Treating Migraines Professor Yasser Metwally www.yassermetwally.com
World prevalence of migraine <ul><li>1-year prevalence rates </li></ul><ul><li>Population-based studies </li></ul><ul><li>...
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) Lip...
Diagnosis of migraine <ul><li>Diagnosis  depends on patient history </li></ul><ul><li>No specific tests or clinical marker...
Migraine Criteria <ul><li> 5 attacks lasting 4 – 72 h </li></ul><ul><li> 2 of the following 4 </li></ul><ul><ul><li>Unil...
SULTANS: two from column A, one from column B <ul><li>evere </li></ul><ul><li>ni </li></ul><ul><li>ateral </li></ul><ul><l...
What is migraine? <ul><li>Migraine without aura (MO) </li></ul>Migraine with aura (MA) Headache Classification Committee o...
Clinical features of migraine Sleepy Anorexia nausea Vomiting yawning Phonophobia Photophobia Phonophobia Photophobia Osmo...
 
 
IMPORTANT DIAGNOSTIC CONSIDERATIONS Recurring moderate to severe headache is migraine until proven otherwise 15% of patien...
Premonitory, aura and postdromal symptoms <ul><li>Prodrome </li></ul><ul><li>Occurs in 60% of attacks </li></ul><ul><li>Al...
MIGRAINE WITH AURA (FORMERLY “CLASSIC” MIGRAINE) Visual > sensory > motor, language, brainstem Gradual evolution:  5–20 mi...
MIGRAINE AURA “Cheiro-oral”
Fortification Spectrum
DIAGNOSIS AND TESTING Detailed History and Examination <ul><li>Primary Headache? </li></ul><ul><li>Preliminary Diagnosis <...
Alice in Wonderland
REASONS FOR MISDIAGNOSIS OF MIGRAINE AS TTH OR SINUS Sinus Up to 50% of migraine patients report their headaches are influ...
Differential diagnosis of  primary headaches Dubose  et al  (1995); Goadsby (1999); Marks and Rapoport (1997) Family histo...
WORRISOME HEADACHE RED FLAGS “SNOOP” O lder: new onset and progressive headache, especially in middle-age >50 (giant cell ...
Headache ‘red flags’ <ul><li>First or worst headache </li></ul><ul><li>Significant change from previous headache pattern <...
EVALUATION STRATEGIES Red Flags” “ Investigate the Atypical  and the
SUDDEN ONSET HEADACHE Primary Secondary SAH Pituitary apoplexy Venous sinus thrombosis Arterial dissection Meningoencephal...
LUMBAR PUNCTURE Headache associated with fever, confusion, meningism, or seizures Thunderclap headache with negative CT he...
SENSITIVITY OF CT SCAN IN SUBARACHNOID HEMORRHAGE (SAH) van Gijn J, van Dongen KJ.  Neuroradiology . 1982. Kassell NF et a...
DIAGNOSIS TESTING CT AND MRI <ul><li>Consensus expert opinion </li></ul><ul><ul><li>MRI is more sensitive </li></ul></ul>R...
DIAGNOSTIC TESTING ELECTROENCEPHALOGRAPHY <ul><li>EEG may be useful in those patients with </li></ul><ul><ul><li>Alteratio...
MR AND CONVENTIONAL ANGIOGRAPHY MR Angiography Angiography Acute SAH Arterial dissection CNS vasculitis Aneurysm (>5 mm) A...
INDICATIONS FOR GADOLINIUM ENHANCED MRI <ul><li>Cerebrovascular </li></ul><ul><ul><li>Arterial dissection (MRA) </li></ul>...
CEREBRAL VENOUS SINUS THROMBOSIS Bousser MG et al. In:  Wolff’s Headache And Other Head Pain . 2001 .
Sleepers Awake!! Treatment
STRATEGIES FOR MIGRAINE TREATMENT Preemptive   treatment Migraine trigger time-limited and predictable Preventive Treatmen...
ACUTE MIGRAINE TREATMENT Discuss problems that arise in the acute management of migraine Evaluate the general principles o...
PRINCIPLES OF MIGRAINE MANAGEMENT <ul><li>Patient education and behavioral management </li></ul><ul><ul><li>Nature and mec...
NONPHARMACOLOGIC TREATMENTS <ul><li>Insufficient evidence to recommend:  GRADE C </li></ul><ul><ul><li>Acupuncture </li></...
