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Studies regarding issues of Fibromyalgia
Fibromyalgia represents one of the most frequent musculoskeletal problems. This condition, associated with widespread pain, is characterized by a number of specific tender points, as well as such symptoms as tiredness, limb stiffness, depression and a lack of refreshing sleep. Patients suffering from fibromyalgia also can demonstrate temporo-mandibular disorders or muscular-fascial pain.
Sleep disturbances are more common in fibromyalgia patients. One study found that 55 percent of fibromyalgia patients suffered from sleep disturbances, and that these sleep disturbances were not related to pain. Alleviating insomnia with anti-depressant medication, melatonin and/or prescription sleep-inducing drugs could alleviate pain.
Anti-depressant drugs have been used with varying degrees of success in treating fibromyalgia. One European study showed that the combination of monoamine oxidase (MAO)-inhibiting drugs, along with 5-hydroxytryptophan, significantly improved fibromyalgia syndrome, whereas other anti-depressant treatments yielded poorer benefits. The doctors who conducted this study stated that a natural analgesic effect occurred when serotonin levels and norepinephrine receptors were enhanced in the brain. The monoamine oxidase-inhibiting drugs did produce some side effects.
European doctors combine 5-hydroxytryptophan with a decarboxylase inhibitor in order to make it available to produce serotonin in the brain. It is difficult for Americans to get 5-hydroxytryptophan with a pharmaceutical decarboxylase inhibitor. The vitamin-B6 Americans use also inhibits the ability of 5-hydroxytryptophan to enhance brain levels of serotonin.
A therapy for Americans to consider would be 3,000 mg a day of the amino acid l-tryptophan, which does not require a decarboxylase inhibitor to elevate serotonin in the brain. Since the FDA banned the sale of tryptophan in 1989, the drug Prozac may be an effective substitute. Some doctors suggest the use of Prozac specifically as a fibromyalgia therapy. Such nutrients as phenylalanine or tyrosine in doses of 1,500 mg a day could boost norepinephrine levels. Refer to the Phenylalanine and Tyrosine Precautions, before using this amino acid supplement.
The European anti-depressant drug S-adenosylmethionine (SAMe) has been shown in several published studies to be specifically effective as a therapy to reduce the chronic pain and depression associated with fibromyalgia. The suggested dose is 400 mg to 800 mg twice a day.
Epidemiological studies have shown that the tendency toward depression in patients with fibromyalgia may be a manifestation of a familial depressive spectrum disorder (alcoholism and/or depression in the family members), not simply a "reactive" depression secondary to pain and other symptoms.
Substantial overlap between chemical sensitivity, fibromyalgia and chronic fatigue syndrome exists. The latter two conditions often involve chemical sensitivity and may even be the same disorder. Those agents associated with symptoms and suspected of causing onset of chemical sensitivity with chronic illness include gasoline, kerosene, natural gas, pesticides (especially chlordane and chlorpyrifos), solvents, new carpet and other renovation materials, adhesives/glues, fiberglass, carbonless copy paper, fabric softener, formaldehyde and glutaraldehyde, carpet shampoos and other cleaning agents, isocyanates, combustion products (poorly vented gas heaters, overheated batteries, etc.), and medications (dinitrochlorobenzene for warts, intranasally packed neosynephrine, prolonged antibiotics and general anesthesia with petrochemicals, for example).
Multiple mechanisms of chemical injury that magnify response to exposures in chemically sensitive patients can include neurogenic inflammation, kindling and time-dependent neurologic sensitization and auto-immune activation.
A study of thyroid function showed that 63 percent of a group of fibromyalgia patients suffered from some degree of hypothyroidism. This percentage is much higher than for the general population. Fibromyalgia patients were shown either to suffer from a thyroid hormone deficiency or from cellular resistance to thyroid hormone. Refer to the Thyroid Deficiency protocol for suggestions that could correct a thyroid hormone defect as a possible underlying cause of fibromyalgia.
A study to ascertain the long-term natural history of fibromyalgia syndrome was conducted on a group of patients seen in an academic rheumatology referral practice. These patients were originally surveyed soon after onset of symptoms, and were again interviewed 10 years later. Of the original 39 patients, there were four deaths, and of the remaining 35 patients, 29 (83 percent) were re-interviewed. Mean age at the followup interview was 55 years, and mean duration of symptoms was 15.8 years.
All patients had persistence of the same fibromyalgia symptoms, although almost half (48 percent) had not seen a doctor for them in the last year. Moderate to severe pain or stiffness was reported in 55 percent of patients; moderate to a great deal of sleep difficulty was noted in 48 percent; and moderate to extreme fatigue was noted in 59 percent. These symptoms showed little change from earlier surveys. In 79 percent of the patients, medications still were being taken to control symptoms. Despite continuing symptoms, 66 percent of patients reported that symptoms were a little or a lot better than when first diagnosed. Fifty-five percent of patients said they felt well or very well in terms of symptoms, and only 7 percent felt they were doing poorly.
With the exception of sleep trouble, which was persistent, baseline survey symptoms correlated poorly with symptoms at the 10-year followup. The conclusion was that fibromyalgia symptoms last, on average, at least 15 years after illness onset. However, most patients experience some improvement in symptoms after fibromyalgia onset.

