What is the best medication for migraine headaches?

Best Medication for Migraine Headaches

For mild to moderate migraines, start with NSAIDs (ibuprofen 400-800mg, naproxen sodium 500-825mg, or aspirin 900-1000mg); for moderate to severe migraines, use triptans as first-line therapy, with oral sumatriptan 50-100mg or rizatriptan 10mg being the most effective options. 1, 2, 3

Treatment Algorithm Based on Migraine Severity

Mild to Moderate Migraine

• NSAIDs are first-line therapy with the strongest evidence supporting ibuprofen (400-800mg every 6-8 hours), naproxen sodium (500-825mg initially), aspirin (900-1000mg), or diclofenac potassium 1, 2, 3
• Take NSAIDs early when pain is still mild for maximum effectiveness 1, 2
• Acetaminophen alone is ineffective and should only be used if NSAIDs are contraindicated 1, 4
• The combination of aspirin + acetaminophen + caffeine has proven efficacy when NSAIDs alone are insufficient 2, 3

Moderate to Severe Migraine

• Triptans are first-line therapy for moderate to severe attacks 1, 2, 3
• Oral sumatriptan 100mg provides pain-free response in 30% of patients at 2 hours (NNT 5.1) and headache relief in 59-79% at 2-4 hours 1, 5, 6
• Oral rizatriptan 10mg provides headache response in 67-77% at 2 hours 7, 2
• Sumatriptan 50mg is also effective with headache relief in 50-78% at 2-4 hours, though slightly less effective than 100mg 5, 6
• The 25mg dose is less effective and should be reserved for patients intolerant of higher doses 1, 5

Route Selection Based on Clinical Presentation

For patients with significant nausea or vomiting:

• Use non-oral routes: subcutaneous sumatriptan 6mg (most effective, 59% pain-free at 2 hours), intranasal sumatriptan 20mg, or intranasal zolmitriptan 1, 2, 3, 8
• Add antiemetic medication: metoclopramide 10mg IV or prochlorperazine 10mg IV 2, 4
• Subcutaneous sumatriptan 6mg is the single most effective acute migraine treatment across all routes, with 70-84% response at 1 hour and 81-87% at 2 hours (NNT 2.1) 9, 10, 8

For rapid-onset or peak-intensity migraines:

• Subcutaneous sumatriptan 6mg provides the fastest relief, with significant improvement within 15 minutes for cluster headaches and within 1 hour for migraine 9, 8

Timing and Dosing Strategy

• Take triptans early when headache is still mild for optimal effectiveness 1, 2
• Do NOT take triptans during the aura phase—wait until headache begins 1, 9
• If one triptan fails, try a different triptan, as failure of one does not predict failure of others 1, 2
• A second dose can be taken for headache recurrence (occurs in 21-57% of patients), but wait at least 2 hours after the first dose 5, 7, 11

Third-Line Options When Triptans Fail

If all triptans fail after adequate trials (no response in at least 3 consecutive attacks) or are contraindicated:

• Consider lasmiditan (ditan class) or ubrogepant/rimegepant (gepant class), though availability is limited 1
• Intranasal dihydroergotamine (DHE) 0.5-1mg has good evidence for efficacy 2, 4

Emergency Department/Severe Refractory Migraine

The most effective IV combination is metoclopramide 10mg + ketorolac 30mg, providing rapid relief with minimal rebound risk 2, 4

Alternative IV options:

• Prochlorperazine 10mg IV (comparable efficacy to metoclopramide) 2, 4
• IV dihydroergotamine 0.5-1mg for refractory cases 2, 4

Critical Contraindications to Avoid

Triptans are contraindicated in:

• Uncontrolled hypertension 3, 4, 9
• Ischemic heart disease, previous MI, or Prinzmetal angina 9, 10
• Basilar or hemiplegic migraine 3, 4

Do not combine:

• Triptans with ergotamines (must wait 24 hours between) 1, 9
• Triptans with MAO inhibitors 9

Medication-Overuse Headache Prevention

• Limit acute medications to no more than 2 days per week to prevent medication-overuse headache 1, 2, 3
• If using acute treatments more frequently, initiate preventive therapy rather than increasing acute medication frequency 2, 3
• Opioids and butalbital-containing compounds carry the highest risk for medication-overuse headache and should be avoided 2, 4

Adverse Events Profile

• Oral triptans: nausea, malaise, fatigue, dizziness in 14% (NNH 7.1 for sumatriptan 100mg) 6, 11
• Subcutaneous sumatriptan: injection site reactions in 10-40%, chest symptoms in 3-5% (rarely associated with myocardial ischemia) 9, 11
• Intranasal formulations: bitter taste commonly reported 11, 8
• Serious cardiovascular events occur in approximately 0.14% of patients 11