What are the treatment options for migraine without aura?

Treatment of Migraine Without Aura

For mild to moderate migraine attacks, start with NSAIDs (ibuprofen 400-800 mg, naproxen 500-825 mg, or aspirin 1000 mg) or acetaminophen 1000 mg as first-line therapy; for moderate to severe attacks or when NSAIDs fail, add a triptan to the NSAID regimen. 1

First-Line Treatment Algorithm

Mild to Moderate Attacks

• NSAIDs are the preferred initial therapy based on demonstrated efficacy, favorable tolerability, and lower cost 1, 2
• Specific evidence-based options include:
  • Ibuprofen 400-800 mg at onset 2, 3
  • Naproxen sodium 500-825 mg at onset (can repeat every 2-6 hours, maximum 1.5 g/day) 2, 3
  • Aspirin 1000 mg as effervescent tablets 2, 4
• Acetaminophen 1000 mg is an alternative first-line option with excellent safety profile, achieving 57.8% headache response at 2 hours versus 38.7% for placebo 2, 5

Moderate to Severe Attacks

• Add a triptan to your NSAID regimen if NSAIDs alone provide inadequate relief after 2-3 migraine episodes 1, 2
• The combination of triptan + NSAID is superior to either agent alone and represents the strongest recommendation from the 2025 ACP guidelines 1
• Evidence-based oral triptans include:
  • Sumatriptan (most studied) 2
  • Rizatriptan 2
  • Naratriptan 2
  • Zolmitriptan 2
  • Eletriptan 20-40 mg (40 mg dose more effective than 20 mg) 6

Combination Therapy for Enhanced Efficacy

When NSAIDs alone fail, the combination of aspirin 500 mg + acetaminophen 500 mg + caffeine 130 mg is highly effective for severe, disabling migraine attacks, with significantly greater response rates than placebo from 1 hour through 6 hours post-dose 2, 7

Adjunctive Antiemetic Therapy

• Add metoclopramide 10 mg or prochlorperazine 25 mg orally 20-30 minutes before your analgesic to provide synergistic analgesia and improve outcomes, not just for nausea control 2, 3
• Metoclopramide provides direct analgesic effects through central dopamine receptor antagonism and enhances absorption of co-administered medications by overcoming gastric stasis 2

Route Selection Based on Severity

Oral Route (Standard)

• Use for attacks without significant nausea or vomiting 2
• Take medication as early as possible during the attack, ideally when pain is still mild, to maximize efficacy 1, 2

Non-Oral Routes (Severe Attacks with Vomiting)

• Subcutaneous sumatriptan 6 mg provides the highest efficacy (59% complete pain relief at 2 hours) and fastest onset (15 minutes to peak concentration) 2
• Intranasal sumatriptan 5-20 mg for moderate to severe attacks with significant nausea 2
• IV metoclopramide 10 mg + IV ketorolac 30 mg for severe attacks requiring emergency/urgent care treatment 2

Critical Frequency Limitation to Prevent Medication-Overuse Headache

Limit all acute migraine medications to no more than 2 days per week (not 2 attacks per week—2 calendar days per week) to prevent medication-overuse headache, which paradoxically increases headache frequency and can lead to daily headaches 1, 2, 6

• If you find yourself needing acute treatment more than twice weekly, initiate preventive therapy immediately rather than increasing acute medication frequency 2
• Preventive therapy options include propranolol 80-240 mg/day, topiramate 50-100 mg/day, or amitriptyline 30-150 mg/day 2

Timing and Dosing Principles

• Take medication at the first sign of migraine pain, not during aura phase if present 2
• If headache not resolved by 2 hours after first dose, may take second dose at least 2 hours after first dose 6
• Maximum daily limits:
  • Eletriptan: 80 mg/day 6
  • Naproxen: 1.5 g/day 2
  • Acetaminophen: 4 g/day from all sources 2

Contraindications and Safety Considerations

Triptans Should NOT Be Used In:

• Ischemic coronary artery disease, prior MI, or coronary vasospasm 6
• History of stroke or TIA 6
• Uncontrolled hypertension 6
• Peripheral vascular disease or ischemic bowel disease 6
• Within 24 hours of ergotamine-containing medications or other triptans 6
• Within 72 hours of potent CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir) 6

NSAIDs Should Be Avoided In:

• Renal impairment (CrCl <30 mL/min) 2
• Active GI bleeding or history of NSAID-induced GI bleeding 2
• Aspirin/NSAID-induced asthma 2

Common Pitfalls to Avoid

• Do NOT wait until pain is severe to take medication—early treatment during mild pain phase is significantly more effective 2
• Do NOT use opioids (hydromorphone, oxycodone) as they lead to dependency, rebound headaches, and loss of efficacy; reserve only for cases where all other options are contraindicated or have failed 2
• Do NOT allow patients to escalate acute medication frequency in response to treatment failure—this creates medication-overuse headache; instead transition to preventive therapy 2
• Do NOT assume treatment failure after one triptan—failure of one triptan does not predict failure of others; try a different triptan or different route before abandoning the class 2

When to Escalate Treatment

If the above regimen fails after adequate trials:

1. Try a different triptan (failure of one does not predict failure of others) 2
2. Consider route change (e.g., subcutaneous or intranasal if oral failed) 2
3. Consider newer agents: CGRP antagonists (rimegepant, ubrogepant, zavegepant) or 5-HT1F agonists (lasmiditan) for patients with triptan contraindications or inadequate response 2
4. Initiate preventive therapy if attacks occur more than 2 days per week or produce significant disability 2