Fibromyalgia is Not A Mental Illness
By Janet Elizabeth Horton, B.G.S., Co-Manager of FIBROM-L, and
Susan Buckelew, Ph.D., Department of Physical Medicine Rehabilitation,
University of Missouri-Columbia
Has anyone ever implied thatyour pain is all in your head? If you have fibromyalgia the answer is verylikely to be yes! Whileresearch has provided much information over the last decade, there isstill much misunderstanding about this painful and at times disablingdisorder. Whether you are a health professional or a person whohas fibromyalgia, it is important to understand what fibromyalgia is andhow it can be effectively managed.
What is fibromyalgia?
Fibromyalgia syndrome (FMS) is a relatively common rheumatic disorder characterized bymuscle pain, stiffness and unrefreshing sleep. People with FMS may experience migraine headaches, irritable bowel syndrome, and other troublesome symptoms. While there are men who suffer from FMS, most of the estimated 10 million people with FMS in the United States are women.
Aren't people who have FMS really just depressed?
We used to think that people with FMS were clinically depressed, but research has not supported that assumption. While some people with FMS do experience depression, we now know that depression is not the cause.
If depression doesn't cause FMS, what does?
Sometimes FMS is precipitated by a specific event, such as an illness or an accident. At other times there are no precipitating events. We don't yet know why some people develop FMS while others do not. The current research path leads towards identifying a central, neurohormonal mechanism that predisposes some people to FMS. The non-restorative sleep associated with FMS appears to interfere with the production of hormones responsible for growth and muscle repair. This disruptive sleep pattern is identical to that of people who have Chronic Fatigue Syndrome, leading some researchers to believe they are closely related disorders.
How is FMS diagnosed?
FMS is the second most common diagnosis seen by rheumatologists (Wolfe, 1995). Rheumatologists are doctors who specialize in arthritis and an array of other diseases that affect the joints and soft tissues around them. In 1990, the American College of Rheumatology established criteria for the diagnosis of FMS. The criteria include the identification of specific tender points, fatigue and overall pain for more than six months.
If a person hurts all the time because of FMS, how can she know when something else is wrong?
Once a person is diagnosed and is appropriately managing her FMS, any dramatic changes in the amount of pain experienced should alert her to the possibility that something else may be wrong. She should not hesitate to seek a professional opinion from her internist or rheumatologist.
How is FMS treated?
The treatment of FMS presently is focused on improving restorative sleep through the use of medication, stress management, and conditioning exercise.
A person with FMS should consult a reputable rheumatologist or personal physician before stopping or starting medications or making any changes in how she approaches the treatment of her FMS. In general, NSAIDS such as ibuprofen are not very effective in FMS pain management, except where inflammation occurs due to injury. The use of alcohol, narcotics, or sleep-aids such as Halcion should be avoided. In the long run, they are injurious and ineffective.
Some doctors prescribe small amounts of amitriptyline, a drug used in the treatment of depression, in order to improve sleep. Amitriptyline is now known to reduce pain and improve sleep at lower dosages than are required to treat depression.
What can a person who has FMS do to cope with her symptoms?
It is very important to realize that no single approach to managing FMS is effective by itself. Some find it helpful to learn cognitive-behavioral techniques for stress management. Biofeedback training has also been used with some success. In addition to treating sleep problems and managing stress, people with FMS are encouraged to begin a very gradual program of flexibility training and aerobic exercise.
People who have FMS can easily become deconditioned. It is unlikely that anybody would feel like exercising when they always have flu-like symptoms! However, the great benefit of even a gentle exercise program is an improvement in the quality of sleep. It is during deep, "restorative" sleep that the body produces the hormones required to repair muscle tissues.
Conditioning exercise also reduces the likelihood of injuring muscle tissues. The challenge for the person with FMS is in the gradual approach to exercise. Doing too much, too soon can hurt deconditioned muscles. That just creates more pain and fatigue. A helpful approach is to learn some gentle stretches that may be used throughout the day, especially before and after walking.
Exercise trainers encourage inactive people with FMS to begin by walking for only five minutes per day. The walking does not need to be vigorous, and it does not need to "feel like exercise." The point is to begin slowly. Adding a few minutes of exercise each week to the amount of daily aerobic exercise makes it possible to increase activity without causing injury or increasing pain.
Is there any support for people with FMS, their families or their friends?
Many cities now have chronic pain support groups. Some have fibromyalgia and chronic fatigue syndrome support groups. The Fibromyalgia Network maintains information about support groups and knowledgeable physicians in many areas.
Does anyone publish reliable information that can be given to a family doctor who has outdated opinions about FMS?
Good information is important for people with chronic diseases as well as for their doctors. The Arthritis Foundation is preparing an updated version of a pamphlet about FMS. The foundation is also testing and developing a Fibromyalgia Self-Help Course that is similar to the Arthritis Self-Help Course developed by Kate Lorig, Ph.D.

Fibromyalgia Syndrome
Carol A. Beals, M.D.
