AptII, 2000/ JcrRsonvIIIe mecIrIne

Migraine: Diagnosis, Prevention And Treatment

Jay A.Van Gerpen, M.D., Stephen Hickey, M.D., and David J. Capobianco, M.D.
Jcy Vcn Oetpen, m.D. Is vI1n 1ne Depct1men1
oI AeotoIogy, mcyo 6IInIr Rornes1et, mA.
51epnen HIrRey, m.D. Is c AeotoIogIs1 In ptI-
vc1e ptcr1Ire In JcrRsonvIIIe Becrn.
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men1 oI AeotoIogy, mcyo 6IInIr JcrRsonvIIIe.
Background
Migraine is a common, but underdiagnosed and
undertreated malady.
1,2
Estimates of the American Mi-
graine Study suggest that 23 million persons older than 12
years of age have migraine headaches, with a 17.6% preva-
lence in females and 5.7% in males.
1
The majority of
migraineurs who seek medical attention consult primary-
care physicians.
2
Therefore, it is important for the generalist
to be conversant with the diagnosis, prevention and treat-
ment of migraine.
It is useful to conceptualize the patient with migraine as
having an inherited susceptibility to headache.
3
A so-called
migrainous threshold likely exists in migraineurs, which
consists of balanced excitatory and inhibitory neural cir-
cuits.
3
This balance may be perturbed by a wide variety of
exogenous and endogenous factors, which can lower the
migrainous threshold, resulting in migraine. The variability
of these migraine triggers in different patients, and even in
individuals, supports the concept of a multi-faceted substrate
for the occurrence of migraine.
4
The primacy of trigger-
identification in the prevention of migraine will be discussed.
An in-depth analysis of current thoughts on the patho-
physiology of migraine is beyond the scope of this article;
however, suffice it to say that the previous concept of
migraine being a primary vascular phenomenon is unten-
able.
3,5
The importance of serotonergic circuitry in the
brainstem in the pathogenesis of migraine is now clear.
5
Its
perturbation can lead to not only intracranial and extracra-
nial vasoconstriction and dilation, but also activation of
pain receptors of the so-called trigeminovascular system.
3,5
This knowledge will prove useful in comprehending the
rationale behind migraine pharmacotherapy, particularly
acute treatments, discussed below.
Diagnosis Of Migraine
The recognition of migraine has been enhanced by the
introduction of diagnostic criteria for both migraine with
and without aura (formerly known as classic and com-
mon migraine, respectively) by the International Head-
ache Society (IHS).
6
These are listed in Tables 1 and 2.
Table 3 contains features distinguishing migraine from the
other two most common headache disorders, tension and
cluster.
4
Particularly salient diagnostic features from these
tables, as well as additional clinical pearls, include: mi-
graine headaches are not necessarily unilateral; the patients
activity during the headache is particularly helpful diagnos-
tically (migraineurs lie still, patients with cluster headache
pace or rock back and forth, and the activity of those with
tension headaches is largely unaffected); individuals may
experience more than one variety of migraine, or even
different headache disorders (typically migraine and ten-
sion); many patients with a history of motion sickness
(especially carsickness during childhood) are migraineurs;
7,8
headaches associated with nausea +/- vomiting after minor
head trauma are probably migrainous (so-called footballers
migraine);
9,10
and migraine frequently manifests initially
in childhood with cyclic vomiting and abdominal pain,
carsickness, footballers migraine or combinations
thereof.
