What medications are used to treat migraines?

Medications for Migraine Treatment

For mild to moderate migraines, start with NSAIDs (ibuprofen 400-800mg, naproxen 500-825mg, or aspirin 650-1000mg) or the combination of acetaminophen-aspirin-caffeine; for moderate to severe migraines, use triptans (sumatriptan, rizatriptan, naratriptan, or zolmitriptan) as first-line therapy. 1, 2

Acute Treatment Algorithm

Mild to Moderate Migraine

• First-line NSAIDs: 1, 2

  • Ibuprofen 400-800mg every 6 hours (max 2.4g daily) 3
  • Naproxen sodium 500-825mg at onset, repeat every 2-6 hours (max 1.5g daily) 1, 3
  • Aspirin 650-1000mg every 4-6 hours (max 4g daily) 3
  • Acetaminophen-aspirin-caffeine combination (acetaminophen alone is ineffective) 1, 2

• Add antiemetic if nausea present: Metoclopramide 10mg or prochlorperazine 10mg given 20-30 minutes before NSAID provides synergistic analgesia 1

• If NSAIDs fail after 2-3 attacks: Escalate to triptans 1

Moderate to Severe Migraine

• First-line triptans: 1, 2

  • Oral options: Sumatriptan, rizatriptan, naratriptan, zolmitriptan 1, 4
  • Subcutaneous sumatriptan 6mg provides highest efficacy (59% complete pain relief by 2 hours, 70-82% relief within 15 minutes) 1
  • Intranasal sumatriptan 5-20mg for patients with significant nausea/vomiting 1

• Triptan contraindications: Do NOT use in patients with uncontrolled hypertension, coronary artery disease, stroke history, hemiplegic/basilar migraine, or within 24 hours of ergot medications 1, 2, 4

• If triptans fail: Try a different triptan first (failure of one does not predict failure of others), then consider dihydroergotamine (DHE) intranasal or IV 1

Emergency Department/Severe Refractory Migraine

• IV combination therapy: Metoclopramide 10mg IV plus ketorolac 30mg IV provides rapid relief with minimal rebound risk 1
• Alternative IV options: 1, 2
  • Prochlorperazine 10mg IV (comparable efficacy to metoclopramide)
  • Dihydroergotamine (DHE) 0.5-1.0mg IV for refractory cases

Newer Second-Line Agents

• Gepants: Rimegepant, ubrogepant, zavegepant (no vascular contraindications, useful when triptans fail or contraindicated) 1
• Ditans: Recently FDA-approved 5-HT1F receptor agonists (no vascular contraindications but may cause sedation) 5

Critical Medication Overuse Warning

Limit ALL acute medications to no more than twice weekly to prevent medication-overuse headache (MOH), which causes transformation to chronic daily headache. 1, 2, 3 If using acute treatments more than 2 days per week, initiate preventive therapy immediately rather than increasing acute medication frequency. 1

Preventive Therapy Indications

Start preventive therapy when: 3

• Two or more migraine attacks per month with 3+ days of disability
• Using acute medications more than twice weekly
• Acute treatments fail or are contraindicated
• Uncommon migraine variants present (hemiplegic, prolonged aura)

First-line preventive options: 3

• Propranolol 80-240mg daily
• Amitriptyline 30-150mg daily
• Divalproex sodium 500-1500mg daily

Medications to AVOID

Never use opioids or butalbital-containing compounds for migraine—they cause dependency, medication-overuse headache, and loss of efficacy. 1, 2, 3 Reserve opioids only for cases where all other options are contraindicated AND abuse risk has been addressed. 1

Route Selection Based on Symptoms

• Significant nausea/vomiting present: Use non-oral routes (subcutaneous, intranasal, rectal, or IV) 1, 2
• Rapid peak intensity or vomiting: Subcutaneous sumatriptan preferred over oral 1
• Most attacks: Oral route acceptable if taken early when pain still mild 1

Timing Principle

Administer medication as early as possible during the attack while headache is still mild to maximize efficacy and prevent progression. 1, 6 Early treatment significantly improves response rates across all medication classes.