Affect more than 3% of women in the general population
Are the second most common arthritic illness seen today
Cause significant disability similar to that of rheumatoid arthritis
Tenderness condition
Sleep disturbance
Numbness, tingling
Chronic headaches
Irritable bowel syndrome
Irritable bladder syndrome
Fatigue: 77%
Sleep disturbance
Morning stiffness: 75%
Irritable bowel syndrome: 37%
Irritable bladder syndrome: 85%
Psychologic abnormalities
Reactive hyperemia
Tender points
Hypothesis: central pain derangement
CNS dysfunction
Nutritional hypothesis: Swedish studies
Magnesium & Malic acid
Limbrio system abnormalities
Sleep disturbance: Elavil, Flexoril, Sinequane, etc.
Manage mechanical stress: ergonomics
Exercise/physical decondition
Psychological problems: therapy, drugs
Injection trigger points
Pain therapy: SSRI (Paxil, Zoloft, Prozac)
Nimotop: calcium channel blocker
Education: support group
Alternative approaches

Fibromyalgia Syndrome: Blueprint for a Reliable Diagnosis

By:Muhammad Yunua
Abstract: Fibromyalgia syndrome (FMS) is usually indicated by symptoms such as fatigue, poor sleep, paresthesias and chronic, widespread musculoskeletal pain. FMS can also cause problems such dysmenorrhea, headaches and restless legs syndrome so the presence of another disease does not rule out FMS. Individuals suffering from FMS should have a history of widespread pain for at least three months. There should also be at least 11 tender points out of the 18 sites on digital palpation. FMS is not a variant of depression but psychological factors can cause aggravation.
Can fibromyalgia be reliably diagnosed?
Isn't it a variation of depression?
What is at the root of the pain?
Can we do anything to help patients with fibromyalgia?
As a frequent lecturer on fibromyalgia syndrome (FMS), these are among the queries that I hear most often. These questions are important in light of the fact that FMS is common in both rheumatology and primary care settings.1 When the diagnosis is based on American College of Rheumatology (ACR) criteria, the prevalence of FMS in this country is 2%.2 However, the percentage is probably much higher when the diagnosis is based on less stringent criteria often used in clinical practice. FMS is more common than RA and causes a comparable degree of disability.3
I will address the concerns physicians most often have about FMS in a two-part series. I will begin by describing the biophysiologic mechanisms and clinical presentation of FMS and how to make the diagnosis. In the second part, I will focus on current approaches to managing this painful and often frustrating condition.
DMK Note: The second part, concerning management of FMS, is not included in this article.
The Biophysiologic Mechanisms of FMS
Recent research has shed interesting light on the biophysiologic mechanisms of FMS. These mechanisms involve neuroendocrine dysfunction with several interacting variables, including genetics, psychological factors, stress, and poor sleep.
The central feature of fibromyalgia is pain. According to controlled studies, this pain cannot be explained by peripheral pathology.1,4 It has recently become clear that the main problem in FMS is probably an aberration of the central pain mechanism, which involves neuroendocrine and immune dysfunctions. However, FMS may be initially triggered by peripheral factors, such as trauma (as in an automobile accident) or peripheral inflammatory arthritis, perhaps in a genetically predisposed person.5,6
The biophysiologic mechanisms of FMS are multifactorial and are probably very complex.5,6 Recent studies have demonstrated abnormalities in several neurotransmitters in patients with FMS (Table 1). These include an increase in CSF substance P level (involved in pain transmission)7 and a decrease in serum serotonin levels (involved in pain inhibition and sleep physiology).8
Several neurotransmitters interact with the hypothalamic-pituitary-adrenal axis, which is abnormal in FMS.5,6,9-12 Decreased cerebral blood flow in caudate nucleus and thalamus (demonstrated by single-photon emission computed tomography13), along with other neurotransmitter abnormalities, can account for the pain associated with FMS.
Important contributing mechanisms include nonrestorative sleep (disturbed stage 4 sleep by electroencephalography),14 psychological factors,5 and muscle deconditioning (usually secondary to pain). Genetic factors seem to play a role in FMS. I and others have noted familial aggregation of FMS. In our recently completed study of 40 multicase families with FMS, we found a significant linkage between FMS and HLA haplotypes.
The Clinical Picture
FMS is characterized by a constellation of symptoms and the presence of multiple tender points. The typical patient with FMS is a middle-aged woman, although the syndrome can affect children and the elderly.1 Only 10% of patients with FMS are men.
The spectrum of clinical manifestations that may be present in FMS is wide. The characteristic symptoms are chronic, widespread aching and stiffness in muscles and joints; poor sleep and fatigue; a subjective feeling of swelling in the soft tissues, including periarticular areas and muscles; and paresthesia (Table 2). The most common sites of pain are the neck, back, shoulders, pelvic girdle areas, and hands, but any part of the body may be involved, often in a migratory fashion.
Paresthesia is most common in the extremities, usually in a nonradicular distribution. However, patients sometimes describe a radiating numbness, as occurs in sciatica. Patients with paresthesia or subjective tissue swelling are not more likely than others to have psychological problems.
