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Treating Migraines Professor Yasser Metwally www.yassermetwally.com World prevalence of migraine Denmark 10% Switzerland 13% France 8%† USA 12% Italy 16% Chile 7% †Prevalence measured over a few years Japan 8% 1-year prevalence rates Population-based studies IHS criteria (or modified) Rasmussen and Olesen (1994); Rasmussen (1995); Lipton et al (1994); Lavados and Tenhamm (1997); Sakai and Igarashi (1997) Prevalence of migraine by sex and age Migraine prevalence (%) 30 Females Males 25 20 15 10 5 0 20 30 40 50 60 Age (years) 70 The American Migraine Study (n=2479 migraine sufferers) 80 100 Lipton and Stewart (1993) Diagnosis of migraine Diagnosis depends on patient history No specific tests or clinical markers for migraine Positive diagnosis if attack history fulfils IHS criteria for migraine Other pointers include: – – – – family history of migraine age of onset <45 presence of aura menstrual association Organic disease must be excluded Cady (1999); Warshaw et al (1998) Migraine Criteria 5 attacks lasting 4–72 h 2 of the following 4 – – – – Unilateral Pulsating Moderate or severe intensity Aggravation by routine physical activity 1 of the following – – Nausea and/or vomiting Photophobia and phonophobia Not attributable to another disorder SULTANS: two from column A, one from column B evere ni ateral hrobbing Ctivity worsens ausea Lite and sound ensitivity What is migraine? Migraine without aura (MO) At least five attacks fulfilling these criteria: Headache lasting 4–72 h (2–48 h in children) With at least two of: – – – – unilateral location pulsating quality moderate/severe intensity aggravated by activity Accompanied by at least one of: – nausea – vomiting – photophobia and/or phonophobia No evidence of organic disease Migraine with aura (MA) 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 No evidence of organic disease Headache Classification Committee of IHS (1988) Clinical features of migraine Normal Headache Appetite Awake/sleep Normal food tolerance Appetite Tired Awake/sleep Light tolerance Feeling high or Noise Light tolerance Noise low Smell Smell Diuresis Fluid balance Normal I II Prodromes Aura III IV Headache Resolution V Postdromes Fluid balance Normal Blau (1992) Migraine Patients Suffer From Pain and Symptoms Moderate to severe pain 99% 81% Photophobia 77% Phonophobia Nausea 74% Vomiting 30% 0 20 40 60 80 100 Percentage of patients reporting symptom Adapted from Lipton et al. Headache. 2001. Migraine Remains Underdiagnosed and Undertreated Percentage of patients 100 75 50 49% 48% 23% 25 23% 5% 0 MD diagnosis Rx medication only OTC medication only Both Rx and OTC No medication Lipton et al. Neurology. 2002. IMPORTANT DIAGNOSTIC CONSIDERATIONS No single criterion necessary nor sufficient for diagnosis 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 Recurring moderate to severe headache is migraine until proven otherwise Russell MB, et al. Cephalalgia. 1996. Pryse-Phillips WEM, et al. Can Med Assoc J. 1997. Premonitory, aura and postdromal symptoms Prodrome Occurs in 60% Alterations in – of attacks mood – alertness – appetite Originate in hypothalamus and frontal lobes Aura Occur in MA (20% patients) Visual symptoms – blurring, rippling – spots or flashes – fortification spectra – scotoma Sensory symptoms – numbness/tingling Motor symptoms – hemiparesis Postdrome Occurs in 90% patients Symptoms can persist for several days – lethargy – exhaustion – impaired concentration – irritability – sluggishness – diminished appetite – euphoria Silberstein and Lipton (1994); Lance (1993); Blau (1992) MIGRAINE WITH AURA (FORMERLY “CLASSIC” MIGRAINE) Complex array of symptoms reflecting focal cortical or brainstem dysfunction Gradual evolution: 5–20 minutes (<60 minutes) May or may not be associated with headache Visual > sensory > motor, language, brainstem International Headache Society. Cephalalgia. 