What is the NSAID (Non-Steroidal Anti-Inflammatory Drug) of choice for acute migraine?

NSAID of Choice in Acute Migraine

For acute migraine treatment, ibuprofen (400-800 mg) or naproxen sodium (500-825 mg) are the NSAIDs of choice, with naproxen sodium preferred for its longer duration of action and potentially better sustained relief over 24 hours. 1, 2

First-Line NSAID Options

The most recent 2025 American College of Physicians guideline establishes NSAIDs as first-line therapy for mild to moderate migraine attacks, with specific agents having the strongest evidence base: 1

• Naproxen sodium (500-825 mg) - Provides headache relief in 45% of patients at 2 hours (NNT 6.0) and sustained relief over 24 hours in 30% (NNT 8.3) 1, 3
• Ibuprofen (400-800 mg) - Equally effective with good tolerability profile 1, 4
• Aspirin (650-1000 mg) - Particularly effective when combined with acetaminophen and caffeine 1
• Diclofenac potassium - Also has strong evidence for efficacy 1, 4

Practical Dosing Algorithm

For initial treatment: 1, 2

• Start with naproxen sodium 500-825 mg or ibuprofen 400-800 mg at migraine onset
• Take when pain is still mild for maximum efficacy
• Can repeat every 4-6 hours for naproxen, 2-6 hours for ibuprofen
• Maximum daily dose: 1.5 g for naproxen, 3.2 g for ibuprofen

If inadequate response after 2 hours: 1, 2

• Add a triptan to the NSAID (combination therapy is superior to either alone)
• Consider switching to a different NSAID if the first fails after 2-3 migraine episodes

Critical Advantage of Naproxen

Naproxen sodium has a longer half-life than other NSAIDs, providing sustained relief over 24 hours with an NNT of 8.3, compared to shorter-acting agents. 3 This makes it particularly valuable for preventing headache recurrence, which occurs in 40% of migraine patients within 48 hours. 2

Enhancing NSAID Efficacy

Add an antiemetic 20-30 minutes before the NSAID: 2, 5

• Metoclopramide 10 mg or prochlorperazine 25 mg
• Provides synergistic analgesia beyond just treating nausea
• Improves gastric motility and medication absorption

Consider combination therapy from the start for moderate-to-severe attacks: 1, 2

• Aspirin 500-1000 mg + acetaminophen 500-1000 mg + caffeine 130 mg has strong evidence
• This combination is more effective than acetaminophen alone (which is ineffective as monotherapy) 1, 5

When to Escalate Beyond NSAIDs

Switch to triptan-based therapy if: 1, 6

• NSAIDs fail after adequate trials (2-3 migraine episodes at appropriate doses)
• Attacks are consistently severe from onset
• Patient reaches peak intensity rapidly
• Significant disability occurs despite NSAID use

Parenteral NSAID Option

Ketorolac (30-60 mg IV/IM) is the parenteral NSAID of choice for severe migraine in emergency or urgent care settings: 1, 2, 7

• Rapid onset of action (approximately 15 minutes)
• Duration of approximately 6 hours
• Minimal risk of rebound headache
• Dose: 30 mg IV for patients ≥65 years or with renal impairment; 60 mg for younger patients

Critical Pitfalls to Avoid

Medication overuse headache: 1, 2

• Limit NSAID use to ≤15 days per month
• If using NSAIDs more than twice weekly, initiate preventive therapy
• Overuse leads to transformation to chronic daily headache

Contraindications to monitor: 1, 2

• Renal impairment (creatinine clearance <30 mL/min)
• Active GI bleeding or history of peptic ulcer disease
• Aspirin/NSAID-induced asthma
• Uncontrolled hypertension or cardiovascular disease

Acetaminophen monotherapy is ineffective - Never recommend acetaminophen alone for migraine; it only works in combination with aspirin and caffeine. 1, 5