migrane

1
MANAGAMENT OF MIGRAINE

• Shiva
• B.Phamacy
• Shiva.pharmacist_at_gmail.com

2
Migraine Facts

• Migraine is one of the common causes of recurrent
  headaches
• According to IHS, migraine constitutes 16 of
  primary headaches
• Migraine afflicts 10-20 of the general
  population
• More than 2/3 of migraine sufferers either have
  never consulted a doctor or have stopped doing so
• Migraine is underdiagnosed and undertreated
• Migraine greatly affects quality of life. The WHO
  ranks migraine among the worlds most disabling
  medical illnesses

3
Burden Of Migraine

• World - 15-20 of women and 10-15 of men suffer
  from migraine
• In India, 15-20 of people suffer from migraine
• Adults Female Male ratio is 2 1
• In childhood migraine, boys and girls are
  affected equally until puberty, when the
  predominance shifts to girls.

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

• Migraine is a familial disorder characterized by
  recurrent attacks of headache widely variable in
  intensity, frequency and duration. Attacks are
  commonly unilateral and are usually associated
  with anorexia, nausea and vomiting
• -World Federation of Neurology

5
Migraine Triggers

• Food
• Disturbed sleep pattern
• Hormonal changes
• Drugs
• Physical exertion
• Visual stimuli
• Auditory stimuli
• Olfactory stimuli
• Weather changes
• Hunger
• Psychological factors

6
Phases of Acute Migraine

• Prodrome
• Aura
• Headache
• Postdrome

7
PRODROME

• Vague premonitory symptoms that begin from 12 to
  36 hours before the aura and headache
• Symptoms include
• Yawning
• Excitation
• Depression
• Lethargy
• Craving or distaste for various foods
• Duration 15 to 20 min

8
AURA

• Aura is a warning or signal before
• onset of headache
• Symptoms
• Flashing of lights
• Zig-zag lines
• Difficulty in focussing
• Duration 15-30 min

9
HEADACHE

• Headache is generally unilateral and is
  associated with symptoms like
• Anorexia
• Nausea
• Vomiting
• Photophobia
• Phonophobia
• Tinnitus
• Duration is 4-72 hrs

10
POSTDROME (RESOLUTION PHASE)

• Following headache, patient complains of
• Fatigue
• Depression
• Severe exhaustion
• Some patients feel unusually fresh
• Duration Few hours or up to 2 days

11
MIGRAINE CLASSIFICATION

• According to Headache Classification
• Committee of the International
• Headache Society, Migraine has been
• classified as
• Migraine without aura (common migraine)
• Migraine with aura (classic migraine)
• Complicated migraine

12
MIGRAINE CLINICAL FEATURES
Migraine Without Aura Migraine With Aura
No aura or Prodrome Aura or prodrome is present
Unilateral throbbing headache may be accompanied by nausea and vomiting Unilateral throbbing headache and later becomes generalised
During headache, patient complains of phonophobia and photophobia Patient complains of visual disturbances and may have mood variations
13
MIGRAINE - PATHOPHYSIOLOGY

• VASCULAR 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 UNDERSTANDING
• Neurovascular process, in which neural events
  result in activation of blood vessels, which in
  turn results in pain and further nerve activation

14
NEUROVASCULAR PROCESS
15
Arterial Activation
Release of Neurotransmitter
Worsening of Pain
16
MIGRAINE DIAGNOSIS

• Medical History
• Headache diary
• Migraine triggers
• Investigations (only to exclude secondary causes)
• EEG
• CT Brain
• MRI

17
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
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THE TREATMENTAPPROACH TO MIGRAINE
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LONG-TERM TREATMENT GOALS FOR THE MIGRAINE
SUFFERER

• Reducing the attack frequency and severity
• Avoiding escalation of headache medication
• Educating and enabling the patient to manage the
  disorder
• Improving the patients quality of life

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MIGRAINE MANAGEMENT

• Non-pharmacological treatment
• Identification of triggers
• Meditation
• Relaxation training
• Psychotherapy
• Pharmacotherapy
• 
  non-specific
• Abortive therapy
• specific
• Preventive therapy

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MIGRAINE ABORTIVE THERAPY
Non-specific treatment
Drug Dose Route
Aspirin 500-650 mg Oral
Paracetamol 500 mg-4 g Oral
Ibuprofen 200- 300 mg Oral
Diclofenac 50-100 mg Oral/IM
Naproxen 500-750 mg Oral
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ABORTIVE THERAPY FOR MIGRAINE
Specific treatment
Drug Dose Route
Ergot alkaloids Ergot alkaloids Ergot alkaloids
Ergotamine 1-2 mg/d max-6 g/d Oral
Dihydroergotamine 0.75-1 mg SC
5-HT receptor agonists 5-HT receptor agonists 5-HT receptor agonists
Sumatriptan 25-300 mg 6 mg Orally SC
Rizatriptan 10 mg Orally
23
ANTI-NAUSEANT DRUGS FOR MIGRAINE TREATMENT
Drug Dose (mg)/d Route
Domperidone 10-80 mg Oral
Metoclopramide 5-10 mg Oral/IV
Promethazine 50-125 mg Oral/IM
Chlorpromazine 10-25 mg Oral/IV
24
WHY THE NEED FOR PROPHYLAXIS ?

