Download Headache - migraineKI

Treating Migraines
Professor Yasser Metwally
www.yassermetwally.com
World prevalence of migraine
Denmark 10%
Switzerland 13%
France 8%†
USA 12%
Italy 16%
Chile 7%
†Prevalence measured over a few years
Japan 8%
 1-year prevalence rates
 Population-based studies
 IHS criteria (or modified)
Rasmussen and Olesen (1994); Rasmussen (1995);
Lipton et al (1994); Lavados and Tenhamm (1997);
Sakai and Igarashi (1997)
Prevalence of migraine by
sex and age
Migraine prevalence (%)
30
Females
Males
25
20
15
10
5
0
20
30
40
50
60
Age (years)
70
The American Migraine Study (n=2479 migraine sufferers)
80
100
Lipton and Stewart (1993)
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 <45
presence of aura
menstrual association
Organic disease must be excluded
Cady (1999); Warshaw et al (1998)
Migraine Criteria
5 attacks lasting 4–72 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
SULTANS: two from column A, one
from column B
evere
ni
ateral
hrobbing
Ctivity worsens
ausea
Lite and sound
ensitivity
What is migraine?
Migraine without aura
(MO)
At least five attacks fulfilling these
criteria:
Headache lasting 4–72 h
(2–48 h in children)
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
Migraine with aura (MA)
At least two attacks fulfilling these
criteria:
At least three of the following:
– one or more fully reversible
aura symptoms
– gradually developing or
sequential aura symptoms
– no one aura symptom lasts
longer than 1 h
– headache shortly follows or
accompanies aura
No evidence of organic disease
Headache Classification Committee of IHS (1988)
Clinical features of migraine
Normal
Headache
Appetite
Awake/sleep
Normal
food tolerance Appetite
Tired
Awake/sleep
Light tolerance
Feeling
high or
Noise
Light tolerance
Noise
low
Smell
Smell
Diuresis
Fluid balance
Normal
I
II
Prodromes Aura
III
IV
Headache Resolution
V
Postdromes
Fluid balance
Normal
Blau (1992)
Migraine Patients Suffer From Pain
and Symptoms
Moderate to severe pain
99%
81%
Photophobia
77%
Phonophobia
Nausea
74%
Vomiting
30%
0
20
40
60
80
100
Percentage of patients reporting symptom
Adapted from Lipton et al. Headache. 2001.
Migraine Remains Underdiagnosed
and Undertreated
Percentage of patients
100
75
50
49%
48%
23%
25
23%
5%
0
MD diagnosis
Rx medication
only
OTC medication
only
Both Rx
and OTC
No medication
Lipton et al. Neurology. 2002.
IMPORTANT DIAGNOSTIC
CONSIDERATIONS
No single criterion necessary nor sufficient for diagnosis
15% of patients have a neurological aura
IHS criteria do not require GI symptoms
Vomiting occurs in < 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
Russell MB, et al. Cephalalgia. 1996.
Pryse-Phillips WEM, et al. Can Med Assoc J. 1997.
Premonitory, aura and postdromal
symptoms
Prodrome
 Occurs in 60%
 Alterations in
–
of attacks
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
Postdrome
 Occurs in 90% patients
 Symptoms can persist for
several days
– lethargy
– exhaustion
– impaired concentration
– irritability
– sluggishness
– diminished appetite
– euphoria
Silberstein and Lipton (1994);
Lance (1993); Blau (1992)
MIGRAINE WITH AURA
(FORMERLY “CLASSIC”
MIGRAINE)
Complex array of symptoms
reflecting focal cortical or
brainstem dysfunction
Gradual evolution:
5–20 minutes (<60 minutes)
May or may not be associated
with headache
Visual > sensory > motor,
language, brainstem
International Headache Society. Cephalalgia. 1988;8;(suppl 7):1-96.
MIGRAINE AURA
“Cheiro-oral”
Fortification Spectrum
DIAGNOSIS AND TESTING
Detailed History and Examination
NO
Primary Headache?

