Migraine
Primary Care Conference
July 29, 2010
Samuel Ash, MD
Resident, Internal Medicine
University of Washington
samash@uw.edu
Outline
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Cases
Epidemiology
Costs
Pathophysiology
Diagnosis
Treatment
• Abortive
• Preventative
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Special considerations
Summary
Cases
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Case Number 1: 32 year old woman
with no other significant medical
history who states that she has
frequent severe headaches and has
previously been diagnosed with
migraine.
Cases
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Case Number 2: 43 year old woman with
self-reported history of:
•
•
•
•
•
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Migraine without aura
Seizure disorder
Depression
Anxiety
PMDD
Chart history of:
• Axis II, cluster B disorder
• Benzodiazepine and opiate dependence/abuse
Epidemiology
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1 year prevalence:
• overall: 11.7%
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women: 17.1%
men: 5.6%
• additional 4.5%
have "probable
migraine“
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Lifetime
prevalence:
• Women: 25%
• Men: 8%
Image from yourhealth.net.au
Epidemiology
Epidemiology
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Chronic migraine:
• 1-year period
prevalence 1-2%
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Migraine among
neurologists
• 50% prevalence
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Migraine among
headache specialists
• 75% prevalence
Epidemiology
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http://www.aiws.info/
Famous migraineurs
(suspected or known)
•
•
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•
Lewis Carroll
Elvis Presley
Joan of Arc
Elizabeth Taylor
Julius Caesar
Napoleon Bonaparte
Thomas Jefferson
Ulysses Grant
Frederich Nietzsche
Sigmund Freud
Claude Monet
Alexander Graham Bell
Terrell Davis
Cost to Society
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Direct Costs:
• Total cost of annual medical care:
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Family with migraineur: $7007 per year
Family without migraineur: $4435 per year
• National Burden: $11 billion
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$4.6
$5.2
$0.5
$0.7
billion
billion
billion
billion
was in prescription drugs
in outpatient costs
in ER
in inpatient costs
Cost to Society
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Indirect Costs:
• Estimated to be approximately $13.3 billion
• Due to missed work days and impaired work
performance
• Does not include:
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unemployment or underemployment
burden experienced between attacks
lost home-worker time due for chores
lost time because of caring for family members with
migraine.
Pathophysiology
?
Genetics
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Familial hemiplegic migraine
• Three different abnormal genes
• Mutations relate to ion channel function
and neuronal hyperexcitability
Genetics
1p13.3
Glutathione S-Transferase
(GST)
MO
1 p36
MTHF-R
MA
4 q24
?
MA & MO
4q31.2
Endothelin type A (ETA-231
A/G)
Not specified
6p21.3
Tumor necrosis factor α
(TNFα)
Not specified
6p21.3
HLA-DRB1
MO
6q25.1
Estrogen receptor 1 (ESR1)
MA & MO
6q25.1
Estrogen receptor 1 (ESR1)
Not specified
Females only
9q34
Dopamine β-hydroxylase
(DBH)
Not specified
11 q24
?
MA
11 p15
DRD4
MO
11q22-23
Progesterone receptor (PGR)
MA & MO
11q23
DRD2 Allele 1 TG
dinucleotide noncoding
MO
11q23
Dopamine D2 (DRD2) NcoI
MA
14 q21-22
?
MO
17q11.1-q12
Human serotonin
transporter (SLC6A4)
MA & MO
17q23
Angiotensin converting
enzyme (ACE)
MO
19p13.3/2
Insulin receptor INSR
Not specified
22q11.2
Catechol-Omethyltransferase
(COMT)
not specified
X q24-28
?
