Exercise and antidepressants improve fibromyalgia

,

Applied Evidence

Exercise and antidepressants improve fibromyalgia

J Fam Pract. 2004 April;53(4):280-291

PDF Download

References

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

2. Fitzcharles MA, Esdaile JM. The overdiagnosis of fibromyalgia syndrome. Am J Med 1997;103:44-50.

3. Dougados M, van der, Linden S, Juhlin R, et al. The European Spondylarthropathy Study Group preliminary criteria for the classification of spondylarthropathy. Arthritis Rheum 1991;34:1218-1227.

4. Suarez-Almazor ME, Gonzalez-Lopez L, Gamez-Nava JI, Belseck E, Kendall CJ, Davis P. Utilization and predictive value of laboratory tests in patients referred to rheumatologists by primary care physicians. J Rheumatol 1998;25:1980-1985.

5. Al-Allaf AW, Ottewell L, Pullar T. The prevalence and significance of positive antinuclear antibodies in patients with fibromyalgia syndrome: 2-4 years’ follow-up. Clin Rheumatol 2002;21:472-477.

6. Yunus MB, Hussey FX, Aldag JC. Antinuclear antibodies and connective tissue disease features in fibromyalgia syndrome: a controlled study. J Rheumatol 1993;20:1557-1560.

7. Delamere JP, Scott DL, Felix-Davies DD. Thyroid dysfunction and rheumatic diseases. J R Soc Med 1982;75:102-106.

8. Carette S, Lefrancois L. Fibrositis and primary hypothyroidism. J Rheumatol 1988;15:1418-1421.

9. Aarflot T, Bruusgaard D. Association between chronic widespread musculoskeletal complaints and thyroid autoimmunity. Results from a community survey. Scand J Prim Health Care 1996;14:111-115.

10. White KP, Speechley M, Harth M, Ostbye T. The London Fibromyalgia Epidemiology Study: comparing the demographic and clinical characteristics in 100 random community cases of fibromyalgia versus controls. J Rheumatol 1999;26:1577-1585.

11. Wolfe F, Hawley DJ. Evidence of disordered symptom appraisal in fibromyalgia: increased rates of reported comorbidity and comorbidity severity. Clin Exp Rheumatol 1999;17:297-303.

12. Leventhal LJ. Management of fibromyalgia. Ann Intern Med 1999;131:850-858.

13. Gedalia A, Garcia CO, Molina JF, Bradford NJ, Espinoza LR. Fibromyalgia syndrome: experience in a pediatric rheumatology clinic. Clin Exp Rheumatol 2000;18:415-419.

14. Yunus MB, Masi AT. Juvenile primary fibromyalgia syndrome. A clinical study of thirty-three patients and matched normal controls. Arthritis Rheum 1985;28:138-145.

15. Tayag-Kier CE, Keenan GF, Scalzi LV, et al. Sleep and periodic limb movement in sleep in juvenile fibromyalgia. Pediatrics 2000;106:E70.-

16. Wolfe F, Ross K, Anderson J, Russell IJ, Hebert L. The prevalence and characteristics of fibromyalgia in the general population. Arthritis Rheum 1995;38:19-28.

17. Buskila D, Press J, Gedalia A, et al. Assessment of nonarticular tenderness and prevalence of fibromyalgia in children. J Rheumatol 1993;20:368-370.

18. Mikkelsson M. One year outcome of preadolescents with fibromyalgia. J Rheumatol 1999;26:674-682.

19. Clark P, Burgos-Vargas R, Medina-Palma C, Lavielle P, Marina FF. Prevalence of fibromyalgia in children: a clinical study of Mexican children. J Rheumatol. 1998;25:2009-2014.

20. Henriksson C, Liedberg G. Factors of importance for work disability in women with fibromyalgia. J Rheumatol 2000;27:1271-1276.

21. White KP, Speechley M, Harth M, Ostbye T. Comparing self-reported function and work disability in 100 community cases of fibromyalgia syndrome versus controls in London, Ontario: the London Fibromyalgia Epidemiology Study. Arthritis Rheum 1999;42:76-83.

