What is the recommended treatment for headache migraines?

Recommended Treatment for Migraine Headaches

For mild to moderate migraine attacks, start with NSAIDs (ibuprofen 400-800 mg, naproxen 500-825 mg, or aspirin 1000 mg) or acetaminophen 1000 mg; for moderate to severe attacks, use combination therapy with a triptan (sumatriptan 50-100 mg) plus an NSAID, which provides superior efficacy compared to either agent alone. 1

First-Line Treatment Algorithm

Mild to Moderate Migraine

• Begin with NSAIDs as first-line therapy: ibuprofen 400-800 mg, naproxen sodium 500-825 mg, or aspirin 1000 mg at migraine onset 1, 2
• Acetaminophen 1000 mg is an alternative first-line option, though NSAIDs generally demonstrate superior efficacy 1
• The combination of acetaminophen + aspirin + caffeine has strong evidence for efficacy and may be used when single-agent NSAIDs provide inadequate relief 2, 3
• Take medication as early as possible during the attack, ideally when pain is still mild, to maximize effectiveness 1, 2

Moderate to Severe Migraine

• Use combination therapy with a triptan plus an NSAID or acetaminophen, which is superior to either agent alone 1, 2
• Sumatriptan 50-100 mg combined with naproxen sodium 500 mg provides 130 more patients per 1000 achieving sustained pain relief at 48 hours compared to monotherapy 2
• Oral triptans with strong evidence include sumatriptan (25-100 mg), rizatriptan, naratriptan, and zolmitriptan 2, 3
• The 50 mg and 100 mg doses of sumatriptan provide greater effect than 25 mg, though 100 mg may not provide greater effect than 50 mg 4

Severe Migraine with Nausea/Vomiting

• Use non-oral routes: subcutaneous sumatriptan 6 mg provides the highest efficacy (59% pain-free at 2 hours) with onset within 15 minutes 2, 3
• Add an antiemetic (metoclopramide 10 mg or prochlorperazine 10 mg) 20-30 minutes before other medications to provide synergistic analgesia and improve gastric motility 2, 5
• Intranasal sumatriptan (5-20 mg) or intranasal zavegepant are alternatives when subcutaneous route is not feasible 2, 3

Second-Line and Rescue Options

When First-Line Therapy Fails

• Consider CGRP antagonists (gepants): rimegepant, ubrogepant, or zavegepant for patients who do not tolerate or have inadequate response to triptan + NSAID combination 1
• Dihydroergotamine (DHE) intranasal or injectable formulations have good evidence for efficacy as monotherapy 1, 2
• Lasmiditan (ditan) should be considered only after inadequate response to all other pharmacologic treatments in this guideline 1

Emergency Department/Urgent Care IV Treatment

• Metoclopramide 10 mg IV plus ketorolac 30 mg IV represents the optimal first-line IV cocktail, providing direct analgesic effects through central dopamine receptor antagonism plus rapid NSAID analgesia 2, 5
• Prochlorperazine 10 mg IV is an alternative to metoclopramide with comparable efficacy and a more favorable side effect profile than chlorpromazine 2
• IV corticosteroids are the mainstay for status migrainosus (migraine lasting >72 hours) 5

Critical Frequency Limitation to Prevent Medication-Overuse Headache

• Restrict all acute migraine medications to no more than 2 days per week to prevent medication-overuse headache, which paradoxically increases headache frequency and can lead to daily headaches 1, 2, 3
• The threshold varies by medication: ≥15 days per month with NSAIDs triggers medication-overuse headache, while ≥10 days per month with triptans does so 1
• If acute treatment is needed more than twice weekly, immediately initiate preventive therapy rather than increasing acute medication frequency 2, 3

Medications to Avoid

• Do not use opioids or butalbital-containing compounds for migraine treatment, as they lead to dependency, rebound headaches, medication-overuse headache, and eventual loss of efficacy 1, 2, 3
• Opioids should only be reserved for rare situations where all other medications are contraindicated, sedation is not a concern, and abuse risk has been addressed 2

Contraindications Requiring Alternative Approach

• Triptans are absolutely contraindicated in patients with uncontrolled hypertension, ischemic heart disease, previous myocardial infarction, basilar or hemiplegic migraine, or significant cardiovascular disease 2, 3, 5
• In patients with triptan contraindications, use NSAIDs alone or consider CGRP antagonists (gepants) or DHE as alternatives 1, 2
• Ketorolac should be used with caution in patients with renal impairment (creatinine clearance <30 mL/min), history of GI bleeding, or aspirin/NSAID-induced asthma 2

When to Initiate Preventive Therapy

• Start preventive therapy for patients with ≥2 migraine attacks per month producing ≥3 days of disability, or those using acute medications more than twice weekly 2, 3, 5
• First-line preventive agents include propranolol 80-240 mg/day, timolol 20-30 mg/day, amitriptyline 30-150 mg/day, or topiramate 2, 5
• Preventive therapy reduces attack frequency and can restore responsiveness to acute treatments 2

Dosing Details and Rescue Strategy

• If migraine has not resolved by 2 hours after initial triptan dose, a second dose may be administered at least 2 hours after the first dose, with maximum daily dose of 200 mg sumatriptan in 24 hours 4
• For patients with hepatic impairment, maximum single sumatriptan dose should not exceed 50 mg 4
• The safety of treating more than 4 headaches in a 30-day period has not been established 4

Special Populations

• In patients of childbearing potential, pregnant, or breastfeeding individuals, discuss adverse effects of pharmacologic treatments during pregnancy and lactation before prescribing 1
• Most triptans are pregnancy category C; NSAIDs should be avoided in the third trimester due to risk of premature closure of ductus arteriosus 1

Cost Considerations

• Prescribe less costly recommended medications when equally effective options exist 1
• Generic NSAIDs and older triptans (sumatriptan, naratriptan) are significantly less expensive than newer CGRP antagonists (annualized cost $4,959-$8,800) while providing comparable or superior efficacy 1