MO
4 q21
Pathophysiology
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Syndromic approach with migraine
as “final common pathway”
Maladaptive activation of trigeminal
cervical pain apparatus
• Early warning system to protect the
brain and cervical cord from injury
Pathophysiology
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Aura
• cortical spreading
depression
• initially decreased
and then increased
blood flow
• may be related to
initiation of
migraine
Image courtesy of http://migraine.co.nz/
Pathophysiology
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Micro-emboli
• Increased prevalence of PFO in patients with
migraine with aura
• Uncontrolled of PFO closure trials promising
• Controlled studies thus far not as promising
Types of Migraine
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Migraine without aura (common
migraine)
Migraine with aura (classic migraine)
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•
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Typical aura with migraine headache
Typical aura with non-migraine headache
Typical aura without headache
Familial hemiplegic migraine
Sporadic hemiplegic migraine
Basilar-type migraine
Diagnosis
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International
Classification of
Headache
Disorders (ICHD)
Very detailed set of
criteria available
at:
http://www.ihsclassification.org/en
Diagnosis
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Alternative (ie shorter) history:
• POUND
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Pulsatile quality of headache
One day duration (usually 4-72 hours)
Unilateral location
Nausea or vomiting
Disabling intensity
• 3/5 criteria = likely migraine
• 4/5 criteria = very likely to be migraine
Diagnosis
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Prodrome vs. Aura
• Prodrome
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Euphoria, depression, fatigue, hypomania,
food cravings, dizziness, cognitive slowing,
or asthenia
Occurs in 60-70% of migraine patients
• Aura
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Visual changes, loss of vision,
hallucinations, numbness, tingling,
weakness, or confusion
Occurs in 15-20% of migraine patients
Diagnosis
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Consider headache diary to better
determine triggers, etc.
http://www.relieve-migraine-headache.com/diary-headache-migraine.html
Developmental History
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Childhood periodic syndromes
that are commonly precursors of
migraine
• Cyclical vomiting
• Abdominal migraine
• Benign paroxysmal vertigo of childhood
Alarm Features
Alarm Features
Based on History
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Changes in headache pattern/freq/intensity
Daily headache
Blurred vision
Dizziness/syncope/discoordination/focal neuro
deficits
Sudden/explosive onset
Pain worse with coughing
Change in personality
Headache that wakes you up from sleep
Onset after 50 years of age
Alarm Features
Based on Physical
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Vitals: fever or hypertension (diastolic >120)
Mental status change
Meningeal signs
Diminished pulse or tenderness of temporal
artery
Focal neurologic deficits: including visual
acuity
Papilledema
Intraocular pressure
Necrotic or tender scalp lesions
Other signs of infection
Labs
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ESR
• Indicated for new onset headache if
age>50
• Screens for temporal arteritis and other
vasculitides
• Obtain even if symptoms consistent with
migraine
• Headache is predominant feature in 6580% of patients with temporal arteritis
Neuro-Imaging
Neuro-Imaging
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Consider if:
• Atypical migraine features
• Substantial change in headache pattern
• Signs or symptoms of neurologic
abnormalities
EEG
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Consider only if associated
symptoms suggest a seizure
disorder.
No useful headache subtype groups
are defined by EEG
EEG is not able to identify patients
with structural cause of headaches
Treatment
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“My migraine only gets better with that ‘d’
drug. You know, d…d…dilaudid…”
“My dilaudid only works IV and only if I
get at least 8mg at once.”
“I have to get benadryl with it or I get
itchy – I need 50mg… It has to be IV.”
“I’m sooo nauseated too. I’m allergic to
all the anti-nausea medications except IV
phenergan.”
- Patient from my last night in the UWMC ED
Treatment
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Brust’s Rule: if we have a lot of
treatments for a disease… none must
work very well…
Images from migraine support blogs
Treatment: Non-Pharmacologic
Treatment: Non-Pharmacologic
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Diet
• Some benefit to elimination diets
• 20% of patients report dietary triggers
• Common triggers:
Caffeine withdrawal
Packaged meats
MSG
Dairy
Fatty foods
Aged cheese
Red wine
Beer
Champagne
Chocolate
Treatment: Non-Pharmacologic
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Alcohol
• “If you must drink, no
more than two normal
size drinks”
• “Suggested drinks:
 Riesling
 Seagram’s VO
 Cutty Sark
 Vodka”
- As per Diamond S and
Dalessio DJ. The practicing
physician’s approach to
headache. New York:
Williams and Wilkings.
