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Definition and
epidemiology
Pathogenesis
Clinical features
and diagnosis
Management
Prophylaxis
The author
Migraine
PROFESSOR ROBERT HELME,
honorary professorial associate,
department of medicine,
Royal Melbourne Hospital;
and consultant neurologist,
Epworth Hospital, Melbourne,
Victoria.
Definition and epidemiology
PRIMARY headache syndromes, that
is, those without a known cause, are
classified according to a patient’s
description of their symptoms. According to the International Headache Society classification update in 2004,
migraine is a primary headache that
occurs with or without aura.
The prevalence of migraine varies
according to age and gender and is
thought to include about 12% of the
population, being three times as
common in females (18% in females
versus 6% in males), except in preadolescents, where it is slightly more
common in boys. It appears to have a
familial predisposition, although with
such a common occurrence, the relevance of a family history in an individual patient is difficult to assess.
Migraine without aura
Migraine without aura, that is,
common migraine, occurs in two-
thirds of affected patients and generally lasts 4-72 hours. To satisfy diagnostic criteria of the International
Headache Society at least five typical
episodes are required.
This type of migraine has at least
two of the following characteristics:
• Unilateral.
• Pulsating.
• Moderate or severe in intensity.
• Causes avoidance of routine physical
activity.
• Associated with nausea and/or vomiting, photophobia or phonophobia.
If the latter two symptoms are
present with bilateral severe headache
but without nausea/vomiting, the criteria for migraine without aura are
still satisfied.
Migraine with aura
Migraine with aura, or classic
migraine, which occurs in one-third
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19 June 2009 | Australian Doctor |
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HOW TO TREAT Migraine
from previous page
of affected patients, requires at
least two attacks preceded within
one hour by fully reversible focal
neurological disturbance, most frequently visual (with flickering
light spots [photopsias] or lines of
varying complexity [eg, teichopsia
and fortification spectra] or distorted vision [eg, shimmering, pixelation, metamorphosis], with or
without loss of vision [scotoma]).
Sensory (paraesthesiae and/or
numbness and/or vertigo), motor
(ophthalmoplegia, limb or facial
weakness) and/or cognitive symptoms,
including speech disturbance, may
also occur.
These symptoms develop over 5-20
minutes and usually last 20-60 minutes. Sporadic basilar-type migraine
implies the existence of aura originat-
ing in posterior fossa neural structures.
The duration of headache is
again defined as being 4-72 hours.
Debilitating headache due to
migraine and lasting beyond this
time in a person known to experience migraine is said to be status
migrainosis.
Hemiplegic migraine is a special
case in which unilateral motor
weakness predominates the aura.
These rare cases, when recognisably familial in origin, have been
associated with genetic abnormalities, most commonly in a particular voltage-gated calcium channel,
and thus form part of the constellation of intermittent neurological
disorders known as ‘channelopathies’.
Persistent aura without headache
can occur for more than two weeks
and is unusual. The fear is that the
migraine has been complicated by
cerebral infarction, a feature now
readily recognised by MRI. In this
situation other causes of stroke
need to be excluded.
Secondary headache syndromes
Secondary headache syndromes,
that is, those with a recognisable
cause, can occur in patients with
known migraine and need to be
considered if there is an exacerbation of headache sufficient to
require medical review.
Medication overuse headache is
frequently associated with migraine
and has to be carefully dissected
from the migrainous diathesis. It
should be suspected if acute
migraine medications are used for
10 or more days a month, or mixed
analgesics for 15 or more days a
month.
Migraine in childhood is often
recognised in retrospect in a
teenager who later develops
migraine, when a history of unexplained recurrent abdominal pain,
cyclic vomiting and benign paroxysmal vertigo is found on clinical
enquiry. Migraine in childhood is
not considered further in this review.
Unilateral cervicogenic headache
often replaces migraine in older
people. The blood pressure, fundi,
temporal arteries, temporomandibular joints and neck should always be
systematically examined in every new
patient presenting with headache to
exclude a secondary cause.
Benign intracranial hypertension
and its causes (eg, tetracyclines, obe-
sity and the oral contraceptive pill)
must not be missed in this population.
Chronic daily headache of the
migraine type, or chronic migraine
(formerly known as transformed
migraine), refers to the situation
when headache occurs at least 15
days a month and has its origin in a
typical history of migraine (with or
without aura) in the past. The pattern of the daily headache is less
readily recognisable as migraine by
the patient, but is usually punctuated from time to time with
episodes of severe headache, with
forced bed rest, nausea and vomiting.
Migraine sine headache (recurrent
visual or sensory auras without
headache) is also recognised to have
a migrainous pathogenesis.
Pathogenesis
THE pathogenesis of
migraine is not yet fully
understood. The two major
central mechanisms include
initiation of activity in the
brainstem reticular formation,
and spreading cortical depression of Leao, in which spontaneous synchronous neuronal
depolarisation
associated with massive
potassium and glutamate
release spreads from a point
injury in the animal cortex at
a rate of 3-5mm a minute.