1988;8;(suppl 7):1-96. MIGRAINE AURA “Cheiro-oral” Fortification Spectrum DIAGNOSIS AND TESTING Detailed History and Examination NO Primary Headache? Preliminary Diagnosis YES Secondary Headache Diagnostic Testing Atypical Features Alice in Wonderland REASONS FOR MISDIAGNOSIS OF MIGRAINE Sinus AS TTH OR SINUS Migraine is a referred pain syndrome (V1, C1-C3) 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. Differential diagnosis of primary headaches Clinical feature Migraine Cluster headache Tension headache Family history Yes No Yes Sex More females More males More females Onset Variable During sleep Under stress Location Usually unilateral in adults Behind/around one eye Bilateral in band around head Character/severity Pulsatile Throbbing Excruciating/ sharp Steady Dull Persistent Tightening/pressing Frequency/ duration Associated symptoms 2–72 h/attack 1 attack/year to >8 per month Visual aura Phonophobia Photophobia Pallor Nausea/vomiting 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 30 min to 7 days 3–4 attacks/week to 1–2 attacks/year Mild photophobia Mild phonophobia Anorexia Dubose et al (1995); Goadsby (1999); Marks and Rapoport (1997) 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) Headache ‘red flags’ First or worst headache Significant change from previous headache pattern – no longer fulfils IHS criteria New onset headache in middle age or later New or progressive headache that lasts for days Precipitation of headache by coughing/sneezing/ bending down Systemic symptoms such as myalgia, fever, malaise, weight loss, scalp tenderness, jaw claudication Focal symptoms, seizures, confusion, impaired conciousness, physical examination Pryse-Phillips abnormalities et al (1997) EVALUATION STRATEGIES “Investigate the Atypical and the Red Flags” SUDDEN ONSET HEADACHE Primary Idiopathic thunderclap headache (TCH) Sexual headache Exertional headache Cough headache Secondary SAH Venous sinus thrombosis Pituitary apoplexy Arterial dissection Meningoencephalitis Acute hydrocephalus Acute hypertension deBruijn, SF, et al. Lancet. 1996; Lancet. 1998. Spontaneous intracranial hypotension LUMBAR PUNCTURE The first unusually severe headache Thunderclap headache with negative CT head Subacute progressive headache Headache associated with fever, confusion, meningism, or seizures High or low CSF pressure suspected (even if papilledema is absent) Evans RE, Rozen TD, Adelman JU. In: Wolff’s Headache And Other Head Pain. 2001. SENSITIVITY OF CT SCAN IN SUBARACHNOID HEMORRHAGE (SAH) TIME AFTER HEADACHE ONSET PROBABILITY (%) DAY 0 95 DAY 3 80 1 WEEK 50 2 WEEKS 30 3 WEEKS ~0 van Gijn J, van Dongen KJ. Neuroradiology. 1982. Kassell NF et al. J Neurosurg. 1990. 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 neurologic symptoms or signs Role of CT or MRI in patients with nonmigraine headache is unclear Consensus expert opinion MRI is more sensitive Report of Quality Standards Subcommittee of AAN. Neurology. 1994. DIAGNOSTIC TESTING ELECTROENCEPHALOGRAPHY EEG is not useful In the routine evaluation of patients with headache to exclude structural cause EEG may be useful in those patients with Alteration or loss of consciousness Residual focal neurologic defects or encephalopathy Atypical migrainous aura Report of Quality Standards Subcommittee of AAN. Neurology. 1995. MR AND CONVENTIONAL ANGIOGRAPHY MR Angiography Angiography Aneurysm (>5 mm) Acute SAH AV malformation CNS vasculitis Arterial dissection Arterial dissection Venous thrombosis (MR venography) Leclerc X et al. Neuroradiology. 1999. INDICATIONS FOR GADOLINIUM ENHANCED MRI Cerebrovascular – – – Arterial dissection (MRA) Cerebral venous sinus thrombosis (MRV) CNS vasculitis Herpes encephalitis 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. Tumors – – – Posterior fossa Pituitary Leptomeninges High and low intracranial pressure syndromes MRA = magnetic resonance angiography. MRV = magnetic resonance venography. CEREBRAL VENOUS SINUS THROMBOSIS Bousser MG et al. In: Wolff’s Headache And Other Head Pain. 2001. Sleepers Awake!! Treatment STRATEGIES FOR MIGRAINE TREATMENT Acute treatment To stop pain and prevent progression Preemptive treatment Preventive Treatment Migraine trigger time-limited and predictable Decrease in migraine frequency warranted Silberstein SD. Cephalalgia. 