USA 12% Chile 7% Japan 8% Italy 16% Denmark 10% France 8% † Switzerland 13% Rasmussen and Olesen (1994); Rasmussen (1995); Lipton et al ( 1994); Lavados and Tenhamm (1997); Sakai and Igarashi (1997) † Prevalence measured over a few years
Prevalence of migraine by sex and age 30 25 20 15 10 5 0 20 30 40 50 60 70 80 100 Migraine prevalence (%) Age (years) Lipton and Stewart (1993) The American Migraine Study ( n =2479 migraine sufferers) Females Males
Migraine with aura (MA) Headache Classification Committee of IHS (1988)
At least five attacks fulfilling these criteria:
Headache lasting 4–72 h
(2–48 h in children)
At least two attacks fulfilling these criteria:
At least three of the following:
one or more fully reversible aura symptoms
gradually developing or sequential aura symptoms
no one aura symptom lasts longer than 1 h
headache shortly follows or accompanies aura
Accompanied by at least one of:
photophobia and/or phonophobia
No evidence of organic disease
With at least two of:
aggravated by activity
No evidence of organic disease
Clinical features of migraine Sleepy Anorexia nausea Vomiting yawning Phonophobia Photophobia Phonophobia Photophobia Osmophobia Osmophobia Vomiting Deep sleep Headache III IV Headache Resolution Blau (1992) I II Normal Prodromes Aura Normal Appetite Awake/sleep Light tolerance Smell Noise Fluid balance Craving Tired yawning Heightened perception Fluid retention V Postdromes Normal Limited Light tolerance Noise Smell Fluid balance Tired Feeling high or low Diuresis Appetite Awake/sleep food tolerance Normal
IMPORTANT DIAGNOSTIC CONSIDERATIONS Recurring moderate to severe headache is migraine until proven otherwise 15% of patients have a neurological aura IHS criteria do not require GI symptoms Vomiting occurs in < 1/3 of patients 41% of migraine patients report bilateral pain 50% of the time, pain is non-pulsating Russell MB, et al. Cephalalgia . 1996. Pryse-Phillips WEM, et al. Can Med Assoc J . 1997. No single criterion necessary nor sufficient for diagnosis
Silberstein and Lipton (1994); Lance (1993); Blau (1992)
Occur in MA (20% patients)
spots or flashes
Occurs in 90% patients
Symptoms can persist for several days
MIGRAINE WITH AURA (FORMERLY “CLASSIC” MIGRAINE) Visual > sensory > motor, language, brainstem Gradual evolution: 5–20 minutes (<60 minutes) May or may not be associated with headache Complex array of symptoms reflecting focal cortical or brainstem dysfunction International Headache Society. Cephalalgia. 1988;8;(suppl 7):1-96.
REASONS FOR MISDIAGNOSIS OF MIGRAINE AS TTH OR SINUS Sinus Up to 50% of migraine patients report their headaches are influenced by weather 45% of migraine patients report attack related ‘sinus’ symptoms including lacrimation, rhinorrhea, nasal congestion Tension-Type Headache 75% of migraine patients report posterior neck pain/tightness/stiffness during attacks Stress/anxiety frequent migraine trigger Migraine is bilateral in up to 40% of patients Raskin NH. Headache. 2nd ed. 1988; Barbanti P, et.al. Cephalalgia. 2001; Kaniecki R. Cephalalgia . 2001. Migraine is a referred pain syndrome (V1, C1-C3)
Differential diagnosis of primary headaches Dubose et al (1995); Goadsby (1999); Marks and Rapoport (1997) Family history Yes Sex More females Onset Variable Location Usually unilateral in adults Character/severity Pulsatile Throbbing Frequency/ 2–72 h/attack duration 1 attack/year to >8 per month Associated Visual aura symptoms Phonophobia Photophobia Pallor Nausea/vomiting Clinical feature Migraine No More males During sleep Behind/around one eye Excruciating/ sharp Steady 15–90 min/attack 1–8 attacks/day for 3–16 weeks 1–2 bouts/year Sweating Facial flushing Nasal congestion Ptosis Lacrimation Conjunctival injection Pupillary changes Cluster headache Yes More females Under stress Bilateral in band around head Dull Persistent Tightening/pressing 30 min to 7 days 3–4 attacks/week to 1–2 attacks/year Mild photophobia Mild phonophobia Anorexia Tension headache
WORRISOME HEADACHE RED FLAGS “SNOOP” O lder: new onset and progressive headache, especially in middle-age >50 (giant cell arteritis) S ystemic symptoms (fever, weight loss) or S econdary risk factors (HIV, systemic cancer) N eurologic symptoms or abnormal signs (confusion, impaired alertness, or consciousness) O nset: sudden, abrupt, or split-second P revious headache history: first headache or different (change in attack frequency, severity, or clinical features)
LUMBAR PUNCTURE Headache associated with fever, confusion, meningism, or seizures Thunderclap headache with negative CT head Subacute progressive headache High or low CSF pressure suspected (even if papilledema is absent) The first unusually severe headache Evans RE, Rozen TD, Adelman JU. In: Wolff’s Headache And Other Head Pain . 2001.
