TOPIC OUTLINE

·
INTRODUCTION

·
PATIENT
EDUCATION

·
Discussing
the diagnosis of fibromyalgia

·
Effectiveness
of patient education

·
MEDICATIONS

·
Antiinflammatory
medications

·
Analgesics

·
CNS
active medications

·
Tricyclic
antidepressants

·
Cyclobenzaprine

·
SSRIs

·
Dual
uptake inhibition

·
Anticonvulsants

·
Others

·
Carisoprodol

·
Sodium
oxybate

·
Investigational
approaches

·
Noncompliance

·
NONMEDICINAL
TREATMENT

·
Cardiovascular
fitness training

·
Muscle
strengthening

·
EMG
biofeedback, hypnotherapy, and cognitive behavioral therapy

·
Trigger
point or tender point injections

·
Acupuncture

·
Specialized
treatment centers

·
PROGNOSIS

·
INFORMATION
FOR PATIENTS

·
SUMMARY
AND RECOMMENDATIONS

·
REFERENCES

GRAPHICS

·
FIGURES

·
Tender points in fibromyalgia

·
TABLES

·
Diagnostic criteria for CFS

RELATED TOPICS

·
Clinical manifestations and diagnosis of fibromyalgia in adults

·
Differential diagnosis of fibromyalgia

·
Pathogenesis of fibromyalgia

·
Fibromyalgia in children and adolescents

·
Overview of soft tissue rheumatic disorders

·
Clinical features and diagnosis of chronic fatigue syndrome

·
Nocturnal leg cramps; night starts; and nocturnal myoclonus

·
Risk factors for and possible causes of systemic sclerosis
(scleroderma)

·
Acupuncture for rheumatic conditions

·
Patient information: Fibromyalgia

Treatment of fibromyalgia in adults

Author

Don L Goldenberg, MD

Section Editor

Peter H Schur, MD

Deputy Editor

Paul L Romain, MD

Last
literature review version 16.3: October 2008  |  This topic last updated:
October 7, 2008   (More)

INTRODUCTION — Fibromyalgia
is a chronic pain disorder that is difficult to treat. It is most important
to educate the patient and family regarding the uncertainty involved in
pathogenesis, diagnosis, and treatment [1].
There is no test that confirms this diagnosis, which is currently based
upon the following clinical criterion [1]:

Widespread
musculoskeletal pain

Excess
tenderness in at least 11 of 18 predefined anatomic sites (show
figure 1)

The
treatment of fibromyalgia will be reviewed here. Patients with fibromyalgia
generally respond best to a multidisciplinary treatment program that
incorporates physician as well as non-physician providers. This includes a
team of physical medicine, rehabilitation, and mental health specialists.

Other
issues related to fibromyalgia, including clinical manifestations,
diagnosis, the differential diagnosis of widespread pain, pathogenesis, and
fibromyalgia in children, and pathogenesis are discussed separately. (See "Clinical manifestations and diagnosis of
fibromyalgia in adults" and see "Differential diagnosis of fibromyalgia""
and see "Pathogenesis of fibromyalgia"
and see "Fibromyalgia in children and
adolescents").

PATIENT EDUCATION — Patients
with fibromyalgia (as well as those with the myofascial pain syndrome and
the chronic fatigue syndrome) need to understand their illness before any
medications are prescribed [2]
(see
"Information for patients" below).

The
myofascial pain syndrome may be a localized form of fibromyalgia.
Patients with this disorder complain of pain in one anatomic region,
such as the right side of the neck and shoulder, and tenderness is
confined to that area [3].
(See "Overview of soft tissue rheumatic
disorders", section on Regional myofascial pain).

There
also appears to be a close relationship between the chronic fatigue
syndrome and fibromyalgia. Diagnostic criteria for the classification
of chronic fatigue syndrome (CFS) are similar to those for
fibromyalgia, and the majority of patients with CFS meet tender point
criteria for fibromyalgia [4];
similarly, approximately 70 percent of patients with fibromyalgia meet
the criteria for CFS [5].
(See "Clinical features and diagnosis of
chronic fatigue syndrome").

Discussing the diagnosis of fibromyalgia — Most
patients have had fibromyalgia for years before the diagnosis is finally
made. They often have undergone multiple diagnostic evaluations and have
consulted with many different specialists. Some patients may feel rejected
by the medical profession, while others may fear that a life-threatening
illness will eventually be found.

Providing
a diagnosis may have a beneficial effect for patients. This salutary effect
was illustrated in one study of patients' self-reported symptoms and
function prior to, and up to three years after, diagnosis [6].
Significantly fewer symptoms and an improvement in health status were noted
after the patients were informed of the diagnosis. These results should
help allay the fears, expressed by some physicians, that labeling people
with a diagnosis of fibromyalgia worsens their health rather than improving
it [7].

Thus,
the patient must be reassured that fibromyalgia is a real illness, and not
imagined or "in your head." The benign nature of the disorder
should also be emphasized. As an example, patients must be told that this
is not a deforming or deteriorating condition, and that it is neither
life-threatening nor a cosmetic problem. The relationship of neurohormones
to pain perception, fatigue, abnormal sleep, and mood disturbances should
be discussed; this will help the patient to understand the rationale of
therapy with medications such as tricyclic antidepressants and serotonin
reuptake inhibitors.

Some
patients with fibromyalgia, particularly those who also meet the criteria
for chronic fatigue syndrome (show
table 1) may believe that their illness is caused by an undiagnosed
infection. Although infections may be important precipitating factors,
there is no evidence that these syndromes are related to persistent
infection. Patients generally have a better response to treatment when they
understand that they are not harboring some infectious agent over which
they have no control. (See "Clinical features and diagnosis of chronic
fatigue syndrome").

It
has been suggested that blood flow to muscle and skin may be sluggish in
fibromyalgia. A discussion of the role of muscle 'spasm' and deficient
muscle blood flow are useful when prescribing exercise and physical
therapy.

Physical
or emotional stress may precipitate or aggravate fibromyalgia.
Approximately 30 percent of patients with fibromyalgia have coexisting depression
and/or anxiety. In addition, a review of the role of stress and mood
disturbances in fibromyalgia will encourage the patient to learn simple
relaxation techniques and to consider formal stress-reduction programs. The
patient must be taught to recognize the role of sleep disturbances and
methods to correct them.

