What is the typical presentation, evaluation, and acute and preventive management of migraine?

Migraine: Presentation, Evaluation, and Management

Typical Clinical Presentation

Migraine is a recurrent headache disorder characterized by moderate-to-severe, typically unilateral, throbbing pain lasting 4–72 hours when untreated, accompanied by nausea (>90% of patients), photophobia, phonophobia, and aggravation by routine physical activity. 1, 2

Core Diagnostic Features

• Headache characteristics: Unilateral location, pulsating quality, moderate-to-severe intensity, worsened by physical activity 1
• Associated symptoms: Nausea occurs in >90% of attacks, vomiting in ~70%, photophobia and phonophobia are nearly universal 2
• Attack duration: 4–72 hours if untreated or unsuccessfully treated 1, 3
• Diagnostic threshold: ≥5 lifetime attacks meeting these criteria 1

Migraine with Aura

• Aura occurs in >90% as visual phenomena, classically fortification spectra (zigzag lines) 1
• Sensory aura manifests as unilateral paresthesia spreading gradually over ≥5 minutes in ~31% of patients 1
• Key differentiating feature from TIA: Aura symptoms spread gradually (over ≥5 minutes) and occur in succession, whereas TIA symptoms have sudden, simultaneous onset 1
• Critical point: Many patients experience both migraine with and without aura; both diagnoses should be recorded when this pattern exists 1

Evaluation and Red-Flag Assessment

Neuroimaging is indicated only when red-flag features suggest secondary headache; routine imaging for typical recurrent migraine with normal examination is not recommended. 1, 4

Red Flags Requiring Urgent MRI

• Thunderclap headache (sudden, severe onset) 4
• Progressive worsening of headache pattern 4
• New neurological deficits or atypical aura 1, 4
• Recent head trauma 4
• Fever with neck stiffness 1
• Impaired memory or consciousness 4
• New-onset headache after age 50 4

Essential Clinical Assessment

• Record detailed headache history including frequency, duration, severity, triggers, and medication use 1
• Apply International Headache Society diagnostic criteria 1
• Perform neurological examination to exclude secondary causes 1
• Identify predisposing factors: family history, onset at puberty, sleep deprivation, stress, hormonal triggers 1, 4
• Screen for comorbidities: depression, anxiety, hypertension, obesity, sleep apnea 1, 4

Acute Treatment Algorithm

First-Line: Mild-to-Moderate Attacks

NSAIDs are the recommended first-line therapy for mild-to-moderate migraine, with the strongest evidence supporting ibuprofen 400–800 mg, naproxen sodium 500–825 mg, or aspirin 1000 mg. 1, 4

• Acetaminophen 1000 mg + aspirin 500–1000 mg + caffeine 130 mg is an effective combination for mild-to-moderate attacks 4
• Critical timing: Medication should be taken early in the attack while pain is still mild for maximum effectiveness 4
• Acetaminophen alone lacks evidence for efficacy 1

Second-Line: Moderate-to-Severe Attacks

Triptans are first-line therapy for moderate-to-severe migraine, with oral sumatriptan 50–100 mg, rizatriptan 10 mg, and eletriptan 40 mg demonstrating the highest efficacy. 1, 4, 5

• Combination therapy is superior: Sumatriptan + naproxen provides 130 additional patients per 1,000 achieving sustained pain relief at 48 hours compared to sumatriptan alone 4
• Route selection: Subcutaneous sumatriptan 6 mg provides the highest efficacy (59% pain-free at 2 hours) with onset within 15 minutes 4, 5
• Intranasal sumatriptan 5–20 mg is preferred when significant nausea or vomiting is present early in the attack 4, 5

Antiemetic Therapy

Antiemetics should not be restricted to patients who are vomiting; nausea itself is one of the most disabling symptoms and warrants treatment. 1, 4

• Metoclopramide 10 mg IV provides direct analgesic effects through central dopamine receptor antagonism, beyond its antiemetic properties 4
• Prochlorperazine 10 mg IV is comparable in efficacy to metoclopramide 4
• Administer antiemetics 20–30 minutes before oral migraine medication when nausea is prominent 4

