What is the recommended acute and preventive treatment for a typical adult with migraine without aura?

Treatment of Migraine Without Aura

Acute Treatment Algorithm

For mild to moderate migraine attacks, start with NSAIDs (ibuprofen 400-800 mg, naproxen 500-825 mg, or aspirin 900-1000 mg) or acetaminophen 1000 mg as first-line therapy; for moderate to severe attacks or when NSAIDs fail, escalate immediately to a triptan, and the combination of triptan plus NSAID provides superior efficacy compared to either agent alone. 1, 2

First-Line Treatment Selection

• Mild to moderate attacks: Begin with NSAIDs at the onset of pain, ideally when headache is still mild 1, 2

  • Ibuprofen 400-800 mg every 6-8 hours as needed 2
  • Naproxen sodium 500-825 mg, can be repeated every 2-6 hours (maximum 1.5 g/day) 1
  • Aspirin 900-1000 mg 2
  • Acetaminophen 1000 mg (when NSAIDs are contraindicated) 1

• Moderate to severe attacks: Use triptans as first-line therapy 1, 2, 3

  • Sumatriptan 50-100 mg orally (most studied) 2, 3
  • Rizatriptan 10 mg (fastest oral triptan, reaching peak concentration in 60-90 minutes) 1
  • Eletriptan 40 mg or zolmitriptan 2.5-5 mg (reportedly more effective with fewer adverse reactions than sumatriptan) 1
  • Naratriptan (longest half-life, may decrease recurrence headaches) 1

Combination Therapy for Enhanced Efficacy

The combination of sumatriptan 50-100 mg PLUS naproxen sodium 500 mg is superior to either agent alone, with 130 more patients per 1000 achieving sustained pain relief at 48 hours. 1

• This combination represents the strongest recommendation from recent guidelines for moderate to severe migraine 1
• Combination therapy addresses the 40% of patients who experience symptom recurrence within 48 hours 1

Route Selection Based on Symptoms

• When significant nausea or vomiting is present: Use non-oral routes 1, 2

  • Subcutaneous sumatriptan 6 mg provides the highest efficacy (59% complete pain relief by 2 hours) with onset within 15 minutes 1, 3
  • Intranasal sumatriptan 5-20 mg or other nasal spray triptans 1, 2
  • Rectal formulations when oral absorption is impaired 1

• Add an antiemetic 20-30 minutes before the primary medication when nausea is present 1

  • Metoclopramide 10 mg (provides synergistic analgesia beyond antiemetic effects) 1
  • Prochlorperazine 25 mg 1

Escalation Strategy for Treatment Failures

• If one triptan fails after 2-3 migraine episodes, try a different triptan before abandoning the class entirely, as failure of one does not predict failure of others 1, 4, 3

• If all oral triptans fail: Consider subcutaneous sumatriptan 6 mg, which has the highest efficacy rate among all triptan formulations 1, 3

• If triptans are contraindicated or all fail: Escalate to newer CGRP antagonists (ubrogepant 50-100 mg or rimegepant) 1

• For severe refractory attacks: Dihydroergotamine (DHE) nasal spray or IV has good evidence for efficacy as monotherapy 1, 3

Critical Frequency Limitation to Prevent Medication-Overuse Headache

Limit all acute migraine medications to no more than 2 days per week (approximately 10 days per month) to prevent medication-overuse headache, which paradoxically increases headache frequency and can lead to daily headaches. 1, 2

• Triptans trigger medication-overuse headache at ≥10 days/month 1
• NSAIDs trigger medication-overuse headache at ≥15 days/month 1
• If acute treatment is needed more than twice weekly, initiate preventive therapy immediately 1, 5

Medications to Avoid

• Opioids (hydromorphone, meperidine, codeine combinations) should be avoided as they have questionable efficacy, lead to dependency, cause rebound headaches, and result in loss of efficacy over time 1, 3
• Butalbital-containing compounds should similarly be avoided due to high risk of medication-overuse headache 6, 1
• These agents should be reserved only for cases where all other evidence-based treatments are contraindicated, sedation is acceptable, and abuse risk has been addressed 1

