migrane

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MANAGAMENT OF MIGRAINE: 

MANAGAMENT OF MIGRAINE Shiva B.Phamacy Shiva.pharmacist@gmail.com

Migraine Facts: 

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: 

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 - 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: 

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: 

Phases of Acute Migraine Prodrome Aura Headache Postdrome

PRODROME: 

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

POSTDROME (RESOLUTION PHASE): 

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 : 

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 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 MIGRAINE: CLINICAL FEATURES

MIGRAINE - PATHOPHYSIOLOGY: 

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: 

NEUROVASCULAR PROCESS

PowerPoint Presentation: 

Arterial Activation Release of Neurotransmitter Worsening of Pain

MIGRAINE: DIAGNOSIS: 

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

DIFFERENTIATING COMMON PRIMARY HEADACHES: 

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: 

THE TREATMENT APPROACH TO MIGRAINE

LONG-TERM TREATMENT GOALS FOR THE MIGRAINE SUFFERER: 

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: 

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

MIGRAINE: ABORTIVE THERAPY: 

Drug Dose Route Aspirin 500-650 mg Oral Paracetamol 500 mg-4 g Oral MIGRAINE: ABORTIVE THERAPY Non-specific treatment Ibuprofen 200- 300 mg Oral Diclofenac 50-100 mg Oral/IM Naproxen 500-750 mg Oral

ABORTIVE THERAPY FOR MIGRAINE: 

ABORTIVE THERAPY FOR MIGRAINE 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 6 mg Orally SC Rizatriptan 10 mg Orally Specific treatment

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 ANTI-NAUSEANT DRUGS FOR MIGRAINE TREATMENT

WHY THE NEED FOR PROPHYLAXIS ?: 

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?: 

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 Dose (mg/d) Betablockers Propranolol 40-320 Calcium Channel Blockers Flunarizine Verapamil 10-20 120-480 TCAs Amitriptyline 10-20 SSRIs Fluoxetine 20-60 PREVENTIVE THERAPY FOR MIGRAINE

PREVENTIVE THERAPY FOR MIGRAINE (CONTD.): 

Drugs Dose (mg/d) Anti-convulsant Sodium valproate 600-1200 Anti-histaminic Cyproheptadine 4-8 PREVENTIVE THERAPY FOR MIGRAINE (CONTD.)

ROLE OF BETA BLOCKERS IN MIGRAINE PROPHYLAXIS: 

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: 

ROLE OF PROPRANOLOL IN MIGRAINE PROPHYLAXIS

PROPRANOLOL – MECHANISMS OF ACTION: 

PROPRANOLOL – MECHANISMS OF ACTION Mechanisms proposed Vasoconstriction Anxiolytic action Decreased sympathetic activity

LIMITATIONS OF IMMEDIATE-RELEASE PROPRANOLOL: 

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

ADVANTAGES OF EXTENDED-RELEASE PREPARATION OF PROPRANOLOL: 

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-LA CLINICAL EFFICACY IN MIGRAINE

PROPRANOLOL REDUCES THE FREQUENCY OF ATTACKS PER MONTH IN BOTH COMMON AS WELL AS CLASSIC MIGRAINE PATIENTS: 

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 Cephalalgia 1990; 10: 101-105 n = 51 Duration = 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: 

Propranolol long-acting reduces the attack severity Parameter Baseline End-period Severity score 11.1 6.7* * p = 0.003 Headache 1998; 28: 607-611 n = 48

Propranolol vs. Flunarizine: 

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% % of Patients Headache 1989; 29: 218-223

Propranolol showed a significant reduction in the severity of attacks: 

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 Severity score Baseline 16 weeks * p<0.05 Headache 1989; 29: 218-223

Propranolol significantly reduced the number of analgesics used: 

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 analgesics/month * Headache 1989; 29: 218-223 *p<0.0005

DOSAGE OF PROPRANOLOL: 

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

SHIFTING PATIENT FROM IR TO ER: 

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