The cause of fibromyalgia is unknown, but is believed to involve a combination of genetic and environmental factors.[4] Environmental factors may include
psychological stress,
trauma, and certain
infections.[4] The pain appears to result from processes in the
central nervous system and the condition is referred to as a "central sensitization syndrome".[4][13]
Fibromyalgia is estimated to affect 2–4% of the population.[21] Women are affected about twice as often as men.[4][21] Rates appear similar in different areas of the world and among different cultures.[4] Fibromyalgia was first defined in 1990, with updated criteria in 2011,[4] 2016,[9] 2019.[12] The term "fibromyalgia" is from
Neo-Latinfibro-, meaning "fibrous tissues",
Greek μυο- myo-, "muscle", and Greek άλγος algos, "pain"; thus, the term literally means "
muscle and
fibrous connective tissue pain".[22]
Fibromyalgia is predominantly a chronic
pain disorder.[12] According to the
NHS, widespread pain is one major symptom, which could feel like an ache, a burning sensation, or a sharp, stabbing pain.[28]
Fatigue
Fatigue is one of the defining symptoms of fibromyalgia.[12] Patients may experience physical or mental fatigue. Physical fatigue can be demonstrated by a feeling of exhaustion after
exercise or by a limitation in daily activities.[12]
Sleep problems
Sleep problems are a core symptom in fibromyalgia.[12] These include
difficulty falling asleep or staying asleep, awakening while sleeping and waking up feeling unrefreshed.[12] A
meta-analysis compared objective and subjective sleep metrics in people with fibromyalgia and healthy people. Individuals with fibromyalgia had lower sleep quality and efficiency, as well as longer wake time after sleep start, shorter sleep duration, lighter sleep, and greater trouble initiating sleep when objectively assessed, and more difficulty initiating sleep when subjectively assessed.[10] Sleep problems may contribute to pain by decreased release of
IGF-1 and
human growth hormone, leading to decreased tissue repair.[29] Improving sleep quality can help people with fibromyalgia minimize pain.[30][31]
Cognitive problems
Many people with fibromyalgia experience
cognitive problems (known as fibrofog or
brainfog). One study found that approximately 50% of fibromyalgia patients had subjective cognitive dysfunction and that it was associated with higher levels of pain and other fibromyalgia symptoms.[32] The
American Pain Society recognizes these problems as a major feature of fibromyalgia, characterized by trouble
concentrating,
forgetfulness and disorganized or slow thinking.[12] About 75% of fibromyalgia patients report significant problems with concentration, memory, and multitasking.[33] A 2018 meta-analysis found that the largest differences between fibromyalgia patients and healthy subjects were for
inhibitory control, memory, and
processing speed.[33] It is hypothesized that the increased pain compromises attention systems, resulting in cognitive problems.[33]
Hypersensitivity
In addition to a hypersensitivity to pain, patients with fibromyalgia show hypersensitivity to other stimuli,[11] such as bright lights, loud noises, perfumes and
cold.[12] A
review article found that they have a lower cold
pain threshold.[34] Other studies documented an acoustic hypersensitivity.[35]
Nearly all the genes suggested as potential risk factors for fibromyalgia are associated with neurotransmitters and their receptors.[53]Neuropathic pain and
major depressive disorder often co-occur with fibromyalgia — the reason for this
comorbidity appears to be due to shared
genetic abnormalities, which leads to impairments in
monoaminergic,
glutamatergic,
neurotrophic,
opioid and
proinflammatory cytokine signaling. In these vulnerable individuals,
psychological stress or illness can cause abnormalities in inflammatory and stress pathways that regulate mood and pain. Eventually, a sensitization and kindling effect occurs in certain
neurons leading to the establishment of fibromyalgia and sometimes a
mood disorder.[54]
Stress
Stress may be an important precipitating factor in the development of fibromyalgia.[55] A 2021
meta-analysis found
psychological trauma to be strongly associated with fibromyalgia.[56][57] People who suffered abuse in their lifetime were three times more likely to have fibromyalgia, people who suffered medical trauma or other stressors in their lifetime were about twice as likely.[56]
Some authors have proposed that, because exposure to stressful conditions can alter the function of the
hypothalamic-pituitary-adrenal (HPA) axis, the development of fibromyalgia may stem from stress-induced disruption of the HPA axis.[58][59]
Personality
Although some have suggested that fibromyalgia patients are more likely to have specific personality traits, when depression is statistically controlled for, it appears that their personality is no different than that of people in the general population.[60]
Other risk markers
Other risk markers for fibromyalgia include premature birth, female sex, cognitive influences, primary pain disorders, multiregional pain, infectious illness, hypermobility of joints, iron deficiency and small-fiber polyneuropathy.[61]Metal-induced allergic inflammation has also been linked with fibromyalgia, especially in response to
nickel but also inorganic
mercury,
cadmium, and
lead.[62] Following the
COVID-19 pandemic, some have suggested that the
SARS-CoV-2 virus may trigger fibromyalgia.[63]
Pathophysiology
As of 2022, the pathophysiology of fibromyalgia has not yet been elucidated[64] and several theories have been suggested. The prevailing perspective considers fibromyalgia as a condition resulting from an amplification of pain by the central nervous system.[53] Substantial biological evidence backs up this notion, leading to the term of
nociplastic pain.[53]
Fibromyalgia can be viewed as a condition of nociplastic pain.[66] Nociplastic pain is caused by an altered function of pain-related sensory pathways in the
periphery and the
central nervous system, resulting in hypersensitivity.[67]
Nociplastic pain is commonly referred to as "Nociplastic pain syndrome" because it is coupled with other symptoms.[21] These include
fatigue,
sleep disturbance,
cognitive disturbance,
hypersensitivity to environmental stimuli, anxiety, and depression.[21] Nociplastic pain is caused by either (1) increased processing of
pain stimuli or (2) decreased suppression of pain stimuli at several levels in the
nervous system, or both.[21]
Some suggest that fibromyalgia is caused or maintained by a decreased vagal tone, which is indicated by low levels of heart rate variability,[55] signaling a heightened
sympathetic response.[70] Accordingly, several studies show that clinical improvement is associated with an increase in heart rate variability.[71][70][72] Some examples of interventions that increase the heart rate variability and vagal tone are meditation, yoga, mindfulness and exercise.[55] In 2023 the Fibromyalgia: Imbalance of Threat and Soothing Systems (FITSS) model was suggested as a working hypothesis.[73] According to the FITSS model, the
salience network (also known as the midcingulo-insular network) may remain continuously hyperactive due to an imbalance in
emotion regulation, which is reflected by an overactive "threat" system and an underactive "soothing" system. This hyperactivation, along with other mechanisms, may contribute to fibromyalgia.[73]
Neurotransmitters
Some neurochemical abnormalities that occur in fibromyalgia also regulate mood,
sleep, and energy, thus explaining why mood, sleep, and
fatigue problems are commonly
co-morbid with fibromyalgia.[23] Serotonin is the most widely studied neurotransmitter in fibromyalgia. It is hypothesized that an imbalance in the serotoninergic system may lead to the development of fibromyalgia.[74] There is also some data that suggests altered dopaminergic and noradrenergic signaling in fibromyalgia.[75] Supporting the monoamine related theories is the efficacy of monoaminergic
antidepressants in fibromyalgia.[17] Glutamate/creatine ratios within the bilateral ventrolateral prefrontal cortex were found to be significantly higher in fibromyalgia patients than in controls, and may disrupt glutamate neurotransmission.[57][76]
Neurophysiology
Neuroimaging studies have observed that fibromyalgia patients have increased
grey matter in the right
postcentral gyrus and left
angular gyrus, and decreased grey matter in the right
cingulate gyrus, right paracingulate gyrus, left
cerebellum, and left
gyrus rectus.[77] These regions are associated with affective and cognitive functions and with motor adaptations to pain processing.[77] Other studies have documented decreased grey matter of the
