What is the recommended treatment approach for fibromyalgia in adults, including non‑pharmacologic therapies and first‑ and second‑line medications?

Treatment for Fibromyalgia

Begin immediately with aerobic and strengthening exercise as the primary intervention, which has the strongest evidence (Level Ia, Grade A) for improving pain, function, and quality of life in fibromyalgia. 1, 2

Non-Pharmacological Management (First-Line)

Exercise Protocol

• Start low-impact aerobic exercise (walking, swimming, cycling) at 20-30 minutes, 2-3 times weekly, gradually increasing to 30-60 minutes, 5 days weekly over 4-8 weeks. 2
• Add progressive resistance training 2-3 times weekly once aerobic tolerance is established. 2
• All forms of exercise improve pain (effect size -0.72 to -0.96) and depression (effect size -0.35 to -1.22) except flexibility exercise alone. 3
• Mind-body exercises (yoga, tai chi) and strengthening exercises specifically improve fatigue (effect size -0.77 to -1.00), while aerobic and strengthening exercises improve sleep (effect size -0.74 to -1.33). 3

Heated Pool Therapy

• Heated pool treatment with or without exercise is effective (Level IIa, Grade B) and may improve exercise tolerance in patients who struggle with land-based activity. 1, 2

Cognitive Behavioral Therapy

• Add CBT for patients with depression, anxiety, or maladaptive coping strategies (Level Ia, Grade A). 1, 2
• CBT improves pain, sleep, and depression (effect size -0.35 to -0.55) but does not significantly impact fatigue. 3

Additional Modalities

• Acupuncture provides pain reduction with Level Ia, Grade A evidence. 2
• Meditative movement therapies (tai chi, yoga, qigong) are recommended as second-line interventions, particularly for patients with prominent sleep disturbances (effect size -0.61) and fatigue (effect size -0.66). 1, 2
• Mindfulness-based stress reduction programs can be added for comprehensive symptom management. 1, 2

Pharmacological Management (Second-Line)

Add medication only after initiating exercise, or simultaneously if symptoms are severe enough to prevent exercise participation. 1, 2

First-Line Medications

For Patients with Prominent Sleep Disturbance and Pain:

• Amitriptyline 10 mg at bedtime, increase by 10 mg weekly to target 25-50 mg nightly (maximum 75 mg/day). 1, 2
• Number needed to treat for 50% pain relief is 4.1 (Level Ia, Grade A). 1
• Caution: Avoid in older adults (≥65 years) due to anticholinergic effects. 1

For Patients with Pain Plus Depression or Anxiety:

• Duloxetine 30 mg daily for 1 week, then increase to 60 mg daily. 1, 2
• Approximately 50% of patients achieve at least 30% pain reduction (Level Ia, Grade A). 1
• Do not escalate beyond 60 mg/day—no additional benefit but increased adverse events. 1

For Patients with Predominant Pain Without Mood Symptoms:

• Pregabalin 75 mg twice daily, titrate to 150 mg twice daily (300 mg/day total) over 1 week, maximum 450 mg/day. 1, 2
• Patients are more likely to achieve 30% pain reduction (RR 1.38,95% CI 1.25 to 1.51) with Level Ia, Grade A evidence. 1
• Do not escalate beyond 450 mg/day—no additional benefit but increased dose-dependent adverse reactions. 1
• Adjust dose in renal insufficiency (creatinine clearance <60 mL/min). 1

Alternative SNRI:

• Milnacipran 100-200 mg/day in divided doses shows similar efficacy to duloxetine for pain reduction (RR 1.38,95% CI 1.25 to 1.51) and provides small but significant benefits on fatigue (SMD -0.14) and disability (SMD -0.16). 1
• Titrate starting at lower doses over approximately 1 week to minimize side effects. 1

Second-Line Medication

When First-Line Medications Are Ineffective:

• Tramadol for pain management (Level Ib, Grade A), used with caution given opioid-related risks. 1, 4

Alternative Off-Label Options

• Cyclobenzaprine can be considered for pain management (Level Ia, Grade A). 1
• Gabapentin is an alternative to pregabalin with similar mechanism of action, though not FDA-approved for fibromyalgia; requires careful titration due to nonlinear pharmacokinetics. 1

Treatment Algorithm

Initial 4-8 Weeks:

• Begin aerobic and strengthening exercise program immediately. 1, 2
• Add heated pool therapy if land-based exercise is not tolerated. 1
• Provide patient education about fibromyalgia as a chronic condition with central sensitization to set realistic expectations. 1, 2

If Insufficient Response After 4-8 Weeks:

• Add first-line medication based on predominant symptom profile (sleep disturbance → amitriptyline; depression/anxiety → duloxetine; pain alone → pregabalin). 1, 2
• Add CBT for patients with mood disorders or maladaptive coping. 1, 2
• Consider acupuncture, mindfulness-based stress reduction, or meditative movement therapies. 1, 2

If Partial Response to Medication:

• Consider adding another first-line medication from a different class. 1

If No Response to First-Line Medication at Target Dose:

• Switch to an alternative first-line medication from a different class. 1

If First-Line Medications Ineffective:

• Add tramadol with caution regarding opioid risks. 1, 4

Ongoing Management:

• Reassess every 4-8 weeks using pain scores (0-10 scale), functional status, and patient global impression of change. 1, 2
• Expect 30-50% pain reduction rather than complete resolution—most treatments show modest effect sizes. 1, 2
• Multicomponent therapy (combining exercise, CBT, and medication) provides greater benefit than any single intervention. 1, 2

Critical Medications to Avoid

• Corticosteroids have no role in fibromyalgia treatment—no efficacy demonstrated. 1, 2, 4
• Strong opioids (morphine, oxycodone, hydrocodone) are not recommended—they lack demonstrated benefit and carry significant harm. 1, 2, 4
• NSAIDs (ibuprofen, naproxen) should not be used as monotherapy—no evidence of improved outcome compared with placebo since fibromyalgia is not an inflammatory condition. 1

Common Pitfalls

• Relying solely on pharmacological therapy without implementing exercise and behavioral approaches—exercise has the strongest evidence base. 1
• Escalating duloxetine beyond 60 mg/day or pregabalin beyond 450 mg/day—this increases adverse events without additional benefit. 1
• Not providing adequate patient education about the chronic nature of fibromyalgia and realistic treatment expectations. 1
• Failing to individualize exercise programs and increase intensity gradually—rapid escalation causes symptom flare-ups. 1
• Prescribing strong opioids or corticosteroids, which lack efficacy and cause significant harm. 1, 2, 4