Treating Migraines

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Treating Migraines
Charles Yanofsky M.D. www.susqneuro.com
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How Common is Migraine?

• 30,000,000 Americans
• 20 of women
• 7 of men at any given time
• Most of us have some migraine manifestations
  occasionally

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Recognizing Migraine

• Pounding unilateral headache
• Preceded by visual or other aura
• Nausea, vomiting
• Light and sound sensitivity

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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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World prevalence of migraineA disorder of First
World
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Diagnosis of migraine

• Diagnosis depends on patient history
• No specific tests or clinical markers

• 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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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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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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Physiology

• Vasospasm Lance
• Spreading Wave of Depression Leao
• Trigeminocentric
• Allodynia

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Vasospasm

• I. Aura Arteries Spasm
• Visual and focal neurological symtoms
• Pial and Occipital small artery branches
• II. Headache Compensatory Vasodilation
• Pounding unilateral sick headache
• III. Inflammation and muscle spasm second pain
  phase

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Phases of Migraine

• Vague Prodrome psychic change and cravings e.g.
  chocolate
• Aura Focal symptoms and vision
• Headache Throbbing unilateral pain
• Inflammation Prolonged phase and TTH
• Postdrome
• Migraine related stroke

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Spreading Wave

• Brainstem controls Cortical Activity
• Epileptic like phenomenon that spreads over
  Cortex
• Visual Phenomenon that spreads over surface of
  brain like shimmering C
• Cheiro-oral Jacksonian phenomena
• Concurrence of migraine and epilepsy
• Why epilepsy drugs work for migraine

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Trigeminal Theory

• Serotonin again
• Trigeminal Afferents sensory function of face
  and meninges
• Trigeminal efferents to vessels
• Cause vessel spasm and sensitivity
• This theory primarily explains action of
  Triptans 5-HT 1b,d agonists

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Migraine Pathophysiology
Goadsby NEJM 346 257-70,2002
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Allodynia Theory

• Migraine is a state of hypersensitivity
• Light, sounds, smells, touch (head in headache)
• Need for dark room
• Best preventives decrease sensitivity.
• Anticonvulsants, tricyclics, beta and calcium
  channel blockers

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What is Central Sensitization?

• Central Sensitization is a time-dependent
  physiological event
• During a migraine attack, neuronal pathways
  become sensitized in stages
• Peripheral neurons are activated early in the
  attack (mild pain phase throbbing)
• Central neurons are activated later in the attack
  (full-blown migraine)

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Cutaneous allodynia

• Phenomenon later in migraine attack
• Once it develops pts less likely to respond to
  triptans
• In small sample 15 of pts with and 93 of pts
  without CA responded to triptan (Burstein et al)

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• Each of these Theories explains some migraine
  phenomena

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Migraine Phenomena

• Focal and paroxysmal onset of symptoms
• Specific visual phenomena
• Spreading numbness and moving visual phenomena
  and sensory distortions.
• Nausea, vomiting sick headache
• Pounding unilateral or bilateral pain
• Psychic changes
• Light and sound sensitivity even between attacks
• Effectiveness of triptans
• Effect of anticonvulants
• Role of serotonin

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Some Dicta

• Any paroxysmal headache is likely to be migraine
  unless proven otherwise
• Sinus headaches and tension headaches are
  almost always migraine headaches
• First ever severe headache or sudden
  thunderclap headaches may be SAH

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Treatment

• Effective treatment of attack
• Prevention
• Address comorbidities

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Mechanisms for treatment
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Acute Attack

• Triptans
• sumatriptan, zolmitriptan, almotriptan,
  naratriptan, frovatriptan, elitriptriptan,
  riaztriptan
• NSAIDs
• Fioricet
• Midrin (isometheptane, chlorphenoxazone, apap
• OTC Caffeine, apap, phenacitin, asa
• Ergots Caffergot, DHE nasal, injected
• Narcotics
• Depacon

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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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Triptans

• Learn to use one or two
• Effective medicines

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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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Elitriptan or RelpaxAdvantages

• Quick oral absorption
• Reliable oral absorption
• Relatively long half life
• Numerous Clinical trials where proven superior to
  Imitrex
• Gets in fast, and stays around
• Low rebound recurrence rate
• Works for all migraine phenonena
• Pain, photosonophobia, nausea

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Relpax Cautions

• Available only in oral form
• CYP 3A4
• Do not give within 72 hours of Ketoconazole,
  Nefazadone, clarithromycin, rotonavir,
  nelfinavir, others. caution with verapamil,
  erythromycin.
• Contraindications (all triptans)
• Suspected Coronary disease
• Basilar or hemiplegic, ophthalmoplegic migraine
• Uncontrolled hypertension
• lt18 or gt65
• Within a day of any other triptan
• Hypersensitivity to the drug

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Migraine visual Aura from classic oph textbook
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Autoscopy
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Relpax Dosing

• 40 mg. May repeat X1 in 2 hours
• Max dose in 24 hours is 80 mg
• Repeating dose most efficacious if headache
  returns

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Parenteral triptans

• Imitrex injections Very good fast reliable onset
  but peaks quickly with short half life
• Imitrex and Zomig nasal absorption not reliable,
  taste not so good but may be tried if a lot of
  nausea
• Zomig ZMT and Maxalt MLT on tongue not strictly
  parenteral absorbed thru gut

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Triptan worries

• Not released under age 18
• If you even suspect CAD dont use or get proper
  exclusionary tests.
• Man or woman of a certain age
• Smoker or other risk factors
• Cerebrovascular disease or complicated migraine -
  contraindicated
• Watch for overuse. These are rescue medicines

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Consider Combinations

• Triptan NSAID
• Triptan anti-nausea
• Unconventional agents
• Phenergan, Compazine alone or in combination.
  Zyprexa or atypicals
• We dont have enough alternatives

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Prophylaxis

• Anticonvulsants topiramate, valproate, Keppra,
  gabapentin
• Tricyclics
• Amitriptylene, nortriptylene, trazodone
• Beta Blockers
• Timolol, propranolol, nadolol
• Calcium channel blocker verapamil
• ACE inhibitors
• SSRIs
• Atypicals

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Plea

• Listen to patients
• Migraine is mixed up with a lot of things
• Emotional factors ennui, husbands, bosses,
  general dissatisfaction with life
• Sleep disturbances
• Hormonal changes
• If you do not address these you will not be
  treating your patients
• Dont just throw drugs at your patients
• Be attentive and empathetic