Spreading cortical depression is associated with altered
vascular reactivity in the arterial circulation; firstly a small
brief reduction in central
blood flow, then an increase
for several minutes before a
final reduction.
A peripheral mechanism
for migraine involves the
release of neuromodulators
from trigeminal primary afferents that innervate arterioles
and venules in the intracranial circulation. This has been
more closely associated with
the pain of migraine. These
neuromodulator effects can
be blocked with ergots and
triptans, used to treat acute
migraine, but not by neuromodulator-blocking agents.
It is likely that all these
mechanisms interact to cause
the symptoms we closely
associate with migraine.
However, none of them
There is
continuing
controversy over
the role of
precipitant
factors such as
trauma, stress,
diet, weather
change and other
environmental
factors.
accounts for the intermittent
heightened sensitivity of
migraineurs, as seen in the
premonitory headache phase
or in chronic migraine. This is
thought to possibly represent
intermittent dyshabituation
rather than hyperexcitability,
and is of central origin.
Once initiated, brain systems involved in all somatic
pain are activated, including
facilitatory and inhibitory
pathways in the brainstem
reticular system, particularly
those relaying through the
peri-aqueductal grey matter of
the midbrain, where high iron
levels have been found in
patients who develop chronic
migraine. It is thought this
may represent permanent
brain damage in these
patients, reinforcing the idea
that intervention before this
pattern is established is desirable, although there is no
proof that such changes have
irreversible clinical consequences.
The genetic mechanisms
that underlie all these manifestations of migraine remain
obscure. Three monogenic
subtypes have been identified:
• Familial hemiplegic migraine
(three genes).
• Some cases of sporadic
hemiplegic migraine.
• Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoen-
cephalopathy (CADASIL).
However, typical migraine
is most likely to involve many
genes acting in different combinations in different families.
There is also continuing
controversy over the role of
precipitant factors such as
trauma, stress, diet, weather
change and other environmental factors. There are advocates for intense management
of all these factors. A useful
perspective is that ‘when holding a hammer everything
looks like a nail’; the enthusiasm and belief of the therapist is important in determining a successful outcome, as
seen in the management of
many medical conditions.
Clinical features and diagnosis
CLASSIC migraine is readily recognised in teenage patients with typical
visual symptoms followed within half
an hour by pounding unilateral
headache, photophobia and vomiting,
and requiring bed rest, even if it is the
first attack.
A sensory march, or spread of sensory change (for example, up the arm
to the shoulder and on to the face
over a few minutes), which reinforces
the correlation with spreading cortical
depression (unlike the march of
seizures over a few seconds from hand
to shoulder to face to leg) is a con-
vincing indicator of migraine.
The acute headache is often accompanied by allodynia, that is, pain
evoked by non-noxious stimuli such
as brushing the hair. Recurrent
episodes confirm the diagnosis.
In late-age adults, in whom migraine
sine headache becomes more common,
the differentiation from transient
ischaemic attacks is often problematic.
It is better to assume a vascular pathogenesis in these patients until proven
otherwise.
Headache attributed to sinus disease often turns out to be common
migraine after imaging is undertaken
and/or ENT opinion sought, and this
disorder is excluded. Other differential
diagnoses include:
• Infrequent episodic tension
headache, which is associated
with nausea.
• Thunderclap headaches.
• The various hemicranias among
the primary headache disorders.
• Secondary headaches as noted
above.
It is my own opinion that stress,
and its sudden release, is a common
precipitant of migraine, and headache
is known as a common symptom of
depression. Hence, asking about life
stressors and mood disturbance is
essential in the history. Headache is
also a common symptom of menstrual disorders and medication use,
so careful enquiry as to recent or associated changes in medication are
needed.
Some patients and therapists
focus on the effects of foods, often
idiosyncratic to the patient. The
most important is caffeine-containing beverages (coffee and colas).
Many other suspected precipitants
are probably a manifestation of premonitory features of the migraine
rather than precipitants. For example, when weather changes have
been examined, no relationship to
migraine peaks have been found.
Well-recognised premonitory
symptoms include mood change,
hyperactivity and fatigue, yawning,
neck pain, smell dysfunction, food
craving and water retention. The
effects of hormonal changes in
women are best documented over
several months in a headache diary,
with menses also plotted.
Management
MANAGEMENT of the
patient with migraine requires
an empathetic, prolonged and
detailed co-operation between
patient and doctor. The first
premise is to establish the
diagnosis by means of a comprehensive history of the
headache pattern over a lifetime, with attention to past
and family history as well as
lifestyle pattern and psychosocial perspectives, including
past and present life stressors.
In this way mood disturbance and functional disability are identified and can be
included in the management
strategy. The GP is in the for-
22
tunate position of having
most of this background at
the time of presentation, but
this information is rarely pro-
| Australian Doctor | 19 June 2009
vided to the consultant who is
asked for a management plan
after initial GP assessment,
thus prolonging the time
needed to effect improvement.
GPs are also able to provide
timely advice to their patients
about the detrimental effects
on vascular disease of the
interaction of smoking, use of
the oral contraceptive pill and
migraine.
