Management of migraine
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Management of Migraine
Overview
Migraine management divides into two broad strategies: acute (abortive) therapy to stop an attack in progress, and preventive (prophylactic) therapy to reduce attack frequency and severity. A stepped approach is typical, with treatment intensity matching headache severity and disability.
1. Diagnosis Recap
The POUND mnemonic aids ED diagnosis - Pulsatile quality, duration One day (4-72 h), Unilateral, Nausea/vomiting, Disabling severity. Meeting 4/5 criteria carries a positive likelihood ratio of 24 for migraine. A migraine attack can include up to four phases: premonitory, aura, headache, and postdrome.
- Episodic migraine: < 15 headache days/month
- Chronic migraine: ≥ 15 headache days/month (≥ 8 being migraine-type) for > 3 months
2. Acute (Abortive) Treatment
A. Mild-to-Moderate Attacks - Step 1
| Drug | Dose | Notes |
|---|---|---|
| Aspirin | 500-1000 mg PO | Often combined with metoclopramide |
| Ibuprofen | 400-600 mg PO | First-line NSAID |
| Naproxen | 500-550 mg PO | Longer half-life |
| Paracetamol (acetaminophen) | 1000 mg PO | Useful in pregnancy |
| Diclofenac | 50-100 mg PO/rectal | Rectal route useful with vomiting |
B. Moderate-to-Severe Attacks - Triptans (5-HT1B/1D Agonists)
Triptans are the first-line abortive therapy for moderate-to-severe migraine and should be taken early in the attack.
Mechanism: Triptans (5-HT1B/1D receptor agonists) work by:
- Constriction of dilated intracranial blood vessels
- Inhibition of neuropeptide release from trigeminal nerve endings
- Inhibition of pain signal transmission in the trigeminal nucleus caudalis
- Goodman & Gilman's, p. 3053-3060
Available triptans:
| Triptan | Oral Dose | Route Options | Onset | Notable Feature |
|---|---|---|---|---|
| Sumatriptan | 25-100 mg | PO, SC, intranasal, rectal | Fast SC | Prototype; SC fastest onset |
| Zolmitriptan | 2.5-5 mg | PO, nasal | Fast | Nasal spray useful with vomiting |
| Rizatriptan | 5-10 mg | PO, orally disintegrating | Moderate | Avoid with propranolol (use 5 mg) |
| Almotriptan | 12.5 mg | PO | Moderate | Fewest side effects |
| Eletriptan | 20-40 mg | PO | Moderate | Highest efficacy |
| Frovatriptan | 2.5 mg | PO | Slow | Long half-life; used for menstrual migraine |
| Naratriptan | 2.5 mg | PO | Slow | Fewest recurrences |
Key triptan rules:
- Take at headache onset (not during aura)
- Can repeat dose after 2 hours if partial response
- Maximum 2 doses/24 hours; limit to 2-3 days/week to avoid medication overuse headache
- Contraindications: coronary artery disease, uncontrolled hypertension, stroke/TIA, hemiplegic migraine, basilar migraine, concurrent MAOI or ergotamine use, pregnancy
C. Newer Acute Options
Gepants (CGRP receptor antagonists) - particularly useful for patients with cardiovascular contraindications to triptans, or triptan non-responders:
- Ubrogepant (50-100 mg PO)
- Rimegepant (75 mg PO)
- No vasoconstriction - safe in cardiovascular disease
Lasmiditan (5-HT1F receptor agonist):
- 50-200 mg PO; no vasoconstriction
- Indicated for triptan non-responders or contraindications
- CNS side effects (dizziness, sedation); driving restriction for 8 hours
A 2024 network meta-analysis (Karlsson et al., BMJ 2024) compared acute drug interventions for migraine and found triptans remain highly effective; gepants and lasmiditan provide meaningful alternatives for triptan-inadequate responders - confirmed by a 2024 systematic review in J Headache Pain (PMID 39516789).
D. Ergot Alkaloids
- Ergotamine + caffeine (Cafergot): older option, largely replaced by triptans
- Dihydroergotamine (DHE): IV/IM/intranasal; still used for refractory cases and status migrainosus
- Contraindicated in: pregnancy, cardiovascular disease, within 24 h of triptan use
E. Antiemetics / Adjuncts
Helpful for nausea and as prokinetics to improve oral drug absorption:
- Metoclopramide 10 mg IV/PO (first choice)
- Prochlorperazine 10 mg IV/PO
- Domperidone 10-20 mg PO
- Ondansetron (if dopamine antagonists not tolerated)
3. Emergency Department Management
In the ED, most patients have already failed home abortive therapy and require rescue treatment.
First-line ED regimen:
- IV dopamine receptor antagonist (prochlorperazine 10 mg IV, metoclopramide 10 mg IV, or droperidol 0.625-1.25 mg IV) + IV NSAID (ketorolac 15-30 mg IV)
- Add diphenhydramine 25-50 mg IV to prevent akathisia from antiemetics
- IV fluids if dehydrated
Dexamethasone (10 mg IV) reduces headache recurrence after ED discharge and is recommended before discharge.
