Preferred First-Line Analgesic for Acute Migraine
Start with an NSAID (such as ibuprofen, naproxen, or aspirin) or acetaminophen at adequate doses for first-line treatment of acute migraine in adults without contraindications. 1
Treatment Algorithm Based on Severity
For Mild to Moderate Migraine
- First-line: NSAID monotherapy (ibuprofen, naproxen, aspirin, diclofenac, or celecoxib) OR acetaminophen at appropriate doses 1
- Alternative first-line: Aspirin-acetaminophen-caffeine combination (number needed to treat = 4 for pain relief at 2 hours) 2
- Ensure patients are using adequate dosing before declaring treatment failure 1
For Moderate to Severe Migraine
- If NSAIDs/acetaminophen fail: Add a triptan to the NSAID (or to acetaminophen if NSAIDs contraindicated) 1
- Combination therapy is superior to monotherapy: The combination of a triptan plus NSAID results in 180 more people per 1000 achieving sustained pain relief at 48 hours compared to triptan alone (high-certainty evidence) 1
- Begin treatment as early as possible after migraine onset for maximum efficacy 1
Specific NSAID and Triptan Selection
NSAIDs with evidence: Aspirin, celecoxib, diclofenac, ibuprofen, naproxen 1
Triptans with evidence: Almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan 1
Choice among these should be based on route of administration preference, cost, and individual patient factors 1
Critical Pitfalls to Avoid
Medication Overuse Headache
- NSAIDs: Limit to <15 days per month 1
- Triptans: Limit to <10 days per month 1
- This is a threshold issue—exceeding these frequencies for ≥3 months can cause medication overuse headache in patients with preexisting headache disorders 1
What NOT to Use
Do not use opioids or butalbital-containing medications for acute episodic migraine 1. These are explicitly contraindicated by the 2025 American College of Physicians guidelines.
Second-Line Options (After Combination Therapy Failure)
If adequate doses of triptan plus NSAID (or acetaminophen) fail:
- CGRP antagonists (gepants): Rimegepant, ubrogepant, or zavegepant 1
- Ergot alkaloid: Dihydroergotamine 1
- Ditan: Lasmiditan (only after all other options fail due to adverse effects including driving restrictions) 1
These newer agents have the advantage of no vascular contraindications unlike triptans and ergots 3, but cost significantly more (gepants ~$5,994/year vs. triptans ~$500/year) 1
Special Considerations
For severe nausea/vomiting: Use non-oral triptan formulations plus antiemetics 1
For childbearing potential/pregnancy/lactation: Discuss adverse effects of all pharmacologic treatments; acetaminophen remains preferred for pregnant women 1, 4
Strength of Evidence
The 2025 American College of Physicians guideline 1 represents the most recent and highest-quality evidence, published in Annals of Internal Medicine. This guideline is based on high-certainty evidence for NSAID and triptan combination therapy, with moderate-certainty evidence supporting the stepwise approach starting with simple analgesics.