1997. ACUTE MIGRAINE TREATMENT Objectives Evaluate the general principles of treatment Review the clinical evidence for acute treatment alternatives Present an approach for selecting and sequencing acute therapies Discuss problems that arise in the acute management of migraine PRINCIPLES OF MIGRAINE MANAGEMENT Establish a therapeutic partnership Patient education and behavioral management Nature and mechanism of the disorder Strategies for identifying and avoiding triggers Behavioral strategies Regular sleep, exercise, meals Stress management, biofeedback Cognitive behavioral therapy Pharmacologic management Acute treatment Preventative strategies NONPHARMACOLOGIC TREATMENTS Effective: GRADE A Relaxation training Thermal biofeedback with relaxation training EMG biofeedback Cognitive behavioral therapy Insufficient evidence to recommend: GRADE C Acupuncture TENS Cervical manipulation Occlusal adjustment Hyperbaric oxygen Hypnosis 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. Goals of Treatment Establish diagnosis Educate patient Discuss findings Establish reasonable expectations Involve patient in decisions Encourage Pt to avoid triggers Choose the best treatment (tailoring) Create treatment plan MIGRAINE TRIGGERS Physical exertion Diet Hormonal changes Head trauma Stress and anxiety Sleep deprivation or excess Environmental factors ACUTE MIGRAINE MEDICATIONS Nonspecific NSAIDs Combination analgesics Opioids Neuroleptics/antiemetics Corticosteroids Specific Ergotamine/DHE Triptans ACUTE THERAPIES FOR MIGRAINE GROUP 1a: Substantial empirical evidence and pronounced clinical benefit in migraine Migraine-Specific Medications Triptans DHE Nonspecific Prescription Medications Butorphanol IN Ibuprofen/Naproxen sodium SC, IM, IN, IV (plus antiemetic) Prochlorperazine IV Silberstein SD. Neurology. 2000. ACUTE THERAPIES FOR MIGRAINE GROUP 1b: Substantial empirical evidence of clinical benefit in restricted populations Over-the-Counter Analgesics Aspirin Acetaminophen, aspirin, plus caffeine GROUP 2: Opioids Moderate empirical evidence and clinical benefit Silberstein SD. Neurology. 2000. Others CONSIDERATIONS IN INITIAL ACUTE THERAPY Match treatment intensity to attack severity (stratified care) Ask about migraine disability and impact 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 Silberstein SD. Neurology. 2000. Cranium Dura mater Trigeminovascular model of migraine Afferent Trigeminal ganglion Dura mater Peptide releasing neurones Blood vessels Efferent Trigeminal nerve Afferent Efferent CGRP/SP release Dilatation Adapted from Goadsby and Olesen (1996) Mechanisms for treatment Trigeminal nerve INHIBITION 5-HT1D 5-HT1F CGRP triptan NK SP CGRP calcitonin gene related peptide NK neurokinin A SP substance P CONSTRICTION 5-HT1B Blood vessel Adapted from Goadsby (1997) TRIPTANS Selective 5-HT1B/1D/1F agonists As a class, relative to nonspecific therapies, triptans provide Rapid onset of action High efficacy Favorable side effect profile Adverse events and contraindications Silberstein SD. Neurology. 2000. TRIPTANS: TREATMENT CHOICES Almotriptan Sumatriptan Tablet Tablet (25, 50, 100 mg) Injection (6 mg) Nasal spray (5, 20 mg*) Frovatriptan Tablet Tablet (1, 2.5 mg) Rizatriptan Tablet Tablet (2.5, 5 mg) Nasal spray (5 mg) Naratriptan Tablet (5, 10 mg) * Pediatric efficacy shown (2.5 mg) Eletriptan Zolmitriptan (6.25, 12.5 mg) (20, 40 mg) Question and Answer Are there differences between the triptans? If one triptan fails, will another triptan work? Ferrari MD et al. Lancet. 