Avoid in the ED: opioids and butalbital-containing compounds are not routinely recommended (risk of dependence and medication overuse headache). - Tintinalli's Emergency Medicine, p. 1332-1336
Status migrainosus (attack lasting > 72 h):
- IV dihydroergotamine protocol (Raskin protocol)
- IV valproic acid: 15 mg/kg loading then 5 mg/kg every 8 h, or 1 g over 1 hour
- IV dexamethasone 10 mg before discharge
- Minimize opioid use
4. Preventive (Prophylactic) Treatment
Indications for Prevention
Consider prophylaxis when:
- Attacks occur 2 or more times/month causing significant disability
- Attacks last > 48 h despite acute treatment
- Acute medications are overused, contraindicated, or ineffective
- Patient preference
The goal is ≥ 50% reduction in attack frequency. Prevention medications are titrated slowly and maintained for at least 3-6 months before assessing response. - Bradley and Daroff's Neurology in Clinical Practice
First-Line Preventive Agents (AAN/AHS Guidelines)
Beta-blockers (strongest evidence):
- Propranolol 80-240 mg/day (long-acting preferred)
- Metoprolol 50-200 mg/day
- Timolol 10-30 mg/day
- Mechanism unclear; avoid in asthma, depression, severe bradycardia
- Contraindicated in pregnancy
Antiepileptics:
- Topiramate 25-100 mg/day - highly effective; side effects include cognitive slowing, weight loss, paresthesias; teratogenic (avoid in pregnancy)
- Valproate/divalproex 500-1500 mg/day - first-line; contraindicated in pregnancy and women of childbearing age (teratogen)
Antidepressants:
- Amitriptyline 10-75 mg at night - particularly useful if comorbid insomnia or depression; anticholinergic side effects
- Venlafaxine 75-150 mg/day - useful with comorbid depression/anxiety
Second-Line Preventive Agents
- Candesartan 16 mg/day - ARB; evidence comparable to propranolol; well tolerated
- Lisinopril - ACE inhibitor; moderate evidence
- Flunarizine 5-10 mg/day (calcium channel blocker; not available in US) - widely used in Europe
- Magnesium 400-600 mg/day elemental - modest evidence; very safe; useful in pregnancy
- Riboflavin (Vitamin B2) 400 mg/day - modest reduction in frequency; very safe
- Coenzyme Q10 100-300 mg/day - mild evidence
CGRP-Targeted Preventive Therapies (Newer)
CGRP plays a central role in migraine pathophysiology. Anti-CGRP monoclonal antibodies are highly effective with once-monthly or quarterly dosing:
| Agent | Target | Dose/Frequency |
|---|---|---|
| Erenumab (Aimovig) | CGRP receptor | 70-140 mg SC monthly |
| Fremanezumab (Ajovy) | CGRP ligand | 225 mg SC monthly or 675 mg quarterly |
| Galcanezumab (Emgality) | CGRP ligand | 120 mg SC monthly |
| Eptinezumab (Vyepti) | CGRP ligand | 100-300 mg IV quarterly |
Gepants for prevention:
- Atogepant - oral, daily; approved for episodic and chronic migraine
- Rimegepant - oral, every other day
Onabotulinumtoxin A (Botox)
- Approved for chronic migraine only (≥ 15 headache days/month)
- 155-195 units injected across 31-39 sites on head/neck every 12 weeks
- Reduces monthly headache days by approximately 8-9 days
5. Special Populations
Menstrual Migraine
- Short-term prevention: frovatriptan or naratriptan (2 days before and through menstruation) due to long half-life
- Mini-prophylaxis: NSAIDs (naproxen 500 mg twice daily) starting 2 days before expected onset
- A 2024 meta-analysis (Khoo et al., J Headache Pain, PMID 39227797) supports both acute and preventive approaches for menstrual migraine
Pregnancy
- Safest acute options: paracetamol (first choice), opioids (short-term), corticosteroids
- Metoclopramide: category B; acceptable
- NSAIDs: acceptable until third trimester
- Avoid: triptans, ergotamines, valproate, topiramate, caffeine combinations
- Prevention: magnesium, amitriptyline (low dose), beta-blockers (with caution - risk of fetal growth restriction)
Elderly
- Beta-blockers and amitriptyline with caution (falls, bradycardia)
- Topiramate may worsen cognitive function
- Gepants and anti-CGRP antibodies: growing evidence, generally well tolerated
6. Non-Pharmacological Management
- Lifestyle: regular sleep schedule, consistent mealtimes, aerobic exercise, stress management, hydration
- Trigger identification and avoidance: stress, sleep disruption, hormonal changes, certain foods (tyramine, alcohol), bright lights
- Cognitive behavioural therapy (CBT) and biofeedback: evidence-based; reduce frequency and disability
- Acupuncture: evidence comparable to prophylactic drugs in some trials
- Neuromodulation devices (FDA-cleared):
- Cefaly (transcutaneous supraorbital nerve stimulation) - for prevention and acute
- SpringTMS/eNeura (single-pulse TMS) - for acute treatment of migraine with aura
- gammaCore (non-invasive vagus nerve stimulation)
7. Medication Overuse Headache (MOH)
Overuse of acute treatments (especially opioids, triptans, ergotamines, combination analgesics > 10-15 days/month) leads to MOH - a chronic daily headache pattern.
Management:
- Withdraw the overused medication (abrupt withdrawal for most; gradual for opioids/barbiturates)
- Bridge therapy: NSAIDs, steroids (prednisone 60 mg/day tapering over 10 days)
- Initiate preventive therapy
- Patient education is key to preventing relapse
Key References:
- Bradley and Daroff's Neurology in Clinical Practice, Chapter 102 (Migraine, Primary Headaches)
- Goodman & Gilman's Pharmacological Basis of Therapeutics, Chapter on Serotonergic Pharmacology
- Tintinalli's Emergency Medicine: A Comprehensive Study, Chapter 165
- Karlsson WK et al., BMJ 2024 - network meta-analysis of acute migraine treatments [PMID: 39293828]
- Laohapiboolrattana W et al., J Headache Pain 2024 - gepants and lasmiditan in triptan non-responders [PMID: 39516789]
- Khoo CC et al., J Headache Pain 2024 - menstrual migraine meta-analysis [PMID: 39227797]
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