default mode network in people with fibromyalgia.[78] These deficits are associated with pain processing.[78]
Neuroendocrine system
Studies on the neuroendocrine system and
HPA axis in fibromyalgia have been inconsistent. Depressed function of the HPA axis results in
adrenal insufficiency and potentially chronic fatigue.[79]
One study found fibromyalgia patients exhibited higher plasma
cortisol, more extreme peaks and troughs, and higher rates of
dexamethasone non-suppression. However, other studies have only found correlations between a higher
cortisol awakening response and pain, and not any other abnormalities in cortisol.[31] Increased baseline
ACTH and increase in response to
stress have been observed, hypothesized to be a result of decreased negative feedback.[75]
Oxidative stress
Pro-oxidative processes correlate with pain in fibromyalgia patients.[79] Decreased
mitochondrial membrane potential, increased
superoxide activity, and increased
lipid peroxidation production are observed.[79] The high proportion of lipids in the central nervous system (CNS) makes the CNS especially vulnerable to
free radical damage. Levels of lipid peroxidation products correlate with fibromyalgia symptoms.[79]
Immune system
Inflammation has been suggested to have a role in the pathogenesis of fibromyalgia.[80] People with fibromyalgia tend to have higher levels of inflammatory
cytokinesIL-6,[74][81][82] and
IL-8.[74][81][82] There are also increased levels of the pro-inflammatory cytokines
IL-1 receptor antagonist.[81][82] Increased levels of pro-inflammatory cytokines may increase sensitivity to pain, and contribute to mood problems.[83] Anti-inflammatory interleukins such as
IL-10 have also been associated with fibromyalgia.[74]
A repeated observation shows that
autoimmunity triggers such as traumas and
infections are among the most frequent events preceding the onset of fibromyalgia.[84] Neurogenic inflammation has been proposed as a contributing factor to fibromyalgia.[85]
Digestive system
Gut microbiome
Though there is a lack of evidence in this area, it is hypothesized that
gut bacteria may play a role in fibromyalgia.[86] People with fibromyalgia are more likely to show
dysbiosis, a decrease in microbiota diversity.[87] There is a bidirectional interplay between the gut and the nervous system. Therefore, the gut can affect the nervous system, but the nervous system can also affect the gut. Neurological effects mediated via the
autonomic nervous system as well as the
hypothalamic pituitary adrenal axis are directed to intestinal functional
effector cells, which in turn are under the influence of the gut microbiota.[88]
Despite being a small percentage of the body's total mass, the brain consumes approximately 20% of the energy produced by the body.[57][non-primary source needed] Parts of the brain—the anterior cingulate cortex (ACC), thalamus, and insula—were studied using
proton magnetic resonance spectroscopy (MRS) in patients with fibromyalgia and compared to healthy
controls. The fibromyalgia patients were found to have lower phosphocreatine (PCr) and lower creatine (Cr) than the control group. Phosphocreatine is used in the
phosphagen system to produce
ATP. The study found that low creatine and low phosphocreatine were associated with high pain, and that high stress, including PTSD, may contribute to these low levels.[57][non-primary source needed]
Low phosphocreatine levels may disrupt glutamate neurotransmission within the brains of those with fibromyalgia. Glutamate/creatine ratios within the bilateral ventrolateral prefrontal cortex were found to be significantly higher than in controls.[57][76][non-primary source needed]
Diagnosis
There is no single pathological feature, laboratory finding, or biomarker that can diagnose fibromyalgia and there is debate over what should be considered diagnostic criteria and whether an objective diagnosis is possible.[61] In most cases, people with fibromyalgia symptoms may have laboratory test results that appear normal and many of their symptoms may mimic those of other rheumatic conditions such as arthritis or osteoporosis. The specific diagnostic criteria for fibromyalgia have evolved over time.[95]
American College of Rheumatology 1990
The first widely accepted set of classification criteria for research purposes was elaborated in 1990 by the Multicenter Criteria Committee of the
American College of Rheumatology. These criteria, which are known informally as "the ACR 1990", defined fibromyalgia according to the presence of the following criteria:
A history of widespread pain lasting more than three months – affecting all four quadrants of the body, i.e., both sides, and above and below the waist.
Tender points – there are 18 designated possible tender points (although a person with the disorder may feel pain in other areas as well).
The ACR criteria for the classification of patients were originally established as inclusion criteria for research purposes and were not intended for clinical diagnosis but have later become the de facto diagnostic criteria in the clinical setting. A controversial study was done by a legal team looking to prove their client's disability based primarily on tender points and their widespread presence in non-litigious communities prompted the lead author of the ACR criteria to question now the useful validity of tender points in diagnosis.[96] Use of control points has been used to cast doubt on whether a person has fibromyalgia, and to claim the person is malingering.[97]
American College of Rheumatology 2010 provisional criteria
In 2010, the American College of Rheumatology approved provisional revised diagnostic criteria for fibromyalgia that eliminated the 1990 criteria's reliance on tender point testing.[98] The revised criteria used a widespread pain index (WPI) and symptom severity scale (SSS) in place of tender point testing under the 1990 criteria. The WPI counts up to 19 general body areas[a] in which the person has experienced pain in the preceding week.[9] The SSS rates the severity of the person's fatigue, unrefreshed waking, cognitive symptoms, and general somatic symptoms,[b] each on a scale from 0 to 3, for a composite score ranging from 0 to 12.[9] The revised criteria for diagnosis were:
WPI ≥ 7 and SSS ≥ 5 OR WPI 3–6 and SSS ≥ 9,
Symptoms have been present at a similar level for at least three months, and
No other diagnosable disorder otherwise explains the pain.[98]: 607
American College of Rheumatology 2016 revisions
In 2016, the provisional criteria of the American College of Rheumatology from 2010 were revised.[9] The new diagnosis required all of the following criteria:
"Generalized pain, defined as pain in at least 4 of 5 regions, is present."
"Symptoms have been present at a similar level for at least 3 months."
"Widespread pain index (WPI) ≥ 7 and symptom severity scale (SSS) score ≥ 5 OR WPI of 4–6 and SSS score ≥ 9."
"A diagnosis of fibromyalgia is valid irrespective of other diagnoses. A diagnosis of fibromyalgia does not exclude the presence of other clinically important illnesses."[9]
American Pain Society 2019
In 2019, the
American Pain Society in collaboration with the U.S.
Food and Drug Administration developed a new diagnostic system using two dimensions.[12] The first dimension included core diagnostic criteria and the second included common features. In accordance to the 2016 diagnosis guidelines, the presence of another medical condition or pain disorder does not rule out the diagnosis of fibromyalgia. Nonetheless, other conditions should be ruled out as the main explaining reason for the patient's symptoms. The core diagnostic criteria are:[99]
Multisite pain defined as six or more pain sites from a total of nine possible sites (head, arms, chest, abdomen, upper back, lower back, and legs), for at least three months
Some research has suggested using a multidimensional approach taking into consideration somatic symptoms, psychological factors, psychosocial stressors and subjective belief regarding fibromyalgia.[100] These symptoms can be assessed by several self-report questionnaires.[9]
Widespread Pain Index (WPI)
The Widespread Pain Index (WPI) measures the number of painful body regions.[98]
Symptom Severity Scale (SSS)
The Symptom Severity Scale (SSS) assesses the severity of the fibromyalgia symptoms.
Fibromyalgia Impact Questionnaire (FIQ)
The Fibromyalgia Impact Questionnaire (FIQ)[101] and the Revised Fibromyalgia Impact Questionnaire (FIQR)[102] assess three domains: function, overall impact and symptoms.[102] It is considered a useful measure of disease impact.[103]
Other questionnaires
Other measures include the Hospital Anxiety and Depression Scale,Multiple Ability Self-Report Questionnaire,[104]Multidimensional Fatigue Inventory, andMedical Outcomes Study Sleep Scale.