Third-Line: Refractory Attacks

• Dihydroergotamine (DHE) 0.5–1.0 mg IV or intranasal has good evidence for efficacy when triptans fail 1, 4
• CGRP antagonists (ubrogepant 50–100 mg, rimegepant) are recommended when triptans are contraindicated or ineffective 4
• Lasmiditan 50–200 mg (5-HT1F agonist) is an alternative for patients with cardiovascular contraindications to triptans 4

Medications to Absolutely Avoid

Opioids (hydrocodone, oxycodone, morphine, codeine, tramadol) and butalbital-containing compounds are contraindicated for migraine treatment due to limited efficacy, high risk of medication-overuse headache, potential for dependence, and worse long-term outcomes. 1, 4, 5

Critical Frequency Limitation

All acute migraine medications must be limited to ≤2 days per week (≤10 days per month) to prevent medication-overuse headache, which paradoxically increases headache frequency and can lead to daily headaches. 1, 4

• NSAIDs and acetaminophen trigger medication-overuse headache at ≥15 days/month 4
• Triptans, ergots, and combination analgesics trigger medication-overuse headache at ≥10 days/month 4
• If acute treatment is needed more than twice weekly, preventive therapy must be initiated immediately 1, 4

Preventive Therapy Indications

Preventive therapy is indicated for patients with ≥2 migraine attacks per month producing disability lasting ≥3 days, use of acute medication >2 days per week, contraindication to or failure of acute treatments, or uncommon migraine variants. 1, 4

First-Line Preventive Medications

• Beta-blockers: Propranolol 80–240 mg/day or timolol 20–30 mg/day (strongest evidence) 1, 4
• Antiepileptics: Divalproex sodium 500–1500 mg/day or sodium valproate 800–1500 mg/day 1
  • Absolute contraindication: Valproate is strictly prohibited in women of childbearing potential due to teratogenic risk 1, 4
• Tricyclic antidepressants: Amitriptyline 30–150 mg/day, particularly useful for comorbid depression, anxiety, or mixed migraine/tension-type headache 1, 4
• Topiramate: 50–100 mg/day, especially beneficial in obese patients 4, 6

Third-Line: Chronic Migraine (≥15 Headache Days/Month)

• OnabotulinumtoxinA 155–195 units to 31–39 sites every 12 weeks is the only FDA-approved therapy specifically for chronic migraine 4
• CGRP monoclonal antibodies: Erenumab 70–140 mg subcutaneous monthly, fremanezumab 225 mg monthly or 675 mg quarterly, galcanezumab, eptinezumab 100–300 mg IV quarterly 4, 6

Treatment Duration and Assessment

• Oral preventives: Assess efficacy after 2–3 months at therapeutic dose 1, 4
• CGRP monoclonal antibodies: Assess after 3–6 months 4
• OnabotulinumtoxinA: Assess after 6–9 months 4
• Consider tapering or discontinuing after 6–12 months of stability 1, 4

Special Populations

Pregnancy and Breastfeeding

• Acute treatment: Paracetamol (acetaminophen) is the safest option 1
• Preventive treatment: Avoid if possible; valproate is absolutely contraindicated 1

Children and Adolescents

• Presentation may differ from adults; bed rest alone can be sufficient for mild attacks 1
• Acute treatment: Ibuprofen is first-line 1
• Preventive options: Propranolol, amitriptyline, or topiramate 1

Older Adults

• Secondary headache, comorbidities, and adverse events are all more likely 1
• Poor evidence base for all drugs in this age group; start with lower doses 1

Common Pitfalls to Avoid

• Do not prescribe opioids or butalbital simply because a patient requests them or reports "nothing else works" without ensuring adequate trials of NSAIDs, triptans, and combination therapy 4
• Do not abandon triptan therapy after a single failed attempt—failure of one triptan does not predict failure of others; try at least 2–3 different triptans before escalating 4, 5
• Do not delay preventive therapy while trialing multiple acute strategies when patients require acute treatment >2 days/week 4
• Do not allow patients to increase acute medication frequency in response to treatment failure; this creates a vicious cycle of medication-overuse headache 4
• Do not perform routine neuroimaging for typical recurrent migraine without red flags; this leads to unnecessary radiation, cost, and incidental findings 4

Contraindications to Triptans

• Ischemic heart disease or previous myocardial infarction 4, 5
• Uncontrolled hypertension 4, 5
• Cerebrovascular disease or history of stroke/TIA 4
• Basilar or hemiplegic migraine 4
• Concurrent use of ergots or MAO inhibitors 5