My patient s pain in the head, is a pain in Greg Jicha, M.D., Ph.D.

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1 My patient s pain in the head, is a pain in Greg Jicha, M.D., Ph.D. Kentucky Neurologic Institute University of Kentucky, Lexington, KY

2 Migraine is More Common than Asthma & Diabetes Combined Disease prevalence in the US population 12% 5% 6% 7% 1% Rheumatoid arthritis Asthma Diabetes Osteoarthritis Migraine Data from the Centers for Disease Control and Prevention, US Census Bureau, and the Arthritis Foundation. 2

3 HEADACHE IS AN IMPORTANT PROBLEM FOR NEUROLOGISTS Proportion of Outpatient Visits to Neurologists by Disease 20% 20% Migraine and Headache Epilepsy 55% 17% 4% 3% Alzheimer's Disease Stroke Parkinson's Disease Other IMS Audit. January %

4 WHERE DO MIGRAINE SUFFERERRS SEEK MEDICAL CARE? Primary Care 67% Headache Specialty Care 16% Other 17% Lipton RB et al. Headache

5 AGE- AND GENDER-SPECIFIC PREVALENCE OF MIGRAINE Migraine Prevalence (5) Lipton RB, Stewart WF. Neurology

6 ADJUSTED MIGRAINE PREVALENCE BY HOUSEHOLD INCOME IN THE UNITED STATES Females Males Prevalence Ratio Less than 10,000 10,000 to 19,999 20,000 to 29,999 30,000 to 44,999 45,000 and over 0.0 Less than 10,000 10,000 to 19,999 20,000 to 29,999 30,000 to 44,999 45,000 and over Lipton RB et al. Neurology

7 Migraine Is Associated With Significant Indirect Costs Annual Healthcare Costs per Family 1 Annual Work Loss Days, Employed Families 1 12,000 Migraine Controls 9 Migraine Controls 10,000 8 Annual costs per family ($) 8,000 6,000 4,000 2,000 Days per year Total healthcare costs Indirect costs of migraine total approximately $12 billion annually 2 Direct costs of migraine total approximately $1 billion annually 2 0 Absence Short-term disability Work loss days Workman's comp 1. Stang PE, et al. Am J Manag Care. 2004;10: Hawkins K, et al. J Occup Environ Med. 2007;49:

8 MEDICALLY DIAGNOSED MIGRAINE IS THE TIP OF THE ICEBERG The Migraine Iceberg is Rising Diagnosed 39% Migraine 48% 61% 52% Undiagnosed Migraine Lipton RB et al. Headache

9 PATTERNS OF MEDICATION USE FOR MIGRAINE IN THE US % of IHS Migraine Sufferers None Celentano DD et al. Headache Lipton RB et al. Headache OTC Exclusively Type of Medication R x OTC

10 UNDERTREATMENT OF MIGRAINE Only 29% of migraine sufferers in the US are very satisfied with their usual acute treatment Reasons for Dissatisfaction Pain relief takes too long Does not relieve all the pain Does not always work 87% 87% 85% Headache comes back 71% Too many side effects 35% Lipton RB, Stewart WF. Headache

11 CLINICAL PRESENTATION OF HEADACHES Primary Migraine Tension-type Cluster Other (benign cough headache) Secondary Infection Hemorrhage Increased ICP Brain tumor

12 DIAGNOSIS AND TESTING Detailed History and Examination Preliminary Diagnosis YES Secondary Headache Diagnostic Testing NO Primary Headache? Atypical Features

13 WORRISOME HEADACHE RED FLAGS SNOOP Systemic symptoms (fever, weight loss) or Secondary risk factors (HIV, systemic cancer) Neurologic symptoms or abnormal signs (confusion, impaired alertness or consciousness) Onset: sudden, abrupt, or split-second Older: new onset and progressive headache, especially in middle-age > 50 (giant cell arteritis) Previous headache history: first headache or different (change in attack frequency, severity or clinical features)

