Man as His Own Maker A Response to Leon R. Kass’s “Keeping Life Human,” A 32, Spring 2008 e nature of all other beings is limited and constrained within the boundsof laws prescribed by Us. ou, constrained by no limits, in accordancewith thine own free will, in whose hand We have placed thee, shalt ordain for thyself the limits of thy nature. Both common sense an
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Management of Fibromyalgia Syndrome
Don L. Goldenberg, MD
Context The optimal management of fibromyalgia syndrome (FMS) is unclear and
comprehensive evidence-based guidelines have not been reported.
Objective To provide up-to-date evidence-based guidelines for the optimal treat-
ment of FMS.
ized controlled trials and meta-analyses of randomized controlled trials) of FMS was made using Cochrane Collaboration Reviews (1993-2004), MEDLINE (1966-2004), CINAHL (1982-2004), EMBASE (1988-2004), PubMed (1966-2004), Healthstar (1975- 2000), Current Contents (2000-2004), Web of Science (1980-2004), PsychInfo (1887- 2004), and Science Citation Indexes (1996-2004). The literature review was per- formed by an interdisciplinary panel, composed of 13 experts in various pain management will fit the classification criteria for fi- disciplines, selected by the American Pain Society (APS), and supplemented by se- lected literature reviews by APS staff members and the Utah Drug Information Ser-vice. A total of 505 articles were reviewed.
Data Synthesis There are major limitations to the FMS literature, with many treat-
ment trials compromised by short duration and lack of masking. There are no medicaltherapies that have been specifically approved by the US Food and Drug Administra- tion for management of FMS. Nonetheless, current evidence suggests efficacy of low- dose tricyclic antidepressants, cardiovascular exercise, cognitive behavioral therapy, and patient education. A number of other commonly used FMS therapies, such as trig- ger point injections, have not been adequately evaluated.
ogy classification criteria for the diag- Conclusions Despite the chronicity and complexity of FMS, there are pharmaco-
logical and nonpharmacological interventions available that have clinical benefit. Based on current evidence, a stepwise program emphasizing education, certain medica- tions, exercise, cognitive therapy, or all 4 should be recommended.
using these criteria have found an FMSprevalence of 2% in the United States,including 3.4% of women and 0.5% of tologists (after osteoarthritis), yet rheu- Author Affiliations: Department of Rheumatology,
Newton-Wellesley Hospital, Newton, Mass, and De-
partment of Medicine, Tufts University School of Medi- cine, Boston, Mass (Dr Goldenberg); Psychiatric Men-tal Health Nursing, Oregon Health and Science University, School of Nursing, Portland (Dr Burck- hardt); and Department of Internal Medicine, Rheu- cal characteristics. Questions often arise matology Division, University of Michigan, School ofMedicine, Ann Arbor (Dr Crofford).
Corresponding Author: Don L. Goldenberg, MD,
Department of Rheumatology, Newton-WellesleyHospital, 2000 Washington St, Newton, MA 02462 Clinical Review Section Editor: Michael S. Lauer, MD.
CME available online at
We encourage authors to submit papers for con- www.jama.com
sideration as a “Clinical Review.” Please contact Michael S. Lauer, MD, at firstname.lastname@example.org.
2388 JAMA, November 17, 2004—Vol 292, No. 19 (Reprinted)
2004 American Medical Association. All rights reserved.
less, some clinicians have speculated that inconsistent results from RCTs, or both).
sive patient education is an effective treat- contribute greatly to the clinical expres- wait-listed or untreated controls or with ing scales or visual analog scales. Simi- tive treatment exists.25 Nevertheless, ap- from 6 to 17 sessions. Educational groups efficacy, quality of life, and the 6-minute lines for the optimal treatment of FMS.
Data Sources and Study Selection
ing tiredness, pain, stiffness, fatigue, and tients, demonstrated significant improve- well-being during the preceding week.
FIQ total score as well as in pain sever- Medications
Scale30). Most studies that evaluated ex- system agents (BOX 1). Although they
of activities in the brain and spinal cord, Diagnosis and Education
tently checked electronically for any rel- ture, none of the drugs reviewed here are the diagnosis, if integrated with patient 2004 American Medical Association. All rights reserved.
(Reprinted) JAMA, November 17, 2004—Vol 292, No. 19 2389
Box 1. Treatment of Fibromyalgia Syndrome
FMS. Many of these drugs are olderagents for which approval is unlikely to Medications
be sought. Furthermore, the Food andDrug Administration is just beginning Strong Evidence for Efficacy
Amitriptyline: often helps sleep and overall well-being; dose, 25-50 mg at bed- could be granted (J. Witter, written com- Cyclobenzaprine: similar response and adverse effects; dose, 10-30 mg at bedtime.39-41 Modest Evidence for Efficacy
Tricyclic Antidepressant Medica-
Tramadol: long-term efficacy and tolerability unknown; administered with or with- tions. The strongest evidence for medi-
out acetaminophen; dose, 200-300 mg/d.54-56 cation efficacy in FMS is for tricyclic an- Fluoxetine (only one carefully evaluated at this time): dose, 20-80 mg; may be used with tricyclic given at bedtime; uncontrolled report of efficacy using ser- Venlafaxine: 1 RCT ineffective but 2 case reports found higher dose effective.49-51 these results during the next decade.39Cyclobenzaprine, usually marketed as a muscle relaxant but structurally a tri- Pregabalin: second-generation anticonvulsant; effective in single RCT.57 Weak Evidence for Efficacy
Growth hormone: modest improvement in subset of patients with FMS with low 5-Hydroxytryptamine (serotonin): methodological problems.59,60 Tropisetron: not commercially available.58 clic antidepressants were better than pla- No Evidence for Efficacy
Opioids, corticosteroids, nonsteroidal anti-inflammatory drugs, benzodiazepene Keck42 found 9 of 16 studies suitable for and nonbenzodiazepene hypnotics, melatonin, calcitonin, thyroid hormone, guai- meta-analysis. Tricyclic agents were more fenesin, dehydroepiandrosterone, magnesium.
