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Fibromyalgia (FM) is a clinical syndrome characterized by widespread chronic musculoskeletal pain, stiffness and tenderness in addition to a variety of physical and mental symptoms including fatigue, sleep/mood disturbances, depression, anxiety, cognitive dysfunction, headaches, and intestinal disorders. Not everyone with FM will experience the same constellation of symptoms; and even presenting symptoms may fluctuate over time. FM syndrome often results in impairments in activities of daily living as well as diminished quality of life. FM often occurs concurrently with other diseases but given its variable presentation it is considered controversial and often misdiagnosed as other conditions.


Historically, FM was not recognized as a clinical entity, with symptoms being attributed to somatic expressions of underlying psychiatric conditions or mood disorders. This theory has become outdated and is now largely refuted given the increasing body of research. From a medical standpoint, FM is still inexplicable with no identifiable specific etiology.

While genetic polymorphisms have been suggested to be contributory, the main alterations observed are thought to be mono-amine neurotransmission (serotonin and norepinephrine) pathways leading to elevated levels of excitatory neurotransmitters such as glutamate and substance P as well as decreased levels of serotonin and norepinephrine in the spinal cord There are also abnormalities such as the dysregulation of dopamine and endogenous cerebral opioids.1 Peripheral derangements may contribute to increased nociception supply to the spinal cord resulting in central sensitization.1

As we expand our knowledge about the etiologic factors that are contributory to this condition – current research suggests that the cause is likely multifactorial with environmental, psychosocial, inflammatory/immune, endocrine, and genetic elements.1 Environmental triggers include emotional or physical trauma; chronic stress; physical or sexual abuse; or deployment in war. Psychosocial stressors can include anything from depression and anxiety, obsessive-compulsive disorder, and somatization. Inflammatory and immune triggers such as Epstein-Barr virus, Lyme disease, Q-fever, viral hepatitis, and human immunodeficiency virus infections have been associated with FM, with the suggestion that an acute exacerbation of the immune system can act as a trigger for FM.2,3

Epidemiology including risk factors and primary prevention 

  • FM is one of the most common musculoskeletal disorders with unknown cause and the second most common rheumatologic disease, after osteoarthritis. While earlier studies reported the estimated prevalence among the general population was as high as 8%, more recent epidemiological data suggests that the prevalence is closer to 2-4%.2-5 Prevalence of disease is difficult to ascertain as there are multiple tools of diagnoses in addition to ACR criteria, such as the Fibromyalgia Impact Questionnaire (FIQ), International classification of Disease (ICD), and the London Fibromyalgia Epidemiology Study Screening Questionnaire (LFESSQ).18
  • FM is more common among women than men, although not to the degree that was previously reported. Studies using the 2010/2011 American College of Rheumatology (ACR) criteria in the diagnosis of FM suggest a 2:1 female-to-male ratio. In contrast, gender prevalence studies using the original 1990 ACR criteria suggested closer to a 9:1 female-to-male ratio estimating prevalence up to 13% in women, which was largely thought to be due to its sole reliance on tender point assessment.2-4 There are some hypotheses that FM is more common in women due to increased gender prevalence of anxiety and depression, differing behavioral response in response to pain, and menstrual cycle-related changes in CNS input and hormonal effects.7
  • The average age of onset of FM is between ages 30 and 50, with peak prevalence among women age 55 to 64. However, FM has been known to occur at any age. Even in childhood and adolescence, FM has been known to present as primary Juvenile Fibromyalgia Syndrome (JFMS)
  • Demographic and social factors with increased association with FM include female gender, lower educational level, lower household income, divorced status, obesity, physical trauma, negative life events, middle age, and history of disability.4 
  • First-degree relatives of affected patients are more likely to have FM or other types of chronic pain syndromes.2,3 
  • Twin studies show risk of fibromyalgia to be 50% genetic, 50% environmental.2,3 FM has been associated with epigenetic changes characterized by hypomethylation of genes involve with stress response, DNA repair, and autonomic system response.1


FM can be classified under nociplastic pain, a more recently adapted classification that defines chronic pain leading towards an altered nociceptive function. Inputs from peripheral or central mediated sensory pathways are altered resulting in increased pain sensitivity.8 The pathology behind FM is currently conceptualized as being due to an increased sensitization of the central nervous system (CNS) to pain, and a decrease in the function of the descending tracts that inhibit pain. Many research studies suggest an abnormal temporal summation of painful stimuli, indicating pain amplification at the level of the spinal cord and brain. 

