Transcript UCLA Family Practice Update 5/09

HEADACHE
Andrew Charles, M.D.
Professor
Director, Headache Research and Treatment Program
David Geffen School of Medicine at UCLA
COMMON TYPES OF
HEADACHES
PRIMARY HEADACHES
MIGRAINE
TENSION TYPE
CLUSTER HEADACHE AND OTHER
TRIGEMINAL AUTONOMIC CEPHALGIAS
SECONDARY HEADACHES
Headaches due to infection
Headaches due to vascular causes
Headaches due to tumors
Etc., etc.
MIGRAINE: Prevalence and
Impact
LIFETIME CUMULATIVE INCIDENCE
43% of women
18% of men
Stewart et al., Cephalagia, 2008
5% of women have headache more than 15
days per month – Migraine likely represents a
significant component for these patients.
The majority of patients with migraine have
not received an appropriate diagnosis, and
are not receiving appropriate therapy
MIGRAINE – A MULTISYMPTOM COMPLEX
AURA
LANGUAGE SYMPTOMS
MOTOR
DYSFUNCTION
PATHOPHYSIOLOGICAL
MECHANISMS
YAWNING,
POLYURIA
CHANGING CONCEPTS OF
MIGRAINE PATHOGENESIS
MIGRAINE IS A DISORDER OF BRAIN
EXCITABILITY
VASODILATION MAY OCCUR AS PART
OF THE DISORDER, BUT IS NOT
REQUIRED FOR MIGRAINE PAIN
Penfield W. A contribution to the mechanism of intracranial pain.
Assoc Res Nerv Ment Dis. 1935;15:399-416.
Ray BS, Wolff HG. Experimental studies in headache: Painsensitive structures of the head and their significance in headache.
Arch Surg. 1940;41:813-856.
Issues with Studies of
Ray and Wolff, Penfield
Stimulation of vessels was focal external
stimulation or mechanical dilation
There is no evidence that physiological
relaxation of smooth muscle and resultant
dilation can cause pain
Multiple areas of brain that could evoke
pain were not stimulated:
Cingulate cortex
Brainstem – Stimulation or lesions in
brainstem can cause migraine
Vasoactive Drugs Cause Migraine After
Significant Delay (hours), Not Correlated with
Vasodilation
Nitric oxide donors
PDE inhibitors
Histamine
CGRP
Schoonman, et al. Migraine headache is not associated with cerebral or meningeal vasodilatation--a 3T
magnetic resonance angiography study. Brain 131, 2192-2200, 2008.
Kruus, et al. Migraine can be induced by sildenafil without changes in middle cerebral artery diameter. Brain.
26:241-247, 2003.
Rahman et al., Vasoactive intestinal peptide causes marked cerebral vasodilation but does not induce
migraine. Cephalalgia. 28, 226-236, 2008.
Alternative Mechanisms of
“ Vascular” Drugs
-blockers
Inhibit neuronal adrenergic signaling
Calcium channel blockers
Inhibit neuronal calcium channels
Caffeine
Neuronal/glial adenosine receptor antagonist
Ergotamines
Modulate central 5-HT receptors
Triptans
Activate neuronal 5-HT1 receptors in brainstem
and thalamus
CORTICAL “WAVES” IN MIGRAINE WITH AURA
Olesen, et al. 1981
Hadjikhani et al., 2001
Bereczki et al., 2008
Cao et al., 1999
…AND MIGRAINE WITHOUT AURA
Woods et al., 1994
Before sumatriptan
2 to 4 h after the attack onset
After sumatriptan
4 to 6 h after the attack onset
Chalaupka, 2008
Denuelle et al., 2008
Hypothalamic Activation in Migraine
(Denuelle et al., Headache, 2007)
MIGRAINE – A MULTISYMPTOM COMPLEX
Cortical
Activation
Brainstem
Activation
MIGRAINE SHOULD BE IN
DIFFERENTIAL DIAGNOSIS OF
ANY EPISODIC
NEUROLOGICAL DISORDER
Do most headache patients need an
imaging study of the brain?
“I’ll want to get a few tests on you, just to cover my ass”
When Don’t You Need to Get
a Scan?
Patient with established history of
episodic headache
Current headache is consistent with
previous headaches or is consistent
with different manifestation of a
primary headache.
