Medication for migraine
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migraine pharmacological treatment
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Migraine Medications
Migraine pharmacotherapy divides into two categories: acute (abortive) treatment for ongoing attacks, and prophylactic (preventive) treatment to reduce attack frequency. The choice depends on attack frequency, severity, disability, and comorbidities.
Acute (Abortive) Treatment
1. Non-specific Analgesics (mild-to-moderate attacks)
These are the first step for less severe attacks:
| Drug | Notes |
|---|---|
| Aspirin | Well-tolerated, available OTC |
| Ibuprofen / Naproxen | NSAIDs; effective, especially combined with triptans |
| Acetaminophen | Useful if NSAIDs are contraindicated |
| Acetaminophen + isometheptene + dichloralphenazone (Midrin) | 2 caps at onset, max 5 caps/12 hr; causes less nausea |
| Ketorolac (IV/IM) | 15-30 mg IV/IM q6h; useful in ED settings |
Caffeine added to analgesics aids absorption, causes mild vasoconstriction, and may reduce serotonergic brainstem neuron firing, enhancing efficacy.
2. Triptans - 5-HT1B/1D Receptor Agonists (the mainstay for moderate-to-severe attacks)
Triptans are selective serotonin agonists at 5-HT1B receptors (cranial vessel constriction) and 5-HT1D receptors (inhibit sensory neuropeptide release from perivascular trigeminal fibers). They are migraine-specific and significantly more effective than non-specific analgesics for disabling attacks. Treatment should begin as soon as possible after attack onset.
Available triptans and response rates (oral, 2-hour headache response):
| Drug | Dose | 2-hr Response | Recurrence Rate |
|---|---|---|---|
| Sumatriptan (Imitrex) | 25-100 mg oral; 6 mg SC; 20 mg intranasal | 50-56% oral; 75% SC | 35-40% |
| Rizatriptan (Maxalt) | 5-10 mg oral | 60-77% | 10-35% |
| Zolmitriptan (Zomig) | 2.5-5 mg oral or intranasal | 64-66% | 5-31% |
| Eletriptan (Relpax) | 20-40 mg oral | 49-60% | 22-30% |
| Almotriptan (Axert) | 12.5 mg oral | 57% | 23% |
| Frovatriptan (Frova) | 2.5 mg oral | 42% at 2h, 61% at 4h | 10-25% (lowest recurrence) |
| Naratriptan (Amerge) | 1-2.5 mg oral | 42-48% | 17-28% |
Contraindications: Ischemic heart disease, uncontrolled hypertension, history of stroke, hemiplegic/basilar migraine, concomitant ergot use.
When oral triptans are impractical due to nausea/vomiting, subcutaneous or intranasal routes are preferred. Subcutaneous sumatriptan 6 mg gives 70-75% headache response at 1-2 hours.
3. Ergot Alkaloids (older, less commonly used now)
| Drug | Route | Notes |
|---|---|---|
| Ergotamine + caffeine (Cafergot) | Oral | 2 tabs at onset; max 6 tabs/attack or 10 tabs/week |
| Dihydroergotamine (DHE 45, Migranal) | IV, IM, SC, intranasal | DHE SC: 73% headache response at 2h; very low recurrence (18%); preferred for status migrainosus inpatient management |
Ergots are more likely to cause nausea than triptans and carry vasoconstrictor risks. DHE is useful in status migrainosus ("Raskin protocol": 0.5-1.0 mg IV q8h for up to 2-5 days).
4. CGRP-Targeted Agents (newest class)
Calcitonin gene-related peptide (CGRP) is elevated in internal jugular blood during acute migraine attacks and normalizes with sumatriptan treatment. CGRP is now a key target.
Oral gepants (CGRP receptor antagonists) - for acute treatment:
| Drug | Notes |
|---|---|
| Rimegepant | Effective for acute treatment; also used for prevention |
| Ubrogepant | Acute treatment; no vasoconstrictive action, unlike triptans |
Gepants are useful in patients with cardiovascular contraindications to triptans. Side effects include nausea, fatigue, and dry mouth.
5. Lasmiditan (5-HT1F Agonist - "ditan")
A highly selective 5-HT1F agonist. Unlike triptans, it has no vasoconstrictive action, making it a safer option for patients with cardiovascular risk. Oral, half-life ~6 hours. It has potential for abuse/CNS effects (drowsiness, dizziness). Comparable efficacy to triptans in phase III trials.