At the very least a calendarstyle diary, filled in daily,
showing the incidence of mild,
moderate and severe headache,
together with the menstrual
cycle in women, is an essential tool for establishing a baseline of headache frequency and
severity and for monitoring the
effect of any intervention.
A three-month diary is usu-
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ally enough to establish an
action plan for future management in any patient with relatively frequent migraine at two
or more episodes a month. At
that point individual management plans begin to diverge,
with the favoured strategies
being those the treating doctor
and the patient have found to
be helpful in the past and
during the initial three-month
recording period.
This is not of great concern
unless the patient is managed
by a number of doctors and
becomes increasingly concerned at the multiplicity of
approaches. All accepted man-
agement strategies fit into the
broad concept of how the
migraine comes about, and
this biology should be
explained to the patient. The
essence of good management
and a good outcome is confidence in the doctor–patient
relationship.
A short review such as this
can only address a few of the
many complex situations that
can arise. The decision to refer
the patient with a poor
response to several interventions is taken jointly between
doctor and patient. Unfortunately Australia has few multicont’d page 24
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HOW TO TREAT Migraine
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Table 1: Triptans available in Australia
disciplinary headache clinics
available for complex cases,
although multidisciplinary pain
clinics are receptive to referrals
in some situations. Most referrals are made to neurologists.
Patients with severe mood disturbance need psychiatric interventions implemented early.
Name
Formulation
Comment
Sumatriptan (Imigran,
Sumagran, Sumatab, Suvalan)
Tablets 50mg (2, 4*);
100mg (2)
Up to 300mg in any 24 hours
Half-life 2 hours with Tmax 2 hours
Sumatriptan (Imigran)
Injection (SC)
6mg/0.5mL (2)
Quick acting (eg, 10 minutes) but note
side effects
Sumatriptan (Imigran)
Nasal spray
10mg/0.1mL (2)
20 mg/0.1mL (2)*
Nasal spray often better absorbed
Unpleasant taste common
Up to 40mg in any 24-hour period
Onset of action 15-45 minutes
Often inconsistent response
Naratriptan (Naramig)
Tablets 2.5mg (2, 4**)
Up to 5mg in any 24 hours
Half-life 6 hours with Tmax 3-5 hours
Zolmitriptan (Zomig)
Tablets 2.5mg (2, 4**)
Up to 10mg in any 24 hours
Half-life 3 hours with Tmax 2.5 hours
Acute management
Acute management of
migraine is dictated by patient
recognition of the typical premonitory symptoms and/or
aura. Self-treatment with an
NSAID of personal choice is
the approach taken by most
patients. This may be in the
form of a combination therapy with codeine (8-30mg) if
that is the patient’s preference.
A typical regimen would be
ibuprofen 200mg, two tablets
immediately and two tablets in
two hours’ time if the headache is
not settling. Other patients rely
on simple analgesics (aspirin
600mg, paracetamol 1g) alone
or in the form of combination
therapy (eg, Mersyndol and Mersyndol Forte) — whatever gives
the patient confidence that control of symptoms is usually
obtained.
Nausea may respond to oral
metoclopramide 10-20mg,
domperidone 20mg or
prochlorperazine 10mg. If oral
medication is not tolerated,
*Streamlined authority script, repeats ×5
**Authority script
prochlorperazine can be
administered rectally (25mg)
and, if a doctor is present,
intramuscularly or intravenously (12.5mg). Metoclopramide 10mg to 20mg IM or
IV can be used as an alternative. The rate of intravenous
injection is less than
5mg/minute for both metoclopramide and prochlorperazine.
Restlessness, akathisia, dystonia, orofacial dyskinesia and
oculogyric crises occur rarely
and respond readily to IV benztropine 1mg or antihistamine
SC = subcutaneous
Tmax = Mean time to maximal serum concentration
injection (eg, promethazine
hydrochloride 50mg) in most
instances. The doctor’s role is
to ensure medication overuse
does not occur and lifestyle is
maintained.
If NSAIDs and analgesics
are routinely unhelpful when
taken alone, triptans, acting
predominantly as 5-hydroxytryptamine agonists can be
introduced, to be taken concurrently, or as a replacement treatment for the next
attack.
These are available in
oral, subcutaneous and
nasal-spray preparations and
require early recognition of
symptoms (preferably aura)
and self-administration. It is
claimed that they are more
effective if allodynia has not
yet developed.
Available medications are
listed in table 1. Patients usually start with oral preparations
and graduate to subcutaneous
and nasal administration
according to preference, efficacy and cost.
Triptans can give rise to the
serotonin syndrome if used in
patients taking lithium,
moclobemide and other
monoamine oxidase inhibitors
(MAOIs), although this is very
uncommon. Nevertheless they
should be used with extreme
care in patients taking these
medications and the manufacturers of sumatriptan contraindicate the use of sumatriptan with or within two weeks
of discontinuing an MAOI.
Ergotamines, although
cheaper, have largely been
superseded by the triptans. The
dose is ergotamine tartrate 2mg
at onset, combined with caffeine up to a maximum of six
per day and 10 per week
orally, or three per day and five
per week by suppository. Ergotamines and triptans must not
be combined.