Preliminary Diagnosis
YES
Secondary
Headache
Diagnostic
Testing
Atypical
Features
Alice in Wonderland
REASONS FOR
MISDIAGNOSIS OF MIGRAINE
Sinus AS TTH OR SINUS
Migraine is a referred pain syndrome (V1, C1-C3)
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
Raskin NH. Headache. 2nd ed. 1988; Barbanti P, et.al. Cephalalgia. 2001;
Kaniecki R. Cephalalgia. 2001.
Differential diagnosis of
primary headaches
Clinical feature
Migraine
Cluster headache
Tension headache
Family history
Yes
No
Yes
Sex
More females
More males
More females
Onset
Variable
During sleep
Under stress
Location
Usually unilateral
in adults
Behind/around
one eye
Bilateral in band
around head
Character/severity
Pulsatile
Throbbing
Excruciating/
sharp
Steady
Dull
Persistent Tightening/pressing
Frequency/
duration
Associated
symptoms
2–72 h/attack
1 attack/year to
>8 per month
Visual aura
Phonophobia
Photophobia
Pallor
Nausea/vomiting
15–90 min/attack
1–8 attacks/day
for 3–16 weeks
1–2 bouts/year
Sweating
Facial flushing
Nasal congestion
Ptosis
Lacrimation
Conjunctival injection
Pupillary changes
30 min to 7 days
3–4 attacks/week
to 1–2 attacks/year
Mild photophobia
Mild phonophobia
Anorexia
Dubose et al (1995); Goadsby (1999); Marks and Rapoport (1997)
WORRISOME HEADACHE RED
FLAGS
“SNOOP”
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 >50 (giant cell arteritis)
Previous headache history: first headache or different
(change in attack frequency, severity, or clinical features)
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/
bending down
Systemic symptoms such as myalgia, fever, malaise,
weight loss, scalp tenderness, jaw claudication
Focal symptoms, seizures, confusion, impaired
conciousness, physical examination Pryse-Phillips
abnormalities
et al (1997)
EVALUATION STRATEGIES
“Investigate
the
Atypical
and the
Red Flags”
SUDDEN ONSET HEADACHE
Primary
Idiopathic thunderclap
headache (TCH)
Sexual headache
Exertional headache
Cough headache
Secondary
SAH
Venous sinus thrombosis
Pituitary apoplexy
Arterial dissection
Meningoencephalitis
Acute hydrocephalus
Acute hypertension
deBruijn, SF, et al. Lancet. 1996; Lancet. 1998.
Spontaneous intracranial
hypotension
LUMBAR PUNCTURE
The first unusually severe headache
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)
Evans RE, Rozen TD, Adelman JU. In: Wolff’s Headache And Other Head
Pain. 2001.
SENSITIVITY OF CT SCAN IN
SUBARACHNOID HEMORRHAGE
(SAH)
TIME AFTER
HEADACHE
ONSET
PROBABILITY
(%)
DAY 0
95
DAY 3
80
1 WEEK
50
2 WEEKS
30
3 WEEKS
~0
van Gijn J, van Dongen KJ. Neuroradiology. 1982.
Kassell NF et al. J Neurosurg. 1990.
DIAGNOSIS TESTING
CT AND MRI
In patients with recurrent migraine, neither CT nor
MRI is warranted except in cases where:



Recent substantial change in headache pattern
History of seizures
Focal neurologic symptoms or signs
Role of CT or MRI in patients with
nonmigraine headache is unclear
Consensus expert opinion

MRI is more sensitive
Report of Quality Standards Subcommittee of AAN. Neurology. 1994.
DIAGNOSTIC TESTING
ELECTROENCEPHALOGRAPHY
EEG is not useful

In the routine evaluation of patients with headache
to exclude structural cause
EEG may be useful in those patients with
Alteration or loss of consciousness
 Residual focal neurologic defects or
encephalopathy
 Atypical migrainous aura

