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Fibromyalgia (FM) is a clinical syndrome characterized by widespread pain and tenderness in addition to a variety of symptoms including fatigue, sleep disturbances, depression, anxiety, and cognitive dysfunction in the absence of an identifiable cause.  FM syndrome results in impairments in activities of daily living as well as diminished quality of life.


No specific etiology has been identified. While genetic polymorphisms, especially with amine pathways have been suggested, FM seems to be a final common pathway for a myriad of conditions with behavioral and mechanical factors contributing to the biological state.

Epidemiology including risk factors and primary prevention

  1. FM is more common among women than men, Studies based on 1990 American College of Rheumatology (ACR) criteria suggest a 9:1 female-to-male ratio and 2:1 ratio based on the 2010/2011 ACR criteria. 1,2
  2. The estimated prevalence among the general population is between 2% and 8%; that is, approximately 6-24 million adults in the USA. 1,2
  3. The average age of onset of FM is between ages 30 and 50, with peak prevalence among women age 55 to 64. However, FM can occur at any age.
  4. Demographic and social factors associated with FM include female sex, lower educational and household income, divorce status, middle age, and history of disability.
  5. First-degree relatives are more likely to have FM or other types of chronic pain syndromes. 1,2
  6. Twin studies show risk of fibromyalgia to be 50% genetic, 50% environmental. 1,2
  7. FM is the second most common rheumatologic disease.


  1. FM is currently conceptualized as a “disorder of increased sensitization of the central nervous system (CNS) and decreased function of the descending systems that inhibit pain.” The ascending nocioceptive pathway is constantly modulated by a variety of descending pathways that originate from several CNS loci including the periaqueductal gray area, locus ceruleus, and hypothalamus. These pathways are described as “diffuse noxious inhibitory controls,” which has been postulated to be dysfunctional in individuals with FM.
  2. Functional MRI studies have shown increased connectivity between brain regions that increase pain signals and decreased connectivity to regions that decrease pain signals. 1,2
  3. There are studies suggesting “abnormal temporal summation” of painful stimuli, thus individuals with FM undergo pain amplification at the level of the spinal cord and brain.
  4. Abnormalities of the hypothalamic-pituitary-adrenal (HPA) axis are seen not only in patients with FM, but also in those with chronic fatigue syndrome (CFS), chronic pelvic pain (CPP), and post-traumatic stress disorder (PTSD).
  5. FM is believed to have environmental, psychiatric, and viral triggers. Environmental triggers include emotional or physical trauma, chronic stress, physical or sexual abuse history, or deployment in war. Psychiatric stressors such as depression, anxiety, somatization traits and hypochondriasis are associated with FM. Viral triggers such as Epstein bar virus, Lyme disease, Q-fever, viral hepatitis, and human immunodeficiency virus are associated with FM. Acute illness has also been postulated as a trigger for FM. 1,2
  6. Objective measurements of autonomic dysfunction have shown only modest difference in FM from the control populations despite self-reported severe autonomic dysfunction. 3

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

  1. FM is a lifelong syndrome often beginning in adolescent or adulthood with no known cure.
  2. Natural history of FM is variable and inadequately defined.
  3. With proper multimodal treatment that emphasizes education and self-responsibility, symptoms of FM can be controlled.
  4. FM is a common co-morbidity of other chronic pain states including osteoarthritis, rheumatoid arthritis, and lupus.
  5. Differential diagnosis includes hypothyroidism, depression and other psychiatric disorders that may present with diffuse pain.

Specific secondary or associated conditions and complications

There is potential for secondary gain in medicolegal and disability evaluation settings.



Diagnostic: The 1990 American College of Rheumatology (ACR) criteria are based on symptoms of widespread pain above and below the waist as well as on both sides of the body over three months. This was considered to be research driven criteria and was not intended for clinical practice. In 2010 the ACR updated its diagnostic criteria to include symptoms and severity with less emphasis on the number of tender points. The self-reported survey allows for continuous measurement of symptom severity.