Common associated features include irritable bowel syndrome, tension-type headaches or migraine, restless legs syndrome, and periodic limb movement disorder. Anxiety, depression, and mental stress are present in 30% to 40% of patients who have FMS.1-3,5,15 In most cases, these factors are probably secondary to chronic pain, but they also contribute to pain in a vicious cycle. Of note, FMS is not a variant of depression.5
The Dysfunctional Spectrum Syndrome
Although the characteristic clinical features of FMS * widespread pain, fatigue, and poor sleep * have been known since the middle of this century, the fact that FMS is part of a wider spectrum of conditions with many other associated features has only recently been recognized. A number of controlled studies have shown that FMS is significantly associated with irritable bowel syndrome, tension-type headaches, migraine, primary dysmenorrhea, chronic fatigue syndrome, temporomandibular dysfunction, regional fibromyalgia ("myofascial pain syndrome"), restless legs syndrome, and periodic limb movement disorder.5
These disorders form a spectrum of conditions that I refer to as "dysfunctional spectrum syndrome" (DSS).5 The components of DSS share several features, such as:
Predominant (or exclusive) involvement of women
Absence of "hard" physical signs and pathologic changes in the peripheral tissues
Lack of a specific laboratory test for diagnosis
The recognition of DSS is useful because it helps avoid unnecessary laboratory tests. The underlying "common glue" that binds these conditions is probably a neuroendocrine-immune dysfunction, such as serotonin deficiency.
Note that DSS is biologically distinct from depression. Although a sub-group of patients with DSS have depression, most do not.5
Physical Examination
Patients with FMS usually look healthy. Their joints appear normal, and further musculoskeletal examination indicates no objective joint swelling, although there may be tenderness on palpation. In addition, muscle strength, sensory functions, and reflexes are normal despite the patient's complaints of acral numbness.
The most striking and unique finding in FMS is the presence of multiple tender points. Blind studies have established that these tender points are both quantitatively and qualitatively different from those observed in healthy persons and in those with other chronic pain conditions, such as RA.15 Patients with FMS not only hurt more, but they also hurt in many more places than other patients.

Morning fatigue is a sensitive indicator of nonrestorative sleep.
No range available; data obtained from a single study. From Yunus MB, Masi AT.1
Successful examination of tender points depends on knowing where to palpate and how much pressure to apply. Although patients with FMS may be tender in many areas, examination in 18 sites provides the most valuable diagnostic information, as delineated in the ACR guidelines.15 Accurate localization of these specific sites is important.
Apply pressure using the tip of the thumb or index or middle finger (whichever feels most natural to you) with a force of approximately 4 kg. This is roughly the amount of pressure required to blanch the nail of the examining finger when pressed against the patient's forehead. (Such pressure does not usually produce pain in the forehead.)
Teach the patient to distinguish between pressure and pain, since only pain meets the criteria for a tender point. I use gradually increasing pressure in the lateral epicondylar area and ask the patient to report as soon as pressure changes into pain.
A small subgroup of patients with FMS have tenderness virtually everywhere or are sensitive to even bare touch. Remember, these persons do not necessarily have serious psychological problems.
Laboratory Tests
No laboratory tests are currently available for diagnosing FMS. However, studies indicate that the frequency of abnormal findings on neuroendocrine tests, such as single-photon emission computed tomography and sleep electroencephalography, is significantly higher in patients with FMS than in controls.
The results of routine tests, including CBC count, ESR, muscle enzymes, electrolytes, and roentgenograms, are normal in patients with FMS who do not have co-morbid disease. Among patients with FMS, the prevalence of positive antinuclear antibodies (ANAs) or thyroid function abnormalities is not greater than that among healthy controls.1 ANA is present (usually in a low titer) in about 10% of patients with FMS.
I do not generally order thyroid function tests, except when I suspect hypothyroidism and in cases of severe fatigue. Hypothyroidism, when present, is almost always coincidental and not the cause of FMS; full replacement of thyroid hormone does not affect pain or the number of tender points, although it may somewhat diminish the patient's fatigue.
Routine sleep EEG studies are unnecessary in patients with FMS. However, these studies are indicated if you suspect restless legs syndrome, periodic limb movement disorder, or any sleep abnormalities (such as sleep apnea).
Clinching the Diagnosis
Several diseases may mimic FMS, but they can usually be diagnosed by their typical features * for example, arthritis by objective joint swelling, polymyalgia rheumatica by an elevated ESR, and disc herniation by neurologic and radiologic findings. The presence of ANA, joint pain, and fatigue may raise the suspicion of SLE. Other characteristics of SLE, such as objective joint swelling, pleural effusion, rash, renal disease, positive anti-DNA or anti-Sm antibodies, and low serum C3 or C4 levels, are absent in patients with FMS.
Remember, however, that the presence of another disease, such as RA or SLE, does not rule out FMS. FMS is diagnosed by its own characteristic features. The ACR criteria for FMS are disarmingly simple (Table 4). They include widespread pain and the presence of at least 11 tender points among 18 sites, as discussed above.
