What are the best medications for managing fibromyalgia?

Best Medications for Fibromyalgia

For fibromyalgia, start with amitriptyline 10-25 mg at bedtime (especially if sleep disturbance is prominent), duloxetine 60 mg daily (especially if depression or anxiety coexist), or pregabalin 150 mg twice daily (especially if predominant pain without mood symptoms)—all three are first-line options with Level Ia, Grade A evidence. 1, 2

First-Line Pharmacological Options

The three FDA-approved and guideline-recommended first-line medications are:

Amitriptyline (Tricyclic Antidepressant)

• Start at 10-25 mg at bedtime, titrate by 10-25 mg weekly to 50-75 mg as tolerated 2
• Particularly beneficial for patients with prominent sleep disturbance due to sedating properties 1, 2
• Reduces pain and improves function with Level Ia, Grade A evidence 1
• Dosing range: 10-75 mg/day 1

Duloxetine (SNRI)

• Start at 30 mg daily for 1 week, then increase to 60 mg daily 2
• Optimal for patients with pain plus comorbid depression or anxiety 2
• FDA-approved at 60 mg/day for pain reduction, functional improvement, and associated depression 1
• Level Ia, Grade A evidence 1

Pregabalin (Anticonvulsant)

• Start at 75 mg twice daily (150 mg/day), titrate to 150 mg twice daily (300 mg/day) within 1 week 2, 3
• May increase to 225 mg twice daily (450 mg/day) if insufficient benefit at 300 mg/day 3
• Best for patients with predominant pain without mood symptoms 2
• FDA-approved with Level Ia, Grade A evidence; reduces pain and improves sleep 1, 3
• Do not exceed 450 mg/day—no additional benefit at 600 mg/day but increased adverse effects 3

Second-Line Pharmacological Options

Milnacipran (SNRI)

• FDA-approved at 100-200 mg/day for pain reduction and fatigue symptoms 1
• Level Ia, Grade A evidence 1

Cyclobenzaprine (Muscle Relaxant)

• Can be considered for pain management with Level Ia, Grade A evidence 1

Tramadol (Weak Opioid)

• Reserved for pain management when other medications are ineffective 1, 2
• Level Ib, Grade A evidence 1

Gabapentin (Anticonvulsant - Off-Label)

• Alternative to pregabalin with similar mechanism of action 1
• Requires careful titration starting with low doses due to nonlinear pharmacokinetics 1
• Commonly used in clinical practice despite lack of FDA approval for fibromyalgia 4

Critical Medications to Avoid

• Corticosteroids have no role in fibromyalgia treatment 1, 2
• Strong opioids (morphine, oxycodone, hydrocodone) are not recommended—they lack demonstrated benefit and carry significant risks 1, 2
• NSAIDs have limited to no benefit as monotherapy since fibromyalgia is not an inflammatory condition 2

Treatment Selection Algorithm

Step 1: Assess predominant symptom pattern 2

• If sleep disturbance is prominent → Start amitriptyline 10-25 mg at bedtime
• If depression or anxiety coexist → Start duloxetine 30 mg daily, increase to 60 mg after 1 week
• If predominant pain without mood symptoms → Start pregabalin 75 mg twice daily

Step 2: Titrate based on response and tolerability 2

• Evaluate treatment response every 4-8 weeks using pain scores (0-10 scale) and functional status 2
• Expect 30-50% pain reduction rather than complete resolution 2
• Most patients experience benefit within 1 week if medication will be effective 3

Step 3: If partial response 1

• Consider adding another first-line medication from a different class
• Combination therapy may provide greater benefit than monotherapy 2

Step 4: If inadequate response after adequate trial 1

• Switch to alternative first-line medication
• Consider second-line options (tramadol, cyclobenzaprine, gabapentin)

Important Clinical Considerations

Dosing Pitfalls

• Most patients in real-world practice remain on starting doses—only 40% have dose increases during follow-up 4
• However, therapeutic doses are often higher than starting doses: amitriptyline 50-75 mg, duloxetine 60 mg, pregabalin 300-450 mg 1, 3
• Inadequate dosing is a common reason for treatment failure 4

Treatment Persistence

• Only one-fifth of patients continue treatment for ≥1 year 4
• Regular reassessment is essential to evaluate efficacy and adjust approach 1, 2

Renal Dosing for Pregabalin

• Pregabalin is eliminated primarily by renal excretion and requires dose adjustment in renal impairment 3
• Use Cockcroft-Gault equation to estimate creatinine clearance and adjust accordingly 3

Common Adverse Effects

• Pregabalin: dizziness, somnolence, weight gain, peripheral edema (dose-related) 5, 6, 7
• Duloxetine: nausea, dry mouth, constipation 8
• Amitriptyline: sedation, dry mouth, constipation, weight gain 1

Medication Interactions

• Pregabalin may worsen sedation when combined with CNS depressants 5
• Monitor for emergence or worsening of depression and suicidal thoughts with pregabalin 5
• Pregabalin has minimal drug interactions due to lack of protein binding and negligible hepatic metabolism 5

Integration with Non-Pharmacological Therapy

• Pharmacological therapy should be combined with aerobic and strengthening exercise, which has the strongest evidence (Level Ia, Grade A) for improving pain, function, and quality of life 1, 2
• Multicomponent therapy (combining exercise, cognitive behavioral therapy, and medication) provides greater benefit than any single intervention 2
• Medications are considered second-line to non-pharmacological interventions in the treatment hierarchy 1, 8