What are the treatment options for migraine headaches?

Treatment Options for Migraine Headaches

For mild to moderate migraine attacks, start with combination therapy of acetaminophen plus aspirin plus caffeine or an NSAID (ibuprofen, naproxen, aspirin) taken as early as possible when pain is still mild; for moderate to severe attacks, use triptans (sumatriptan, rizatriptan, zolmitriptan) as first-line therapy, ideally within the first hour of symptom onset. 1, 2

First-Line Treatment Algorithm

Mild to Moderate Migraine

• Combination therapy with acetaminophen 1000 mg plus aspirin 500-1000 mg plus caffeine 130 mg is the most effective first-line option, superior to acetaminophen monotherapy 1, 2
• NSAIDs alone are highly effective alternatives: naproxen sodium 500-825 mg, ibuprofen 400-800 mg, or aspirin 900-1000 mg 1, 2, 3
• Acetaminophen 1000 mg as monotherapy is less effective than NSAIDs or combination therapy and should only be used when NSAIDs are contraindicated 1
• Early administration is critical—treatment should begin when headache is still mild, not after it reaches peak intensity 1, 2

Moderate to Severe Migraine

• Triptans are first-line therapy for moderate to severe attacks: oral sumatriptan 50-100 mg, rizatriptan 10 mg, naratriptan 2.5 mg, or zolmitriptan 2.5-5 mg 2, 4
• Sumatriptan 100 mg achieves headache relief in 50-67% of patients at 2 hours versus 10-31% with placebo 5, 6
• For rapid onset or severe nausea/vomiting, use subcutaneous sumatriptan 6 mg (70-80% response rate within 1 hour) or intranasal formulations 2, 7, 4
• Combination triptan plus NSAID therapy is more effective than either alone—consider sumatriptan 100 mg plus naproxen 500 mg 2, 4

Second-Line and Rescue Treatments

When First-Line Therapy Fails

• If one triptan fails, try a different triptan—failure of one does not predict failure of others 2
• Escalate to CGRP antagonists (gepants: rimegepant, ubrogepant, zavegepant) or dihydroergotamine for patients who fail combination triptan plus NSAID therapy 1, 2
• Lasmiditan may be considered only after failure of all other pharmacologic treatments 1

Parenteral Therapy for Severe Attacks

• For severe migraine requiring IV treatment, use ketorolac 30 mg IV plus metoclopramide 10 mg IV as first-line combination therapy 1, 2
• Prochlorperazine 10 mg IV is an effective alternative to metoclopramide with comparable efficacy 2
• Dihydroergotamine (DHE) IV or intranasal has good evidence for efficacy and safety 2

Adjunctive Antiemetic Therapy

• Metoclopramide 10 mg or prochlorperazine 10-25 mg should not be restricted only to patients who are vomiting—nausea itself is one of the most disabling migraine symptoms and warrants treatment 2
• Antiemetics provide synergistic analgesia beyond just treating nausea, enhancing absorption of co-administered medications through prokinetic effects 2
• Administer antiemetics 20-30 minutes before NSAIDs or triptans for optimal benefit 2

Critical Medication-Overuse Headache Prevention

• Limit acute medication use to ≤10 days per month for triptans and ≤15 days per month for NSAIDs to prevent medication-overuse headache 1, 2
• Initiate preventive therapy if acute treatment is needed more than 2 days per week 1, 2
• Avoid opioids and butalbital-containing compounds—they lead to dependency, rebound headaches, and loss of efficacy 1, 2, 3

Preventive Therapy Indications

• Start preventive medications when: attacks occur more than 2 days per week, acute medications are contraindicated or ineffective, or quality of life is significantly impaired despite optimized acute therapy 2
• First-line preventive options include propranolol, timolol, amitriptyline, or divalproex sodium 3
• Preventive therapy requires 2-3 months for oral agents to demonstrate efficacy 2

Special Population Considerations

Pregnant or Breastfeeding Patients

• Acetaminophen is first-line treatment during pregnancy 1
• NSAIDs can be used prior to the third trimester but should be avoided in the third trimester 1
• Triptans are generally avoided during pregnancy unless benefits clearly outweigh risks 1

Patients with Cardiovascular Disease

• Triptans are contraindicated in patients with coronary artery disease, previous myocardial infarction, Prinzmetal angina, or uncontrolled hypertension 8, 7, 9
• Use NSAIDs with caution in patients with cardiovascular disease—consider acetaminophen or CGRP antagonists as alternatives 2

Essential Lifestyle Modifications

• Counsel all patients on: adequate hydration, regular meals, consistent sleep schedule (7-9 hours), regular aerobic exercise, stress management techniques, and weight loss if overweight 1, 3
• These modifications reduce attack frequency and improve response to acute treatments 1, 3

Common Pitfalls to Avoid

• Do not delay treatment—waiting until headache reaches peak intensity significantly reduces medication efficacy 1, 2
• Do not use the "step-care" approach (starting with safest/cheapest and escalating)—the "stratified-care" approach (matching treatment intensity to attack severity) is superior 8
• Do not allow patients to increase frequency of acute medication use in response to treatment failure—this creates medication-overuse headache; instead transition to preventive therapy 2
• Do not assume all triptans are equivalent for an individual patient—if one triptan fails after 2-3 adequate trials, try a different triptan before abandoning the class 2
• Approximately 40% of patients experience headache recurrence within 24 hours after initial triptan response—a second dose is usually effective 5, 6, 7

Cost-Effective Prescribing

• Prescribe generic NSAIDs and older triptans (sumatriptan, naratriptan) when equally effective options exist—they are significantly less expensive than newer agents 1
• Generic sumatriptan 100 mg is cost-effective and has the most robust evidence base among triptans 1, 5, 6