There is no universally accepted treatment or cure for fibromyalgia, and treatment typically consists of symptom management and improving patient quality of life.[14] A personalized, multidisciplinary approach to treatment that includes both non-pharmacologic and pharmacologic therapy and begins with effective patient education is most beneficial.[14] Developments in the understanding of the pathophysiology of the disorder have led to improvements in treatment, which include prescription medication, behavioral intervention, and exercise.
Exercise is the only fibromyalgia treatment which has been given a strong recommendation by the European Alliance of Associations for Rheumatology (
EULAR). There is strong evidence indicating that exercise improves fitness, sleep and quality of life and may reduce pain and fatigue for people with fibromyalgia.[113][20][114] Exercise has an added benefit in that it does not cause any serious adverse effects.[114]
Exercise may diminish fibromyalgia symptoms through a number of hypothesized biological mechanisms.[115] Exercise may improve pain modulation[116][117] through serotoninergic pathways.[117] It may reduce pain by altering the hypothalamic-pituitary-adrenal axis and reducing cortisol levels.[118] It also has anti-inflammatory effects that may improve fibromyalgia symptoms.[119][120] Aerobic exercise can improve muscle metabolism and pain through mitochondrial pathways.[119]
When comparing different exercise programs, aerobic exercise is capable of modulating the autonomic nervous function of fibromyalgia patients, whereas resistance exercise does not show such effects.[121] A 2022 meta-analysis found that aerobic training showed a high effect size while strength interventions showed moderate effects.[122] Meditative exercise seems preferable for improving sleep,[123][124] with no differences between resistance, flexibility and aquatic exercise in their favorable effects on fatigue.[123]
Despite its benefits, exercise is a challenge for patients with fibromyalgia, due to the chronic fatigue and pain they experience.[125] They perceive it as more effortful than healthy adults.[126] Exercise may intimidate them, in fear that they will be asked to do more than they are capable of.[127] They may also feel that those who recommend or deliver exercise interventions do not fully understand the possible negative impact of exercise on fatigue and pain.[127] This is especially true for non-personalized exercise programs.[127] Adherence is higher when the exercise program is recommended by doctors or supervised by nurses.[128] Depression and higher pain intensity serve as barriers to physical activity.[129] A recommended approach to a graded exercise program begins with small, frequent exercise periods and builds up from there.[122][130] In order to reduce pain, it is recommended to use an exercise program of 13 to 24 weeks, with each session lasting 30 to 60 minutes.[122]
Aerobic
Aerobic exercise for fibromyalgia patients is the most investigated type of exercise.[114] It includes activities such as walking, jogging, spinning, cycling, dancing and exercising in water,[119][121] with walking being named as one of the best methods.[131] A 2017 cochrane summary concluded that aerobic exercise probably improves quality of life, slightly decreases pain and improves physical function and makes no difference in fatigue and stiffness.[132] A 2019 meta-analysis showed that exercising aerobically can reduce autonomic dysfunction and increase heart rate variability.[121] This happens when patients exercise at least twice a week, for 45–60 minutes at about 60%-80% of the maximum heart rate.[121] Aerobic exercise also decreases anxiety and depression and improves the quality of life.[121]
Flexibility
Combinations of different exercises such as flexibility and aerobic training may improve stiffness.[133] However, the evidence is of low-quality.[133] It is not clear if flexibility training alone compared to aerobic training is effective at reducing symptoms or has any adverse effects.[134]
Resistance
In
resistance exercise, participants apply a load to their body using weights, elastic band, body weight or other measures.
Two meta-analyses on fibromyalgia have shown that resistance training can reduce anxiety and depression,[121][135] one found that it decreases pain and disease severity[136] and one found that it improves quality of life.[121] Resistance training may also improve sleep, with a greater effect than that of flexibility training and a similar effect to that of aerobic exercise.[137]
The dosage of
resistance exercise for women with fibromyalgia was studied in a 2022
meta-analysis.[138] Effective dosages were found when exercising twice a week, for at least eight weeks. Symptom improvement was found for even low dosages such as 1–2 sets of 4–20 repetitions.[138] Most studies use moderate
exercise intensity of 40% to 85%
one-repetition maximum. This level of
intensity was effective in reducing pain.[138] Some treatment regimes increase the intensity over time (from 40% to 80%), whereas others increase it when the participant is able to perform 12 repetitions.[138] High-intensity exercises may cause lower
treatment adherence.
Meditative
A 2021
meta-analysis found that
meditative exercise programs (
tai chi,
yoga,
qigong) were superior to other forms of exercise (
aerobic,
flexibility,
resistance) in improving
sleep quality.[123] Other meta-analyses also found positive effects of tai chi for sleep,[139] fibromyalgia symptoms,[140] and pain, fatigue, depression and quality of life.[141] These tai chi interventions frequently included 1-hour sessions practiced 1-3 times a week for 12 weeks. Meditative exercises, as a whole, may achieve desired outcomes through biological mechanisms such as
antioxidation,
anti-inflammation, reduction in
sympathetic activity and modulation of
glucocorticoid receptor sensitivity.[119]
Aquatic
Several reviews and meta-analyses suggest that aquatic training can improve symptoms and wellness in people with fibromyalgia.[142][143][144][145][146][147] It is recommended to practice aquatic therapy at least twice a week using a low to moderate intensity.[146] However,
aquatic therapy does not appear to be superior to other types of exercise.[148]
Other
Limited evidence suggests
vibration training in combination with exercise may improve pain, fatigue, and stiffness.[149]
Medications
A few countries have published guidelines for the management and treatment of fibromyalgia. As of 2018, all of them emphasize that medications are not required. However, medications, though imperfect, continue to be a component of treatment strategy for fibromyalgia patients. The
German guidelines outlined parameters for drug therapy termination and recommended considering
drug holidays after six months.[16]
Antidepressants are one of the common drugs for fibromyalgia. A 2021 meta-analysis concluded that antidepressants can improve the quality of life for fibromyalgia patients in the medium-term.[17] For most people with fibromyalgia, the potential benefits of treatment with the serotonin and norepinephrine reuptake inhibitors duloxetine and milnacipran and the tricyclic antidepressants, such as amitriptyline, are outweighed by significant adverse effects (more adverse effects than benefits), however, a small number of people may experience relief from symptoms with these medications.[152][153][154]
The length of time that antidepressant medications take to be effective at reducing symptoms can vary. Any potential benefits from the antidepressant amitriptyline may take up to three months to take effect and it may take between three and six months for duloxetine, milnacipran, and pregabalin to be effective at improving symptoms.[155] Some medications have the potential to cause withdrawal symptoms when stopping so gradual discontinuation may be warranted particularly for antidepressants and pregabalin.[97]
Serotonin and norepinephrine reuptake inhibitors
A 2023 meta analysis found that duloxetine improved fibromyalgia symptoms, regardless of the dosage.[156] SSRIs may be also be used to treat depression in people diagnosed with fibromyalgia.[157]
Tricyclic antidepressants
While amitriptyline has been used as a first line treatment, the quality of evidence to support this use and comparison between different medications is poor.[158][154] Very weak evidence indicates that a very small number of people may benefit from treatment with the
tetracyclic antidepressantmirtazapine, however, for most, the potential benefits are not great and the risk of adverse effects and potential harm outweighs any potential for benefit.[159] As of 2018, the only
tricyclic antidepressant that has sufficient evidence is
amitriptyline.[16][158]
Monoamine oxidase inhibitors
Tentative evidence suggests that
monoamine oxidase inhibitors (MAOIs) such as
pirlindole and
moclobemide are moderately effective for reducing pain.[160] Very low-quality evidence suggests pirlindole as more effective at treating pain than moclobemide.[160] Side effects of MAOIs may include nausea and vomiting.[160]
Central nervous system depressants
Central nervous system depressants include drug categories such as sedatives, tranquilizers, and hypnotics. A 2021 meta-analysis concluded that such drugs can improve the quality of life for fibromyalgia patients in the medium-term.[17]
Anti-seizure medication
The anti-convulsant medications
gabapentin and
pregabalin may be used to reduce pain.[8] There is tentative evidence that gabapentin may be of benefit for pain in about 18% of people with fibromyalgia.[8] It is not possible to predict who will benefit, and a short trial may be recommended to test the effectiveness of this type of medication. Approximately 6/10 people who take gabapentin to treat pain related to fibromyalgia experience unpleasant side effects such as dizziness, abnormal walking, or swelling from fluid accumulation.[161] Pregabalin demonstrates a benefit in about 9% of people.[162] Pregabalin reduced time off work by 0.2 days per week.[163]
Cannabinoids