Parenteral medication may
be used in the office or emergency room. The primary aim
is to limit the use of narcotics,
although occasional treatment with a single dose of
morphine is warranted. Pethidine should be avoided
because of the risks of
metabolite toxicity and habituation/addiction.
As noted above, the first
approach to parenteral treatment is to use anti-nauseants,
including metoclopramide (1020mg) or prochlorperazine
(12.5mg), but if this approach
is unsuccessful, emergency
ward referral becomes necessary.
Treatment in the
emergency ward
The patient with migraine who
comes to the emergency
department has usually tried
their standard approach to
controlling the migraine and is
now worn out by sleeplessness,
dehydrated by vomiting and
incapacitated by pain. Despite
their distress, most respond
readily to treatment and do not
require inpatient care.
The management requires
empathy, calmness and confidence that a good treatment
outcome will be achieved. After
obtaining a history, undertaking an examination to exclude
secondary causes and determining whether brain imaging
is required, treatment is instituted.
The mainstay is rehydration
with IV saline and a parenteral
sedative/anti-nauseant. A
common choice is chlorpromazine 12.5mg in one litre of
saline over four hours, repeated
over the subsequent 12 hours if
needed. An ECG should be
undertaken before use to
ensure a prolonged QT interval
is not present. Some hospitals
prefer metoclopramide 20mg
instead of chlorpromazine.
Thereafter the pain can be
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| Australian Doctor | 19 June 2009
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AD_ 0 2 5 _ _ _ J UN1 9 _ 0 9 . p d f
treated with oral analgesics,
from simple to narcotic,
depending on the response to
an initial choice. Occasionally
ongoing vomiting requires
prochlorperazine in addition to
chlorpromazine, but rarely
ondansetron. The patient needs
to be monitored for several
hours after the headache has
resolved and treatment has
been withdrawn. This may be
up to 24 hours but is usually
less than eight hours.
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Inpatient treatment
A neurologist should be consulted if the patient does not
respond appropriately to the
above regimen. The basis of
inpatient care is to continue a
calm, confident approach,
although bearing in mind that
ischaemic stroke is a possible
outcome in migraine patients
with prolonged auras, and
brain MRI or magnetic resonance angiogram is required
in this situation.
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Management in a simple
dark room is essential. Intravenous therapy is maintained
with continuing sedation, and
a decision made about use of
ergotamines. The usual practice is to administer dihydroergotamine 1mg IV for a
total of three doses at eighthourly intervals after loading
with metoclopramide 1020mg IV to prevent vomiting.
Dihydroergotamine should
not be prescribed if a triptan
or another ergot has been
used in the preceding 24
hours.
If this is unsuccessful, oral
or parenteral steroids may be
used subsequently at doses up
to 20mg dexamethasone daily,
tapering as the headache
resolves. Parenteral analgesia
and further sedation may be
required. The last resort is IV
lignocaine at an infusion rate
of 2mg/minute, with ECG
monitoring.
The outcome is usually
excellent, probably because of
the self-limiting nature of the
disease, although patients with
concomitant psychiatric disease may take much time and
effort to stabilise.
Dihydroergotamine is contraindicated in patients with:
• Hemiplegic or basilar type
migraine.
• Ergot alkaloid hypersensitivity.
• Ischaemic heart disease.
• Poorly controlled hypertension.
• Peripheral vascular disease.
Antibiotic cross-reactivity
needs to be checked if the
patient is taking one. These
include macrolide antibiotics,
HIV protease inhibitors and
reverse-transcriptase inhibitors,
and some antifungals. Use may
be precluded if muscle cramps
supervene or vomiting persists
despite treatment with antinauseants.
Prophylaxis
MIGRAINE prophylaxis is
considered when the frequency and severity of
headache interferes with the
preferred lifestyle of the
patient. Many patients are
quite prepared to put up
with a debilitating headache
once a week as long as they
know they can control it
reliably with their own practised regimen.
If the headache is present
for half the patient’s waking
time or is interfering with
work or domestic duties to the
extent that it is impacting on
their lifestyle, prophylaxis is
recommended. Firstly, however, the baseline of headache
prevalence and severity needs
to be established, routine
treatment for individual
headaches established, and a
realistic view of the patient’s
goals and the doctor’s preferred strategies of management need to be discussed.
For example, it is my personal practice not to manage
prophylaxis of migraine in
patients who will not undertake a formal daily relaxation
program. A response of “I
haven’t got the time” is met
with a firm but gentle
response that the choice is
theirs over “headache or
relaxation”.
The hierarchy of relaxation
approaches is for simple daily
relaxation using a relaxation
CD of the patient’s choice,
used in private and, preferably, at the same time each
day, over yoga, meditation
and direct psychological
supervision of a cognitive
behaviour program, because
of cost and convenience.
The CD, obtained at a
music or alternative health
care shop, comprises soothing
background music, with a
superimposed voiceover giving
instruction on how to relax
muscles, control breathing and
focus on some external imagined or real imagery. The
alternative approach of having
cognitive behavioural therapy
supervised by a clinical psychologist for several sessions
is now more affordable
through the MBS.