SENSITIVITY OF CT SCAN IN SUBARACHNOID HEMORRHAGE (SAH) van Gijn J, van Dongen KJ. Neuroradiology . 1982. Kassell NF et al. J Neurosurg. 1990. TIME AFTER HEADACHE ONSET PROBABILITY (%) DAY 0 95 DAY 3 80 1 WEEK 50 2 WEEKS 30 3 WEEKS ~0
Herpes encephalitis High and low intracranial pressure syndromes MRA = magnetic resonance angiography. MRV = magnetic resonance venography. Bousser MG et al; Wall M et al; Mokri B; and Newman C, Solomon S. In: Wolff’s Headache And Other Head Pain . 2001 . Tien RD et al. AJR Am J Roentgenol. 1993 .
CEREBRAL VENOUS SINUS THROMBOSIS Bousser MG et al. In: Wolff’s Headache And Other Head Pain . 2001 .
STRATEGIES FOR MIGRAINE TREATMENT Preemptive treatment Migraine trigger time-limited and predictable Preventive Treatment Decrease in migraine frequency warranted Acute treatment To stop pain and prevent progression Silberstein SD. Cephalalgia . 1997.
ACUTE MIGRAINE TREATMENT Discuss problems that arise in the acute management of migraine Evaluate the general principles of treatment Review the clinical evidence for acute treatment alternatives Present an approach for selecting and sequencing acute therapies Objectives
The benefits of behavioral therapy (eg, biofeedback, relaxation) are in addition to preventive drug therapy (eg, propranolol, amitriptyline): GRADE B Goslin RE et al. Behavioral and Physical Treatments for Migraine Headache . 1999.
GROUP 1a: Substantial empirical evidence and pronounced clinical benefit in migraine Silberstein SD. Neurology . 2000.
SC, IM, IN, IV (plus antiemetic)
ACUTE THERAPIES FOR MIGRAINE GROUP 2: Moderate empirical evidence and clinical benefit
Acetaminophen, aspirin, plus caffeine
Silberstein SD. Neurology . 2000. GROUP 1b: Substantial empirical evidence of clinical benefit in restricted populations
CONSIDERATIONS IN INITIAL ACUTE THERAPY As disability increases, nonspecific treatments less likely to work In the most severely afflicted 25% of migraine sufferers, an NSAID-metoclopramide combination is successful in only 25% of patients Try to get the treatment “right” the first time
Match treatment intensity to attack severity (stratified care)
Ask about migraine disability and impact
Silberstein SD. Neurology . 2000.
Trigeminovascular model of migraine Efferent Adapted from Goadsby and Olesen (1996) Dura mater Afferent Trigeminal ganglion Peptide releasing neurones Dura mater Efferent Trigeminal nerve Afferent Blood vessels Efferent CGRP/SP release Dilatation Cranium
Mechanisms for treatment CGRP NK SP 5-HT 1F 5-HT 1D 5-HT 1B Blood vessel Trigeminal nerve Adapted from Goadsby (1997) CGRP calcitonin gene related peptide NK neurokinin A SP substance P triptan CONSTRICTION INHIBITION
Headache responses continue to improve over time after eletriptan dosing Time course for headache response 0 20 40 60 80 100 0 1 2 3 4 Time post dose (h) n =563 Pfizer, data on file % Patients with response Placebo 20 mg eletriptan 40 mg eletriptan Study 314 ** P <0.05 vs placebo for all doses 80 mg eletriptan ** ** **
ACUTE TREATMENT PRINCIPLES Early intervention Use correct dose and formulation Use a maximum of 2 – 3 days/week Use preventive therapy in selected patients stratified care Silberstein SD. Neurology . 2000; Lipton RB, et al. JAMA . 2000.
STEP VS. STRATIFIED CARE Start Start A B C A B C
Escalate treatment to zolmitriptan if ASA + M fails 2/3 or 3/3
Stratification based on disability
MIDAS Grade II — ASA + M
MIDAS Grade III, IV — Triptan (zolmitriptan)
Step care within attacks
ASA + M Assess response at 2 hours
Rescue with zolmitriptan prn
Stratified care produces better headache response less disability time Disability can be used to predict treatment needs Compared 3 strategies of migraine management over 6 attacks Lipton RB et al. JAMA. 2000.
