What is the recommended acute treatment for an adult with a migraine attack who has no known contraindications?

Management of Acute Migraine Attack

For an adult with an acute migraine attack and no contraindications, begin with NSAIDs (ibuprofen 400–800 mg, naproxen sodium 500–825 mg, or aspirin 1000 mg) for mild-to-moderate attacks, and immediately add or switch to a triptan (sumatriptan 50–100 mg, rizatriptan 10 mg, or eletriptan 40 mg) for moderate-to-severe attacks or when NSAIDs fail after 2–3 episodes. 1

First-Line Treatment Algorithm

Mild-to-Moderate Migraine Attacks

• NSAIDs are the recommended first-line therapy, with the strongest evidence supporting ibuprofen 400–800 mg, naproxen sodium 500–825 mg, aspirin 1000 mg, or diclofenac potassium. 1, 2
• Combination analgesics (acetaminophen 1000 mg + aspirin 500–1000 mg + caffeine 130 mg) provide synergistic analgesia and achieve pain reduction to mild or none in 59.3% of patients at 2 hours, making them an effective alternative when single-agent NSAIDs are insufficient. 1
• Acetaminophen 1000 mg alone has limited efficacy for migraine but can be used when NSAIDs are contraindicated. 1, 2

Moderate-to-Severe Migraine Attacks

• Triptans are first-line therapy for moderate-to-severe attacks, with oral sumatriptan 50–100 mg, rizatriptan 10 mg, eletriptan 40 mg, zolmitriptan 2.5–5 mg, almotriptan, naratriptan, and frovatriptan all demonstrating Level A evidence for efficacy. 1, 2, 3, 4
• The combination of a triptan plus an NSAID (e.g., sumatriptan 50–100 mg + naproxen 500 mg) is superior to either agent alone, providing 130 additional patients per 1,000 who achieve sustained pain relief at 48 hours, with a number-needed-to-treat of 3.5 for headache relief at 2 hours. 1
• Treat early when pain is still mild rather than waiting for moderate-to-severe intensity; early treatment results in approximately 50% pain-free response at 2 hours versus only 28% when treatment is delayed. 1, 5

Route-Specific Considerations

• Subcutaneous sumatriptan 6 mg provides the highest efficacy among all triptan formulations, achieving complete pain relief in 59% of patients within 2 hours with onset of action within 15 minutes (NNT 2.3), making it ideal for rapidly progressing attacks or when significant nausea/vomiting is present. 1, 6
• Intranasal sumatriptan 5–20 mg or intranasal zolmitriptan are effective alternatives when oral administration is impaired by nausea or vomiting. 1, 2
• Oral triptans reach peak efficacy at 2 hours, with sumatriptan 100 mg (NNT 4.7), rizatriptan 10 mg (fastest oral triptan, reaching peak concentration in 60–90 minutes), and eletriptan 40 mg demonstrating superior efficacy profiles. 1, 6, 5

Adjunctive Antiemetic Therapy

• Metoclopramide 10 mg IV or oral provides direct analgesic effects through central dopamine receptor antagonism beyond its antiemetic properties, and should be given 20–30 minutes before or concurrently with NSAIDs or triptans to achieve synergistic analgesia. 1
• Prochlorperazine 10 mg IV or 25 mg oral is equally effective to metoclopramide for both headache pain and nausea, with a more favorable side-effect profile than chlorpromazine (21% versus 50% adverse events). 1
• Antiemetics are indicated not only for patients with vomiting but also for those with nausea alone, as nausea is one of the most disabling migraine symptoms. 1

Second-Line and Rescue Options

When First-Line Therapies Fail

• Try a different triptan if one fails after 2–3 headache episodes, as failure of one triptan does not predict failure of others; eletriptan 40 mg and zolmitriptan 2.5–5 mg are reportedly more effective with fewer adverse reactions than sumatriptan. 1, 3, 4
• Intranasal or intravenous dihydroergotamine (DHE) 0.5–1.0 mg has good evidence for efficacy as monotherapy when triptans are contraindicated or ineffective, and can be repeated every hour up to a maximum of 2 mg IV per day. 1, 2
• CGRP antagonists (gepants)—ubrogepant 50–100 mg or rimegepant 75 mg—are recommended as third-line options for patients who do not tolerate or have inadequate response to triptan-NSAID combinations, with the advantage of no vasoconstriction (safe in cardiovascular disease). 1, 7
• Lasmiditan 50–200 mg (a 5-HT1F receptor agonist without vasoconstrictor activity) is a second-line alternative when gepants are unavailable, but patients must not drive or operate machinery for at least 8 hours due to CNS effects. 1

