ, Arnold LM, et al (March 2008). "A randomized, double-blind, placebo-controlled, phase III trial of pregabalin in the treatment of patients with fibromyalgia". The Journal of Rheumatology 35 (3): 502–14. PMID 18278830. [e] Trial registration number not provided by authors, but is likely to be NCT00333866 Cite error: Invalid <ref> tag; name "pmid18278830" defined multiple times with different content
  22. ↑ 22.0 22.1 Crofford LJ, Rowbotham MC, Mease PJ, et al (2005). "Pregabalin for the treatment of fibromyalgia syndrome: results of a randomized, double-blind, placebo-controlled trial". Arthritis Rheum. 52 (4): 1264–73. DOI:10.1002/art.20983. PMID 15818684. Research Blogging.
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