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  1. 1. MANAGAMENT OF MIGRAINE Shiva B.PhamacyShiva.pharmacist@gmail.com
  2. 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. 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. 4. Migraine - Definition“Migraine is a familial disorder characterizedby recurrent attacks of headache widelyvariable in intensity, frequency and duration.Attacks are commonly unilateral and areusually associated with anorexia, nausea andvomiting” -World Federation of Neurology
  5. 5. Migraine Triggers Food Disturbed sleep pattern Hormonal changes Drugs Physical exertion Visual stimuli Auditory stimuli Olfactory stimuli Weather changes Hunger Psychological factors
  6. 6. Phases of Acute Migraine Prodrome Aura Headache Postdrome
  7. 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. 8. AURAAura is a warning or signal beforeonset of headacheSymptoms Flashing of lights Zig-zag lines Difficulty in focussingDuration : 15-30 min
  9. 9. HEADACHE Headache is generally unilateral and is associated with symptoms like:  Anorexia  Nausea  Vomiting  Photophobia  Phonophobia  Tinnitus Duration is 4-72 hrs
  10. 10. POSTDROME (RESOLUTION PHASE)Following headache, patient complains of Fatigue Depression Severe exhaustion Some patients feel unusually freshDuration: Few hours or up to 2 days
  11. 11. MIGRAINE – CLASSIFICATIONAccording to Headache ClassificationCommittee of the InternationalHeadache Society, Migraine has beenclassified as: Migraine without aura (common migraine) Migraine with aura (classic migraine) Complicated migraine
  12. 12. MIGRAINE: CLINICAL FEATURES Migraine Without Aura Migraine With AuraNo aura or Prodrome Aura or prodrome is presentUnilateral throbbing headache Unilateral throbbing headachemay be accompanied by nausea and later becomes generalisedand vomitingDuring headache, patient Patient complains of visualcomplains of phonophobia and disturbances and may havephotophobia mood variations
  13. 13. MIGRAINE - PATHOPHYSIOLOGYVASCULAR THEORYIntracerebral blood vessel vasoconstriction – aura Intracranial/Extracranial blood vessel vasodilation –headacheSEROTONIN THEORYDecreased serotonin levels linked to migraine Specific serotonin receptors found in blood vessels of brainPRESENT UNDERSTANDINGNeurovascular process, in which neural events result inactivation of blood vessels, which in turn results in painand further nerve activation
  15. 15. Arterial ActivationRelease ofNeurotransmitter Worsening of Pain
  16. 16. MIGRAINE: DIAGNOSIS Medical History Headache diary Migraine triggers Investigations (only to exclude secondary causes)  EEG  CT Brain  MRI
  17. 17. DIFFERENTIATING COMMON PRIMARY HEADACHES Strictly unilateralTension headaches: Do not have the associated features like nausea,vomiting, photophobia, phonophobia. The muscle contraction leads toheadache. Headache quality is of a tightening (non-pulsating) quality. Usuallybilateral. Intensity is mild or moderateCluster headaches: Severe unilateral pain. Headache associated withlacrimation, nasal congestion, rhinorrhea, facial sweating or eyelid edema.Pain lasts for 15 to 180 minutes. More common in men
  19. 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. 20. MIGRAINE MANAGEMENT  Non-pharmacological treatment  Identification of triggers  Meditation  Relaxation training  Psychotherapy  Pharmacotherapy non-specific  Abortive therapy specific  Preventive therapy
  21. 21. MIGRAINE: ABORTIVE THERAPY Non-specific treatment Drug Dose Route Aspirin 500-650 mg Oral Paracetamol 500 mg-4 g OralIbuprofen 200- 300 mg OralDiclofenac 50-100 mg Oral/IMNaproxen 500-750 mg Oral
  22. 22. ABORTIVE THERAPY FOR MIGRAINESpecific treatment Drug Dose RouteErgot alkaloidsErgotamine 1-2 mg/d; max-6 g/d OralDihydroergotamine 0.75-1 mg SC5-HT receptor agonistsSumatriptan 25-300 mg Orally 6 mg SCRizatriptan 10 mg Orally
  23. 23. ANTI-NAUSEANT DRUGS FORMIGRAINE TREATMENT Drug Dose (mg)/d RouteDomperidone 10-80 mg OralMetoclopramide 5-10 mg Oral/IVPromethazine 50-125 mg Oral/IMChlorpromazine 10-25 mg Oral/IV
  24. 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. 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. 26. PREVENTIVE THERAPY FORMIGRAINE Drugs Dose (mg/d)1. Betablockers  Propranolol 40-3202. Calcium Channel Blockers 10-20  Flunarizine 120-480  Verapamil3. TCAs  Amitriptyline 10-204. SSRIs  Fluoxetine 20-60
  27. 27. PREVENTIVE THERAPY FOR MIGRAINE (CONTD.) Drugs Dose (mg/d)5. Anti-convulsant  Sodium valproate 600-12006. Anti-histaminic  Cyproheptadine 4-8
  28. 28. ROLE OF BETA BLOCKERS INMIGRAINE PROPHYLAXIS ‘Gold standard’ in migraine prophylaxis Established efficacy and safety in migraine prophylaxis Especially preferred if hypertension or anxiety co-exist
  30. 30. PROPRANOLOL – MECHANISMS OF ACTIONMechanisms proposed Vasoconstriction Anxiolytic action Decreased sympathetic activity
  31. 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. 32. ADVANTAGES OF EXTENDED-RELEASEPREPARATION 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. 34. PROPRANOLOL REDUCES THE FREQUENCY OF ATTACKS PER MONTH IN BOTH COMMON AS WELL AS CLASSIC MIGRAINE PATIENTS n = 51 Duration = 12 weeksVariable Placebo (run in) Propranolol-LA Propranolol-LA 160 80Frequency (per 6.1 3.4* 3.9*month)Side effects n = 27 n = 18Propranolol-LA 80 mg appears to have adequate prophylacticeffect for migraine and may be better tolerated thanpropranolol-LA 160 mg, which appears to offer no additionalbenefits. *p < 0.001 Cephalalgia 1990; 10: 101-105
  35. 35. Propranolol long-acting reduces the attack severityParameter Baseline End-periodSeverity score 11.1 6.7** p = 0.003 n = 48 Headache 1998; 28: 607-611
  36. 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. 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. 38. Propranolol significantly reduced the number of analgesics used 7 6.3No 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. 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. 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