Goals of Treatment <ul><li>Establish diagnosis </li></ul><ul><li>Educate patient </li></ul><ul><li>Discuss findings </li><...
MIGRAINE TRIGGERS Diet Hormonal changes Head trauma Stress and anxiety Sleep deprivation or excess Environmental factors P...
ACUTE MIGRAINE MEDICATIONS <ul><li>Nonspecific </li></ul><ul><ul><li>NSAIDs </li></ul></ul><ul><ul><li>Combination analges...
ACUTE THERAPIES FOR MIGRAINE <ul><li>Nonspecific Prescription Medications </li></ul><ul><ul><li>Butorphanol IN </li></ul><...
ACUTE THERAPIES FOR MIGRAINE GROUP 2:   Moderate empirical evidence and  clinical benefit <ul><li>Opioids    Others </li>...
CONSIDERATIONS IN INITIAL ACUTE THERAPY As disability increases, nonspecific treatments less likely to work In the most se...
Trigeminovascular model of migraine Efferent Adapted from Goadsby and Olesen (1996) Dura mater Afferent Trigeminal  gangli...
Mechanisms for treatment CGRP NK SP 5-HT 1F 5-HT 1D 5-HT 1B Blood vessel Trigeminal  nerve Adapted from Goadsby (1997) CGR...
TRIPTANS <ul><li>  As a class, relative to nonspecific therapies, triptans provide </li></ul><ul><ul><li>Rapid onset of ac...
TRIPTANS: TREATMENT CHOICES <ul><li>Are there differences between the triptans? </li></ul><ul><li>If one triptan fails, wi...
ROUTES OF ADMINISTRATION Suppositories: antiemetics, ergots, opioids Oral therapies: most medications Nasal sprays: sumatr...
FORMULATION: ONSET Increasing Speed Parenteral Oral Tablet SL IN PR IM/SC IV
Sumatriptan <ul><li>Sumatriptan (Glaxo Wellcome)  </li></ul><ul><ul><li>5-HT 1B/1D  agonist </li></ul></ul><ul><li>Major a...
 
 
Headache responses continue to improve over time after eletriptan dosing Time course for headache response 0 20 40 60 80 1...
ACUTE TREATMENT PRINCIPLES Early intervention Use correct dose and formulation Use a maximum of 2 – 3 days/week     Us...
STEP VS. STRATIFIED CARE Start Start A B C A B C
BASIS OF STRATIFICATION <ul><li>Symptom profile </li></ul><ul><ul><li>Prominent nausea and vomiting may require parenteral...
MIDAS Score Days in Last 3 months <ul><li>You’ve missed  work or school due to your headaches?  </li></ul><ul><li>Your pro...
GradeDefinitionScore <ul><li>I  Minimal or infrequent disability  0-5 </li></ul><ul><li>II  Mild or infrequent disability ...
DISABILITY IN STRATEGIES OF CARE (DISC) STUDY <ul><li>Step care across attacks </li></ul><ul><ul><li>ASA + M </li></ul></u...
TREAT MIGRAINE WHEN PAIN IS MILD Retrospective analysis of 3 studies confirmed triptan treatment while pain is mild provid...
TRIPTANS IN THE SPECTRUM OF MIGRAINE In patients with migraine, sumatriptan effectively treats all 3 types In patients wit...
RECURRENCE & REBOUND Rebound:   Recurring headache induced by repetitive and chronic overuse of acute headache medication ...
APPROACH TO DIFFICULT HEADACHE PROBLEMS Problem Strategy  Headache recurrence Treat earlier, add NSAID, increase dose,  ch...
SUMMARY OF ACUTE MIGRAINE MANAGEMENT Identify coexistent conditions that influence therapy Make a specific, credible diagn...
 
 
 
Chronic Daily HA
Tension (v. migraine) <ul><li> 10 attacks lasting 30 min–7 days </li></ul><ul><li> 2 of the following 4 </li></ul><ul><u...
MIGRAINE ADDITIONAL FEATURES Abatement with sleep Stereotyped premonitory symptoms Characteristic triggers Positive family...
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 ...
LATE-LIFE MIGRAINE ACCOMPANIMENTS VS TIA Mild headache in 50% Progression from one accompaniment to another Repetition ( ...
MIGRAINE AND STROKE Clinical manifestations of underlying disease (MELAS, CADASIL) Causal Comorbid Coexistent Bousser MG e...