TREAT MIGRAINE WHEN PAIN IS MILD Retrospective analysis of 3 studies confirmed triptan treatment while pain is mild provided higher pain-free response at 2 h than ergotamine plus caffeine or aspirin plus metoclopramide, and reduced need for redosing Prospective rizatriptan study of 1919 patients confirms triptan effectiveness at all levels of pain but enhanced benefit if taken while pain is mild Post-hoc analysis of Spectrum study (26 patients) showed sumatriptan provided more effective relief with less recurrence when taken while pain was still mild Cady RK et al. Headache . 2000; Cady RK et al. Clin Ther . 2000; Hu XH et al. Headache . 2002.
TRIPTANS IN THE SPECTRUM OF MIGRAINE In patients with migraine, sumatriptan effectively treats all 3 types In patients with pure TTH, sumatriptan is not effective In migraine sufferers TTH, has a migraine-like mechanism, whereas pure TTH has a different mechanism Therefore, sumatriptan can effectively treat TTH in migraine sufferers, probably because it is a form of mild migraine Patients with disabling migraine have different headache types, including migraine, migrainous, and tension-type headache (TTH) Lipton et al. Headache. 2000; Cady RK et al. Cephalalgia. 1997.
RECURRENCE & REBOUND Rebound: Recurring headache induced by repetitive and chronic overuse of acute headache medication
Recurrence: Return of episodic headache during the same attack following acute treatment
Prevention: Treat early, add NSAID. Use long duration triptan or DHE
Treatment: Repeat initial acute headache drug; almost always effective
Tfelt-Hansen P et al. Drugs . 2000; Capobianco DJ et al. Headache . 2001.
APPROACH TO DIFFICULT HEADACHE PROBLEMS Problem Strategy Headache recurrence Treat earlier, add NSAID, increase dose, change triptans (consider naratriptan or frovatriptan), or switch to DHE Elderly Use acetaminophen, COX 2 inhibitors, opioids, atypical neuroleptics Pregnancy Use acetaminophen, opioids, corticosteroids, neuroleptics Adverse effects Switch triptans, use a different class
Lack of response
Treat earlier, increase dose, add metoclopramide or NSAID, change formulation or triptan. Add preventive. Silberstein SD et al. Wolff’s Headache and Other Head Pain . 2001.
SUMMARY OF ACUTE MIGRAINE MANAGEMENT Identify coexistent conditions that influence therapy Make a specific, credible diagnosis and communicate it Assess migraine severity and it’s impact on the patient Determine the patient’s preferences and needs (eg, fast relief, adverse effects tolerance) Develop a therapeutic partnership with realistic expectations Create plan based on migraine type and severity, as well as patient’s needs, preferences, and comorbidities Consider need for preventive treatment
MIGRAINE ADDITIONAL FEATURES Abatement with sleep Stereotyped premonitory symptoms Characteristic triggers Positive family history Childhood precursors (motion sickness, episodic vomiting, episodic vertigo) Osmophobia Predictable timing around menstruation (or ovulation) Pryse-Phillips WEM, et al. Can Med Assoc J . 1997.
UNDIAGNOSED MIGRAINE SUFFERERS OFTEN RECEIVE OTHER MEDICAL DIAGNOSES Lipton RB et al. Headache . 2001.
AURA: MIMICS AND SECONDARY CAUSES TIA Carotid artery dissection Venous sinus thrombosis Vasculitis Tumor Simple partial seizure AVM Bousser MG et al. In: Wolff’s Headache And Other Head Pain . 2001; Campbell JK, Sakai F. In: The Headaches . 2000; Silberstein SD, Lipton RB, Goadsby PJ. Headache in Clinical Practice . 2002.
LATE-LIFE MIGRAINE ACCOMPANIMENTS VS TIA Mild headache in 50% Progression from one accompaniment to another Repetition ( 2 similar attacks) Duration 15 – 25 minutes Characteristic midlife flurry of attacks Build up of scintillations — “march” of paresthesias Fisher CM. Can J Neurol Sci . 1980; Silberstein SD, Saper JR, Freitag FG. In: Wolff’s Headache And Other Head Pain . 2001.
MIGRAINE AND STROKE Clinical manifestations of underlying disease (MELAS, CADASIL) Causal Comorbid Coexistent Bousser MG et al. In: Wolff’s Headache And Other Head Pain . 2001 .