Normal neurological exam
When You Do Need to Get a
Scan
Extremely abrupt onset of headache
Persistent unremitting headache
New onset of headache in patient
over age of 50
Fever
Papilledema
Abnormal neurological examination
General Approach to The
Headache Patient
Make a diagnosis (or challenge the diagnosis
that a patient has already been given)
Identify and change exacerbating
environmental factors and medications
Establish regimen for acute therapy of
headache
Determine if preventive therapy is appropriate
IHS CRITERIA FOR MIGRAINE
WITHOUT AURA
At least 5 attacks fulfulling the following:
Headaches lasting 4 to 72 hours
During headache, at least one of the following:
Nausea and/or vomiting
Photophobia and phonophobia
At least 2 of the following criteria
Unilateral location
Pulsating quality
Moderate or severe intensity
Aggravated by physical activity
Simplified Diagnostic Criteria:
ID Migraine
Light sensitivity with headache
Nausea with headache
Decreased ability to function with
headache
Any 2 out of 3 = Migraine
Migraine should be the default diagnosis
for any headache that is brought to
the attention of a health care provider
Migraine: Other Features
Perimenstrual timing
Stereotypical prodromal symptoms
Characteristic triggers
Abatement with sleep
Childhood precursors (motion
sickness, somnambulism, episodic
vomiting, episodic vertigo)
Osmophobia
Diarrhea during attack
Landmark: How Likely Is it That
“Headache” Is Migraine?
In a prospective, open-label study of 1203 patients with episodic headache
•
•
•
94% (of 377 evaluable patients) had migraine or probable migraine
25% with migraine were not diagnosed by their physician
Headaches had a severe impact (HIT–6 score 64)
Probable migraine (n=67)
18%
Migraine (n=288)
Episodic tension-type (n=11)
76%
3%
Unclassifiable (n=11)
3%
Adapted from Tepper SJ et al. Headache. 2004;44:856–864.
Landmark: Patient and Physician
Diagnoses
In a prospective, open-label study of 1203 patients with episodic headache
Patient
• If patient self-reports
migraine, 99.5%
chance migraine or
probable migraine
• If patient self-reports
non-migraine, 86%
chance migraine or
probable migraine
Physician
• If physician diagnoses
migraine, 98% chance
migraine or
probable migraine
• If physician diagnoses
non-migraine, 82%
chance migraine or
probable migraine
• Self-report or physician diagnosis of migraine was almost always correct
• Self-report or physician diagnosis of non-migraine was almost always
later found out to be migraine
Adapted from Tepper SJ et al. Headache. 2004;44:856–864.
MIGRAINES ARE OFTEN
MISDIAGNOSED
SINUS HEADACHES
SIMILAR DISTRIBUTION OF PAIN
MIGRAINES CAN BE SEASONAL
DECONGESTANTS CAN “TAKE THE EDGE
OFF” OF MIGRAINE
WITHDRAWAL FROM DECONGESTANTS
CAN PRECIPITATE MIGRAINES
“SINUS HEADACHE”
OTHER COMMON MIGRAINE
MISDIAGNOSES
TENSION HEADACHE/CERVICOGENIC
HEADACHE
NECK PAIN IS A SYMPTOM OF MIGRAINE
MIGRAINE COMMONLY ASSOCIATED WITH
NECK PAIN
NECK PAIN MAY OCCUR BEFORE, DURING,
OR AFTER HEADACHE
ARE THERE MIGRAINE
TRIGGERS?
COMMON HEADACHE
TRIGGERS
IRREGULAR MEALS
IRREGULAR CAFFEINE, CHOCOLATE,
NUTS, BANANAS, ETC.
IRREGULAR SLEEP (PARTICULARLY
EXCESSIVE SLEEP)
STRESS OR “LET-DOWN” FROM STRESS
AIR TRAVEL, CHANGE IN BAROMETRIC
PRESSURE
MENSTRUAL PERIOD
THE MIGRAINE LIFESTYLE
CONSISTENCY
TIMING OF MEALS, BALANCE OF DIET –Don’t skip meals, mix of different food
groups
SLEEP --- Don’t oversleep or undersleep
CAFFEINE – “Minimum daily dose” of
caffeine on a daily basis
EXERCISE – The more aerobic exercise the
better
MEDICATIONS THAT MAY
MAKE MIGRAINES WORSE
ORAL CONTRACEPTIVES
HORMONE REPLACEMENT
SSRI ANTIDEPRESSANTS
STEROIDS (TAPERING)
DECONGESTANTS
SHORT ACTING SEDATIVES (e.g.
Ambien (?)
BONE DENSITY MEDICATIONS (?)