6. Antiemetics (adjuncts)
When nausea/vomiting are prominent, dopamine D2 antagonists are added and may themselves reduce headache:
- Prochlorperazine (IV/IM) - effective acute migraine treatment in ED settings
- Metoclopramide (IV/IM) - also enhances GI absorption of oral analgesics
- Promethazine
Prophylactic (Preventive) Treatment
Preventive treatment is indicated when attacks occur more than 4 days/month, are severely disabling, or are poorly responsive to acute therapy.
1. Beta-Blockers (first-line)
- Propranolol (most studied): 40-240 mg/day
- Metoprolol, timolol, atenolol also used
- Avoid in asthma, bradycardia, depression
2. Antidepressants
- Amitriptyline (TCA): 10-150 mg at night; particularly useful when comorbid depression or insomnia is present
- Venlafaxine (SNRI): weight-neutral option; useful with comorbid anxiety
- SSRIs are generally not consistently effective for migraine and may worsen headaches
3. Antiepileptics
- Valproic acid/Divalproex sodium: 500-1750 mg/day in divided doses; ~50% of patients achieve 50%+ reduction in migraine frequency. Contraindicated in pregnancy (neural tube defects)
- Topiramate: 75-200 mg/day; titrate slowly (15-25 mg/week); reduces migraine frequency with added benefit of weight loss; side effects include paresthesia, cognitive slowing, kidney stones
- Gabapentin: 900-2400 mg/day; useful if comorbid pain conditions present; well-tolerated
4. Calcium Channel Blockers
- Verapamil: modest preventive efficacy
- Flunarizine (Europe): reduces both attack severity and recurrence
5. Anti-CGRP Monoclonal Antibodies (newest preventives)
These are injected subcutaneously once monthly and are among the most effective preventives available, including in patients who have failed multiple prior treatments.
| Drug | Target |
|---|---|
| Erenumab (Aimovig) | CGRP receptor |
| Fremanezumab (Ajovy) | CGRP peptide |
| Galcanezumab (Emgality) | CGRP peptide |
| Eptinezumab (Vyepti) | CGRP peptide (IV quarterly) |
Indicated per AHS consensus when:
- 4-7 headache days/month + moderate disability: after failing 2 preventive trials
- 8-14 headache days/month: indicated at any disability level after 2 failed trials
- Chronic migraine: after failing 2 oral preventive trials or 2 cycles of onabotulinumtoxinA
Side effects: injection site discomfort, constipation. Long-term (3-year) data have not shown the theoretical vascular adverse effects.
6. OnabotulinumtoxinA (Botox)
Approved specifically for chronic migraine (>15 headache days/month). Injected every 3 months into pericranial and cervical muscles.
7. Nutraceuticals (level B evidence)
- Petasites (butterbur extract): 75 mg twice daily
- Riboflavin (Vitamin B2): 400 mg/day
- Magnesium: 400-600 mg/day
Treatment Strategy Summary
Acute attack:
Mild-moderate → NSAIDs / acetaminophen ± caffeine
Moderate-severe → Triptan (oral/SC/intranasal)
CV contraindication to triptans → Gepant or lasmiditan
With vomiting → Parenteral route + antiemetic
Status migrainosus → IV DHE / IV valproate / IV prochlorperazine
Prevention (≥4 headache days/month or disabling):
1st line: Propranolol, topiramate, valproate, amitriptyline
Refractory: Anti-CGRP mAbs, onabotulinumtoxinA (chronic migraine)
Newer acute dual-use: Rimegepant (acute + prevention)
Note on medication overuse headache (MOH): Acute analgesics, triptans, and ergots used more than 10-15 days/month can paradoxically worsen headache frequency. Patients should be counseled on frequency limits.
Key recent evidence: A 2025 evidence-based guideline from the Italian Society for the Study of Headache and the International Headache Society (Ornello et al., Cephalalgia 2025, PMID 40277321) provides the most current recommendations using the GRADE framework. A 2024 network meta-analysis in the BMJ (Karlsson et al., PMID 39293828) compared all acute interventions and can guide head-to-head drug selection.
Sources: Bradley and Daroff's Neurology in Clinical Practice; Goodman & Gilman's Pharmacological Basis of Therapeutics; Katzung's Basic & Clinical Pharmacology 16e; Textbook of Family Medicine 9e
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