What are the recommended medications for treating fibromyalgia?

Medication Treatment for Fibromyalgia

First-Line Pharmacological Options

For fibromyalgia, start with amitriptyline (10-75 mg/day), duloxetine (60 mg/day), or pregabalin (300-450 mg/day) as first-line medications, but only after implementing non-pharmacological therapies including exercise and patient education. 1, 2

Amitriptyline

• Start at 10 mg at bedtime and increase by 10 mg weekly to a target of 25-50 mg nightly (maximum 75 mg/day) 2
• Provides pain reduction and improved function with the strongest evidence (Level Ia, Grade A) 1
• Particularly beneficial for patients with sleep disturbances due to sedating properties 1
• Monitor for anticholinergic effects (dry mouth, constipation, urinary retention) and morning sedation 2

Duloxetine (SNRI)

• Begin at 30 mg once daily for 1 week, then increase to 60 mg once daily 2, 3
• The recommended dosage is 60 mg once daily; there is no evidence that doses greater than 60 mg/day confer additional benefit 3
• Effective for pain reduction, functional improvement, and treating comorbid depression (Level Ia, Grade A) 1
• Higher dosages are associated with higher rates of adverse reactions without additional benefit 3

Pregabalin

• Start at 75 mg twice daily (150 mg/day), increase to 150 mg twice daily (300 mg/day) within 1 week based on tolerability 2, 4
• The recommended dose for fibromyalgia is 300-450 mg/day 4
• Patients not responding to 300 mg/day may increase to 225 mg twice daily (450 mg/day) 4
• Doses above 450 mg/day are not recommended due to dose-dependent adverse reactions without additional benefit 4
• Effective for pain reduction and sleep improvement (Level Ia, Grade A) 1
• Requires dose adjustment in renal insufficiency 1

Milnacipran (SNRI Alternative)

• Recommended dosing is 100-200 mg/day in divided doses 1
• Dose escalation should start at lower doses and titrate up over approximately 1 week to minimize side effects 1
• Effective for pain reduction and fatigue symptoms 1
• FDA-approved specifically for fibromyalgia management 5

Second-Line Pharmacological Options

Tramadol

• Recommended for pain management (Level Ib, Grade A) when first-line medications are ineffective 1
• Use as a second-line option after inadequate response to amitriptyline, duloxetine, or pregabalin 1

Cyclobenzaprine

• Can be considered for pain management (Level Ia, Grade A) 1
• Useful as an alternative muscle relaxant option 1

Gabapentin

• Not FDA-approved for fibromyalgia but considered an alternative to pregabalin with similar mechanism of action 1
• Requires careful titration due to nonlinear pharmacokinetics (saturable absorption), starting with low doses and gradually increasing 1
• Requires dosage adjustment in patients with renal insufficiency 1

Treatment Algorithm

Step 1: Non-Pharmacological Foundation (Always First)

• Provide patient education about central sensitization and the chronic nature of fibromyalgia 2
• Initiate graduated exercise program starting with low-intensity aerobic exercise (10-15 minutes of walking, swimming, or cycling, 2-3 times weekly) 2
• Add cognitive behavioral therapy for patients with mood disorders, depression, anxiety, or maladaptive coping strategies 2

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

• Choose one first-line medication: amitriptyline, duloxetine, or pregabalin based on patient-specific factors 2:
  • Amitriptyline: Best for patients with prominent sleep disturbances 1
  • Duloxetine: Best for patients with comorbid depression 1
  • Pregabalin: Best for patients with prominent sleep problems and anxiety 1

Step 3: Reassess Every 4-8 Weeks

• Evaluate pain scores, functional status, and patient global impression of change 1
• If partial pain relief at target dosage, consider adding another first-line medication from a different class 1
• If no or inadequate pain relief at target dosage after adequate trial, switch to an alternative first-line medication 1

Step 4: Consider Combination Therapy

• Multicomponent therapy combining exercise, cognitive behavioral therapy, and medication may provide greater benefit than any single intervention 1
• Pregabalin combined with other approved medications may be synergistic 6

Medications to Avoid

Absolutely Contraindicated

• Corticosteroids: Not recommended for fibromyalgia treatment; lack efficacy 1, 2
• Strong opioids: Not recommended; have not demonstrated benefits and cause significant harm 1, 2

Critical Pitfalls to Avoid

• Do not rely solely on pharmacological therapy without implementing exercise and behavioral approaches first 1
• Do not start medications before patient education about the chronic nature of fibromyalgia and central sensitization 2
• Do not exceed recommended maximum doses: Higher doses of duloxetine (>60 mg/day) and pregabalin (>450 mg/day) increase adverse effects without additional benefit 4, 3
• Do not abruptly discontinue duloxetine: Gradual dose reduction is required to avoid withdrawal symptoms including dizziness, headache, nausea, and paresthesia 3
• Do not use pregabalin or gabapentin without dose adjustment in renal impairment: Both require careful dosing based on creatinine clearance 1, 4
• Do not prescribe strong opioids or corticosteroids: These lack efficacy and cause harm in fibromyalgia 1, 2

Important Monitoring Considerations

• The effect size for most treatments is relatively modest, with most showing small to moderate benefits 1
• Dropout rates due to side effects with milnacipran are approximately double compared to placebo, though serious adverse events are similar 1
• Common adverse events with pregabalin include dizziness, somnolence, weight gain, and peripheral edema, which are dose-related 6
• Monitor pregabalin-treated patients for emergence or worsening of depression or suicidal thoughts 6
• Pregabalin may worsen sedation when combined with central nervous system depressants 6