The ascending nociceptive pathway (spinothalamic tract) is constantly modulated by a variety of descending pathways that originate from several CNS loci including the periaqueductal gray area, locus coeruleus, and hypothalamus. These pathways, which have been postulated to be dysfunctional in individuals with FM, are described as noxious inhibitory controls and act at the level of the dorsal horns of the spinal cord.

Clinical studies based on functional magnetic resonance imaging (fMRI) have confirmed a central neuronal alteration in nociceptive processes.1 Functional MRI-based research has shown increased connectivity between brain regions that increase pain signals and decreased connectivity to regions that decrease pain inhibition in those with FM. Studies have demonstrated brain activation patterns in areas involved in pain processing when exposed to mild heat or pressure at levels that would be non-painful to most individuals in the general population.2,3 

Recent studies reveal that neurogenic derived inflammatory processes can also be responsible for the pathophysiology of FM with the increased release of chemokines and cytokines that activate the immune system. Increase in IL-6, IL-8, IL-1beta and TNF-alpha levels have been studied to evaluate their correlation to symptom severity in FM. Increased levels of IL-8 were found in the cerebrospinal fluid of patients with FM. IL-8 activation is associated with the activation of glial cells and the ortho-sympathetic system which could contribute to the central sensitization process and the correlation between stress and FM symptoms.9 Other pro-inflammatory cytokines such as nitric oxide production, IL-1beta, IL-6, and TNF-alpha can activate and sensitize nociceptors which can augment pain signals and induce hyperalgesia.10

Linkage studies over the years have revealed a 50% correlation rate between genetic variants and chronic pain which suggest the prevalence of FM has a genetic predisposition.1 In one genome-wide linkage scan study, first-degree relatives were found to have increased risk in developing FM.11 Currently there are about 100 genes found that are thought to be relevant to pain sensitivity, mostly those that encode for voltage-dependent Na channels, GABAergic pathways, mu-opioid receptors, catechol-O-methyltransferase and GTP cyclohydrolase 1.12 Unfortunately, genetic studies are currently limited as FM is a multifactorial disorder, and further studies are needed to elucidate genetic predispositions and possible FM variants.

Stress is a motif in the exacerbation of FM symptoms widely described in the FM population. As such, the Hypothalamic-pituitary-adrenal axis was studied in its relation to FM. Despite multitudes of studies, there is no correlation in total or free cortisol levels or Corticotropin-Releasing Factor in FM patients. Regardless of the discrepancies between studies of FM on cortisol levels, dysregulation of sleep and the circadian rhythm is commonly observed. Growth hormone and insulin-like growth factor 1 has been found to be impacted by FM, as about one third of FM patients were found to have a lower IFG-1 level than control groups.13 Additionally, there has been no found correlation between FM and estrogen levels, despite the increased prevalence of FM in women. Some speculate that the increased prevalence of anxiety disorders, altered behavior in response to pain, and altered CNS input in women may have some parallel to higher female presentation of FM.7

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

The natural history of FM is variable and inadequately defined. It is a chronic syndrome that has an unknown age onset, no specific genetic predisposition, unknown causative agents or pathology, and often results in impairments in activities of daily living with concomitant diminished quality of life. One theory is that FM (and other disorders with a centralized basis for pain) may be a lifelong condition that, while may be present early in life in a quiescent form, has a variable expression throughout its course, affecting different body regions/systems at different times.2 These changes are the result of immune system inflammatory changes, genetic predisposition, endocrine changes, and psychopathology that may be associated with onset and progression of FM.

Patients with FM commonly display abnormally enhanced sensitivity to different types of stimuli (mechanical and ischemic pressure, temperature), which elicit a pain response at lower levels than those in the general population.1 This sensitization to pain which can result in hyperalgesia or allodynia, can occur in a variety of body regions; patients will often present with complaints of “pain all over.”  

