Migraine Treatment

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Treating Migraines
Charles Yanofsky M.D. www.susqneuro.com
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World prevalence of migraine
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Prevalence of migraine by sex and age
Migraine prevalence ()
30
25
20
15
10
5
0
20
30
40
50
60
70
80
100
Age (years)
The American Migraine Study (n2479 migraine
sufferers)
Lipton and Stewart (1993)
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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 lt45
• presence of aura
• menstrual association
• Organic disease must be excluded

Cady (1999) Warshaw et al (1998)
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Migraine Criteria

• ?5 attacks lasting 472 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

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SULTANS two from column A, one from column B

• ausea
• Lite and sound ensitivity

N
S

• evere
• ni
• ateral
• hrobbing
• Ctivity worsens

U
S
L
T
A
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What is migraine?

• Migraine without aura (MO)

Migraine with aura (MA)

• At least five attacks fulfilling these criteria
• Headache lasting 472 h
• (248 h in children)

• At least two attacks fulfilling these criteria
• At least three of the following
• one or more fully reversibleaura symptoms
• gradually developing orsequential aura symptoms
• no one aura symptom lastslonger than 1 h
• headache shortly follows or accompanies aura

• 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

• No evidence of organic disease

Headache Classification Committee of IHS (1988)
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Clinical features of migraine
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IMPORTANT DIAGNOSTIC CONSIDERATIONS
15 of patients have a neurological aura
IHS criteria do not require GI symptoms
Vomiting occurs in lt 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
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Premonitory, aura and postdromal symptoms

• Prodrome
• Occurs in 60 of attacks
• Alterations in
• 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

Silberstein and Lipton (1994) Lance (1993)
Blau (1992)
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MIGRAINE WITH AURA(FORMERLY CLASSIC MIGRAINE)
Gradual evolution 520 minutes (lt60 minutes)
May or may not be associated with headache
Visual gt sensory gt motor, language, brainstem
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MIGRAINE AURACheiro-oral
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Fortification Spectrum
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DIAGNOSIS AND TESTING
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Alice in Wonderland
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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
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Differential diagnosis of primary headaches
Dubose et al (1995) Goadsby (1999) Marks and
Rapoport (1997)
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WORRISOME HEADACHE RED FLAGSSNOOP
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 gt50 (giant cell
arteritis)
Previous headache history first headache or
different (change in attack frequency, severity,
or clinical features)
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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/be
  nding down
• Systemic symptoms such as myalgia, fever,
  malaise, weight loss, scalp tenderness, jaw
  claudication
• Focal symptoms, seizures, confusion, impaired
  conciousness, physical examination abnormalities

Pryse-Phillips et al (1997)
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EVALUATION STRATEGIES
Investigate
the
Atypical
and the
Red Flags
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SUDDEN ONSET HEADACHE
Primary
Secondary
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LUMBAR PUNCTURE
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)
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SENSITIVITY OF CT SCAN IN SUBARACHNOID HEMORRHAGE
(SAH)
van Gijn J, van Dongen KJ. Neuroradiology.
1982. Kassell NF et al. J Neurosurg. 1990.
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DIAGNOSIS TESTINGCT AND MRI
Role of CT or MRI in patients with nonmigraine
headache is unclear

• Consensus expert opinion
• MRI is more sensitive

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DIAGNOSTIC TESTING ELECTROENCEPHALOGRAPHY

• EEG may be useful in those patients with
• Alteration or loss of consciousness
• Residual focal neurologic defects or
  encephalopathy
• Atypical migrainous aura

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MR AND CONVENTIONAL ANGIOGRAPHY
MR Angiography
Angiography
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INDICATIONS FOR GADOLINIUM ENHANCED MRI

• Cerebrovascular
• Arterial dissection (MRA)
• Cerebral venous sinus thrombosis (MRV)
• CNS vasculitis

• Tumors
• Posterior fossa
• Pituitary
• Leptomeninges

High and low intracranial pressure syndromes
Herpes encephalitis
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CEREBRAL VENOUS SINUS THROMBOSIS
Bousser MG et al. In Wolffs Headache And Other
Head Pain. 2001.
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Sleepers Awake!!
Treatment
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STRATEGIES FOR MIGRAINE TREATMENT
Preventive Treatment Decrease in migraine
frequency warranted
Preemptive treatment Migraine trigger time-limite
d and predictable
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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
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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

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NONPHARMACOLOGIC TREATMENTS

• 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
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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

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

• Nonspecific
• NSAIDs
• Combination analgesics
• Opioids
• Neuroleptics/antiemetics
• Corticosteroids

• Specific
• Ergotamine/DHE
• Triptans

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ACUTE THERAPIES FOR MIGRAINE

• Nonspecific Prescription Medications
• Butorphanol IN
• Ibuprofen/Naproxen sodium
• Prochlorperazine IV

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ACUTE THERAPIES FOR MIGRAINE

• Over-the-Counter Analgesics
• Aspirin
• Acetaminophen, aspirin, plus caffeine

GROUP 2 Moderate empirical evidence and
clinical benefit

• Opioids ? Others

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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
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Trigeminovascular model of migraine
Cranium
Dura mater
Afferent
Peptide releasing neurones
Trigeminal ganglion
Dura mater
Blood vessels
Efferent
Trigeminal nerve
Afferent
Efferent
CGRP/SPrelease
Efferent
Dilatation
Adapted from Goadsby and Olesen (1996)
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Mechanisms for treatment
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TRIPTANS

• As a class, relative to nonspecific therapies,
  triptans provide
• Rapid onset of action
• High efficacy
• Favorable side effect profile

Adverse events and contraindications
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TRIPTANSTREATMENT CHOICES

• Almotriptan
• Tablet (6.25, 12.5 mg)

• Frovatriptan
• Tablet (2.5 mg)

• Zolmitriptan
• Tablet (2.5, 5 mg)
• Nasal spray (5 mg)

• Naratriptan
• Tablet (1, 2.5 mg)

• Are there differences between the triptans?
• If one triptan fails, will another triptan work?