Cannabinoids may have some benefits for people with fibromyalgia. However, as of 2022, the data on the topic is still limited.[164][165][166] Cannabinoids may also have adverse effects and may negatively interact with common rheumatological drugs.[167]
Opioids
The use of opioids is controversial. As of 2015, no opioid is approved for use in this condition by the FDA.[168] A 2016
Cochrane review concluded that there is no good evidence to support or refute the suggestion that
oxycodone, alone or in combination with
naloxone, reduces pain in fibromyalgia.[169] The
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) in 2014 stated that there was a lack of evidence for opioids for most people.[5] The
Association of the Scientific Medical Societies in Germany in 2012 made no recommendation either for or against the use of weak
opioids because of the limited amount of scientific research addressing their use in the treatment of fibromyalgia. They strongly advise against using strong opioids.[110] The
Canadian Pain Society in 2012 said that opioids, starting with a weak opioid like tramadol, can be tried but only for people with moderate to severe pain that is not well-controlled by non-opioid painkillers. They discourage the use of strong opioids and only recommend using them while they continue to provide improved pain and functioning. Healthcare providers should monitor people on opioids for ongoing effectiveness, side effects, and possible unwanted drug behaviors.[112]
A 2015 review found fair evidence to support tramadol use if other medications do not work.[168] A 2018 review found little evidence to support the combination of
paracetamol (acetaminophen) and tramadol over a single medication.[170] Goldenberg et al suggest that tramadol works via its serotonin and norepinephrine reuptake inhibition, rather than via its action as a weak opioid receptor agonist.[171]
A large study of US people with fibromyalgia found that between 2005 and 2007 37.4% were prescribed short-acting opioids and 8.3% were prescribed long-acting opioids,[3] with around 10% of those prescribed short-acting opioids using tramadol;[172] and a 2011 Canadian study of 457 people with fibromyalgia found 32% used opioids and two-thirds of those used strong opioids.[112]
Topical treatment
Capsaicin has been suggested as a topical pain reliever. Preliminary results suggest that it may improve sleep quality and fatigue, but there are not enough studies to support this claim.[173]
Unapproved or unfounded
Sodium oxybate increases growth hormone production levels through increased slow-wave sleep patterns. However, this medication was not approved by the FDA for the indication for use in people with fibromyalgia due to the concern for
abuse.[174]
The muscle relaxants
cyclobenzaprine,
carisoprodol with acetaminophen and caffeine, and
tizanidine are sometimes used to treat fibromyalgia; however, as of 2015 they are not approved for this use in the United States.[175][176] The use of nonsteroidal anti-inflammatory drugs is not recommended as first-line therapy.[177] Moreover, nonsteroidal anti-inflammatory drugs cannot be considered as useful in the management of fibromyalgia.[178]
Very low-quality evidence suggests
quetiapine may be effective in fibromyalgia.[179]
No high-quality evidence exists that suggests synthetic
THC (
nabilone) helps with fibromyalgia.[180]
Nutrition and dietary supplements
Nutrition is related to fibromyalgia in several ways. Some nutritional risk factors for fibromyalgia complications are obesity, nutritional deficiencies, food allergies and consuming food additives.[181] The consumption of fruits and vegetables, low-processed foods, high-quality proteins, and healthy fats may have some benefits.[181] Low-quality evidence found some benefits of a vegetarian or
vegan diet.[182]
Although
dietary supplements have been widely investigated in relation to fibromyalgia, most of the evidence, as of 2021, is of poor quality. It is therefore difficult to reach conclusive recommendations.[183] It appears that
Q10 coenzyme and
vitamin D supplements can reduce pain and improve quality of life for fibromyalgia patients.[20][184] Q10 coenzyme has beneficial effects on
fatigue in fibromyalgia patients, with most studies using doses of 300 mg per day for three months.[185] Q10 coenzyme is hypothesized to improve mitochondrial activity and decrease inflammation.[186] Vitamin D has been shown to improve some fibromyalgia measures, but not others.[184][187]
Due to the uncertainty about the pathogenesis of fibromyalgia, current treatment approaches focus on management of symptoms to improve quality of life,[190] using integrated pharmacological and non-pharmacological approaches.[4] There is no single intervention shown to be effective for all patients.[191] In a 2020 Cochrane review,
cognitive behavioral therapy was found to have a small but beneficial effect for reducing pain and distress but adverse events were not well evaluated.[192] Cognitive behavioral therapy and related psychological and behavioural therapies have a small to moderate effect in reducing symptoms of fibromyalgia.[193][194] Effect sizes tend to be small when cognitive behavioral therapy is used as a stand-alone treatment for patients with fibromyalgia, but these improve significantly when it is part of a wider multidisciplinary treatment program.[194]
A 2010 systematic review of 14 studies reported that cognitive behavioral therapy improves self-efficacy or coping with pain and reduces the number of physician visits at post-treatment, but has no significant effect on pain, fatigue, sleep, or health-related quality of life at post-treatment or follow-up. Depressed mood was also improved but this could not be distinguished from some risks of bias.[195] A 2022 meta-analysis found that cognitive behavioral therapy reduces insomnia in people with chronic pain, including people with fibromyalgia.[196]Acceptance and commitment therapy, a type of cognitive behavioral therapy, has also proven effective.[197]
Patient education
Patient education is recommended by the
European League Against Rheumatism (EULAR) as an important treatment component.[15] As of 2022, there is only low-quality evidence showing that patient education can decrease pain and fibromyalgia impact.[198][199]
Sleep hygiene interventions show low effectiveness in improving insomnia in people with chronic pain.[196]
Manual therapy
A 2021 meta-analysis concluded that
massage and
myofascial release diminish pain in the medium-term.[17] As of 2015, there was no good evidence for the benefit of other mind-body therapies.[200]
Acupuncture
A 2013 review found moderate-level evidence on the usage of acupuncture with electrical stimulation for improvement of the overall well-being. Acupuncture alone will not have the same effects, but will enhance the influence of exercise and medication in pain and stiffness.[201]
Transcutaneous electrical nerve stimulation (TENS) is the delivery of pulsed electrical currents to the
skin to stimulate
peripheral nerves. TENS is widely used to treat pain and is considered to be a low-cost, safe, and self-administered treatment.[204] As such, it is commonly recommended by clinicians to people suffering from pain.[205] On 2019, an overview of eight
Cochrane reviews was conducted, covering 51 TENS-related
randomized controlled trials.[205] The review concluded that the quality of the available evidence was insufficient to make any recommendations.[205] A later review concluded that transcutaneous electrical nerve stimulation may diminish pain in the short-term, but there was uncertainty about the relevance of the results.[17]
Preliminary findings suggest that electrically stimulating the
vagus nerve through an implanted device can potentially reduce fibromyalgia symptoms.[206] However, there may be adverse reactions to the procedure.[206]
Noninvasive brain stimulation
Noninvasive brain stimulation includes methods such as transcranial direct current stimulation and high-frequency repetitive
transcranial magnetic stimulation (TMS). Both methods have been found to improve pain scores in
neuropathic pain and fibromyalgia.[207]
A 2021 meta-analysis of multiple intervention types concluded that magnetic field therapy and transcranial magnetic stimulation may diminish pain in the short-term, but conveyed an uncertainty about the relevance of the result.[17] Several 2022 meta-analyses focusing on transcranial magnetic stimulation found positive effects on fibromyalgia.[209][210][211] Repetitive transcranial magnetic stimulation improved pain in the short-term[210][211] and quality of life after 5–12 weeks.[210][211] Repetitive transcranial magnetic stimulation did not improve anxiety, depression, and fatigue.[211] Transcranial magnetic stimulation to the left dorsolateral prefrontal cortex was also ineffective.[210]
EEG neurofeedback
A systematic review of
EEG neurofeedback for treatment of fibromyalgia found most treatments showed significant improvements of the main symptoms of the disease.[212] However, the protocols were so different, and the lack of
controls or randomization impede drawing conclusive results.[212]
Hyperbaric oxygen therapy
Hyperbaric oxygen therapy (HBOT) has shown beneficial effects in treating chronic pain by reducing inflammation and oxidative stress.[79] However, treating fibromyalgia with hyperbaric oxygen therapy is still controversial, in light of the scarcity of large-scale clinical trials.[119] In addition, hyperbaric oxygen therapy raises safety concerns due to the
oxidative damage that may follow it.[119] An evaluation of nine trials with 288 patients in total found that HBOT was more effective at relieving fibromyalgia patients' pain than the control intervention. In most of the trials HBOT improved sleep disturbance, multidimensional function, patient satisfaction, and tender spots. 24% of the patients experienced negative outcomes.[213]
Prognosis
Although in itself fibromyalgia is neither
degenerative nor fatal, the
chronic pain of fibromyalgia is pervasive and persistent. Most people with fibromyalgia report that their symptoms do not improve over time. However, most patients learn to adapt to the symptoms over time. The
German guidelines for patients explain that:
The symptoms of fibromyalgia are persistent in nearly all patients.
