Fibromyalgia

• Fibromyalgia is a chronic pain condition in which pain processing in the central nervous system is amplified: ordinary or even trivial signals are felt as pain.
• It is defined clinically by widespread pain present for at least 3 months and a burden of somatic symptoms, diagnosed with the 2016 ACR criteria by scoring the 19 body areas of the Widespread Pain Index (WPI) and a 0 to 12 Symptom Severity Scale (SSS). ^[2]
• Pain, fatigue, unrefreshing sleep and problems with thinking often travel together; low mood and anxiety are common comorbidities, not character flaws. ^[3]
• Blood tests and imaging are used to exclude other disease, not to "prove" fibromyalgia. Inflammatory markers are typically normal.
• Treatment is graduated and multimodal: education, a build-up of aerobic or strengthening exercise, and psychological therapy first; medicines such as amitriptyline, duloxetine and pregabalin are weak, symptom-targeted additions, not cures. ^[1]

By the end of this page you should be able to:

1. Explain fibromyalgia as a disorder of central pain processing (nociplastic pain) rather than joint, muscle or tissue damage.
2. Apply the 2016 ACR diagnostic criteria to a clinical vignette and score the WPI and SSS.
3. List the tests used to exclude inflammatory and endocrine disease, and state what result is expected in uncomplicated fibromyalgia.
4. Outline a graduated management plan that matches treatment to the dominant symptoms (pain, sleep, mood, disability), with typical starting and target doses.
5. Contrast fibromyalgia with inflammatory arthritis, polymyalgia rheumatica, hypothyroidism and depression.
6. Recognise when to avoid opioid and gabapentinoid prescribing and what to do instead.

The International Association for the Study of Pain (IASP) introduced the term nociplastic pain for pain that arises from altered nociception without ongoing tissue damage or a lesion of the nervous system in 2016, and fibromyalgia is its best-known example. ^[2] Under the ICD-11 classification, fibromyalgia is listed as a chronic primary pain syndrome, meaning the pain condition is the diagnosis rather than a symptom of an underlying disease. ^[2]

This represents a shift from the older view of fibromyalgia as a "soft tissue" or muscle disorder. The muscles and joints are not inflamed or damaged; the sensitivity of the pain system itself is changed. Thinking of fibromyalgia this way is what explains the apparently paradoxical findings that follow.

Fibromyalgia is common. Worldwide mean prevalence is about 2.7%, higher in women (global mean about 4.2%) than in men (about 1.4%), a female to male ratio of roughly 3 to 1. ^[3] Method and criteria change the number: prevalence estimates range from under 1% to about 5% depending on the criteria used and the population sampled. ^{[2] [1]}

Women are diagnosed far more often in specialist clinics, but unbiased population surveys show the difference is smaller than the 9 to 1 ratio once quoted: selected referral samples produce far more extreme ratios than community samples. ^{[1] [3]}

Diagnosis is often delayed. In surveys, more than 2 years and an average of 3.7 consultations with different physicians can pass before a diagnosis is made. ^[2]

No single cause has been established. Fibromyalgia is best understood as the end result of multiple interacting contributors.

• Central mechanisms. Altered central pain processing (central sensitisation) and reduced descending inhibition are central to the condition. ^[3] Fibromyalgia belongs to the nociplastic pain syndromes, grouped with idiopathic low back pain, irritable bowel syndrome and chronic tension-type headache. ^[2]
• Sleep. Non-restorative, light sleep is a core feature of fibromyalgia and may precede and amplify pain. ^[2]
• Psychological factors. Depression, anxiety, perceived stress and past trauma are associated with onset and worsen the course, but they are neither necessary nor sufficient, and they do not mean the pain is imagined. ^{[2] [3]}
• Peripheral contributions. Peripheral inflammation and, more recently described, autoantibodies against satellite glial cells have been reported in subsets, although their role is not settled. ^[6]
• Genetics. Familial clustering is common, but no single gene is diagnostic. ^[2]

Risk factors a clinician can recognise include female sex, middle age, a personal or family history of chronic pain syndromes, poor sleep, low physical activity, depression or anxiety. ^[3]

Everything about fibromyalgia follows from one idea: the volume control of the pain system is turned up.

