Charles Yanofsky M'D'

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Migraine
The Dark Side Pitfalls of therapy
www.pneuro.com
Charles Yanofsky M.D. PA Neurological Assocs.
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World prevalence of migraineA disorder of First
World
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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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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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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 Without Aura

• Diagnostic Criteria
• A. At least 5 attacks fulfilling criteria B-D
• B. HA attacks lasting 4-72 hours
• C. HA has at least 2 of following
• 1. Unilateral location
• 2. pulsatile quality
• 3. moderate to severe pain
• 4. aggravation by routine physical activity
• D. During attack at least one of follg
• 1. Nausea and/or vomitting
• 2. photophobia and/or phonophobia

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Migraine Pathophysiology
Goadsby NEJM 346 257-70,2002
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Mechanisms for treatment
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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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Triptans

• Major Advance in treatment of migraines
• Useful for Occasional Highly paroxysmal headaches
• Oral administration Newer agents may be more
  effective than Imitrex (sumatriptan)
• Imitrex Nasal and SQ form available
• Triptans Partial answer

serotonin
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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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Individual eletriptansumatriptan comparison
trials Headache response at 2 h
Patients with response
100 80 60 40 20 0
Study 314
n605


Sumatriptan
Goadsby et al (2000)
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Elitriptan in Pts poorly tolerance or response to
Sumatriptan

• 446 pts, 40 or 80 mg v placebo
• 2 hr ha response up to 70 for 80mg, 59 for 40
  mg
• 2 hr pain free 35 E40, 42 E80
• Farkkila et al, Cephalalgia 2003,23,463-471

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Pharmacokinetic parameters for eletriptan and
sumatriptan
Intersubject variability 37 60 Oral
bioavailability 50 14
Renal clearance 10 20 Metabolic
pathway P450 MAO4
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Relpax (Eletriptan) Advantages

• Favorable pain free, 1 and 2 hour efficacy vs.
  Sumatriptan
• Longer half life, quick absorption
• Peak 1.5-2 hrs, T1/24 hrs, 50 oral absorption
• Cerebro (vs. Cardio) Selective
• Avid binder to relevant receptors

Eletriptan (Relpax)
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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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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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After Triptans
Refractory Migraine
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Why we fail (and what to do about it)

• Misdiagnosis exclusion, inclusion
• Unrealistic expectations
• Chronic Daily headache and rebound
• Logic and Persistence
• Ignoring psychological factors
• Missing Red Flags

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Sinus Headache and Tension Headaches are almost
always migraine headachesTension headache
pharmacologically is Migraine
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Sinus Headache Fallacy

• Paroxysmal headaches are migraine until proved
  otherwise.
• Most Sinus headaches are migraines
• Sinus headaches are rare in comparison to
  migraine.
• Patients commonly present years or decades after
  failed treatment for sinus headaches
• ENTs among our most frequent referrers for head
  pain

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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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Expectations

• Two thirds of patients will have a 50 reduction
  of headaches
• Migraine is a Chronic Disease
• No Preventive therapy will eliminate all
  headaches
• Patients should expect breakthrough headache
• Give patient some means of escape
• You cant kill every headache with medicine
• Rules of the game have to be explained

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Morphed Migraine

• Conversion from headache attacks to chronic
  headache.
• Paroxysmal headache becomes chronic headache
• Patients describe multiple headache types
• All of them are migraine variants
• Migraine natural history
• Asthma becomes COPD
• RR MS becomes secondary progressive MS

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Chronic Daily HA
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Treating Morphed Migraine

• Cut prn meds
• Tough to convince pts to give up prn meds
• Emphasize preventive meds
• Treat psychosocial comorbidities
• Psychotherapy, counseling
• Medicine
• Ancillary modalities
• Relaxation, biofeedback, exercise, healthtful
  habits

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Comorbidities
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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
• New onset headache in middle age or later
• New progressive headache lasting for days
• Precipitation by cough, sneeze, bending down
• Systemic symptoms fever, myalgia, malaise, wt
  loss, scalp tenderness, jaw claudication
• Focal symptoms or altered sensorium, seizures
• Pryce-Phillips et al, 1997

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Children red flags

• AM headache
• Posterior Headache
• Vomiting without nausea
• Papilledema
• Focal signs or ataxia
• Consider tumor or pseudotumor

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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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But the vast majority of these headaches turn out
to be migraines!!
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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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Headache Crisis

• Rule out serious Cause
• DHE Reglan i.v.
• Toradol i.v. Reglan
• Depacon i.v. 1000 mg.
• Decadron
• Morphine infusion
• Consider outpatient Actiq-saves trip to ER
• Dependence

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Medication Impersistence
Treatment
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Changing Meds

• Most preventives reqr 1-2 month trial
• Long lists of meds
• Inadequate trial
• Inadequate dosage
• I want relief now!!
• 2 headache (for PRNs), 2 month (for prophylaxis)
  rule

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Inadequate trials

• Pick a medication
• Good track record Type IA evidence
• Treat comorbidities
• Sleep disturbance
• Depression
• Hypertension
• Use it long enough for reasonable trial
• 2 months No medicine works immediately
• Headache calendar
• Give patient an out for breakthru headache

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Ignoring psychological factors

• Underlying migraine diathesis (history)
• Very frequent gnawing headache or
• Screamingly urgent headache frequently
• State of being overwhelmed
• Sub-optimal life strategies
• Ennui vs. pointless moto-perpetuo pattern

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When ? paramount

• Dont abandon patient
• Give her an out
• Continue to treat headaches
• Get Help!!
• Dont just keep trying medicines and throwing
  SSRIs at patient
• Therapy in guise in non-drug treatment
• Exercise, getting away, regularization of sleep,
  diet, Counseling
• Surprisingly, some few patients respond
  dramatically, sadly, most dont

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HA prophylaxis

• Anti-convulsants are in
• Topamax, Depakote ER and i.v., Zonegran,
  Neurontin, Keppra
• Tricyclics, not SSRIs for headache and sleep,
  depression comorbidity
• ACE inhibitors Prinivil, Atacand
• Botox, Myobloc

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Our Armamentarium expands
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Botox (from B. Todd Troost, m.d.)
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Conquering Headache
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Thats the Tale of the Comet
Fini