Report of Quality Standards Subcommittee of AAN. Neurology. 1995.
MR AND CONVENTIONAL
ANGIOGRAPHY
MR Angiography
Angiography
Aneurysm (>5 mm)
Acute SAH
AV malformation
CNS vasculitis
Arterial dissection
Arterial dissection
Venous thrombosis
(MR venography)
Leclerc X et al. Neuroradiology. 1999.
INDICATIONS FOR GADOLINIUM
ENHANCED MRI
Cerebrovascular
–
–
–
Arterial dissection
(MRA)
Cerebral venous
sinus thrombosis
(MRV)
CNS vasculitis
Herpes encephalitis
Bousser MG et al; Wall M et al; Mokri B; and
Newman C, Solomon S. In: Wolff’s
Headache And Other Head Pain. 2001. Tien
RD et al. AJR Am J Roentgenol. 1993.
Tumors
–
–
–
Posterior fossa
Pituitary
Leptomeninges
High and low
intracranial pressure
syndromes
MRA = magnetic resonance angiography.
MRV = magnetic resonance venography.
CEREBRAL VENOUS SINUS
THROMBOSIS
Bousser MG et al. In: Wolff’s Headache And Other Head Pain. 2001.
Sleepers Awake!!
Treatment
STRATEGIES FOR MIGRAINE
TREATMENT
Acute
treatment
To stop pain
and prevent
progression
Preemptive
treatment
Preventive
Treatment
Migraine trigger
time-limited and
predictable
Decrease in
migraine frequency
warranted
Silberstein SD. Cephalalgia. 1997.
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
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
NONPHARMACOLOGIC
TREATMENTS
Effective: GRADE A




Relaxation training
Thermal biofeedback with relaxation training
EMG biofeedback
Cognitive behavioral therapy
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
Goslin RE et al. Behavioral and Physical Treatments for Migraine Headache. 1999.
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
MIGRAINE TRIGGERS
Physical exertion
Diet
Hormonal changes
Head trauma
Stress and anxiety
Sleep deprivation or excess
Environmental factors
ACUTE MIGRAINE MEDICATIONS
Nonspecific
 NSAIDs
 Combination
analgesics
 Opioids
 Neuroleptics/antiemetics
 Corticosteroids
Specific
 Ergotamine/DHE
 Triptans
ACUTE THERAPIES FOR
MIGRAINE
GROUP 1a:
Substantial empirical evidence and
pronounced clinical benefit in
migraine
Migraine-Specific
Medications
 Triptans
 DHE

Nonspecific Prescription
Medications
 Butorphanol IN
 Ibuprofen/Naproxen sodium
SC, IM, IN, IV (plus antiemetic)
 Prochlorperazine IV
Silberstein SD. Neurology. 2000.
ACUTE THERAPIES FOR
MIGRAINE
GROUP 1b:
Substantial empirical evidence of
clinical benefit in restricted
populations
Over-the-Counter Analgesics
 Aspirin
 Acetaminophen, aspirin, plus caffeine
GROUP 2:

Opioids
Moderate empirical evidence and
clinical benefit

Silberstein SD. Neurology. 2000.
Others
CONSIDERATIONS IN INITIAL
ACUTE THERAPY
Match treatment intensity to attack severity
(stratified care)

Ask about migraine disability and impact
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
Silberstein SD. Neurology. 2000.
Cranium
Dura mater
Trigeminovascular
model of migraine
Afferent
Trigeminal
ganglion
Dura mater
Peptide releasing
neurones
Blood
vessels
Efferent
Trigeminal
nerve
Afferent
Efferent
CGRP/SP
release
Dilatation
Adapted from Goadsby and Olesen (1996)
Mechanisms for treatment
Trigeminal
nerve
INHIBITION
5-HT1D
5-HT1F
CGRP triptan
NK
SP
CGRP
calcitonin gene
related peptide
NK
neurokinin A
SP
substance P
CONSTRICTION
5-HT1B
Blood vessel
Adapted from Goadsby (1997)
TRIPTANS
Selective 5-HT1B/1D/1F agonists
As a class, relative to nonspecific therapies,
triptans provide
 Rapid
onset of action
 High efficacy
 Favorable side effect profile
Adverse events and contraindications
Silberstein SD. Neurology. 2000.
TRIPTANS:
TREATMENT CHOICES
Almotriptan
Sumatriptan



