MANAGAMENT OF MIGRAINE

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

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

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

Migraine Triggers
          

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

Phases of Acute Migraine
   

Prodrome Aura Headache Postdrome

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

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

HEADACHE

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

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

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

MIGRAINE: CLINICAL FEATURES
Migraine Without Aura No aura or Prodrome Migraine With Aura 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 complains of phonophobia and photophobia Patient complains of visual disturbances and may have mood variations

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

NEUROVASCULAR PROCESS

Arterial Activation

Release of Neurotransmitter

Worsening of Pain

MIGRAINE: DIAGNOSIS
Medical History  Headache diary  Migraine triggers  Investigations (only to exclude secondary causes)  EEG  CT Brain  MRI

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 severity Avoiding escalation of headache medication Educating and enabling the patient to manage the disorder Improving the patient’s quality of life

MIGRAINE MANAGEMENT

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

MIGRAINE: ABORTIVE THERAPY
Non-specific treatment
Drug
Aspirin Paracetamol Ibuprofen Diclofenac Naproxen

Dose
500-650 mg 500 mg-4 g 200- 300 mg 50-100 mg 500-750 mg

Route
Oral Oral Oral Oral/IM Oral

ABORTIVE THERAPY FOR MIGRAINE
Specific treatment
Drug
Ergot alkaloids Ergotamine Dihydroergotamine Sumatriptan Rizatriptan 1-2 mg/d; max-6 g/d 0.75-1 mg 25-300 mg 6 mg 10 mg Oral SC Orally SC Orally

Dose

Route

5-HT receptor agonists

ANTI-NAUSEANT DRUGS FOR MIGRAINE TREATMENT
Drug
Domperidone Metoclopramide Promethazine Chlorpromazine

Dose (mg)/d
10-80 mg 5-10 mg 50-125 mg 10-25 mg

Route
Oral Oral/IV Oral/IM Oral/IV

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

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

PREVENTIVE THERAPY FOR MIGRAINE
Drugs
1.

Dose (mg/d) 40-320 10-20 120-480

Betablockers  Propranolol Calcium Channel Blockers  Flunarizine  Verapamil TCAs  Amitriptyline SSRIs  Fluoxetine

2.

3.

10-20 20-60

4.

PREVENTIVE THERAPY FOR MIGRAINE (CONTD.)
Drugs
5.

Dose (mg/d)
600-1200 4-8

Anti-convulsant

Sodium valproate Cyproheptadine

6.

Anti-histaminic

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

ROLE OF PROPRANOLOL IN MIGRAINE PROPHYLAXIS

PROPRANOLOL – MECHANISMS OF
ACTION Mechanisms proposed
  

Vasoconstriction Anxiolytic action Decreased sympathetic activity

LIMITATIONS OF IMMEDIATERELEASE 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

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

PROPRANOLOL-LA CLINICAL EFFICACY IN MIGRAINE

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 3.9* n = 18

Frequency (per month) Side effects

6.1

3.4* n = 27

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

Propranolol long-acting reduces the attack severity
Parameter
Severity score
* p = 0.003

Baseline
11.1

End-period
6.7*

n = 48

Headache 1998; 28: 607-611

Propranolol vs. Flunarizine
70 60 No. of attacks reduced by more than 50% 48 50 50 40 30 20 10 0 Flunarizine (p<0.01) Propranolol (p<0.0005)
Headache 1989; 29: 218-223

% of Patients

Propranolol showed a significant reduction in the severity of attacks
1.8 1.6 1.4 1.2 1 0.8 0.6 0.4 0.2 0 Flunarizine * p<0.05 Propranolol 1.6 1.4 1.2* Baseline 16 weeks 1.6

Severity score

Headache 1989; 29: 218-223

Propranolol significantly reduced the number of analgesics used
No of analgesics/month
7 6 5 4 3 2 1 0 Flunarizine
*p<0.0005

6.3

4.5

4.1

*
3.4 Baseline 16 weeks

Propranolol
Headache 1989; 29: 218-223

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

Propranolol extended-release produces low blood levels as compared to immediaterelease

SHIFTING PATIENT FROM IR TO ER

The dose of the long-acting formulation may need to be higher than the total daily dose of the conventional formulation

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