There is also the presentation of a possible FM variant, primary JFMS, that presents in children and adolescents that continues to have no medical explanation with possible different causation, pathophysiology, and etiology. Further investigation continues to elucidate JFMS and the possibility if it is contributory to adult FM.16

Other common complaints of those affected by FM involve fatigue and cognitive problems. Sometimes known as “fibro fog,” this can manifest as an inability to focus/concentrate, inattention, impaired memory, and slowed processing speed.1,2 FM patients often report generalized fatigue, and sleep disturbances or feeling unrefreshed even after sleeping. It is unclear whether the cognitive deficits are simply the result of impaired sleep cycles, or are a by-product of altered neurotransmission, chronic pain states, or affective disorders.17 

Objective measurements of autonomic dysfunction continue to show only a modest difference in FM from the control populations despite self-reported severe autonomic dysfunction, including increased average heart rate, decreased heart rate variability, and reduced reactivity to physical and psychological stressors.17 

Specific secondary or associated conditions and complications

In addition to its classification as a nociplastic pain, FM is part of a family of disorders known as chronic overlapping pain conditions (COPCs) (formerly known by terms such as functional somatic syndromes or central sensitivity syndromes). These include chronic fatigue syndrome, irritable bowel syndrome, multiple chemical sensitivity disorder, tension headache, migraine headache, interstitial cystitis, temporomandibular disorders, and chronic pelvic pain.18 These syndromes have a higher prevalence in FM patients than in the general population, thought to be due to “clustering” in affected patients from possible shared central nervous system mechanisms.18 

Approximately 10% to 30% of those with known diagnoses of rheumatological conditions (for example, rheumatoid arthritis, lupus, osteoarthritis, ankylosing spondylitis) also meet diagnostic criteria for FM. This phenomenon is sometimes referred to as “secondary fibromyalgia.” It is hypothesized that the central sensitization that occurs with FM has an additive effect on peripheral nociception experienced with these conditions.2

Psychiatric co-morbidities in FM have become apparent as there is a close correlation between stress, depression, anxiety disorders – with the prevalence of psychiatric comorbidities reaching 60% in certain subpopulations.14 Depressive symptoms, sleep dysregulation, and fatigue have been associated as a negative prognosticator as they are associated with pain-evoked neuronal activation in the amygdala and contralateral anterior insula which are brain areas associated with affective pain processing. This connection highlights the possible pathophysiologic overlap between depressive disorders and fibromyalgia and existence of parallel neuronal pain processing networks.15 Often, experiences such as stress or trauma can serve as a common trigger for both FM and mental health issues. Rates of attempted suicide among FM patients has been estimated to be as high as 16.7%.17

Essentials of Assessment


FM is primarily a pain disease with a wide array of concomitant physical and mental effects. As such, diagnosis can be obfuscated given the prominent overlap of symptoms with other diseases. The list of differential diagnoses is extensive and includes (but is not limited to) other rheumatologic disorders, headaches, psychiatric conditions, neuropathies, dyssomnias, and other functional pain disorders.  While fibromyalgia can co-exist with other disease states, it is important to recognize patterns of symptomatology that may be better explained by other diagnoses to prevent misdiagnosis. A thorough history-taking to delineate the full breadth of symptoms is essential in accurate assessment. 

2010 American College of Rheumatology (ACR) Fibromyalgia Diagnostic Criteria

The revision by the ACR of its diagnostic criteria for FM in 2010 involves the use of two scales, the Widespread Pain Index (WPI), and Symptom Severity (SS) scale, which focuses on patient-reported symptom prominence in combination with physician assessment.4 This revised framework was in stark contrast to the original ACR criteria established in 1990 which relied on the use of tender points over a variety of body areas to make the diagnosis of FM, which has since fallen out of favor due to limited predictive validity and interrater inconsistencies.4,18,9 Comparatively, the 2010 criteria take into consideration many other symptoms as key features of FM, including fatigue, cognitive and somatic symptoms.2,3 

The WPI consists of a list of 19 body areas where patients may be experiencing pain, with a score range of 0 to 19. These body areas include the neck, chest, abdomen, upper and lower back, and bilateral shoulder girdle, upper and lower arm, hip, upper and lower leg, and jaw.4 

The SS scale is divided into two parts. The first section specifically assesses fatigue, unrefreshed waking, and cognitive symptoms each on a scale of 0 to 3 (from 0 representing “no problems” to 3 representing “severe”). This is then followed by a second section which lists 41 different symptoms that can be associated with FM; those with none of these listed symptoms receive a score of 0, 1-10 symptoms receive a score of 1, 11-24 symptoms receive a score of 2, while 25 or greater symptoms receive a score of 3. The complete SS scale has an overall score range of 0 to 12.4 

