This document provides information on the management of migraines. It defines migraines and discusses their prevalence, burden, triggers, phases, and classification. It also covers the pathophysiology of migraines and outlines approaches to diagnosis, abortive treatment, and preventive treatment including medications like propranolol. Propranolol is positioned as the gold standard preventive treatment and its mechanisms of action, formulations, efficacy, dosage, and advantages over immediate-release versions are detailed.
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Migrane
1. MANAGAMENT OF
MIGRAINE
Shiva
B.Phamacy
Shiva.pharmacist@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 world’s 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
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 Unilateral throbbing headache
may be accompanied by nausea and later becomes generalised
and vomiting
During headache, patient Patient complains of visual
complains of phonophobia and disturbances and may have
photophobia 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
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
19. 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 patient’s quality of life
20. MIGRAINE MANAGEMENT
Non-pharmacological treatment
Identification of triggers
Meditation
Relaxation training
Psychotherapy
Pharmacotherapy
non-specific
Abortive therapy
specific
Preventive therapy
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 > 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 patient’s daily
routine, despite acute treatment
Special circumstances such as hemiplegic migraine or
attacks with a risk of permanent neurologic injury
Patient preference
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
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
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 Propranolol-LA
160 80
Frequency (per 6.1 3.4* 3.9*
month)
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.
*p < 0.001 Cephalalgia 1990; 10: 101-105
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
48 50
50
% of Patients
40
30
20
10
0
Flunarizine (p<0.01) Propranolol (p<0.0005)
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*
Severity score
1.2
1 Baseline
0.8 16 weeks
0.6
0.4
0.2
0
Flunarizine Propranolol
* p<0.05
Headache 1989; 29: 218-223
38. Propranolol significantly reduced the
number of analgesics used
7
6.3
No of analgesics/month
6
5 4.5 *
4.1
4 3.4 Baseline
3 16 weeks
2
1
0
Flunarizine Propranolol
*p<0.0005 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