What is the initial treatment for acute migraine?

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Initial Treatment for Acute Migraine

Start with NSAIDs (ibuprofen 400-800 mg, naproxen sodium 500-825 mg, aspirin 1000 mg, or diclofenac potassium) as first-line therapy for mild to moderate migraine attacks, and escalate to triptans (sumatriptan 50-100 mg, rizatriptan 10 mg, or other triptans) for moderate to severe attacks or when NSAIDs fail. 1, 2, 3

First-Line Treatment Algorithm

For Mild to Moderate Attacks

  • Administer NSAIDs early in the headache phase while pain is still mild, as effectiveness depends critically on timely use 1, 2
  • Specific NSAID options with strong evidence:
    • Ibuprofen 400-800 mg 2, 4
    • Naproxen sodium 500-825 mg 2, 5
    • Aspirin 1000 mg 1, 6
    • Diclofenac potassium 1, 3
  • Soluble formulations of ibuprofen 400 mg provide more rapid 1-hour relief compared to standard tablets 4
  • Critical frequency limitation: Restrict use to no more than 2 days per week to prevent medication-overuse headache, which paradoxically increases headache frequency and can lead to daily headaches 1, 2, 3

For Moderate to Severe Attacks or NSAID Failure

  • Escalate to triptans as second-line therapy 1, 2, 3
  • Oral triptan options with strong evidence:
    • Sumatriptan 50-100 mg (most studied, 61-62% achieve headache response at 2 hours) 7, 6
    • Rizatriptan 10 mg (67-77% achieve headache response at 2 hours) 8, 6
    • Zolmitriptan, naratriptan, eletriptan, almotriptan, frovatriptan 1, 6
  • Subcutaneous sumatriptan 6 mg provides highest efficacy (59% complete pain relief at 2 hours) for rapidly escalating or severe attacks, particularly when nausea/vomiting is present 2, 5
  • Intranasal formulations (sumatriptan 5-20 mg, zolmitriptan) are useful alternatives when oral route is compromised by nausea 2, 5

Combination Therapy for Enhanced Efficacy

Combine a triptan with a fast-acting NSAID simultaneously for superior efficacy compared to either agent alone, particularly to prevent headache recurrence within 48 hours 1, 2, 3

  • Example: 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

Adjunctive Antiemetic Therapy

  • Add prokinetic antiemetics for nausea/vomiting: metoclopramide 10 mg or domperidone 1, 2
  • Metoclopramide provides direct analgesic effects through central dopamine receptor antagonism beyond its antiemetic properties 2
  • Prochlorperazine 10 mg IV is equally effective as metoclopramide for headache pain relief 2
  • Administer antiemetics 20-30 minutes before NSAIDs to enhance absorption and provide synergistic analgesia 2

Third-Line Options for Refractory Cases

When both NSAIDs and triptans fail after adequate trials:

  • Ditans (lasmiditan): comparable efficacy to triptans but patients cannot operate machinery for at least 8 hours after intake 1, 3
  • Gepants (rimegepant, ubrogepant, zavegepant): CGRP antagonists for patients who don't respond to or cannot tolerate triptans 2, 3
  • Dihydroergotamine (DHE): intranasal or IV formulations have good evidence for efficacy as monotherapy 2, 9

Medications to Avoid

  • Oral ergot alkaloids: poorly effective and potentially toxic, should not substitute for triptans 1
  • Opioids and barbiturates: questionable efficacy, considerable adverse effects, risk of dependency, and should be avoided 1, 2, 9
  • Reserve opioids only when other medications cannot be used, sedation is not a concern, and abuse risk has been addressed 2

Critical Pitfalls to Avoid

  • Do not delay treatment: administer medication early in the headache phase while pain is still mild for maximum effectiveness 1, 2, 3
  • Do not exceed frequency limits: using acute medications more than twice weekly creates medication-overuse headache, requiring transition to preventive therapy 1, 2, 3
  • Do not assume triptan failure is universal: if one triptan fails, try another triptan as failure of one does not predict failure of others 2, 3
  • Do not use triptans in patients with ischemic vascular disease, vasospastic coronary disease, or uncontrolled hypertension 2, 10

When to Initiate Preventive Therapy

Consider preventive therapy if migraine continues to impair quality of life despite optimized acute therapy, or if acute medications are needed more than 2 days per month 1, 9

  • Preventive therapy reduces attack frequency and can restore responsiveness to acute treatments 2
  • Efficacy requires 2-3 months for oral agents, 3-6 months for CGRP monoclonal antibodies, and 6-9 months for onabotulinumtoxinA 1, 2

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Acute Headache Treatment Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Acute Migraine Treatment Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Ibuprofen with or without an antiemetic for acute migraine headaches in adults.

The Cochrane database of systematic reviews, 2013

Research

Medical Treatment Guidelines for Acute Migraine Attacks.

Acta neurologica Taiwanica, 2017

Guideline

Emergency Management of Migraine

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Acute Migraine Treatment.

Continuum (Minneapolis, Minn.), 2015

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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