Finally,
patients need to appreciate that their symptoms will wax and wane but that
the pain and fatigue generally persist. Despite the presence of these
chronic symptoms, it is reassuring to emphasize that the great majority of
patients live normal and active lives.

Effectiveness of patient education — Patient
education has a therapeutic effect. A 2004 systematic review of treatment
of fibromyalgia assessed the reported effectiveness of educational
interventions when compared to controls who were waiting for care or
receiving training in gentle stretching exercises [8].
The studies reviewed were typically unblinded. Small group sessions,
printed materials, lectures, and demonstrations were used to inform
patients of the nature of fibromyalgia. Numbers of sessions ranged from 6
to 17. Those receiving the educational intervention had significantly more
improvement than the controls, and beneficial effects lasted from three to
12 months after the sessions ended.

A
single intensive educational intervention may also be beneficial, as was
the case in a study in which patients received education from a
multidisciplinary team over 1.5 days [9].
A month afterward there was significantly less pain and more improvement in
self-reported function, fatigue, stiffness, anxiety, and depressed mood in
those who received the educational intervention.

MEDICATIONS — Antiinflammatory
and analgesic drugs and central nervous system (CNS) active medication have
all been used in the treatment of fibromyalgia [8].

Antiinflammatory medications — There
is no evidence that tissue inflammation is present in patients with
fibromyalgia. Thus, it is not surprising that antiinflammatory medications
are not an effective form of treatment. As an example, therapeutic doses of
naproxen,
ibuprofen,
and prednisone
(20 mg/day) were found to be no better than placebo in clinical trials [8].
However, nonsteroidal antiinflammatory drugs (NSAIDs) may have a
synergistic effect when combined with central-nervous system (CNS) active
medications (see
"CNS active medications" below). At present, there is no
data concerning the efficacy of selective COX-2 inhibitors in this
disorder.

Glucocorticoids
are also ineffective and also have the potential for serious adverse
effects when used chronically [8].

Analgesics — Other
analgesics, such as acetaminophen
and tramadol,
alone or in combination, may be helpful [10,11].
They are generally used in combination with CNS active medications when the
latter are not effective alone.

The
modest clinical efficacy of the fixed combination of these two agents (up
to 650 mg acetaminophen
and 75 mg tramadol
four times daily) in relieving pain was illustrated in a study that
randomly assigned 315 predominantly white female patients to active
combination therapy or placebo [11].
Discontinuation rates and secondary measures such as pain, pain relief, and
self reported health status were assessed over a three month period. The
following results were noted:

A
greater proportion of the patients treated with acetaminophen and
tramadol had a 50 percent or greater reduction in pain (35 versus 18
percent with placebo)

Those on
the active combination had significantly greater overall decrease in
pain (19 mm versus 7 mm on a 100 mm scale).

Discontinuation
rates were lower with active treatment (48 versus 62 percent). Nausea
was more than twice as common among those on the active medication
than placebo (9 versus 4 percent).

While
these findings are encouraging, the patients had received little treatment
before enrollment, and prior use of tricyclic antidepressants, cyclobenzaprine,
and analgesics (including acetaminophen)
were criteria for exclusion. How effective the combination of acetaminophen
and tramadol
would be for patients who had tried and failed other treatments, and how
the combination would perform if added to ongoing treatment with one or
more of the CNS active medications is unclear.

There
is some concern regarding the long-term potential for abuse of tramadol,
although the risk is less than with more potent narcotic analgesics that
have also been tried in fibromyalgia. Prolonged use of such agents is
controversial and should be avoided unless prescribed by a pain management
specialist.

CNS active medications — Certain
CNS active medications, most notably tricyclic antidepressants and the
skeletal muscle relaxant cyclobenzaprine
(also a tricyclic compound), have proven to be of some efficacy in
controlled trials [12-15],
and are generally considered to be first-line therapy for fibromyalgia.

Tricyclic antidepressants — Tricyclic
antidepressants and related agents are often used as initial treatment for
patients with fibromyalgia. Individual randomized trials have demonstrated
that clinically important improvement occurs in 25 to 45 percent of
patients treated with these medications [12-18].
However, their use is limited by a lack of uniform effectiveness and
relatively high frequency of side effects. In addition, the efficacy of the
tricyclic drugs may decrease over time in some patients [16].

The
doses of amitriptyline
studied have been 25 to 50 mg, usually given as a single bedtime dose.
These doses are usually lower than those required to treat depression.
Nevertheless, even at low doses, dry mouth, constipation, fluid retention,
weight gain, grogginess, and difficulty concentrating are common. Such side
effects and possible cardiotoxicity limit use in elderly patients.

Desipramine
is a tricyclic antidepressant that has been less well studied for
fibromyalgia but remains a possible alternative because it generally has
fewer anticholinergic side effects.

Regardless
of the agent chosen, patients with fibromyalgia should be started on very low
doses; a typical starting dose of amitriptyline
or desipramine
is 5 to 10 mg one to three hours before bedtime. The dose may be increased
by 5 mg at two week intervals. The final dose should be set by the patient,
based upon efficacy and side effects, always keeping the dose as low as
possible.

Cyclobenzaprine — Various
doses of cyclobenzaprine
have been used in placebo-controlled trials, including 10 mg in the morning
and 20 mg at night [15],
10 mg three times daily [19],
10 mg in the morning and 30 mg in the evening [20],
and 10 to 40 mg daily as needed [14].
Doses are typically begun at 10 mg near bedtime and increased as tolerated
to the larger doses.

The
best evidence of the efficacy of cyclobenzaprine
was provided by a 2004 meta-analysis of five placebo-controlled trials that
included 312 patients [16].
Self-reported 'improvement' (measured in three studies) was more likely in
subjects receiving cyclobenzaprine than placebo (odds ratio 3.0, 95 percent
confidence interval 1.6 to 5.6), the absolute difference in the rate of
improvement was 21 percent, suggesting that approximately five patients
would need to be treated with cyclobenzaprine for one to improve. The
effect size was similar to that of two meta-analyses of the effectiveness
of amitriptyline
in this disorder [17,18].

