MANAGAMENT OF MIGRAINE

Migraine Facts Migraine is one of the common causes of recurrent Migraine is one of the common causes of recurrent

headachesheadaches According to IHS, migraine constitutes 16% of According to IHS, migraine constitutes 16% of

primary headachesprimary headaches Migraine afflicts 10-20% of the general populationMigraine afflicts 10-20% of the general population More than 2/3 of migraine sufferers either have More than 2/3 of migraine sufferers either have

never consulted a doctor or have stopped doing sonever consulted a doctor or have stopped doing so Migraine is underdiagnosed and undertreated Migraine is underdiagnosed and undertreated Migraine greatly affects quality of life. The WHO Migraine greatly affects quality of life. The WHO

ranks migraine among the world’s most disabling ranks migraine among the world’s most disabling medical illnessesmedical illnesses

Burden Of Migraine

World - 15-20% of women and 10-15% of World - 15-20% of women and 10-15% of men suffer from migrainemen suffer from migraine

In India, 15-20% of people suffer from In India, 15-20% of people suffer from migrainemigraine

Adults – Female: Male ratio is 2 : 1Adults – Female: Male ratio is 2 : 1 In childhood migraine, boys and girls are In childhood migraine, boys and girls are

affected equally until puberty, when the affected equally until puberty, when the predominance shifts to girls.predominance shifts to girls.

NEJM 2002; 346(4): 257-269; XI Congress of the IHS, 2004

Migraine - Definition““Migraine is a familial disorder characterized Migraine is a familial disorder characterized

by recurrent attacks of headache widely by recurrent attacks of headache widely

variable in intensity, frequency and duration. variable in intensity, frequency and duration.

Attacks are commonly unilateral and are Attacks are commonly unilateral and are

usually associated with anorexia, nausea and usually associated with anorexia, nausea and

vomiting”vomiting”

-World Federation of Neurology-World Federation of Neurology

Migraine Triggers

FoodFood

Disturbed sleep patternDisturbed sleep pattern

Hormonal changesHormonal changes

DrugsDrugs

Physical exertionPhysical exertion

Visual stimuli Visual stimuli

Auditory stimuli Auditory stimuli

Olfactory stimuli Olfactory stimuli

Weather changes Weather changes

HungerHunger

Psychological factorsPsychological factors

Phases of Acute Migraine

ProdromeProdrome

AuraAura

HeadacheHeadache

PostdromePostdrome

PRODROME

Vague premonitory symptoms that begin from 12 Vague premonitory symptoms that begin from 12 to 36 hours before the aura and headacheto 36 hours before the aura and headache

Symptoms includeSymptoms include YawningYawning ExcitationExcitation DepressionDepression LethargyLethargy Craving or distaste for various foods Craving or distaste for various foods

Duration – 15 to 20 minDuration – 15 to 20 min

AURAAura is a warning or signal beforeAura is a warning or signal before

onset of headacheonset of headache

SymptomsSymptoms

Flashing of lightsFlashing of lights

Zig-zag linesZig-zag lines

Difficulty in focussingDifficulty in focussing

Duration : 15-30 minDuration : 15-30 min

HEADACHE

Headache is generally unilateral and is associated Headache is generally unilateral and is associated with symptoms like: with symptoms like: Anorexia Anorexia NauseaNausea Vomiting Vomiting PhotophobiaPhotophobia PhonophobiaPhonophobia Tinnitus Tinnitus

Duration is 4-72 hrs Duration is 4-72 hrs

POSTDROME (RESOLUTION PHASE)

Following headache, patient complains ofFollowing headache, patient complains of

FatigueFatigue

DepressionDepression

Severe exhaustionSevere exhaustion

Some patients feel unusually freshSome patients feel unusually fresh

Duration: Few hours or up to 2 daysDuration: Few hours or up to 2 days

MIGRAINE – CLASSIFICATION

According to Headache ClassificationAccording to Headache Classification

Committee of the InternationalCommittee of the International

Headache Society, Migraine has beenHeadache Society, Migraine has been

classified as:classified as:

