Headache Disorders

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Headache Disorders

• Jessica W. Lea, Pharm.D, BCPP
• Assistant Clinical Professor of Pharmacy Practice

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References

• http//www.annals.org/cgi/content/full/137/10/840
• http//www.neurology.org/cgi/reprint/55/6/754.pdf

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Headache Classification

• Primary
• Migraine
• w/o aura
• w/ aura
• Chronic
• Cluster
• Tension-type
• Secondary
• Organic
• Medication Overuse Headache (MOH)

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Headache History

• Age of onset
• Frequency and Timing
• Duration
• Precipitating Event
• Relief
• Aura?
• Intensity, Quality, Location, Radiation
• What worked before?
• Family and Social History
• Social Impact/Work/Family Life

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Tension Headache

• More common in women, earlier onset
• Dull, steady, achy pain that is bilateral
• Pressure or tightness in head, neck, face and
  shoulders
• Vise pressing on the head
• Anxiety, depression and stress related
• Treated with NSAIDS and OTC pain medications

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Cluster Headache

• Severe, unilateral orbital, supraorbital, and/or
  temporal head pain lasting for weeks or months
  separated by remission
• Lacrimation, nasal congestion, rhinorrhea,
  forehead and facial sweating, eyelid edema
• More common in men
• Abortive therapy oxygen, triptans, ergotamines
• Prophylactic therapy

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Migraines

• Over 28 million Americans have migraines
• Migraines 70 of all migraine sufferers are
  women
• Industry loses 50 billion dollars per year due to
  absenteeism expenses caused by headaches
• Direct costs-Average 817/person/year
• Over 4 billion dollars spent annually on
  over-the-counter pain relievers for headache

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Migraines

• Females 2-3X more likely than males
• Usually onset ages 10-29 years old
• Highest prevalence in ages 35-45
• Comorbid disease states
• Stroke, epilepsy, major depression and anxiety
• Genetic link

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Migraine DiagnosisMigraine without Aura

• Headache has 2 of the following
• Unilateral
• Throbbing/pulsating
• Moderate-Severe
• Aggravated by movement
• One of the following
• Nausea and/or vomiting
• Photo or phonophobia
• Similar pain in past and no evidence of organic
  disease

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Migraine Diagnosis Migraine With Aura

• Headache preceded by 1 neurologic symptom
• Visual
• Scintillating scotoma
• Fortification spectra
• Photopsia
• Sensory
• Numbness
• Paresthesia
• Other
• Weakness
• Aphasia

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Phases of Migraine Attack

• Premonitory Symptoms (Prodrome)
• Aura
• Headache
• Resolution Phase (Postdrome)

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Pathophysiology

• Ischemia vs. Neuronal dysfunction
• Trigeminovascular System
• CGRP (calcitonin gene-related peptide)
• Neurokinin A
• Substance P
• Cortical spreading excitation and depression
• Brainstem generator/modulator

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Pathophysiology

• Serotonin (5-HT) role
• Trigeminal sensory C fibers have 5-HT1D
  presynaptic receptors
• Cranial vessel constriction (5-HT 1B)

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Triggers

• Lifestyle Factors
• Hormonal Factors
• Psychological Factors
• Environment Factors
• Dietary Factors
• Alcohol
• MSG (processed meats, salad dressing)
• Tyramine-Containing Foods (bacon, hot dogs, lunch
  meats, sausage, aged cheeses)

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Goals of Therapy

• Acute
• Reduction in pain intensity, duration and
  frequency
• Reduction in disability due to pain
• Prevent further recurrence
• Chronic
• Reduce number of migraines
• Improve daily functioning
• Reduce frequency of medications needed to treat
  acute headaches
• Educate and enable patients to manage disease

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Non-pharmacological Treatment of Migraine

• Biofeedback
• Avoidance of triggers
• Relaxation techniques
• Sleep
• Decrease stimulation (dark room)
• Cold compresses
• Stop tobacco use

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Drug Selection Considerations

• Headache severity, frequency, and level of
  disability
• Associated Symptoms
• Concurrent medications and contraindications
• Drug efficacy and side effect profile (AHS US
  Consortium Guidelines)
• Concurrent disease states
• Patients treatment response/past response
• Drug Dosage Formulations

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Abortive Treatment-Mild/Moderate

• Acetaminophen and NSAIDS
• Combination agents Excedrin Migraine, Midrin,
  Fiorinal, Norgesic
• Included caffeine, barbiturates, opioids, and
  sedatives
• Use of analgesics with butalbital and
  narcoticsrisk of habituation and dependence
• Frequent consumption of combo products and/or
  APAP or ASA aloneMOH

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Abortive Treatment-Mild/Moderate

• APAP
• Dosage 650-4000mg daily in divided dose
• NSAIDS
• Ibuprofen (400-2400 mg daily in divided dose)
• Naproxyn (750-1750 mg daily in divided dose)
• Aspirin (325-4000 mg daily in divided dose)
• Ketorlac (30-60 mg) available in IM formulation
• Combination
• APAP (250mg) ASA (250mg) Caffeine (65mg)

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Abortive Treatment-Mild/Moderate

• Combinations
• APAP, ASA, Caffeine
• APAP 250mg, isometheptene 65 mg,
  dichloralphneazone 100 mg (Midrin)
• Butalbital, ASA, Caffeine (codeine)
• Butalbital, APAP, Caffeine

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Abortive Therapy

• Opiate Analgesics
• Relief of intractable migraine
• Reserved for last choice or rescue relief, ED
• Butorphanol intranasal
• Medication Abuse multiple pain meds, persistent
  calls for refills, creative excuses, more than
  one doctor, more than one pharmacy