This
meta-analysis also found that pain decreased more in those who received cyclobenzaprine
than placebo for four weeks, but the change in pain was not significantly
different in active or placebo groups after eight or 12 weeks. Changes in pain
and the number of tender points were not significantly different between
the groups at any time.

SSRIs — Other CNS active
medications that have some efficacy in fibromyalgia include the serotonin
reuptake inhibitors (SSRIs) [21,22].

Fluoxetine
— While a study that compared a fixed dose of fluoxetine (20
mg/day) found it was not superior to placebo [23],
another that allowed dose escalation, from 20 to a maximum of 80
mg/day, found fluoxetine to be significantly more effective than
placebo [22].
In this study the effect on pain was independent of change in mood.

Paroxetine
— In the largest study to date, an escalating dose of a
continuous release formulation of paroxetine (12.5 mg/day to 62.5
mg/day) was compared to placebo in a trial that randomly assigned 116
patients and followed their composite scores on the fibromyalgia
impact questionnaire (FIQ) from baseline to 12 weeks [24].
Significantly more of those assigned to paroxetine than to placebo
achieved a ≥25 percent improvement in FIQ score (57 versus 33
percent). Among those who completed the assigned treatment, the
response rates were higher in those receiving paroxetine than placebo
(66 versus 33 percent, respectively).

Other
SSRIs — Fluvoxamine
was compared to amitriptyline
in a study that randomly assigned 68 patients to one of the two active
treatments for four weeks [25].
Withdrawals were more common in the amitriptyline than fluvoxamine
groups (40 versus 16 percent). Pain relief was not significantly
different in the two groups.

Inconsistent
results have been noted in small studies using citalopram
to treat patients with fibromyalgia [26,27].

Dual uptake inhibition — Combinations
of agents that individually inhibit reuptake of serotonin and
norepinephrine, or use of single drugs that inhibit reuptake of both
neurotransmitters (SNRIs) may be more useful than a drug that targets one
or the other.

Combination
of SSRI and tricyclic — The combination of 20 mg of fluoxetine
in the morning with 25 mg of amitriptyline
at bedtime was more effective than either medication used alone in a
randomized trial [21].

Dual
reuptake inhibition with one agent — Duloxetine
and venlafaxine
inhibit both norepinephrine and serotonin reuptake and have been
studied in patients with fibromyalgia. Another dual reuptake
inhibitor, milnacipran, may also be effective for pain relief when
used in patients with fibromyalgia but is not currently as widely
available [28,29].

Duloxetine
has been approved by the FDA for treatment of fibromyalgia, and is also
approved for the treatment of depression and diabetic neuropathy. The
efficacy of duloxetine was initially demonstrated in two multicenter trials
of 12 weeks duration [30,31].
A longer term benefit was demonstrated in a subsequent six month
multicenter, randomized, double-blind placebo-controlled trial of 520
patients who were assigned to single daily dose of either 60 mg or 120 mg
of duloxetine or to placebo [32].

Duloxetine
significantly reduced pain severity and improved global assessments at
three and six months. The reductions in pain were seen in the first week of
therapy and occurred in patients with and without major depression. Mental
fatigue improved, but general fatigue did not.

The
most common side effects were nausea, headache, and dry mouth. They usually
occurred within the first three months of therapy.

There
are fewer data on the efficacy of venlafaxine
for fibromyalgia. A small study using a flexible dose design in which the
final mean dose of venlafaxine was 167 mg per day, suggested that this dual
uptake inhibitor may be effective [33].

Anticonvulsants

Gabapentin
— The efficacy and safety of gabapentin were assessed in a trial
that randomly assigned 150 patients to receive gabapentin (1200 to
2400 mg/day) or placebo for 12 weeks [34].
A response was defined as a ≥30 percent decrease in the Brief
Pain Inventory (BPI) score. A significantly greater proportion of
patients receiving gabapentin were responders than were those in the
placebo group (51 and 31 percent, respectively) and the difference in
the mean BPI scores between the two groups was also significant
(-0.92, 95% CI -1.75 to -0.71) and favored gabapentin treatment.
Gabapentin was generally well tolerated, although dizziness, sedation,
lightheadedness, and weight gain were reported significantly more
often by those in the gabapentin group. There was no significant
difference in the incidence of serious adverse events.

Pregabalin
— Pregabalin, a second generation anticonvulsant may be
beneficial for patients with fibromyalgia. This was illustrated in a
study that randomly assigned 529 patients to placebo or pregabalin
(150 mg, 300 mg, or 450 mg/day) for eight weeks [35].
Pregabalin, 450 mg/day, significantly reduced the average severity of
pain compared to placebo (difference in means -0.93 on a 1 to 10
visual analog scale). Among those receiving the highest dose, more
pregabalin-treated patients had a >50 percent improvement in pain
(29 versus 13 percent). There were also significant improvements in
sleep, fatigue, and health-related quality of life among those
receiving 300 and 450 mg/day. Higher doses, up to 600 mg/day, were
used in another controlled trial [36];
this dose (given as 300 mg twice daily) may be more effective than
lower doses, but is also more likely to cause adverse effects such as
somnlence and dizziness.

Clonazepam
— Patients with associated nocturnal myoclonus or repetitive
limb movements may respond well to low doses of benzodiazepines, such
as clonazepam, 0.5 mg at bedtime. However, patients with suspected
nocturnal myoclonus or sleep apnea should be referred to a sleep
clinic for sleep polysomnography. (See "Nocturnal leg cramps; night starts; and
nocturnal myoclonus").

Others — Other agents that
may be effective include the muscle relaxant carisoprodol,
the sedative sodium oxybate, and various investigational approaches that
are discussed below.

Carisoprodol — The
combination of carisoprodol,
paracetamol (acetaminophen),
and caffeine
was more effective than placebo in one trial that randomly assigned 58
women and reported the results in the 43 who completed the eight-week study
[37].
Significant improvement was noted in pain, sleep quality, and overall
feeling of well being. Increased thresholds for pain elicited by pressure
were noted at 70 percent and 30 percent of sites in actively treated and
control patients, respectively.