8,11,12
A meticulous history is essential in assessing any head-
ache patient. The following headache information should
be elicited:
age of onset;
family history;
1obIe 1. lnternotionoI Heodoche 5ociety
criterio for Migroine without Auro
o
A. Ar |eosr 5 orrocks rhor |u||||| cr|rer|o |n 8, C, b, ond L
8. Peodoche orrocks rhor |osr 4 ro 72 hrs (unrreored or
unsuccess|u||y rreored]
C. Peodoche hos or |eosr 2 o| rhe |o||ow|ng chorocrer|sr|cs:
1. Un||orero| s|re
2. lu|sor|ng quo||ry
3. Moderore ro severe |nrens|ry
4. Aggrovor|on by wo|k|ng sro|rs or s|m||or rour|ne
phys|co| ocr|v|ry
b. bur|ng heodoche, or |eosr 1 o| rhe |o||ow|ng symproms:
1. Nouseo or vom|r|ng (or borh]
2. lhorophob|o ond phonophob|o
L. No ev|dence o| re|ored orgon|c d|seose
1obIe 2- lnternotionoI Heodoche 5ociety
criterio for Migroine with Auro
o
A. Ar |eosr 2 orrocks rhor |u||||| cr|rer|o |n 8 ond C
8. Ar |eosr 3 o| rhe |o||ow|ng 4 chorocrer|sr|cs:
1. One or more comp|ere|y revers|b|e ouro symproms rhor
|nd|core |oco| cerebro| corr|co| or bro|n-srem
dys|uncr|on (or borh]
2. Ar |eosr one ouro symprom deve|ops groduo||y over
>4 m|n or rwo or more symproms occcur |n success|on
3. No ouro symprom |osrs >60 m|n
4. Peodoche |o||ows ouro |n <1 hr
C. No ev|dence o| re|ored orgon|c d|seose
JcrRsonvIIIe mecIrIne / AptII, 2000
site or sites of pain;
duration;
character;
intensity;
mode of onset;
time between onset to peak pain;
temporal profile;
aggravating or precipitaing factors;
alleviating factors;
associated neurologic, ophthalmologic and autonomic
features;
prior and current medication use, including dosage,
schedule, and efficacy (inquiry into use of over-the-
counter (OTC) medications, as well as prescribed ones,
is vital);
caffeine use;
history of head trauma;
results of prior neuroimaging studies;
a complete review of systems; and
why the patient is currently seeking medical attention.
4
Although most headaches are benign, one should be
vigilant in searching for red flags, potentially indicating
more ominous etiologies, including:
abrupt onset of a new, severe headache (worst head-
ache of my life);
a progressive headache course;
onset with exertion, including sexual intercourse;
onset of headache during or after middle age;
headache associated with a decreased level of con-
sciousness;
headache associated with meningeal signs, fever, indu-
rated temporal arteries or other significant physical
findings;
clear postural features of the headache, especially exac-
erbation supine and relief standing;
significant worsening of headache with Valsalva ma-
neuver;
failure to fit a benign headache profile (see Table 3);
and any headache in a patient with a known, serious,
medical condition, such as cancer, immunocompromise,
or infection.
13
A patient without any red flags, whose presentation
conforms to one of the common headache disorders, and
with a normal physical examination, does not necessarily
need any ancillary tests. For an in-depth discussion of
further evaluation and treatment of headaches associated
with red flags, which may represent dangerous condi-
tions such as subarachnoid hemorrhage; infectious or car-
cinomatous meningitis or encephalitis; raised intracranial
pressure secondary to neoplasm, abscess, or intracranial
hemorrhage; temporal arteritis or other vasculitides, the
reader is directed to several excellent reviews.
13-15
General Principles Of Migraine Treatment
Bartleson reminds us that
the physicians approach to
the migraineur is crucial in
maximizing the likelihood of
successful treatment.
16
The
doctor should strive to enter
into a therapeutic alliance with
the patient. This can be fos-
tered by empathic, active lis-
tening to the patients history,
as well as by educating the
patient about migraine. Pa-
tients are more likely to be
active participants in their
treatment if they have a better
understanding of their condi-
tion.
4
It may be useful to ex-
plain to patients, that they were
born with a sensitive neu-
rovascular system, which
may overreact to internal
changes or external stimuli and
produce migraine headaches,
4
but that this condition is treat-
able.