Physical examination: 2010 ACR Criteria

The 2010 ACR diagnostic criteria of FM focuses on measurement of symptom severity, and does not rely on tender point examination. Instead, many other symptoms were promoted as key features of FM. 1,2,4 These include fatigue, cognitive symptoms and somatic symptoms. The 2010 criteria rely on a series of questions based on the Widespread Pain Index (WPI), and Symptom Severity (SS) scale. 4 According to this new ACR “Proposed Criteria,” FM is defined as: 4

  • WPI score greater than or equal to 7 and SS score greater than or equal to 5 or WPI greater than or equal to 3-6 and a SS score of greater than or equal to 9. 4
  • Symptoms remaining at approximately that level for three months 4
  • The patient having no disorder that would otherwise explain the pain. 4
  • The areas of pain include 4
    • shoulder girdle, left
    • shoulder girdle, right;
    • upper arm, left;
    • upper arm, right
    • lower arm, left
    • lower arm, right
    • hip (buttock, trochanter), left
    • hip (buttock, trochanter), right
    • upper leg, left
    • upper leg, right
    • lower leg, left
    • lower leg, right
    • jaw, left
    • jaw, right
    • chest
    • abdomen
    • upper back
    • lower back
    • neck

Differential diagnosis includes rheumatoid arthritis, systemic lupus erythematosis, Sjogren syndrome, polymyalgia rheumatica, polymyositis, ankylosing spondylitis, depression and other psychiatric disorders, compressive and other peripheral neuropathies. The diagnosis of any of these other conditions, does not exclude FM, since many of these conditions may be coexistent with FM.

FM shares significant overlap with other functional pain disorders. These include chronic fatigue syndrome, irritable bowel syndrome, multiple chemical sensitivity disorder, tension headache, migraine headache, interstitial cystitis, temporomandibular disorders, chronic pelvic pain, depression and anxiety.

Functional assessment

  1. Research protocols often call for outcome measures (e.g., 36-item Short Form Health Survey, SF-36 and the Fibromyalgia Impact Questionnaire, FIQ), and pain severity scales (e.g., Visual Analog Scale, VAS).
  2. A 2016 study published in the American Journal of Physical Medicine and Rehabilitation identified the minimal clinically important difference for the 6-minute walk test (6MWT) which correlated to meaningful changes in the SF-36-physical function domain and the FIQ (167 meters and 156 meters respectively). 5 The 6MWT is a simple, inexpensive, and commonly used test in rehabilitation protocols, that has the potential to monitor FM response to medical and exercise interventions in everyday clinical practice. 5

Laboratory studies

There are no biomarkers for fibromyalgia.  As such, laboratory testing is generally unremarkable but necessary to rule out other diseases. Basic laboratory tests such as complete blood count, basic metabolic panel, thyrotropin, vitamin D, erythrocyte sedimentation rate, and C-reactive protein should be collected.

Supplemental assessment tools

Psychological assessment to explore for depression, anxiety, catastrophizing, somatization, coping skills and motivation is important.

Early predictions of outcomes

  1. Positive predictors of outcomes include higher baseline values for the State Trait Anxiety Inventory II and early intervention with pregabalin (doses of 300-600 mg/day) in a Korean study. 6
  2. Negative predictors include a diagnosis of depression, which may negatively impact pain, global treatment effect and quality of life. 6


  1. It is unclear whether environmental toxins could play a role in initiating FM.
  2. Twin studies have suggested a 50% environmental role in FM. 1,2

Social role and social support system

Disability associated with FM may lead to a loss of family and societal roles. This result may worsen the syndrome’s effects, increase depression, and become a barrier to recovery.

Professional Issues

Many times, FM is brought on by an accident that requires legal action. Such action can overtly or covertly become a barrier to improvement.