Migraine without aura Migraine without aura (common migraine) (common migraine)

Migraine with auraMigraine with aura (classic migraine)(classic migraine)

Complicated migraineComplicated migraine

Migraine Without AuraMigraine Without Aura Migraine With AuraMigraine With Aura

No aura or ProdromeNo aura or Prodrome Aura or prodrome is presentAura or prodrome is present

Unilateral throbbing headache Unilateral throbbing headache may be accompanied by nausea may be accompanied by nausea and vomitingand vomiting

Unilateral throbbing headache Unilateral throbbing headache and later becomes generalisedand later becomes generalised

During headache, patient During headache, patient complains of phonophobia and complains of phonophobia and photophobiaphotophobia

Patient complains of visual Patient complains of visual disturbances and may have disturbances and may have mood variationsmood variations

MIGRAINE: CLINICAL FEATURES

MIGRAINE - PATHOPHYSIOLOGYVASCULAR THEORY

Intracerebral blood vessel vasoconstriction – aura

Intracranial/Extracranial blood vessel vasodilation –

headache

SEROTONIN THEORY

Decreased serotonin levels linked to migraine

Specific serotonin receptors found in blood vessels of brain

PRESENT UNDERSTANDINGNeurovascular process, in which neural events result in activation of blood vessels, which in turn results in pain and further nerve activation

NEUROVASCULAR PROCESS

Arterial Activation

Release of Neurotransmitter

Worsening of Pain

MIGRAINE: DIAGNOSIS Medical HistoryMedical History Headache diaryHeadache diary Migraine triggersMigraine triggers Investigations Investigations (only to exclude secondary causes)(only to exclude secondary causes)

EEGEEG CT BrainCT Brain MRIMRI

DIFFERENTIATING COMMON PRIMARY HEADACHES

Strictly unilateral

Tension headaches: Do not have the associated features like nausea, vomiting, photophobia, phonophobia. The muscle contraction leads to headache. Headache quality is of a tightening (non-pulsating) quality. Usually bilateral. Intensity is mild or moderate

Cluster headaches: Severe unilateral pain. Headache associated with lacrimation, nasal congestion, rhinorrhea, facial sweating or eyelid edema. Pain lasts for 15 to 180 minutes. More common in men

THE TREATMENT

APPROACH TO

MIGRAINE

LONG-TERM TREATMENT GOALS FOR THE MIGRAINE SUFFERER

Reducing the attack frequency and Reducing the attack frequency and

severityseverity

Avoiding escalation of headache Avoiding escalation of headache

medicationmedication

Educating and enabling the patient to Educating and enabling the patient to

manage the disordermanage the disorder

Improving the patient’s quality of lifeImproving the patient’s quality of life

MIGRAINE MANAGEMENT Non-pharmacological treatmentNon-pharmacological treatment

Identification of triggersIdentification of triggers MeditationMeditation Relaxation trainingRelaxation training PsychotherapyPsychotherapy

PharmacotherapyPharmacotherapy non-specificnon-specific

Abortive therapy Abortive therapy specificspecific Preventive therapyPreventive therapy

