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.

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

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 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

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

18. THE TREATMENT
APPROACH TO
MIGRAINE

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

21. 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

22. ABORTIVE THERAPY FOR
MIGRAINE
Specific treatment
Drug Dose Route
Ergot alkaloids
Ergotamine 1-2 mg/d; max-6 g/d Oral
Dihydroergotamine 0.75-1 mg SC
5-HT receptor agonists
Sumatriptan 25-300 mg Orally
6 mg 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 > 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

26. PREVENTIVE THERAPY FOR
MIGRAINE
Drugs Dose (mg/d)
1. Betablockers
 Propranolol 40-320
2. Calcium Channel
Blockers 10-20
 Flunarizine
120-480
 Verapamil
3. TCAs
 Amitriptyline 10-20
4. SSRIs
 Fluoxetine 20-60

27. PREVENTIVE THERAPY FOR
MIGRAINE (CONTD.)
Drugs Dose (mg/d)
5. Anti-convulsant
 Sodium valproate 600-1200
6. 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

29. 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

33. PROPRANOLOL-LA
CLINICAL 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 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