What first‑line pain medication is recommended for an adult with fibromyalgia who has no severe renal impairment, uncontrolled hypertension, recent myocardial infarction, or substance‑misuse history?

First-Line Pain Medication for Fibromyalgia

For an adult with fibromyalgia and no contraindications, duloxetine 60 mg once daily, pregabalin 300-450 mg/day, or amitriptyline 25-50 mg at bedtime are the recommended first-line pharmacological options, with duloxetine or pregabalin preferred due to FDA approval and superior tolerability. 1, 2, 3

Recommended First-Line Medications

Duloxetine (Preferred Option)

• Start at 30 mg once daily for 1 week, then increase to 60 mg once daily as the target maintenance dose 2, 3
• Duloxetine 60 mg demonstrates statistically significant pain reduction, with approximately 50% of patients achieving at least 30% pain reduction in controlled trials 3
• Do not escalate beyond 60 mg/day — doses of 120 mg provide no additional benefit but increase adverse events and discontinuation rates 1, 3
• Benefits include pain reduction, functional improvement, and treatment of comorbid depression 2, 3
• FDA-approved specifically for fibromyalgia 3, 4

Pregabalin (Alternative First-Line)

• Start at 75 mg twice daily, increase to 150 mg twice daily (300 mg/day total) within 1 week based on tolerance 2
• Target dose range is 300-450 mg/day in divided doses 1, 2
• Patients receiving pregabalin are more likely to achieve 30% pain reduction (RR 1.38,95% CI 1.25 to 1.51) 1
• Do not exceed 450 mg/day — higher doses show no additional efficacy but increase dose-dependent adverse reactions 1
• Provides small but significant benefits on fatigue (SMD −0.14) and disability (SMD −0.16), though no effect on sleep 1
• FDA-approved for fibromyalgia 2, 4
• Requires dose adjustment in renal impairment (creatinine clearance <60 mL/min) 2

Amitriptyline (Cost-Effective Alternative)

• Start at 10 mg at bedtime, increase by 10 mg weekly to target 25-50 mg nightly 2, 5
• Demonstrates moderate effect on pain (SMD −0.40), sleep problems (SMD 0.47), and fatigue (SMD 0.48) 1
• Number needed to treat for 50% pain relief is 4.1, meaning approximately one in four patients achieves substantial benefit 5
• Particularly beneficial for patients with prominent sleep disturbances due to sedating properties 2
• Therapeutic effects typically emerge over 3-7 weeks 5
• Caution in older adults (≥65 years) due to anticholinergic effects including dry mouth, orthostatic hypotension, constipation, urinary retention, and morning sedation 2, 5

Second-Line Option When First-Line Fails

Tramadol

• Recommended for pain management when first-line medications (duloxetine, pregabalin, amitriptyline) are ineffective 1, 2
• Effect size 0.657 for pain reduction 1
• Use with caution given opioid-related risks including potential for dependence 2
• Simple analgesics such as paracetamol (acetaminophen) and other weak opioids can also be considered, though evidence is limited 1, 2

Medications to Avoid

Strong Opioids and Corticosteroids

• Corticosteroids and strong opioids are NOT recommended — they lack efficacy and cause significant harm in fibromyalgia 1, 2, 5
• Strong opioids have not demonstrated benefits and carry substantial risk of abuse and severe side effects 2, 6

NSAIDs

• NSAIDs show no evidence of improved outcome compared with placebo as monotherapy 1
• Weak recommendation against NSAIDs (100% expert agreement) 1

Treatment Algorithm

Step 1: Initial Pharmacological Choice

• Select duloxetine 60 mg daily OR pregabalin 300-450 mg/day as first choice based on patient factors 1, 2, 3:
  • Choose duloxetine if comorbid depression is present 2, 3
  • Choose pregabalin if sleep disturbance is prominent (though evidence for sleep benefit is limited) 1, 2
  • Choose amitriptyline if cost is a major concern or sleep disturbance is severe, but avoid in elderly patients 2, 5

Step 2: Assess Response at 4-6 Weeks

• Evaluate pain reduction using 0-10 numeric rating scale 2
• Assess functional improvement and quality of life, not just pain scores 2
• If <30% pain reduction, switch to alternative first-line medication from different class 2
• If partial response (30-50% pain reduction), consider adding medication from different class 2

Step 3: If First-Line Options Fail

• Consider tramadol for moderate to severe pain, with careful monitoring for opioid-related risks 1, 2
• Reassess every 4-8 weeks using pain scores, functional status, and patient global impression of change 2

Critical Pitfalls to Avoid

• Never escalate duloxetine beyond 60 mg/day or pregabalin beyond 450 mg/day — no additional benefit, only increased adverse events 1, 3
• Never prescribe strong opioids or corticosteroids for fibromyalgia 1, 2, 5
• Do not use NSAIDs as monotherapy — they are ineffective 1
• Avoid abrupt discontinuation of any medication — taper gradually over 2-4 weeks to prevent withdrawal symptoms 5
• Do not rely solely on pharmacological therapy — the evidence shows modest effect sizes at best, and non-pharmacological interventions (exercise, cognitive behavioral therapy) should be implemented concurrently 1, 2

Important Nuances

• Pain reduction may be greater in patients with comorbid major depressive disorder when using duloxetine 3
• Some patients experience pain decrease as early as week 1 with duloxetine or pregabalin, which persists throughout treatment 3
• The effect size for most pharmacological treatments is relatively modest (small to moderate benefits), with most showing SMD of 0.3-0.8 1
• None of the currently available drugs are fully effective against the whole spectrum of fibromyalgia symptoms (pain, fatigue, sleep disturbances, depression) 4, 7
• Combination therapy may be more effective than monotherapy, though more research is needed 2, 4