An 11-year
follow-up study on 1,555 patients found that most remained with high levels of self-reported symptoms and distress.[non-primary source needed][214] However, there was a great deal of patient
heterogeneity accounting for almost half of the
variance. At the final observation, 10% of the patients showed substantial improvement with minimal symptoms. An additional 15% had moderate improvement. This state, though, may be transient, given the fluctuations in symptom severity.[non-primary source needed][214]
A study of 97
adolescents diagnosed with fibromyalgia followed them for eight years.[non-primary source needed] After eight years, the majority of youth still experienced pain and
disability in physical, social, and psychological areas. At the last follow-up, all participants reported experiencing one or more fibromyalgia symptoms such as pain, fatigue, and/or
sleep problems, with 58% matching the complete ACR 2010 criteria for fibromyalgia. Based on the WPI and SS score cut-points, the remaining 42% exhibited subclinical symptoms. Pain and emotional symptom trajectories, on the other hand, displayed a variety of longitudinal patterns. The study concluded that while most patient's fibromyalgia symptoms endure, the severity of their pain tends to reduce over time.[215]
Baseline
depressive symptoms in adolescents appear to predict worse pain at follow-up periods.[216][217]
A meta-analysis based on close to 200,000 fibromyalgia patients found that they were at a higher risk for
all-cause mortality. Specific mortality causes that were suggested were
accidents,
infections and
suicide.[218]
Epidemiology
Fibromyalgia is estimated to affect 1.8% of the population.[219]
Despite the fact that more than 90% of fibromyalgia patients are women, only 60% of people with fibromyalgia symptoms are female in the general population.[220]
History
Chronic widespread pain had already been described in the literature in the 19th century but the term fibromyalgia was not used until 1976 when Dr P.K. Hench used it to describe these symptoms.[97] Many names, including "muscular rheumatism", "fibrositis", "psychogenic rheumatism", and "
neurasthenia" were applied historically to symptoms resembling those of fibromyalgia.[221] The term fibromyalgia was coined by researcher Mohammed Yunus as a synonym for fibrositis and was first used in a scientific publication in 1981.[222] Fibromyalgia is from the
Latinfibra (fiber)[223] and the
Greek words myo (muscle)[224] and algos (pain).[225]
Historical perspectives on the development of the fibromyalgia concept note the "central importance" of a 1977 paper by Smythe and Moldofsky on fibrositis.[226][227] The first
clinical, controlled study of the characteristics of fibromyalgia syndrome was published in 1981,[228] providing support for symptom associations. In 1984, an interconnection between fibromyalgia syndrome and other similar conditions was proposed,[229] and in 1986, trials of the first proposed medications for fibromyalgia were published.[229]
People with fibromyalgia generally have higher healthcare costs and utilization rates. A review of 36 studies found that fibromyalgia causes a significant economic burden on health care systems.[232] Annual costs per patient were estimated to be up to $35,920 in the US and $8,504 in Europe.[232]
Controversies
Fibromyalgia was defined relatively recently. In the past, it was a disputed diagnosis. Frederick Wolfe, lead author of the 1990 paper that first defined the diagnostic guidelines for fibromyalgia, stated in 2008 that he believed it "clearly" not to be a disease but instead a physical response to depression and stress.[233] In 2013, Wolfe added that its causes "are controversial in a sense" and "there are many factors that produce these symptoms – some are psychological and some are physical and it does exist on a continuum".[234] Some members of the medical community do not consider fibromyalgia a disease because of a lack of abnormalities on physical examination and the absence of objective diagnostic tests.[226][235]
In the past, some psychiatrists have viewed fibromyalgia as a type of
affective disorder, or a
somatic symptom disorder. These controversies do not engage healthcare specialists alone; some patients object to fibromyalgia being described in purely somatic terms.[236]
As of 2022,
neurologists and pain specialists tend to view fibromyalgia as a pathology due to dysfunction of muscles and connective tissue as well as functional abnormalities in the central nervous system.
Rheumatologists define the syndrome in the context of "
central sensitization" – heightened brain response to normal stimuli in the absence of disorders of the muscles, joints, or connective tissues. Because of this symptomatic overlap, some researchers have proposed that fibromyalgia and other analogous syndromes be classified together as central sensitivity syndromes.[237][13]
Notes
^Shoulder girdle (left & right), upper arm (left & right), lower arm (left & right), hip/buttock/trochanter (left & right), upper leg (left & right), lower leg (left & right), jaw (left & right), chest, abdomen, back (upper & lower), and neck.[98]: 607
^Somatic symptoms include, but are not limited to: muscle pain, irritable bowel syndrome, fatigue or tiredness, problems thinking or remembering, muscle weakness, headache, pain or cramps in the abdomen, numbness or tingling, dizziness, insomnia, depression, constipation, pain in the upper abdomen, nausea, nervousness, chest pain, blurred vision, fever, diarrhea, dry mouth, itching, wheezing, Raynaud's phenomenon, hives or welts, ringing in the ears, vomiting, heartburn, oral ulcers, loss of or changes in taste, seizures, dry eyes, shortness of breath, loss of appetite, rash, sun sensitivity, hearing difficulties, easy bruising, hair loss, frequent or painful urination, and bladder spasms.[98]: 607
References
^"fibromyalgia". Collins Dictionaries.
Archived from the original on 4 October 2015. Retrieved 16 March 2016.
^Ferri FF (2010). "Chapter F". Ferri's differential diagnosis: a practical guide to the differential diagnosis of symptoms, signs, and clinical disorders (2nd ed.). Philadelphia, PA: Elsevier/Mosby.