In order to diagnose FM based on the 2010 ACR criteria, the following must be met: 

  • A WPI score ≥7 and a SS score ≥5 


  • A WPI score between 3 and 6 and a SS score ≥9 
  • Symptoms must have been present at a similar level for three months 
  • The patient does not have a disorder that would otherwise explain the pain 

Modifications to the 2010 ACR Fibromyalgia Diagnostic Criteria

Two modifications to the above listed 2010 framework have since been proposed, one in 2011 and another in 2016, although it should be noted that neither of these have officially been adopted by ACR. The 2011 modification recommended changes that would allow for self-administration of the WPI and SS scales by patients themselves, which could theoretically allow for continuous measurement of symptom severity. The SS2b section (checklist of 41 symptoms) was replaced with a section evaluating the presence of absence of 3 specific items: headaches, pain/cramping in the lower abdomen, and depressive symptoms. One major criticism of the 2011 modification is that patients may not be able to distinguish/recognize the presence of another primary disorder as the source of their pain.4 

The novel 2016 criteria followed a systematic review of the 2010/2011 diagnosis criteria, which found that they were not able to distinguish FM from certain regional pain syndromes, and did not address FM diagnoses in the presence of other conditions.18  

New criteria were proposed as follows:4 

  • Presence of “generalized” pain in at least 4 of 5 regions (axial plus 4 quadrants) (*does not include headache, face/jaw, chest or abdomen) 
  • A WPI score ≥7 and a SS score ≥5 


  • A WPI score between 4 and 6 and a SS score ≥9 
  • Symptoms must have been present at a similar level for three months 
  • A diagnosis of FM is valid irrespective of other diagnoses, and a diagnosis of FM does not exclude the presence of other clinically important illnesses 

Newer Research into Diagnostic Frameworks

In 2018, a new proposal for FM diagnostic criteria was put forward as part of a larger effort for consistent diagnosis for all types of chronic pain disorders. This was spearheaded by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks (ACTTION) in conjunction with the American Pain Society (APS). Their collaborative pain taxonomy, or AAPT, was developed by an international working group of both clinicians and researchers, and bases diagnosis on 5 “dimensions:” (1) core diagnostic criteria; (2) common features; (3) common medical co-morbidities; (4) neurobiological, psychosocial, and functional consequences; and (5) putative neurobiological and psychosocial mechanisms, risk factors, and protective factors.19 It should be noted, however, that this framework has yet to be validated for clinical use.4 

Functional assessment 

Evaluation of the patient should be comprehensive — encompassing musculoskeletal, neurological, endocrinologic, and psychological testing. Given the significant overlap of FM with other conditions, this is necessary to rule out other more likely conditions.  

Laboratory studies 

There are no current biomarkers for fibromyalgia. As such, laboratory testing is generally not recommended for diagnosing FM, but rather to rule out other diseases.3 Basic laboratory tests such as a complete blood count, erythrocyte sedimentation rate, and C-reactive protein can be used as an initial screening panel for other inflammatory conditions.1 Additional testing (thyroid stimulating hormone, rheumatoid factor, creatine kinase, etc.) can be ordered based on clinical suspicion of other disease processes. 

As highlighted earlier, the hypothalamic-pituitary-adrenal (HPA) axis has had no proven correlation with FM Cortisol levels are not pathognomonic for the disease and cannot differentiate FM from chronic fatigue syndrome (CFS), chronic pelvic pain (CPP), and post-traumatic stress disorder (PTSD).1

Considering the prevalence of the disease, there is much interest in finding a biomarker to diagnose FM. There have been some studies associated antipolymer antibody (APA) with FM being found in 17.6% of patients, however still lacking diagnostic significance.20 Environmental factors may modulate genome function through epigenetic mechanisms which may play a role in the upregulation of FM prevalence. Fibromyalgia appears to be characterized by a hypomethylated DNA pattern in genes involved in the stress response, DNA repair, the autonomic system response and subcortical neuronal abnormalities. Furthermore, microRNAs have revealed to be promising as novel biomarkers. Genome expression analysis of microRNAs reveals associations with FM as well as other psychiatric conditions, but there is need for additional study as FM has not been specifically related to a single gene.21