Tablet
Tablet (25, 50, 100 mg)
Injection (6 mg)
Nasal spray (5, 20 mg*)
Frovatriptan
Tablet


Tablet (1, 2.5 mg)
Rizatriptan

Tablet
Tablet (2.5, 5 mg)
Nasal spray (5 mg)
Naratriptan
Tablet (5, 10 mg)
* Pediatric efficacy shown
(2.5 mg)
Eletriptan
Zolmitriptan

(6.25, 12.5 mg)
(20, 40 mg)
Question and Answer

Are there differences
between the triptans?

If one triptan fails, will
another triptan work?
Ferrari MD et al. Lancet. 2001.
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
FORMULATION: ONSET
Increasing Speed
Oral
Parenteral
Tablet
IN
SL
PR
IM/SC
IV
Sumatriptan
Sumatriptan (Glaxo Wellcome)
NMe 2
– 5-HT1B/1D agonist
MeNHSO 2
N
H
Major advance – good efficacy with
subcutaneous formulation
Slow onset (2–4 h p.o.); LogD -1.5
Short t1/2 (2 h)
Ferrari et al (1995)
Efficacy of Eletriptan:
Comprehensive Relief at 2 Hours
Placebo
Sumatriptan 100 mg
Eletriptan 40 mg
Headache response, %
80
*†
60 *
Pain-free response, %
*†
40
Relief of Nausea, %
40
*
30
†
* * 80
20
20
10
0
40
20
60
20 20
40
Relief of Photophobia, %
*†
* 60
80
40
60
*
*†
Relief of Phonophobia, %
80
Sumatriptan was blinded using encapsulation. Encapsulated sumatriptan was bioequivalent to commercial tablets.
*P<.001 vs placebo. †P<.05 vs sumatriptan.
Adapted from Mathew et al. Headache. 2003.
Incidence of Adverse Events*
Placebo
20 mg
Eletriptan
40 mg
80 mg
(n=988)
(n=431)
(n=1774)
(n=1932)
Asthenia
3%
4%
5%
10%
Nausea
5%
4%
5%
8%
Somnolence
4%
3%
6%
7%
Dizziness
3%
3%
6%
7%
Headache
3%
4%
3%
4%
Paresthesia
2%
3%
3%
4%
Dry mouth
2%
2%
3%
4%
Chest tightness/pain/pressure
1%
1%
2%
4%
*Events experienced by 2% of patients. Incidence following a single dose of study medication.
The maximum recommended single dose of eletriptan is 40 mg.
Relpax® (eletriptan HBr) Prescribing Information. Data on file. Pfizer Inc., New York, NY.
Headache responses continue to
improve over time after eletriptan
dosing
% Patients with response
100
Time course for headache response
**
80 mg eletriptan
n=563
80
**
40 mg eletriptan
20 mg eletriptan
60
**
40
Placebo
20
0
0
1
Study 314
**P<0.05 vs placebo for all doses
2
3
4
Time post dose (h)
Pfizer, data on file
ACUTE TREATMENT
PRINCIPLES
 stratified care
 Early intervention
 Use correct dose and formulation
 Use a maximum of 2–3 days/week
 Use preventive therapy in selected patients
Silberstein SD. Neurology. 2000; Lipton RB, et al. JAMA. 2000.
STEP VS. STRATIFIED CARE
Start
A
B
C
C
Start
B
A
BASIS OF STRATIFICATION
 Headache onset and severity


Fast onset may benefit from parenteral therapy
Disability predicts treatment needs
 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
Silberstein SD. Neurology. 2000.
MIDAS Score
Days in Last 3 months
You’ve 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??
GradeDefinitionScore
I Minimal or infrequent disability 0-5
II Mild or infrequent disability 6-10
III Moderate disability 11-20
IV Severe disability 21+
DISABILITY IN STRATEGIES OF
CARE (DISC) STUDY
Compared 3 strategies of migraine management over 6 attacks
Stratification based on disability