ISBN978-0-323-07699-9.
^Schneider MJ, Brady DM, Perle SM (2006). "Commentary: differential diagnosis of fibromyalgia syndrome: proposal of a model and algorithm for patients presenting with the primary symptom of chronic widespread pain". Journal of Manipulative and Physiological Therapeutics. 29 (6): 493–501.
doi:
10.1016/j.jmpt.2006.06.010.
PMID16904498.
^
abcPrabhakar A, Kaiser JM, Novitch MB, Cornett EM, Urman RD, Kaye AD (March 2019). "The Role of Complementary and Alternative Medicine Treatments in Fibromyalgia: a Comprehensive Review". Current Rheumatology Reports. 21 (5): 14.
doi:
10.1007/s11926-019-0814-0.
PMID30830504.
S2CID73482737.
^Martinez JE, Guimarães I (February 2024). ""Fibromyalgia - are there any new approaches?"". Best Pract Res Clin Rheumatol: 101933.
doi:
10.1016/j.berh.2024.101933.
PMID38355316.
^Besiroglu MD, Dursun MD (July 2019). "The association between fibromyalgia and female sexual dysfunction: a systematic review and meta-analysis of observational studies". International Journal of Impotence Research. 31 (4): 288–297.
doi:
10.1038/s41443-018-0098-3.
PMID30467351.
S2CID53717513.
^"Archived copy". academic.oup.com.
Archived from the original on 21 May 2023. Retrieved 11 February 2024.{{
cite web}}: CS1 maint: archived copy as title (
link)
^Spaeth M, Rizzi M, Sarzi-Puttini P (April 2011). "Fibromyalgia and sleep". Best Practice & Research. Clinical Rheumatology. 25 (2): 227–239.
doi:
10.1016/j.berh.2011.03.004.
PMID22094198.
^
abcdefghKleykamp BA, Ferguson MC, McNicol E, Bixho I, Arnold LM, Edwards RR, et al. (February 2021). "The Prevalence of Psychiatric and Chronic Pain Comorbidities in Fibromyalgia: an ACTTION systematic review". Seminars in Arthritis and Rheumatism. 51 (1): 166–174.
doi:
10.1016/j.semarthrit.2020.10.006.
PMID33383293.
S2CID229948862.
^Habibi Asgarabad M, Salehi Yegaei P, Jafari F, Azami-Aghdash S, Lumley MA (March 2023). "The relationship of alexithymia to pain and other symptoms in fibromyalgia: A systematic review and meta-analysis". European Journal of Pain. 27 (3): 321–337.
doi:
10.1002/ejp.2064.
PMID36471652.
S2CID254273680.
^Løge-Hagen JS, Sæle A, Juhl C, Bech P, Stenager E, Mellentin AI (February 2019). "Prevalence of depressive disorder among patients with fibromyalgia: Systematic review and meta-analysis". Journal of Affective Disorders. 245: 1098–1105.
doi:
10.1016/j.jad.2018.12.001.
PMID30699852.
S2CID73411416.
^Anderson G, Maes M (December 2020). "Mitochondria and immunity in chronic fatigue syndrome". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 103: 109976.
doi:
10.1016/j.pnpbp.2020.109976.
PMID32470498.
S2CID219104988.
^D'Onghia M, Ciaffi J, Lisi L, Mancarella L, Ricci S, Stefanelli N, et al. (April 2021). "Fibromyalgia and obesity: A comprehensive systematic review and meta-analysis". Seminars in Arthritis and Rheumatism. 51 (2): 409–424.
doi:
10.1016/j.semarthrit.2021.02.007.
PMID33676126.
S2CID232136088.
^Goldberg N, Tamam S, Weintraub AY (December 2022). "The association between overactive bladder and fibromyalgia: A systematic review and meta-analysis". International Journal of Gynaecology and Obstetrics. 159 (3): 630–641.
doi:
10.1002/ijgo.14290.
PMID35641437.
S2CID249236213.
^
abcAblin JN, Buskila D (February 2015). "Update on the genetics of the fibromyalgia syndrome". Best Practice & Research. Clinical Rheumatology. 29 (1): 20–28.
doi:
10.1016/j.berh.2015.04.018.
PMID26266996.
^Lee YH, Choi SJ, Ji JD, Song GG (February 2012). "Candidate gene studies of fibromyalgia: a systematic review and meta-analysis". Rheumatology International. 32 (2): 417–426.
doi:
10.1007/s00296-010-1678-9.
PMID21120487.
S2CID6239018.
^
abcMartins DF, Viseux FJ, Salm DC, Ribeiro AC, da Silva HK, Seim LA, et al. (December 2021). "The role of the vagus nerve in fibromyalgia syndrome". Neuroscience and Biobehavioral Reviews. 131: 1136–1149.
doi:
10.1016/j.neubiorev.2021.10.021.
PMID34710514.
S2CID239772451.
^Casale R, Sarzi-Puttini P, Botto R, Alciati A, Batticciotto A, Marotto D, Torta R (January 2019).
"Fibromyalgia and the concept of resilience". Clinical and Experimental Rheumatology. 37 (1): 105–113.
PMID30747098.
Archived from the original on 9 April 2022. Retrieved 9 April 2022.
^de Tommaso M, Vecchio E, Nolano M (March 2022). "The puzzle of fibromyalgia between central sensitization syndrome and small fiber neuropathy: a narrative review on neurophysiological and morphological evidence". Neurological Sciences. 43 (3): 1667–1684.
doi:
10.1007/s10072-021-05806-x.
PMID35028777.
S2CID245909381.
^den Boer C, Dries L, Terluin B, van der Wouden JC, Blankenstein AH, van Wilgen CP, et al. (February 2019). "Central sensitization in chronic pain and medically unexplained symptom research: A systematic review of definitions, operationalizations and measurement instruments". Journal of Psychosomatic Research. 117: 32–40.
doi:
10.1016/j.jpsychores.2018.12.010.
PMID30665594.
S2CID58565532.
^Bidari A, Ghavidel-Parsa B (October 2022). "Nociplastic pain concept, a mechanistic basis for pragmatic approach to fibromyalgia". Clinical Rheumatology. 41 (10): 2939–2947.
doi:
10.1007/s10067-022-06229-5.
PMID35701625.
S2CID249650477.
^
abcRodriguez-Pintó I, Agmon-Levin N, Howard A, Shoenfeld Y (October 2014). "Fibromyalgia and cytokines". Immunology Letters. 161 (2): 200–203.
doi:
10.1016/j.imlet.2014.01.009.
PMID24462815.
^Dell'Osso L, Bazzichi L, Baroni S, Falaschi V, Conversano C, Carmassi C, Marazziti D (1 January 2015). "The inflammatory hypothesis of mood spectrum broadened to fibromyalgia and chronic fatigue syndrome". Clinical and Experimental Rheumatology. 33 (1 Suppl 88): S109–S116.
PMID25786052.
^
abBazzichi L, Giacomelli C, Consensi A, Giorgi V, Batticciotto A, Di Franco M, Sarzi-Puttini P (2020). "One year in review 2020: fibromyalgia". Clinical and Experimental Rheumatology. 38 (1): 3–8.
PMID32116216.
^Littlejohn G (November 2015). "Neurogenic neuroinflammation in fibromyalgia and complex regional pain syndrome". Nature Reviews. Rheumatology. 11 (11): 639–648.
doi:
10.1038/nrrheum.2015.100.
PMID26241184.
S2CID4368913.
^Minerbi A, Fitzcharles MA (January 2020). "Gut microbiome: pertinence in fibromyalgia". Clinical and Experimental Rheumatology. 38 (1): 99–104.
PMID32116215.
^Bengtsson A, Henriksson KG, Larsson J (July 1986). "Reduced high-energy phosphate levels in the painful muscles of patients with primary fibromyalgia". Arthritis and Rheumatism. 29 (7): 817–821.
doi:
10.1002/art.1780290701.
