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, begin with combination therapy of an NSAID (ibuprofen 400 mg, naproxen sodium, or aspirin) plus acetaminophen, or use the combination of acetaminophen/aspirin/caffeine. 1

• NSAIDs alone (aspirin, ibuprofen, naproxen sodium, diclofenac potassium) are highly effective first-line options, with ibuprofen 400 mg providing 2-hour headache relief in 57% of patients versus 25% with placebo (NNT 3.2) 2
• The combination of acetaminophen, aspirin, and caffeine has strong evidence as first-line therapy 1, 3
• Acetaminophen 1000 mg can be used as monotherapy but is less effective than NSAIDs or combination therapy 1
• Start treatment as early as possible during the attack—early administration significantly improves efficacy 1, 3

First-Line Treatment for Moderate to Severe Migraine

For moderate to severe migraine, use combination therapy with a triptan plus an NSAID or acetaminophen as first-line treatment. 1

• Oral triptans with strong evidence include sumatriptan (50-100 mg), rizatriptan, naratriptan, and zolmitriptan 3, 4
• Sumatriptan 100 mg provides 2-hour headache relief in 62% of patients and 4-hour relief in 79% 4
• Combination triptan + NSAID therapy is superior to either agent alone 1, 5
• The 50 mg and 100 mg doses of sumatriptan show no statistically significant difference in efficacy, making 50 mg the preferred dose for cost-effectiveness 4

Route Selection Based on Symptoms

When severe nausea or vomiting is present, use non-oral routes: subcutaneous or intranasal sumatriptan plus an antiemetic (metoclopramide 10 mg IV or prochlorperazine 10 mg IV). 1, 3

• Subcutaneous sumatriptan 6 mg provides the highest efficacy (59% pain-free at 2 hours) but with higher adverse event rates 3
• Intranasal sumatriptan (5-20 mg) is effective when oral administration is not feasible 3
• Metoclopramide and prochlorperazine provide both antiemetic effects and synergistic analgesia 3

Second-Line Options for Treatment-Resistant Cases

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

• These agents are reserved for inadequate response or intolerance to first-line combination therapy 1
• Lasmiditan (ditan class) is considered only after failure of all other pharmacologic treatments in this guideline 1
• CGRP antagonists may have lower likelihood of pain freedom compared to triptan + NSAID combination but offer an alternative mechanism of action 1

Emergency Department/Urgent Care Treatment

For severe migraine requiring parenteral therapy, use IV ketorolac 30 mg plus IV metoclopramide 10 mg as first-line combination therapy. 3

• Ketorolac provides rapid onset with approximately 6 hours duration and minimal rebound headache risk 3
• Prochlorperazine 10 mg IV is equally effective as metoclopramide with comparable efficacy 3
• IV dihydroergotamine is an alternative for patients with contraindications to NSAIDs 3
• Avoid IV dexamethasone for routine acute treatment—corticosteroids are more appropriate for status migrainosus 3

Critical Medications to Avoid

Do not use opioids (including hydromorphone) or butalbital-containing compounds for acute migraine treatment. 1, 3

• These agents lead to dependency, medication-overuse headache, and eventual loss of efficacy 1, 3
• Opioids should only be reserved for exceptional cases where all other options are contraindicated, sedation is acceptable, and abuse risk has been addressed 3

Medication-Overuse Headache Prevention

Limit acute medication use to prevent medication-overuse headache: ≤10 days per month for triptans, ≤15 days per month for NSAIDs. 1

• Medication-overuse headache develops when acute medications are used ≥15 days/month for ≥3 months (NSAIDs) or ≥10 days/month (triptans) 1
• If acute treatment is needed more than 2 days per week, initiate preventive therapy 1, 3
• This pattern indicates need for prophylactic medication rather than increased acute treatment frequency 3

Algorithm for Failed Triptan Response

When current medication stops working, follow this escalation:

1. Try a different triptan first—failure of one triptan does not predict failure of others 3
2. Ensure early administration—triptans are most effective when taken while headache is still mild 3
3. Add fast-acting NSAID to prevent relapse—addresses the 40% who experience symptom recurrence within 48 hours 3
4. Consider route change—switch from oral to subcutaneous or intranasal formulation 3
5. Rule out medication-overuse headache—if using acute medications >2 days/week 3
6. Initiate preventive therapy—if headaches continue despite optimized acute therapy 3

Special Populations

For pregnant or breastfeeding patients, acetaminophen is first-line; NSAIDs can be used prior to third trimester. 1, 6

• Discuss adverse effects of all pharmacologic treatments during pregnancy and lactation 1
• Triptans should generally be avoided during pregnancy 6
• Opiates may be considered in refractory cases during pregnancy only 6

Essential Lifestyle Modifications

Counsel all patients on lifestyle modifications: adequate hydration, regular meals, consistent sleep (7-9 hours), regular aerobic exercise, stress management techniques, and weight loss if overweight. 1

• Identify and address modifiable migraine triggers through detailed history 1
• These modifications reduce attack frequency and improve treatment response 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 agents 1
• CGRP antagonists have annualized costs of $4,959-$8,800 compared to generic triptans at <$100 annually 1