14 IHS MIGRAINE AND TENSION TYPE HEADACHE 5 (10) attacks lasting 4-72 hrs (30 min 7 days) 2 of the following 4 Unilateral (bilateral) Pulsating (not pulsating) Moderate or severe intensity (mild or moderate) Aggravation by routine physical activity (not) 1 of the following Nausea and/or vomiting (no nausea/vomiting) Photophobia and phonophobia (one or neither) No evidence on history or examination of disease that might cause headaches

15 THE MIGRAINE SPECTRUM COMMON types Migraine without aura Migraine with aura Migraine aura without headache UNCOMMON types Basilar migraine Familial hemiplegic migraine Migrainous infarction Migraine with prolonged aura

16 MIGRAINE WITHOUT AURA PEDIATRIC 5 attacks lasting (1-48 hrs) Unilateral (bifrontal/bitemporal 60%) Photophobia or phonophobia Winner P et al. Headache

17 MIGRAINE AURA DIFFERENTIAL DIAGNOSIS Clinical Condition AVM TIA Carotid dissection Vasculitis Venous thrombosis Aura Other Causes Late age of onset Vascular risk factors Negative visual symptoms No migraine history Short duration 2-10 min Brief evolution <1 min Tumor Seizure Positive motor symptoms or multicolored spherical or circular visual aura

18 NEUROIMAGING NONACUTE HEADACHE / NORMAL NEUROLOGICAL EXAMINATION HEADACHE TYPE (# STUDIES) n SIGNIFICANT ABNORMALITY PREVALENCE (%) MIGRAINE (11) TTH (2) UNSPECIFIED (10) Headache Consortium Guidelines. Neurology. 2000: in press.

19 Report of Quality Standards Subcommittee of AAN. Neurology DIAGNOSIS TESTING CT AND MRI In patients with recurrent migraine, neither CT nor MRI is warranted except in cases where: Recent substantial change in headache pattern History of seizures Focal neurological symptoms or signs Role of CT or MRI in patients with non-migraine headache is unclear Consensus expert opinion MRI is more sensitive

20 DISORDERS NOT EXCLUDED BY NORMAL CT Vascular Dural venous sinus thrombosis Arterial dissection CNS vasculitis Tumor Posterior fossa lesion (tumor, Chiari malformation) Infiltrative CNS glioma Pituitary tumor/apoplexy Temporal arteritis Infectious Encephalitis Meningitis Sinusitis (Sphenoid) Leptomeningeal cancer Other Idiopathic intracranial hypertension Low-pressure headache syndrome (CSF leak) Isodense subdural hematomas

21 LUMBAR PUNCTURE The first unusually severe headache Thunderclap headache with negative CT head Subacute progressive headache Headache associated with fever, confusion, meningismus or seizures High or low CSF pressure suspected (even if papilledema is absent)

22 ACUTE MIGRAINE MEDICATIONS Nonspecific NSAIDs Combination analgesics Opioids Neuroleptics/antiemetics Corticosteroids Specific Ergotamine/DHE Triptans

23 ACUTE THERAPIES FOR MIGRAINE GROUP 1: Substantial empirical evidence and pronounced clinical benefit Over-The-Counter Analgesics Aspirin Acetaminophen, aspirin, plus caffeine Nonspecific Prescription Medications Butorphanol IN Ibuprofen Naproxen sodium Prochlorperazine IV US Headache Consortium Migraine Specific Medications Triptans Sumatriptan Zolmitriptan Frovatriptan Any-triptan DHE SC, IM, IN, IV (plus antiemetic)

24 Sumatriptan vs Non-Triptans: Pain-Free Results % of Attacks Pain-Free at 2 Hours Ergotamine/Caffeine Sumatriptan 100 mg 69* ASA/Metoclopromide Sumatriptan 100 mg Mild Moderate/Severe Mild Moderate/Severe Ergot/caffeine: Eur Neurol. 1991;31: Aspirin/metoclopramide: Eur Neurol. 1992;32: Cady et al. Clinical Therapeutics. 2000;22(9): *OR=4.4, P<0.0001; OR=3.4, P<0.0001; OR=7.4, P<0.0001; OR=7.9, P<