22. Kaplan RM, Schmidt SM, Cronan TA. Quality of well being in patients with fibromyalgia. J Rheumatol 2000;27:785-789.

23. 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.

24. Swezey RL, Adams J. Fibromyalgia: a risk factor for osteoporosis. J Rheumatol 1999;26:2642-2644.

25. ter Borg EJ, Gerards-Rociu E, Haanen HC, Westers P. High frequency of hysterectomies and appendectomies in fibromyalgia compared with rheumatoid arthritis: a pilot study. Clin Rheumatol 1999;18:1-3.

26. Forseth KO, Forre O, Gran JT. A 5.5 year prospective study of self-reported musculoskeletal pain and of fibromyalgia in a female population: significance and natural history. Clin Rheumatol 1999;18:114-121.

27. Wolfe F, Anderson J, Harkness D, et al. Health status and disease severity in fibromyalgia: results of a six-center longitudinal study. Arthritis Rheum 1997;40:1571-1579.

28. Kennedy M, Felson DT. A prospective long-term study of fibromyalgia syndrome. Arthritis Rheum 1996;39:682-685.

29. Waylonis GW, Perkins RH. Post-traumatic fibromyalgia. A long-term follow-up. Am J Phys Med Rehabil 1994;73:403-412.

30. Baumgartner E, Finckh A, Cedraschi C, Vischer TL. A six year prospective study of a cohort of patients with fibromyalgia. Ann Rheum Dis 2002;61:644-645.

31. Mengshoel AM, Haugen M. Health status in fibromyalgia—a followup study. J Rheumatol 2001;28:2085-2089.

32. Poyhia R, Da Costa D, Fitzcharles MA. Pain and pain relief in fibromyalgia patients followed for three years. Arthritis Rheum 2001;45:355-361.

33. Makela M, Heliovaara M. Prevalence of primary fibromyalgia in the Finnish population. BMJ 1991;303:216-219.

34. Buskila D, Neumann L, Hershman E, Gedalia A, Press J, Sukenik S. Fibromyalgia syndrome in children—an outcome study. J Rheumatol 1995;22:525-528.

35. Siegel DM, Janeway D, Baum J. Fibromyalgia syndrome in children and adolescents: clinical features at presentation and status at follow-up. Pediatrics 1998;101:377-382.

36. Jason LA, Taylor RR, Kennedy CL. Chronic fatigue. Psychosom Med 2000;62:655-663.

37. Hedenberg-Magnusson B, Ernberg M, Kopp S. Presence of orofacial pain and temporomandibular disorder in fibromyalgia. A study by questionnaire. Swed Dent J 1999;23:185-192.

38. Buskila D, Odes LR, Neumann L, Odes HS. Fibromyalgia in inflammatory bowel disease. J Rheumatol 1999;26:1167-1171.

39. Goldenberg DL. Clinical manifestations and diagnosis of fibromyalgia. UpToDate [computer database]. Wellesley, Mass: UpToDate; 2001.

40. Croft P, Schollum J, Silman A. Population study of tender point counts and pain as evidence of fibromyalgia. BMJ 1994;309:696-699.

41. Croft P, Burt J, Schollum J, Thomas E, Macfarlane G, Silman A. More pain, more tender points: is fibromyalgia just one end of a continuous spectrum? Ann Rheum Dis 1996;55:482-485.

42. Wolfe F. The relation between tender points and fibromyalgia symptom variables: evidence that fibromyalgia is not a discrete disorder in the clinic. Ann Rheum Dis 1997;56:268-271.

43. Smythe H. Examination for tenderness: learning to use 4 kg force. J Rheumatol 1998;25:149-151.

44. Tunks E, McCain GA, Hart LE, et al. The reliability of examination for tenderness in patients with myofacial pain, chronic fibromyalgia and controls. J Rheumatol 1995;22:944-952.

45. Jacobs JW, Geenen R, van der Heide A, Rasker JJ, Bijlsma JW. Are tender point scores assessed by manual palpation in fibromyalgia reliable? An investigation into the variance of tender point scores. Scand J Rheumatol 1995;24:243-247.