PMID3741498.
^
abcdefWolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Katz RS, Mease P, et al. (May 2010). "The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity". Arthritis Care & Research. 62 (5): 600–610.
doi:
10.1002/acr.20140.
hdl:2027.42/75772.
PMID20461783.
S2CID17154205.
^Wang SM, Han C, Lee SJ, Patkar AA, Masand PS, Pae CU (June 2015). "Fibromyalgia diagnosis: a review of the past, present and future". Expert Review of Neurotherapeutics. 15 (6): 667–679.
doi:
10.1586/14737175.2015.1046841.
PMID26035624.
S2CID2412984.
^Seidenberg M, Haltiner A, Taylor MA, Hermann BB, Wyler A (February 1994). "Development and validation of a Multiple Ability Self-Report Questionnaire". Journal of Clinical and Experimental Neuropsychology. 16 (1): 93–104.
doi:
10.1080/01688639408402620.
PMID8150893.
^
abcGoldenberg DL (December 2009). "Diagnosis and differential diagnosis of fibromyalgia". The American Journal of Medicine (Review). 122 (12 Suppl): S14–S21.
doi:
10.1016/j.amjmed.2009.09.007.
PMID19962492.
^
abRossi A, Di Lollo AC, Guzzo MP, Giacomelli C, Atzeni F, Bazzichi L, Di Franco M (2015). "Fibromyalgia and nutrition: what news?". Clinical and Experimental Rheumatology. 33 (1 Suppl 88): S117–S125.
PMID25786053.
^
abMarchesoni A, De Marco G, Merashli M, McKenna F, Tinazzi I, Marzo-Ortega H, McGonagle DG (January 2018). "The problem in differentiation between psoriatic-related polyenthesitis and fibromyalgia". Rheumatology (Review). 57 (1): 32–40.
doi:
10.1093/rheumatology/kex079.
PMID28387854.
S2CID205309871.
^Busch AJ, Barber KA, Overend TJ, Peloso PM, Schachter CL (October 2007). "Exercise for treating fibromyalgia syndrome". The Cochrane Database of Systematic Reviews (4): CD003786.
doi:
10.1002/14651858.CD003786.pub2.
PMID17943797.
^
abcAndrade A, Dominski FH, Sieczkowska SM (December 2020). "What we already know about the effects of exercise in patients with fibromyalgia: An umbrella review". Seminars in Arthritis and Rheumatism. 50 (6): 1465–1480.
doi:
10.1016/j.semarthrit.2020.02.003.
PMID32147091.
S2CID212638860.
^Andrade A, Vilarino GT, Sieczkowska SM, Coimbra DR, Steffens RA, Vietta GG (March 2018). "Acute effects of physical exercises on the inflammatory markers of patients with fibromyalgia syndrome: A systematic review". Journal of Neuroimmunology. 316: 40–49.
doi:
10.1016/j.jneuroim.2017.12.007.
PMID29254627.
S2CID46879701.
^
abcdefgAndrade A, Vilarino GT, Serafim TT, Pereira Júnior AA, de Souza CA, Sieczkowska SM (October 2019). "Modulation of Autonomic Function by Physical Exercise in Patients with Fibromyalgia Syndrome: A Systematic Review". PM&R. 11 (10): 1121–1131.
doi:
10.1002/pmrj.12158.
PMID30900831.
S2CID85448644.
^
abcAlbuquerque ML, Monteiro D, Marinho DA, Vilarino GT, Andrade A, Neiva HP (November 2022). "Effects of different protocols of physical exercise on fibromyalgia syndrome treatment: systematic review and meta-analysis of randomized controlled trials". Rheumatology International. 42 (11): 1893–1908.
doi:
10.1007/s00296-022-05140-1.
hdl:10400.8/7188.
PMID35604435.
S2CID248970279.
^McVeigh JG, Lucas A, Hurley DA, Basford JR, Baxter GD (September 2003). "Patients' perceptions of exercise therapy in the treatment of fibromyalgia syndrome: a survey". Musculoskeletal Care. 1 (2): 98–107.
doi:
10.1002/msc.45.
PMID20217670.
^
abcRussell D, Álvarez Gallardo IC, Wilson I, Hughes CM, Davison GW, Sañudo B, McVeigh JG (March 2018). "'Exercise to me is a scary word': perceptions of fatigue, sleep dysfunction, and exercise in people with fibromyalgia syndrome-a focus group study". Rheumatology International. 38 (3): 507–515.
doi:
10.1007/s00296-018-3932-5.
PMID29340774.
S2CID3395036.
^Sanz-Baños Y, Pastor-Mira MÁ, Lledó A, López-Roig S, Peñacoba C, Sánchez-Meca J (October 2018). "Do women with fibromyalgia adhere to walking for exercise programs to improve their health? Systematic review and meta-analysis". Disability and Rehabilitation. 40 (21): 2475–2487.
doi:
10.1080/09638288.2017.1347722.
PMID28687050.
S2CID9032840.
^Vilarino GT, Andreato LV, de Souza LC, Branco JH, Andrade A (November 2021). "Effects of resistance training on the mental health of patients with fibromyalgia: a systematic review". Clinical Rheumatology. 40 (11): 4417–4425.
doi:
10.1007/s10067-021-05738-z.
PMID33987785.
S2CID234489153.
^
abcdda Silva JM, de Barros BS, Almeida GJ, O'Neil J, Imoto AM (March 2022). "Dosage of resistance exercises in fibromyalgia: evidence synthesis for a systematic literature review up-date and meta-analysis". Rheumatology International. 42 (3): 413–429.
doi:
10.1007/s00296-021-05025-9.
PMID34652480.
S2CID238991065.
^Li H, Chen J, Xu G, Duan Y, Huang D, Tang C, Liu J (September 2020). "The Effect of Tai Chi for Improving Sleep Quality: A Systematic Review and Meta-analysis". Journal of Affective Disorders. 274: 1102–1112.
doi:
10.1016/j.jad.2020.05.076.
PMID32663938.
S2CID219743962.
^Vasileios P, Styliani P, Nifon G, Pavlos S, Aris F, Ioannis P (November 2022). "Managing fibromyalgia with complementary and alternative medical exercise: a systematic review and meta-analysis of clinical trials". Rheumatology International. 42 (11): 1909–1923.
doi:
10.1007/s00296-022-05151-y.
PMID35796820.
S2CID250317143.
^Cheng CA, Chiu YW, Wu D, Kuan YC, Chen SN, Tam KW (October 2019). "Effectiveness of Tai Chi on fibromyalgia patients: A meta-analysis of randomized controlled trials". Complementary Therapies in Medicine. 46: 1–8.
doi:
10.1016/j.ctim.2019.07.007.
PMID31519264.
S2CID199039433.
^Lima TB, Dias JM, Mazuquin BF, da Silva CT, Nogueira RM, Marques AP, et al. (October 2013). "The effectiveness of aquatic physical therapy in the treatment of fibromyalgia: a systematic review with meta-analysis". Clinical Rehabilitation. 27 (10): 892–908.
doi:
10.1177/0269215513484772.
PMID23818412.
S2CID25701866.
^Galvão-Moreira LV, de Castro LO, Moura EC, de Oliveira CM, Nogueira Neto J, Gomes LM, Leal PD (July 2021). "Pool-based exercise for amelioration of pain in adults with fibromyalgia syndrome: A systematic review and meta-analysis". Modern Rheumatology. 31 (4): 904–911.
doi:
10.1080/14397595.2020.1829339.
PMID32990113.
S2CID222167851.