DrugDrug DoseDose RouteRoute

AspirinAspirin 500-650 mg500-650 mg OralOral

ParacetamolParacetamol 500 mg-4 g 500 mg-4 g Oral Oral

MIGRAINE: ABORTIVE THERAPY

Non-specific treatment

Ibuprofen Ibuprofen 200- 300 mg200- 300 mg OralOral

DiclofenacDiclofenac 50-100 mg50-100 mg Oral/IMOral/IM

NaproxenNaproxen 500-750 mg500-750 mg OralOral

ABORTIVE THERAPY FOR MIGRAINE

DrugDrug DoseDose RouteRoute

Ergot alkaloidsErgot alkaloids

ErgotamineErgotamine 1-2 mg/d; max-6 g/d1-2 mg/d; max-6 g/d OralOral

DihydroergotamineDihydroergotamine 0.75-1 mg0.75-1 mg SCSC

5-HT receptor5-HT receptor agonistsagonists

SumatriptanSumatriptan 25-300 mg25-300 mg

6 mg6 mg

OrallyOrally

SCSC

RizatriptanRizatriptan 10 mg10 mg OrallyOrally

Specific treatment

Drug Drug Dose (mg)/dDose (mg)/d RouteRoute

DomperidoneDomperidone 10-80 mg10-80 mg OralOral

MetoclopramideMetoclopramide 5-10 mg5-10 mg Oral/IVOral/IV

PromethazinePromethazine 50-125 mg50-125 mg Oral/IMOral/IM

ChlorpromazineChlorpromazine 10-25 mg10-25 mg Oral/IVOral/IV

ANTI-NAUSEANT DRUGS FOR MIGRAINE TREATMENT

WHY THE NEED FOR PROPHYLAXIS ?

Abortive drugs should not be used more than 2-3 Abortive drugs should not be used more than 2-3

times a weektimes a week

Long-term prophylaxis improves quality of life by Long-term prophylaxis improves quality of life by

reducing frequency and severity of attacks reducing frequency and severity of attacks

80% of migraineurs may require prophylaxis80% of migraineurs may require prophylaxis

WHEN IS PROPHYLAXIS INDICATED?

According to the US Headache Consortium Guidelines,According to the US Headache Consortium Guidelines,indications for preventive treatment include:indications for preventive treatment include: Patients who have very frequent headaches (more than 2 per Patients who have very frequent headaches (more than 2 per

week)week) Attack duration is > 48 hoursAttack duration is > 48 hours Headache severity is extremeHeadache severity is extreme Migraine attacks are accompanied by prolonged auraMigraine attacks are accompanied by prolonged aura Unacceptable adverse effects occur with acute migraine Unacceptable adverse effects occur with acute migraine

treatmenttreatment Contraindication to acute treatmentContraindication to acute treatment Migraine substantially interferes with the patient’s daily routine, Migraine substantially interferes with the patient’s daily routine,

despite acute treatmentdespite acute treatment Special circumstances such as hemiplegic migraine or attacks Special circumstances such as hemiplegic migraine or attacks

with a risk of permanent neurologic injurywith a risk of permanent neurologic injury Patient preferencePatient preference

DrugsDrugs Dose (mg/d)Dose (mg/d)

1.1. BetablockersBetablockers PropranololPropranolol 40-32040-320

2.2. Calcium Channel Calcium Channel BlockersBlockers FlunarizineFlunarizine VerapamilVerapamil

10-2010-20

120-480120-480

3.3. TCAsTCAs AmitriptylineAmitriptyline 10-2010-20

4.4. SSRIsSSRIs FluoxetineFluoxetine 20-60 20-60

PREVENTIVE THERAPY FOR MIGRAINE

DrugsDrugs Dose (mg/d)Dose (mg/d)

5.5. Anti-convulsantAnti-convulsant Sodium valproateSodium valproate 600-1200600-1200

6.6. Anti-histaminicAnti-histaminic CyproheptadineCyproheptadine 4-84-8

PREVENTIVE THERAPY FOR MIGRAINE (CONTD.)

ROLE OF BETA BLOCKERS IN MIGRAINE PROPHYLAXIS

‘‘Gold standard’ in migraine prophylaxisGold standard’ in migraine prophylaxis

Established efficacy and safety in migraine Established efficacy and safety in migraine

prophylaxisprophylaxis

Especially preferred if hypertension or anxiety Especially preferred if hypertension or anxiety

