What are the treatment options for a patient with migraines?

Migraine Treatment

For acute migraine, start with NSAIDs (ibuprofen 400-800 mg, naproxen 500-825 mg, or aspirin-acetaminophen-caffeine combination) for mild-to-moderate attacks, and escalate immediately to a triptan combined with an NSAID for moderate-to-severe attacks, taken as early as possible when pain is still mild. 1, 2, 3

First-Line Acute Treatment Algorithm

Mild-to-Moderate Migraine

• Ibuprofen 400-800 mg every 6 hours is the most effective over-the-counter option 3, 4
• Naproxen sodium 500-825 mg provides longer duration of action and can be repeated every 2-6 hours, with maximum 1.5 g per day 1, 3
• Aspirin-acetaminophen-caffeine combination has strong evidence with NNT of 9 for pain freedom at 2 hours and NNT of 4 for pain relief at 2 hours 2, 3
• Never use acetaminophen alone—it is ineffective for migraine as monotherapy 2, 3

Moderate-to-Severe Migraine

• Combine a triptan with an NSAID from the start—this combination is superior to either agent alone 1, 2, 3
• Sumatriptan 50-100 mg plus naproxen sodium 500 mg provides 130 more patients per 1000 achieving sustained pain relief at 48 hours compared to either alone 1
• Alternative oral triptans include rizatriptan 10 mg (fastest oral triptan, reaching peak in 60-90 minutes), eletriptan 40 mg, or zolmitriptan 2.5-5 mg 1
• Take medication as early as possible when pain is still mild—triptans lose effectiveness if delayed 1, 2, 3, 5

Route Selection Based on Symptoms

When Nausea or Vomiting is Present

• Use non-oral routes of administration 1, 2, 3
• Subcutaneous sumatriptan 6 mg provides highest efficacy (59% complete pain relief by 2 hours) with onset within 15 minutes 1, 3, 5
• Intranasal sumatriptan 5-20 mg is an alternative non-oral option 1, 3
• Add metoclopramide 10 mg IV or prochlorperazine 10 mg IV for both antiemetic effect and direct analgesic benefit through central dopamine receptor antagonism 1, 2

IV Treatment for Severe Attacks

• Metoclopramide 10 mg IV plus ketorolac 30 mg IV is first-line combination therapy for severe migraine requiring intravenous treatment 1
• Ketorolac has rapid onset with approximately 6 hours duration and minimal rebound headache risk 1
• Prochlorperazine 10 mg IV is comparable to metoclopramide in efficacy 1

Critical Medication Frequency Limits

Limit ALL acute migraine medications to no more than 2 days per week (10 days per month) to prevent medication-overuse headache. 1, 2, 3, 5

• NSAIDs trigger medication overuse at ≥15 days/month; triptans at ≥10 days/month 1, 3
• Medication overuse headache presents as daily headaches or marked increase in migraine frequency 1, 5
• If requiring acute treatment more than twice weekly, initiate preventive therapy immediately 1, 2, 3

Alternative Options When Triptans Fail or Are Contraindicated

Try Different Triptans First

• Failure of one triptan does not predict failure of others—try 2-3 different triptans before abandoning the class 1, 2
• Each triptan should be tried for 2-3 headache episodes before switching 1

CGRP Antagonists (Gepants)

• Ubrogepant 50-100 mg or rimegepant are primary alternatives when triptans are contraindicated or ineffective 1, 2
• Gepants have no vasoconstriction, making them safe for patients with cardiovascular disease, uncontrolled hypertension, or cerebrovascular disease 1
• NNT for pain freedom at 2 hours is 13 2

Ditans

• Lasmiditan 50-200 mg is a 5-HT1F receptor agonist without vasoconstrictor activity 1, 2
• Patients must not drive or operate machinery for at least 8 hours after taking lasmiditan due to CNS effects 1

Dihydroergotamine (DHE)

• Intranasal or IV DHE has good evidence for efficacy as monotherapy 1, 2

Triptan Contraindications (Use Alternatives Above)

Triptans are contraindicated in: 3, 5

• Ischemic heart disease or previous myocardial infarction
• Prinzmetal's variant angina or coronary artery vasospasm
• Wolff-Parkinson-White syndrome or cardiac accessory pathway disorders
• History of stroke or transient ischemic attack
• Uncontrolled hypertension
• Hemiplegic or basilar migraine

Medications to Absolutely Avoid

Never use opioids (hydromorphone, meperidine, oxycodone) or butalbital-containing compounds—they lead to dependency, rebound headaches, and loss of efficacy over time. 1, 2, 3, 6

Preventive Therapy Indications

Start preventive therapy when: 1, 2, 3

• Using acute medications more than twice per week
• Two or more attacks per month producing disability lasting 3+ days
• Contraindication to or failure of acute treatments
• Presence of uncommon migraine conditions (hemiplegic migraine, migraine with prolonged aura)

First-Line Preventive Medications

• Propranolol 80-240 mg/day has the strongest evidence 1, 2, 7
• Topiramate 100 mg/day is highly effective but requires discussion of teratogenic effects with women of childbearing potential 1, 2
• Amitriptyline 30-150 mg/day for patients with mixed migraine and tension-type headache 1
• Avoid valproate in women of childbearing age due to teratogenic effects 1, 2

Chronic Migraine (≥15 headache days/month)

• OnabotulinumtoxinA 155 units is FDA-approved and effective for chronic migraine based on large-scale, double-blind, placebo-controlled trials 2

Common Pitfalls to Avoid

• Taking medication too late in the attack—triptans lose effectiveness if not taken when pain is still mild 1, 2, 3, 5
• Not combining triptan with NSAID—combination therapy is superior to either agent alone 1, 2, 3
• Allowing patients to increase acute medication frequency—this creates medication-overuse headache; transition to preventive therapy instead 1, 3
• Using acetaminophen alone—it has no efficacy for migraine as monotherapy 2, 3
• Prescribing opioids or butalbital compounds—these worsen long-term outcomes 1, 2, 3, 6

Non-Pharmacologic Adjuncts

• Regular moderate-to-intense aerobic exercise (40 minutes three times weekly) is as effective as some preventive medications 2
• Cognitive-behavioral therapy, biofeedback, and relaxation training have good evidence for efficacy and should be offered to all patients 2
• Maintain regular meals, stay well hydrated, and ensure sufficient sleep 2