MIDAS Grade II—ASA + M
MIDAS Grade III, IV—Triptan (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
Lipton RB et al. JAMA. 2000.
TREAT MIGRAINE WHEN PAIN IS MILD
Post-hoc analysis of Spectrum study (26 patients)
showed sumatriptan provided more effective relief with
less recurrence when taken while pain was still 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
Cady RK et al. Headache. 2000; Cady RK et al. Clin Ther. 2000;
Hu XH et al. Headache. 2002.
TRIPTANS IN THE SPECTRUM
OF MIGRAINE
Patients with disabling migraine have different headache
types, including migraine, migrainous, and tension-type
headache (TTH)
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
Lipton et al. Headache. 2000; Cady RK et al. Cephalalgia. 1997.
RECURRENCE & REBOUND
Recurrence: Return of episodic
headache during the same attack
following acute treatment
 Prevention:
Treat early, add NSAID. Use long
duration triptan or DHE
 Treatment:
Repeat initial acute headache drug;
almost always effective
Rebound: Recurring headache induced
by repetitive and chronic overuse of
acute headache medication
Tfelt-Hansen P et al. Drugs. 2000; Capobianco DJ et al. Headache. 2001.
APPROACH TO DIFFICULT
HEADACHE PROBLEMS
Problem
Strategy
Lack of response
Treat earlier, increase dose, add
metoclopramide or NSAID, change
formulation or triptan. Add preventive.
Headache recurrence
Treat earlier, add NSAID, increase dose,
change triptans (consider naratriptan or
frovatriptan), or switch to DHE
Elderly
Use acetaminophen, COX 2 inhibitors,
opioids, atypical neuroleptics
Pregnancy
Use acetaminophen, opioids,
corticosteroids, neuroleptics
Adverse effects
Switch triptans, use a different class
Silberstein SD et al. Wolff’s Headache and Other Head Pain. 2001.
SUMMARY OF ACUTE
MIGRAINE MANAGEMENT
Make a specific, credible diagnosis and communicate it
Assess migraine severity and it’s impact on the patient
Determine the patient’s 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 patient’s needs, preferences, and comorbidities
Consider need for preventive treatment
Eletriptan Dosing and Administration
• RELPAX should be taken at the onset of a migraine
headache.
• RELPAX can be taken with or without food.
• RELPAX should not be used within at least 72 hours
of treatment with the following potent CYP3A4
inhibitors: ketoconazole, itraconazole, nefazodone,
troleandomycin, clarithromycin, ritonavir and
nelfinavir.
• Studies have shown that the pharmacokinetics of
eletriptan are generally unaffected by age, gender, or
menstrual cycle.
Relpax® (eletriptan HBr) Prescribing Information. Pfizer Inc., New York, NY.
Eletriptan: Key Clinical Trials
Double-blind, Placebo-controlled, Randomized Trials
Phase II/III/III-b
clinical program
8 trials; N=8105
Placebo
8 trials; n=1508
25 mg
1 trial;
n=180
50 mg
2 trials;
n=362
Sumatriptan
4 trials; n=1690
100 mg
3 trials;
n=1148
Eletriptan
8 trials; n=4704
20 mg
2 trials;
n=434
40 mg
8 trials;
n=2797
Cafergot®