Occasionally patients prefer
to undertake a course of meditation or yoga and practise
this daily. Rarely, patients
understand the need but
prefer their own approach. I
recall one young patient running a very busy, small noisy
prophylactic is amitriptyline.
When introduced in low
dose, for example, 10mg
one hour before bedtime,
and incremented slowly
with small doses to a maximum of 100mg, it is usually
well tolerated.
Dry mouth is universal.
Drowsiness and dizziness are
usually precluded by dosing
in the evenings. Weight gain
occurs at higher doses. Urinary retention is uncommon
in young and middle-aged
adults. Constipation is managed symptomatically.
Concurrent use of MAOIs,
SSRIs and tramadol are contraindications, as are recent
seizures and cardiac arrhythmias. Care needs to be used
if there is active psychiatric
disease. The evidence of benefit from other tricyclic antidepressants is limited,
although nortriptyline can be
used if side effects preclude
the use of amitriptyline. The
evidence for benefit from
other antidepressants, such
as SSRIs, is limited.
Table 2: Prophylactic medications
Drug class
Medication
NHMRC evidence level
Comment
Beta blockers
Propranolol
Metoprolol
Atenolol
I
II
II
Care in asthma and depression, check for
cardiac disease, precluded in athletes, warn of
vivid dreams and hair loss in women
Antidepressants
Amitriptyline
Nortriptyline
II*
IV
Side effects common: dry mouth, drowsiness,
weight gain
Sodium valproate
Topiramate
I
I
Gabapentin
III-3
All precluded in pregnancy
Weight gain, tremor, hair loss, encephalopathy
Weight loss, rare psychiatric symptoms, red eye,
urinary stones
Weight gain
Pizotifen
Methysergide
I
II*
Drowsiness, weight gain
Pericardial, pleural, retroperitoneal fibrosis
Verapamil
Diltiazem
Oestradiol gel
II
IV
IV
II
Not used as a first choice
Ibuprofen
Aspirin
IV
II
Anti-epileptics
Ergotamines
Others:
Calcium antagonists
Oestrogens
Magnesium salts
NSAIDs
Useful in menstrual migraine
Not used as a first choice as study outcomes
vary
Useful in menstrual migraine
For detailed adverse events and drug interactions check with formularies
* Several positive randomised controlled trials but no meta-analysis
Migraine
prophylaxis is
considered when
the frequency and
severity of
headache
interferes with
the preferred
lifestyle of the
patient.
best done over at least two
weeks.
Some general comments on
prophylactic medications
available in Australia follow.
These are well summarised in
Therapeutic Guidelines: Neurology (Version 3, 2007).
Beta blockers
and dirty business who attributed his marked improvement
to joining a local bonsai club!
I also insist that patients avoid
coffee and colas whenever
possible and remain consistent
as to their preferred food
intake during any trial of
treatments.
Several medications have
been shown to be of benefit
as migraine prophylactics. The
choice is made after discussion
of possible and likely side
effects (table 2). The patient
is reassured that if the first
medicine used proves unsatisfactory, another will be available.
There are very few comparative studies of efficacy, so no
one medication stands out as
the initial preferred choice.
The initial dose of medication
is low, with an outline of dose
increments, at weekly or twoweekly intervals, provided.
Treatment for three-monthly
intervals is preferred.
Encourage comparison of
pre- and post-treatment
diaries and discussing what
the patient attributes any
improvement or worsening to.
Often patients will have made
other life adjustments that
make all the difference.
Prophylactic medications
are used seriatim and not concurrently, although some combinations are used in difficult
cases. Tapering of the dose is
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The mainstay of migraine
prophylaxis with beta
blockade is propranolol, for
which there is good evidence
from double-blind, randomised controlled trials.
Selective beta blockade
appears less useful. These
medications can also cause
headache and are associated
with weight gain. Patients
with asthma are precluded
from using propranolol.
Patients who are active in
sporting activities find the
interference with cardiac rate
has unacceptable side effects
with vigorous exertion,
although hypotension is
uncommon. Dramatic dreaming may occur, and young
women are sensitive to any
accompanying hair loss. The
starting dose can begin at
20mg bd. The maximum dose
rarely exceeds 320mg/day.
Antidepressants
The most favoured antidepressant used as a migraine
Anti-epileptic drugs
Several anti-epileptic drugs
have been shown in randomised controlled trials to be
of benefit as migraine prophylactics.
Women must be told that
these medicines are associated
with a small but definite
increase in fetal malformations, and enquiry made into
their preferred form of contraception and intentions
regarding any future pregnancy. However, the doses
used for migraine prophylaxis are usually at the lower
end of the therapeutic range
and are thought to be less
likely to have an effect on the
fetus. Nevertheless, they
should be avoided if pregnancy is possible.
The main medications in
this category are sodium valproate and topiramate. The
former is associated with
weight gain, and the latter
with weight loss. Although
often preferred by overweight
women, topiramate can be
associated with alarming
weight reduction, and this
needs to be monitored.
