Explain How to Approach Migraine

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Approach to Migraine

Migraine pathophysiology — trigeminovascular system, CSD, and pain pathways

1. Understanding the Condition

Definition & Epidemiology

Migraine (from Greek hemikranios, "half head") is a primary headache disorder affecting ~12% of the general population — 18% of women and 6% of men. It ranks among the WHO's most disabling medical conditions worldwide, with lifetime prevalence of 33% in women and 13% in men. Peak prevalence is in the 4th decade. Attacks occur 1–4 times/month in most patients (episodic migraine); 2% of the population has chronic migraine (≥15 headache days/month, ≥8 fulfilling migraine criteria). (Bradley and Daroff's Neurology in Clinical Practice)

2. The Four Phases of a Migraine Attack

Phase	Timing	Features
Premonitory	Hours–days before	Fatigue, mood changes, yawning, food cravings, neck stiffness
Aura	~1 hr before headache	Visual (scintillating scotoma, zigzag lines), sensory (marching paresthesias), motor, speech
Headache	4–72 hours	Unilateral, pulsating, moderate–severe; photophobia, phonophobia, nausea/vomiting
Postdrome	After headache	Fatigue, cognitive fog, mood changes — may last 24–48 hrs

Osmophobia, though not part of formal IHS criteria, is highly specific for migraine when present.

3. Diagnostic Criteria (ICHD-3)

Migraine Without Aura — at least 5 attacks meeting:

Duration 4–72 hours
≥2 of: unilateral, pulsating, moderate/severe intensity, aggravated by routine activity
During headache ≥1 of: nausea/vomiting or photophobia + phonophobia

Migraine With Aura — same criteria plus fully reversible aura with ≥3 of: ≥1 aura symptom spreading gradually, each symptom lasting 5–60 min, at least one unilateral aura symptom, positive symptom (flickering lights) or negative (scotoma), onset within 60 min of headache.

Special subtypes to recognize:

Basilar-type migraine — aura from brainstem/bilateral hemispheres: dysarthria, vertigo, tinnitus, diplopia, bilateral paresthesias
Hemiplegic migraine — reversible hemiplegia during aura (linked to CACNA1A, ATP1A2, SCN1A gene mutations)
Chronic migraine — ≥15 headache days/month for >3 months
Status migrainosus — continuous migraine >72 hours

4. Pathophysiology

Cortical spreading depression propagation in migraine aura

The trigeminovascular system is central to migraine pain:

Cortical Spreading Depression (CSD) — a slowly propagating wave of neuronal/glial depolarization (~3–5 mm/min, moving anteriorly from the occipital lobe) underlies the aura and triggers trigeminal activation.
Activation of trigeminal nerve terminals around meningeal vessels causes release of CGRP (calcitonin gene-related peptide), substance P, and neurokinin A → neurogenic inflammation of dural vessels → pain signal transmitted via the trigeminal nucleus caudalis (TNC) → thalamus → cortex.
Serotonin (5-HT) from the dorsal raphe nucleus and norepinephrine from the locus coeruleus modulate pain processing and descending pain inhibition.
Central sensitization (allodynia — pain from normally non-painful stimuli like brushing hair or light touch) develops during prolonged attacks, reflecting activation of second- and third-order trigeminal neurons.
Genetics: Familial hemiplegic migraine is autosomal dominant; common migraine is polygenic with ~44 susceptibility loci identified by GWAS, enriched in smooth/vascular tissue and synaptic regulation genes.

5. Diagnostic Workup

Most patients do NOT need testing — migraine is a clinical diagnosis.

Red flags requiring imaging/workup (secondary headache exclusion):

Thunderclap onset ("worst headache of life") → SAH
New headache after age 50
Progressive/worsening pattern
Neurological deficits not typical of known aura
Fever, meningismus
Headache with Valsalva, exertion, or positional change

When indicated:

MRI brain (preferred over CT for most non-acute settings)
Blood tests: TSH, ESR/CRP (to exclude temporal arteritis)
LP if SAH suspected and CT negative
MR angiography/venography if vascular cause suspected

6. Management

A. Non-Pharmacological (Always First-Line)

Identify and avoid triggers: alcohol, caffeine (or withdrawal), hormonal contraceptives, nitrates, aged cheese, chocolate, missed meals, sleep disruption, strong odors, weather changes, stress
Maintain regular sleep, meals, exercise, hydration
Stress management (CBT, biofeedback, relaxation training)
Headache diary — essential for tracking frequency, triggers, medication use

B. Acute (Abortive) Pharmacotherapy

The choice of abortive agent is based on attack severity:

Mild–Moderate Attacks:

Drug	Dose	Notes
Aspirin 900 mg + metoclopramide	At onset	First-line; antiemetic improves absorption
Ibuprofen 400–600 mg	At onset	Effective, widely available
Naproxen sodium 500–825 mg	At onset	Longer-acting NSAID
Acetaminophen 1000 mg	At onset	Less effective alone; useful in pregnancy

Moderate–Severe Attacks — Triptans (5-HT1B/1D agonists):

Triptan	Dose	Route
Sumatriptan	25–100 mg PO / 6 mg SC / 20 mg intranasal	Gold standard; SC fastest onset
Rizatriptan	10 mg PO	Faster onset than sumatriptan PO
Zolmitriptan	2.5–5 mg PO or nasal	Good efficacy
Eletriptan	20–40 mg PO	Longer half-life; fewer recurrences
Naratriptan	2.5 mg PO	Slower onset; lower recurrence rate

Triptans are contraindicated in: hemiplegic migraine, basilar migraine, ischaemic heart disease, uncontrolled hypertension, prior stroke/TIA.