BOTOX
FREQUENT OPIOID OR BARBITURATE
(BUTALBITAL) USE IS A RISK FACTOR FOR
MIGRAINE PROGRESSION
GROWING EVIDENCE THAT OVERUSE
OF ANALGESIC MEDICATIONS LEADS
TO WORSENING OF MIGRAINE
AMPP DATA (Bigal et al., Neurology 2008)
Frequent use of opioids or butalbital
(more than 8 days/month) is a risk factor
for progression to chronic migraine
Triptan use is neutral for progression
Nonsteroidal use is protective
ACUTE THERAPIES
TRIPTANS – Selective 5HT 1b 1d agonists
SUMATRIPTAN (IMITREX TABLETS, NASAL SPRAY,
INJECTION), SUMATRIPTAN NAPROXEN
COMBINATION
RIZATRIPTAN (MAXALT “MELTABS”, TABLETS)
NARATRIPTAN (AMERGE TABLETS)
ZOLMITRIPTAN (ZOMIG)
ALMOTRIPTAN (AXERT)
FROVATRIPTAN (FROVA)
ELETRIPTAN (RELPAX)
DHE NASAL SPRAY (MIGRANAL), INJECTION
NSAIDS
METACLOPRAMIDE
TRIPTAN NEWS
TRIPTANS ARE NOW AVAILABLE WIDELY
WITHOUT A PRESCRIPTION IN EUROPE.
SUMATRIPTAN WILL SOON BE
AVAILABLE AS A GENERIC IN MULTIPLE
PREPARATIONS.
SUMATRIPTAN/NAPROXEN
COMBINATION TABLET (TREXIMET) IS
NOW AVAILABLE.
EVIDENCE-BASED NON-PRESCRIPTION
APPROACHES TO MIGRAINE
Magnesium (300-500 mg. per day)
Riboflavin (400 mg. per day)
CoQ10 (300 -1200 mg. per day)
Melatonin (3 mg. qhs)
Petasites (Butterbur 75 mg. BID)
THERAPEUTIC OPTIONS FOR MIGRAINE
PROPHYLAXIS
BETA BLOCKERS
TRICYCLICS
CALCIUM CHANNEL BLOCKERS
VALPROIC ACID (Depakote)
TOPIRAMATE (Topamax)
?? MEMANTINE
MEMANTINE FOR MIGRAINE
PREVENTION?
Activity dependent blocker of NMDA
receptors
Identified as a blocker of CSD in rodents
Appears to be effective as a migraine
preventive therapy for significant
percentage of patients with frequent
migraine who had failed other preventive
therapies
It is generally very well tolerated
Well designed studies are warranted
Peeters et al., JPET, 2007
Charles, et al., Journal of Headache and Pain, 2007
Bigal et al., Headache, 2008
MIGRAINE AND PREGNANCY
THE SIGNIFICANT MAJORITY OF WOMEN HAVE AN
IMPROVEMENT IN MIGRAINE FREQUENCY DURING
THE 2nd and 3rd TRIMESTERS OF PREGNANCY
THERE IS NO CONSENSUS OR EVIDENCED BASED
APPROACH TO TREATMENT OF HEADACHE DURING
PREGNANCY
REGULAR SMALL AMOUNTS OF CAFFEINE,
MAGNESIUM SUPPLEMENTATION ARE REASONABLE
NON-PRESCRIPTION ALTERNATIVES
THE ONLY ADVERSE EVENT THAT HAS BEEN IDENTIFIED
WITH TRIPTANS AND PREGNANCY IS A SLIGHTLY
INCREASED RISK OF PREMATURE DELIVERY….i.e. OK
TO USE TRIPTANS IN SEVERE CASES
NEW THERAPIES ON THE HORIZON
ACUTE THERAPIES
CGRP Antagonist – Initial placebo
controlled trials look very promising.
Transcranial magnetic stimulation
Inhaled ergotamines
PREVENTIVE THERAPIES
PFO Closure – Multiple closure devices in
clinical trials
Memantine – Initial uncontrolled results
are promising
Occiptial nerve stimulation
Tonabersat
TAKE HOME MESSAGES
MIGRAINE IS A COMPLEX DISORDER OF BRAIN
EXCITABILITY AND NOT SIMPLY A “VASCULAR
HEADACHE”
MIGRAINE IS EXTRAORDINARILY COMMON AND
UNDERDIAGNOSED.
THE MAJORITY OF MIGRAINE PATIENTS CAN BE
EFFECTIVELY AND SAFELY TREATED WITH AN
ORGANIZED PLAN OF LIFESTYLE MANAGEMENT ,
ACUTE THERAPY, AND PREVENTIVE THERAPY IF
NEEDED
PROMISING NEW THERAPIES ARE ON THE
HORIZON