What are the treatment options for a patient experiencing migraines?

Migraine Treatment

Acute Treatment Algorithm

For mild to moderate migraine attacks, start with NSAIDs (ibuprofen 400-800 mg, naproxen sodium 500-825 mg, or aspirin 1000 mg) or the combination of aspirin-acetaminophen-caffeine; for moderate to severe attacks or when NSAIDs fail after 2-3 attempts, escalate immediately to a triptan plus NSAID combination, which provides superior efficacy compared to either agent alone. 1, 2

First-Line Treatment for Mild to Moderate Attacks

• NSAIDs are the recommended first-line therapy with proven efficacy including ibuprofen (400-800 mg), naproxen sodium (500-825 mg), aspirin (1000 mg), or diclofenac potassium 1, 2, 3
• The aspirin-acetaminophen-caffeine combination has strong evidence with a number needed to treat of 9 for pain freedom at 2 hours and 4 for pain relief at 2 hours 2
• Acetaminophen 1000 mg has less efficacy than NSAIDs and should only be used when NSAIDs are contraindicated 2
• Take medication as early as possible during the attack while pain is still mild to maximize effectiveness 1, 2

First-Line Treatment for Moderate to Severe Attacks

• Triptans combined with NSAIDs represent the strongest recommendation, providing 130 more patients per 1000 achieving sustained pain relief at 48 hours compared to either agent alone 1
• Specific triptan options with good evidence include sumatriptan (50-100 mg), rizatriptan (10 mg), eletriptan (40 mg), zolmitriptan (2.5-5 mg), naratriptan, almotriptan, and frovatriptan 1, 3, 4
• If one triptan fails after 2-3 headache episodes, try a different triptan as failure of one does not predict failure of others 1
• Rizatriptan 10 mg reaches peak concentration fastest (60-90 minutes) among oral triptans 1

Route Selection Based on Symptoms

• For patients with significant nausea or vomiting, use non-oral routes: subcutaneous sumatriptan 6 mg (onset within 15 minutes, 59% pain-free at 2 hours) or intranasal formulations 1, 2
• Subcutaneous sumatriptan provides the highest efficacy (70-82% response within 15 minutes) but has higher adverse event rates 1

Antiemetic Adjuncts

• Add metoclopramide 10 mg IV or prochlorperazine 10 mg IV/25 mg oral 20-30 minutes before analgesics for synergistic analgesia beyond just treating nausea 1
• These dopamine antagonists provide independent analgesic benefit through central receptor antagonism 1

Emergency Department/Urgent Care IV Treatment

The optimal IV cocktail combines metoclopramide 10 mg IV plus ketorolac 30 mg IV, providing rapid pain relief with minimal rebound headache risk. 1

• Ketorolac has rapid onset with approximately 6 hours duration and minimal rebound risk 1
• Metoclopramide provides direct analgesic effects independent of antiemetic properties 1
• Prochlorperazine 10 mg IV is equally effective as metoclopramide with a more favorable side effect profile (21% vs 50% adverse events) 1
• Dihydroergotamine (DHE) IV or intranasal is an alternative with good efficacy evidence 1, 3, 4

Alternative Agents When Triptans Fail or Are Contraindicated

CGRP antagonists (gepants) are the preferred alternative when triptans fail or are contraindicated due to cardiovascular disease, as they have no vasoconstrictor activity. 1, 2

• Ubrogepant (50-100 mg) or rimegepant are first-line alternatives with a number needed to treat of 13 for pain freedom at 2 hours 1, 2
• Lasmiditan (50-200 mg), a 5-HT1F agonist without vasoconstriction, is second-line but requires an 8-hour driving restriction due to CNS effects 1, 2
• Zavegepant is another gepant option 1

Triptan Contraindications Requiring Alternative Approach

• Ischemic heart disease, vasospastic coronary disease, uncontrolled hypertension, cerebrovascular disease, or significant cardiovascular disease 1

Critical Medication Frequency Limits

Strictly limit all acute migraine medications to no more than 2 days per week (10 days per month for triptans, 15 days per month for NSAIDs) to prevent medication-overuse headache, which paradoxically increases headache frequency and can lead to daily headaches. 1, 2, 5

• If patients require acute treatment more than twice weekly, initiate preventive therapy immediately 1, 5

Medications to Absolutely Avoid

Never use opioids or butalbital-containing compounds routinely for migraine as they have questionable efficacy, lead to dependency, cause rebound headaches, and result in loss of efficacy over time 1, 2, 3, 4

Preventive Therapy Indications

Initiate preventive therapy when patients experience ≥2 attacks per month producing disability lasting ≥3 days, use acute medications more than twice weekly, have contraindications to acute treatments, or suffer from uncommon migraine variants. 1, 5

First-Line Preventive Medications

• Beta-blockers without intrinsic sympathomimetic activity (propranolol 80-240 mg/day or timolol 20-30 mg/day) have consistent efficacy evidence 1, 5
• Topiramate is effective for both episodic and chronic migraine but requires discussion of teratogenic effects with patients of childbearing potential 2, 5
• Amitriptyline 30-150 mg/day is particularly useful for patients with mixed migraine and tension-type headache 1, 5
• OnabotulinumtoxinA 155 units is FDA-approved specifically for chronic migraine (≥15 headache days per month) based on large-scale placebo-controlled trials 2, 5
• CGRP monoclonal antibodies should be considered when oral preventives fail, with efficacy assessed after 3-6 months 1

Non-Pharmacologic Treatments

• Regular moderate-to-intense aerobic exercise for 40 minutes three times weekly is as effective as topiramate or relaxation therapy for prevention 2, 5
• Cognitive-behavioral therapy, biofeedback, and relaxation training have good efficacy evidence and should be integrated into comprehensive management 2, 5
• Neuromodulation devices (single-pulse transcranial magnetic stimulation, external trigeminal nerve stimulation, remote electrical neuromodulation, noninvasive vagus nerve stimulation) are alternative options when medications are contraindicated or not tolerated 6

Lifestyle Modifications

• Maintain regular meals, adequate hydration, and sufficient sleep 2
• Identify and reduce trigger factors using a headache diary 2, 5
• Manage stress with relaxation techniques or mindfulness practices 2

Special Populations

Pregnancy

• Acetaminophen is the safest acute migraine medication during pregnancy 4
• Sumatriptan may be an option for selected patients and is compatible with breastfeeding 4
• Valproate is strictly contraindicated due to teratogenic risk 1

Chronic Migraine (≥15 headache days per month)

• Rule out secondary causes before establishing diagnosis 2
• OnabotulinumtoxinA 155 units is the specific FDA-approved treatment 2, 5
• Monitor closely for medication overuse headache 2

Common Pitfalls to Avoid

• 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 1
• Do not assume all triptans will fail if one fails; try at least 2-3 different triptans before abandoning the class 1
• Do not use prednisone or corticosteroids for routine acute headache; they are more appropriate for status migrainosus 1
• Do not restrict metoclopramide only to patients who are vomiting; nausea itself is disabling and warrants treatment, plus metoclopramide provides independent analgesia 1