effective than placebo for all clinical out-comes, especially quality of sleep. A sig- Nonmedicinal Therapies
Strong Evidence for Efficacy (Wait-List or Flexibility Controls But Not Blinded
Cardiovascular exercise: efficacy not maintained if exercise stops.66-75 CBT: improvement often sustained for months.83-87 Patient education: group format using lectures, written materials, demonstra- tigue, pain, and sense of well-being, but tions; improvement sustained for 3 to 12 months.32-36 Multidisciplinary therapy, such as exercise and CBT or education and exer- better evidence for the efficacy of tricy-clic medications than other classes of an- Moderate Evidence for Efficacy
Strength training,75,79 acupuncture,104-106 hypnotherapy,99,100 biofeedback,101,103 longest study of tricyclic medications fol- Weak Evidence for Efficacy
Chiropractic, manual, and massage therapy; electrotherapy, ultrasound.107-110 triptyline, cyclobenzaprine, or placebofor 6 months and reported that the ini- No Evidence for Efficacy
Tender (trigger) point injections, flexibility exercise.
CBT indicates cognitive behavioral therapy; RCT, randomized controlled trial; SSRI, selec- Other Antidepressant Medications.
tive serotonin reuptake inhibitor; SNRI, serotonin and norepinephrine reuptake inhibitor.
There is moderate evidence that the se-lective serotonin reuptake inhibitor 2390 JAMA, November 17, 2004—Vol 292, No. 19 (Reprinted)
2004 American Medical Association. All rights reserved.
(SSRI) fluoxetine is effective in FMS. In Hormones and Supplements.The
treatment.55 The most recent article com- scores for pain, fatigue, and depression.
scores were not significantly improved.
ment for change in depression score.
RCTs of opioids in patients with FMS.
Exercise.There is strong evidence that
cardiovascular exercise is effective treat- Anticonvulsant Medications. Al-
pregabalin in 529 patients with FMS.
The benefits of aerobic exercise67-71 and –0.93; PϽ.001) and significantly more ever, it was found useful in 2 small open- tolerated and especially helpful.70,73,74 label studies using higher doses.50,51 Two Other Medications. Tropisetron, a
according to whether the intervention in- ter than placebo in a second study in pa- volved 1 type of exercise (aerobic train- Analgesic Medications. Tramadol,
ing, strength training, or flexibility train- controlled trial initially suggested that tra- 2004 American Medical Association. All rights reserved.
(Reprinted) JAMA, November 17, 2004—Vol 292, No. 19 2391
ies65,67,76-80 were high-quality training studies: 4 aerobic training, with 1 a mix- ture of aerobic, strength, and flexibility training; 1 strength training; and 2 with control group did. Eight sessions of hyp- Multidisciplinary Treatment. There
found beneficial effects on patient self- 6-minute walk.33,67,73,74,92,93 Treatment physical activity, and physician rating of not in global well-being or self-efficacy.80 perception and sleep quality, pain thresh- puncture control group.105 However, a re- being, fatigue, and sleep in patients with posttest clinical trials, using multidis- ness in patients with FMS.107,108 The chi- found significant positive changes in the efficacy for function in an aerobic train- FIQ, pain severity, self-efficacy, and the 6-minute walk.83,84,86,94-97 Five of these the trial.86,94-96 Improvements in the out- Cognitive Therapies.There is strong
Other Treatments. Although com-
monly used, there are no RCTs of trigger- related symptoms of pain, fatigue, stiff- 2392 JAMA, November 17, 2004—Vol 292, No. 19 (Reprinted)
2004 American Medical Association. All rights reserved.
Box 2. Stepwise Fibromyalgia
FUTURE TREATMENT TRIALS
plete results of some trials are not avail- ists for the efficacy of strength training ferences in FMS clinical trials may be re- lated to the heterogeneity of this illness.
thritis or systemic lupus erythematosus.
ommended (BOX 2).
the patient and family. Any comorbid ill- consider initially are low doses of tricy- groups.115 Such studies suggest that cer- tocols for all treatments, including both tain treatments may be differentially ef- gin a cardiovascular exercise program.
these steps should be referred to a rheu- matologist, physiatrist, psychiatrist, or such as individualized patient trials can doses during the clinical trial but failed 2004 American Medical Association. All rights reserved.
(Reprinted) JAMA, November 17, 2004—Vol 292, No. 19 2393
tion of noxious and innocuous heat stimulation among tion and physical training for women with fibromyalgia.
healthy women and women with fibromyalgia. Pain.
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ation of a patient-centered approach in generalized Funding/Support: This study was sponsored by the
13. Staud R, Cannon RC. Temporal summation of pain
musculoskeletal chronic pain/fibromyalgia patients in from mechanical stimulation of muscle tissue in nor- primary care. Patient Educ Couns. 2002;48:23-31.
Role of the Sponsor: The American Pain Society did
mal controls and subjects with fibromyalgia syndrome.
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(Reprinted) JAMA, November 17, 2004—Vol 292, No. 19 2395
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