Sodium oxybate — The
sedative drug, sodium oxybate, a commercially available preparation of
naturally occurring gamma
hydroxybutyrate (GHB), may have beneficial effects on sleep and
pain. A short term, placebo controlled, crossover study of sodium oxybate
(6.0 g at bedtime) in 24 patients found significant improvements in an
index of tender points, and measures of pain, and fatigue [38].
Because these results are as yet unconfirmed, and because of the potential
for abuse (GHB has been used surreptitiously to sedate victims prior to
sexual assault) further investigation is warranted.

Investigational approaches — Since
chronic fatigue syndrome has more often been considered to be a viral
disease with immune abnormalities, controlled treatment trials have
involved antiviral agents and immune modulators. However, therapeutic
response to antiviral and immune modulating agents, such as acyclovir
and immune globulin, have been disappointing. As noted above, there is a
large clinical overlap between the CFS (show
table 1) and fibromyalgia [4,5].
At present, therapeutic regimens in these two disorders are similar.

Preliminary
evidence suggests that hormonal manipulation may be effective in the
treatment of fibromyalgia. As an example, stimulated by the observation
that insulin growth factor-1 levels are occasionally diminished in
fibromyalgia, the efficacy of human
growth hormone was examined in a randomized, double-blind,
placebo-controlled study [39].
In this report, daily subcutaneous injections of human growth hormone for
nine months resulted in more improvement than placebo. In addition,
patients treated with hormone tended to relapse when the study was
concluded, but symptoms of carpal tunnel syndrome developed in seven
individuals. However, the cost of such treatment may be prohibitive. An
accurate assessment of the role of hormonal manipulation therapy therefore
requires additional study.

In
contrast to the promising preliminary results with growth hormone discussed
above, supplementation with oral androgen dehydroepiandrosterone (DHEA)
does not appear to be effective in treating fibromyalgia in postmenopausal
women. In a well-designed randomized, placebo-controlled study, treatment
with DHEA (50 mg/day) for three months did not result in significant improvements
in patient reported pain, fatigue, or physical function [40].

There
is a single report that the nutritional supplement, 5-hydroxytryptophan,
was beneficial [41],
but commercial preparations of this amino acid have been found to contain
varying amounts of an oxidation product that is a putative neurotoxin and
has been associated with eosinophilia myalgia like illness. (See "Risk factors for and possible causes of
systemic sclerosis (scleroderma)", section on L-tryptophan).

An
antagonist of the serotonin 5-HT3 receptor (tropisetron) appeared promising
in preliminary trials [42,43].

Pramipexole,
a dopamine agonist, may have some beneficial effects for those with
fibromyalgia. This was illustrated in a study that randomly assigned patients
in a 2:1 ratio to either pramipexole (0.5 to a maximum of 4.5 mg every
evening) or placebo [44].
A dose and/or time dependent trend was apparent in pain relief, with
significantly greater improvement in the mean pain score in the pramipexole
group. After 14 weeks of treatment pain scores decreased in the pramipexole
and placebo groups by 36 and 9 percent, respectively, from baseline.
Anxiety and weight loss were significantly more frequently observed in the
pramipexol-treated patients and diarrhea, morning somnolence, tachycardia,
and bloating were noted in this group also. The dose used in this study is
higher than many patients can tolerate. Furthermore, patients were left on
their current medications, in many instances including opioids. The use of
pramipexole in fibromyalgia patients who are refractory to multiple
medications can be considered, but further study is needed to evaluate its
efficacy and safety.

Transcranial
direct current stimulation (tDCS) was assessed for pain-relieving effects
in a study that randomly assigned 32 patients with fibromyalgia to receive
sham stimulation, real tDCS with the anode centered over the primary motor
cortex, or stimulation of the dorsolateral prefrontal cortex [45].
Direct current stimulation consisted of 2 mA for 20 minutes on 5
consecutive days with the anode placed on the scalp over the appropriate
brain region. The change in pain was significantly greater in those who
received real tDCS to the motor cortex than that for the groups receiving
sham or dorsolateral prefrontal cortex stimulation. The authors of this
study characterized it as "proof of principal". Further study is
warranted to assess the efficacy and safety of tDCS.

Noncompliance — Noncompliance,
whether due to forgetfulness, carelessness, or as an exercise of patient
autonomy, may contribute to a lack of effectiveness of medications
prescribed for patients with fibromyalgia. Adherence to advice by 127 women
with fibromyalgia cared for by 10 rheumatologists was assessed in an
observational study [46].
Overall, 47 percent of the women reported noncompliance with medications.
The degree of discordance between a physician's and patient's assessments
of communication during, and patient satisfaction at the conclusion of, a
physician-patient encounter were significant determinants of overall
compliance.

NONMEDICINAL TREATMENT — Nonmedicinal
treatments that have been evaluated in controlled studies include
cardiovascular fitness training, muscle strengthening, physical therapy,
EMG (electromyogram) biofeedback, hypnotherapy, and cognitive behavioral
therapy.

A
2004 systematic review found strong evidence for effectiveness of
cardiovascular exercise, cognitive behavioral therapy (CBT), patient
education, and multidisciplinary interventions that combined elements of
aerobic exercise, CBT, and patient education [8].
The same review found moderate evidence for efficacy of strength training,
hypnotherapy, biofeedback, and mineral springs or salt baths
(balneotherapy). Weak evidence exists for manipulative and manual therapies
(chiropractic, massage) and physical modalities including electrotherapy
and therapeutic ultrasound. While moderate evidence was also found for
acupuncture [8],
a subsequent well designed randomized and sham-controlled trial did not
find any advantage of traditional Chinese acupuncture over a variety of
sham procedures (see
"Acupuncture" below) [47].

Cardiovascular fitness training — A
2002 systematic review of controlled trials of aerobic exercise for
fibromyalgia found beneficial effects on aerobic performance, pain, and
pressure thresholds over tender points in those subjects who received
aerobic exercise training [48].
Pooled results were as follows for the exercise and control groups,
respectively:

Increased
aerobic capacity (17.1 percent increase versus 0.5 percent increase).