Supplemental assessment tools 

  • One unique characteristic of FM is that it does not cause destruction or distortion of anatomy; as such, there are no FM-specific findings on imaging. As with laboratory testing, imaging would only be used to rule out other diseases in the differential diagnosis, rather than to establish the diagnosis of FM. 
  • Formal sleep studies can be helpful to establish sleep disorder diagnoses, which have a high prevalence in those with FM. Polysomnography studies of FM patients often show alpha-delta sleep patterns which are consistent with non-restorative or interrupted sleep, which may explain the symptoms of poor-quality sleep, insomnia, the lack of feeling refreshed despite adequate sleep, fatigue and low energy levels.1 
  • Electrodiagnostic studies are generally not recommended in the diagnosis of FM, despite paresthesias being a common complaint in FM patients. While approximately 40% of those with FM also have evidence of small-fiber polyneuropathy, this may represent simple overlap in symptomatology rather than a direct causative link or diagnostic indicator.22,23
  • Psychological assessment to assess for depression, anxiety, catastrophizing, somatization, coping skills and motivation is important. 

Early predictions of outcomes 

  • A tendency to catastrophize their condition, or a fear of movement due to their pain are poor prognostic factors for patients.2,3 
  • Some studies have found a correlation between the level of disability from FM and childhood/adolescent traumas (including physical trauma, neglect, and negative life events).17 


Environmental triggers include emotional or physical trauma, chronic stress, physical or sexual abuse, toxin/chemical exposure, or deployment in war. 

Social role and social support system

FM may negatively impact a person’s physical, psychological, and social well-being and may prevent full participation in societal roles. Relationships may be disrupted due to pain, fatigue, cognitive changes, and associated mental health disorders. Lack of understanding of the symptoms associated with FM by friends, family, and employers may create an additional barrier to participation.17  

Professional issues

FM may be brought on by multiple triggers that can occur in the workplace setting, including stressors or physical/emotional injury. Gainful employment may be difficult to maintain and accommodations at work should be considered, consistent with the concepts set forth in the International Classification of Functioning, Disability and Health. Accusations of secondary gain or malingering may be wrongly leveled against the patient when applying for disability due to FM, given the lack of objective evidence and limited diagnosis criteria for the condition (lab work, imaging, etc.).

Rehabilitation Management and Treatments

Available or current treatment guidelines

Guidelines have been published by professional organizations, including the European League Against Rheumatism (EULAR) in 2017 and the Canadian Rheumatology Association (CRA) in 2012, to inform diagnosis and treatment of this complex syndrome. There is no definitive treatment for FM. Attempts to create a standardized, algorithmic approach to management have proved challenging due to the lack of high-quality evidence and consensus between guidelines. Behavioral-based therapies play an increasingly important role in this population. Studies investigating the efficacy of medications to address FM-related symptoms reveal only modest improvement, at best. Pharmacological agents can be used as adjunctive therapy but only if sustained benefit is demonstrated.  

Patient & family education

  • Patients should be reassured and informed that FM is a real illness and has a heterogeneous presentation; it is not a progressive illness, and the symptoms may be controlled with active participation in one’s own care. 
  • Patients and their support systems should be provided with information about the disease and treatment options. Education should emphasize an understanding of centralized pain and the importance of exercise, sleep, and stress reduction. 
  • 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. 

Coordination of care

Interdisciplinary, multimodal treatment is essential for FM patients with severe functional disability, limited understanding of the condition, significant pain and disability behaviors. Treatment modalities for FM currently revolve around the four pillars: patient/family education; psychotherapy; pharmacotherapy; and rehabilitation.


Cognitive behavioral therapies (CBTs) are commonly employed in chronic pain conditions. These psychological treatments are geared towards restructuring the negative thoughts surrounding pain and modifying behaviors with the desired outcome of improved function and ability to cope with pain.  

  • In FM, CBT has been shown to be more effective than controls in the improvement in pain and health-related quality of life (HRQOL) at the end of treatment and reducing negative mood and disability at long-term follow up.13 CBT is also the most cost-effective treatment for FM, but implementation in primary care would require widespread public access.24
  • Activity management training may improve FM-related pain by changing pain-related activity patterns. Racine et al found: (1) a reduction in avoidance behaviors was associated with improvement in psychological function; and (2), greater improvement in physical function was seen when subjects learned how to pace themselves when performing day-to-day activities.25   
  • There is insufficient evidence endorsing the use of mind and body therapies including biofeedback, mindfulness, and relaxation techniques in FM, but it can be beneficial for some and utilized as conjunctive treatment. 