Does a patient have FMS if he or she has characteristic symptoms but only 7 to 10 tender points? To answer this, remember that the ACR criteria, while clinically useful, were developed primarily for uniform case classification for researchers.
Some patients have what I call "incomplete fibromyalgia." They have typical symptoms but fewer than 11 tender points, or they have 11 or more tender points but with pain limited to a region, such as the neck, arms, or upper back. Be sure to ask patients if they have pain in areas other than the one they are concerned about. Patients with incomplete fibromyalgia should be treated as having FMS.
If the patient with FMS has a concomitant disease or condition, such as osteoarthritis, RA, or disc herniation, treat the concomitant problem separately. Extensive clinical experience has shown that when FMS and RA coexist * as they frequently do * satisfactory treatment of RA does not alleviate the widespread pain, fatigue, and tender points of FMS.
Table 1
Abnormalities in Neurohormonal Function in FMS
Low serum tryptophan level16,17
Low transport ratio of serum tryptophan17
Low serum serotonin level8,18,19
Low CSF 5HIAA level20,21
Decreased imipramine binding (v depression)22
Low CSF MHPG and homovanillic acid levels21
Elevated CSF substance P level6,23
Loss of diurnal fluctuation of cortisol level9,12
Increased prolactin response to TRH10
Increased ACTH release by CRH with normal cortisol response11
Decreased net integrated cortisol response to CRH; low urinary free cortisol level12
Decreased plasma neuropeptide Y level12
Decreased serum somatomedin C level24
Alpha intrusion of non-REM sleep by electroencephalography14,25
Decreased blood flow in thalamus, caudate nucleus, and cortex by SPECT13
HIAA, hydroxyindoleacetic acid; MHPG, 3-methoxy-4-hydroxyphenylglycol; TRH, thyrotropin-releasing hormone; ACTH, adrenocorticotropin hormone; CRH, corticotropin-releasing hormone; REM, rapid eye movement; SPECT, single-photon emission computed tomography.
Related Article
Table 4:
ACR Criteria for Classifying Fibromyalgia Syndrome(*)
1. History of widespread pain
Pain is considered widespread when it occurs in the left and right sides of the body, and above and below the waist. Axial skeletal pain (cervical spine, anterior chest, thoracic spine, or low back) must also be present. Shoulder and buttock pain is considered pain for each involved side. "Low back" pain is considered lower segment pain. Widespread pain must have been present for at least 3 months.
2. Pain in 11 of 18 tender point sites on digital palpation(**)
Pain is assessed bilaterally at the following sites:
Occiput. At the suboccipital muscle insertions
Low cervical. At the anterior aspects of the intertransverse spaces at C5-C7
Trapezius. At the midpoint of the upper border
Supraspinatus. At origins, above the scapular spine near the medial border
Second rib. At the second costochondral junctions, just lateral to the junctions on upper surfaces
Lateral epicondyle. 2 cm distal to the epicondyles
Gluteal. In upper outer quadrants of buttocks in anterior fold of muscle
Greater trochanter. Posterior to the trochanteric prominence
Knee. At the medial fat pad proximal to the joint line
ACR, American College of Rheumatology
*Patients are classified as having fibromyalgia if both criteria 1 and 2 are met. The presence of a second clinical disorder does not exclude the diagnosis of fibromyalgia.
** Digital palpation should be performed with an approximate force of 4 kg. For a tender point to be considered positive, the patient must state that the palpation was painful; "tender" is not considered "painful."
From Wolfe F et al.15
1. Yunus MB, Masi AT. Fibromyalgia, restless legs syndrome, periodic limb movement disorder and psychogenic pain. In: McCarty DJ Jr, Koopman WJ, eds. Arthritis and Allied Conditions: A Textbook of Rheumatology. Philadelphia: Lea & Febiger; 1992:1383-1405.
2. Wolfe F, Ross K, Anderson J, et al. The prevalence and characteristics of fibromyalgia in the general population. Arthritis Rheum. 1995; 38:19-28.
3. Cathey MA, Wolfe F, Kleinheksel SM. Functional ability and work status in patients with fibromyalgia. Arthritis Care Res. 1988;1:85-88.
4. Yunus MB. Muscle biopsy findings in primary fibromyalgia and other forms of nonarticular rheumatism. Rheum Dis Clin North Am. 1989; 15:115-134.
5. Yunus MB. Psychological aspects of fibromyalgia syndrome - a component of the dysfunctional spectrum syndrome. In: Masi AT, ed. Bailliere's Clinical Rheumatology: Fibromyalgia and Myofascial Pain Syndromes. London: WB Saunders Co; 1994:811-837.
6. Yunus MB. Towards a model of pathophysiology of fibromyalgia: aberrant central pain mechanisms with peripheral modulation. J Rheumatol. 1992; 19:846-850.
7. Russell IJ, Orr MD, Littman B, et al. Elevated cerebrospinal fluid levels of substance P in patients with the fibromyalgia syndrome. Arthritis Rheum. 1904; 37:1593-1601.
8. Russell IJ, Michalek JE, Vipraio GA, et al. Platelet 3H-imipramine uptake receptor density and serum serotonin levels in patients with fibromyalgia/fibrositis syndrome. J Rheumatol. 1992; 19:104-109.