2001. ROUTES OF ADMINISTRATION Oral therapies: most medications Nasal sprays: sumatriptan, DHE, butorphanol, zolmitriptan Injectable (SL, IM, IV) sumatriptan, DHE, injectable NSAIDs, opioids, neuroleptics Suppositories: antiemetics, ergots, opioids FORMULATION: ONSET Increasing Speed Oral Parenteral Tablet IN SL PR IM/SC IV Sumatriptan Sumatriptan (Glaxo Wellcome) NMe 2 – 5-HT1B/1D agonist MeNHSO 2 N H Major advance – good efficacy with subcutaneous formulation Slow onset (2–4 h p.o.); LogD -1.5 Short t1/2 (2 h) Ferrari et al (1995) Efficacy of Eletriptan: Comprehensive Relief at 2 Hours Placebo Sumatriptan 100 mg Eletriptan 40 mg Headache response, % 80 *† 60 * Pain-free response, % *† 40 Relief of Nausea, % 40 * 30 † * * 80 20 20 10 0 40 20 60 20 20 40 Relief of Photophobia, % *† * 60 80 40 60 * *† Relief of Phonophobia, % 80 Sumatriptan was blinded using encapsulation. Encapsulated sumatriptan was bioequivalent to commercial tablets. *P<.001 vs placebo. †P<.05 vs sumatriptan. Adapted from Mathew et al. Headache. 2003. Incidence of Adverse Events* Placebo 20 mg Eletriptan 40 mg 80 mg (n=988) (n=431) (n=1774) (n=1932) Asthenia 3% 4% 5% 10% Nausea 5% 4% 5% 8% Somnolence 4% 3% 6% 7% Dizziness 3% 3% 6% 7% Headache 3% 4% 3% 4% Paresthesia 2% 3% 3% 4% Dry mouth 2% 2% 3% 4% Chest tightness/pain/pressure 1% 1% 2% 4% *Events experienced by 2% of patients. Incidence following a single dose of study medication. The maximum recommended single dose of eletriptan is 40 mg. Relpax® (eletriptan HBr) Prescribing Information. Data on file. Pfizer Inc., New York, NY. Headache responses continue to improve over time after eletriptan dosing % Patients with response 100 Time course for headache response ** 80 mg eletriptan n=563 80 ** 40 mg eletriptan 20 mg eletriptan 60 ** 40 Placebo 20 0 0 1 Study 314 **P<0.05 vs placebo for all doses 2 3 4 Time post dose (h) Pfizer, data on file ACUTE TREATMENT PRINCIPLES stratified care Early intervention Use correct dose and formulation Use a maximum of 2–3 days/week Use preventive therapy in selected patients Silberstein SD. Neurology. 2000; Lipton RB, et al. JAMA. 2000. STEP VS. STRATIFIED CARE Start A B C C Start B A BASIS OF STRATIFICATION Headache onset and severity Fast onset may benefit from parenteral therapy Disability predicts treatment needs Symptom profile Prominent nausea and vomiting may require parenteral therapy Headache frequency Consider risk of medication overuse Patient history and preferences Consider adverse events and prior experience Silberstein SD. Neurology. 2000. MIDAS Score Days in Last 3 months You’ve missed work or school due to your headaches? Your productivity at work or school reduced by half or more due to your headaches? (Please do not include days you counted in question 1 where you missed work or school) You not do household work because of your headaches? Your productivity in household work reduced by half or more because of your headaches? (Do not include days you counted in question 3 where you did not do household work) You missed family, social or leisure activities because of your headaches? A. Had a Headache? If a headache lasted more than one day count each day. B. On a scale of 1-10 on average how painful were those headaches? (Where 0 is no pain, 10 is as bas as pain could be?? GradeDefinitionScore I Minimal or infrequent disability 0-5 II Mild or infrequent disability 6-10 III Moderate disability 11-20 IV Severe disability 21+ DISABILITY IN STRATEGIES OF CARE (DISC) STUDY Compared 3 strategies of migraine management over 6 attacks 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 Step care across attacks ASA + M Assess response after 3 attacks Escalate treatment to zolmitriptan if ASA + M fails 2/3 or 3/3 Stratified care produces better headache response less disability time Disability can be used to predict treatment needs Lipton RB et al. JAMA. 2000. TREAT MIGRAINE WHEN 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 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 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 Patients with disabling migraine have different headache types, including migraine, migrainous, and tension-type headache (TTH) 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 Lipton et al. Headache. 2000; Cady RK et al. Cephalalgia. 