Pharmacological treatment of FM is common despite modest evidence of efficacy. 

  • Three agents are approved by the US Food and Drug Administration (FDA) for the treatment of FM including duloxetine, milnacipran, and pregabalin. 
  • Serotonin and noradrenaline reuptake inhibitors (SNRIs) duloxetine and milnacipran have been shown to reduce pain by 30% or more when compared to placebo but have not been found to have any effect on other FM symptoms (low-quality evidence).26 In another systematic review for duloxetine treatment use, it was revealed that the number needed to treat is eight and it was found to improve pain severity regardless of a comorbid major depressive disorder.27
  • Gabapentinoids used in FM include pregabalin and gabapentin. The exact mechanism of action is 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. High-quality evidence suggests that pregabalin reduces pain associated with FM. However, use may be limited by its side effects.28 Although some trials report improvement with gabapentin, a systematic review could not support the use of this medication to reduce FM-related pain.29 
  • Despite lack of high-quality evidence, amitriptyline, a tricyclic antidepressant, continues to be used in past years for the treatment of FM and its use is recommended in the above-mentioned guidelines.30 
  • Cyclobenzaprine is structurally related to tricyclic antidepressants and is a centrally-acting muscle relaxant. A systematic review found that subjects prescribed this medication were three times more likely to report overall improvement. However, use may be limited by side effect profile.30  
  • Older generation selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, sertraline, and paroxetine have shown some effect in improving FM-related pain; however, these medications may provide greater benefit in treating the mood disorders commonly seen with FM.30 
  • Little benefit has been found with the use of analgesics such as nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, and opioid analgesics. There is no evidence that nonopioid analgesics are effective in FM. Opioid analgesics continue to be prescribed in fibromyalgia despite lack of evidence proving their efficacy, but it should be emphasized FM patients on opioids have poorer outcomes than their counterparts.31
  • Steroids have little to no role in FM. 
  • While some studies indicate promising results of cannabinoids in reducing pain and improving sleep in FM patients, the overall effectiveness of cannabinoids in treating fibromyalgia remains uncertain.32 


  • Aerobic exercise is an essential component of treatment. A Cochrane review of 13 studies found moderate-quality evidence that aerobic exercise improved HRQOL and low-quality evidence that it may improve physical function and reduce pain, fatigue, and stiffness in this population. Aerobic exercise is generally well tolerated, especially if performed in a graduated, supervised fashion.33  
  • Mixed exercise, defined as regular sessions of two or more types of exercise including aerobic, strengthening, or flexibility exercise, did not appear to provide statistically significant benefit or harm when compared to other types of exercise, medication, or non-exercise treatment such as biofeedback.34 
  • With the exception of acupuncture, there is limited data to support complementary and alternative therapies in the treatment of FM including manual therapy, chiropractic manipulation, and tai chi. There is promising research that acupuncture is more effective in reducing FM-related pain than sham acupuncture.35 
  • An individualized approach should be taken when prescribing exercise and should incorporate patient preferences and accessibility to services and facilities. 
  • Dietary treatment with some antioxidants, supplements, and vitamins have been evaluated to impact FM symptoms (lower quality data). In conjunction with pharmacologic treatment, supplements such as melatonin, Coenzyme Q10, and Vitamin E have been shown to improve FIQ scores, decrease pain levels, and improve quality of life, respectively.1
  • Osteopathic Manipulation Treatment (OMT) can be effective when used in conjunction with standard medical care, however OMT alone have shown no significant benefit over sham treatment in a RCT.36,37

Emerging/unique interventions


Impairment-based measurement

Occasionally, functional capacity examination is required to demonstrate vocational limitations.