25 ACUTE THERAPIES FOR MIGRAINE GROUP 2: Moderate empirical evidence and clinical benefit Opioids Acetaminophen plus codeine Butalbital, aspirin, caffeine, plus codeine Butorphanol IM Meperidine IM, IV Methadone IM US Headache Consortium Other Naproxen Flurbiprofen Isometheptene CPD, PO Metoclopramide IV Lidocaine IN Chlorpromazine IM, IV Diclofenac K Ketorolac IM Prochlorperazine IM, PR Ergotamine plus caffeine plus pentobarbital plus Bellafoline

26 ACUTE THERAPIES FOR MIGRAINE GROUP 3: Statistically significant but clinical benefit not established OR Consensus of clinical benefit without empiric evidence Butalbital, aspirin, plus caffeine Ergotamine ± caffeine Metoclopramide IM, PR GROUP 4: Empiric evidence indicating clinically ineffective Acetaminophen Chlorpromazine IM Lidocaine IV GROUP 5: Clinical and statistical benefits unknown Dexamethasone IV Hydrocortisone IV US Headache Consortium

27 ACUTE TREATMENT PRINCIPLES Treat early in attack Use correct dose and formulation Use a maximum of 2-3 days a week Everyone needs acute treatment Add on preventive therapy in selected patients

28 HOW DO ACUTE MEDICATIONS WORK? Trigeminovascular Anti-migraine Targets Hargreaves RJ et al. Can J Neurol Sci (Modified)

29 SUMMARY OF ACUTE MIGRAINE MANAGEMENT Make a specific, credible diagnosis and clearly communicate it Assess the severity of migraine as a disease and the impact of headaches on the patient s life Determine the patient s therapeutic preferences and needs (eg, very fast relief, side effect tolerance) Identify comorbid conditions that influence therapy Develop a therapeutic partnership and realistic expectations Formulate a treatment plan appropriate to the diagnosis and severity of the illness, as well as patient s needs, preferences and comorbidities

30 Trigeminal Nucleus Caudalis Receives Afferent Messages and Acts as a Sensory Relay Center 30

31 MIGRAINE TRIGGERS Physical exertion Diet Hormonal changes Head trauma Stress and anxiety Sleep deprivation or excess Environmental factors

32 Migraine-Precipitating Factors: Triggers Food Alcohol, caffeine, chocolate, monosodium glutamate, tyramine-foods, nitrite-foods (wine) Behavioral/physiologic triggers Too much/little sleep, skipped meal, menstruation, fatigue, physical in/activity Environmental Loud noises, weather changes, fumes, high altitude, glare or flickering lights Snow et al. Ann Inetern Med. 2002; 137:

33 Factors in Determining Therapy Intensity mild, moderate, severe, status Duration Frequency Interference with activities Long-term effects 33

34 Nonpharmacologic Therapy Education!!! Avoid peaks and troughs Regularity! Sleep Meals Exercise Alternatives Biofeedback Relaxation training Acupuncture Cognitive behavioral therapy Stress management Minimize triggers Headache diary Goadsby PJ, Lipton RB, Ferrari MD. Migraine - current understanding and 34

35 Preventative Pharmacotherapy Calcium channel blockers Tricyclic antidepressants Beta blockers Serotonin Antagonists Anticonvulsants Dietary supplements 35

36 When to Consider Prevention Therapy? Individualized Generally: if severe enough to impair quality of life or if 3 attacks per month which fail abortive therapy Depends Frequency, duration, severity Tractability, responsiveness Disability, patient preference Side effect profile of medication # of Attacks per month Migraine diary, risk of rebound 36

37 Preventative AE s Beta-blockers Fatigue, dizziness, sexual dysfunction Antidepressants TCAs Dry mouth, drowsiness, weight gain, constipation Antiepileptics: Divalproex sodium Weight gain, hair loss, nausea, tremor, LFT s Topiramate Cognitive dysfunction and weight loss, glaucoma Gabapentin Drowsiness, weight gain, fatigue, renal Levetiracetam Fatigue, asthenia, dizziness Calcium channel antagonists Methysergide NSAIDs Muscle relaxants Constipation, edema Fibrosis, water retention, leg cramps Dyspepsia, peptic ulcers, renal disease Sedation, dizziness