1982.
Treatment: Non-Pharmacologic
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Behavioral
• Shown to be effective
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30-50% reduction of migraine frequency
Modalities
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Relaxation training
Thermal biofeedback with relaxation training
Electromyogram biofeedback
Cognitive behavioral therapy
• No data to guide selection of modality…
Treatment: Abortive
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Tenets:
• Educate migraine sufferers
• Use migraine specific agents in severe
disease
• Non-oral route for patients with
significant nausea and vomiting
• Be aware of medication overuse and
rebound
Treatment: Abortive
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When to treat?
• EARLY
• Within 2 hours
• Treatment during
prodrome or aura is
even more effective
Image courtesy of denverpost.com
Treatment: Mild to Moderate
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NSAIDS
• Ibuprofen
• Naproxen
• Diclofenac
• Tolfenamic acid
• Indomethacin suppository
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Aspirin
Tylenol
Combinations
Treatment: Severe
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If severe symptoms present then
don’t bother with OTC preparations
• Improved outcomes with migraine
specific therapy
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Consider route of administration
Consider contraindications/PMH
Treatment: Triptans
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First line
• More effective
• Less nausea
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Contraindications
• CAD
• Cost
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Routes
• Oral
• Intranasal
• Subcutaneous
Image courtesy of headaches.about.com
Treatment: Triptans
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Mechanism of Action
• Selective serotonin agonist
• 5HT1B/1D
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Pharmacokinetics/dynamics
• Both long and short acting available
• Long acting more effective during aura
but take longer to act
• Short acting have more side effects
Treatment: Triptans
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Options
• Sumatriptan (subq/nasal/oral)
• Almotriptan (oral)
• Eletriptan (oral)
• Frovatriptan (oral)
• Naratriptan (oral)
• Rizatriptan (oral/ODT)
• Zolmitriptan (oral)
Treatment: Triptans
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Which one to choose…
• No class effect
• Recurrent headache may indicate need
for repeat dose, not new triptan
• Pharmacokinetics/dynamics
• Side effect profile
Treatment: Triptans
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Which one to choose…
• Specific concerns
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Teratogenicity
Menstrual migraine
Subq
• not effective during prodrome/aura
• More contraindications
Treatment: Dihydroergotamine
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Mechanism of Action
• Non-selective serotonin agonist
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Routes
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Nasal
Subq
IM
IV
Contraindications
• Pregnancy (category X)
• Cannot be used with a triptan
• IV contraindicated in CAD
Treatment: Adjuncts
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Anti-emetics
• Metoclopromide both as adjunct and
mono-therapy
• Ondansetron IV/oral/ODT
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Caffeine
• Rebound
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Steroids
• Dexamethasone
• Prednisone
Treatment: Rescue
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Opiates
• Should be used only a few times per
year
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Up to ½ of patients with recurrent
headache do not adhere to drug
treatment regimen
Treatment: Prevention
Treatment: Prevention
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Definitely consider:
• Disabling
headaches > 2x per
month
• Poor relief from
abortive therapy
• Uncommon
migraine
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Basilar
Hemiplegic
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Might consider:
• Contraindication to
acute therapy
• Failure of acute
therapy
• Preference for
preventative
therapy
Treatment: Prevention
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Rules to live by:
• Headache diary
• Patience
• No right agent
• Consider:
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Side effects
Other benefits
Treatment: Prevention
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Antihypertensives
• All agents effective
• Best evidence for beta blockers
• Limited evidence for CCB
• ACE and ARB also effective
• No evidence for diuretics
Treatment: Prevention
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Antidepressants
• Depression or other psychiatric disorder
often co-morbid condition
• Lack of evidence for SSRIs
• Tricyclics and mirtazepine shown to
have some benefit
Treatment: Prevention
