What are the treatment options for migraine headaches?

Treatment of Migraine Headaches

Start with combination therapy of an NSAID plus acetaminophen for mild to moderate migraine, and escalate to a triptan combined with an NSAID or acetaminophen for moderate to severe attacks or when first-line therapy fails. 1

First-Line Treatment Algorithm

For Mild to Moderate Migraine

• Begin with NSAIDs (ibuprofen 400-800 mg, naproxen 500-1000 mg, or aspirin 900-1000 mg) or the combination of acetaminophen 1000 mg + aspirin 900 mg + caffeine 130 mg 1, 2
• Acetaminophen 1000 mg can be used as monotherapy but is less effective than NSAIDs or combination therapy 2
• Ibuprofen 400 mg provides 2-hour headache relief in 57% of patients versus 25% with placebo (NNT 3.2), with 2-hour pain-free rates of 26% versus 12% (NNT 7.2) 3
• Initiate treatment as early as possible during the attack—early administration significantly improves efficacy 1, 2

For Moderate to Severe Migraine

• Add a triptan to an NSAID, or to acetaminophen when NSAIDs are contraindicated 1
• Triptans are first-line therapy for moderate to severe attacks, with oral options including sumatriptan 50-100 mg, rizatriptan 10 mg, eletriptan 40-80 mg, almotriptan 12.5 mg, naratriptan 2.5 mg, frovatriptan 2.5 mg, or zolmitriptan 2.5-5 mg 1, 4
• Sumatriptan 100 mg provides 2-hour headache relief in 62% of patients versus 27% with placebo, with 4-hour relief in 79% versus 38% 5
• Combination therapy of triptan plus NSAID prevents the 40% recurrence rate within 48 hours seen with triptan monotherapy 6

Route of Administration Considerations

• Use non-oral triptans (subcutaneous sumatriptan 6 mg or intranasal formulations) plus an antiemetic for patients with severe nausea or vomiting 1, 6
• Subcutaneous sumatriptan 6 mg provides the highest efficacy with 59% achieving complete pain relief by 2 hours, though with higher adverse event rates 6
• Intranasal sumatriptan (5-20 mg) or zolmitriptan are particularly useful when significant nausea or vomiting is present 6, 7

Second-Line and Rescue Therapy

When Combination Triptan + NSAID Therapy Fails

• Escalate to CGRP antagonists (gepants: rimegepant 75 mg, ubrogepant 50-100 mg, or zavegepant 10 mg nasal spray) or dihydroergotamine 1, 2
• Consider lasmiditan 50-100 mg only after failure of all other pharmacologic treatments included in this guideline 1, 2

For Severe Attacks Requiring Parenteral Therapy

• IV ketorolac 30 mg plus IV metoclopramide 10 mg is first-line combination therapy for severe migraine in emergency or urgent care settings 2, 6
• IV prochlorperazine 10 mg is comparable to metoclopramide in efficacy and can be used as an alternative 6
• IV dihydroergotamine is an effective option for refractory cases 1, 4

Critical Medications to Avoid

• Do not use opioids or butalbital-containing compounds for acute episodic migraine treatment 1, 2
• These medications lead to dependency, rebound headaches, medication-overuse headache, and eventual loss of efficacy 2, 6

Medication-Overuse Headache Prevention

• Limit acute medication use to ≤10 days per month for triptans and ≤15 days per month for NSAIDs 1, 2
• Medication overuse headache is defined as headache occurring on ≥15 days per month for at least 3 months in patients with a preexisting headache disorder that develops due to overuse of acute medication 1
• Initiate preventive therapy if acute treatment is needed more than 2 days per week 2, 6

Treatment Failure Algorithm

When Current Medication Stops Working

• First, try a different triptan—failure of one triptan does not predict failure of others 6
• Ensure early administration during the attack while headache is still mild, as triptans are most effective when taken early 6
• Consider route change (e.g., subcutaneous sumatriptan if oral fails), particularly for patients who rapidly reach peak intensity or have vomiting 6
• Rule out medication-overuse headache if using acute medications more than twice weekly 6

Transition to Preventive Therapy

• If headaches continue to impair quality of life despite optimized acute therapy, or if acute medications are used more than 2 days per week, preventive therapy is indicated 2, 6
• Preventive therapy reduces attack frequency and can restore responsiveness to acute treatments 6
• Do not allow patients to increase frequency of acute medication use in response to treatment failure—this creates a vicious cycle of medication-overuse headache 6

Special Populations

Pregnancy and Lactation

• Acetaminophen is first-line treatment for pregnant or breastfeeding patients 2
• NSAIDs can be used prior to the third trimester 2, 7
• Discuss adverse effects of pharmacologic treatments during pregnancy and lactation with all patients of childbearing potential 1

Pediatric Patients

• Acetaminophen, ibuprofen, intranasal sumatriptan, and intranasal zolmitriptan appear effective in children and adolescents, though data are limited 7

Essential Lifestyle Modifications

• Counsel all patients on lifestyle modifications including adequate hydration, regular meals, consistent sleep schedule, regular aerobic exercise, stress management techniques, and weight loss if overweight 2

Cost Considerations

• Prescribe less costly recommended medications when equally effective options exist—generic NSAIDs and older triptans (sumatriptan, naratriptan) are significantly less expensive than newer agents 2
• Over-the-counter medications (acetaminophen, ibuprofen, naproxen, aspirin) have lower cost, fewer adverse effects, and more favorable routes of administration compared with prescription medications 8

Common Pitfalls to Avoid

• Do not delay treatment—early administration is critical for efficacy 1, 2
• Do not assume all triptans are equivalent for an individual patient—response varies and switching within the class is appropriate 1, 6
• Do not restrict antiemetics only to patients who are vomiting—nausea itself is one of the most disabling symptoms and warrants treatment 6
• Do not establish patterns of frequent opioid use, as this leads to medication-overuse headache and dependency 6