CADASIL
CSF XANTHOCHROMIA AFTER SAH SPECTROPHOTOMETRY Vermeulen M et al.  J Neurol Neurosurg Psychiatry . 1989. TIME AFTER  HEMORR...
Preventive Management of Migraine
GUIDELINES: WHEN TO USE PREVENTIVE MANAGEMENT Uncommon migraine conditions Acute medications contraindicated, ineffective,...
GOALS OF PREVENTIVE TREATMENT Improve responsiveness to acute R x   Improve function and decrease disability Silberstein S...
Migraine Prevention
GENERAL PRINCIPLES OF PREVENTIVE TREATMENT <ul><li>Evaluate therapy </li></ul><ul><ul><li>Use headache calendar (diary) </...
PREVENTIVE MEDICATIONS: DRUG CLASSES Ca 2+ -Channel blockers Antidepressants  -Blockers NSAIDs 5-HT antagonists <ul><li>O...
GENERAL PRINCIPLES OF PREVENTIVE TREATMENT Assess Coexisting Conditions Be aware of drug interactions Do not use migraine ...
Comorbidities
Depression “SALSA” <ul><li>S leep Disturbance </li></ul><ul><li>A nhedonia </li></ul><ul><li>L ow </li></ul><ul><li>S elf-...
COMORBID AND COEXISTENT CONDITIONS Coexistent disorders are commonly present <ul><li>Therapeutic limitations </li></ul><ul...
PREVENTIVE TREATMENT: DRUG CHOICE COMORBID CONDITION DRUG EFFICACY* SIDE EFFECTS* RELATIVE CONTRAINDICATION RELATIVE  INDI...
PREVENTIVE TREATMENT: DRUG CHOICE COMORBID CONDITION DRUG EFFICACY* SIDE EFFECTS* RELATIVE CONTRAINDICATION RELATIVE INDIC...
PREVENTIVE TREATMENT: DRUG CHOICE COMORBID CONDITION DRUG EFFICACY* SIDE EFFECTS* RELATIVE CONTRAINDICATION RELATIVE INDIC...
PREVENTIVE TREATMENT:  USE OF ACUTE MEDICATION <ul><li>Can use acute and preventive treatment together </li></ul><ul><ul><...
CAUTIONS IN ACUTE MEDICATION USE Silberstein SD.  Cephalalgia . 1997. PREVENTIVE CAUTION CONTRAINDICATION Methysergide Erg...
NONPHARMACOLOGIC TREATMENT: POTENTIAL INDICATIONS Poor tolerance, response, or contraindications to drug therapy Pregnancy...
SUMMARY OF PREVENTION Use preventive medications when needed Treat long enough Avoid acute medication overuse Take coexist...
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Neurological lectures...Migraine

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Neurological lectures...Migraine
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  • Transcript of "Neurological lectures...Migraine"

    1. 1. Treating Migraines Professor Yasser Metwally www.yassermetwally.com
    2. 2. World prevalence of migraine <ul><li>1-year prevalence rates </li></ul><ul><li>Population-based studies </li></ul><ul><li>IHS criteria (or modified) </li></ul>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
    3. 3. 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
    4. 4. Diagnosis of migraine <ul><li>Diagnosis depends on patient history </li></ul><ul><li>No specific tests or clinical markers for migraine </li></ul>Cady (1999); Warshaw et al (1998) <ul><li>Positive diagnosis if attack history fulfils IHS criteria for migraine </li></ul><ul><li>Other pointers include: </li></ul><ul><ul><li>family history of migraine </li></ul></ul><ul><ul><li>age of onset <45 </li></ul></ul><ul><ul><li>presence of aura </li></ul></ul><ul><ul><li>menstrual association </li></ul></ul><ul><li>Organic disease must be excluded </li></ul>
    5. 5. Migraine Criteria <ul><li> 5 attacks lasting 4 – 72 h </li></ul><ul><li> 2 of the following 4 </li></ul><ul><ul><li>Unilateral </li></ul></ul><ul><ul><li>Pulsating </li></ul></ul><ul><ul><li>Moderate or severe intensity </li></ul></ul><ul><ul><li>Aggravation by routine physical activity </li></ul></ul><ul><li> 1 of the following </li></ul><ul><ul><li>Nausea and/or vomiting </li></ul></ul><ul><ul><li>Photophobia and phonophobia </li></ul></ul><ul><li>Not attributable to another disorder </li></ul>
    6. 6. SULTANS: two from column A, one from column B <ul><li>evere </li></ul><ul><li>ni </li></ul><ul><li>ateral </li></ul><ul><li>hrobbing </li></ul><ul><li>Ctivity worsens </li></ul><ul><li>ausea </li></ul><ul><li>Lite and sound ensitivity </li></ul>S U T A L N S