46. Okifuji A, Turk D, Sinclair J, Starz T, Marcus D. A standardized manual tender point survey. I. Development and determination of a threshold point for the identification of positive tender points in fibromyalgia syndrome. J Rheumatol 1997;24:377-383.

47. Cathey M, Wolfe F, Kleinheksel S, Hawley D. Socioeconomic impact of fibrositis. A study of 81 patients with primary fibrositis. Am J Med 1986;81:78-84.

48. Bandolier. Fibromyalgia: diagnosis and treatment. Bandolier 2001;110:90-92.

49. Busch A, Schachter CL, Peloso PM, Bombardier C. Exercise for treating fibromyalgia syndrome. Cochrane Database Syst Rev 2002;3:CD003786.-

50. Sim J, Adams N. Systematic review of randomized controlled trials of nonpharmacological interventions for fibromyalgia. Clin J Pain 2002;18:324-336.

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

52. Karjalainen K, Malmivaara A, van Tulder M, et al. Multidisciplinary rehabilitation for fibromyalgia and musculoskeletal pain in working age adults. The Cochrane Library 2003(1).

53. Berman BM, Ezzo J, Hadhazy V, Swyers JP. Is acupuncture effective in the treatment of fibromyalgia? J Fam Pract 1999;48:213-218.

54. O’Malley PG, Balden E, Tomkins G, Santoro J, Kroenke K, Jackson JL. Treatment of fibromyalgia with antidepressants: a meta-analysis. J Gen Itern Med 2000;15:659-666.

55. Arnold LM, Keck PE, Welge JA. Antidepressment treatment of fibromyalgia. A meta-analysis and review. Psychosomatics 2000;41:104-113.

56. Burckhardt C, Clark S, Bennett R. The fibromyalgia impact questionnaire: development and validation. J Rheumatol 1991;18:728-733.

In contrast, other investigators have concluded that multidisciplinary treatment incorporating physically and psychologically based treatments was more successful than treatment with a single modality.⁵¹ A systematic review of acupuncture identified only 1 high-quality randomized controlled trial (Table 2), which did show some improvement in symptoms (SOR: C).⁵³

TABLE 2
Alternative nonpharmacologic therapies for fibromyalgia: the evidence

Multidisciplinary rehabilitation (physician and psychological, social, or vocational interventions) (SOR: C)
Study (LOE)	Treatment specifics	Results	Comments
Karjalainen et al⁵²(2)	Education plus physical training vs education; education plus cognitive treatment vs education and group discussion; behavioral therapy vs education; stress management vs aerobic exercise.	Benefits over controls: not significant.	Heterogeneous studies.No high-quality randomized controlled trials identified.
Karjalainen et al⁵²(2)		Adverse effects: not reported.
Acupuncture (SOR: B)
Berman et al⁵³(2)	Systematic review.	Benefits over placebo: improvements in pain, stiffness, global improvement.	Only 1 randomized controlled trial.No long-term results.
Berman et al⁵³(2)	Systematic review.	Adverse effects: pain with needle insertion.	Only 1 randomized controlled trial.No long-term results.
SOR,strength of recommendation; LOE,level of evidence.For an explanation of these ratings.

Therapy with antidepressants

Of all pharmacologic treatments, antidepressants have undergone the most thorough study. Although the optimal role of medications in fibromyalgia has not been delineated, 3 metaanalyses have reported that antidepressants, most commonly amitriptyline, reduce symptoms during treatment of a few months duration (SOR: A) (Table 3).^54,55

Any antidepressants. Pooled results from 13 studies (8 of tricyclics, 3 of selective serotonin reuptake inhibitors, 2 of s-adenosylmethionine) revealed a moderate effect on pain, sleep, and global well-being, and a mild effect on fatigue and number of trigger points.⁵⁴ The authors calculated that persons with fibromyalgia treated with antidepressants were 4 times more likely to improve than persons treated with placebo (number need to treat [NNT]=4). Adverse effects appeared insignificant but were poorly reported in the individual studies.