1. Sensory amplification. In fibromyalgia, brain imaging and dynamic testing show an exaggerated response to experimental pain and other sensory stimuli, together with changes in resting connectivity between pain-processing and salience networks. ^[3]
2. Descending inhibition failure. Normally the brain suppresses incoming pain signals; in fibromyalgia this braking system is weakened, so afferent signals are less filtered. ^[3]
3. Neurochemistry. Substance P and glutamate are higher, and serotonin and noradrenaline lower, in cerebrospinal fluid in many studies. Central nervous system depressants and drugs that enhance serotonin and noradrenaline therefore have a mechanistic rationale, whereas peripheral anti-inflammatory drugs do not. ^[6]
4. Sleep disruption. Fibromyalgia sleep is typically light and fragmented, which deprives the patient of restorative sleep and can lower the pain threshold. ^[3]
5. Autonomic and stress-response features are described in subsets but remain research findings rather than diagnostic or treatment guides.

This chain explains why exercise helps (it promotes descending inhibition and sleep), why CBT helps (it changes attention, catastrophising and activity patterns), why medicines that act centrally help modestly, and why NSAIDs and opioids do not.

• Pain. Widespread musculoskeletal aching or burning, often described as "I hurt all over". It usually starts in one region (classically the neck and shoulders) and becomes generalised over months or years. Morning stiffness is common, and both over-activity and prolonged inactivity worsen it. ^[2]
• Fatigue. Debilitating and disproportionate to activity, often worse in the morning and after minimal effort.
• Sleep. Non-restorative, light sleep with frequent awakenings and early morning waking; many patients say they never feel rested. ^[2]
• Cognition. Poor concentration, memory lapses and "fibro fog" are frequent, and a large internet survey found that these symptoms, together with fatigue and sleep disturbance, were often rated more severe than pain itself. ^{[3] [1]}
• Other somatic symptoms. Headache, abdominal pain or cramps, irritable bowel symptoms, palpitations, numbness and tingling, dizziness, sensitivity to noise, temperature and light are common.
• Mood. Low mood, anxiety and panic are common comorbidities and change how the pain is experienced and reported.
• Exacerbating factors. Weather changes, stress, deconditioning and poor sleep all worsen symptoms.

There are no objective physical signs of tissue damage in fibromyalgia. Joints are not swollen; strength is normal when the patient is not too fatigued. The purpose of examination is to look for the conditions that mimic or coexist with fibromyalgia.

Specifically:

• Look for synovitis, muscle wasting or neurological deficit, which would redirect the diagnosis.
• Tender points were the hallmark of the 1990 ACR classification criteria (11 or more of 18 sites painful to digital palpation with about 4 kg of force), but they were abandoned as a diagnostic requirement because performance was poor and the results were unreliable. ^[2]
• Palpation of widespread tenderness (allodynia, hyperalgesia) reflects the central state: light pressure is felt as pain.

Clinical suspicion arises when a patient reports widespread pain for more than 3 months with unrefreshing sleep, fatigue and cognitive difficulty, while examination and basic tests are normal.

Sleep disturbance, fatigue and cognitive and mood symptoms are not side issues; they are part of the condition and they modify treatment choice. ^[3]

• Sleep problems are present in the majority and include difficulty initiating sleep, early waking and light, non-restorative sleep. ^[2]
• Depression and anxiety are far more common in people with fibromyalgia than in the general population. ^[3]
• Treatment that only targets pain leaves the symptoms patients often rate as worst untreated, so the plan should explicitly address sleep and mood. ^[6]

No test confirms fibromyalgia. Tests are used to exclude inflammatory, endocrine, haematological and structural disease before the diagnosis is accepted. In uncomplicated fibromyalgia they are expected to be normal.

It is worth ordering a limited, rational panel and then stopping. Repeating broad panels looking for "the cause" without a clinical lead rarely helps and often delays the diagnosis. ^{[1] [2]}

The 2016 revision of the American College of Rheumatology (ACR) criteria is the current standard clinical tool, combining the earlier physician 2010 criteria and the patient self-report 2011 survey criteria. ^[2]

The Widespread Pain Index (WPI) counts how many of 19 body regions have been painful in the last week (score 0 to 19). The Symptom Severity Scale (SSS) rates fatigue, waking unrefreshed and cognitive symptoms each from 0 to 3, plus 1 point for each of headache, lower abdominal pain or cramps, and depression in the last 6 months (score 0 to 12). The Fibromyalgia Severity (FS) score is WPI plus SSS (0 to 31). ^[2]

A useful summary is that widespread pain plus compatible symptoms for 3 months identifies the condition; the FS score usefully quantifies overall symptom burden in research and in clinical monitoring. ^{[2] [3]}

Because the 2016 revision removed the exclusion of any "other disorder sufficient to explain the pain", fibromyalgia can be diagnosed alongside rheumatoid arthritis, lupus or osteoarthritis. The two conditions often coexist, and when they do each must be treated on its own terms. ^[2]

The central problem is to distinguish fibromyalgia from disease that is inflammatory, structural, endocrine or psychiatric, and from other chronic pain syndromes.