    7. 7. What is migraine? <ul><li>Migraine without aura (MO) </li></ul>Migraine with aura (MA) Headache Classification Committee of IHS (1988) <ul><li>At least five attacks fulfilling these criteria: </li></ul><ul><li>Headache lasting 4–72 h </li></ul><ul><li>(2–48 h in children) </li></ul><ul><li>At least two attacks fulfilling these criteria: </li></ul><ul><li>At least three of the following: </li></ul><ul><ul><li>one or more fully reversible aura symptoms </li></ul></ul><ul><ul><li>gradually developing or sequential aura symptoms </li></ul></ul><ul><ul><li>no one aura symptom lasts longer than 1 h </li></ul></ul><ul><ul><li>headache shortly follows or accompanies aura </li></ul></ul><ul><li>Accompanied by at least one of: </li></ul><ul><ul><li>nausea </li></ul></ul><ul><ul><li>vomiting </li></ul></ul><ul><ul><li>photophobia and/or phonophobia </li></ul></ul><ul><li>No evidence of organic disease </li></ul><ul><li>With at least two of: </li></ul><ul><ul><li>unilateral location </li></ul></ul><ul><ul><li>pulsating quality </li></ul></ul><ul><ul><li>moderate/severe intensity </li></ul></ul><ul><ul><li>aggravated by activity </li></ul></ul><ul><li>No evidence of organic disease </li></ul>
    8. 8. 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
    9. 11. 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
    10. 12. Premonitory, aura and postdromal symptoms <ul><li>Prodrome </li></ul><ul><li>Occurs in 60% of attacks </li></ul><ul><li>Alterations in </li></ul><ul><ul><li>mood </li></ul></ul><ul><ul><li>alertness </li></ul></ul><ul><ul><li>appetite </li></ul></ul><ul><li>Originate in hypothalamus and frontal lobes </li></ul>Silberstein and Lipton (1994); Lance (1993); Blau (1992) <ul><li>Aura </li></ul><ul><li>Occur in MA (20% patients) </li></ul><ul><li>Visual symptoms </li></ul><ul><ul><li>blurring, rippling </li></ul></ul><ul><ul><li>spots or flashes </li></ul></ul><ul><ul><li>fortification spectra </li></ul></ul><ul><ul><li>scotoma </li></ul></ul><ul><li>Sensory symptoms </li></ul><ul><ul><li>numbness/tingling </li></ul></ul><ul><li>Motor symptoms </li></ul><ul><ul><li>hemiparesis </li></ul></ul><ul><li>Postdrome </li></ul><ul><li>Occurs in 90% patients </li></ul><ul><li>Symptoms can persist for several days </li></ul><ul><ul><li>lethargy </li></ul></ul><ul><ul><li>exhaustion </li></ul></ul><ul><ul><li>impaired concentration </li></ul></ul><ul><ul><li>irritability </li></ul></ul><ul><ul><li>sluggishness </li></ul></ul><ul><ul><li>diminished appetite </li></ul></ul><ul><ul><li>euphoria </li></ul></ul>
    11. 13. 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.
    12. 14. MIGRAINE AURA “Cheiro-oral”
    13. 15. Fortification Spectrum
    14. 16. DIAGNOSIS AND TESTING Detailed History and Examination <ul><li>Primary Headache? </li></ul><ul><li>Preliminary Diagnosis </li></ul>NO Secondary Headache Diagnostic Testing Atypical Features YES
    15. 17. Alice in Wonderland
    16. 18. 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)
    17. 19. 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
    18. 20. 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)
    19. 21. Headache ‘red flags’ <ul><li>First or worst headache </li></ul><ul><li>Significant change from previous headache pattern </li></ul><ul><ul><li>no longer fulfils IHS criteria </li></ul></ul><ul><li>New onset headache in middle age or later </li></ul><ul><li>New or progressive headache that lasts for days </li></ul><ul><li>Precipitation of headache by coughing/sneezing/ bending down </li></ul><ul><li>Systemic symptoms such as myalgia, fever, malaise, weight loss, scalp tenderness, jaw claudication </li></ul><ul><li>Focal symptoms, seizures, confusion, impaired conciousness, physical examination abnormalities </li></ul>Pryse-Phillips et al (1997)
    20. 22. EVALUATION STRATEGIES Red Flags” “ Investigate the Atypical and the
    21. 23. SUDDEN ONSET HEADACHE Primary Secondary SAH Pituitary apoplexy Venous sinus thrombosis Arterial dissection Meningoencephalitis Acute hydrocephalus Acute hypertension Spontaneous intracranial hypotension Idiopathic thunderclap headache (TCH) Exertional headache Cough headache Sexual headache deBruijn, SF, et al. Lancet . 1996; Lancet . 1998.
