First-Line Treatment for Migraine Without Aura (Non-Refractory)
For mild to moderate migraine attacks, start with NSAIDs (ibuprofen 400-800 mg, naproxen 500-825 mg, or aspirin 1000 mg) as first-line therapy; for moderate to severe attacks or when NSAIDs fail, add a triptan to the NSAID regimen, as this combination is superior to either agent alone. 1
Treatment Algorithm Based on Attack Severity
Mild to Moderate Attacks
- NSAIDs are the first-line choice for mild to moderate migraine attacks, with strong evidence supporting ibuprofen, naproxen sodium, aspirin, and diclofenac potassium 2, 1, 3
- Specific dosing: ibuprofen 400-800 mg, naproxen 500-825 mg, or aspirin 1000 mg at attack onset 1
- Alternative first-line option: combination of acetaminophen (1000 mg) plus aspirin plus caffeine, which provides synergistic analgesia 2, 4
- Acetaminophen alone (1000 mg) has less efficacy and should only be used when NSAIDs are contraindicated 2
Moderate to Severe Attacks
- Add a triptan to an NSAID for moderate to severe attacks that don't respond adequately to NSAIDs alone (strong recommendation) 2, 1
- Triptans with the best evidence include oral sumatriptan, naratriptan, rizatriptan, and zolmitriptan 2, 3, 4
- The triptan + NSAID combination represents the strongest recommendation from current guidelines and is superior to either agent alone 1
Critical Timing and Administration Principles
When to Take Medication
- Treat early in the attack when headache is still mild to maximize efficacy 2, 5
- Do not use triptans during the aura phase if aura is present 2
- Early treatment improves outcomes across all medication classes 1, 5
Route Selection Based on Symptoms
- For attacks with significant nausea or vomiting, select non-oral routes: subcutaneous sumatriptan or nasal spray formulations 2, 1
- Add an antiemetic (metoclopramide 10 mg or prochlorperazine) even if vomiting is not present, as it provides synergistic analgesia 2, 1
Medication-Overuse Headache Prevention
The most critical pitfall to avoid is medication overuse headache, which occurs with frequent use of acute medications. 1, 6
- Limit all acute migraine medications to no more than 2 days per week (or 10 days per month maximum) 1, 6, 5
- Using acute medications more than twice weekly can paradoxically increase headache frequency and lead to daily headaches 1
- If needing acute treatment more than twice weekly, initiate preventive therapy immediately 1
When Initial Treatment Fails
If NSAIDs Fail After 2-3 Attacks
- Escalate to a triptan for subsequent attacks 1
- Consider combination therapy (triptan + NSAID) from the start for future attacks 2, 1
If One Triptan Fails
- Try a different triptan, as failure of one does not predict failure of others 2
- Consider subcutaneous sumatriptan (6 mg) for patients who rapidly reach peak intensity or have vomiting 2, 1
For Relapse (Return of Symptoms Within 48 Hours)
- Repeat triptan treatment or combine with fast-acting NSAIDs 2
- This addresses the 40% of patients who experience symptom recurrence 1
Third-Line Options When All Triptans Fail
If all available triptans fail or are contraindicated, alternatives include:
- Ditans (lasmiditan) 2
- Gepants (ubrogepant, rimegepant) 2, 1
- Dihydroergotamine (DHE) nasal spray or IV/IM formulations 1, 4
Contraindications and Special Populations
Triptan Contraindications
- Ischemic heart disease or previous myocardial infarction 1
- Uncontrolled hypertension 1
- Other significant cardiovascular disease 1
NSAID Contraindications
- Renal impairment (creatinine clearance <30 mL/min) 1
- Active GI bleeding or history of GI bleeding 1
- Aspirin/NSAID-induced asthma 1