What are the treatment guidelines for a patient experiencing migraines?

Treatment Guidelines for Migraines

Acute Treatment of Migraine

For moderate to severe migraine attacks, start with combination therapy of a triptan plus an NSAID (such as sumatriptan 50-100 mg with naproxen 500 mg), as this provides superior efficacy compared to either agent alone. 1

First-Line Acute Treatment Algorithm

Mild to Moderate Attacks:

• Begin with NSAIDs (ibuprofen 400-800 mg, naproxen 500-825 mg, or aspirin 1000 mg) or acetaminophen 1000 mg 1, 2
• If NSAIDs alone fail after 2-3 episodes, escalate to triptan + NSAID combination 1

Moderate to Severe Attacks:

• Initiate combination therapy immediately: triptan + NSAID (or acetaminophen if NSAIDs contraindicated) 1
• This combination provides 130 more patients per 1000 achieving sustained pain relief at 48 hours compared to monotherapy 1
• Counsel patients to treat early in the attack while pain is still mild for maximum effectiveness 1, 2

Specific Triptan Options (choose based on patient factors):

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

Route Selection Based on Symptoms

Severe Nausea/Vomiting Present:

• Use non-oral routes: subcutaneous sumatriptan 6 mg (provides 70-82% pain relief within 15 minutes) 2
• Alternative: intranasal sumatriptan 5-20 mg or zolmitriptan nasal spray 2
• Add antiemetic: metoclopramide 10 mg IV or prochlorperazine 10 mg IV/25 mg rectal 2

Rapid Progression to Peak Intensity:

• Subcutaneous sumatriptan 6 mg provides highest efficacy with onset within 15 minutes 2

Second-Line Options When Triptans Fail or Are Contraindicated

If one triptan fails, try a different triptan—failure of one does not predict failure of others 2, 3

If all triptans fail or are contraindicated (cardiovascular disease, uncontrolled hypertension):

• CGRP antagonists-gepants: rimegepant, ubrogepant 50-100 mg, or zavegepant 1, 2
• Ditan: lasmiditan 50-200 mg (warning: no driving for 8 hours due to CNS effects) 1, 2
• Dihydroergotamine (DHE) nasal spray or IV 1, 2

Emergency Department/IV Treatment

Optimal IV "Headache Cocktail":

• Metoclopramide 10 mg IV (provides direct analgesic effects beyond antiemetic properties) 2
• PLUS Ketorolac 30 mg IV (rapid onset, 6-hour duration, minimal rebound risk) 2
• Alternative: Prochlorperazine 10 mg IV (comparable efficacy to metoclopramide, 21% adverse event rate vs 50% for chlorpromazine) 2

Alternative IV Options:

• Dihydroergotamine (DHE) IV 2
• Avoid: Opioids and butalbital (lead to dependency, rebound headaches, medication overuse headache) 1, 2

Critical Frequency Limitation

Limit ALL acute migraine medications to no more than 2 days per week (10 days per month) to prevent medication-overuse headache 1, 2

• NSAIDs/acetaminophen: ≥15 days/month triggers medication-overuse headache 1
• Triptans: ≥10 days/month triggers medication-overuse headache 1
• If needing acute treatment more than twice weekly, initiate preventive therapy immediately 1, 2

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Preventive Treatment of Migraine

Preventive therapy should be initiated for patients experiencing ≥2 migraine attacks per month with disability lasting ≥3 days, or those using acute medications more than twice weekly. 1, 4

Indications for Preventive Therapy

• Two or more migraine attacks per month producing disability lasting ≥3 days 4
• Use of abortive medication more than twice per week 4
• Contraindications to or failure of acute treatments 4
• Uncommon migraine conditions (hemiplegic migraine, prolonged aura, migrainous infarction) 4

First-Line Preventive Medications (Start Here)

The 2025 American College of Physicians guideline prioritizes cost-effective options first:

Beta-Blockers (first choice for most patients):

• Propranolol 80-240 mg/day (FDA-approved, strong evidence) 1, 4
• Metoprolol 1, 4
• Timolol 20-30 mg/day 4
• Atenolol or bisoprolol 4
• Particularly useful for patients with comorbid hypertension 1, 4

Antiseizure Medications:

• Topiramate 50-100 mg/day (typically 50 mg twice daily) 1, 4
  • Especially beneficial in obese patients due to weight loss effects 4
  • Common adverse effects: cognitive inefficiency, paresthesia, fatigue 5
  • Teratogenic: requires effective birth control and folate supplementation in women of childbearing potential 1, 4

Angiotensin Receptor Blocker:

• Candesartan (first-line, particularly useful for hypertensive patients) 1, 4

SNRI:

• Venlafaxine 1

Tricyclic Antidepressant:

