What is the recommended dose regimen for naproxen (nonsteroidal anti-inflammatory drug (NSAID)) in acute migraine?

Naproxen Dose Regimen for Acute Migraine

For acute migraine treatment, administer naproxen sodium 500-825 mg at migraine onset (ideally when pain is still mild), which can be repeated every 2-6 hours as needed, with a maximum daily dose of 1.5 g, limited to no more than twice weekly to prevent medication-overuse headache. 1

Initial Dosing Strategy

• Start with 500 mg of naproxen sodium at the first sign of migraine pain, preferably when the headache is still mild, as early treatment significantly improves efficacy 1, 2
• The FDA-approved dosing for acute pain management allows an initial dose of 500 mg, followed by 500 mg every 12 hours or 250 mg every 6-8 hours, with a maximum first-day dose of 1250 mg and subsequent days not exceeding 1000 mg 2
• However, for migraine-specific treatment, the American Academy of Family Physicians recommends 500-825 mg initially, repeatable every 2-6 hours as needed 1

Critical Frequency Limitation

• Restrict naproxen use to no more than 2 days per week to prevent medication-overuse headache, which can paradoxically increase headache frequency and lead to daily headaches 1, 3
• Naproxen can be safely used for up to 3 consecutive days per migraine episode, but the overall weekly frequency must remain limited 1

Enhancing Efficacy with Adjunctive Therapy

• Add an antiemetic 20-30 minutes before naproxen administration (metoclopramide 10 mg or prochlorperazine 25 mg) to provide synergistic analgesia and improve outcomes compared to naproxen alone 1
• This combination addresses both the pain and the gastric stasis that occurs during migraine attacks, enhancing absorption of the NSAID 1

When Naproxen Fails: Escalation Algorithm

If naproxen provides inadequate relief after treating 2-3 migraine episodes, escalate to triptan therapy (sumatriptan, rizatriptan, or zolmitriptan) for moderate-to-severe attacks 1

• Consider combination therapy with sumatriptan 85 mg plus naproxen sodium 500 mg, which demonstrates superior efficacy compared to either agent alone, with 52% of patients achieving pain-free status at 2 hours versus 17% with placebo 4
• The fixed-dose combination (sumatriptan/naproxen) shows significantly better 24-hour pain relief response (46%) compared to sumatriptan alone (29%), naproxen alone (25%), or placebo (17%) 5
• For severe attacks unresponsive to NSAIDs, dihydroergotamine (DHE) represents another escalation option 1

Contraindications and Safety Precautions

Avoid naproxen in patients with:

• Renal impairment with creatinine clearance <30 mL/min 1, 2
• Active gastrointestinal bleeding or history of NSAID-induced ulcers 1
• Aspirin/NSAID-induced asthma or hypersensitivity 1
• Significant cardiovascular disease where NSAID use may increase risk 2

Clinical Efficacy Evidence

While naproxen demonstrates statistical superiority over placebo, the clinical benefit is modest. The number needed to treat (NNT) for pain-free response at 2 hours is 11 (17% response with naproxen versus 8% with placebo), suggesting naproxen alone is effective in fewer than 2 in 10 patients 6. This relatively high NNT indicates that naproxen works best as first-line therapy for mild-to-moderate migraine 3, 1, with triptans reserved as second-line for moderate-to-severe attacks or when NSAIDs fail 3.

Common Pitfall to Avoid

Do not allow patients to increase frequency of naproxen use when attacks become more frequent. Instead, this pattern indicates the need for preventive therapy rather than more aggressive acute treatment 3, 1. Patients requiring acute medication more than 2 days per week should be transitioned to preventive therapy while optimizing the acute treatment strategy 3.