Migraine: Complete Treatment and Management

Diagnosis (brief context)

Migraine without aura requires ≥5 attacks lasting 4-72 hours with ≥2 of (unilateral, pulsating, moderate-severe, worse with activity) plus ≥1 of (nausea/vomiting, photophobia/phonophobia). Migraine with aura adds visual, sensory, motor, or speech aura symptoms preceding or accompanying the headache (Textbook of Family Medicine, p. 1216; Bradley and Daroff's Neurology in Clinical Practice).

1. Acute (Abortive) Treatment

Choice is stratified by attack severity, and treatment should be given early in the attack for best effect.

Mild-moderate attacks:

NSAIDs (ibuprofen, naproxen) or aspirin
Acetaminophen (less effective alone)
Combination analgesics (acetaminophen/aspirin/caffeine)

Moderate-severe attacks / NSAID-refractory:

Triptans (5-HT1B/1D agonists) - first-line specific antimigraine drugs, effective in ~70% of patients:
- Sumatriptan 25-100 mg PO (or 6 mg SC, 5-20 mg intranasal)
- Rizatriptan 5-10 mg, Zolmitriptan 2.5 mg, Eletriptan 40 mg, Naratriptan/Frovatriptan (slower onset, better tolerated for longer attacks), Almotriptan
- Contraindicated with coronary artery disease, uncontrolled hypertension, or within 24h of an ergot (Goodman & Gilman's Pharmacological Basis of Therapeutics, p. 3038-3075; Lippincott Illustrated Reviews Pharmacology, p. 4019-4029)
Ergotamine/dihydroergotamine (DHE) - Cafergot (ergotamine 1 mg + caffeine 100 mg), or DHE 1 mg IV/IM/SC or intranasal spray; causes vasoconstriction, avoid in pregnancy and vascular disease (Textbook of Family Medicine, p. 1217)
Gepants (oral CGRP receptor antagonists) - newer option, especially for triptan-intolerant/contraindicated patients or those with cardiovascular risk:
- Ubrogepant 50-100 mg, Rimegepant 75 mg
Lasmiditan (5-HT1F agonist, "ditan" class) 50-200 mg - effective without vasoconstrictive activity, but causes sedation/driving impairment (Katzung's Basic and Clinical Pharmacology, p. 885-892; Harrison's Principles of Internal Medicine 22E, p. 746-752)
Antiemetics with dopamine D2-antagonist activity (metoclopramide, prochlorperazine) - added for nausea/vomiting and can independently reduce headache; combining NSAID + triptan/ergot + antiemetic targets multiple pathophysiologic substrates and improves response (Bradley and Daroff's Neurology in Clinical Practice, p. 347-352)
Parenteral rescue options (ED/refractory attacks): ketorolac 15-30 mg IM/IV, IV dopamine antagonists, IV DHE, or peripheral nerve blocks

Important caution - Medication Overuse Headache (MOH): limit simple analgesics (NSAIDs/acetaminophen) to ≤14 days/month and triptans, ergots, combination analgesics, or opioids to ≤9 days/month to avoid MOH and reduced efficacy of preventive drugs. Opioids and butalbital should generally be avoided for routine migraine management (Bradley and Daroff's Neurology in Clinical Practice, p. 151-153).

2. Preventive (Prophylactic) Treatment

Indicated when attacks are frequent (typically ≥4 headache days/month), disabling, or poorly responsive to/contraindicated for acute therapy.

Beta-blockers: propranolol 80-240 mg/day, metoprolol - long-standing first-line agents
Tricyclic antidepressants: amitriptyline
Anticonvulsants: topiramate, divalproex/valproate sodium (avoid in women of childbearing potential without contraception due to teratogenicity)
Calcium channel blockers: verapamil, flunarizine (not in the US)
CGRP-targeted therapies (for patients failing older agents or with chronic migraine):
- Monoclonal antibodies (injectable/IV): erenumab, fremanezumab, galcanezumab, eptinezumab
- Oral gepants: rimegepant, atogepant
OnabotulinumtoxinA - for chronic migraine (≥15 headache days/month)
Start oral preventives at low dose, titrate slowly, and trial for at least 8 weeks before judging efficacy

(Lippincott Illustrated Reviews Pharmacology, p. 4047-4056; Bradley and Daroff's Neurology in Clinical Practice, p. 438-643; Katzung's Basic and Clinical Pharmacology, p. 3916-3923)

3. Non-Pharmacologic Management

Identify and avoid triggers: alcohol, oral contraceptives/hormone therapy, caffeine or withdrawal, stress, weather changes, strong odors, dietary triggers (nitrates, aged cheese, chocolate), skipped meals, poor sleep
Regular sleep, exercise, stress management, relaxation therapy
Non-invasive neuromodulation devices (newer evidence-based option per 2025 IHS guidelines)
Physical therapy for associated cervical/muscular contribution

(Textbook of Family Medicine, p. 1216)

4. Special Considerations

Pregnancy: avoid ergotamines, valproate, and topiramate (teratogenic); acetaminophen and select triptans (sumatriptan has the most safety data) are generally preferred when needed
Status migrainosus (attack >72 hours): often requires parenteral therapy (IV fluids, dopamine antagonists, DHE, steroids as bridge therapy)
Chronic migraine: CGRP monoclonal antibodies and onabotulinumtoxinA have the strongest evidence for prevention

Recent Evidence Update

The 2025 International Headache Society evidence-based pharmacological treatment guidelines (Ornello et al., Cephalalgia 2025) and companion summary reinforce triptans and gepants as first-line acute options and CGRP monoclonal antibodies/gepants for prevention, generally consistent with the textbook material above - PMID 40277319 and PMID 40277321. A 2025 systematic review of preventive RCTs for episodic migraine (PMID 40901671) further supports this preventive drug hierarchy. No major contradictions with the textbook-based summary were found, though these guidelines provide more granular evidence grading than older texts.

Disclaimer: This is educational information synthesized from medical textbooks and guidelines, not a personalized prescription. Actual drug selection, dosing, and contraindication screening (cardiovascular disease, pregnancy, hepatic/renal function, drug interactions) must be individualized by a treating clinician.

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