Uncommon psychotic and dissociative states are also associated with this medication, and
patients with migraine who
experience them report them
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HOW TO TREAT Migraine
from previous page
Aspirin can also
be used as
prophylactic
treatment in
migraine,
although the
doses used are
often irritating to
the stomach.
to be unpleasant.
The doses used start at
200mg bd for valproate and
25mg daily for topiramate.
It is unusual to exceed
800mg bd and 200mg daily,
respectively. Other precautions, adverse events and
drug interactions need to be
checked before starting these
drugs. The evidence for benefit from gabapentin used as
a migraine prophylactic is
much less convincing than
for valproate and topiramate.
Ergotamine derivatives
Pizotifen is also associated
with obvious weight gain. It
may be sedating and cause
dizziness, oedema, muscle
pain, impotence, paraesthesiae
and hallucinations. The starting dose is 0.5mg daily, with a
maximum of 4.5mg daily in
divided doses. It is frequently
used in migraine patients with
vestibular auras.
Methysergide is a potent
migraine prophylactic but
has been associated with
pleural, pericardial and
retroperitoneal fibrosis and
its use needs close monitoring. Recommended courses
are limited to six months
with one-month drug-free
intervals, which can be disruptive to the patient’s
lifestyle.
Methysergide is contraindicated in:
• Hemiplegic and basilar
type migraine.
• Ischaemic heart and
peripheral vascular disease.
• Uncontrolled hypertension.
• Pulmonary heart disease.
• Hepatic and renal disease.
Concurrent antibiotic use
should be checked for interactions. The major side
effects otherwise are nausea
and vomiting, insomnia, vertigo, skin reactions and
mood disturbance. The dose
for administration is 1-2mg,
2-3 times daily, and withdrawal should be tapered.
Although difficult to use, the
results can be most gratifying in the right patient.
Methysergide is best reserved
for treatment of difficult
patients by someone experienced in its use.
Others
Verapamil is a calcium-channel blocker occasionally used
as an adjunctive treatment in
the most difficult patients
with migraine. The dose used
is at the highest end of the
therapeutic range, up to
480mg daily, and conduction
defects need to be excluded
before use and monitored
during treatment. Cardiology
review before use is recommended.
Topical oestradiol gel 1.5mg
applied to the inner thigh
daily for seven days starting
48 hours before the expected
onset of menstrual-associated
migraine is often useful in this
setting. Transdermal patches
are less effective. Sometimes a
change or cessation of the oral
contraceptive pill will diminish
the migraine symptoms and
can be trialled, even if the current preparation has been
used for a few years. Progestin-only oral contraception
is less likely to aggravate
migraine.
Pregnancy often abolishes
migraine, especially during
the second and third
trimester. However, occasionally pregnancy aggravates migraine. Many
patients are concerned about
the effects of migraine treatments on breastfeeding.
These patients may benefit
from specialist referral.
Lignocaine infusion for
severe chronic migraine,
intractable single migraine
events, and resistant medication-withdrawal headache is
undertaken as an inpatient
procedure by neurologists
experienced in its use.
Magnesium salts have been
shown to be helpful in trial
settings in some instances, but
there are conflicting results
and trial numbers are gener-
ally small with both oral prophylactic and intravenous
acute use.
Aspirin can also be used as
prophylactic treatment in
migraine, although the doses
used are often irritating to the
stomach. It is often recommended in migraine sine
headache. NSAIDs are also
used, particularly in migraine
associated with menstruation.
A typical regimen is to start
treatment four days before the
expected time of menstruation
and continue for 10 days.
The use of botulinum toxin
and clonidine in the treatment
of migraine remains controversial. Emerging treatments
include the use of ACE
inhibitors (lisinopril) and
angiotensin-II-receptor antagonists (candesartan). A more
promising approach is likely
to be treatment with calcitonin gene-related peptide
(CGRP) antagonists following
the recent positive study with
telcagepant.
Although there is interest in
the role of patent foramen
ovale in the pathogenesis of
migraine, closure should be
considered an unproven
experimental approach. Similarly, occipital and vagal nerve
stimulation are not yet recognised as proven therapies.
Medication-overuse
headache
The headache in this situation
is of varying severity, location
and quality, and may occur
with prolonged frequent use
of acute migraine treatments,
including ergotamines, triptans, opioids, other analgesics
and caffeine. There is recent
evidence that progression to
chronic migraine may especially be associated with opioids and triptans.
The headache recurs as the
effect of each dose wears off,
usually in the early morning,
and may be precipitated by
minimal physical or intellectual stimulation. It may be
accompanied by asthenia,
nausea, restlessness, irritability, memory impairment and
sleeplessness.
To develop this condition it
takes about:
• Four years at exposures of
two days a week for opioids, and five days a week
for combined analgesics.
• Two-and-a-half years for
ergots at exposure of two
days a week.
• One year for triptans at
exposure of three days a
week.
If implicated, these medications must be weaned carefully, but not necessarily
slowly, and the patient advised
that headache may increase
temporarily before subsiding.
