What are the treatment and prophylaxis options for migraines?

Migraine Treatment and Prophylaxis

Acute Treatment

For most migraine sufferers, NSAIDs are first-line therapy, with aspirin, ibuprofen, or naproxen sodium showing the most consistent evidence. 1

First-Line Acute Treatment Algorithm

• Start with NSAIDs (aspirin, ibuprofen, naproxen sodium) or the combination of acetaminophen plus aspirin plus caffeine for initial attacks 1
• Acetaminophen alone has no evidence for efficacy and should not be used 1
• Treat early in the attack to maximize effectiveness 1

Second-Line: Migraine-Specific Agents

• If NSAIDs fail, escalate to triptans or DHE 1
• Evidence-based triptans include: oral sumatriptan, rizatriptan, zolmitriptan, and naratriptan; subcutaneous sumatriptan; and DHE nasal spray 1
• If one triptan fails, try another triptan or combine an NSAID with a triptan 1
• Sumatriptan works through 5-HT1B/1D receptor agonism, causing cranial vessel constriction and inhibiting pro-inflammatory neuropeptide release 2

Special Considerations for Acute Treatment

• Use non-oral routes (nasal spray, subcutaneous) when nausea or vomiting presents early 1
• Add antiemetics for nausea even without vomiting, as nausea itself is disabling 1
• Avoid opioids and butalbital-containing compounds except as absolute last resort due to risk of medication overuse headache 3

Emergency/Intractable Migraine

• IV metoclopramide 10 mg plus IV ketorolac 30 mg is the most effective parenteral combination for severe migraine requiring emergency treatment 3

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Prophylactic Treatment

Preventive therapy should be initiated when patients have ≥2 attacks per month producing disability lasting ≥3 days, or when acute medications are used more than twice weekly. 1

Indications for Prophylaxis

• Two or more disabling attacks per month lasting ≥3 days 1
• Contraindication to or failure of acute treatments 1
• Use of abortive medication more than twice per week 1
• Uncommon migraine conditions (hemiplegic migraine, prolonged aura, migrainous infarction) 1

First-Line Prophylactic Agents

Beta-blockers (propranolol 80-240 mg/d, timolol 20-30 mg/d, metoprolol, atenolol, bisoprolol), topiramate, or candesartan are first-line options. 1

• Propranolol: 80-240 mg/d 1
• Timolol: 20-30 mg/d 1
• Topiramate: dose titrated to effect 1
• Candesartan: evidence-based alternative 1

Second-Line Prophylactic Agents

• Amitriptyline 30-150 mg/d 1
• Flunarizine (where available) 1
• Divalproex sodium 500-1500 mg/d or sodium valproate 800-1500 mg/d 1
  • Strictly contraindicated in women of childbearing potential due to teratogenic effects 1
  • If used, patients must use effective birth control and take folate 1

Third-Line: CGRP Monoclonal Antibodies

• Erenumab, fremanezumab, galcanezumab, and eptinezumab are FDA-approved for migraine prevention 1
• Reserved for patients who have failed other preventive drugs or have contraindications 1
• Assess efficacy only after 3-6 months of treatment 1

Chronic Migraine (≥15 headache days/month)

• OnabotulinumtoxinA 155 units is the only FDA-approved therapy specifically for chronic migraine prophylaxis 1, 3
• Assess efficacy after 6-9 months 1
• Topiramate has proven efficacy in randomized controlled trials for chronic migraine 1

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Treatment Principles and Monitoring

Dosing and Duration

• Start with low doses and titrate slowly to minimize adverse effects 1
• Allow 2-3 months to assess efficacy of oral preventive medications before declaring failure 1, 3
• Consider pausing preventive therapy after 6-12 months of successful treatment to determine if it can be discontinued 1

Medication Overuse Headache

• Rule out medication overuse headache if acute medications are used >2 days per week 3
• This creates a vicious cycle requiring withdrawal rather than escalation 3
• Excessive acute medication intake is itself a strong indication for preventive therapy 1

Patient Education and Monitoring

• Use headache diaries to track attack frequency, severity, duration, disability, and medication response 1
• Educate patients that preventive therapy efficacy takes weeks to months 1
• Calculate percentage reduction in monthly migraine days to quantify success 1

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Non-Pharmacological Approaches

• Cognitive-behavioral therapy (CBT) and biofeedback have evidence for efficacy 1, 3
• Exercise (40 minutes three times weekly) is as effective as topiramate or relaxation therapy 3
• Non-invasive neuromodulatory devices have supporting evidence 1
• Acupuncture may be beneficial, though not superior to sham acupuncture 1
• Little to no evidence exists for physical therapy, spinal manipulation, or dietary approaches 1

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Special Populations

Children and Adolescents

• Ibuprofen is first-line for acute treatment 1
• In adolescents, consider sumatriptan/naproxen oral, zolmitriptan nasal, sumatriptan nasal, rizatriptan ODT, or almotriptan oral 1
• Discuss with families that placebo was as effective as studied medications in many pediatric preventive trials 1
• Consider amitriptyline combined with CBT, topiramate, or propranolol for prevention 1

Pregnancy and Breastfeeding

• Discuss maternal disability versus fetal/neonatal risks when considering pharmacologic treatment 3
• Many standard prophylactic agents have contraindications or require careful risk-benefit analysis 3

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Common Pitfalls

• Failure of one preventive class does not predict failure of others (except when due to poor adherence) 1
• Poor adherence is common; simplified once-daily dosing improves compliance 1
• Avoid escalating treatment without first ruling out medication overuse headache 3
• Do not abandon preventive therapy prematurely—efficacy requires adequate trial duration 1