co-existco-exist

ROLE OF PROPRANOLOL IN MIGRAINE PROPHYLAXIS

PROPRANOLOL – MECHANISMS OF ACTION

Mechanisms proposedMechanisms proposed

VasoconstrictionVasoconstriction

Anxiolytic actionAnxiolytic action

Decreased sympathetic activityDecreased sympathetic activity

LIMITATIONS OF IMMEDIATE-RELEASE PROPRANOLOL

Short t½ of 3-5 hrsShort t½ of 3-5 hrs

Multiple daily dosing required to maintain Multiple daily dosing required to maintain

adequate degree of beta-receptor blockade adequate degree of beta-receptor blockade

throughout 24 hrthroughout 24 hr

Poor patient compliance may compromise Poor patient compliance may compromise

efficacyefficacy

ADVANTAGES OF EXTENDED-RELEASE PREPARATION OF PROPRANOLOL

Migraine patients are asymptomatic Migraine patients are asymptomatic

between attacksbetween attacks

Important to minimize number of daily Important to minimize number of daily

doses during prophylactic treatmentdoses during prophylactic treatment

Once-daily administration improves Once-daily administration improves

compliancecompliance

Stable drug concentration for 24 hrsStable drug concentration for 24 hrs

PROPRANOLOL-LACLINICAL EFFICACY

IN MIGRAINE

VariableVariable Placebo (run in)Placebo (run in) Propranolol-LAPropranolol-LA

160160

Propranolol-LA Propranolol-LA

8080

Frequency (per Frequency (per

month)month)

6.16.1 3.4*3.4* 3.9*3.9*

Side effectsSide effects n = 27n = 27 n = 18n = 18

Cephalalgia 1990; 10: 101-105

n = 51Duration = 12 weeks

PROPRANOLOL REDUCES THE FREQUENCY OF ATTACKS PER MONTH IN BOTH COMMON AS WELL AS CLASSIC MIGRAINE PATIENTS

Propranolol-LA 80 mg appears to have adequate prophylactic effect for migraine and may be better tolerated than propranolol-LA 160 mg, which appears to offer no additional benefits.

*p < 0.001

Propranolol long-acting reduces the attack severity

ParameterParameter BaselineBaseline End-periodEnd-period

Severity scoreSeverity score 11.111.1 6.7*6.7*

* p = 0.003

Headache 1998; 28: 607-611n = 48

Propranolol vs. Flunarizine

48 50

0

10

20

30

40

50

60

70

Flunarizine (p<0.01) Propranolol (p<0.0005)

No. of attacks reduced by more than 50%

% o

f Pat

ient

s

Headache 1989; 29: 218-223

Propranolol showed a significant reduction in the severity of attacks

1.6 1.6

1.4

1.2*

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

1.8

Flunarizine Propranolol

Sev

erity

sco

re

Baseline

16 weeks

* p<0.05Headache 1989; 29: 218-223

Propranolol significantly reduced the number of analgesics used

4.5

6.3

4.1

3.4

0

1

2

3

4

5

6

7

Flunarizine Propranolol

Baseline

16 weeks

No

of a

nalg

esic

s/m

onth

*

Headache 1989; 29: 218-223*p<0.0005

DOSAGE OF PROPRANOLOL

Starting dose: 40-80 mg once dailyStarting dose: 40-80 mg once daily Max. dose/day: 240 mgMax. dose/day: 240 mg If satisfactory response is not obtained If satisfactory response is not obtained

within 4-6 weeks, after reaching the within 4-6 weeks, after reaching the maximal dose, therapy should be maximal dose, therapy should be discontinueddiscontinued

Taper slowly to avoid rebound headache Taper slowly to avoid rebound headache and adrenergic side effectsand adrenergic side effects

Max. duration: 9 to 12 monthsMax. duration: 9 to 12 months

SHIFTING PATIENT FROM IR TO ER

Propranolol extended-release produces low Propranolol extended-release produces low

blood levels as compared to immediate-blood levels as compared to immediate-

releaserelease

The dose of the long-acting formulation may The dose of the long-acting formulation may

need to be higher than the total daily dose of need to be higher than the total daily dose of

the conventional formulationthe conventional formulation