9. McCain GA. Nonmedical treatment in primary fibromyalgia. Rheum Dis Clin North Am. 1989; 15:73-90.
10. Ferraccioli G, Cavalieri F, Salaffi F, et al. Neuroendocrinologic findings in primary fibromyalgia (soft tissue chronic pain syndrome) and in other chronic rheumatic conditions (rheumatoid arthritis, low back pain). J Rheumatol. 1990; 17:869-873.
11. Griep EN, Boersma JW, deKloet ER. Altered reactivity of the hypothalamic-pituitary-adrenal axis in the primary fibromyalgia syndrome. J Rheumatol. 1993; 20:469-474.
12. Crofford LJ, Pillemer SR, Kalogeras KT, et al. Hypothalamic-pituitary-adrenal axis perturbations in patients with fibromyalgia. Arthritis Rheum. 1994; 37:1583-1592.
13. Mountz JM, Bradley LA, Modell JG, et al. Fibromyalgia in women: abnormalities of regional cerebral blood flow in the thalamus and the caudate nucleus are associated with low pain threshold levels. Arthritis Rheum. 1995; 38:926-938.
14. Moldofsky H, Scarisbrick P, England R, Smythe H. Musculoskeletal symptoms and non-REM sleep disturbance in patients with fibrositis syndrome and healthy subjects. Psychosom Med. 1975; 37:341-351.
15. Wolfe F, Smythe HA, Yunus MB, et al. The American College of Rheumatology 1990 criteria for classification of fibromyalgia: Report of the Multi-center Criteria Committee. Arthritis Rheum. 1990; 33:160-172.
16. Russell IJ, Michalek JE, Vipraio GA, et al. Serum amino acids in fibrositis/fibromyalgia syndrome. J Rheumatol. 1989; 16(suppl 19):158-163.
17. Yunus MB, Dailey JW, Aldag JC, et al. Plasma tryptophan and other amino acids in primary fibromyalgia: a controlled study. J Rheumatol. 1992; 19:90-94.
18. Russell IJ, Vipraio GA, Lopez YG. Serum serotonin in fibromyalgia syndrome, rheumatoid arthritis, osteoarthritis and healthy normal controls. Arthritis Rheum. 1993; 36(suppl):S222
19. Hrycaj P, Stratz P, Muller W. Platelet 3H-imipramine uptake receptor density and serum serotonin levels in patients with fibromyalgia/fibrositis syndrome. J Rheumatol. 1993; 20:1986-1987.
20. Houvenagel E, Forzy G, Cortet B, Vincent G. 5-hydroxy indole acetic acid in cerebrospinal fluid in fibromyalgia. Arthritis Rheum. 1990; 33(suppl):S55.
21. Russell IJ, Vaeroy H, Javors M, Nyberg F. Cerebrospinal fluid biogenic amine metabolites in fibromyalgia/fibrositis syndrome and rheumatoid arthritis. Arthritis Rheum. 1992; 35:550-556.
22. Kravitz HM, Katz R, Kkot E, et al. Biochemical clues to fibromyalgia-depression link: imipramine binding in patients with fibromyalgia or depression and in healthy controls. J Rheumatol. 1992; 19:1428-1432.
23. Vaeroy H, Helle R, Forre O, et al. Elevated CSF levels of substance P and high incidence of Raynaud's phenomenon in patients with fibromyalgia: new features for diagnosis. Pain. 1988; 32:21-26.
24. Bennett RM, Clark SR, Campbell SM, Burckhardt CS. Low levels of somatomedin C in patients with fibromyalgia syndrome. Arthritis Rheum. 1992; 35:1113-1116.
25. Carette S, Oakson G, Guimont C, Steriade M. Sleep electroencephalography and the clinical response to amitriptyline in patients with fibromyalgia. Arthritis Rheum. 1995; 38:1211-1217.
26. Yunus MB. Fibromyalgia syndrome: clinical features and spectrum. J Musculoskel Pain. 1994; 2:5-21.
Dr. Yunus is professor of medicine in the section of rheumatology at the University of Illinois College of Medicine at Peoria. He is well known for his research, patient care, and teaching on fibromyalgia syndrome.
Copyright * 1996 Cliggott Publishing Company. Copyright * 1997 Information Access Company.

Fibromyalgia Syndrome: Is There Any Effective Therapy?
From:Consultant. Jun. 1996; 36(6)
Abstract: Fibromyalgia syndrome (FMS) can be treated using a variety of nonpharmacologic and pharmacologic therapies. A warm empathetic attitude on the part of the physician is critical for building rapport. For mild cases of FMS, patient education, exercise, physical therapy, simple analgesics and tricyclic antidepressants can be effective. In more severe cases, higher doses of drugs in combination with tricyclic agents and serotonin uptake inhibitors may be required. Acetaminophen and low-dose codeine may also be necessary for recalcitrant symptoms or acute flare-ups.
While the management of fibromyalgia syndrome (FMS) is more of an art than a science at this time, a better understanding of this potentially disabling condition has been reached in recent years. We now know that FMS is not simply stress or depression, and that psychological factors are only one component of this syndrome.