16
AptII, 2000/ JcrRsonvIIIe mecIrIne
Prevention Of Migraine
More than a century ago, Sir William Osler recognized the
importance of migraine precipitation by triggers and advo-
cated that its treatment should be directed toward the
removal of the conditions upon which the attacks de-
pend...
17
Arguably, not enough emphasis is placed on
educating patients to discern potential triggers in the induc-
tion of their migraines. Table 4 lists the major, reported
migraine triggers, but this list is by no means exhaustive.
Discussing some of the more common ones with patients,
such as menstruation, sleep and eating habits, bright light,
and cafffeine is useful in preparing them to keep an effec-
tive headache diary. By having patients record the time,
date, and circumstances pertaining to each of their migraine
headaches, they acquire knowledge of how these may be
prevented. While it is true that triggers may be variable,
even in individual patients, and that some are unavoidable,
Blau found that 50% of patients with intractable migraine
could reduce the frequency of their attacks by 50% by
eliminating various triggers.
19
Pharmacotherapy Of Migraine
Medical treatment of migraine consists of two approaches,
which are not mutually exclusive: acute (also known as
symptomatic or abortive treatment) and prophylactic
therapy.
Acute Migraine Therapy
A wide range of medications with variable routes of
administration may be used to abort migraine headaches,
including aspirin (ASA), non-steroidal anti-inflammatory
drugs (NSAIDs), acetaminophen (APAP), selective seroto-
nin agonists, ergot derivatives, combination drugs (e.g., an
analgesic plus caffeine), and phenothiazines. Rarely, opio-
ids or corticosteroids may be necessary. Useful, acute
migraine treatment principles include:
taking an abortive medication as early as possible after
the onset of headache increases the likelihood of termi-
nating it;
rest, and especially sleep, in a dark, quiet environment
is helpful in decreasing the duration of the attack;
regular use of abortive medications, especially the com-
bination drugs, can lead to chronic daily headache (also
known as analgesic-rebound headaches or transformed
migraine, discussed below).
A Step-Care treatment approach is prudent.
20
This
entails utilizing ASA, APAP, or an NSAID for mild-mod-
erate headaches; if this fails, an OTC combination prepara-
tion could be tried; if nausea and vomiting are prominent,
and the patient can afford to go to sleep, an anti-emetic, such
as promethazine (orally or rectally) or metoclopramide,
may be used along with the analgesic. In more difficult
situations, a prescription combination medication (such as
isometheptene/ dichloralphenazone/ APAP), an ergotamine,
or a triptan may be necessary. The patients comorbidities
and other medications are important in the decision-making
process as well. Table 5 lists the most commonly used acute
migraine medications and doses, along with their potential
adverse effects and relative costs per dose.
A few words regarding the so-called triptans are war-
ranted, due to their relatively recent development and
emergence as some of the most effective, acute migraine
medications. These drugs are all selective serotonin (5-
hydroxy-tryptamine
1
[5-HT
1
] receptor) agonists and are
thought to act by inhibiting the activation of the
trigeminovascular system.
21
They reverse both the pain and
nausea of migraine without clouding the sensorium, are not
habit-forming, and may be helpful even if administered
well after the onset of headache.
16
Currently, there are four
triptans available in the United States: sumatriptan,
zolmitriptan, naratriptan, and rizatriptan. If a patient does
not respond to one, they still may respond to another.