Decreased
pain (11.4 percent decrease versus 1.6 percent increase)

Higher
pressure threshold for pain (28.1 percent increase versus 7 percent
decrease)

In
practice, it has been difficult to start and maintain fibromyalgia patients
in a structured cardiovascular exercise program, because patients generally
perceive that their pain and fatigue worsen as they begin to exercise.
Thus, it is important to instruct patients in the principles and methods of
gradual incremental cardiovascular fitness programs. Low impact aerobic
activities such as fast walking, biking, swimming or water aerobics are
most successful. The type and intensity of the program should be
individualized, and physical therapists or exercise physiologists can
provide helpful instruction. Optimal cardiovascular fitness training requires
a minimum of 30 minutes of aerobic exercise three times per week in a range
near target heart rate.

Muscle strengthening — A
controlled trial compared muscle strengthening (using free weights or
elastic bands) to flexibility training in 68 women with fibromyalgia, most
of whom were obese and sedentary [49].
Both groups had improvement in several measures including pain, number of
tender points, and muscle strength. Those in the strength training group
had a significant decrease in the mean score on a depression screening
instrument (Beck Depression Inventory) while the flexibility group had no
change in this measure. A similar small number of patients in both groups
experienced increased symptoms during the study (three per group).

EMG biofeedback, hypnotherapy, and cognitive
behavioral therapy — These methods of therapy have
shown some usefulness in selected patients with fibromyalgia.

EMG
biofeedback intervention resulted in significant improvement in pain,
morning stiffness and tender points in one study [50]
and in pain, depression and function in another uncontrolled and
unblinded trial in 12 patients that used biofeedback to manipulate
heart rate variability, a marker of autonomic dysfunction [51].

Hypnotherapy
was found to be better than physical therapy in 40 patients with
refractory fibromyalgia [52].
The hypnotherapy group demonstrated better outcome in parameters such
as pain, fatigue, sleep and global assessment, although not in tender
point examination.

Both
mindfulness meditation-based relaxation response program and cognitive
behavioral therapy (CBT) have been helpful in studies of patients with
fibromyalgia [53-56].
Meditative stress reduction was beneficial for depression in an
eight-week study that randomly assigned 91 women with fibromyalgia and
depressive symptoms to meditation or a waiting list [53].
CBT resulted in improvement in ten different target variables in 22
patients with fibromyalgia studied for a mean of 30 months after
completion of the therapy [54].
A small, randomized trial (n=47) found CBT for insomnia in patients
with fibromyalgia significantly improved sleep quality compared to
sleep hygiene instructions, or usual care [55].

A
systematic review of 13 published trials compared mind-body therapies to
other active treatments, placebo, or usual care. Although better than
placebo or usual care in improving quality of life, these non-pharmacologic
interventions were not superior for relieving pain or improving function [57].
However, the combination of a nonpharmacologic treatment with an exercise
program was associated with better long term outcomes than exercise alone.

Trigger point or tender point injections — Other
uncontrolled reports have evaluated transcutaneous nerve stimulation
(TENS), laser treatment and tender point injections in fibromyalgia
patients. TENS has been of limited effectiveness and more controlled
studies need to be done.

There
have been very few controlled studies of trigger point or tender point
injections in the treatment of fibromyalgia; these injections are more
often used in patients with localized myofascial pain syndrome. This
technique may be performed in patients with fibromyalgia by injecting 1
percent lidocaine
into the tender point, although injections of saline, botulinum toxin and
"dry needling" have been advocated by some authors. The
injections may be most effective when they are combined with muscle
stretching and manipulation (myofascial release).

Acupuncture — Traditional
Chinese acupuncture and more modern alternatives such as electrical
stimulation applied through acupuncture needles (electroacupuncture) have
been evaluated in the treatment of fibromyalgia. Controlled trials of
acupuncture are difficult to accomplish, in part because there are no
standards for sham or placebo interventions. The effectiveness of
acupuncture in various rheumatic disorders, including fibromyalgia, is
discussed in more detail elsewhere. (See "Acupuncture for rheumatic conditions").

Traditional
Chinese acupuncture does not appear to be significantly more effective for
relieving pain in patients with fibromyalgia than various sham procedures [47,58].
This was best illustrated in a study that randomly assigned 100 patients to
one of four groups: traditional Chinese acupuncture for widespread pain,
acupuncture needling for an unrelated condition (irregular menses),
needling at points on the body other than those recognized in traditional
Chinese acupuncture, or touching the skin with a sharp object without
needle insertion [47].
Patients were effectively blinded to the treatment group. Although all four
groups experienced a substantial decrease in pain from baseline, the mean
difference in pain relief between the traditional acupuncture group and all
the sham groups was insignificant (0.5 cm on 10 cm scale, 95% CI -0.3-1.2
cm). Nor was there a significant difference in any of the secondary
measures of efficacy including: fatigue, sleep quality, and overall
well-being. The 30 percent improvement in pain in each group is intriguing,
indicating again the important "placebo" effect of treatment in
chronic illness.

A
2007 systematic review of acupuncture in fibromyalgia found only 5
randomized clinical trials that met inclusion criteria. Two trials yielded
negative results, three were positive but quality of studies was low. The
positive reports incorporated electroacupuncture [59].

Specialized treatment centers — Multi-disciplinary
treatment may be needed in chronic pain disorders such as fibromyalgia.
These programs may be developed in physical medicine and rehabilitation, or
chronic pain units [60].
Rheumatologists or others may also provide this care, particularly if they
work closely with physiatrists, physical therapists, and mental health
professionals [61].
The advantage of such a program is to provide a structured, multimodality
treatment program under one roof, and in a relatively brief time frame.
This type of program may be especially helpful in patients who are
resistant to medications, and to those patients with the most complicated
psychosocial issues, including disability proceedings.

A
systematic review of the efficacy of such a multidisciplinary
rehabilitation approach to the treatment of fibromyalgia in 2008 concluded
that this was the best strategy in clinical practice [62].

Patients
with fibromyalgia are frequently treated with analgesics, including
opioids, despite an absence of evidence of their efficacy.
Multidisciplinary rehabilitation programs may aid in weaning patients from
narcotics. As an example, an uncontrolled study admitted 159 fibromyalgia
patients to a multidisciplinary pain rehabilitation program based on
cognitive behavioral therapy [63].
Physical and emotional function improved and the use of analgesics,
including opioids was reduced.

