What are the treatment options for migraine?

Migraine Treatment

Acute Treatment Algorithm

For mild to moderate migraine attacks, start with NSAIDs (ibuprofen 400-800 mg, naproxen 500-825 mg, or aspirin 1000 mg) or aspirin-acetaminophen-caffeine combination; for moderate to severe attacks, use a triptan (sumatriptan 50-100 mg, rizatriptan, or naratriptan) combined with an NSAID, taken as early as possible when pain is still mild. 1, 2, 3

First-Line Treatment by Attack Severity

Mild to Moderate Attacks:

• NSAIDs are first-line therapy, with proven efficacy for aspirin, ibuprofen, naproxen sodium, and diclofenac potassium 1, 2, 3
• Aspirin-acetaminophen-caffeine combination receives strong recommendation with NNT of 4 for pain relief at 2 hours 1
• Paracetamol (acetaminophen) 1000 mg has less efficacy and should only be used if NSAIDs are not tolerated 1
• Combination analgesics containing caffeine enhance absorption and provide synergistic analgesia 1, 2

Moderate to Severe Attacks:

• Triptans are first-line therapy, with oral sumatriptan 50-100 mg, rizatriptan, naratriptan, and zolmitriptan having the strongest evidence 1, 2, 3
• Combining a triptan with an NSAID is superior to either agent alone, with 130 more patients per 1000 achieving sustained pain relief at 48 hours 1, 2
• Sumatriptan 100 mg provides pain-free response in 28% at 2 hours (NNT 4.7) versus 11% with placebo 1, 4, 5
• Take medication early when pain is still mild for maximum effectiveness—this significantly improves outcomes compared to treating established moderate/severe pain 1, 3, 5

Route Selection Based on Symptoms

Oral Route (Standard):

• Use for patients without significant nausea or vomiting 1, 2
• Sumatriptan 50 mg (NNT 6.1) or 100 mg (NNT 4.7) for pain-free at 2 hours 1, 4, 5
• If one triptan fails, try a different triptan as failure of one does not predict failure of others 1, 2

Subcutaneous Route (Most Effective):

• Subcutaneous sumatriptan 6 mg is the most effective option, providing pain relief in 70-82% within 15 minutes and complete pain-free response in 59% at 2 hours (NNT 2.3) 1, 2, 6
• Use for patients with rapid progression to peak intensity, severe attacks, or significant vomiting 1, 2
• Reaches peak concentration in approximately 15 minutes, faster than any other route 2, 6

Intranasal Route:

• Intranasal sumatriptan (5-20 mg) or zolmitriptan for patients with nausea/vomiting who cannot tolerate oral medications 1, 2, 3
• Intranasal sumatriptan 20 mg has NNT 3.5 for headache relief at 2 hours 6

Managing Associated Symptoms

Nausea and Vomiting:

• Add metoclopramide 10 mg IV/PO or prochlorperazine 10 mg IV/25 mg PO, which provide direct analgesic effects beyond antiemetic properties through central dopamine receptor antagonism 1, 2
• Antiemetics improve gastric motility and enhance absorption of co-administered medications 1, 2
• Do not restrict antiemetics only to patients who are vomiting—nausea itself is highly disabling and warrants treatment 2

Advanced Treatment Options (Third-Line)

For patients who fail all triptans or have contraindications:

• CGRP antagonists (gepants): rimegepant or ubrogepant (NNT 13 for pain freedom at 2 hours) 1, 2
• Lasmiditan (ditan): robust benefit but significant adverse effects including driving restrictions (NNH 4) 1
• Dihydroergotamine (DHE) intranasal or IV has good evidence for efficacy and safety 1, 2

Emergency Department/Urgent Care IV Cocktail

Recommended IV combination for severe attacks:

• Metoclopramide 10 mg IV plus ketorolac 30 mg IV provides rapid pain relief with minimal rebound headache risk 2
• Prochlorperazine 10 mg IV is comparable to metoclopramide in efficacy 2
• Ketorolac has rapid onset with approximately 6 hours duration 2

Critical Medication Overuse Prevention

Limit all acute migraine medications to no more than 2 days per week (≤10 days/month for triptans, ≤15 days/month for NSAIDs) to prevent medication overuse headache. 1, 2, 3

• Medication overuse headache presents as daily headaches or marked increase in migraine frequency 1, 4
• If patients need acute treatment more than twice weekly, immediately initiate preventive therapy rather than increasing acute medication frequency 1, 2

Medications to Avoid

Avoid opioids and butalbital-containing analgesics as they lead to dependency, rebound headaches, and eventual loss of efficacy 1, 2

• Opioids should only be reserved for cases where all other medications cannot be used, sedation is not a concern, and abuse risk has been addressed 2

Preventive Therapy Indications

Consider preventive therapy for patients with:

• Two or more attacks per month producing disability lasting ≥3 days 1, 3
• Contraindication to or failure of acute treatments 1, 3
• Use of acute medication more than twice per week 1, 3
• Presence of uncommon migraine conditions (hemiplegic migraine, migraine with prolonged aura) 1

First-line preventive options:

• Topiramate (discuss teratogenic effects with patients of childbearing potential) 1
• Beta-blockers (propranolol 80-240 mg/day or timolol 20-30 mg/day) 1, 3
• ACE inhibitors, ARBs, or candesartan 1, 3
• OnabotulinumtoxinA 155 units for chronic migraine (≥15 headache days/month) 1

Non-Pharmacologic Interventions

Lifestyle modifications:

• Regular moderate to intense aerobic exercise 40 minutes three times weekly (as effective as some preventive medications) 1
• Maintain regular meals, adequate hydration, and consistent sleep schedule 1, 3
• Stress management with relaxation techniques or mindfulness practices 1, 3

Behavioral therapies:

• Cognitive-behavioral therapy, biofeedback, and relaxation training should be offered to all patients as part of comprehensive management 1, 3

Monitoring and Follow-Up

Have patients maintain a headache diary tracking severity, frequency, duration, disability, treatment response, and adverse effects to determine treatment efficacy and identify analgesic overuse 1, 3

Contraindications to Triptans

Triptans are contraindicated in:

• Ischemic heart disease, previous myocardial infarction, or coronary artery disease 2, 4
• Prinzmetal's variant angina or vasospastic coronary disease 4
• Uncontrolled hypertension 2, 4
• History of stroke or transient ischemic attack 4
• Wolff-Parkinson-White syndrome or arrhythmias with accessory cardiac conduction pathways 4