• Rizatriptan
• Tablet (5, 10 mg)

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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
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FORMULATION ONSET
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Sumatriptan

• Sumatriptan (Glaxo Wellcome)
• 5-HT1B/1D agonist

• Major advance good efficacy with subcutaneous
  formulation
• Slow onset (24 h p.o.) LogD -1.5
• Short t1/2 (2 h)

Ferrari et al (1995)
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Headache responses continue to improve over time
after eletriptan dosingTime course for headache
response
Patients with response
100
n563
80
60
40
20
0
0
1
2
3
4
Time post dose (h)
Pfizer, data on file
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ACUTE TREATMENT PRINCIPLES
?
?
Early intervention
?
Use correct dose and formulation
?
Use a maximum of 23 days/week
?
Use preventive therapy in selected patients
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STEP VS. STRATIFIED CARE
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BASIS OF STRATIFICATION
?
?

• 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

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MIDAS ScoreDays in Last 3 months

• Youve 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??

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GradeDefinitionScore

• I Minimal or infrequent disability 0-5
• II Mild or infrequent disability 6-10
• III Moderate disability 11-20
• IV Severe disability 21

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DISABILITY IN STRATEGIES OF CARE (DISC) STUDY

• Stratification based on disability
• MIDAS Grade IIASA M
• MIDAS Grade III, IVTriptan (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
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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
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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
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RECURRENCE REBOUND
Rebound Recurring headache induced by
repetitive and chronic overuse of acute headache
medication
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APPROACH TO DIFFICULT HEADACHE PROBLEMS
Problem
Strategy
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SUMMARY OF ACUTE MIGRAINE MANAGEMENT
Make a specific, credible diagnosis and
communicate it
Assess migraine severity and its impact on the
patient
Determine the patients 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 patients needs, preferences, and
comorbidities
Consider need for preventive treatment
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Chronic Daily HA
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Tension (v. migraine)

• ?10 attacks lasting 30 min7 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

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MIGRAINEADDITIONAL FEATURES
Stereotyped premonitory symptoms
Characteristic triggers
Abatement with sleep
Positive family history
Childhood precursors (motion sickness, episodic
vomiting, episodic vertigo)
Osmophobia
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UNDIAGNOSED MIGRAINE SUFFERERS OFTEN RECEIVE
OTHER MEDICAL DIAGNOSES
Lipton RB et al. Headache. 2001.
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AURA MIMICS AND SECONDARY CAUSES
Tumor
Simple partial seizure
TIA
Carotid artery dissection
Venous sinus thrombosis
Vasculitis
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LATE-LIFE MIGRAINE ACCOMPANIMENTS VS TIA
Progression from one accompaniment to another
Repetition (?2 similar attacks)
Mild headache in 50
Duration 1525 minutes
Characteristic midlife flurry of attacks
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MIGRAINE AND STROKE
Causal
Comorbid
Clinical manifestations of underlying disease
(MELAS, CADASIL)
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CADASIL
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CSF XANTHOCHROMIA AFTER SAH SPECTROPHOTOMETRY
Vermeulen M et al. J Neurol Neurosurg Psychiatry.
1989.
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Preventive Management of Migraine
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GUIDELINES WHEN TO USE PREVENTIVE MANAGEMENT
Acute medications contraindicated, ineffective,
intolerable AEs, or overused
Frequent headache (?2 attacks per week)
Uncommon migraine conditions
Cost considerations
Patient preference
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GOALS OF PREVENTIVE TREATMENT
Improve responsiveness to acute Rx
Improve function and decrease disability
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Migraine Prevention
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GENERAL PRINCIPLES OF PREVENTIVE TREATMENT
Adequate trial (23 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

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PREVENTIVE MEDICATIONSDRUG CLASSES
NSAIDs
5-HT antagonists
Antidepressants

• Other
• Vitamins
• Minerals
• Herbs
• Botulinum Toxin A

?-Blockers
Ca2-Channel blockers
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GENERAL PRINCIPLES OF PREVENTIVE TREATMENT
Assess Coexisting Conditions
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
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Comorbidities
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Depression SALSA

• Sleep Disturbance
• Anhedonia
• Low
• Self-esteem
• Appetite Change

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COMORBID AND COEXISTENT CONDITIONS
Coexistent disorders are commonly present

• Therapeutic limitations
• Avoid ?-blockers with depression, asthma, or
  hypotension

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PREVENTIVE TREATMENTDRUG CHOICE
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PREVENTIVE TREATMENTDRUG CHOICE
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PREVENTIVE TREATMENTDRUG CHOICE
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PREVENTIVE TREATMENT USE OF ACUTE MEDICATION
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

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CAUTIONS IN ACUTE MEDICATION USE
Silberstein SD. Cephalalgia. 1997.
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NONPHARMACOLOGIC TREATMENTPOTENTIAL 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
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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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Thats the Tale of the Comet
Fini