What are the medication options for persistent migraine headaches?

Medication Options for Persistent Migraine Headaches

For persistent migraines, start with NSAIDs (ibuprofen 400-800 mg, naproxen sodium 275-550 mg, or aspirin 650-1000 mg) as first-line acute treatment, and if attacks occur ≥2 times per month with ≥3 days of disability, initiate preventive therapy with propranolol (80-240 mg/day), topiramate (100 mg/day), or candesartan. 1, 2

Acute Treatment Strategy

First-Line: NSAIDs

• Ibuprofen 400-800 mg every 6 hours (maximum 2.4 g/day) is the most effective over-the-counter option 1
• Naproxen sodium 275-550 mg every 2-6 hours (maximum 1.5 g/day) provides longer duration of action 1
• Aspirin 650-1000 mg every 4-6 hours (maximum 4 g/day) has proven efficacy 1
• Aspirin 250 mg + acetaminophen 250 mg + caffeine 65 mg combination is more effective than acetaminophen alone 1
• Acetaminophen alone is ineffective and should not be used 1

Second-Line: Triptans (When NSAIDs Fail)

Triptans should be taken early when pain is still mild for maximum effectiveness 1, 3

• Sumatriptan 50 mg orally is the most studied dose with NNT 3.2 for headache relief at 2 hours; provides pain-free response in 28% vs 11% with placebo 4, 3
• Sumatriptan 100 mg orally is more effective (NNT 4.7 for pain-free at 2 hours) but causes more adverse events than 50 mg 4, 5, 3
• Rizatriptan 10 mg reaches peak concentration faster (60-90 minutes) than most triptans 1
• Subcutaneous sumatriptan 6 mg is the most effective route (59% pain-free at 2 hours vs 15% placebo; NNT 2.3) but has highest adverse event rate 1, 6
• If one triptan fails, try a different triptan before abandoning this class—patients should trial 2-3 headache episodes before switching 1

Critical contraindications for triptans: ischemic vascular disease, vasospastic coronary disease, uncontrolled hypertension, significant cardiovascular disease, pregnancy 1

Third-Line: Gepants or Ditans (When All Triptans Fail)

• Ubrogepant or rimegepant (gepants) are alternatives when triptans are contraindicated or ineffective after adequate trial (no response in ≥3 consecutive attacks) 1, 7
• Lasmiditan (ditan) has comparable efficacy to triptans but causes temporary driving impairment 1

For Migraine with Nausea/Vomiting

• Use non-oral routes: subcutaneous sumatriptan 6 mg, intranasal sumatriptan, or rizatriptan orally disintegrating wafer 1
• Add metoclopramide 10 mg IV or orally 20-30 minutes before or with analgesic/triptan to treat nausea and improve gastric motility 1
• Prochlorperazine can effectively relieve both headache pain and nausea 1

Rescue Medications (Use Sparingly)

• Ketorolac 60 mg IM for severe attacks unresponsive to oral medications (maximum 120 mg/day, limit to 5 days) 1
• Dihydroergotamine (DHE) 0.5-1.0 mg IM/IV for severe migraines (maximum 3 mg IM or 2 mg IV per day) 1
• Limit opioids (meperidine, butorphanol) to situations where other treatments are contraindicated and abuse risk has been addressed—they cause dependency and rebound headaches 1

Preventive Therapy

Indications for starting preventive therapy: 1, 2

• ≥2 migraine attacks per month causing ≥3 days of disability
• Using acute medications >2 times per week (risk of medication overuse headache)
• Contraindication to or failure of acute treatments
• Uncommon migraine variants (hemiplegic, prolonged aura, migrainous infarction)

First-Line Preventive Medications

• Propranolol 80-240 mg/day has strongest evidence for efficacy 1, 2
• Timolol 20-30 mg/day is equally effective beta-blocker alternative 1, 2
• Topiramate 100 mg/day (typically 50 mg twice daily) is highly effective 2
• Candesartan is particularly useful for patients with comorbid hypertension 2

Second-Line Preventive Medications

• Amitriptyline 30-150 mg/day is effective, especially for mixed migraine and tension-type headache 1, 2
• Divalproex sodium 500-1500 mg/day or sodium valproate 800-1500 mg/day are effective but strictly contraindicated in women of childbearing potential due to teratogenic effects 1, 2

Third-Line: CGRP Monoclonal Antibodies

• Galcanezumab 120 mg subcutaneously monthly (after 240 mg loading dose) reduces monthly migraine days by 4.7 days vs 2.7 with placebo 8
• Erenumab, fremanezumab, eptinezumab are alternatives when other preventives fail or are contraindicated 2
• Assess efficacy only after 3-6 months of treatment 2

Implementation Principles

• Start low, titrate slowly over 2-3 months to assess efficacy before abandoning a preventive 1, 2
• Avoid medication overuse during preventive therapy—limit acute medications to <2 days per week 1, 2
• Consider tapering after 6-12 months of successful prevention to determine if continued treatment is necessary 2

Critical Pitfalls to Avoid

• Medication overuse headache: Occurs with frequent use of triptans, ergotamine, opioids, or caffeine/butalbital-containing analgesics—limit acute treatment to <2 days per week 1
• Inadequate triptan trial: Patients must try a medication for 2-3 headache episodes before declaring failure 1
• Treating too late: Triptans are most effective when taken during mild pain phase, not after pain becomes moderate/severe 1, 3
• Insufficient preventive trial duration: Must allow 2-3 months before determining preventive efficacy 1, 2
• Starting preventive dose too high: Leads to poor tolerability and discontinuation 2
• Using valproate in women of childbearing age: Absolute contraindication due to teratogenicity 2