PROGNOSIS — Most
patients with fibromyalgia continue to have chronic pain and fatigue. After
an average follow-up of 14 years, we have found that there is usually
little change in the patient's symptoms. However, two-thirds of patients
reported that they were working full-time and that fibromyalgia interfered
only modestly with their lives.

Most
longitudinal long-term studies of outcome in fibromyalgia have been from
tertiary referral centers. One study of 538 patients followed at six
referral centers found that pain, fatigue, sleep disturbances, anxiety, and
depression were essentially unchanged over a follow-up period of
approximately eight years [64].
However, patients treated by primary care physicians in the community have
a much better prognosis. In one community survey of 141 fibromyalgia
subjects, only 35 percent of those with chronic widespread pain at the
initial assessment still had widespread pain two years later [65].

Approximately
10 to 30 percent of patients with fibromyalgia report that they are work
disabled, a higher incidence than some other groups with chronic pain. In a
Canadian study, for example, the incidence of disability was evaluated in
100 patients with fibromyalgia, 76 patients with widespread musculoskeletal
pain, and 135 control individuals [66].
Thirty-one percent of fibromyalgia patients reported being work disabled
versus 2 and 10 percent of the control group and those with chronic pain,
respectively. Fibromyalgia patients were also much more likely to be
receiving a disability pension (26 versus 3 and 9 percent, respectively).

Certain
psychological factors may be associated with a better prognosis. This was
illustrated in a study of 198 patients among whom the following were
beliefs or sentiments that were more often shared by those with better
outcomes [67]:

An
increased sense of control over pain

A belief
that one is not disabled

That
pain is not a sign of damage

Behaviors
that were associated with better outcomes included:

Seeking
help from others

Decreased
guarding during examination

Exercising
more

Pacing
activities

Conversely,
"catastrophizing" about the pain of fibromyalgia is associated
with increased awareness of pain (as indicated by increased brain
activation in response to painful stimuli in functional MR images), and
also is associated with worsening rather than improvement in symptoms [68].

INFORMATION
FOR PATIENTS — Educational materials on this topic
are available for patients. (See "Patient information: Fibromyalgia").
We encourage you to print or e-mail this topic, or to refer patients to our
public web site www.uptodate.com/patients,
which includes this and other topics.

SUMMARY AND RECOMMENDATIONS — Fibromyalgia
is a chronic pain disorder that is difficult to treat. The following is a
recommended stepwise approach to the treatment of fibromyalgia that
includes many of the evidence-based recommenations from the 2008 European
League Against Rheumatism (EULAR) guidelines for the management of
fibromyalgia [69].
The following recommendations do not include some of the management options
in the guidelines, such as heated pool therapy (with or without exercise), acetaminophen
and weak opioids other than tramadol.

Therapy
begins by confirming the diagnosis and offering an explanation to the
patient of the chronic but generally nonprogressive nature of
fibromyalgia. If there are other disorders present (eg, depression,
restless legs syndrome, sleep apnea, regional musculoskeletal
disorders such as bursitis or tendinitis, etc) these should be
identified and treated. (See
"Patient education" above).

We
usually begin patients on either a low dose of a tricyclic medication
at nighttime or cyclobenzaprine
and use simple analgesics as needed during the day. (See
"CNS active medications" above). Nonsteroidal
antiinflammatory drugs are not recommended as first-line therapy but
maybe useful in combination with CNS active drugs. (See
"Antiinflammatory medications" above).

Low
impact aerobic activities such as walking, biking, swimming, or water
aerobic exercises are begun and individualized to meet each patient's
needs. Referral for cognitive behavioral therapy is appropriate at
this step and is most effective if combined with an ongoing exercise
program. (See
"Nonmedicinal treatment" above).

Patients
who have not responded to the above measures should be referred to a
specialist to confirm the diagnosis and provide additional advice on
management (eg, rheumatologist, physiatrist, psychiatrist, or pain
management specialist). Addition of an SSRI (eg, fluoxetine
20 to 80 mg/day) to a tricyclic, or use of a dual norepinephrine and
serotonin reuptake inhibitor such as duloxetine
(initial dose 40 to 60 mg/day) can also be considered. Where
available, moclobemide
and pirlidole are alternatives. An alternative in those who are
inadequately treated by, or are intolerant of, antidepressants, is the
addition of other CNS acting agents such as gabapentin
or pregabalin.
Tramadol may be added to assist in pain management at this step if
necessary.

Use of UpToDate is subject to
the Subscription
and License Agreement.

REFERENCES

1.
Wolfe,
F, Smythe, HA, Yunus, MB, Bennett, RM, 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.

2.
Burckhardt,
CS, Bjelle, A. Education programmes for fibromyalgia patients: description
and evaluation. Baillieres Clin Rheumatol 1994; 8:935.

3.
Wolfe,
F, Simons, DG, Fricton, J, Bennett, RM, et al. The fibromyalgia and
myofascial pain syndromes: A preliminary study of tender points and trigger
points in persons with fibromyalgia, myofascial pain syndrome and no
disease. J Rheumatol 1992; 19:944.

4.
Goldenberg,
DL, Simms, RW, Geiger, A, Komaroff, AL. High frequency of fibromyalgia in
patients with chronic fatigue seen in a primary care practice. Arthritis
Rheum1990; 33:381.

5.
Aaron,
LA, Burke, MM, Buchwald, D. Overlapping conditions among patients with chronic
fatigue syndrome, fibromyalgia, and temporomandibular disorder. Arch Intern
Med 2000; 160:221.

6.
White,
KP, Nielson, WR, Harth, M, et al. Does the label "fibromyalgia"
alter health status, function, and health service utilization? A
prospective, within-group comparison in a community cohort of adults with
chronic widespread pain. Arthritis Rheum 2002; 47:260.

7.
Ehrlich, GE. Pain is real; fibromyalgia isn't. J Rheumatol 2003;
30:1666.

8.
Goldenberg,
DL, Burckhardt, C, Crofford, L. Management of fibromyalgia syndrome. JAMA
2004; 292:2388.

9.
Pfeiffer,
A, Thompson, JM, Nelson, A, et al. Effects of a 1.5-day multidisciplinary
outpatient treatment program for fibromyalgia: a pilot study. Am J Phys Med
Rehabil 2003; 82:186.