1 trial; n=203
80 mg
6 trials;
n=1473
The maximum recommended single dose of eletriptan is 40 mg.
Data on file. Pfizer Inc., New York, NY.
Efficacy of Eletriptan:
Pain-free at 2 Hours
50
Percentage of patients
40
36%*†
30
27%*
20
10
5%
0
Placebo
(n=406)
Sumatriptan
100 mg
(n=799)
Eletriptan
40 mg
(n=782)
Sumatriptan was blinded using encapsulation. Encapsulated sumatriptan was bioequivalent to commercial tablets.
*P<.0001 vs placebo. †P<.001 vs sumatriptan.
Adapted from Mathew et al. Headache. 2003.
Data on file. Pfizer Inc., New York, NY.
Chronic Daily HA
Tension (v. migraine)
10 attacks lasting 30 min–7 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
MIGRAINE
ADDITIONAL FEATURES
Predictable timing around menstruation (or ovulation)
Stereotyped premonitory symptoms
Characteristic triggers
Abatement with sleep
Positive family history
Childhood precursors (motion sickness, episodic vomiting,
episodic vertigo)
Osmophobia
Pryse-Phillips WEM, et al. Can Med Assoc J. 1997.
UNDIAGNOSED MIGRAINE SUFFERERS
OFTEN RECEIVE OTHER MEDICAL
DIAGNOSES
32%
Tension-type HA
42%
Sinus HA
0%
10%
Lipton RB et al. Headache. 2001.
20%
30%
40%
50%
AURA: MIMICS AND
SECONDARY CAUSES
AVM
Tumor
TIA
Simple partial
seizure
Carotid artery dissection
Venous sinus thrombosis
Vasculitis
Bousser MG et al. In: Wolff’s Headache And Other Head Pain. 2001; Campbell JK,
Sakai F. In: The Headaches. 2000; Silberstein SD, Lipton RB, Goadsby PJ. Headache
in Clinical Practice. 2002.
LATE-LIFE MIGRAINE
ACCOMPANIMENTS VS TIA
Build up of scintillations—“march” of paresthesias
Progression from one accompaniment to another
Repetition (2 similar attacks)
Mild headache in 50%
Duration 15–25 minutes
Characteristic midlife flurry of attacks
Fisher CM. Can J Neurol Sci. 1980; Silberstein SD, Saper JR, Freitag FG. In: Wolff’s
Headache And Other Head Pain. 2001.
MIGRAINE AND STROKE
Coexistent
Causal
Comorbid
Clinical manifestations of underlying disease
(MELAS, CADASIL)
Bousser MG et al. In: Wolff’s Headache And Other Head Pain. 2001.
CADASIL
CSF XANTHOCHROMIA AFTER SAH
SPECTROPHOTOMETRY
TIME AFTER
HEMORRHAGE
PROBABILITY
(%)
12 HOURS
100
1 WEEK
100
2 WEEKS
100
3 WEEKS
>70
4 WEEKS
>40
Vermeulen M et al. J Neurol Neurosurg Psychiatry. 1989.
Preventive Management of Migraine
GUIDELINES: WHEN TO USE
PREVENTIVE MANAGEMENT
Migraine significantly interferes with patient’s
daily routine, despite acute Rx
Acute medications contraindicated, ineffective,
intolerable AEs, or overused
Frequent headache (2 attacks per week)
Uncommon migraine conditions
Cost considerations
Patient preference
Silberstein SD et al. Wolff’s Headache And Other Head Pain. 2001.
GOALS OF PREVENTIVE
TREATMENT
Decrease attack frequency (by 50%),
intensity, and duration
Improve responsiveness to acute Rx
Improve function and decrease
disability
Silberstein SD et al. Headache in Clinical
Practice. 2nd ed. 2002.
Migraine Prevention
GENERAL PRINCIPLES OF
PREVENTIVE TREATMENT
Start low and increase dose slowly