Available or current treatment guidelines

No cure exists for FM; treatment should focus on improving functional activities and quality of life, and on decreasing pain and other associated symptoms. The 2012 Canadian Guidelines for the Diagnosis and Management of Fibromyalgia Syndrome provides a comprehensive review of available treatment and is endorsed by the ACR.  Treatment options include pharmacological and nonpharmacological modalities with education, cognitive behavioral therapy (CBT) and exercise showing the strongest evidence of efficacy.

Patient & family education

  1. Patients should be informed that FM is a clinical syndrome and not a disease. It has a heterogeneous presentation; it is not a progressive illness, and the symptoms can be controlled with active participation in one’s own care. Patient education should emphasize the importance of exercise, sleep, and stress reduction.
  2. Family members and/or caregivers are an important part of the treatment team, providing a supportive environment to promote adherence to treatment plans.  Lack of access and adherence to exercise programs may impede attainment of goals.  Patients may overcome these barriers with the help from others.
  3. Educational approaches aimed toward self-efficacy using a range of multimodal therapies are key to long-term control of symptoms and minimizing disability (Evidence level 1A).

Coordination of care

  1. Parallel practice may be appropriate for mild cases.
  2. Interdisciplinary, multimodal treatment is essential for FM patients with severe functional disability, limited understanding of the condition, significant pain and disability behaviors.


  1. Cognitive-behavioral therapy has the best evidence of the psychological methods in FM. It improves one’s ability to cope with pain, reduces depressed mood, decreases health-care seeking behavior and improves self-efficacy by promoting more positive, adaptive thoughts and behaviors (Evidence level 1A).
  2. Psychological therapies are directed at providing patients with:
    1. an increased sense of control over their pain
    2. a belief that one is not necessarily ‘disabled’ by FM
    3. a belief that pain is not a sign of damage

Pharmacological 1,2

  1. Tricyclic antidepressants, gabapentinoids, serotonin-norepinephrine reuptake inhibitors and g-hydroxybutyrate (GHB) have the strongest evidence of efficacy.
  2. Pain interference with sleep should be treated.
  3. Tricyclic compounds such as amitriptyline and cyclobenzaprine have shown improvements in pain, sleep, irritable bowel symptoms, and irritable bladder symptoms believed to be mediated through the serotonin-norepinephrine reuptake inhibitor pathway (Evidence level 1A).
  4. Gabapentinoids used in FM include gabapentin (Neurontin) and pregabalin (Lyrica). The exact mechanisms are unknown, and likely relate to the binding of alpha-2-delta ligands. These drugs bind to the voltage gated channels and modulate calcium ion influx. This action inhibits the release of excitatory neurotransmitters, such as glutamate and substance P, which are believed to be involved in pain processing. Pregabalin is FDA approved for the treatment of FM (Evidence level 1A).
  5. Fatigue, pain, and depression should be treated with duloxetine (Cymbalta) or milnacipram (Savella). Duloxetine and milnacipram both are FDA approved for treatment of FM (Evidence level 1A).
  6. g-hydroxybutyrate (GHB) is a neurotransmitter similar to GABA that binds to GABA receptors and has shown efficacy in treatment of fibromyalgia. However, it is not approved by the FDA and is used off label for fibromyalgia treatment (Evidence level 1A).
  7. Older generation selective serotonin reuptake inhibitors such as fluoxetine, sertraline, and paroxetine at higher doses have been shown to improve pain (Evidence level 1A).
  8. Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used. Most anecdotal reports suggest temporary improvement of pain during flare-ups and are no longer recommended for long-term treatment (Evidence level 5D).
  9. Steroids have little to no role in FM. Opioid analgesics: With the exception of tramadol (Ultram), no evidence supports the use of any opioids in FM. There is increasing evidence that opioids not only lack efficacy, but may actually be associated with increased sensitivity to pain termed opioid induced hyperalgesia (Evidence level 5D). Naltrexone is an emerging pharmacologic option due to theory of FM patients having a hyperactive endogenous opioid system. More research is needed.
  10. Cannabinoids are reported to be effective in reducing pain in fibromyalgia. While the FDA has not approved any form of cannabis for medical use the state level has approved it for treatment of chronic pain in17 states (Level 1A evidence).