10.
Biasi,
G, Manca, S, Manganelli, S, Marcolongo, R. Tramadol in the fibromyalgia
syndrome: a controlled clinical trial versus placebo. Int J Clin Pharmacol
Res 1998; 18:13.

11.
Bennett,
RM, Kamin, M, Karim, R, Rosenthal, N. Tramadol and acetaminophen
combination tablets in the treatment of fibromyalgia pain: a double-blind,
randomized, placebo-controlled study. Am J Med 2003; 114:537.

12.
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.

13.
Carette,
S, McCain, GA, Bell, DA, Fam, AG. Evaluation of amitriptyline in primary
fibrositis. A double-blind, placebo-controlled study. Arthritis Rheum 1986;
29:655.

14.
Bennett,
RM, Gatter, RA, Campbell, SM, et al. A comparison of cyclobenzaprine and
placebo in the management of fibrositis. A double-blind controlled study.
Arthritis Rheum 1988; 31:1535.

15.
Carette,
J, Bell, MJ, Reynolds, WJ, Haraoui, B, et al. Comparison of amitriptyline,
cyclobenzaprine, and placebo in the treatment of fibromyalgia. A
randomized, double-blind clinical trial. Arthritis Rheum 1994; 37:32.

16.
Tofferi,
JK, Jackson, JL, O'Malley, PG. Treatment of fibromyalgia with
cyclobenzaprine: a meta-analysis. Arthritis Rheum 2004; 51:9.

17.
Arnold,
LM, Keck, PE Jr, Welge, JA. Antidepressant treatment of fibromyalgia. A
meta-analysis and review. Psychosomatics 2000; 41:104.

18.
O'Malley,
PG, Balden, E, Tomkins, G, et al. Treatment of fibromyalgia with
antidepressants: a meta-analysis. J Gen Intern Med 2000; 15:659.

19.
Reynolds,
WJ, Moldofsky, H, Saskin, P, Lue, FA. The effects of cyclobenzaprine on
sleep physiology and symptoms in patients with fibromyalgia. J Rheumatol
1991; 18:452.

20.
Quimby,
LG, Gratwick, GM, Whitney, CD, Block, SR. A randomized trial of
cyclobenzaprine for the treatment of fibromyalgia. J Rheumatol Suppl 1989;
19:140.

21.
Goldenberg,
DL, Mayskiy, M, Mossey,CJ, et al. A randomized, double-blind crossover
trial of fluoxetine and amitriptyline in the treatment of fibromyalgia.
Arthritis Rheum 1996; 39:1852.

22.
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.

23.
Wolfe,
F, Cathey, MA, Hawley, DJ. Double-blind placebo controlled trial of
flluoxetine in fibromyalgia. Scand J Rheumatol 1994;23:255.

24.
Patkar,
AA, Masand, PS, Krulewicz, S, et al. A randomized, controlled, trial of
controlled release paroxetine in fibromyalgia. Am J Med 2007; 120:448.

25.
Nishikai, M, Akiya, K. Fluvoxamine therapy for fibromyalgia. J
Rheumatol 2003; 30:1124.

26.
Anderberg,
UM, Marteinsdottir, I, von Knorring, L. Citalopram in patients with
fibromyalgia--a randomized, double-blind, placebo-controlled study. Eur J
Pain 2000; 4:27.

27.
Norregaard,
J, Volkmann, H, Danneskiold-Samsoe, B. A randomized controlled trial of
citalopram in the treatment of fibromyalgia. Pain 1995; 61:445.

28.
Vitton,
O, Gendreau, M, Gendreau, J, et al. A double-blind placebo-controlled trial
of milnacipran in the treatment of fibromyalgia. Hum Psychopharmacol 2004;
19 Suppl 1:S27.

29.
Gendreau,
RM, Thorn, MD, Gendreau, JF, et al. Efficacy of milnacipran in patients
with fibromyalgia. J Rheumatol 2005; 32:1975.

30.
Arnold,
LM, Lu, Y, Crofford, LJ, et al. A double-blind, multicenter trial comparing
duloxetine with placebo in the treatment of fibromyalgia patients with or
without major depressive disorder. Arthritis Rheum 2004; 50:2974.

31.
Arnold,
LM, Rosen, A, Pritchett, YL, et al. A randomized, double-blind,
placebo-controlled trial of duloxetine in the treatment of women with
fibromyalgia with or without major depressive disorder. Pain 2005; 119:5.

32.
Russell,
IJ, Mease, PJ, Smith, TR, et al. 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 2008; 136:432.

33.
Sayar,
K, Aksu, G, Ak, I, Tosun, M. Venlafaxine treatment of fibromyalgia. Ann
Pharmacother 2003; 37:1561.

34.
Arnold,
LM, Goldenberg, DL, Stanford, SB, et al. Gabapentin in the treatment of
fibromyalgia: a randomized, double-blind, placebo-controlled, multicenter
trial. Arthritis Rheum 2007; 56:1336.

35.
Crofford,
LJ, Rowbotham, MC, Mease, PJ, et al. Pregabalin for the treatment of
fibromyalgia syndrome: results of a randomized, double-blind,
placebo-controlled trial. Arthritis Rheum 2005; 52:1264.

36.
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.

37.
Vaeroy,
H, Abrahamsen, A, Forre, O, Kass, E. Treatment of fibromyalgia (fibrositis
syndrome): a parallel double blind trial with carisoprodol, paracetamol and
caffeine (Somadril comp) versus placebo. Clin Rheumatol 1989; 8:245.

38.
Scharf,
MB, Baumann, M, Berkowitz, DV. The effects of sodium oxybate on clinical
symptoms and sleep patterns in patients with fibromyalgia. J Rheumatol
2003; 30:1070.

39.
Bennett,
RM, Clark, SC, Walczyk, J. A randomized, double-blind, placebo-controlled
study of growth hormone in the treatment of fibromyalgia. Am J Med 1998;
104:227.

40.
Finckh,
A, Berner, IC, Aubry-Rozier, B, So, AK. A randomized controlled trial of
dehydroepiandrosterone in postmenopausal women with fibromyalgia. J
Rheumatol 2005; 32:1336.

41.
Caruso,
I, Sarzi Puttini, P, Cazzola, M, Azzolini, V. Double-blind study of
5-hydroxytryptophan versus placebo in the treatment of primary fibromyalgia
syndrome. J Int Med Res 1990; 18:201.

