What are the treatment options for migraine?

Migraine Treatment: A Structured Approach

For acute migraine treatment, start with NSAIDs or acetaminophen for mild-to-moderate attacks, escalate to triptan-NSAID combination therapy for moderate-to-severe attacks or inadequate response, and reserve newer agents (gepants, ditans, DHE) for patients who fail or cannot tolerate triptans. 1

First-Line Treatment Strategy

Mild-to-Moderate Attacks

• Begin with NSAIDs as first-line therapy: aspirin 900-1000 mg, ibuprofen 400-800 mg, naproxen sodium 500-825 mg, or diclofenac potassium 50-100 mg 1, 2
• Acetaminophen 1000 mg is an alternative but less effective than NSAIDs; use only when NSAIDs are contraindicated or not tolerated 1, 2
• Combination therapy (acetaminophen 250 mg + aspirin 250 mg + caffeine 65 mg) is more effective than monotherapy for mild-to-moderate attacks 2, 3
• Ensure adequate dosing before declaring treatment failure—many patients use subtherapeutic doses 1

Moderate-to-Severe Attacks

• Add a triptan to an NSAID (or acetaminophen if NSAIDs contraindicated) when first-line therapy fails 1, 2
• Triptans with strongest evidence: sumatriptan 50-100 mg, rizatriptan 10 mg, eletriptan 40-80 mg, almotriptan 12.5 mg, naratriptan 2.5 mg, zolmitriptan 2.5-5 mg, frovatriptan 2.5 mg 1, 4
• Sumatriptan 100 mg provides better efficacy than 50 mg (NNT 4.7 vs 6.1 for pain-free at 2 hours), while 50 mg offers better tolerability 5, 6
• Treat early during mild pain phase for superior outcomes: NNTs improve significantly compared to treating established moderate-severe pain 5

Critical Timing Principle

Begin treatment as soon as possible after migraine onset—early treatment during mild pain significantly improves efficacy of all medications, particularly triptans 1, 2, 5

Escalation Algorithm for Treatment Failures

When NSAIDs Fail

1. Add a triptan to the NSAID (or acetaminophen if NSAIDs contraindicated)—combination therapy is more effective than either alone 1, 2
2. If one triptan fails after 2-3 adequate trials, try a different triptan—failure of one does not predict failure of others 1, 2
3. Consider route change: subcutaneous sumatriptan 6 mg provides highest efficacy (59% pain-free at 2 hours) for patients with rapid pain escalation or vomiting 2, 7

When Triptan-NSAID Combination Fails

Escalate to CGRP antagonists (gepants) or ergot alkaloids 1:

• Rimegepant, ubrogepant, or zavegepant (gepants) 1, 8
• Dihydroergotamine (DHE) intranasal or IV 1, 8

Last-Line Option

Lasmiditan (ditan) should be considered only after failure of all other pharmacologic treatments including triptan-NSAID combinations and gepants 1, 3

Route-Specific Considerations

Non-Oral Routes (for severe nausea/vomiting)

• Subcutaneous sumatriptan 6 mg: highest efficacy but more adverse events 2, 7
• Intranasal sumatriptan 20 mg or zolmitriptan 5 mg 2, 4
• Add antiemetic: metoclopramide 10 mg IV or prochlorperazine 10 mg IV provides synergistic analgesia beyond treating nausea 1, 2, 8

Emergency/Urgent Care IV Therapy

First-line IV combination: ketorolac 30 mg + metoclopramide 10 mg—provides rapid relief with minimal rebound risk 8, 3

Medications to Avoid

Do not use opioids or butalbital-containing compounds for migraine treatment—they lead to medication overuse headache, dependency, and loss of efficacy 1, 2, 8

Medication Overuse Headache Prevention

This is a critical pitfall that worsens migraine over time:

• Limit triptans to ≤10 days per month 1, 2, 3
• Limit NSAIDs to ≤15 days per month 1, 2, 3
• If acute medication needed >2 days per week, initiate preventive therapy 2, 3

Triptan Safety Considerations

Contraindications (from FDA label)

Triptans are contraindicated in 9:

• Coronary artery disease, Prinzmetal's angina, or other significant cardiovascular disease
• History of stroke or transient ischemic attack
• Peripheral vascular disease
• Uncontrolled hypertension
• Hemiplegic or basilar migraine
• Wolff-Parkinson-White syndrome or arrhythmias with accessory cardiac pathways

Important Warnings

• Chest/throat/jaw tightness is common (usually non-cardiac) but requires cardiac evaluation in high-risk patients 9
• Monitor for serotonin syndrome when combining with SSRIs, SNRIs, TCAs, or MAOIs 9
• Significant blood pressure elevation can occur even without hypertension history 9

Special Populations

Pregnancy and Lactation

• Acetaminophen is first-line in pregnancy 3
• NSAIDs can be used prior to third trimester 3
• Discuss adverse effects of all pharmacologic treatments with patients of childbearing potential 1

Chronic Migraine (≥15 headache days/month)

• Rule out medication overuse headache first 2
• OnabotulinumtoxinA 155 units is FDA-approved and effective for chronic migraine 2
• Preventive therapy is essential—acute treatment alone is insufficient 2

When to Initiate Preventive Therapy

Consider preventive medications when 2:

• ≥2 attacks per month producing disability lasting ≥3 days per month
• Contraindication to or failure of acute treatments
• Acute medication use >2 days per week
• Presence of hemiplegic migraine or migraine with prolonged aura

Essential Lifestyle Modifications

Counsel all patients on 2, 3:

• Maintain regular meals and adequate hydration
• Ensure consistent, sufficient sleep (address poor sleep quality)
• Engage in regular moderate-to-intense aerobic exercise 40 minutes three times weekly—as effective as some preventive medications 2
• Manage stress with relaxation techniques or mindfulness practices
• Identify and reduce triggers using a headache diary

Cost Considerations

Prescribe generic NSAIDs and older triptans (sumatriptan, naratriptan, rizatriptan) when equally effective—they are significantly less expensive than newer agents 3