38 Beta Blockers Efficacy: propranolol mg/day; timolol mg/day Limited data for atenolol, metoprolol, nadolol MOA Modulation of central catecholaminergic system and brain serotonin 1 st line Reduce frequency, intensity, and duration Side Effects Fatigue, bradycardia, hypotension, depression, impotence, bronchospasm Contraindications asthma, COPD, heart block, caution diabetics 38

39 Calcium Channel Blockers Use: decrease frequency Evidence: nifedipine, nimodipine, verapamil (poor quality, difficult to interpret modest effect) Verapamil mg/day (long acting preferred) MOA: likely modulation of neurotransmitters Maximum effect may take several months Side effects Verapamil Constipation, leg swelling, atrioventricular conduction disturbances Contraindications/precautions CHF, arrhythmias, hypotension 39

40 Tricyclic Antidepressants Amitriptyline most studied: mg/day (can be lower in elderly) MOA Central neuromodulator of noradrenaline & serotonin system 1 st line Other concomitant uses Depression, chronic pain, tension headaches Start low and titrate up to decrease side effects Anticholinergic SE, dizziness, drowsiness, postural hypotention, weight gain Nortriptyline = less adverse effects than amitriptyline Contraindications Caution in elderly 40

41 Anticonvulsants Good Evidence: divalproex sodium, sodium valproate Ineffective: carbamazepine Limited data: gabapentin Others = topirmate (Topamax), lamotrigine (Lamictal) 1 st line for severe migraine Decrease severity and duration Use typically with prolonged or atypical migraine Side effects Nausea, weight gain, alopecia, increase LFTs, diarrhea Contraindications Liver disease Monitor (mainly for rare side effects) CBC, Platelets, LFTs 41

42 Dietary Supplements Riboflavin (Vitamin B2) 400 mg/day Magnesium mg/day Butterbur (Petadolex) Feverfew mg/day Goadsby PJ, Lipton RB, Ferrari MD. Migraine - current understanding and 42

43 Failure with Prophylactic Therapy Possibly because: Overuse Inadequate trial time Failure to incorporate non-pharmacologic treatment Combination attempt not made Subtherapeutic dosing 43

44 Summary Use one prophylactic agent at a time Start low Titrate up Minimum of 3 month trial once at effective dose Benefits seen ~1-2 months D/C analgesics causing rebound or daily headache Combination if fail single agent Neuro consult? Duration of treatment: ~9-12 months 44

45 GUIDELINES Snow et al Ann Intern Med 2002; 137: Pharmacologic Management of Acute Attacks of Migraine and Prevention of Migraine Headache Clinical Guidelines 45

46 Recommendation 1 1 st Line For most migraine sufferers NSAIDS Aspirin, ibuprofen, naproxen sodium Combination: acetaminophen + aspirin + caffeine Not acetaminophen alone Snow et al. Ann Inter Med. 2002;137:

47 Recommendation 2 Migraine not responding to NSAIDs Migraine specific agents Triptans Little data on which triptans are more effective DHE Consider PO combination: butorphanol + PO opiate Snow et al. Ann Inter Med. 2002;137:

48 Recommendation 3 Non-oral route Migraine presents early with nausea or vomiting as significant component of symptoms N/V treatment: Antiemetic Or Antiemetic + PO migraine treatment Snow et al. Ann Inter Med. 2002;137:

49 Recommendation 4 Evaluation for preventative therapy Indications 2+ attacks/month that produce disability 3 days/month Contraindication or failure to acute treatment Abortive meds > 2 times/week Uncommon migraine conditions Hemiplegic migraine, migraine with prolong aura, migrainous infarction Snow et al. Ann Inter Med. 2002;137:

50 Recommendation 5 1 st line for prevention Propranolol mg/day Timolol mg/day Amitriptyline mg/day Sodium valproate ( mg/day) Topiramate ( mg/day) Snow et al. Ann Inter Med. 2002;137:

51 Recommendation 6 EDUCATION! Control of acute attacks Preventative therapy Engage them in forming a management plan Re-evaluation regularly Realistic expectations discussion Medication overuse awareness Diary use Snow et al. Ann Inter Med. 2002;137:

52 Questions????????????????????