CLINICIAN’S CORNER 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.
ATANYONETIME,10%TO12% DataSources,Selection,andExtractionAsearchofallhumantrials(random-
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 lauerm@ccf.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). Outcome Measures
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 TREATMENTS
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. Nonmedicinal Therapy 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. CONCLUSIONS AND RECOMMENDATIONS FOR Box 2. Stepwise Fibromyalgia FUTURE TREATMENT TRIALS Management
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.
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Acknowledgment: We thank the other members of
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2004 American Medical Association. All rights reserved.
(Reprinted) JAMA, November 17, 2004—Vol 292, No. 19 2395
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
Die Parkinson Krankheit Immer wieder stel t sich den an Parkinson Erkrankten die Frage „Warum bin gerade ich erkrankt?“ Leider kann man bis heute darauf noch keine eindeutige Antwort geben; zahlreiche Vermutungen und der Hinweis auf verschiedene mögliche Ursachen sind aber richtungweisend. Was geschieht im Gehirn? Auch wenn die genaue Ursache der Parkinson-Krankheit nicht bekannt ist,