  1. Aerobic exercise is essential. A Cochrane review of 34 studies in FM indicate that moderate intensity aerobic training for 12 weeks may improve global well being and physical function. They also found that strength training for 12 weeks may result in large reductions in pain, tender points and depression, as well as improved global well being. 1,2
  2. Case studies have shown trigger point injections, acupuncture, tai chi, yoga, and chiropractic manipulation to reduce FM pain although evidence is limited. 7

Emerging/unique Interventions

Impairment-based measurement:

Occasionally, functional capacity examination is required to demonstrate vocational limitations. Other functional measures are used as required.

Measurement of patient outcomes:

  1. The Fibromyalgia Impact Questionnaire has been used as a research tool. Other general outcome measures such as the SF-36, depression and the Pain Assessment Inventory (PAI), Pain Disability Index (PDI), Sickness Impact Profile (SIP), and the Combined Index of Fibromyalgia Severity (ICAF) can be considered.
  2. The interdisciplinary rehabilitation of patients with chronic widespread pain (IMPROvE trial) showed objective, measurable improvement of activates of daily living with a 2 week multidisciplinary rehabilitation approach at 6 months. However the patients’ subjective response to treatment as determined by self reported surveys showed no improvement in self efficacy. 8

Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

Recognizing FM early can prevent “doctor shopping/hopping” and can prompt education and treatment that may decrease unnecessary morbidity and disability.


Cutting edge concepts and practice

  1. With increasing understanding of neuromodulation of pain, central sensitization and ion channel based therapy, more pharmacological options will emerge.
  2. Genetic studies may shed more light on this disorder, which probably has many subtypes.


Gaps in the evidence-based knowledge

Controversy exists regarding the diagnostic criteria and the pathophysiology with many postulated mechanisms. Evidence is lacking with many of the treatments.


  1. Clauw, D. J. Fibromyalgia and Related Conditions. Mayo Clin Proc. 2015; 90(5), 680-692.
  2. Clauw, D. J. Fibromyalgia: A clinical review. JAMA. 2014; 311(15), 1547-
  3. Vincent, A., Whipple, M. O., & Low, P. , et al. Patients With Fibromyalgia Have Significant Autonomic Symptoms But Modest Autonomic Dysfunction. PM&R Journal. 2016; 8(5), 425-435.
  4. Wolfe F, Clauw DJ, Fitzcharles M-A, et al. The American College of Rheumatology Preliminary Diagnostic Criteria for Fibromyalgia and Measurement of Symptom Severity. Arthritis Care & Research. 2010;62(5):600-610. doi:10.1002/acr.20140.
  5. Kaleth, A., Slaven, J., & Ang, D. Determining the Minimal Clinically Important Difference for 6-Minute Walk Distance in Fibromyalgia. J. Phys. Med. Rehabil. 2016; 95(10), 738-745.
  6. Kim, J. E., Park, D. J., & Choi, S. E., et al. Predictors of a favorable outcome in patients with fibromyalgia: Results of a 1-year follow-up. Clinical and Experimental Rheumatology. 2016; 34, 521-526.
  7. Taw, L. B., & Henry, E. Acupuncture and Trigger Point Injections for Fibromyalgia: East-West Medicine Case Report. Alternative Therapies. 2016; 22(1), 58-61.
  8. Amris, K., Waehrens, E. E., & Christensen, R. Interdisciplinary rehabilitation of patients with chronic widespread pain: Primary endpoint of the randomized, nonblinded, parallel-group IMPROvE trial. Pain. 2014; 155, 1356-1364.

Original Version of the Topic

Sridhar Vasudevan, MD. Fibromyalgia. 01/23/2013

Author Disclosure

Matthew Davies, MD
Nothing to Disclose

Claudine Ward MD
Motion Intelligence; Stock options; S

Jaspreet Singh, MD
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