Parenteral Therapy for Severe Attacks

• Intravenous ketorolac 30 mg + metoclopramide 10 mg is the recommended first-line parenteral combination for severe migraine requiring emergency or urgent-care treatment, providing rapid pain relief with minimal rebound headache risk. 1
• Subcutaneous sumatriptan 6 mg remains the most effective parenteral option when IV access is unavailable or when rapid onset is critical. 1, 6
• Intravenous corticosteroids (e.g., dexamethasone) are the mainstay for status migrainosus (continuous migraine >72 hours), though supporting evidence is limited. 1, 2

Critical Medication-Overuse Prevention

• 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, 2, 8
• If acute treatment is required more than twice weekly, immediately initiate preventive therapy rather than increasing the frequency of acute medications. 1, 9
• Medication-overuse headache occurs with NSAIDs at ≥15 days/month and with triptans/combination analgesics at ≥10 days/month. 1

Contraindicated Therapies

• Opioids (hydrocodone, oxycodone, morphine, codeine, tramadol) are absolutely contraindicated for migraine treatment because they provide questionable efficacy, carry high risk of dependence, precipitate rebound headaches, and worsen overall migraine outcomes. 1, 2, 3, 4
• Butalbital-containing compounds should be avoided due to high risk of medication-overuse headache and should be reserved only when all other evidence-based treatments are contraindicated. 1
• Opioids should be reserved exclusively for cases where every other evidence-based acute treatment is contraindicated, sedation is acceptable, and a formal assessment of abuse risk has been completed; even then, butorphanol nasal spray has better evidence than oral opioids. 1

Triptan Contraindications and Safety

• Triptans are contraindicated in patients with ischemic heart disease, previous myocardial infarction, coronary artery vasospasm, uncontrolled hypertension, cerebrovascular disease, history of stroke or TIA, or basilar/hemiplegic migraine. 1
• Triptans remain safe in patients with controlled hypertension or sodium-sensitive hypertension without cardiovascular disease. 1
• Serious cardiovascular events with triptans occur only in rare isolated cases; adverse events are generally mild and transient. 6, 5

When to Initiate Preventive Therapy

• Preventive therapy is indicated when patients experience ≥2 migraine attacks per month producing disability lasting ≥3 days, use acute medications >2 days per week, have contraindications to or failure of acute treatments, or have uncommon migraine conditions. 1, 2
• First-line preventive agents include beta-blockers (propranolol 80–240 mg/day, timolol 20–30 mg/day), topiramate 50–200 mg/day, amitriptyline 30–150 mg/day (especially when comorbid anxiety, depression, or insomnia is present), and divalproex sodium 500–1500 mg/day (strictly avoided in women of childbearing potential due to teratogenic risk). 1, 9, 2

Special Populations

Pregnancy and Lactation

• Acetaminophen 1000 mg is the safest acute migraine treatment during pregnancy, with acetaminophen plus codeine as a second option. 3, 4
• Sumatriptan may be considered during pregnancy for selected patients after risk-benefit discussion and is compatible with breastfeeding. 3, 4
• NSAIDs and triptans should generally be avoided during pregnancy. 2

Chronic Migraine (≥15 Headache Days per Month)

• Strict adherence to the 2-days-per-week limit for acute medications is essential to prevent perpetuating the chronic pattern. 1, 8
• OnabotulinumtoxinA is the only FDA-approved preventive therapy specifically for chronic migraine and should be used as first-line when three oral preventives have failed, with efficacy assessed after 6–9 months. 1
• If medication-overuse headache is present (acute medications used ≥10 days/month for triptans or ≥15 days/month for NSAIDs), abrupt cessation of the overused medication is recommended, with temporary headache worsening expected for 2–10 days. 1