Tricyclics only. In another meta-analysis, 9 high-quality studies of tricyclic antidepressants (amitriptyline, dothiepin, clomipramine, maprotiline and cyclobenzaprine—classified by the authors as a tricyclic antidepressant) were analyzed for 7 outcomes (patient self-rating of pain, fatigue, stiffness, and sleep; the patient and physician global assessment of improvement; and tenderness of tender points). Significant responses were observed in 25% to 37% of patients. On meta-analysis, outcome measures improved moderately overall with tricyclic treatment, mostly in sleep and global assessment, least in stiffness and tenderness. Long-term safety (more than 8 weeks) and efficacy of tricyclic therapy for fibromyalgia have not been demonstrated.⁵⁵

Combined trials.A third meta-analysis demonstrated improvement when trials of different antidepressants were combined.⁵¹ By pooling studies of antidepressants (amitriptyline, dothiepin, fluoxetine, citalopram, and S-adenosylmethionine) improvements in physical status, fibromyalgia symptoms, and psychological status were found, with no improvement in daily functioning.⁵¹ Although the effect was smaller than physicallybased treatments, the effect size was still comparable to drug treatment for arthritis.⁵¹

Muscle relaxants (primarily cyclobenzaprine) and nonsteroidal anti-inflammatories have been studied, with no evidence of a positive effect.⁵¹ Thus, the best evidence currently supports the use of aerobic exercise and antidepressants, particularly tricyclics, for the treatment of fibromyalgia.

TABLE 3
Antidepressant therapy for fibromyalgia: the evidence

Antidepressants (SOR: A)
Study (LOE)	Treatment specifics	Results	Comments
Arnold et al⁵⁵(1)	Tricyclic antidepressants:	Benefits over placebo: significant response in 25%–37% of patients with moderate improvements in sleep, pain, and globel assessment by patient and physician, and modest improvements in fatigue tenderness and stiffness.	Studies short-term, most less than 6 weeks.In the only trial of 26 weeks, by the end of the study, the effectiveness of amitriptyline and cyclobenzaprine were no greater than placebo.
	Amitriptyline 25–50 mg daily (n=4 trials)
	Dothiepin 75 mg daily (n=1)
	Cyclobenzaprine 10–40 mg daily (n=4)
	Clomipramine 75 mg daily (n=1)
	Maprotiline 75 mg daily (n=1)
O’Malley et al⁵⁴(2)	Amitriptyline 50 mg daily (n=8 trials)	Benefits over placebo: number needed to treat of 4 with moderate improvements in sleep, overall well-being, and pain severity. Mild improvements in fatigue and number of tender points.	Combined effects from heterogeneous classes of antidepressants.
	S-adenosylmethionine 200–800 mg daily (n=2)
	Cyclobenzaprine 20 mg daily (PM), 10 mg daily (PM) (n=1)
	Fluoxetine 20 mg daily (n=2)
	Citalopram 20 mg daily (n=1)
	Clomipramine 75 mg once daily (n=1)
Rossy et al⁵¹(2)	Amitriptyline (n=7 trials)	Benefits over placebo: improvement in physical status and fibromyalgia symptoms with effectiveness comparable with pharmacologic treatment for arthritis pain.	Heterogeneous studies. No effect on daily functioning or psychological status.
	Dothiepin (n=1)
	Fluoxetine (n=2)
	Citalopram (n=1)
	5-hydroxytryptophan (n=1)
		Adverse effects: not reported.
SOR,strength of recommendation; LOE,level of evidence.For an explanation of these ratings.

Instructions to patients, management follow-up

Persons with fibromyalgia should know that although specific symptoms, particularly pain, may be not be dramatically reduced with treatment, aerobic exercise and tricyclic antidepressants alleviate some symptoms with minimal adverse effects (SOR: A). Emphasize that these treatments have been shown to improve one’s ability to cope with fibromyalgia symptoms. The best-studied antidepressant for treating fibromyalgia is amitriptyline, usually given at 25 to 50 mg, nightly.

Exercise. Prescribe aerobic exercise, at least twice per week for 20 to 60 minutes, targeting a heart rate of 55% to 90% of the predicted maximum (180 beats per minute-age) (SOR: A). One caveat: aerobic exercise in the literature was usually supervised, so the ideal exercise regimen might be a fibromyalgia-specific program.