CGRP Receptor Antagonists (Gepants) — newer class:

Ubrogepant, rimegepant — oral, effective without vasoconstrictive side effects; useful when triptans are contraindicated or poorly tolerated

Antiemetics (also enhance analgesia):

Metoclopramide 10 mg IV/IM, prochlorperazine 10 mg IV — first-line in ED; also have direct antimigraine effect
Domperidone 10 mg — useful for nausea + enhances oral drug absorption

For severe/refractory attacks (ED setting):

IV prochlorperazine or metoclopramide + diphenhydramine (reduce akathisia)
IV ketorolac 30 mg
IV valproate sodium
Dexamethasone 10 mg IV (reduces recurrence)
Avoid opioids — risk of medication overuse headache and hyperalgesia

Status Migrainosus (>72 hrs):

IV dihydroergotamine (DHE) + antiemetic — highly effective
Short course IV methylprednisolone
Inpatient admission often required

C. Preventive (Prophylactic) Pharmacotherapy

Indications for initiating prophylaxis:

≥4 migraine days/month with significant disability
≥8 headache days/month (regardless of disability)
Attacks unresponsive to acute therapy
Contraindications to acute medications
Medication overuse headache (>10–15 days/month of analgesic use)
Special subtypes (hemiplegic, basilar, or migrainous infarction)

First-line agents:

Drug Class	Examples	Target
Beta-blockers	Propranolol 40–240 mg, metoprolol	Reduces attack frequency 50%+; first-line
Tricyclic antidepressants	Amitriptyline 10–75 mg	Useful with comorbid depression/insomnia
Anticonvulsants	Topiramate 25–100 mg, valproate 500–1500 mg	FDA-approved; topiramate also causes weight loss
Calcium channel blockers	Verapamil, flunarizine	Useful in menstrual migraine
CGRP pathway mAbs (monoclonal antibodies)	Erenumab, fremanezumab, galcanezumab, eptinezumab	SC/IV monthly or quarterly; FDA-approved; highly effective for chronic/refractory migraine

CGRP monoclonal antibodies represent the most significant advance in migraine prevention in decades — they target CGRP or its receptor directly and are well-tolerated with minimal systemic side effects.

Allow 2–3 months to assess efficacy before changing prophylaxis
Continue for at least 6–12 months before considering tapering

D. Non-Pharmacological Preventive Measures

Biofeedback + relaxation training — Level A evidence, comparable to pharmacotherapy
Cognitive behavioral therapy (CBT) — especially effective combined with medications
Transcranial magnetic stimulation (TMS) — FDA-cleared for acute and preventive use
Neuromodulation devices — CEFALY (supraorbital nerve stimulation) approved for prevention
Acupuncture — evidence supports modestly; equivalent to prophylactic drugs in some trials
Magnesium supplementation 400–600 mg/day — particularly for menstrual migraine
Riboflavin (Vitamin B2) 400 mg/day — well-tolerated, modest benefit
Coenzyme Q10 100 mg TID

7. Special Situations

Menstrual Migraine:

Often more severe and refractory
Perimenstrual prophylaxis: naproxen sodium 550 mg twice daily starting 2 days before expected menses, or triptan mini-prophylaxis (frovatriptan 2.5 mg BD for 6 days)

Migraine in Pregnancy:

Triptans and ergotamines generally avoided (limited safety data)
Acetaminophen ± metoclopramide — safest acute options
Magnesium IV (1–2 g) — safe and effective
Prophylaxis: low-dose amitriptyline, metoprolol (with obstetric guidance)

Pediatric Migraine:

Affects 4–10% of school-age children
Ibuprofen 10 mg/kg and paracetamol are first-line
Sumatriptan nasal spray approved ≥12 years
Prophylaxis: amitriptyline, topiramate (FDA-approved in adolescents)

Medication Overuse Headache (MOH):

Occurs with analgesic/triptan use >10–15 days/month for >3 months
Treatment: withdraw the overused medication (may require bridging with naproxen or prednisolone), then establish preventive therapy
Patient education is critical to prevent recurrence

8. When to Refer

Uncertain diagnosis
Frequent (≥4/month) or disabling migraine unresponsive to 2–3 preventive agents
Suspected MOH requiring structured withdrawal
Hemiplegic or basilar migraine
Consideration for CGRP biologics or neuromodulation

Recent Evidence

A 2025 evidence-based guideline in Cephalalgia (Ornello et al., PMID 40277319) consolidates pharmacological recommendations and confirms CGRP-targeting therapies (both gepants for acute treatment and mAbs for prevention) as first-tier options in appropriate patients. A 2024 network meta-analysis in the BMJ (Karlsson et al., PMID 39293828) found that triptans combined with NSAIDs ranked highest for acute migraine relief, and gepants offer a viable alternative with fewer cardiovascular contraindications.

Key takeaway: Migraine management is individualized. The cornerstone is: (1) confirming the diagnosis, (2) identifying and modifying triggers, (3) stratified acute therapy based on severity, and (4) preventive therapy for frequent/disabling attacks — with CGRP-targeting agents now transforming the landscape for refractory cases.

Sources: Bradley and Daroff's Neurology in Clinical Practice; Textbook of Family Medicine 9e; Cummings Otolaryngology; BMJ 2024; Cephalalgia 2025

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