Red flags (fever, weight loss, focal neurological signs, night pain that wakes from sleep, local bone tenderness, new onset in older adults) should redirect the investigation rather than being attributed to fibromyalgia. ^[1]

Fibromyalgia management is unusual in that no single body of evidence is decisive, and several respected guidelines disagree in detail. The named guidelines used here are:

• EULAR revised recommendations for the management of fibromyalgia, 2017. ^[1] The closest thing to an international standard; it specifies exercise as the only "strong for" recommendation and uses a graduated, patient-centred approach. ^[1]
• ACR diagnostic criteria, 2016 revision. ^[2] Diagnostic, not a treatment guideline, but it defines the condition and removes the older exclusion of comorbid disease.
• NICE NG193, chronic pain (primary and secondary) in over 16s (2021). ^[7] Covers fibromyalgia as chronic primary pain and supports supervised group exercise, CBT or acceptance and commitment therapy, and an antidepressant trial (aged 18 and over). It does not recommend gabapentinoids, NSAIDs, opioids or paracetamol for chronic primary pain.
• NICE NG59, low back pain and sciatica (2016). ^[8] Is a guideline for a different condition (low back pain with or without sciatica) and is not a fibromyalgia guideline; it is cited here only to avoid confusing the two.

Other regional guidelines (Canadian 2012, German 2017, Italian 2021) agree on the broad approach but differ on the strength assigned to pharmacotherapy, and the Spanish Rheumatology Society 2021 guideline recommends no specific drug. ^[2]

EULAR gives exercise a "strong for" recommendation on the strength of consistent effects on pain, function and well-being, and on safety, availability and cost. ^[1] There is insufficient evidence to prefer aerobic over strengthening exercise, or land-based over aquatic exercise; consistency rather than intensity is what matters. ^{[1] [2]} A practical starting point from the EULAR review is 20 to 30 minutes of low to moderate intensity exercise, 2 to 3 times a week, built up from just below the patient's current capacity. ^[2]

• Education comes first in the graduated approach: explain the condition, give written information, and agree realistic aims (improved function and quality of life, not cure). ^[1]
• Cognitive behavioural therapy ("weak for" in EULAR, stronger in other guidelines) reduces pain, disability and mood symptoms long-term and is useful for people with mood disorder or unhelpful coping, including catastrophising and fear of movement. ^{[1] [2]} Acceptance and commitment therapy is an alternative recommended in NICE NG193. ^[7]
• Multicomponent programmes (education plus exercise plus psychological therapy) outperform single measures in severe disability, although effects fade without reinforcement. ^{[1] [2]}
• Physical therapies such as acupuncture or hydrotherapy have a "weak for" recommendation. ^[1]
• Meditative movement (tai chi, yoga, qigong) and mindfulness-based stress reduction are "weak for" and may help sleep, fatigue, pain and quality of life. ^[1]
• Avoid. EULAR gives "strong against" for chiropractic on safety grounds and does not recommend biofeedback, capsaicin, hypnosis, massage, S-adenosyl methionine or other complementary and alternative therapies on efficacy grounds. ^[1]

Sleep hygiene is not specifically listed in the guidelines but is implicit in the multimodal plan: regular sleep and wake times, avoidance of late caffeine and alcohol, and treatment of obstructive sleep apnoea when present. ^[3]

Medicines have a supporting, not a curative, role. EULAR found the effect sizes of all pharmacological treatments to be relatively modest, and all were graded "weak for". ^[1] EULAR recommends not starting NSAIDs, MAOIs, SSRIs, strong opioids, sodium oxybate, growth hormone or corticosteroids for uncomplicated fibromyalgia, because of lack of efficacy and, for some, risk of harm and dependence. ^[1] Separately, NICE NG193 recommends not initiating antiepileptic drugs (including gabapentinoids), antipsychotic drugs, benzodiazepines, corticosteroid trigger point injections, ketamine, local anaesthetics, NSAIDs, opioids or paracetamol for chronic primary pain, but it does consider an antidepressant trial (amitriptyline, citalopram, duloxetine, fluoxetine, paroxetine or sertraline) for people aged 18 years and over. ^[7] It follows that opioids and gabapentin should not be prescribed simply because the patient is in pain; if they are already in use, review and stop them where benefit is poor. ^[7]