    22. 24. 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.
    23. 25. 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
    24. 26. DIAGNOSIS TESTING CT AND MRI <ul><li>Consensus expert opinion </li></ul><ul><ul><li>MRI is more sensitive </li></ul></ul>Role of CT or MRI in patients with nonmigraine headache is unclear <ul><li>In patients with recurrent migraine, neither CT nor MRI is warranted except in cases where: </li></ul><ul><ul><li>Recent substantial change in headache pattern </li></ul></ul><ul><ul><li>History of seizures </li></ul></ul><ul><ul><li>Focal neurologic symptoms or signs </li></ul></ul>Report of Quality Standards Subcommittee of AAN. Neurology . 1994.
    25. 27. DIAGNOSTIC TESTING ELECTROENCEPHALOGRAPHY <ul><li>EEG may be useful in those patients with </li></ul><ul><ul><li>Alteration or loss of consciousness </li></ul></ul><ul><ul><li>Residual focal neurologic defects or encephalopathy </li></ul></ul><ul><ul><li>Atypical migrainous aura </li></ul></ul><ul><li>EEG is not useful </li></ul><ul><ul><li>In the routine evaluation of patients with headache to exclude structural cause </li></ul></ul>Report of Quality Standards Subcommittee of AAN. Neurology . 1995.
    26. 28. MR AND CONVENTIONAL ANGIOGRAPHY MR Angiography Angiography Acute SAH Arterial dissection CNS vasculitis Aneurysm (>5 mm) Arterial dissection Venous thrombosis (MR venography) AV malformation Leclerc X et al. Neuroradiology . 1999.
    27. 29. INDICATIONS FOR GADOLINIUM ENHANCED MRI <ul><li>Cerebrovascular </li></ul><ul><ul><li>Arterial dissection (MRA) </li></ul></ul><ul><ul><li>Cerebral venous sinus thrombosis (MRV) </li></ul></ul><ul><ul><li>CNS vasculitis </li></ul></ul><ul><li>Tumors </li></ul><ul><ul><li>Posterior fossa </li></ul></ul><ul><ul><li>Pituitary </li></ul></ul><ul><ul><li>Leptomeninges </li></ul></ul>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 .
    28. 30. CEREBRAL VENOUS SINUS THROMBOSIS Bousser MG et al. In: Wolff’s Headache And Other Head Pain . 2001 .
    29. 31. Sleepers Awake!! Treatment
    30. 32. 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.