• Abortive drugs should not be used more than 2-3
  times a week
• Long-term prophylaxis improves quality of life by
  reducing frequency and severity of attacks
• 80 of migraineurs may require prophylaxis

25
WHEN IS PROPHYLAXIS INDICATED?

• According to the US Headache Consortium
  Guidelines,
• indications for preventive treatment include
• Patients who have very frequent headaches (more
  than 2 per week)
• Attack duration is gt 48 hours
• Headache severity is extreme
• Migraine attacks are accompanied by prolonged
  aura
• Unacceptable adverse effects occur with acute
  migraine treatment
• Contraindication to acute treatment
• Migraine substantially interferes with the
  patients daily routine, despite acute treatment
• Special circumstances such as hemiplegic migraine
  or attacks with a risk of permanent neurologic
  injury
• Patient preference

26
PREVENTIVE THERAPY FOR MIGRAINE
Drugs Dose (mg/d)
Betablockers Propranolol 40-320
Calcium Channel Blockers Flunarizine Verapamil 10-20 120-480
TCAs Amitriptyline 10-20
SSRIs Fluoxetine 20-60
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PREVENTIVE THERAPY FOR MIGRAINE (CONTD.)
Drugs Dose (mg/d)
Anti-convulsant Sodium valproate 600-1200
Anti-histaminic Cyproheptadine 4-8
28
ROLE OF BETA BLOCKERS IN MIGRAINE PROPHYLAXIS

• Gold standard in migraine prophylaxis
• Established efficacy and safety in migraine
  prophylaxis
• Especially preferred if hypertension or anxiety
  co-exist

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ROLE OF PROPRANOLOL IN MIGRAINE PROPHYLAXIS
30
PROPRANOLOL MECHANISMS OF ACTION

• Mechanisms proposed
• Vasoconstriction
• Anxiolytic action
• Decreased sympathetic activity

31
LIMITATIONS OF IMMEDIATE-RELEASE PROPRANOLOL

• Short t½ of 3-5 hrs
• Multiple daily dosing required to maintain
  adequate degree of beta-receptor blockade
  throughout 24 hr
• Poor patient compliance may compromise efficacy

32
ADVANTAGES OF EXTENDED-RELEASE PREPARATION OF
PROPRANOLOL

• Migraine patients are asymptomatic between
  attacks
• Important to minimize number of daily doses
  during prophylactic treatment
• Once-daily administration improves compliance
• Stable drug concentration for 24 hrs

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PROPRANOLOL-LACLINICAL EFFICACY IN MIGRAINE
34
PROPRANOLOL REDUCES THE FREQUENCY OF ATTACKS PER
MONTH IN BOTH COMMON AS WELL AS CLASSIC MIGRAINE
PATIENTS
n 51 Duration 12 weeks
Variable Placebo (run in) Propranolol-LA 160 Propranolol-LA 80
Frequency (per month) 6.1 3.4 3.9
Side effects n 27 n 18
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.

Cephalalgia 1990 10 101-105
p lt 0.001
35
Propranolol long-acting reduces the attack
severity
Parameter Baseline End-period
Severity score 11.1 6.7
p 0.003
n 48
Headache 1998 28 607-611
36
Propranolol vs. Flunarizine
70
No. of attacks reduced by more than 50
60
50
48
50
40
of Patients
30
20
10
0
Flunarizine (plt0.01)
Propranolol (plt0.0005)
Headache 1989 29 218-223
37
Propranolol showed a significant reduction in the
severity of attacks
1.8
1.6
1.6
1.6
1.4
1.4
1.2
1.2
1
Baseline
Severity score
16 weeks
0.8
0.6
0.4
0.2
0
Flunarizine
Propranolol
plt0.05
Headache 1989 29 218-223
38
Propranolol significantly reduced the number of
analgesics used
7
6.3
6

5
4.5
4.1
No of analgesics/month
4
3.4
Baseline
16 weeks
3
2
1
0
Flunarizine
Propranolol
plt0.0005
Headache 1989 29 218-223
39
DOSAGE OF PROPRANOLOL

• Starting dose 40-80 mg once daily
• Max. dose/day 240 mg
• If satisfactory response is not obtained within
  4-6 weeks, after reaching the maximal dose,
  therapy should be discontinued
• Taper slowly to avoid rebound headache and
  adrenergic side effects
• Max. duration 9 to 12 months

40
SHIFTING PATIENT FROM IR TO ER

• Propranolol extended-release produces low blood
  levels as compared to immediate-release
• The dose of the long-acting formulation may need
  to be higher than the total daily dose of the
  conventional formulation