What is the first‑line acute treatment for a moderate‑to‑severe migraine attack in an adult without contraindications such as uncontrolled hypertension, coronary artery disease, cerebrovascular disease, or pregnancy?

First-Line Treatment for Moderate-to-Severe Migraine Attacks

For moderate-to-severe migraine attacks in adults without contraindications, the combination of a triptan plus an NSAID is the strongest first-line recommendation, providing superior efficacy compared to either agent alone. 1

Primary Treatment Algorithm

Step 1: Combination Therapy (Strongest Evidence)

• Sumatriptan 50–100 mg PLUS naproxen sodium 500 mg is the most strongly recommended regimen, yielding 130 additional patients per 1,000 who achieve sustained pain relief at 48 hours compared to sumatriptan alone. 1
• This combination achieves a number-needed-to-treat of 3.5 for headache relief at 2 hours, which is superior to either medication used as monotherapy. 1
• The combination should be taken as early as possible during the attack—ideally when pain is still mild—because early treatment results in approximately 50% of patients becoming pain-free at 2 hours versus only 28% when treatment is delayed until pain is moderate or severe. 1

Step 2: Alternative Triptan Options if Sumatriptan Fails

• If sumatriptan fails after 2–3 headache episodes, switch to a different triptan because failure of one triptan does not predict failure of others. 1
• Rizatriptan 10 mg reaches peak concentration in 60–90 minutes, making it the fastest oral triptan. 1
• Eletriptan 40 mg or zolmitriptan 2.5–5 mg are reportedly more effective with fewer adverse reactions than sumatriptan. 1, 2
• Each alternative triptan should be tried for 2–3 headache episodes before abandoning that specific agent. 1

Step 3: Route of Administration Change for Severe Attacks

• Subcutaneous sumatriptan 6 mg provides the highest efficacy among all triptan formulations, achieving complete pain relief in approximately 59% of patients within 2 hours and onset of action within 15 minutes. 1, 3
• Subcutaneous administration is particularly indicated when the patient has rapid progression to peak intensity, significant nausea/vomiting preventing oral medication, or when oral triptans have failed. 1, 3
• Intranasal sumatriptan 20 mg is an alternative for patients who prefer to avoid injections but still need non-oral administration due to nausea or vomiting. 1, 3

Critical Frequency Limitation to Prevent Medication-Overuse Headache

• 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
• If the patient requires acute treatment more than twice weekly, initiate preventive therapy immediately rather than increasing the frequency of acute medications. 1

Adjunctive Antiemetic Therapy

• Metoclopramide 10 mg should be given 20–30 minutes before the triptan-NSAID combination when nausea is present, as it provides synergistic analgesia beyond its antiemetic properties through central dopamine receptor antagonism. 1
• Metoclopramide is not restricted only to patients who are vomiting—nausea itself is one of the most disabling symptoms and warrants treatment. 1

Absolute Contraindications to Triptans

• Do not prescribe triptans to patients with ischemic heart disease, previous myocardial infarction, Prinzmetal's angina, uncontrolled hypertension, cerebrovascular disease, history of stroke or TIA, or basilar/hemiplegic migraine. 1, 4
• For patients with multiple cardiovascular risk factors (increased age, diabetes, hypertension, smoking, obesity, strong family history of CAD), a cardiovascular evaluation should be performed before prescribing triptans. 4

Alternative First-Line Options When Triptans Are Contraindicated

• CGRP antagonists (gepants) such as ubrogepant 50–100 mg or rimegepant are the primary oral alternative for moderate-to-severe migraine when triptans are contraindicated, as they have no vasoconstriction and are safe in patients with cardiovascular disease. 1
• Intravenous dihydroergotamine (DHE) 0.5–1.0 mg has good evidence for efficacy as monotherapy when NSAIDs are contraindicated, but it is contraindicated with concurrent triptan use within 24 hours, beta-blockers, uncontrolled hypertension, coronary artery disease, pregnancy, and sepsis. 1

Common Pitfalls to Avoid

• Never use opioids or butalbital-containing compounds as first-line therapy for migraine because they have questionable efficacy, lead to dependency, cause rebound headaches, and result in loss of efficacy over time. 1
• Do not abandon triptan therapy after a single failed attempt—if one triptan is ineffective, try a different triptan or change the route of administration before escalating to third-line agents. 1
• Do not delay treatment until pain becomes severe; early administration when pain is still mild dramatically improves outcomes. 1

Expected Adverse Events

• The sumatriptan-NSAID combination produces approximately 90 more mild adverse events per 1,000 treated patients compared to placebo, including fatigue, dizziness, and nausea, which are generally transient and mild. 1