Migraine Pharmacotherapy

Migraine pharmacotherapy treats acute attacks and prevents recurrent attacks in a disorder of trigeminovascular activation and CGRP release. Acute treatment should work within 2 hours without causing medication overuse.

Classification. Acute: analgesics and NSAIDs, antiemetics, triptans, CGRP receptor antagonists (gepants), ergots. Preventive: beta blockers, candesartan, amitriptyline, topiramate, venlafaxine, flunarizine, botulinum toxin, CGRP monoclonal antibodies.

• Acute: aspirin 900 mg, ibuprofen 400 to 600 mg, naproxen 500 to 550 mg, or paracetamol 1 g, with metoclopramide 10 mg; triptans; rimegepant 75 mg; ubrogepant 50 to 100 mg.
• Preventive: propranolol 40 mg twice daily, up to 160 mg daily; candesartan 8 to 16 mg daily; amitriptyline 10 mg at night, up to 50 to 75 mg; topiramate 25 mg at night, up to 50 mg twice daily; venlafaxine 75 to 150 mg daily; flunarizine 5 to 10 mg at night; botulinum toxin A 155 to 195 units every 12 weeks for chronic migraine.

Differences. Beta blockers suit people with hypertension or anxiety; amitriptyline suits those with insomnia or tension-type headache; candesartan suits those with hypertension.

• Acute attack: treat early. Start with an NSAID plus an antiemetic; add a triptan if no response in 2 attacks.
• Status migrainosus: intravenous fluids, metoclopramide 10 mg or prochlorperazine 10 mg intravenously, sumatriptan 6 mg subcutaneously, dexamethasone 8 to 10 mg intravenously to reduce recurrence.
• Prevention: offer when there are 4 or more migraine days a month with disability, acute treatment fails or is contraindicated, or attacks are prolonged. Try each drug for 2 to 3 months at the target dose.
• Menstrual migraine: frovatriptan 2.5 mg twice daily or naratriptan 1 mg twice daily for 6 days around menstruation.
• Medication overuse: limit simple analgesics to under 15 days a month and triptans, ergots, opioids and combination analgesics to under 10 days a month. Avoid opioids.
• Regional: headache with fever needs malaria testing and exclusion of meningitis before migraine is assumed.

Selection. Combined oestrogen contraceptives are contraindicated in migraine with aura.

Contraindications. Triptans and ergots in ischaemic heart disease, stroke, uncontrolled hypertension and peripheral vascular disease. Propranolol in asthma and heart block. Valproate and topiramate in pregnancy.

Adverse effects. Class-specific: medication overuse headache, gastrointestinal bleeding with NSAIDs, fatigue with propranolol, sedation and weight gain with amitriptyline, cognitive effects and paraesthesia with topiramate.

Interactions. Propranolol raises rizatriptan levels. NSAIDs with anticoagulants. Amitriptyline with other serotonergic and anticholinergic drugs.

Special groups.

• Pregnancy: paracetamol and metoclopramide first; sumatriptan if needed; avoid NSAIDs after 20 weeks, topiramate, valproate and ergots; propranolol or amitriptyline for prevention.
• Breastfeeding: paracetamol, ibuprofen and sumatriptan acceptable.
• Children: paracetamol or ibuprofen; nasal triptans from 12 years where licensed.
• Older adults: avoid triptans, ergots and amitriptyline.
• Kidney impairment: avoid NSAIDs.

Monitoring. Headache diary, days of acute drug use, blood pressure and heart rate, mood and weight.

Referral and escalation. Thunderclap onset, new headache over 50 years, fever or neck stiffness, neurological signs, papilloedema, positional headache, headache in pregnancy or immunosuppression (including HIV), or a change in pattern needs imaging and lumbar puncture as indicated.