Prophylactic medication
should usually be introduced
before the weaning process
begins. Occasionally inpatient
supervision and sedation with
antipsychotic and anti-nauseant agents is required. Steroids
and lignocaine are rarely
required.
Summary
IN conclusion, the
management of migraine
can be a most rewarding
experience for doctor and
patient. Like any medical
condition, difficult cases
do occasionally arise, for
which referral to an expert
with more experience is
helpful. This is highly
recommended if:
• Comorbid psychiatric
disease is present.
• Narcotics are commonly
prescribed.
• There are recurrent visits
to the emergency ward.
• Prescription of unfamiliar
medications with
potentially serious side
effects is contemplated.
Further reading
• Silberstein SD, et al,
editors. Wolff’s Headache
and Other Head Pain. 8th
edn. Oxford University
Press, Oxford, 2008.
Online resources
For practitioners
• US Headache Consortium
Guidelines:
www.americanheadache
society.org/professional
resources/USHeadache
ConsortiumGuidelines.asp
For patients
• American Headache
Society Committee for
Headache Education:
achenet.org
Author’s case studies
Migraine underlying another
clinical diagnosis
A conglomeration of different
headache types
MS AB, 48, presented with a clinical
diagnosis of Ménière’s disease for
more than 20 years, which manifested as recurrent vertigo, tinnitus
and hearing loss, and was treated
with betahistine.
Over the previous six months she
had become aware that some of her
episodes were associated with
headaches. The headache was unilateral, either left or right, and lasted
half an hour. On one occasion the
headache was associated with visual
disturbance rather than dizziness.
She responded to a combination of
relaxation, ibuprofen and pizotifen
0.5mg increasing to 0.5mg tds over
three weeks. She remained well and
tapered the medication after six
months. A recurrence was similarly
treated four years later.
Migraine is often mistaken for
other episodic conditions. Vestibular
symptoms often respond to treatment with pizotifen, as recurrent
simple vertigo is often due to
migraine.
Ms CD, 24 and a single mother of
two, presented with four years of
recurrent left- or right-sided headache
that became bifrontal at a frequency
of three per week. They were associated with occasional nausea.
A second type of headache occurred
on the left about twice a month, lasting four hours and associated with
vomiting, blurring of vision in her left
eye and left-sided pins and needles one
hour later. Her main treatment was
Panadeine Forte, with occasional parenteral injections of narcotics.
Past medical treatment had
included Imigran tablets, Inderal
40mg daily, Endep 100mg daily,
and Epilim 1000mg daily, all without benefit. There was a strong
family history of migraine in her
mother and maternal grandfather.
She smoked but was not taking oral
contraceptives. She readily acknowledged the stress of raising two small
children alone. Physical examination was unremarkable.
A diagnosis of chronic migraine
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| Australian Doctor | 19 June 2009
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was made. She was asked to keep a
diary of headache and her menses
and use a relaxation CD daily. She
was to use Nurofen Plus and Imigran nasal spray as soon as possible
after headache onset. Topamax
25mg daily was introduced, increasing to 50mg daily in six weeks.
Three months later it was clear
that peri-menstrual headache was
her main remaining symptom, with
marked improvement of her other
headaches after the dose of topiramate reached 50mg per day. She had
needed to use Imigran only once.
She was started on serial Nurofen three days before her periods
and continued for 10 days. Three
months later her menstrual
headaches were still a problem
although all others were well controlled. She was started on topical
oestrogen in place of Nurofen. She
has remained well for the past year.
Even if numerous treatment
strategies have failed previously
there is always hope that careful
attention to detail will lead to
improved outcomes.
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HOW TO TREAT Migraine
GP’s contribution
DR HANI BITTAR
Glendenning, NSW
Case study
MO, a 23-year-old university
graduate, presented with
increasing
attacks
of
headaches usually felt in both
parietal regions. These attacks
had been occurring monthly
just before her menstruation,
but since her graduation and
employment at a finance company they had increased in
frequency and intensity.
She had no neurological
symptoms apart from photophobia during the attack and
nausea. She had a cerebral CT
scan done at the local medical centre, which was apparently reported as normal.
She recalled suffering from
headache and abdominal
pains since she was nine and
being treated with an antihistamine and paracetamol.
She had been previously
treated with propranolol,
which she stopped because it
caused nightmares and
fatigue, and pizotifen bd was
ineffective, although she
admitted to poor compliance.
She also admitted to seeing
many GPs, so there was a
lack of continuity of care.
She had recently been
treated with aspirin 900mg,
ergotamine suppositories,
metoclopramide and sumatriptan, with moderate success. She had read about a
new tablet and wanted to try
it.
General and neurological
examination was unremarkable and there were no signs
of neck or musculoskeletal
tenderness.
MO was counselled about
the importance of continuity
of care in optimising the regimen and doses. The patho-
physiology and treatment
modalities of migraine were
discussed with her as well as
recent indications for new
medications such as topiramate.
Questions for the author
What is the best approach to
treat resistant recurrent
migraine and when would
you reconsider the diagnosis?
How to Treat Quiz
Every long-term patient
needs re-evaluation from time
to time, including those with
migraine. The usual triggers
in this context are reported
changes in the pattern of
headache. The first consideration is to exclude new-onset
secondary causes of headache.