Contraindications Requiring Alternative Approach

• 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, 2
• NSAIDs should be avoided in patients with renal impairment (creatinine clearance <30 mL/min), aspirin/NSAID-induced asthma, or active GI bleeding 1

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Preventive Therapy Indications and Selection

When to Initiate Preventive Therapy

Preventive therapy is indicated for patients with two or more attacks per month producing disability lasting 3 or more days, use of abortive medication more than twice per week, contraindication to or failure of acute treatments, or presence of uncommon migraine conditions. 6, 5

• Additional factors include adverse events with acute therapies, patient preference, and cost considerations 6
• The goal is to reduce attack frequency by ≥50% and restore responsiveness to acute treatments 1

First-Line Preventive Medications

Topiramate is the first-line evidence-based preventive medication for both episodic and chronic migraine, supported by robust randomized controlled trial data, and is the only oral preventive with strong RCT evidence specifically for chronic migraine. 5

• Topiramate 50-100 mg/day (typically 50 mg twice daily) 2, 5

  • Preferred in patients with obesity due to associated weight loss 5
  • Start low and titrate slowly over 2-3 months 5
  • Substantially lower cost compared to onabotulinumtoxinA and CGRP monoclonal antibodies 5

• Beta-blockers without intrinsic sympathomimetic activity 6, 5

  • Propranolol 80-240 mg/day (FDA-approved, strong evidence) 6, 5
  • Timolol 20-30 mg/day (strong evidence) 6, 5
  • Metoprolol, atenolol, or nadolol (moderate evidence) 6

• Candesartan (particularly useful for patients with comorbid hypertension) 5

Second-Line Preventive Medications

• Amitriptyline 30-150 mg/day 6, 5

  • Preferred for patients with comorbid depression, anxiety, or sleep disturbances 5
  • Superior for patients with mixed migraine and tension-type headache 6
  • No robust RCT evidence for chronic migraine prophylaxis; efficacy mainly demonstrated in episodic migraine 5

• Sodium valproate 800-1500 mg/day or divalproex sodium 500-1500 mg/day 6, 5

  • Strictly contraindicated in women of childbearing potential due to teratogenic effects 5

Third-Line: CGRP Monoclonal Antibodies

• Erenumab, fremanezumab, or galcanezumab administered monthly via subcutaneous injection 5
  • Reserved for patients who have failed 2-3 oral preventive medications 5
  • Efficacy requires 3-6 months for assessment 1, 5
  • Significantly more expensive ($5,000-$6,000 annually) 5

Implementation Strategy

• Start with a low dose and titrate slowly until clinical benefits are achieved or side effects limit further increases 5
• Allow an adequate trial period of 2-3 months before determining efficacy 5, 7
• Use headache diaries to track attack frequency, severity, duration, disability, treatment response, and adverse effects 5
• Consider pausing preventive treatment after 6-12 months of successful therapy to determine if it can be discontinued 5

Non-Pharmacological Adjuncts

• Cognitive behavioral therapy, biofeedback, and relaxation training are effective adjuncts alongside medication 5, 8
• Identifying and modifying triggers (sleep hygiene, regular meals, hydration, stress management) 5
• Neuromodulatory devices can be considered as adjuncts or stand-alone treatments when medications are contraindicated 5

Common Pitfalls to Avoid

• Failing to recognize medication-overuse headache from frequent use of acute medications before starting preventive therapy 1, 5
• Inadequate duration of preventive trial (less than 2-3 months) 5
• Starting with too high a dose, leading to poor tolerability and discontinuation 5
• Using amitriptyline as first-line for chronic migraine when topiramate has stronger evidence 5
• Prescribing valproate to women of childbearing potential 5