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Anticonvulsants
• Valproate (FDA approved)
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At least as effective as b-blocker
May be better tolerated
• Topiramate (FDA approved)
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Requires slightly higher doses
Weight loss benefit
• Gabapentin
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Not FDA approved but appears effective
Treatment: Prevention
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Other agents
• Botulinum toxin injections: not
recommended
• Coenzyme Q10: small studies
• Magnesium: mixed results
• Butterbur (herbal): minimal evidence
• Feverfew (herbal): results
Special Consideration:
Rebound and Overuse
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Can occur with almost any headache
medication
To avoid:
• Limit acute medications to no more than 10
days per month
• Preventative therapies as mainstay of
treatment
• Use headache diary
Special Consideration:
Hospitalization
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Status migranosis
• Prolonged (>72h), intractable migraine
• Associated nausea and vomiting
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Overuse headache
• Inpatient weaning
Special Consideration:
Menstrual Migraine
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Estrogen effects
Two types
• Pure menstrual migraine
• Menstrually related migraine
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Treatment
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Usual abortive therapy
Estrogen-progestin OCP in extended cycle
Menstrually targeted supplemental estrogen
Long acting triptan prophylaxis
Some evidence for SERMs
Special Consideration:
Migraine and Stroke
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WHO
• Avoid estrogen containing OCPs:
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Migraine + over age of 35
Migraine with aura
ACOG
• Avoid estrogen containing OCPs:
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Migraine + over age of 35
Migraine + focal neurologic signs
Migraine + smoking
Special Consideration:
Other Migraine Disorders
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Retinal migraine
Complications of migraine
• Chronic migraine
• Status migrainosus
• Persistent aura without infarction
• Migrainous infarction
• Migraine-triggered seizure
Special Consideration:
Other Migraine Disorders
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Probable migraine
• Probable migraine without aura
• Probable migraine with aura
• Probable chronic migraine
Summary
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Migraine is exceedingly common
• 1 in 4 women, nearly 1 in 10 men
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Unclear pathophysiology
Diagnosis based primarily on history
• POUND
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Treatment
• Abortive: focus on migraine specific therapies
• Preventative: focus on patience
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Special cases
Resources and Further Reading
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Bartleson JD and Cutrer M. Migraine
Update: Diagnosis and Treatment. Minn
Med. May 2010.
In the Clinic: Migraine. Annals of Int Med.
2007;9:1-16.
Dr. Natalia Murinova
• UWMC Headache Clinic
References
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Catterall WA, Dib-Hajj S, Meisler MH, Pietrobon D. Inherited
neuronal ion channelopathies: new windows on complex
neurological diseases. J Neurosci. 2008;28(46):11768-77.
Charles A. Advances in the basic and clinical science of migraine.
Ann Neurol. 2009;65(5):491-8.
Cutrer FM. Pathophysiology of Migraine. Semin Neurol 2010;
30(2): 120-130.
Evans RW, Lipton RB, Silberstein SD. The prevalence of migraine
in neurologists. Neurology 2003;61:1271-2.
Evans RW. Migraine: A question and answer review. Med Clin N
Am 2009;93:245-62.
General Household Survey, Office for National Statistics. Fourth
National Morbidity Study from General Practice 1991/92, Office for
National Statistics. http://www.statistics.gov.uk/
Hawkins K, Rupnow M, Wang S. Direct cost burden of migraine
among members of US employers. Value Health 2006;9:A85.
References
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Hazard E, Munakata J, Bigal ME, Rupnow MF, Lipton RB. The
burden of migraine in the United States. Value Health
2009;12:55-64.
Hu XH, Markson LE, Lipton RB, et al. Burden of migraine in the
United States: disability and economic costs. Arch Intern
Med 1999;159:813–8.
IHS – International Headache Society; http://www.ihsclassification.org/en/
Lipton RB, Bigal, ME, Diamond M, et al. Migraine prevalence,
disease burden, and the need for preventive therapy. Neurology
2007;68:348-9.
Michel P, Dartigues JF, Henry P, et al. Validity of the IDHS criteria
for migraine. Neuroepidemiology. 1993;12:51-7.
Silberstein S, Loder E, Diamond S, et al. Probable migraine in the
United States: results of the American Migraine Prevalence and
Prevention Study. Cephalagia 2007;27:220-34.
UpToDate. Online 18.2.