In fact, many different factors interact to cause symptoms, and their relative importance varies from patient to patient.1 Thus, FMS requires both a multifaceted and an individualized approach to treatment. Although most patients with FMS continue to have chronic pain, appropriate management can improve function and quality of life for many.
The Components of Therapy
The most important elements of the management of FMS are shown in Table 1.
Table 1: Components of Therapy for Fibromyalgia Syndrome
A positive and empathetic physician
Firm diagnosis
Patient education
Reassurance that the pain is real but does not cause tissue damage
Individualized therapy, considering severity and relative contribution of aggravating factors
Addressing psychological factors (anxiety, stress, and depression); referral to a mental health professional in difficult cases
Behavior modification through cognitive behavior therapy, focusing on positive attitude and self-responsibility
Improvement of sleep quality
Gradual increase of physical activities to achieve physical fitness
Physical/occupational therapy, including flexibility and muscle-strengthening exercises
Other nonpharmacologic approaches (electromyographic biofeedback, meditation, hypnotherapy, electroacupuncture)
Simple analgesics (acetaminophen and low-dose NSAIDs)
Serotonergic/noradrenergic (mostly antidepressant) medications; anxiolytic drugs (in patients with significant anxiety)
Myofascial therapy, including injection of symptomatic tender points with a local anesthetic
Multidisciplinary approach under "one umbrella," incorporating cognitive behavior therapy, physical fitness exercises, relaxation techniques, and other forms of therapy
A Positive and Empathetic Physician
The management of FMS begins with your first contact with the patient. A warm, empathetic attitude is readily discerned by the patient and builds rapport immediately. Many patients with FMS are defensive because of unpleasant experiences with previous noncaring physicians, so it is particularly important that you reassure them that you understand their suffering and are willing to help.2
Firm Diagnosis
FMS can be reliably diagnosed by clinical characteristics alone. Clearly convey the certainty of your diagnosis and do not imply that the problem is "all in the patient's head." This does not mean minimizing significant psychological problems, if present, but depicting them as aggravating factors.
Patient Education
Patient education is an integral part of management. A patient information sheet or booklet is always useful. Use layperson's language to explain what is known about the biophysiologic mechanisms and contributory factors of FMS. Neuroendocrine dysfunction, which includes a deficiency of serotonin and an excess of substance P, may be simply explained as "chemical imbalance." Explain that this imbalance is different from that in psychiatric illnesses, such as depression.
Encourage patients to accept that their pain is likely to remain chronic. They should focus on being as functional and active as possible, rather than focusing on symptoms. Tell them that their active participation in therapy is vital to their success.
Many patients are concerned about having a serious illness, such as SLE or cancer. This is often caused by a "positive test result," such as the presence of antinuclear antibodies. These patients need special reassurance. I usually tell my patients "I fully understand your genuine suffering, but please be assured that fibromyalgia will not cripple you or cause tissue damage." Avoid using the term "benign pain"; this term is particularly objectionable to patients who have disabling pain.
Individualized Therapy
The severity of symptoms and aggravating factors vary from patient to patient. Consequently, "one-size treatment" does not fit all patients. Carefully evaluate these factors in each patient, and address the pertinent ones. Most patients need counseling on physical fitness and sleep; however, FMS can occur in physically fit persons and in those with no sleep difficulties.
The concomitant presence of another disease, such as RA, migraine, irritable bowel syndrome, or hypothyroidism, may augment symptoms and should be appropriately managed. Psychological factors are very important in some patients with FMS and require special attention.
Make every attempt to keep the patient employed. A working patient has less time to focus on pain, and employment provides a sense of self-worth, which is particularly important in patients with chronic illness. Job modifications, changes in ergonomics, and a reduction in work hours may be necessary, however. When appropriate, work with the patient's supervisors, educating them about FMS and discussing aggravating factors, such as shift work. Patients are more likely to stay employed if they perceive that their physician and employer are working together to help them.
Walking and stretching for a few minutes after sitting for 2 to 3 hours helps alleviate pain and stiffness. Recommend against frequent bending and weight lifting. "Return to work" centers often provide a valuable service by evaluating ergonomic factors, teaching proper body mechanics, and instituting a program of gradual work hardening for the same or a modified job. It is important that you closely interact with these centers.
Addressing Psychological Factors
Pain, irrespective of its cause, is significantly influenced by psychological factors and is accentuated by anxiety, stress, and depression. While these factors are better evaluated by validated questionnaires,1 simple questions can provide valuable information. You might ask: "Are you an anxious person or do you have worries?" "Do you have mental stress?" "Do you feel depressed, sad, or low in spirits?"
Significant psychological distress can be helped by emotional support coupled with pharmacologic agents, such as antidepressant and anxiolytic drugs. While the pain of FMS usually responds to low doses of serotonergic/noradrenergic medications, the presence of significant depression requires higher doses. Only a minority of patients need referral to a psychologist or psychiatrist.
Not all patients with severe pain or fatigue have significant psychological problems. Many of them, however, have poor coping skills; they wrongly believe that their symptoms will cripple them and that they have no control. These patients may particularly benefit from cognitive behavior therapy.