16
All
are available as tablets (PO); sumatriptan also comes as a
subcutaneous (SC) autoinjector and nasal spray, and
1obIe 4. common Migroine 1riggers
18
foods
Aged cheese
A|coho| (porr|cu|or|y red w|ne ond chompogne]
Monosod|um g|uromore (conro|ned |n seoson|ngs ond
processed |oods]
Choco|ore
Nurs, oronges, ond romoroes
Co||e|nored beveroges
N|rrores ond n|rr|res (hor dogs, sousoges, |uncheon meors]
Avocodo
Smoked or p|ck|ed ||sh or meors
On|ons
Asporrome (d|erory sweerener]
eosr or prore|n errocrs (brewer's yeosr, morm|re]
Medicotions
vosod||orors (n|rrog|ycer|n, |sosorb|de d|n|rrore]
Pormones (oro| conrrocepr|ves, esrrogens, c|om|phene,
donoro|]
Anr|-hyperrens|ves (n||ed|p|ne, copropr||, proros|n,
reserp|ne, m|no|d||]
P|srom|ne -2 b|ockers (c|mer|d|ne, ron|r|d|ne]
Anr|b|or|cs (rr|merhopr|m-su||o, gr|seo|u|v|n]
Se|ecr|ve Seroron|n keuproke lnh|b|rors
LifestyIe
losr|ng or sk|pp|ng meo|s
S|eep (roo ||rr|e or roo much, chonges |n porrerns, e.g., [er |og,
sh||r chonges]
Lerdown |o||ow|ng sress (weekends, vocor|ons, o|rer eoms]
Co||e|ne w|rhdrowo|
Others
Weorher chonges
P|gh o|r|rude (o|r rrove|, mounro|n c||mb|ng]
JcrRsonvIIIe mecIrIne / AptII, 2000
rizatriptan is available as an oral-dissolving tablet. SC
sumatriptan may be particularly useful in patients with
severe vomiting or who have failed different PO triptans,
but paradoxically should not be administered until the
actual onset of headache for maximal efficacy.
22,23
Naratriptan has the slowest onset of action and the longest
half-life; it is therefore not the optimal choice in patients
with rapid-onset migraine.
22
On the other hand, the likeli-
hood of headache recurrence often correlates inversely
with its speed of onset, and thus naratriptan may be the
treatment of choice in migraineurs with slow-onset at-
tacks.
22
Sumatriptan, rizatriptan, and a pharmacologically
active metabolite of zolmitriptan are metabolized by
monoamine oxidase and thus should not be used concomi-
tantly with monoamine oxidase inhibitors (MAOIs).
22
Theo-
retical adverse interactions, including the Serotonin
Syndrome, also exist between sumatriptan and selective
serotonin reuptake inhibitors (SSRIs), as well as lithium.
22,24
Patients taking propranolol should use the smaller dose of
rizatriptan (5mg.) but this caveat does not apply to other
beta-blockers.
22
Chest tightness is an alarming potential
side effect of the triptans, and though it probably usually
stems from an esophageal origin,
22
these medications are
contraindicated in patients with known coronary artery
disease, because of the theoretical risk of coronary vaso-
constriction.
16,22
Other contraindications to the use of triptans
include severe peripheral vascular disease, uncontrolled
hypertension, significant liver disease and migraine accom-
panied by significant, prolonged neurologic deficit(s) (e.g.,
hemiplegic or basilar migraine).
16
Also, triptans, dihydroer-
gotamine (DHE) and ergot derivatives should not be used
within 24 hours of each other.
16
A final point regarding acute migraine treatment that
cannot be over-emphasized, is the risk of migraineurs
developing analgesic-rebound headache. This vicious cycle,
the cause of the majority of cases of chronic daily headache
(CDH), is set in motion by the overuse of abortive therapies,
including OTC medications.
20
Although virtually any im-
mediate-relief medication may induce this process (even
the triptans), combination drugs, particularly ones contain-
ing caffeine, ergots, barbiturates or narcotics, are notorious
for doing so.
25
The risk of this phenomenon occurring
increases significantly if these medications are used more
than three times per week.
20
Patients consistently requiring
this much acute migraine medication are usually best served
by being placed on a prophylactic medication.
Prophylactic Migraine Therapy
Initiating prophylactic therapy depends to a great extent
on patient preference, but there are some useful, general
guidelines. Prophylactic migraine medications are indi-
cated if: attacks occur more than 2-3 times a month; attacks
last more than 48 hours; migraines are so severe, that the
patient is unable psychologically to cope with them; abor-
tive therapy(ies) are inadequate or cause significant side
effects; attacks are associated with prolonged aura.