    31. 33. 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
    32. 34. PRINCIPLES OF MIGRAINE MANAGEMENT <ul><li>Patient education and behavioral management </li></ul><ul><ul><li>Nature and mechanism of the disorder </li></ul></ul><ul><ul><li>Strategies for identifying and avoiding triggers </li></ul></ul><ul><ul><li>Behavioral strategies </li></ul></ul><ul><ul><ul><li>Regular sleep, exercise, meals </li></ul></ul></ul><ul><ul><ul><li>Stress management, biofeedback </li></ul></ul></ul><ul><ul><ul><li>Cognitive behavioral therapy </li></ul></ul></ul>Establish a therapeutic partnership <ul><li>Pharmacologic management </li></ul><ul><ul><li>Acute treatment </li></ul></ul><ul><ul><li>Preventative strategies </li></ul></ul>
    33. 35. NONPHARMACOLOGIC TREATMENTS <ul><li>Insufficient evidence to recommend: GRADE C </li></ul><ul><ul><li>Acupuncture </li></ul></ul><ul><ul><li>TENS </li></ul></ul><ul><ul><li>Cervical manipulation </li></ul></ul><ul><ul><li>Occlusal adjustment </li></ul></ul><ul><ul><li>Hyperbaric oxygen </li></ul></ul><ul><ul><li>Hypnosis </li></ul></ul>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. <ul><li>Effective: GRADE A </li></ul><ul><ul><li>Relaxation training </li></ul></ul><ul><ul><li>Thermal biofeedback with relaxation training </li></ul></ul><ul><ul><li>EMG biofeedback </li></ul></ul><ul><ul><li>Cognitive behavioral therapy </li></ul></ul>
    34. 36. Goals of Treatment <ul><li>Establish diagnosis </li></ul><ul><li>Educate patient </li></ul><ul><li>Discuss findings </li></ul><ul><li>Establish reasonable expectations </li></ul><ul><li>Involve patient in decisions </li></ul><ul><li>Encourage Pt to avoid triggers </li></ul><ul><li>Choose the best treatment (tailoring) </li></ul><ul><li>Create treatment plan </li></ul>
    35. 37. MIGRAINE TRIGGERS Diet Hormonal changes Head trauma Stress and anxiety Sleep deprivation or excess Environmental factors Physical exertion
    36. 38. ACUTE MIGRAINE MEDICATIONS <ul><li>Nonspecific </li></ul><ul><ul><li>NSAIDs </li></ul></ul><ul><ul><li>Combination analgesics </li></ul></ul><ul><ul><li>Opioids </li></ul></ul><ul><ul><li>Neuroleptics/antiemetics </li></ul></ul><ul><ul><li>Corticosteroids </li></ul></ul><ul><li>Specific </li></ul><ul><ul><li>Ergotamine/DHE </li></ul></ul><ul><ul><li>Triptans </li></ul></ul>
    37. 39. ACUTE THERAPIES FOR MIGRAINE <ul><li>Nonspecific Prescription Medications </li></ul><ul><ul><li>Butorphanol IN </li></ul></ul><ul><ul><li>Ibuprofen/Naproxen sodium </li></ul></ul><ul><ul><li>Prochlorperazine IV </li></ul></ul>GROUP 1a: Substantial empirical evidence and pronounced clinical benefit in migraine Silberstein SD. Neurology . 2000. <ul><li>Migraine-Specific Medications </li></ul><ul><ul><li>Triptans </li></ul></ul><ul><ul><li>DHE </li></ul></ul><ul><ul><li>SC, IM, IN, IV (plus antiemetic) </li></ul></ul>
    38. 40. ACUTE THERAPIES FOR MIGRAINE GROUP 2: Moderate empirical evidence and clinical benefit <ul><li>Opioids  Others </li></ul><ul><li>Over-the-Counter Analgesics </li></ul><ul><ul><li>Aspirin </li></ul></ul><ul><ul><li>Acetaminophen, aspirin, plus caffeine </li></ul></ul>Silberstein SD. Neurology . 2000. GROUP 1b: Substantial empirical evidence of clinical benefit in restricted populations
    39. 41. 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 <ul><li>Match treatment intensity to attack severity (stratified care) </li></ul><ul><ul><li>Ask about migraine disability and impact </li></ul></ul>Silberstein SD. Neurology . 2000.
    40. 42. 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
    41. 43. 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
    42. 44. TRIPTANS <ul><li> As a class, relative to nonspecific therapies, triptans provide </li></ul><ul><ul><li>Rapid onset of action </li></ul></ul><ul><ul><li>High efficacy </li></ul></ul><ul><ul><li>Favorable side effect profile </li></ul></ul>Adverse events and contraindications Selective 5-HT 1B/1D/1F agonists Silberstein SD. Neurology . 2000.