Doses below are typical adult oral doses from the licensed product information and from a recent practice review; always check the local formulary and adjust for renal impairment, age and comorbidity. ^{[4] [5] [6]}

Tricyclic antidepressants, for dominant sleep and pain disturbance:

• Amitriptyline at low dose is "weak for" in EULAR. ^[1] The evidence comes from low doses: amitriptyline 25 mg/day improved pain, sleep and fatigue at 6 to 8 weeks but not at 12 weeks in older trials, while 50 mg/day did not show efficacy. ^[1] Clinical practice uses amitriptyline 5 to 25 mg at night, building by small increments to a maintenance of 30 to 60 mg as tolerated. ^[6] Avoid or use with great caution in older adults because of anticholinergic burden and falls, and avoid in narrow-angle glaucoma and significant cardiac conduction disease. ^[6]
• Cyclobenzaprine is "weak for" and improves sleep more than pain. Fibromyalgia studies report benefit at very low doses of 1 to 4 mg at bedtime, titrating to 5 to 10 mg over about 14 weeks, rather than the higher doses used for muscle spasm. ^{[2] [6] [1]}

Serotonin and noradrenaline reuptake inhibitors, for pain and mood:

• Duloxetine is "weak for" in EULAR and is licensed for fibromyalgia. ^{[1] [4]} Start at 30 mg once daily for 1 week, then increase to 60 mg once daily; the maximum is 60 mg daily for this indication, and there is no evidence that more than 60 mg/day confers additional benefit, while adverse effects increase with dose. ^[4] The evidence review behind EULAR found that doses of 20 to 30 mg/day were not significantly effective and that 60 and 120 mg/day did not differ in effect; the licensed starting and target doses above reconcile those findings. ^[1] A 2024 practice review reports greater benefit at 120 mg/day, particularly when depression is comorbid, but that lies above the licensed maximum for fibromyalgia and EULAR found no difference between 60 and 120 mg/day. ^[6] Exercise caution with serotonergic drug combinations to avoid serotonin syndrome. ^[2]
• Milnacipran is also licensed in the United States for fibromyalgia and is started at 12.5 mg, building to 100 mg daily; it improves pain, fatigue and well-being but not sleep quality. ^[6]

Anticonvulsants, for pain and sleep:

• Pregabalin is "weak for" in EULAR. ^[1] The licensed regimen for fibromyalgia is 75 mg twice daily (150 mg/day) at first, increased to 150 mg twice daily (300 mg/day) within 1 week as tolerated, and, if benefit is still insufficient, to 225 mg twice daily (450 mg/day). ^[5] Although it was studied at 600 mg/day, there is no evidence of additional benefit above 450 mg/day and that dose was less well tolerated. ^[5] A 2024 practice review reports better sleep and depression at 600 mg/day and an initiation of 25 to 75 mg increased weekly, but those figures conflict with the label and with the same review's report of no consistent benefit at 300 or 600 mg/day. ^[6] Adjust the dose in renal impairment. ^[5]

Other drugs, used in selected cases:

• Tramadol, possibly combined with paracetamol, is "weak for" in EULAR and may help when pain is severe. ^{[1] [2]}
• Tapentadol (50 to 250 mg twice daily) is reported in the practice review for severe pain with a neuropathic component. ^[6]
• Gabapentin has a much weaker evidence base than pregabalin in fibromyalgia and is not recommended by NICE for chronic primary pain. ^[7]
• Quetiapine (50 to 100 mg) may be useful where depression and sleep disturbance predominate but less so than amitriptyline. ^[6]
• Strong opioids, corticosteroids, NSAIDs, benzodiazepines and nabilone/cannabidiol are either not recommended or not funded. ^{[1] [6] [7]}

When single-modality treatment fails, combination therapy (for example pregabalin with an SNRI) can be tried; the strongest caution is to avoid combining serotonergic agents. ^[2]

• Mood disorder and suicide risk are elevated and should be treated directly and never dismissed as inevitable. ^[3]
• Accidental injury and infection have been reported at higher rates in some studies; these findings need larger confirmation. ^[3]
• Polypharmacy and misuse are real risks when diagnosis is delayed and pain is treated without a plan. ^[7]
• Worsening of comorbid pain conditions (chronic overlapping pain conditions) because the central state amplifies all of them. ^[3]

