What are the pharmacological options for migraine headaches and when is a neurology referral warranted?

Pharmacological Treatment of Acute Migraine

For mild to moderate migraine, start with an NSAID (ibuprofen 400-800 mg, naproxen 500-825 mg, or aspirin 900-1000 mg); for moderate to severe migraine, use a triptan combined with an NSAID or acetaminophen, taken as early as possible in the attack. 1

First-Line Acute Treatment Algorithm

Mild to Moderate Migraine

• NSAIDs are the initial treatment of choice 1, 2
  • Ibuprofen 400-800 mg every 6-8 hours as needed 3
  • Naproxen sodium 500-825 mg at onset, can repeat every 2-6 hours (maximum 1.5 g/day) 2
  • Aspirin 900-1000 mg as needed 3
• Alternative: Acetaminophen 1000 mg for patients who cannot tolerate NSAIDs 1
• Combination therapy: Acetaminophen + aspirin + caffeine has Level A evidence for efficacy 4

Moderate to Severe Migraine

• Combination therapy is superior to monotherapy: Triptan + NSAID or triptan + acetaminophen 1, 4
• Triptan options (all have equivalent efficacy; choose based on route preference and cost) 1:
  • Oral: sumatriptan 25-100 mg, rizatriptan, naratriptan, zolmitriptan, eletriptan, almotriptan, frovatriptan 1, 3
  • Subcutaneous sumatriptan 6 mg: fastest onset (15 minutes), highest efficacy (59% pain-free at 2 hours) but more adverse effects 2, 5
  • Intranasal: sumatriptan 5-20 mg or zolmitriptan for patients with significant nausea/vomiting 2, 3
• Timing is critical: Administer triptans early in the attack while pain is still mild for maximum efficacy 1, 2

When Nausea/Vomiting is Prominent

• Use non-oral routes of administration (subcutaneous, intranasal, or rectal) 2, 3
• Add an antiemetic: metoclopramide 10 mg IV or prochlorperazine 10 mg IV/25 mg rectal 1, 2
  • These provide synergistic analgesia beyond just treating nausea 2
  • Do not restrict antiemetics only to vomiting patients—nausea itself is disabling and warrants treatment 1

Second-Line Options (When First-Line Fails or is Contraindicated)

• CGRP antagonists (gepants): rimegepant, ubrogepant, or zavegepant for patients who fail triptan + NSAID combination 1, 6
• Ergot alkaloid: dihydroergotamine (DHE) 0.5-1 mg IM/IV or intranasal 1, 3
• Ditan: lasmiditan for patients who fail all other treatments 1

Critical Medications to AVOID

• Do not use opioids or butalbital for acute migraine treatment 1
  • These lead to medication-overuse headache, dependency, and loss of efficacy 2
  • If opioids must be used (contraindications to all other options), butorphanol nasal spray has better evidence than other opioids 2

Medication-Overuse Headache Prevention

• Limit acute treatment to ≤2 days per week 1, 2
• Specific thresholds: ≥15 days/month with NSAIDs or ≥10 days/month with triptans triggers medication-overuse headache 1
• If using acute medications >2 days/week, initiate preventive therapy 1, 2

Preventive Therapy Indications

Consider preventive medications when: 1

• ≥2 attacks per month producing disability lasting ≥3 days per month
• Contraindication to or failure of acute treatments
• Use of abortive medication >2 times per week
• Presence of hemiplegic migraine, prolonged aura, or migrainous infarction

First-line preventive agents: 1

• Propranolol 80-240 mg/day
• Timolol 20-30 mg/day
• Amitriptyline 30-150 mg/day
• Divalproex sodium 500-1500 mg/day
• Sodium valproate 800-1500 mg/day

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When to Refer to Neurology

Refer to neurology when patients have frequent migraines requiring acute treatment >2 days per week despite optimized therapy, when first-line preventive medications fail, or when red flags suggest secondary headache. 1, 2

Absolute Indications for Urgent Neurology Referral

• Red flag features suggesting secondary headache: 2
  • Thunderclap headache (sudden onset, maximal intensity within seconds)
  • Progressive headache worsening over time
  • Fever with neck stiffness
  • New neurological deficits
  • Headache after age 50 with no prior history
  • Change in established headache pattern

Routine Neurology Referral Indications

• Failure of multiple acute treatments: Patient has tried and failed adequate trials of NSAIDs, multiple triptans, and combination therapy 2
• Need for advanced preventive therapy: Failure of ≥2 first-line preventive agents at therapeutic doses for adequate duration (2-3 months) 2
• Frequent attacks requiring preventive therapy: ≥2 attacks per month causing significant disability 1
• Medication-overuse headache: Headache ≥15 days/month for ≥3 months due to overuse of acute medications 1
• Uncommon migraine variants: Hemiplegic migraine, migraine with prolonged aura, migrainous infarction, or basilar migraine 1, 7
• Diagnostic uncertainty: Atypical features not clearly fitting migraine criteria 1
• Need for specialized treatments: Consideration of CGRP monoclonal antibodies, onabotulinumtoxinA, or nerve blocks 2

Common Pitfall to Avoid

Do not allow patients to escalate acute medication frequency in response to treatment failure—this creates medication-overuse headache. Instead, transition to preventive therapy while optimizing the acute treatment strategy. 2