What are the first line treatments for a patient with fibromyalgia?

First-Line Treatment for Fibromyalgia

Begin with non-pharmacological interventions—specifically aerobic and strengthening exercise combined with patient education—as these have the strongest evidence (Level Ia, Grade A) and should be implemented before any medications. 1, 2

Treatment Algorithm

Step 1: Non-Pharmacological Interventions (First-Line)

Exercise is the cornerstone of fibromyalgia treatment and must be started immediately upon diagnosis. 1, 2

• Start with low-intensity aerobic exercise: 10-15 minutes of walking, swimming, or cycling 2-3 times weekly 2
• Gradually increase intensity over 8-12 weeks to reach 30 minutes 5 times weekly 3
• Add strengthening exercises once aerobic tolerance is established 1
• Critical pitfall: Patients often experience initial symptom flare-ups; emphasize gradual progression to avoid discouragement and treatment abandonment 1

Heated pool therapy with or without exercise is highly effective (Level IIa, Grade B) and may be better tolerated than land-based exercise initially. 1

Cognitive behavioral therapy (CBT) should be prioritized for patients with comorbid mood disorders, depression, anxiety, or maladaptive coping strategies (Level Ia, Grade A). 1, 2 CBT shows the strongest benefit in these subgroups and addresses the central sensitization component of fibromyalgia. 2

Patient education about central sensitization and the chronic nature of fibromyalgia is essential for setting realistic expectations. 1, 2

Step 2: Pharmacological Interventions (Second-Line)

Add medications only if non-pharmacological interventions provide insufficient relief after 4-6 weeks. 2 The three first-line medications with Level Ia, Grade A evidence are:

Amitriptyline

• Dosing: Start 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: 4.1 for 50% pain relief 1
• Benefits: Pain reduction, improved sleep, particularly effective for patients with prominent sleep disturbances 1, 4
• Caution: Avoid in older adults (≥65 years) due to anticholinergic effects (dry mouth, constipation, urinary retention, orthostatic hypotension) 2
• Onset: Therapeutic effects emerge over 3-7 weeks 2

Duloxetine

• Dosing: Start 30 mg once daily for 1 week, then increase to 60 mg once daily 1, 2, 3, 5
• Maximum dose: 60 mg/day—higher doses provide no additional benefit but increase adverse events 1, 5
• Benefits: Pain reduction, improved function, treats comorbid depression 1, 3, 5
• Advantage: Less anticholinergic burden than amitriptyline 2
• Evidence: Approximately 50% of patients achieve at least 30% pain reduction 1

Pregabalin

• Dosing: Start 75 mg twice daily, increase to 150 mg twice daily (300 mg/day total) within 1 week based on tolerance 1, 2, 6
• Target range: 300-450 mg/day 1, 6
• Maximum: 450 mg/day—doses above this provide no additional benefit but increase adverse effects 1, 6
• Benefits: Pain reduction, improved sleep 1, 2, 6
• Renal adjustment: Required for creatinine clearance <60 mL/min 1
• Evidence: 53.6% responder rate (≥50% seizure reduction in epilepsy trials; similar pain reduction in fibromyalgia) 6

Alternative First-Line Options

Milnacipran (SNRI): 100-200 mg/day in divided doses, with gradual titration over 1 week to minimize side effects. 1 Similar efficacy to duloxetine for pain reduction with additional benefits on fatigue. 1

Cyclobenzaprine: Can be considered for pain management (Level Ia, Grade A). 1

Tramadol: Reserved as second-line when first-line medications are ineffective (Level Ib, Grade A), used with caution given opioid-related risks. 1, 2

Reassessment and Monitoring

• Evaluate treatment response every 4-8 weeks using pain scores (0-10 numeric rating scale), functional status, and patient global impression of change 1, 2
• Target outcomes: ≥30% pain reduction from baseline, improved function, better sleep quality 1, 3
• If partial response: Consider adding a medication from a different class (e.g., amitriptyline to duloxetine) 2
• If no response: Switch to an alternative first-line medication rather than escalating dose 1

Critical Medications to Avoid

Never prescribe the following for fibromyalgia:

• Strong opioids: Lack efficacy and cause significant harm (Level Ia, Grade A) 1, 2, 3
• Corticosteroids: No demonstrated efficacy (Level Ia, Grade A) 1, 2, 3
• NSAIDs as monotherapy: No evidence of benefit compared to placebo 1

Common Pitfalls

• Starting with medications instead of exercise: Non-pharmacological interventions have stronger evidence and should always be first-line 1, 2, 7
• Escalating duloxetine beyond 60 mg/day or pregabalin beyond 450 mg/day: No additional benefit, only increased adverse events 1, 5
• Expecting complete pain resolution: Most treatments show small to moderate benefits; realistic expectations are crucial 1
• Combining gabapentin with pregabalin: Pharmacologically redundant as they bind identical targets 2
• Inadequate exercise progression: Too rapid increases cause flare-ups and treatment abandonment 1