1997. RECURRENCE & REBOUND 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 Rebound: Recurring headache induced by repetitive and chronic overuse of acute headache medication Tfelt-Hansen P et al. Drugs. 2000; Capobianco DJ et al. Headache. 2001. APPROACH TO DIFFICULT HEADACHE PROBLEMS Problem Strategy Lack of response Treat earlier, increase dose, add metoclopramide or NSAID, change formulation or triptan. Add preventive. 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 Silberstein SD et al. Wolff’s Headache and Other Head Pain. 2001. SUMMARY OF ACUTE MIGRAINE MANAGEMENT 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) Identify coexistent conditions that influence therapy 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 Eletriptan Dosing and Administration • RELPAX should be taken at the onset of a migraine headache. • RELPAX can be taken with or without food. • RELPAX should not be used within at least 72 hours of treatment with the following potent CYP3A4 inhibitors: ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir and nelfinavir. • Studies have shown that the pharmacokinetics of eletriptan are generally unaffected by age, gender, or menstrual cycle. Relpax® (eletriptan HBr) Prescribing Information. Pfizer Inc., New York, NY. Eletriptan: Key Clinical Trials Double-blind, Placebo-controlled, Randomized Trials Phase II/III/III-b clinical program 8 trials; N=8105 Placebo 8 trials; n=1508 25 mg 1 trial; n=180 50 mg 2 trials; n=362 Sumatriptan 4 trials; n=1690 100 mg 3 trials; n=1148 Eletriptan 8 trials; n=4704 20 mg 2 trials; n=434 40 mg 8 trials; n=2797 Cafergot® 1 trial; n=203 80 mg 6 trials; n=1473 The maximum recommended single dose of eletriptan is 40 mg. Data on file. Pfizer Inc., New York, NY. Efficacy of Eletriptan: Pain-free at 2 Hours 50 Percentage of patients 40 36%*† 30 27%* 20 10 5% 0 Placebo (n=406) Sumatriptan 100 mg (n=799) Eletriptan 40 mg (n=782) Sumatriptan was blinded using encapsulation. Encapsulated sumatriptan was bioequivalent to commercial tablets. *P<.0001 vs placebo. †P<.001 vs sumatriptan. Adapted from Mathew et al. Headache. 2003. Data on file. Pfizer Inc., New York, NY. Chronic Daily HA Tension (v. migraine) 10 attacks lasting 30 min–7 days 2 of the following 4 – – – – Bilateral Not pulsating Mild or moderate intensity Not aggravated by routine physical activity No nausea or vomiting One or neither photophobia or phonophobia Not attributable to another disorder MIGRAINE ADDITIONAL FEATURES Predictable timing around menstruation (or ovulation) Stereotyped premonitory symptoms Characteristic triggers Abatement with sleep Positive family history Childhood precursors (motion sickness, episodic vomiting, episodic vertigo) Osmophobia Pryse-Phillips WEM, et al. Can Med Assoc J. 1997. UNDIAGNOSED MIGRAINE SUFFERERS OFTEN RECEIVE OTHER MEDICAL DIAGNOSES 32% Tension-type HA 42% Sinus HA 0% 10% Lipton RB et al. Headache. 2001. 20% 30% 40% 50% AURA: MIMICS AND SECONDARY CAUSES AVM Tumor TIA Simple partial seizure Carotid artery dissection Venous sinus thrombosis Vasculitis 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 Build up of scintillations—“march” of paresthesias Progression from one accompaniment to another Repetition (2 similar attacks) Mild headache in 50% Duration 15–25 minutes Characteristic midlife flurry of attacks 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 Coexistent Causal Comorbid Clinical manifestations of underlying disease (MELAS, CADASIL) Bousser MG et al. In: Wolff’s Headache And Other Head Pain. 2001. CADASIL CSF XANTHOCHROMIA AFTER SAH SPECTROPHOTOMETRY TIME AFTER HEMORRHAGE PROBABILITY (%) 12 HOURS 100 1 WEEK 100 2 WEEKS 100 3 WEEKS >70 4 WEEKS >40 Vermeulen M et al. J Neurol Neurosurg Psychiatry. 