What medications are recommended for a patient experiencing frequent or severe migraine headaches?

Migraine Headache Medications

For acute moderate to severe migraine, start with combination therapy of a triptan (sumatriptan 50-100 mg or rizatriptan 10 mg) plus an NSAID (naproxen 500 mg or ibuprofen 400 mg), as this provides superior efficacy compared to either agent alone. 1

First-Line Treatment Algorithm

Mild to Moderate Migraine

• Begin with NSAIDs or acetaminophen as monotherapy 1

  • Ibuprofen 400-800 mg provides 2-hour headache relief in 57% of patients (NNT 3.2) 2
  • Naproxen sodium 500-825 mg at migraine onset, can repeat every 2-6 hours (maximum 1.5 g/day) 3
  • Acetaminophen 1000 mg provides 2-hour headache relief in 56% of patients (NNT 5.0) 4
  • Aspirin 1000 mg is equally effective 1

• If NSAIDs fail after 2-3 migraine episodes, escalate to triptan monotherapy 3

Moderate to Severe Migraine

• Initiate combination therapy immediately: triptan + NSAID 1, 3

  • 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 3
  • This combination is the strongest recommendation from the 2025 American College of Physicians guidelines 1

• Alternative triptans if sumatriptan fails or is not tolerated: 3

  • Rizatriptan 10 mg (fastest oral triptan, peak concentration in 60-90 minutes) 3
  • Eletriptan 40 mg or zolmitriptan 2.5-5 mg (more effective with fewer adverse reactions than sumatriptan) 3
  • Naratriptan (longest half-life, may decrease recurrence headaches) 3
  • Try each triptan for 2-3 headache episodes before abandoning it, as failure of one does not predict failure of others 3

Route Selection Based on Symptoms

Severe Nausea or Vomiting Present

• Use non-oral routes: 1, 3
  • Subcutaneous sumatriptan 6 mg provides highest efficacy (59% pain-free at 2 hours) with onset within 15 minutes 3
  • Intranasal sumatriptan 5-20 mg 3
  • Add antiemetic: metoclopramide 10 mg or prochlorperazine 10 mg (provides synergistic analgesia beyond antiemetic effect) 3

Rapid Progression to Peak Intensity

• Subcutaneous sumatriptan 6 mg is the optimal choice 3

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

CGRP Antagonists (Gepants)

• Ubrogepant 50-100 mg or rimegepant 1, 3
  • No vasoconstriction, safe for patients with cardiovascular disease, uncontrolled hypertension, or cerebrovascular disease 3
  • Use when triptans are contraindicated or after failure of triptan + NSAID combination 1

Ditans

• Lasmiditan 50-200 mg 1, 3
  • 5-HT1F receptor agonist without vasoconstrictor activity 3
  • Critical warning: patients must not drive or operate machinery for at least 8 hours after taking lasmiditan due to CNS effects (dizziness, vertigo, somnolence) 3
  • Reserve for patients who have failed all other treatments 1

Dihydroergotamine (DHE)

• Intranasal or IV dihydroergotamine 1, 3
  • Good evidence for efficacy as monotherapy 3
  • Consider when combination therapy fails 1

Intravenous Treatment for Severe Attacks

First-Line IV Cocktail

• Metoclopramide 10 mg IV PLUS ketorolac 30 mg IV 3
  • Metoclopramide provides direct analgesic effects through central dopamine receptor antagonism, not just antiemetic benefit 3
  • Ketorolac has rapid onset with approximately 6 hours duration and minimal rebound headache risk 3

Alternative IV Options

• Prochlorperazine 10 mg IV (comparable efficacy to metoclopramide) 3
• Dihydroergotamine IV 3

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, which paradoxically increases headache frequency and can lead to daily headaches. 1, 3

• If requiring acute treatment more than twice weekly, initiate preventive therapy immediately 3
• Medication-overuse headache occurs with triptans at ≥10 days/month and NSAIDs at ≥15 days/month 3

Medications to Absolutely Avoid

Never use opioids (hydromorphone, meperidine) or butalbital-containing compounds for migraine treatment. 1, 3

• These have questionable efficacy, lead to dependency, cause rebound headaches, and result in loss of efficacy over time 3
• Reserve opioids only for cases where all other medications are contraindicated, sedation is not a concern, and abuse risk has been addressed 3

Contraindications to Triptans (Use Gepants or Lasmiditan Instead)

Triptans are contraindicated in: 5, 6

• Ischemic heart disease or previous myocardial infarction
• Prinzmetal's variant angina
• Wolff-Parkinson-White syndrome or arrhythmias with accessory cardiac conduction pathways
• History of stroke or transient ischemic attack
• Uncontrolled hypertension
• Peripheral vascular disease
• Hemiplegic or basilar migraine

Preventive Therapy Indications

Initiate preventive therapy if: 7

• Two or more migraine attacks per month with disability lasting 3+ days
• Using acute medications more than twice per week
• Contraindication to or failure of acute treatments
• Uncommon migraine conditions (hemiplegic migraine, prolonged aura, migrainous infarction)

First-Line Preventive Medications

• Propranolol 80-240 mg/day (strongest evidence) 7
• Topiramate 50-100 mg/day (particularly useful in patients with obesity due to weight loss benefit) 7
• Candesartan (particularly useful with comorbid hypertension) 7

Second-Line Preventive Medications

• Amitriptyline 30-150 mg/day (optimal for comorbid depression/anxiety or mixed migraine and tension-type headache) 7
• Divalproex sodium 500-1500 mg/day (strictly contraindicated in women of childbearing potential due to teratogenic effects) 7

Third-Line: CGRP Monoclonal Antibodies

• Erenumab, fremanezumab, or galcanezumab (monthly subcutaneous injection) 7
• Use after failure of 2-3 oral preventive medications 7
• Requires 3-6 months for efficacy assessment 7
• Significantly more expensive ($5,000-$6,000 annually) 7

Common Pitfalls to Avoid

• Do not allow patients to increase frequency of acute medication use in response to treatment failure—this creates medication-overuse headache; instead transition to preventive therapy 3
• Do not abandon triptan therapy after a single failed attempt—try different triptans, as failure of one does not predict failure of others 3
• Do not use triptans and ergotamines within 24 hours of each other due to additive vasoconstrictive effects 3
• Do not fail to screen for cardiovascular risk factors before prescribing triptans 5, 6
• Do not use acetaminophen exceeding 4000 mg per day from all sources 3