    43. 45. TRIPTANS: TREATMENT CHOICES <ul><li>Are there differences between the triptans? </li></ul><ul><li>If one triptan fails, will another triptan work? </li></ul><ul><li>Zolmitriptan </li></ul><ul><ul><li>Tablet (2.5, 5 mg) </li></ul></ul><ul><ul><li>Nasal spray (5 mg) </li></ul></ul><ul><li>Rizatriptan </li></ul><ul><ul><li>Tablet (5, 10 mg) </li></ul></ul><ul><li>Naratriptan </li></ul><ul><ul><li>Tablet (1, 2.5 mg) </li></ul></ul><ul><li>Almotriptan </li></ul><ul><ul><ul><li>Tablet (6.25, 12.5 mg ) </li></ul></ul></ul><ul><li> Frovatriptan </li></ul><ul><li>Tablet (2.5 mg) </li></ul>Question and Answer <ul><li>Sumatriptan </li></ul><ul><ul><li>Tablet (25, 50, 100 mg) </li></ul></ul><ul><ul><li>Injection (6 mg) </li></ul></ul><ul><ul><li>Nasal spray (5, 20 mg*) </li></ul></ul>* Pediatric efficacy shown Ferrari MD et al. Lancet . 2001. <ul><li> Eletriptan </li></ul><ul><li>Tablet (20, 40 mg) </li></ul>
    44. 46. ROUTES OF ADMINISTRATION Suppositories: antiemetics, ergots, opioids Oral therapies: most medications Nasal sprays: sumatriptan, DHE, butorphanol, zolmitriptan Injectable (SL, IM, IV) sumatriptan, DHE, injectable NSAIDs, opioids, neuroleptics
    45. 47. FORMULATION: ONSET Increasing Speed Parenteral Oral Tablet SL IN PR IM/SC IV
    46. 48. Sumatriptan <ul><li>Sumatriptan (Glaxo Wellcome) </li></ul><ul><ul><li>5-HT 1B/1D agonist </li></ul></ul><ul><li>Major advance – good efficacy with subcutaneous formulation </li></ul><ul><li>Slow onset (2–4 h p.o.); LogD -1.5 </li></ul><ul><li>Short t 1/2 (2 h) </li></ul>Ferrari et al (1995)
    47. 51. 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 ** ** **
    48. 52. 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.
    49. 53. STEP VS. STRATIFIED CARE Start Start A B C A B C
    50. 54. BASIS OF STRATIFICATION <ul><li>Symptom profile </li></ul><ul><ul><li>Prominent nausea and vomiting may require parenteral therapy </li></ul></ul><ul><li>Headache frequency </li></ul><ul><ul><li>Consider risk of medication overuse </li></ul></ul><ul><li>Patient history and preferences </li></ul><ul><ul><li>Consider adverse events and prior experience </li></ul></ul>    <ul><li>Headache onset and severity </li></ul><ul><ul><li>Fast onset may benefit from parenteral therapy </li></ul></ul><ul><ul><li>Disability predicts treatment needs </li></ul></ul>Silberstein SD. Neurology . 2000.
    51. 55. MIDAS Score Days in Last 3 months <ul><li>You’ve missed work or school due to your headaches? </li></ul><ul><li>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) </li></ul><ul><li>You not do household work because of your headaches? </li></ul><ul><li>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) </li></ul><ul><li>You missed family, social or leisure activities because of your headaches? </li></ul><ul><li>A. Had a Headache? If a headache lasted more than one day count each day.         </li></ul><ul><li>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?? </li></ul>
    52. 56. GradeDefinitionScore <ul><li>I Minimal or infrequent disability 0-5 </li></ul><ul><li>II Mild or infrequent disability 6-10 </li></ul><ul><li>III Moderate disability 11-20 </li></ul><ul><li>IV Severe disability 21+ </li></ul>
    53. 57. DISABILITY IN STRATEGIES OF CARE (DISC) STUDY <ul><li>Step care across attacks </li></ul><ul><ul><li>ASA + M </li></ul></ul><ul><ul><li>Assess response after 3 attacks </li></ul></ul><ul><ul><li>Escalate treatment to zolmitriptan if ASA + M fails 2/3 or 3/3 </li></ul></ul><ul><li> Stratification based on disability </li></ul><ul><ul><li>MIDAS Grade II — ASA + M </li></ul></ul><ul><ul><li>MIDAS Grade III, IV — Triptan (zolmitriptan) </li></ul></ul><ul><li> Step care within attacks </li></ul><ul><ul><li>ASA + M  Assess response at 2 hours </li></ul></ul><ul><li> Rescue with zolmitriptan prn </li></ul>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.
    54. 58. 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.
    55. 59. 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.
    56. 60. RECURRENCE & REBOUND Rebound: Recurring headache induced by repetitive and chronic overuse of acute headache medication <ul><li>Recurrence: Return of episodic headache during the same attack following acute treatment </li></ul><ul><ul><li>Prevention: Treat early, add NSAID. Use long duration triptan or DHE </li></ul></ul><ul><ul><li>Treatment: Repeat initial acute headache drug; almost always effective </li></ul></ul>Tfelt-Hansen P et al. Drugs . 2000; Capobianco DJ et al. Headache . 2001.
    57. 61. 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 <ul><li>Lack of response </li></ul>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.
