What is the best treatment for a patient with typical migraine symptoms?

Best Migraine Treatment

For acute migraine treatment, use combination therapy of a triptan (sumatriptan 50-100 mg) plus an NSAID (naproxen 500 mg) for moderate to severe attacks, or NSAIDs alone (ibuprofen 400-800 mg, naproxen 500-825 mg, or aspirin-acetaminophen-caffeine) for mild to moderate attacks, taken early in the attack while pain is still mild. 1, 2

Acute Treatment Algorithm

Mild to Moderate Migraine (First-Line)

• Start with NSAIDs or aspirin-acetaminophen-caffeine combination as first-line therapy for mild to moderate attacks 1, 2
• Aspirin-acetaminophen-caffeine received a "strong for" recommendation with number needed to treat of 9 for pain freedom at 2 hours and 4 for pain relief at 2 hours 1
• Alternative NSAIDs include ibuprofen 400-800 mg, naproxen sodium 500-825 mg, or aspirin 1000 mg 2, 3
• Take medication at the earliest signs of headache while pain is still mild to maximize effectiveness 2

Moderate to Severe Migraine (First-Line)

• Use combination therapy: triptan + NSAID simultaneously for moderate to severe attacks, as this is superior to either agent alone 2
• 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 2
• Oral sumatriptan achieves headache response (reduction to mild or no pain) in 50-62% of patients at 2 hours versus 17-27% with placebo 4
• Alternative oral triptans include rizatriptan 10 mg (fastest oral triptan, peak at 60-90 minutes), eletriptan 40 mg, or zolmitriptan 2.5-5 mg 2, 3

Severe Migraine with Nausea/Vomiting

• Use subcutaneous sumatriptan 6 mg for fastest and most effective relief, achieving pain relief in 70-82% within 15 minutes and complete pain freedom in 59% by 2 hours 2
• Alternative: intranasal sumatriptan 5-20 mg when significant nausea or vomiting limits oral administration 2
• Add antiemetic 20-30 minutes before other medications: metoclopramide 10 mg or prochlorperazine 10 mg provides synergistic analgesia beyond treating nausea 1, 2

Second-Line Options (When Triptans Fail or Contraindicated)

• Try gepants (ubrogepant 50-100 mg or rimegepant) as third-line option after triptan-NSAID combination fails 1, 2
• Gepants received "weak for" recommendation with number needed to treat of 13 for pain freedom at 2 hours, with no vasoconstriction making them safe for cardiovascular disease 1
• Lasmiditan 50-200 mg is an alternative 5-HT1F agonist without vasoconstriction, but requires 8-hour driving restriction due to CNS effects (dizziness, somnolence) 1, 2
• Dihydroergotamine (DHE) intranasal or IV has good evidence for efficacy as monotherapy for refractory attacks 1, 2

Emergency/IV Treatment

• IV metoclopramide 10 mg plus IV ketorolac 30 mg is the recommended first-line IV combination for severe migraine in emergency settings 2
• Ketorolac provides rapid onset with 6-hour duration and minimal rebound headache risk 2
• Metoclopramide provides direct analgesic effects through central dopamine receptor antagonism beyond antiemetic properties 2
• Alternative: IV prochlorperazine 10 mg has comparable efficacy to metoclopramide with 21% adverse event rate versus 50% for chlorpromazine 2

Critical Frequency Limitation

• Limit ALL acute migraine medications to no more than 2 days per week (10 days per month) to prevent medication-overuse headache 1, 2
• Medication-overuse headache occurs with triptans ≥10 days/month or NSAIDs ≥15 days/month, leading to daily headaches 5, 2
• Initiate preventive therapy immediately if requiring acute treatment more than twice weekly 5, 2

Preventive Therapy Indications

• Start preventive therapy for patients with ≥2 migraine attacks per month with disability lasting ≥3 days per month 5
• Also indicated for: contraindications to acute treatments, using abortive medication >2 days/week, or uncommon migraine conditions (hemiplegic migraine, prolonged aura, migrainous infarction) 5

First-Line Preventive Medications

• Propranolol 80-240 mg/day or timolol 20-30 mg/day (beta-blockers) have strong evidence for efficacy 5
• Topiramate 50-100 mg/day (typically 50 mg twice daily) is particularly useful for patients with obesity due to weight loss benefits 5
• Candesartan is first-line for patients with comorbid hypertension 5

Second-Line Preventive Medications

• Amitriptyline 30-150 mg/day is optimal for patients with comorbid depression, anxiety, or mixed migraine-tension headache 5
• Sodium valproate 800-1500 mg/day or divalproex sodium 500-1500 mg/day are effective but strictly contraindicated in women of childbearing potential due to teratogenic effects 5

Third-Line: CGRP Monoclonal Antibodies

• Erenumab, fremanezumab, or galcanezumab (monthly subcutaneous injection) for patients who have failed 2-3 oral preventive medications 5
• Require 3-6 months for efficacy assessment versus 2-3 months for oral agents 5
• Cost is $5,000-$6,000 annually versus lower cost oral agents 5

Chronic Migraine Specific

• OnabotulinumtoxinA is the only FDA-approved therapy specifically for chronic migraine (≥15 headache days/month), reducing headache days, episodes, and severity 5
• OnabotulinumtoxinA is specifically contraindicated for episodic migraine prevention 5

Implementation Strategy

• Start preventive medications at low dose and titrate slowly until clinical benefits achieved or side effects limit increases 5
• Allow adequate trial period: 2-3 months for oral agents, 3-6 months for CGRP antibodies, 6-9 months for onabotulinumtoxinA before determining efficacy 5, 2
• Use headache diaries to track attack frequency, severity, duration, disability, and treatment response 5
• Consider tapering after 6-12 months of successful therapy to determine if preventive treatment can be discontinued 5

Critical Pitfalls to Avoid

• Never use opioids or butalbital-containing compounds for migraine treatment due to questionable efficacy, dependency risk, rebound headaches, and loss of efficacy over time 2, 6
• Do not abandon triptan therapy after single failed attempt—failure of one triptan does not predict failure of others; try different triptan for 2-3 episodes before escalating 2, 3
• Screen for medication-overuse headache before escalating therapy if patient uses acute medications ≥10 days/month for triptans or ≥15 days/month for NSAIDs 5, 2
• Avoid starting preventive medications at too high a dose, leading to poor tolerability and discontinuation 5
• Do not use triptans in patients with ischemic heart disease, previous MI, coronary artery vasospasm, uncontrolled hypertension, cerebrovascular disease, stroke/TIA history, or basilar/hemiplegic migraine 2, 3

Non-Pharmacological Adjuncts

• Cognitive behavioral therapy, biofeedback, and relaxation training are effective adjuncts alongside medication 5
• Neuromodulatory devices can be considered as adjuncts or stand-alone treatments when medications are contraindicated 5
• Identify and modify triggers: sleep hygiene, regular meals, hydration, stress management, weight loss in obesity 5