Use long-acting formulation if compliance an issue
Adequate trial (2–3 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

Silberstein SD et al. Headache in Clinical Practice. 2nd ed. 2002.
PREVENTIVE MEDICATIONS:
DRUG CLASSES
Anticonvulsants
NSAIDs
Antidepressants
5-HT antagonists
-Blockers
Other
Ca2+-Channel
blockers
Silberstein SD. Cephalalgia. 1997.
Vitamins
 Minerals
 Herbs
 Botulinum
Toxin A

GENERAL PRINCIPLES OF
PREVENTIVE TREATMENT
Assess Coexisting Conditions
Select drug to treat both disorders
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
Silberstein SD et al. Headache in Clinical Practice. 2nd ed. 2002.
Comorbidities
Depression “SALSA”
Sleep Disturbance
 Anhedonia
 Low
 Self-esteem
 Appetite Change

COMORBID AND COEXISTENT
CONDITIONS
Coexistent disorders are
commonly present
Therapeutic opportunities

Treat two disorders with a single drug
Hypertension or angina—use -blocker
 Depression—use TCAs or SSRIs
 Epilepsy or mania—use divalproex or topiramate

Therapeutic limitations

Avoid -blockers with depression, asthma, or
hypotension
Silberstein SD et al. Headache in Clinical Practice. 2nd ed. 2002.
PREVENTIVE TREATMENT:
DRUG CHOICE
COMORBID CONDITION
EFFICACY*
SIDE
EFFECTS*
Divalproex
4+
2+
Liver disease, bleeding
disorders
Mania, epilepsy,
impulse control
Topiramate
3+
2+
Kidney stones
Epilepsy, mania,
neuropathic pain
Gabapentin
2+
2+
TCAs
4+
2+
Mania, urinary retention,
heart block
Other pain disorders,
depression, anxiety
disorders, insomnia
SSRIs
2+
1+
Mania
Depression, OCD
MAOIs
2+
4+
Unreliable patient
Refractory depression
DRUG
RELATIVE
CONTRAINDICATION
RELATIVE
INDICATION
Anticonvulsants
Epilepsy, neuropathic
pain
Antidepressants
*On a scale of 0 to 4
Silberstein SD et al. Headache in Clinical Practice. 2nd ed. 2002.
Gray RN et al. Drug Treatments for the Prevention of Migraine. 1999.
PREVENTIVE TREATMENT:
DRUG CHOICE
COMORBID CONDITION
DRUG
EFFICACY*
SIDE
EFFECTS*
RELATIVE
CONTRAINDICATION
RELATIVE
INDICATION
4+
4+
Angina, PVD
Orthostatic
hypotension
4+
2+
Asthma, depression, CHF,
Raynaud’s disease, diabetes
HTN, angina
2+
1+
Constipation, hypotension
Migraine with
aura, HTN,
angina, asthma
Antiserotonin
Methysergide
-Blockers
Calcium channel
blockers
Verapamil
*On a scale of 0 to 4
Silberstein SD et al. Headache in Clinical Practice. 2nd ed. 2002.
Gray RN et al. Drug Treatments for the Prevention of Migraine. 1999.
PREVENTIVE TREATMENT:
DRUG CHOICE
COMORBID CONDITION
EFFICACY*
SIDE
EFFECTS*
2+
2+
Riboflavin
2+
1+
Feverfew
Botulinum
Toxin A
2+
2+
2+
1+
DRUG
RELATIVE
CONTRAINDICATION
RELATIVE
INDICATION
NSAIDs
Naproxen
Ulcer disease, gastritis
Arthritis, other
pain disorders
Other
Preference for
natural products
Myasthenia gravis
*On a scale of 0 to 4
Silberstein SD et al. Headache in Clinical Practice. 2nd ed. 2002.
Gray RN et al. Drug Treatments for the Prevention of Migraine. 1999.
Dystonia or
Spasticity
PREVENTIVE TREATMENT:
USE OF ACUTE MEDICATION
Preventive treatment does not eliminate all
attacks
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

Silberstein SD. Cephalalgia. 1997.
CAUTIONS IN ACUTE
MEDICATION USE
PREVENTIVE
CAUTION
Methysergide
Ergots, Triptans
MAOIs
Sumatriptan
(subcutaneous)
and zolmitriptan
Propranolol
Rizatriptan
NSAIDs
Other NSAIDs or
ASA
Divalproex
Butalbital
Silberstein SD. Cephalalgia. 1997.
CONTRAINDICATION
Meperidine, Midrin,
sumatriptan (po, IN) and
rizatriptan
NONPHARMACOLOGIC
TREATMENT:
POTENTIAL INDICATIONS
Patient preference
Poor tolerance, response, or contraindications to
drug therapy
Pregnancy, planned pregnancy, or nursing
History of overuse
Significant life stress or deficient stress-coping
skills
Goslin RE et al. Behavioral and Physical Treatments for Migraine Headache. 1999.
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