    58. 62. 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
    59. 66. Chronic Daily HA
    60. 67. Tension (v. migraine) <ul><li> 10 attacks lasting 30 min–7 days </li></ul><ul><li> 2 of the following 4 </li></ul><ul><ul><li>Bilateral </li></ul></ul><ul><ul><li>Not pulsating </li></ul></ul><ul><ul><li>Mild or moderate intensity </li></ul></ul><ul><ul><li>Not aggravated by routine physical activity </li></ul></ul><ul><li>No nausea or vomiting </li></ul><ul><li>One or neither photophobia or phonophobia </li></ul><ul><li>Not attributable to another disorder </li></ul>
    61. 68. 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.
    62. 69. UNDIAGNOSED MIGRAINE SUFFERERS OFTEN RECEIVE OTHER MEDICAL DIAGNOSES Lipton RB et al. Headache . 2001.
    63. 70. 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.
    64. 71. 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.
    65. 72. 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 .
    66. 73. CADASIL
    67. 74. CSF XANTHOCHROMIA AFTER SAH SPECTROPHOTOMETRY Vermeulen M et al. J Neurol Neurosurg Psychiatry . 1989. TIME AFTER HEMORRHAGE PROBABILITY (%) 12 HOURS 100 1 WEEK 100 2 WEEKS 100 3 WEEKS >70 4 WEEKS >40
    68. 75. Preventive Management of Migraine
    69. 76. 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
    70. 77. 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
    71. 78. Migraine Prevention
    72. 79. GENERAL PRINCIPLES OF PREVENTIVE TREATMENT <ul><li>Evaluate therapy </li></ul><ul><ul><li>Use headache calendar (diary) </li></ul></ul><ul><ul><li>Attempt to taper and discontinue treatment when headaches well controlled </li></ul></ul>Adequate trial (2 – 3 months) at an appropriate dosage Avoid interfering, overused, and contraindicated medications Silberstein SD et al. Headache in Clinical Practice . 2nd ed. 2002. <ul><li>Start low and increase dose slowly </li></ul><ul><ul><li>Use long-acting formulation if compliance an issue </li></ul></ul>
    73. 80. PREVENTIVE MEDICATIONS: DRUG CLASSES Ca 2+ -Channel blockers Antidepressants  -Blockers NSAIDs 5-HT antagonists <ul><li>Other </li></ul><ul><ul><li>Vitamins </li></ul></ul><ul><ul><li>Minerals </li></ul></ul><ul><ul><li>Herbs </li></ul></ul><ul><ul><li>Botulinum Toxin A </li></ul></ul>Silberstein SD. Cephalalgia . 1997. Anticonvulsants
    74. 81. 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
    75. 82. Comorbidities
    76. 83. Depression “SALSA” <ul><li>S leep Disturbance </li></ul><ul><li>A nhedonia </li></ul><ul><li>L ow </li></ul><ul><li>S elf-esteem </li></ul><ul><li>A ppetite Change </li></ul>
    77. 84. COMORBID AND COEXISTENT CONDITIONS Coexistent disorders are commonly present <ul><li>Therapeutic limitations </li></ul><ul><ul><li>Avoid  -blockers with depression, asthma, or hypotension </li></ul></ul>Silberstein SD et al. Headache in Clinical Practice . 2nd ed. 2002. <ul><li>Therapeutic opportunities </li></ul><ul><ul><li>Treat two disorders with a single drug </li></ul></ul><ul><ul><ul><li>Hypertension or angina — use  -blocker </li></ul></ul></ul><ul><ul><ul><li>Depression — use TCAs or SSRIs </li></ul></ul></ul><ul><ul><ul><li>Epilepsy or mania — use divalproex or topiramate </li></ul></ul></ul>
    78. 85. 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
    79. 86. 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
    80. 87. 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.
    81. 88. PREVENTIVE TREATMENT: USE OF ACUTE MEDICATION <ul><li>Can use acute and preventive treatment together </li></ul><ul><ul><li>Limit acute drug use to prevent drug-induced headache </li></ul></ul><ul><ul><li>Certain drugs require caution or cannot be used together </li></ul></ul><ul><ul><li>Acute medications may have more benefit </li></ul></ul>Breakthrough attacks need treatment Silberstein SD. Cephalalgia . 1997. Preventive treatment does not eliminate all attacks
    82. 89. 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
    83. 90. 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
    84. 91. 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
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