What is the first-line treatment for a typical adult patient with migraine?

First-Line Treatment for Migraine

For mild-to-moderate migraine attacks, start with NSAIDs (ibuprofen 400-800 mg, naproxen sodium 500-825 mg, or aspirin 1000 mg) as first-line therapy, and for moderate-to-severe attacks or when NSAIDs fail, escalate to triptans (sumatriptan 50-100 mg, rizatriptan, or zolmitriptan), ideally combined with an NSAID for superior efficacy. 1

Treatment Algorithm by Attack Severity

Mild-to-Moderate Attacks

• Start with NSAIDs as first-line therapy: ibuprofen 400-800 mg, naproxen sodium 500-825 mg, or aspirin 1000 mg 1, 2
• Acetylsalicylic acid (aspirin), ibuprofen, and diclofenac potassium have the strongest evidence for first-line use 1
• Add an antiemetic if nausea is present: metoclopramide 10 mg provides synergistic analgesia beyond just treating nausea 1, 2
• Administer medication early when pain is still mild for maximum effectiveness 1, 2

Moderate-to-Severe Attacks or NSAID Failure

• Escalate to triptans: sumatriptan 50-100 mg, rizatriptan, or zolmitriptan 1, 2
• All triptans are available as oral tablets, with oral sumatriptan 50-100 mg, rizatriptan, and zolmitriptan having the best evidence 1, 3
• Triptans are most effective when taken early while headache is still mild 1

Optimal Combination Therapy

• Combine triptan PLUS NSAID for superior efficacy: sumatriptan 50-100 mg PLUS naproxen sodium 500 mg is superior to either agent alone 1, 2
• This combination prevents relapse and improves outcomes, addressing the 40% of patients who experience symptom recurrence within 48 hours 1
• The NNT for headache relief at two hours with combination therapy is better than monotherapy 1

Critical Medication Frequency Limitation

• Strictly limit all acute migraine medications to no more than 2 days per week to prevent medication-overuse headache (MOH) 1, 2
• Frequent use (>2 days/week) risks development of MOH, leading to daily headaches 1, 2
• Initiate preventive therapy immediately if needing acute treatment more than twice weekly 1

Route of Administration Considerations

Oral Route (Standard)

• Oral tablets are the most commonly used formulation for all triptans 3
• Oral sumatriptan 50 mg provides pain-free response in 28% at two hours (NNT 6.1) compared to 11% with placebo 4
• Oral sumatriptan 100 mg provides pain-free response in higher percentages (NNT 4.7) 4

Alternative Routes for Severe Nausea/Vomiting

• Subcutaneous sumatriptan 6 mg provides the highest efficacy with pain-free response in 59% at two hours (NNT 2.3), with onset within 15 minutes 5, 2
• Intranasal formulations (sumatriptan or zolmitriptan) allow for rapid absorption without need for liquids, with significant pain-free rates as early as 15 minutes 3, 5
• Orally disintegrating tablets (rizatriptan, zolmitriptan) are useful alternatives for patients with difficulty swallowing or nausea 3

Evidence for Efficacy

• Oral sumatriptan 50 mg: NNT 6.1 for pain-free at 2 hours, NNT 4.0 for headache relief at 2 hours 4
• Oral sumatriptan 100 mg: NNT 4.7 for pain-free at 2 hours, NNT 3.5 for headache relief at 2 hours 4
• NSAIDs (ibuprofen, naproxen, aspirin): NNT 3.4-3.5 for headache relief at 2 hours 1

Common Pitfalls to Avoid

• Do not delay treatment: treating early when pain is mild significantly improves efficacy compared to waiting until pain is moderate or severe 1, 4
• Do not repeat the same ineffective triptan: switch to a different triptan after 2-3 failed attempts, as failure of one triptan does not predict failure of others 1
• Do not allow frequent acute medication use: this creates a vicious cycle of MOH; instead transition to preventive therapy 1, 2
• Do not use opioids or butalbital-containing compounds: they have questionable efficacy, lead to dependency, cause rebound headaches, and result in loss of efficacy over time 2

Contraindications Requiring Alternative Approach

• Triptans are contraindicated in patients with ischemic vascular disease, vasospastic coronary disease, uncontrolled hypertension, or significant cardiovascular disease 2
• For patients with cardiovascular contraindications to triptans, consider gepants (ubrogepant 50-100 mg or rimegepant) as they have no vasoconstriction 2
• NSAIDs should be avoided in patients with renal impairment (creatinine clearance <30 mL/min), aspirin/NSAID-induced asthma, or active GI bleeding 2