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Abortive Therapy

• Antiemetics
• Mild to moderate pain, adjunct
• Chlorpromazine, metoclopramide, prochlorperazine
  (ED use often)
• Corticosteroids
• Intranasal lidocaine

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Abortive Therapy-Moderate to Severe

• Ergot Derivatives
• Ergotamine Tartrate (Cafergot, Ercaf, Wigraine)
  available oral and rectal
• Dihydroergotamine Mesylate (DHE, Migranal)
  available IV, IM, or nasal
• Nonselective 5-HT1 receptor agonists
• Constrict intracranial blood vessels
• Inhibit development of neurgenic inflammation in
  trigeminovascular system

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Ergot Alkaloids

• CI Pregnancy, PVD, hepatic/renal impairment,
  CAD, HTN, severe pruritis, sepsis, malnutrition
• Drug interactions ?-blockers, macrolides,
  nitrates, vasodilators triptans
• Precautions ergotism (severe peripheral
  ischemia) and gangrene may result from prolonged
  use dependence may require increasing doses

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Ergot Alkaloids

• Adverse reactions N/V, numbness or tingling in
  fingers and toes, leg weakness, muscle pain
• Patient information
  Initiate therapy at first sign of attack
• Do NOT exceed recommended dosage Notify
  physician of any of the following occurs
  Irregular heart beat, nausea, vomiting, numbness
  or tingling of fingers or toes, or pain or
  weakness of extremities

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Abortive Therapy- Moderate to Severe

• Triptans
• Sumatriptan/Imitrex(oral, IM, IN)
• Naratriptan/Amerge (oral)
• Zomitriptan/Zomig (oral, ZMT, IN)
• Rizatriptan/Maxalt (oral, MLT)
• Almotriptan/Axert (oral)
• Frovatriptan/Frova (oral)
• Eletriptan/Relpax (oral)
• Major differences include potency and kinetics

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The Triptans

• Onset usually between 30 minutes to 2 hours
• QuickestSQ methods
• Slowestnaratriptan (longer acting)
• Elimination half-life approx 2-3 hours
• Frovatriptan26 hours (multiple metabolites)
• Bioavailability
• Sumatriptan SQ 97, PO IN 17
• Eletriptan 50 (increased w/ high fat foods)
• Frovatriptan 20-30

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The Triptans

• Repeat dose usu between 2-4 hours x1
• Naratriptan repeat in 4 hours
• Sumatriptan SQ can repeat in 1 hour
• Duration of action
• Naratriptan long acting
• Contraindicated w/ MAOIs
• Almotriptan, naratriptan
• Dosage adjustment w/ renal impairment
• Naratriptan, almotriptan
• CYP450
• Almotriptan, zolmitriptan, naratriptan

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The Triptans

• CI IHD, uncontrolled HTN, Cerebrovascular
  Disease, concurrent use of ergots (24 hours), MOA
  inhibitors (2 weeks), complicated/hemiplegic
  migraine
• Drug interactions Cimetidine, oral
  contraceptives, propranolol, SSRIs
• Precautions Chest, jaw or neck tightness rare
  reports of seizures with sumatriptan, ophthalmic
  effects

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The Triptans

• Adverse effects paresthesia, asthenia, N/V,
  dizziness, drowsiness, chest or neck tightness or
  heaviness, warm sensation, somnolence
• Patient information
• How to properly use various dosage forms
• Patient should notify MD if at risk for heart
  disease
• Do not use if pregnant or trying to conceive
• Adverse effectsnotify MD

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Prophylactic Therapy Options

• Beta-Blockers
• Antidepressants
• Antiepileptics
• Serotonergic antagonist
• Calcium Channel Blockers
• NSAIDS
• Methysergide
• Others estrogen replacement, clonidine, fish oil
  supplements, feverfew, botulinum toxin,
  montelukast, magnesium, riboflavin

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Prophylactic Therapy

• Goal of Treatment
• Decrease duration, frequency and intensity by 50
• Dosage should be decreased after several months
• gt2 attacks per month or prolonged and refractory
  to short-term therapy, predictable pattern
• Consider coexisting conditions (depression,
  hypertension, epilepsy, weight issues)

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Prophylactic Therapy

• ß-Adrenergic antagonist
• Generally treatment of choice
• Propranolol (40-120 mg/day)
• Nadolol (40-80 mg/day)
• Metoprolol (50-100 mg/day)
• Atenolol (50-100 mg/day)

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Prophylactic Therapy

• Antidepressants
• Amitriptyline (10-150mg/day)
• SSRIs not well studied, but often used due to
  better tolerability
• MAOIs (food restrictions)
• Antiepileptics
• Divalproex, extended release (500-1000mg/day)
• Topiramate (100-200 mg daily, starting 15 mg
  daily)
• Gabapentin, Levitriacetam (evidence lacking)

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Prophylactic Therapy

• Methysergide (Sansert) 5-HT2 antagonist (Dosage
  4-8 mg daily)
• Requires drug free interval every 6 months
• Long term effectfibrosis of lungs and myocardium
• Calcium Channel Blockers
• Verapamil (240-320 mg/day)

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Chronic Migraine attributed to Medication Overuse
Headache (MOH)

• Headache returns as medication wears off
• Leads to consumption of more drug for relief
• Diary shows gradual onset of atypical daily or
  near daily headache with episodic migraine
  attacks
• Biggest offenders simple and combination
  analgesics (butalbital, caffeine, or
  isometheptene), opiates, ergotamine, and triptans
• 10 single doses per month can lead to MOH

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Chronic Migraine attributed to Medication Overuse
Headache (MOH)

• Discontinuation of offending agent
• Decrease in HA frequency and return of original
  HA characteristics
• Prophylactic agent
• Max use of acute migraine therapies to 2 days per
  week to avoid MOH