^
abCalles Plata I, Ortiz-Rubio A, Torres Sánchez I, Cabrera Martos I, Calvache Mateo A, Heredia-Ciuró A, Valenza MC (February 2023). "Effectiveness of aquatic therapy on sleep in persons with fibromyalgia. A meta-analysis". Sleep Medicine. 102: 76–83.
doi:
10.1016/j.sleep.2022.12.016.
PMID36603514.
S2CID255217819.
^Ma J, Zhang T, Li X, Chen X, Zhao Q (September 2022). "Effects of aquatic physical therapy on clinical symptoms, physical function, and quality of life in patients with fibromyalgia: A systematic review and meta-analysis". Physiotherapy Theory and Practice. 40 (2): 205–223.
doi:
10.1080/09593985.2022.2119906.
PMID36062580.
S2CID252079586.
^Häuser W, Wolfe F, Tölle T, Uçeyler N, Sommer C (April 2012). "The role of antidepressants in the management of fibromyalgia syndrome: a systematic review and meta-analysis". CNS Drugs. 26 (4): 297–307.
doi:
10.2165/11598970-000000000-00000.
PMID22452526.
S2CID207301478.
^Nowell WB, Gavigan K, L Silverman S (May 2022). "Cannabis for Rheumatic Disease Pain: a Review of Current Literature". Current Rheumatology Reports. 24 (5): 119–131.
doi:
10.1007/s11926-022-01065-7.
PMID35486218.
S2CID248423563.
^Elijah J, Powell K, Smith MA (June 2022). "The Efficacy of Capsaicin on Sleep Quality and Fatigue in Fibromyalgia". Journal of Pain & Palliative Care Pharmacotherapy. 36 (2): 112–116.
doi:
10.1080/15360288.2022.2063468.
PMID35471125.
S2CID248389141.
^Kaltsas G, Tsiveriotis K (2000).
"Fibromyalgia". Endotext. MDText.com, Inc.
PMID25905317.
Archived from the original on 6 August 2020. Retrieved 20 February 2017.
^
abQu K, Li MX, Zhou YL, Yu P, Dong M (April 2022). "The efficacy of vitamin D in treatment of fibromyalgia: a meta-analysis of randomized controlled studies and systematic review". Expert Review of Clinical Pharmacology. 15 (4): 433–442.
doi:
10.1080/17512433.2022.2081151.
PMID35596576.
S2CID248948241.
^Mehrabani S, Askari G, Miraghajani M, Tavakoly R, Arab A (April 2019). "Effect of coenzyme Q10 supplementation on fatigue: A systematic review of interventional studies". Complementary Therapies in Medicine. 43: 181–187.
doi:
10.1016/j.ctim.2019.01.022.
PMID30935528.
S2CID86467031.
^Erkilic B, Dalgic GS (January 2023). "The preventive role of vitamin D in the prevention and management of Fibromyalgia syndrome". Nutrition and Health. 29 (2): 223–229.
doi:
10.1177/02601060221144801.
PMID36591895.
S2CID255471623.
^
abHemati K, Amini Kadijani A, Sayehmiri F, Mehrzadi S, Zabihiyeganeh M, Hosseinzadeh A, Mirzaei A (February 2020). "Melatonin in the treatment of fibromyalgia symptoms: A systematic review". Complementary Therapies in Clinical Practice. 38: 101072.
doi:
10.1016/j.ctcp.2019.101072.
PMID31783341.
S2CID208497324.
^Gao C, Zhu Q, Gao Z, Zhao J, Jia M, Li T (October 2022). "Can noninvasive Brain Stimulation Improve Pain and Depressive Symptoms in Patients With Neuropathic Pain? A Systematic Review and Meta-Analysis". Journal of Pain and Symptom Management. 64 (4): e203–e215.
doi:
10.1016/j.jpainsymman.2022.05.002.
PMID35550165.
S2CID248715312.
^Teixeira PE, Pacheco-Barrios K, Branco LC, de Melo PS, Marduy A, Caumo W, et al. (November 2022). "The Analgesic Effect of Transcranial Direct Current Stimulation in Fibromyalgia: A Systematic Review, Meta-Analysis, and Meta-Regression of Potential Influencers of Clinical Effect". Neuromodulation. 26 (4): 715–727.
doi:
10.1016/j.neurom.2022.10.044.
PMC 10203058.
PMID36435660.
S2CID253933442.
^
abcdChoo YJ, Kwak SG, Chang MC (July 2022). "Effectiveness of Repetitive Transcranial Magnetic Stimulation on Managing Fibromyalgia: A Systematic Meta-Analysis". Pain Medicine. 23 (7): 1272–1282.
doi:
10.1093/pm/pnab354.
PMID34983056.
^
abcdSun P, Fang L, Zhang J, Liu Y, Wang G, Qi R (March 2022). "Repetitive Transcranial Magnetic Stimulation for Patients with Fibromyalgia: A Systematic Review with Meta-Analysis". Pain Medicine. 23 (3): 499–514.
doi:
10.1093/pm/pnab276.
PMID34542624.
^Leino-Arjas P, Rajaleid K, Mekuria G, Nummi T, Virtanen P, Hammarström A (January 2018). "Trajectories of musculoskeletal pain from adolescence to middle age: the role of early depressive symptoms, a 27-year follow-up of the Northern Swedish Cohort". Pain. 159 (1): 67–74.
doi:
10.1097/j.pain.0000000000001065.
PMID28937577.
S2CID22164186.
^Meuser T, Pietruck C, Radbruch L, Stute P, Lehmann KA, Grond S (September 2001). "Symptoms during cancer pain treatment following WHO-guidelines: a longitudinal follow-up study of symptom prevalence, severity and etiology". Pain. 93 (3): 247–257.
doi:
10.1016/s0304-3959(01)00324-4.
PMID11514084.
S2CID25457728.
^Health Information Team (February 2004).
"Fibromyalgia". BUPA insurance. Archived from
the original on 22 June 2006. Retrieved 24 August 2006.
^Yunus M, Masi AT, Calabro JJ, Miller KA, Feigenbaum SL (August 1981). "Primary fibromyalgia (fibrositis): clinical study of 50 patients with matched normal controls". Seminars in Arthritis and Rheumatism. 11 (1): 151–171.
doi:
10.1016/0049-0172(81)90096-2.
PMID6944796.
^"Fibro-". Dictionary.com.
Archived from the original on 13 December 2009. Retrieved 21 May 2008.
^Smythe HA, Moldofsky H (1977). "Two contributions to understanding of the "fibrositis" syndrome". Bulletin on the Rheumatic Diseases. 28 (1): 928–931.
PMID199304.
^Winfield JB (June 2007). "Fibromyalgia and related central sensitivity syndromes: twenty-five years of progress". Seminars in Arthritis and Rheumatism. 36 (6): 335–338.
doi:
10.1016/j.semarthrit.2006.12.001.
PMID17303220.
^Goldenberg DL (May 1987). "Fibromyalgia syndrome. An emerging but controversial condition". JAMA. 257 (20): 2782–2787.
doi:
10.1001/jama.257.20.2782.
PMID3553636.
^Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, et al. (February 1990). "The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee". Arthritis and Rheumatism. 33 (2): 160–172.
doi:
10.1002/art.1780330203.
PMID2306288.
^
abD'Onghia M, Ciaffi J, Ruscitti P, Cipriani P, Giacomelli R, Ablin JN, Ursini F (October 2022). "The economic burden of fibromyalgia: A systematic literature review". Seminars in Arthritis and Rheumatism. 56: 152060.
doi:
10.1016/j.semarthrit.2022.152060.
PMID35849890.
S2CID250271053.
^Yunus MB (June 2007). "Fibromyalgia and overlapping disorders: the unifying concept of central sensitivity syndromes". Seminars in Arthritis and Rheumatism. 36 (6): 339–356.
doi:
10.1016/j.semarthrit.2006.12.009.
PMID17350675.