What is the recommended workup and management for a female patient presenting with symptoms suggestive of fibromyalgia?

Fibromyalgia Workup

Diagnostic Criteria and Clinical Assessment

Diagnose fibromyalgia using the American College of Rheumatology criteria: widespread pain in all four body quadrants for at least 3 months, plus pain on palpation in at least 11 of 18 specific tender points. 1

• Apply approximately 4 kg of pressure (equivalent to blanching your thumbnail) to the 18 designated tender points; the diagnosis is positive if 11 or more are painful 1
• The Fibromyalgia Rapid Screening Tool is a helpful initial screening method for patients presenting with diffuse chronic pain 2
• Recognize that fibromyalgia is a central nervous system disorder characterized by central sensitization and abnormal pain processing, not peripheral tissue damage or inflammation 3
• Normal laboratory results and imaging support rather than exclude the diagnosis—this is not a diagnosis of exclusion but a positive clinical diagnosis based on characteristic features 1, 3

Essential Laboratory Workup

Order a focused laboratory panel to exclude mimicking conditions, not to diagnose fibromyalgia itself:

• Complete blood count to exclude anemia or hematologic disorders 4
• Comprehensive metabolic panel to assess renal and hepatic function 4
• Thyroid-stimulating hormone (TSH) to exclude hypothyroidism 4
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) to exclude inflammatory conditions 4
• Vitamin D level (25-hydroxyvitamin D) as deficiency can mimic fibromyalgia symptoms 4
• Creatine kinase if muscle weakness is prominent, to exclude myopathy 4

Common pitfall: Ordering extensive autoimmune panels (ANA, rheumatoid factor, anti-CCP) is unnecessary unless specific clinical features suggest an inflammatory rheumatologic condition 4

Associated Symptoms to Assess

Document the presence and severity of:

• Sleep disturbances and non-restorative sleep 2, 5
• Fatigue and daytime somnolence 2
• Cognitive dysfunction ("fibro fog") 2
• Mood disorders (depression, anxiety) 2, 5
• Functional somatic syndromes (irritable bowel syndrome, migraine, temporomandibular joint disorder) 2

Treatment Algorithm

Step 1: Initial Non-Pharmacological Management (First-Line)

Begin immediately with patient education about central sensitization, followed by a graduated exercise program—this has the strongest evidence (Level Ia, Grade A) for improving pain, function, and quality of life. 6, 1

• Start with low-intensity aerobic exercise: 10-15 minutes of walking, swimming, or cycling, 2-3 times weekly 1
• Gradually increase intensity based on tolerance to avoid symptom flare-ups 6
• Add strength training as tolerated 6
• Consider heated pool therapy with or without exercise (Level IIa, Grade B) 6
• Initiate cognitive behavioral therapy (CBT) particularly for patients with comorbid mood disorders, depression, anxiety, or maladaptive coping strategies (Level Ia, Grade A) 6, 1

Step 2: Add Pharmacological Management if Insufficient Response After 4-6 Weeks

If non-pharmacological interventions provide inadequate relief after 4-6 weeks, add one of three first-line medications: amitriptyline, duloxetine, or pregabalin. 1

Amitriptyline (Level Ia, Grade A)

• Start 10 mg at bedtime 1
• Increase by 10 mg weekly to target 25-50 mg nightly (maximum 75 mg/day) 6, 1
• Particularly beneficial for patients with prominent sleep disturbances due to sedating properties 6
• Number needed to treat for 50% pain relief is 4.1 1
• Monitor for anticholinergic effects (dry mouth, constipation, urinary retention) and morning sedation 1
• Caution: Avoid in older adults (≥65 years) due to anticholinergic effects 6
• Therapeutic effects typically emerge over 3-7 weeks 1

Duloxetine (Level Ia, Grade A)

• Start 30 mg once daily for 1 week 1
• Increase to 60 mg once daily 1, 7
• Do not escalate beyond 60 mg/day—doses above 60 mg provide no additional benefit but increase adverse events 6, 7
• Benefits include pain reduction, improved function, and treatment of comorbid depression 1, 7
• FDA-approved for fibromyalgia 6, 8

Pregabalin (Level Ia, Grade A)

• Start 75 mg twice daily (150 mg/day) 1, 9
• Increase to 150 mg twice daily (300 mg/day) within 1 week based on tolerance 1, 9
• May further increase to 225 mg twice daily (450 mg/day) if insufficient benefit at 300 mg/day 9
• Do not exceed 450 mg/day—doses above 450 mg provide no additional benefit but significantly increase adverse events 6, 9
• Benefits include pain reduction and sleep improvement 1
• Adjust dose in renal insufficiency (creatinine clearance <60 mL/min) 6, 9
• FDA-approved for fibromyalgia 6, 8

Step 3: Reassess and Adjust at 4-8 Weeks

• Evaluate pain scores, functional status, and patient global impression of change 6
• If partial response, consider adding another first-line medication from a different class 6
• If no response at target dosage after adequate trial, switch to alternative first-line medication 6

Step 4: Second-Line Options if First-Line Medications Fail

• Milnacipran 100-200 mg/day in divided doses (Level Ia, Grade A): effective for pain reduction and fatigue 6, 8
• Cyclobenzaprine (Level Ia, Grade A): can be considered for pain management 6
• Tramadol (Level Ib, Grade A): reserve for when other medications are ineffective; use with caution given opioid-related risks 6, 8
• Gabapentin (off-label): alternative to pregabalin with similar mechanism; requires careful titration due to nonlinear pharmacokinetics 6, 8

Step 5: Multicomponent Therapy for Refractory Cases

• Combine non-pharmacological and pharmacological approaches—multicomponent therapies show greater benefit than single interventions (Level Ia, Grade A) 6
• Add acupuncture, mindfulness-based stress reduction, or meditative movement therapies (qigong, yoga, tai chi) (Level Ia, Grade A) 6

Critical Medications to AVOID

Never prescribe corticosteroids or strong opioids for fibromyalgia—they lack efficacy and cause significant harm. 6, 1

• Corticosteroids have no demonstrated benefit (Level Ia, Grade A) 6, 1
• Strong opioids have not shown benefits and carry substantial risks 6, 1
• NSAIDs as monotherapy are ineffective compared to placebo 6

Important Clinical Pitfalls

• Do not rely solely on pharmacological therapy without implementing exercise and behavioral approaches—non-pharmacological interventions are first-line 6, 1
• Do not order extensive autoimmune workups unless specific clinical features suggest inflammatory disease 4
• Do not treat fibromyalgia as a diagnosis of exclusion—make a positive diagnosis based on ACR criteria 1, 3
• Do not escalate duloxetine beyond 60 mg/day or pregabalin beyond 450 mg/day—higher doses increase adverse events without additional benefit 6, 9, 7
• Do not expect dramatic improvement—most treatments show small to moderate benefits; set realistic expectations with patients 6
• Do not forget patient education about the chronic nature of fibromyalgia and central sensitization—this is crucial for treatment adherence 6, 1