2012 Chiang Rai

Beyond the frontier of acute migraine therapy
Surat Tanprawate, MD, MSc(London), FRCP(T)
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Division of Neurology, Chiang Mai University

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The Headache, George Cruikshank (1819)
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Why we got headache

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Why we got headache
(2) (1) (3)

(1) primary (2) secondary (3) cranial neuralgia
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Description and Criteria,
Migraine, c/w aura
International Classification of Headache Disorder-II, 2004

1. Primary headache: TTH, migraine, Cluster 2. Secondary headache: Headache attributed to... 3. Cranial neuralgia: e.g., trigeminal neuralgia...

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Leading causes of years of life lived with a disability (YLDs)

Leonardi M. J Headache Pain (2003) 4:S12–S17
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Pathophysiology of acute migraine

Pathophysiology of episodic and chronic migraine


Environmental and factor

episodic become chronic

- Genetic : FHM, TREK -Trigger factor

Pathophysiology - Aura - vasodilatation - neurogenic inflammation - peripheral and central sensitization - Trigemino vascular system Neurotransmitter - Serotonergic system - Dopaminergic system

acute on chronic

Clinical: chronic and transform migraine, allodynia, neck pain Anatomical: PAG, central sensitization

Evolution of Migraine
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Neuroanatomical Processing of Vascular Head Pain

CDS: Cortical Spreading Depression PAG: Periaqueductal gray matter CSD: Cortical spreading depression NRM: Nucleus raphe magnus TG: Trigeminal Ganglia TNC: Trigeminal Nucleus Caudalis

- substance P - Neurokinin A - CGRP - serotonin - glutamate - prostaglandins - inflammatory cytokines

“Peripheral sensitization”
Geoffrey A. Headache 2008

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When headache progress-what happen
Periaqueductal grey matter dysfunction

FEATUREs - neck pain - allodynia - less features of typical migraine
- less throbbing - less N/V - more tension like headache

Central sensitization of Trigeminal nucleus caudalis(TNC)
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How to treat migraine effectively?

Circa 300 AD

Dated 1583
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From papyrus, 2500 BC

Comprehensive treatment plan

• Education, reassurance and life
style modification

• Avoiding triggers to prevent attack • Non-phamacologic treatment • Treating the acute attack • Long-term preventive therapy • Physical and alternative medicine
Silberstein SD. Wolffʼs headache. 2008
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Successful treatment

Episodic Migraine Frequent migraine attack

• Life style modification • Acute migraine

+ Prophylaxis medication

Treatment fail
Inadequate treatment
- Life style modification? - Right drug, dose, duration?

Migraine with co-morbidity
- Psychiatric condition - Sleep condition
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Migraine with MOH

True refractory migraine

use acute medication > 15days/months, > 3 months

failed > 3 preventive medication group

Comprehensive treatment plan

• Education, reassurance and life
style modification

• Avoiding triggers to prevent attack • Non-phamacologic treatment • Treating the acute attack • Long-term preventive therapy • Physical and alternative medicine
Silberstein SD. Wolffʼs headache. 2008
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What do you prescribe when they got headache?

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Pharmacotherapy of acute migraine attack

• Acetaminophen, • NSAIDs • caffeine • opioids • neuroleptic

• Dihydroergotamine • Ergotamine • Triptan


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Non-specific migraine medication:
Analgesics with evidence of efficacy EFNS migraine treatment guideline 2009
Evers, S et al. European Journal of Neurology 2009, 16: 968–981

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• Fixed combination ASA + Paracetamol
+ caffeine more effective than single substance

• selective COX-2 inhibitors
• • •
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Valdecoxib 20-40 mg Celecoxib 400 mg Rofecoxib 25-50 mg


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Cock spur The ergot of Rye

The word “ergot” is derived from “argot”, old French for “cock spur”

Fungus “Claviceps purpurea”
400 BC: ergotism was reported - vasospasm - gangrene - abortion
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1862: ergot use to treat migraine

Specific Medication
• • •

Ergot & Dihydroergotamine

These agents have a strong structural similarity to neurotransmitters, norepilephrine, dopamine(D2), serotonin(5-HT1A, 1B, 1C, 1D, 1F, 2A, 2C, 3, 4) 5-HT1B: constricts the pain-producing intracranial, extracranial blood vessel in the meninges 5-HT1D: presynaptically inhibits trigeminal peptide release and interfere with central trigeminal nucleus caudalis
DHE injection form

Ergotamine tartrate+ Caffeine

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Contraindication of ergot use...
• • • • • • • •
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coronary, cerebral and peripheral vascular disease pregnancy renal or hepatic failure uncontrolled hypertension sepsis hypersensitivity reaction hemiplegic and basilar type migraine migraine with prolong aura