4
Unfor-
AptII, 2000/ JcrRsonvIIIe mecIrIne
tunately, a majority of migraineurs only obtain a 55-65%
reduction in headache frequency on preventive medica-
tions.
4
Thus the goal of migraine prophylaxis is to decrease
the frequency and severity of attacks. Patients should be
told that prophylaxis is infrequently curative, so that they
have realistic expectations.
26
Potential pitfalls in imple-
menting migraine preventive therapy should be empha-
sized:
4
prophylactic failures often are secondary to inad-
equate dosing or trial periods (one to two months, minimally,
are typically necessary before improvement occurs); once
successful prophylaxis is achieved, it need not be continued
indefinitely, but gradually discontinued after 9-12 months;
27
prophylaxis initiated in a patient who is abusing analgesics
will likely fail; with the patient off of the analgesics, that
same agent may be an effective prophylactic;
26
since the
prophylactic medications are potentially teratogenic, women
of childbearing potential should not be placed on one unless
they are utilizing reliable birth control, preferably barrier
contraception.
26
Medications from several different drug classes may be
useful prophylactic agents. While there is some variance in
expert opinion about which medications are the most effi-
cacious,
4, 26
which is complicated by the paucity of well-
designed trials implemented to answer this question, there
is a relative consensus that first-line medications include
certain beta-blockers, such as propranolol and nadolol; the
tricyclic anti-depressants (TCAs) amitriptyline and nortrip-
tyline; and the anti-convulsant divalproex sodium (VPA).
4,16
As with acute migraine treatment, choosing the most appro-
priate agent for a given patient should entail consideration
of coexisting illnesses and medications taken regularly, so
that the prophylactic medication with the highest benefit/
risk ratio can be selected.
26
Once done, prescribing a medi-
cation heeding the old saw, start low and go slow is
prudent.
4
Table 6 contains the most commonly used pro-
phylactic migraine medications, along with their dosing,
cost , and pertinent clinical information. Several points
worth highlighting include: in patients without reactive
airway disease, brittle diabe-
tes mellitus, or some other
contraindication, a beta-
blocker is a good first choice;
why some beta-blockers are
useful for migraine prophy-
laxis and others are not is
unknown;
26
if one of the beta-
blockers that is useful as a
migraine prophylactic is in-
effective in a given patient,
that same patient might ben-
efit significantly from an-
other;
4, 26
starting one of the
tricyclics is particularly ap-
propriate in a migraineur with concomitant depression, and
a reasonable initial dose is 10 mg at bedtime, titrating up by
10mg daily every 3-5 days to an initial plataeu dose of 30-
50mg nightly; while prophylactic monotherapy is ideal,
some patients with severe and frequent migraine head-
aches, who have failed various monotherapies, may im-
prove on dual prophylactic agents, e.g., utilizing VPA plus
either a beta-blocker or TCA.
4
Conclusion
Migraine is the most common cause of severe, recurring
headache. It is estimated that American businesses lose
upwards of 50 billion dollars annually, because of absentee-
ism, reduced worker productivity, and medical expenses
secondary to migraine.
16
The unquantifiable amount of
human suffering is obviously enormous. However, mi-
graine can be effectively treated, and sometimes even
prevented. Migrainous triggers may not always be appar-
ent, even with compilation of a meticulous headache diary
by the patient, nor preventable even when identified. Simi-
larly, neither a particular abortive nor prophylactic mi-
graine therapy is universally efficacious. Thus, combined
treatment and prevention approaches are most likely to
succeed. Moreover, heightened patient awareness of
migraines pervasiveness and core features, coupled with
greater diagnostic acumen and therapeutic knowledge of
migraine among all physicians, are essential to significantly
diminish migraines deleterious effects.
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