1989. Preventive Management of Migraine GUIDELINES: WHEN TO USE PREVENTIVE MANAGEMENT Migraine significantly interferes with patient’s daily routine, despite acute Rx Acute medications contraindicated, ineffective, intolerable AEs, or overused Frequent headache (2 attacks per week) Uncommon migraine conditions Cost considerations Patient preference Silberstein SD et al. Wolff’s Headache And Other Head Pain. 2001. GOALS OF PREVENTIVE TREATMENT Decrease attack frequency (by 50%), intensity, and duration Improve responsiveness to acute Rx Improve function and decrease disability Silberstein SD et al. Headache in Clinical Practice. 2nd ed. 2002. Migraine Prevention GENERAL PRINCIPLES OF PREVENTIVE TREATMENT Start low and increase dose slowly Use long-acting formulation if compliance an issue Adequate trial (2–3 months) at an appropriate dosage Avoid interfering, overused, and contraindicated medications Evaluate therapy Use headache calendar (diary) Attempt to taper and discontinue treatment when headaches well controlled Silberstein SD et al. Headache in Clinical Practice. 2nd ed. 2002. PREVENTIVE MEDICATIONS: DRUG CLASSES Anticonvulsants NSAIDs Antidepressants 5-HT antagonists -Blockers Other Ca2+-Channel blockers Silberstein SD. Cephalalgia. 1997. Vitamins Minerals Herbs Botulinum Toxin A GENERAL PRINCIPLES OF PREVENTIVE TREATMENT Assess Coexisting Conditions Select drug to treat both disorders Do not use migraine drug if contraindicated for other condition Do not use drug for other condition that exacerbates migraine Be aware of drug interactions Special concern for women of childbearing potential Silberstein SD et al. Headache in Clinical Practice. 2nd ed. 2002. Comorbidities Depression “SALSA” Sleep Disturbance Anhedonia Low Self-esteem Appetite Change COMORBID AND COEXISTENT CONDITIONS Coexistent disorders are commonly present Therapeutic opportunities Treat two disorders with a single drug Hypertension or angina—use -blocker Depression—use TCAs or SSRIs Epilepsy or mania—use divalproex or topiramate Therapeutic limitations Avoid -blockers with depression, asthma, or hypotension Silberstein SD et al. Headache in Clinical Practice. 2nd ed. 2002. PREVENTIVE TREATMENT: DRUG CHOICE COMORBID CONDITION EFFICACY* SIDE EFFECTS* Divalproex 4+ 2+ Liver disease, bleeding disorders Mania, epilepsy, impulse control Topiramate 3+ 2+ Kidney stones Epilepsy, mania, neuropathic pain Gabapentin 2+ 2+ 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 DRUG RELATIVE CONTRAINDICATION RELATIVE INDICATION Anticonvulsants Epilepsy, neuropathic pain Antidepressants *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. PREVENTIVE TREATMENT: DRUG CHOICE COMORBID CONDITION DRUG EFFICACY* SIDE EFFECTS* RELATIVE CONTRAINDICATION RELATIVE INDICATION 4+ 4+ Angina, PVD Orthostatic hypotension 4+ 2+ Asthma, depression, CHF, Raynaud’s disease, diabetes HTN, angina 2+ 1+ Constipation, hypotension Migraine with aura, HTN, angina, asthma Antiserotonin Methysergide -Blockers Calcium channel blockers Verapamil *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. PREVENTIVE TREATMENT: DRUG CHOICE COMORBID CONDITION EFFICACY* SIDE EFFECTS* 2+ 2+ Riboflavin 2+ 1+ Feverfew Botulinum Toxin A 2+ 2+ 2+ 1+ DRUG RELATIVE CONTRAINDICATION RELATIVE INDICATION NSAIDs Naproxen Ulcer disease, gastritis Arthritis, other pain disorders Other Preference for natural products Myasthenia gravis *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. Dystonia or Spasticity PREVENTIVE TREATMENT: USE OF ACUTE MEDICATION Preventive treatment does not eliminate all attacks Breakthrough attacks need treatment Can use acute and preventive treatment together Limit acute drug use to prevent drug-induced headache Certain drugs require caution or cannot be used together Acute medications may have more benefit Silberstein SD. Cephalalgia. 1997. CAUTIONS IN ACUTE MEDICATION USE PREVENTIVE CAUTION Methysergide Ergots, Triptans MAOIs Sumatriptan (subcutaneous) and zolmitriptan Propranolol Rizatriptan NSAIDs Other NSAIDs or ASA Divalproex Butalbital Silberstein SD. Cephalalgia. 1997. CONTRAINDICATION Meperidine, Midrin, sumatriptan (po, IN) and rizatriptan NONPHARMACOLOGIC TREATMENT: POTENTIAL INDICATIONS Patient preference 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. 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