• 5-HT 1B/1D receptor agonists • seven different formulations • options for route of delivery
• • •
oral tablets or melts nasal spray subcutaneous injection

Less side effect than ergotamine

• taken as soon as possible
* i.e. as soon as the patient knows that this is a migraine * if there is aura, take at the start of the headache phase
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Possible Sites of Action of Triptans in the Trigeminovascular System

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Triptan available in Thai market


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Time to peak plasma(h)


Sumatriptan Zolmitriptan Eletriptan

2.5 3.3 1.0-2.0


Evers, S et al. European Journal of Neurology 2009, 16: 968–981

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IM 100 mg tramadol = IM 75 mg diclofenac (80% response rate)

Pethidine; Morphine: highly addictive

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Parenteral acute treatment of migraine for use in clinic or emergency department
DHE Sumatriptan Metoclopamide Chlorpromazine Ketorolac Dexamethasone Valproic acid Magnesium

Up to 1 mg 4, 6 mg 10 mg 25-50 mg 30 mg iv 4-10 mg 500-1000 mg 1g

sc, im, iv sc iv iv im, iv im, iv iv iv
Tepper SJ, Spears RC. Neurol Clin 2009;417-427

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whatʼs drug whatʼs route
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early vs late treatment how to evaluate what need to be concern

Choice and route of therapy
• • • • • • •
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severity and frequency of attack associated symptoms coexistent disorders previous treatment response drugʼs efficacy potential for overuse adverse events

Strategies in acute migraine attack
Step care
treatment is escalated after first-line medication fail

Strategic care
initial treatment is based on measurement of the severity of illness or other factors

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Step vs Stratified care
First series of attack Second series of attack Third series of attack

Migraine diagnosis

First-line Rx (simple analgesic)

Second-line Rx (combination therapy)

Third-line Rx (specific antimigraineous)

Stratified care
Impact questionnaire

High need Moderate need Low need

Migraine diagnosis

Assessment of illness severity


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The Disability in Strategies of Care
(DISC study)

• • •

RCT trail: step vs strategic care Participant: 835 adults Result: Strategic care provides significantly better outcomes than step care strategies within or across attacks as measured by headache response and disability time (52.7% vs 40.6% vs 36.4%, p < 0.001)
Lipton RB, Stewart WF et al. JAMA 2000;284:2599-2605

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Stratified care and migraine assessment
Factors need to be considered

• Frequency • Severity • The present and level of disability • Associated non-headache symptoms
US Headache Consortium Guideline 2007
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Scale used in Chiang Mai Headache Clinic

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Criteria for assessing migraine patient severity
Mild to moderate migraine Headache are almost mild-tomoderate intensity Moderate to severe migraine Headache that frequently develop to moderate or severe in intensity

Non-headache associated Significant non-headache symptoms, if present are not severe associated symptoms, which may in intensity be severe in intensity The impact of the headache on the The impact of the headache on the patientʼs lifestyle is not significant: patientʼs lifestyle is significant: MIDAS Gr. 1 or 2, HIT Gr. I or 2 MIDAS Gr. III or IV (moderate or severe impact) Non-triptan
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Triptan or DHE
Curr Med Res Opin 2002.

Should we advise patients to treat migraine attacks early ? “Early intervention prevents escalation and can increase the effectiveness of the treatment”
Cady RK, Clin Therap 2000; 22: 1035–48. Ferrari MD, Eur Neurol 2005;53(Suppl 1):17-21
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Successful treatment of migraine attack

•Pain free after 2 hours •Improvement of headache from moderate or
severe to mild or none after 2 hours

•Consistent efficacy in two of three attacks •No Headache recurrence and no further drug
intake within 24 hours successful treatment (so-called sustained pain relief or pain free)

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When the drug is ineffective
•at least two attacks should be treated •inadequate response •change the dose •change the route •add adjuvant therapy •change medication
SD Silberstein Lancet 2004; 363: 381–91
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Occipital nerve block technique
Location Occipital protuberanceMastoid process

• •

23-gauge needle Bupivacaine or Lidocaine 2-4 cc

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What need to be concerned ?
Medication Overuse Headache (MOH) Migraine co-morbidities

Long term medication side effect
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Diagnosis: Medication Overuse Headache

Classification using ICHD-IIR
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Paemeleleire K et al. Acta neurol. belg., 2006, 106, 43-51
Sun-Edelstein C et al. Cephalalgia, 2008, 29, 445–452

A man with chronic migraine got addict to medication, diazepam, xanax, diazepam

A CM woman with addict to tramadol, cafergot, and pethidine iv

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Ergotism: Limb ischemia

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A 42 Thai woman with ergotamine overuse (15 tab/day)

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อ.ศิวาพร อ.กัมมันต์

Ravichankra, India

อ.สมศักดิ์ อ.สุพจน์

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