42.
Muller,
W, Stratz, T. Results of the intravenous administration of tropisetron in
fibromyalgia patients. Scand J Rheumatol Suppl 2000; 113:59.

43.
Spath,
M, Stratz, T, Neeck, G, et al. Efficacy and tolerability of intravenous
tropisetron in the treatment of fibromyalgia. Scand J Rheumatol 2004;
33:267.

44.
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.

45.
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.

46.
Sewitch,
MJ, Dobkin, PL, Bernatsky, S, et al. Medication non-adherence in women with
fibromyalgia. Rheumatology (Oxford) 2004; 43:648.

47.
Assefi,
NP, Sherman, KJ, Jacobsen, C, et al. A randomized clinical trial of
acupuncture compared with sham acupuncture in fibromyalgia. Ann Intern Med
2005; 143:10.

48.
Busch,
A, Schachter, CL, Peloso, PM, Bombardier, C. Exercise for treating
fibromyalgia syndrome (Cochrane Review). Cochrane Database Syst Rev 2002;
:CD003786.

49.
Jones,
KD, Burckhardt, CS, Clark, SR, et al. A randomized controlled trial of
muscle strengthening versus flexibility training in fibromyalgia. J
Rheumatol 2002; 29:1041.

50.
Ferraccioli,
G, Ghirelli, L, Scita, F, et al. EMG-biofeedback training in fibromyalgia
syndrome. J Rheumatol 1987; 14:820.

51.
Hassett,
AL, Radvanski, DC, Vaschillo, EG, et al. A pilot study of the efficacy of
heart rate variability (HRV) biofeedback in patients with fibromyalgia.
Appl Psychophysiol Biofeedback 2007; 32:1.

52.
Haanen,
HCM, Hoenderdos, HTW, van Romunde, LKJ, et al. Controlled trial of
hypnotherapy in the treatment of refractory fibromyalgia. J Rheumatol 1991;
18:72.

53.
Sephton,
SE, Salmon, P, Weissbecker, I, et al. Mindfulness meditation alleviates
depressive symptoms in women with fibromyalgia: results of a randomized
clinical trial. Arthritis Rheum 2007; 57:77.

54.
Goldenberg, DL, Kaplan, KH, Nadeau, MG, et al. A controlled study
of a stress-reduction, cognitive-behavioral treatment program in
fibromyalgia. J Musculoskeletal Pain 1994; 2:53.

55.
Edinger,
JD, Wohlgemuth, WK, Krystal, AD, Rice, JR. Behavioral insomnia therapy for
fibromyalgia patients: a randomized clinical trial. Arch Intern Med 2005;
165:2527.

56.
White,
KP, Nielson, WR. Cognitive behavioral treatment of fibromyalgia syndrome: A
follow-up assessement. J Rheumatol 1995; 22:717.

57.
Hadhazy,
VA, Ezzo, J, Creamer, P, Berman, BM. Mind-body therapies for the treatment
of fibromyalgia. A systematic review. J Rheumatol 2000; 27:2911.

58.
Martin,
DP, Sletten, CD, Williams, BA, Berger, IH. Improvement in fibromyalgia
symptoms with acupuncture: Results of a randomized controlled trial. Mayo
Clin Proc 2006; 81:749.

59.
Mayhew,
E, Ernst, E. Acupuncture for fibromyalgia--a systematic review of
randomized clinical trials. Rheumatology (Oxford) 2007; 46:801.

60.
Offenbacher,
M, Stucki, G. Physical therapy in the treatment of fibromyalgia. Scand J
Rheumatol Suppl 2000; 113:78.

61.
Bennett,
RM, Burckhardt, CS, Clark, SR, et al. Group treatment of fibromyalgia: A 6
month outpatient program. J Rheumatol 1996; 23:521.

62.
Sarzi-Puttini, P, Buskila, D, Carrabba, M, et al. Treatment
strategy in fibromyalgia syndrome: Where are we now?. Seminars Arthritis
Rheum 2008 In press.

63.
Hooten,
WM, Townsend, CO, Sletten, CD, et al. Treatment outcomes after
multidisciplinary pain rehabilitation with analgesic medication withdrawal
for patients with fibromyalgia. Pain Med 2007; 8:8.

64.
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.

65.
Fitzcharles,
MA, Costa, DD, Poyhia, R. A study of standard care in fibromyalgia
syndrome: a favorable outcome. J Rheumatol 2003; 30:154.

66.
White,
KP, Speechley, M, Harth, M, et al. Comparing self-reported function and
work disability in 100 community cases of fibromyalgia syndrome versus
controls in London, Ontario. Arthritis Rheum 1999; 42:76.

67.
Nielson,
WR, Jensen, MP. Relationship between changes in coping and treatment
outcome in patients with fibromyalgia syndrome. Pain 2004; 109:233.

68.
Gracely,
RH, Geisser, ME, Giesecke, T, et al. Pain catastrophizing and neural
responses to pain among persons with fibromyalgia. Brain 2004; 127:835.

69.
Carville,
SF, Arendt-Nielsen, S, Bliddal, H, et al. EULAR evidence-based
recommendations for the management of fibromyalgia syndrome. Ann Rheum Dis
2008; 67:536.

© 2009 UpToDate, Inc. All rights reserved. | Subscription and License Agreement |Support Tag:
[ecapp0504p.utd.com-207.127.241.2-55C052FDC3-3840]

Licensed to: NYC Health and
Hospitals Corp.

Help
improve UpToDate. Did UpToDate answer your question? Yes
No

UpToDate performs a continuous review of over 400
journals and other resources. Updates are added as important new information
is published. The literature review for version 16.3 is current through
October 2008; this topic was last changed on October 7, 2008. The next
version of UpToDate (17.1) will be released in March 2009.

LOG IN

FEEDBACK

ONLINE 16.3

Home | Contact us | About UpToDate | Careers | Help

New Search

Patient Info

What's New

Treatment
of fibromyalgia in adults

Find

Patient

Print

Email

Treatment
of fibromyalgia in adults

Clinical
manifestations and diagnosis of fibromyalgia in adults

Search
on "fibromyalgia"

Please
wait