• Amitriptyline 30-150 mg/day 1, 4
  • Particularly effective for patients with mixed migraine and tension-type headache, or comorbid depression/anxiety 4

Implementation Strategy

Start low, titrate slowly:

• Begin at low dose and gradually increase until clinical benefits achieved or side effects limit further increases 4
• Allow adequate trial period of 2-3 months at therapeutic dose before determining efficacy 1, 4
• Use headache diaries to track attack frequency, severity, duration, and disability 4

Duration of therapy:

• Consider pausing preventive treatment after 6-12 months of successful control to determine if therapy can be discontinued 1, 4
• Useful measure: calculate percentage reduction in monthly migraine days 4

Second-Line Preventive Medications

Use when first-line agents fail or are contraindicated:

• Flunarizine 5-10 mg once daily (where available; avoid in Parkinsonism or depression) 4
• Sodium valproate 800-1500 mg/day or divalproex sodium 500-1500 mg/day 4
  • Strictly contraindicated in women of childbearing potential due to teratogenic effects 1, 4

Third-Line: CGRP Monoclonal Antibodies

Consider when 2-3 oral preventive medications have failed or are contraindicated:

• Erenumab 70 or 140 mg subcutaneous once monthly 1, 4, 6
• Fremanezumab 225 mg subcutaneous once monthly or 675 mg quarterly 1, 4
• Galcanezumab subcutaneous once monthly 1, 4
• Eptinezumab 100 or 300 mg IV quarterly 1, 4

Important considerations:

• Assess efficacy only after 3-6 months (longer than oral agents) 1, 4
• Significantly more expensive than oral agents: $5,000-$6,000 annually 4
• No vasoconstriction, safe for patients with cardiovascular disease 4

Fourth-Line: OnabotulinumtoxinA

For chronic migraine ONLY (≥15 headache days/month with ≥8 migraine days):

• OnabotulinumtoxinA 155-195 units to 31-39 sites every 12 weeks 5, 4
• FDA-approved for chronic migraine prophylaxis 5
• Specifically NOT recommended for episodic migraine 4
• Assess efficacy after 6-9 months 4

Non-Pharmacological Adjuncts

Recommend alongside medication or as stand-alone when medications contraindicated:

• Cognitive behavioral therapy, biofeedback, relaxation training 4
• Neuromodulatory devices 4
• Acupuncture (though not superior to sham acupuncture in controlled trials) 4
• Lifestyle modifications: regular sleep, hydration, regular meals, stress management, regular exercise 1, 4

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Special Populations

Children and Adolescents

Acute Treatment:

• Ibuprofen as first-line for pain 1
• In adolescents, consider: sumatriptan/naproxen oral, zolmitriptan nasal, sumatriptan nasal, rizatriptan ODT, or almotriptan oral 1
• If one triptan ineffective, try another or NSAID-triptan combination 1
• Add antiemetic for nausea/vomiting 1

Preventive Treatment:

• Discuss with families that placebo was as effective as studied medications in many pediatric trials 1
• Evidence for: amitriptyline combined with cognitive behavioral therapy, topiramate, propranolol 1
• Topiramate and valproate are teratogenic: advise effective birth control and folate supplementation 1

Pregnancy and Lactation

Discuss adverse effects of pharmacologic treatments during pregnancy and lactation before initiating therapy 1

• Valproate is strictly contraindicated due to teratogenic effects 1, 4
• Topiramate requires effective birth control and folate supplementation 1, 4

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Critical Pitfalls to Avoid

Medication-Overuse Headache:

• Most common pitfall: allowing patients to increase frequency of acute medication use in response to treatment failure 2
• This creates a vicious cycle leading to daily headaches 1, 2
• Strict limit: no more than 2 days per week for ALL acute medications 1, 2

Inadequate Trial Duration:

• Oral preventives require 2-3 months at therapeutic dose 1, 4
• CGRP monoclonal antibodies require 3-6 months 1, 4
• OnabotulinumtoxinA requires 6-9 months 4
• Do not abandon treatment prematurely 4

Starting Dose Too High:

• Leads to poor tolerability and discontinuation 4
• Always start low and titrate slowly 4

Failing to Recognize Contraindications:

• Screen for cardiovascular disease before prescribing triptans or ergots 2
• Screen for depression and Parkinsonism before prescribing flunarizine 4
• Verify pregnancy status before prescribing valproate or topiramate 1, 4

Not Counseling on Early Treatment:

• Triptans are most effective when taken early while pain is still mild 1, 2
• Delayed treatment reduces efficacy significantly 1

Abandoning Triptan Class After Single Failure:

• Failure of one triptan does not predict failure of others 2, 3
• Try 2-3 different triptans before declaring class failure 2