Fibromyalgia is usually a chronic, fluctuating condition. Symptoms wax and wane; most adults continue to have symptoms over years, but many function better with a consistent plan. ^[6] Treatment reduces symptoms but does not cure, and the size of benefit for most interventions is modest. ^[1] The outlook is better when diagnosis is made promptly, the patient is believed, the patient keeps moving, and comorbid depression and sleep disorder are treated. ^[1]

Patients seen in tertiary centres often do worse than those managed in primary care, partly because of referral selection. ^[6]

There is no established prevention or universal screening for fibromyalgia. What reduces risk and improves outcome is modifiable at the individual level: physical activity, sleep hygiene, stress management and treatment of depression or anxiety. ^{[1] [3]} Screening with broad laboratory panels has no value; diagnosis rests on the clinical criteria above and on the judicious exclusion of mimics. ^[2]

• Pregnancy and breastfeeding. Evidence for pharmacotherapy is limited and decisions must be individualised; non-pharmacological measures are the backbone. Amitriptyline and, in specialist hands, duloxetine are used in some pregnancies, but any drug should be chosen with obstetric and specialist input. ^{[4] [7]}
• Children and adolescents. Juvenile primary fibromyalgia syndrome is uncommon and diagnosed by specialists. Adult criteria are used cautiously in adolescents; education, graded exercise and (when appropriate) CBT are preferred. ^[2]
• Older adults. Anticholinergic burden, sedation and falls rise with age; avoid high-dose amitriptyline and start all medicines at low dose. ^[6]
• Fibromyalgia with a comorbid inflammatory disease. Each is treated on its own terms: optimise the inflammatory disease and add fibromyalgia-targeted therapy, rather than escalating disease-modifying drugs for symptoms that are nociplastic. ^[1]

• The diagnosis can be made clinically with a careful history and examination and a small basic panel (full blood count, ESR/CRP, thyroid function), without MRI. ^[2]
• Graded exercise (walking programmes, water aerobics where water is available), sleep hygiene and brief psychoeducation are the most cost-effective interventions and need no specialist input. ^[1]
• Amitriptyline is inexpensive and widely available, which is part of why it features in so many formularies despite its modest evidence base. ^[6]
• Where licensed medicines are unavailable, do not prescribe strong opioids or repeat courses of NSAIDs. ^{[1] [7]}

• Fibromyalgia is a chronic nociplastic pain condition driven by central sensitisation, not by tissue damage or inflammation.
• Diagnosis is clinical and rests on the 2016 ACR criteria: WPI 7 or more with SSS 5 or more, or WPI 4 to 6 with SSS 9 or more, plus generalised pain in at least 4 of 5 regions and symptoms for at least 3 months. ^[2]
• Tender points were dropped from the diagnostic criteria because they were unreliable; the concept now is widespread pain plus a symptom burden.
• Blood tests and imaging are for excluding mimics. ESR, CRP, rheumatoid factor and anti-CCP are expected to be normal.
• Sleep and mood problems are part of the condition and should be treated directly.
• Exercise is the only "strong for" EULAR recommendation; it should be graded, regular and sustainable.
• CBT, multicomponent programmes, acupuncture and meditative movement are "weak for" and comorbid-symptom targeted.
• Duloxetine: 30 mg daily for one week, then 60 mg daily; maximum 60 mg daily for this indication.
• Pregabalin: 75 mg twice daily at first, then 150 mg twice daily, up to 225 mg twice daily (450 mg/day).
• Amitriptyline: 5 to 25 mg at night, building to 30 to 60 mg as tolerated; evidence supports low doses.
• Do not start NSAIDs, opioids, corticosteroids, strong opioids, gabapentinoids (in the NICE view) or benzodiazepines for uncomplicated fibromyalgia.
• Fibromyalgia can coexist with inflammatory arthritis; treat both separately rather than escalating anti-inflammatory therapy for nociplastic pain.
• Prompt diagnosis, a named condition, graded exercise and self-management give the best chance of regaining function. ^[1]

Chronic pain; rheumatoid arthritis; polymyalgia rheumatica; hypothyroidism; depression; sleep disorders; chronic fatigue syndrome; myofascial pain syndrome. (Planned MedGrasp topics to be linked when verified.)