Measurement of patient outcomes

  • Severity measures
    • Fibromyalgia Impact Questionnaire 
    • Combined Index of Fibromyalgia Severity (ICAF) 
    • Polysymptomatic Distress Scale (PSD) = WPI + 2011 version of SSS 
  • Pain measures
    • Pain Assessment Inventory (PAI) 
    • Pain Disability Index (PDI) 
    • Visual Analogue Scale (VAS) 
  • Quality of Life
    • 36-Item Short Form Survey (SF-36)

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

Due to the complexity of this disease and the challenges associated with its diagnosis, the diagnosis of FM is often delayed. Health care providers should consider FM in a patient who reports chronic, diffuse pain without a definitive etiology. Recognizing FM early may prevent “doctor shopping/hopping” and can prompt education and treatment that may decrease unnecessary morbidity and disability. Treatment should be directed towards reducing the symptomatology associated with FM including sleep and mood dysregulation. Care should be taken to identify co-morbid conditions that may have specific treatments and contribute to FM exacerbation. Lastly, an individualized multidisciplinary approach to treatment and collaborative goal-setting may improve adherence to therapies and overall quality of life.1,38

Cutting Edge/Emerging and Unique Concepts and Practice

The landscape of treatment for FM is continually evolving as researchers explore new approaches in managing this complex disorder. Some emerging concepts include 

  • Central Nervous System (CNS) Modulators:
    Researchers are investigating medications that target the central nervous system, such as drugs that modulate neurotransmitters like glutamate and substance P.39,40 These medications aim to address the central sensitization seen in fibromyalgia.
  • Electrical neuromodulation:
    Electrical neuromodulation techniques, such as TENS (Transcutaneous Electrical Nerve Stimulation), have been shown to significant effect in decreasing pain, depression and improving function. For example, NeuroMetrix’s Quell, a non-invasive TENS device, became the first FDA-approved wearable device for non-pharmacological neuromodulation in treatment of FM. 41
  • Immunomodulation:
    Medications that modulate the immune response such as low-dose naltrexone (LDN) has been clinically shown to be a potential treatment option for FM.42
  • Biological Therapies:
    Biologics, which are medications derived from living organisms, are being studied for their potential in fibromyalgia treatment. These include anti-cytokine therapies and monoclonal antibodies (i.e., Tocilizumab, Fremanezumab) that target specific molecules involved in pain and inflammation.43,44
  • Nutritional Interventions:
    Some research suggests that dietary changes and nutritional supplements may help manage fibromyalgia symptoms. For example, studies have investigated the effects of vitamin D supplementation and low-FODMAP diets in reducing pain and improving quality of life in patients with FM.45
  • Combination Therapies:
    Combining different treatments, such as medications, physical therapy, and psychological interventions, may offer a more comprehensive approach to managing fibromyalgia symptoms.

Gaps in the Evidence-Based Knowledge

  • Etiology, pathophysiology:
    The exact cause of fibromyalgia remains unclear. Research is needed to better understand the underlying mechanisms and contributing factors, including genetic and environmental factors.  While there is no direct known genetic or epigenetic predisposition to development of FM, studies of genetic polymorphisms involved in pain processing, inflammation and oxidative stress have shown potential connection to the severity of FM symptoms.46 Additionally, environmental factors such as trauma, infection, weather changes, sleep disturbance, psychosocial factors, and chemical exposures have been linked to the onset and exacerbation of FM. Advances in research and a better understanding of pathophysiology of FM will help develop the most efficacious and patient-specific treatments.  
  • Diagnosis:
    There are no reliable biomarkers for FM diagnosis or severity of disease currently. Developing biomarkers could aid in more accurate diagnosis, tracking the condition’s progression and a more targeted therapy.47
  • Treatment:
    Various treatment options are available for fibromyalgia; both pharmacological and non-pharmacological (e.g., Cognitive-behavioral therapy, exercise, lifestyle modifications). However, there is discordance between guidelines on recommendations for FM treatment due to lack of high-quality randomized control trials (RCT). More research is needed to establish an evidence-based guideline and identify which treatment works best for different subgroups of patients for targeted therapy.48


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Original Version of the Topic

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

Previous Revision(s) of the Topic

Matthew Davies, MD, Claudine Ward MD, and Jaspreet Singh, MD. Fibromyalgia. 3/27/2017

Ryan Thachen-Cary, MD, MSc, Claudine Ward MD. Fibromyalgia. 12/1/2020

Author Disclosure

Jason Do, DO, MS
Nothing to Disclose

Ryan Kim, DO
Nothing to Disclose

Sanjeev Agarwal, MD, MS, FAAPMR, CAQSM
Nothing to Disclose