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Treatment of Migraine

Migraine is the second most common cause of primary headache.

More common in females than males Has a genetic influence

Migraine
Classically described as an intense throbbing/pulsatile headache in one side of the head and is commonly accompanied by nausea, vomiting, and extreme sensitivity to light and sound.

Some migraines are preceded or accompanied by sensory warning symptoms (aura), such as flashes of light, blind spots or tingling in arms or legs. Migraine with aura Migraine without aura

Visual aura

Migraine

Headaches

Complex neurological disorder

Pathogenesis of Migraine

The classic 'vascular' theory (Wolff)

The 'brain' hypothesis (Lauritzen, 1987)

The 'inflammation' hypothesis (Waeber &

Moskowitz, 2005)

Vascular theory of migraine

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Cortical Spreading Depression Central Nociceptive Dysmodulation

The 'inflammation' hypothesis

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M e n i n g e a l

v e s s e l s

5HT 1B/1D receptor Trigeminal Nerve

Afferent nerve fibres

Pain !!!
Neurokinin A CGRP Substance P

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Factors precipitating Migraine

Bright or flickering lights

Bright sunlight, glare Computer overuse, incorrect use Loud sounds Pollution Strong smells, e.g. perfume, gasoline, chemicals, smoke-filled rooms, various food odours Travel, travel-related stress, high altitude, flying Weather changes

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Factors precipitating Migraine

Chocolate Citrus fruits Caffeine (in some people) some dairy products (aged cheeses and cultured products) Monosodium glutamate (MSG) nitrates and nitrites found in processed meats such as sausage Aspartame (artificial sweetener)

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Factors precipitating Migraine

Lack of, or too much, sleep

Health problems such as eye and dental problems, sinusitis, colds and flu; spinal problems, and high blood pressure
Sudden, excessive or vigorous exercise Sexual intercourse Blows to the head (footballers migraine) Emotional triggers such as arguments, excitement, stress and muscle tension Relaxation after stress (weekend headache)

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Anything can trigger a migraine !

Each patient will be more prone to be affected by specific triggers

Identify them & avoid !

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Keep a diary to identify triggers

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Diagnosis

Clinical criteria

Treatment of migraine
Non Pharmacological Therapy

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Pharmacological Therapy

Avoid triggers Healthy diet, Regular exercise Avoid alcohol, reduce caffeine Avoid stress Yoga, Medication Biofeedback

Acute abortive therapy

Preventive therapy

Non Specific
NSAIDs Antiemetics

Specific
Triptans Ergot alkaloids

Anti convulsants Beta blockers Tricyclic antidepressants Calcium channel blockers Others

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Non pharmacological treatment

Identification and avoidance of specific headache triggers.

A regulated lifestyle is helpful Healthful diet

Regular exercise
Regular sleep patterns Avoidance of excess caffeine and alcohol

Avoidance of acute changes in stress levels.

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Non specific treatment Pain relief

Drug Ibuprofen Naproxen Diclofenac Aspirin Paracetamol Ketorolac Butorphanol nasal spray Dose 400 mg PO q34h 220550 mg PO bid 50 mg q 12 h 300 600 mg qid 500 mg qid 60 mg IM,30 mg IV 1 mg (1 spray in 1 nostril) Emergency dept. Acute or rescue Moderate to severe migraine, emergency dept, rescue therapy First line for mild to moderate migraine Comments

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Anti emetics

Drug

Dose & Route

Metoclopramide
Promethazine

10 mg IV/IM/oral
25 mg - 50 mg IM, IV

Prochlorperazine

10 mg IV

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Non specific treatment

Non specific treatment works only in mildmoderate cases and efficacy is less. Overuse can cause medication overuse headache

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Specific Pharmacological therapy

Acute abortive treatment

Triptans Ergot alkaloids

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Triptans

Drugs:
Sumatriptan Naratriptan Rizatriptan Eletriptan Zolmitriptan Almotriptan Frovatriptan

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Mechanism of action

Triptans

M e n i n g e a l

v e s s e l s

5HT 1B/1D receptor Trigeminal Nerve

Afferent nerve fibres

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Sumatriptan

50-100 mg oral (fast release tablets)

5-20 mg nasal spray 6 mg subcutaneous injection

Transdermal Patch

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Contraindications

Current/history of: ischemic cardiac, cerebrovascular, or peripheral vascular syndromes (angina, MI, stroke, TIA, ischemic bowel disease)

Uncontrolled hypertension
Within 24 hours of ergot medications Severe hepatic impairment

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Side effects

Paraesthesia (6-10%)
Chest, Jaw or neck tightness (1-5%) Fatigue (1-5%)

Warm/cold sensation (1-5%)

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Ergot alkaloids

Derived from the fungus Claviceps purpurea

Acts on multiple receptors. , 5-HT, dopamine receptors

Mainly acts by vasoconstriction of cerebral blood vessels

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Ergotamine - 2 mg sublingual tablet

(max 3 per day, 5 per week)

Ergotamine 1 mg + caffeine 100 mg - One or two tablets at onset (max 6 per day, 10 per week)
Dihydroergotamine Nasal spray Dihydroergotamine s.c./i.m.

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Ergotamine + Caffeine ??

Caffeine is a vasoconstrictor
Hastens the action of ergotamine (faster absorption & rapid onset of action)

Decreases the GI side effects

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Contraindications

Hypersensitivity

Peripheral Vascular Disease/ Ischemic diseases

Raynaud's phenomenon Pregnancy/lactation

Impaired renal or hepatic function,

Severe Hypertension Concomitant strong CYP3A4 inhibitors

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Side effects

Nausea & Vomiting

Increase in Blood pressure Gangrene

Myocardial infarction
Abortion Severe fatigue

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Risk: Systemic vasoconstriction !!!

Never combine triptans & ergot alkaloids together or within 24 hours of each other

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Risk: Systemic vasoconstriction !!!

Triptans & Ergot alkaloids have daily & weekly dose limits. Never exceed.

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Which formulation?

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Points to ponder

Currently available drugs target cerebral vessels and not the pain centres
Implication: Not 100 % effective and efficacy decreases if time to start therapy is delayed (central nociceptive demodulation has already occurred) Acute abortive therapy has serious side effects on cumulative dose. What if the migraine attack frequency is more? Over use of abortive treatment can cause Medication overuse headache

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Prophylaxis

Anticonvulsants

Calcium channel blockers

Valproic acid Topiramate Gabapentin Propranolol Amitriptyline Dothiepin Nortriptyline

Flunarizine Verapamil

Beta blockers

Methysergide Pizotifen Clonidine

Tricyclic antidepressants

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Severity of migraine

Mild migraine: 1 attack/month, less intense < 8 hrs

Moderate migraine: 1-2 attack/month, more intense, 6-24 hours Severe migraine: 3 to more attacks/month, 12-24 hrs

MIDAS questionnaire

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Mechanism of these drugs not clearly understood

Takes 2 6 weeks for onset of clinical benefit

Reduces the frequency & severity of acute attacks

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Key points

Acute attack: Start treatment early

Preferably do not use the oral route. Nausea & Vomiting interfere with the absorption of drugs. Parenteral formulations act fast. Never combine triptans & ergot alkaloids together or within 24 hours of each other

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Thank you

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