What are the treatment options for migraine headaches?

Migraine Headache Treatment

First-Line Treatment for Mild to Moderate Migraine

For mild to moderate migraine attacks, start with combination therapy of an NSAID plus acetaminophen, or use the combination of acetaminophen/aspirin/caffeine (Excedrin Migraine), as these provide superior efficacy compared to monotherapy. 1

• NSAIDs with strong evidence include ibuprofen 400-800 mg, naproxen sodium 500-825 mg, or aspirin 1000 mg 1, 2
• Acetaminophen 1000 mg can be used as monotherapy but is less effective than NSAIDs or combination therapy 1
• The acetaminophen/aspirin/caffeine combination provides synergistic analgesia and enhanced absorption of analgesics 2

First-Line Treatment for Moderate to Severe Migraine

For moderate to severe attacks, use combination therapy with a triptan PLUS an NSAID, as this is superior to either agent alone. 1, 2

• Oral triptans with strong evidence: sumatriptan 50-100 mg, rizatriptan, naratriptan, or zolmitriptan 2, 3
• Sumatriptan 50-100 mg achieves headache response (reduction to mild or no pain) in 50-62% of patients at 2 hours versus 17-27% with placebo 3
• The 50 mg and 100 mg doses show no significant difference in efficacy, making 50 mg the preferred starting dose 3
• Combining sumatriptan with naproxen sodium 500 mg provides 130 more patients per 1000 achieving sustained pain relief at 48 hours compared to either agent alone 2

Critical Timing Principle

Administer treatment as early as possible during the attack, ideally when pain is still mild, as this significantly improves efficacy. 1, 2

• Early triptan administration is most effective when taken before headache reaches peak intensity 2
• Delaying treatment reduces response rates and increases likelihood of headache recurrence 2

Route Selection Based on Symptoms

For patients with significant nausea or vomiting, use non-oral routes: 2, 4

• Subcutaneous sumatriptan 6 mg provides the highest efficacy (59% pain-free at 2 hours) with fastest onset (15 minutes to peak concentration) 2, 3
• Intranasal sumatriptan 5-20 mg or intranasal zolmitriptan are alternatives 2
• Intranasal dihydroergotamine (DHE) has good evidence for efficacy and safety 2

Emergency Department/Urgent Care Treatment

For severe migraine requiring parenteral therapy, use IV metoclopramide 10 mg plus IV ketorolac 30 mg as first-line combination therapy. 1, 2

• Metoclopramide provides direct analgesic effects through central dopamine receptor antagonism, not just antiemetic effects 2
• Ketorolac has rapid onset with approximately 6 hours duration and minimal rebound headache risk 2
• Prochlorperazine 10 mg IV is an alternative to metoclopramide with comparable efficacy 2

Second-Line and Rescue Treatments

For patients who fail combination triptan + NSAID therapy, escalate to CGRP antagonists (rimegepant, ubrogepant, zavegepant) or dihydroergotamine. 1, 2

• Lasmiditan should only be considered after failure of all other pharmacologic treatments 1
• If one triptan fails, try a different triptan before abandoning the class entirely, as failure of one does not predict failure of others 2

Critical Frequency Limitation to Prevent Medication-Overuse Headache

Limit acute medication use to ≤10 days per month for triptans and ≤15 days per month for NSAIDs, and limit all acute treatments to no more than 2 days per week. 1, 2

• Medication-overuse headache (MOH) results from frequent use of acute medications and can lead to daily headaches 1, 2
• If acute treatment is needed more than 2 days per week, initiate preventive therapy immediately 1, 2

When to Initiate Preventive Therapy

Start preventive therapy if: 1, 2

• Headaches continue to impair quality of life despite optimized acute therapy 2
• Patient uses acute medications more than 2 days per week 1, 2
• Patient has ≥2 attacks per month producing disability lasting ≥3 days 2
• Contraindication to or failure of acute treatments 2

Special Populations: Pregnancy and Breastfeeding

Use acetaminophen as first-line treatment for pregnant or breastfeeding patients, with NSAIDs usable prior to the third trimester. 1

• Avoid triptans and ergotamines during pregnancy unless benefits clearly outweigh risks 1

Contraindications to Triptans

Do not use triptans in patients with: 2, 4

• Ischemic heart disease or previous myocardial infarction 2
• Uncontrolled hypertension 2
• Vasospastic coronary disease 2
• Significant cardiovascular disease 2

Essential Lifestyle Modifications

Counsel all patients on lifestyle modifications including: 1

• Adequate hydration and regular meals 1
• Consistent sleep schedule 1
• Regular aerobic exercise 1
• Stress management techniques 1
• Weight loss if overweight 1

Cost Considerations

Prescribe generic NSAIDs and older triptans (generic sumatriptan, naproxen) when equally effective options exist, as they are significantly less expensive than newer agents. 1

Common Pitfalls to Avoid

Critical mistake: Do not allow patients to increase frequency of acute medication use in response to treatment failure, as this creates a vicious cycle of medication-overuse headache; instead transition to preventive therapy while optimizing acute treatment strategy 2

Avoid opioids: Opioids should be reserved only for cases where other medications cannot be used, when sedation effects are not a concern, or when the risk for abuse has been addressed, as they can lead to dependency, rebound headaches, and eventual loss of efficacy 1, 2