Cognitive Behavior Therapy
Advise your patient that behavioral changes are essential to the successful management of any chronic condition. In patients with severe symptoms, cognitive behavior therapy may be helpful. This can be provided by a psychotherapist * either individually or in a group. In a group format, the therapist usually meets weekly with 10 to 12 patients for 3 to 6 months, with attention to individual needs (including psychotherapy). Such therapy can reduce pain, decrease mental stress, augment coping skills, enhance physical functioning, and improve overall quality of life.3,4
The goal of cognitive behavior therapy is to encourage a positive, "I can help my condition" attitude in patients and impart a sense of optimism and control. This approach minimizes the passive role of the patient. Such therapy also helps change negative perceptions about physical exercise, such as the belief that exercise will worsen pain.
Although several models of cognitive behavior therapy have been described,3-6 all involve patient education to change negative perceptions and behaviors. Patients are taught to set realistic goals, to relax (through electromyographic biofeedback, meditation, and/or counseling to reduce stress), and to remain physically fit. Coping skills are learned through techniques such as self-talk and distraction. Physical activities and social interactions are gradually increased.
Improving Sleep Quality
Most patients with FMS sleep poorly because of pain; psychological distress; endogenous arousal; or an associated sleep disorder, such as restless legs syndrome, periodic limb movement disorder or, perhaps, sleep apnea. Nonrestorative sleep contributes to pain, fatigue, and poor physical and mental performance.
The management of sleep disturbance is therefore important and includes both nonpharmacologic and pharmacologic approaches. Nonpharmacologic measures include going to bed early and at the same time every day, sleeping in a quiet room without distraction, avoiding alcohol and coffee before bed, exercising regularly during the day or early evening, and using relaxation techniques.
Tricyclic antidepressants, taken in low doses (10 to 50 mg after supper or at bedtime), are generally effective. Zolpidem (10 mg at bedtime) has been reported to improve sleep as well as daytime energy in a controlled study.7 An anxiolytic medication, such as alprazolam (0.25 to 0.5 mg in the evening or at bedtime), may also be helpful, particularly in anxious patients.
Routinely ask your patient about the presence of symptoms of restless legs syndrome or periodic limb movement disorder. These conditions require specific therapy, such as clonazepam and L-dopa.8 I have also found zolpidem useful in this setting.
Physical Fitness
Controlled studies have demonstrated that cardiovascular fitness training can reduce symptoms in patients with FMS.9 Some patients do not experience diminished pain but report enhanced well-being.
Many patients with FMS have muscle deconditioning.5,6 Deconditioned muscles use excess energy for a given task and may therefore contribute to fatigue. These muscles may also be susceptible to microtrauma, thus aggravating pain.6 The challenge is to get patients to do aerobic and muscle endurance exercises. Since symptoms are often aggravated afterward, reassure your patients that a moderate degree of pain following exercise is not harmful.
The types of exercises used are individualized, depending on personal choice and pain severity. Poorly motivated patients tend to do better in a group. Others benefit from brisk walking, swimming in a warm pool, and bicycling. The key is to start exercising at a low level for 5 to 10 minutes and build up to 30 to 40 minutes daily to attain a heart rate of 130 to 150 beats per minute. I ask my patients to use a graph to keep track of their progress in exercise tune and symptoms. This provides them with useful feedback.
Physical and Occupational Therapy
No controlled studies have shown the efficacy of physical therapy in FMS. Anecdotally, however, one or more forms of physical therapy provide relief in some patients. Different types of physical therapy are shown in Table 2. Patients should not concentrate on passive modalities, such as massage, heat, and electric stimulation. Active involvement in physical fitness and endurance programs is vital.
Table 2: Physical and Occupational Therapies Commonly Used in Managing Fibromyalgia Syndrome(*)
Heat therapy: hot packs; hydrotherapy
Cold therapy: cold packs
Myotherapy: massage; manipulation; stretch and vapocoolant spray
Stretching exercises, including range of motion
Muscle-strengthening and aerobic exercises
Use of proper posture and body mechanics
Transcutaneous electric stimulation
*It is important to combine a home program of physical therapy with the therapy at an institution. Patients should not completely rely on passive modalities, such as massage, heat, and electric stimulation.
Effective therapists provide encouragement; are persistent but not "pushy"; and stress the importance of aerobic exercise, stretching, muscle strengthening, correct posture, and proper body mechanics in carrying out daily tasks. The technique of stretching and spraying with a vapocoolant (fluoromethane) may provide temporary relief for some patients.10 The therapist should teach physical therapy modalities to both the patient and a family member, to help ensure daily compliance at home. An occupational therapist or rehabilitation specialist may teach patients to conserve energy, use appropriate splints if necessary, and minimize tissue trauma.
Other Nonpharmacologic Approaches
Controlled studies have demonstrated electromyographic biofeedback, electroacupuncture, and hypnotherapy to be useful in patients with FMS.11 An open study concluded that meditation is also helpful.12 Some of these nonpharmacologic approaches may have their beneficial effects via changes in neurohormonal status.