Download - Managament Of Migraine
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