GUIDELINES: WHEN TO USE PREVENTIVE MANAGEMENT Uncommon migraine conditions Acute medications contraindicated, ineffective, intolerable AEs, or overused Frequent headache ( 2 attacks per week) Patient preference Cost considerations Silberstein SD et al. Wolff’s Headache And Other Head Pain . 2001. Migraine significantly interferes with patient’s daily routine, despite acute R x
GOALS OF PREVENTIVE TREATMENT Improve responsiveness to acute R x Improve function and decrease disability Silberstein SD et al. Headache in Clinical Practice . 2nd ed. 2002. Decrease attack frequency (by 50%), intensity, and duration
GENERAL PRINCIPLES OF PREVENTIVE TREATMENT Assess Coexisting Conditions Be aware of drug interactions Do not use migraine drug if contraindicated for other condition Do not use drug for other condition that exacerbates migraine Special concern for women of childbearing potential Silberstein SD et al. Headache in Clinical Practice . 2nd ed. 2002. Select drug to treat both disorders
COMORBID AND COEXISTENT CONDITIONS Coexistent disorders are commonly present
Avoid -blockers with depression, asthma, or hypotension
Silberstein SD et al. Headache in Clinical Practice . 2nd ed. 2002.
Treat two disorders with a single drug
Hypertension or angina — use -blocker
Depression — use TCAs or SSRIs
Epilepsy or mania — use divalproex or topiramate
PREVENTIVE TREATMENT: DRUG CHOICE COMORBID CONDITION DRUG EFFICACY* SIDE EFFECTS* RELATIVE CONTRAINDICATION RELATIVE INDICATION Anticonvulsants Divalproex 4+ 2+ Liver disease, bleeding disorders Mania, epilepsy, impulse control Topiramate 3+ 2+ Kidney stones Epilepsy, mania, neuropathic pain Gabapentin 2+ 2+ Epilepsy, neuropathic pain Antidepressants TCAs 4+ 2+ Mania, urinary retention, heart block Other pain disorders, depression, anxiety disorders, insomnia SSRIs 2+ 1+ Mania Depression, OCD MAOIs 2+ 4+ Unreliable patient Refractory depression Silberstein SD et al. Headache in Clinical Practice . 2nd ed. 2002. Gray RN et al. Drug Treatments for the Prevention of Migraine . 1999. *On a scale of 0 to 4
PREVENTIVE TREATMENT: DRUG CHOICE COMORBID CONDITION DRUG EFFICACY* SIDE EFFECTS* RELATIVE CONTRAINDICATION RELATIVE INDICATION Antiserotonin Methysergide 4+ 4+ Angina, PVD Orthostatic hypotension -Blockers 4+ 2+ Asthma, depression, CHF, Raynaud’s disease, diabetes HTN, angina Calcium channel blockers Verapamil 2+ 1+ Constipation, hypotension Migraine with aura, HTN, angina, asthma Silberstein SD et al. Headache in Clinical Practice . 2nd ed. 2002. Gray RN et al. Drug Treatments for the Prevention of Migraine . 1999. *On a scale of 0 to 4
PREVENTIVE TREATMENT: DRUG CHOICE COMORBID CONDITION DRUG EFFICACY* SIDE EFFECTS* RELATIVE CONTRAINDICATION RELATIVE INDICATION NSAIDs Naproxen 2+ 2+ Ulcer disease, gastritis Arthritis, other pain disorders Other Riboflavin 2+ 1+ Preference for natural products Feverfew Botulinum Toxin A 2+ 2+ 2+ 1+ Myasthenia gravis Dystonia or Spasticity *On a scale of 0 to 4 Silberstein SD et al. Headache in Clinical Practice . 2nd ed. 2002. Gray RN et al. Drug Treatments for the Prevention of Migraine . 1999.
Limit acute drug use to prevent drug-induced headache
Certain drugs require caution or cannot be used together
Acute medications may have more benefit
Breakthrough attacks need treatment Silberstein SD. Cephalalgia . 1997. Preventive treatment does not eliminate all attacks
CAUTIONS IN ACUTE MEDICATION USE Silberstein SD. Cephalalgia . 1997. PREVENTIVE CAUTION CONTRAINDICATION Methysergide Ergots, Triptans MAOIs Sumatriptan (subcutaneous) and zolmitriptan Meperidine, Midrin, sumatriptan (po, IN) and rizatriptan Propranolol Rizatriptan NSAIDs Other NSAIDs or ASA Divalproex Butalbital
NONPHARMACOLOGIC TREATMENT: POTENTIAL INDICATIONS Poor tolerance, response, or contraindications to drug therapy Pregnancy, planned pregnancy, or nursing History of overuse Significant life stress or deficient stress-coping skills Goslin RE et al. Behavioral and Physical Treatments for Migraine Headache . 1999. Patient preference
SUMMARY OF PREVENTION Use preventive medications when needed Treat long enough Avoid acute medication overuse Take coexisting conditions into account Use drug with the best efficacy for individual patient