Once satisfied there are none,
reasons for headache fluctuation need to be explored, particularly in respect of stress
levels (personal, family, work)
and compliance with previous
management.
If no diary record of
headache is available it should
be reinstituted and, when
appropriate, a concurrent
menstrual diary instituted.
The current strategy for
management needs to be documented in writing and a
review appointment arranged.
At that review the issues for
the patient are reviewed again
and a multi-pronged strategy
agreed to again in writing. If
no progress is observed over a
further three months, special-
ist referral is warranted (see
Author’s case study 2, page
26).
What would be the best treatment for juvenile migraine?
The approach to the management of migraine in children and adolescents follows
the same principles used in
adults, with the major caveat
that dose adjustments for
body weight need to be
made. Thus, most of the
emphasis is on diaries, education of patient and parents,
stress reduction and other
non-pharmacological strategies, and the use of simple
analgesics (paracetamol up to
90mg/kg/day and ibuprofen
up to 40mg/kg/day) for the
usually shorter duration
headaches that occur at this
age.
Anti-emetics can be used
but are more likely to produce
extrapyramidal side-effects.
Triptans have replaced ergotamines, with sumatriptan nasal
spray 10mg favoured for ado-
lescents. Studies of prophylactic medicines for children are
not as available but all classes
of drugs have been used with
appropriate dose adjustment.
Cyproheptadine is used more
often in children than in
adults, and pizotifen and
methysergide are generally
not used in this context. For
more details, specialised
sources should be consulted.
Could you discuss ‘migrainous vertigo’ and the best way
of treating it?
The major challenge in the
patient with episodic unexplained vertigo lasting from
minutes to hours is to think of
migraine as a possible cause.
This is less difficult if there is
a past or family history of
migraine headache. Management is the same as for any
other form of migraine. Some
experts favour pizotifen as the
prophylactic of choice, but
there is little evidence for this
view (see Author’s case study
1, page 26).
INSTRUCTIONS
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The mark required to obtain points is 80%. Please note that some questions have more than one correct answer.
Migraine — 19 June 2009
ONLINE ONLY
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1. Which THREE statements about the
definition and epidemiology of migraine are
correct?
a) Migraine is a primary headache (ie, without a
known cause) that occurs with or without aura
b) The prevalence of migraine in the general
population is about 6%
c) Migraine is three times more common in adult
women than in adult men
d) In children migraine is slightly more common in
boys than in girls
4. Which TWO statements are correct?
a) Persistent aura without infarction can last for
more than two weeks
b) Migraine sine headache refers to recurrent
visual or sensory auras without headache
c) Status migrainosis is debilitating migraine
headache lasting more than 48 hours in a
person with known migraine
d) Chronic migraine is when headache occurs at
least five days a month in a patient with a
previous typical history of migraine
2. Which TWO statements about the
International Headache Society (IHS)
classification of migraine without aura
(common migraine) are correct?
a) About two-thirds of patients with migraine have
migraine without aura
b) The duration of the headache is up to 48
hours
c) At least five typical episodes are required to
satisfy the diagnostic criteria
d) Headaches must be unilateral
5. Since a teenager, Carol, 26, has had
episodic, severe unilateral headaches,
associated with nausea and sometimes
photophobia, usually lasting about 24 hours.
She has no aura symptoms. Her mother
suffers from migraine. Which TWO statements
about her assessment are correct?
a) It would be useful to ask Carol to keep a
diary for several months recording the
incidence of her headaches, including any
relation to her menstrual cycle
b) It is not useful to enquire about life stressors
and mood changes in relation to migraine
c) Asking about weather changes as a
precipitant of headaches is important, as
there is a definite link between these and
migraine incidence
d) Carol’s intake of caffeine-containing
beverages should be enquired about
3. Which TWO statements about the IHS
classification of migraine with aura (classic
migraine) are correct?
a) At least five attacks are required to satisfy the
diagnostic criteria
b) The headaches are preceded within one hour
by fully reversible focal neurological
disturbance
c) Aura symptoms develop over 5-20 minutes
and usually last 20-60 minutes
d) Paraesthesiae and numbness are the most
common aura symptoms
6. Carol usually takes an NSAID–codeine
combination. She has also previously been
given a script for a triptan but hasn’t tried it
yet. Which THREE statements about the
acute management of migraine are correct?
a) Triptans can give rise to the serotonin
syndrome
b) Ergotamines and triptans must not be
combined
c) If parenteral treatment is required, the first
approach is to use an anti-nauseant
d) If a narcotic is required, pethidine is the
drug of first choice
7. Recently Carol’s headaches have
increased from once to twice a month. She
often gets a headache with her period.
Carol’s examination is unremarkable, and a
recent cerebral CT scan ordered by another
GP was normal. Which TWO statements are
correct?
a) A patient with migraines lasting for one day
twice a month should definitely be
prescribed a prophylactic agent
b) Relaxation therapy is recommended in
patients requiring prophylactic treatment for
migraine
c) No one medication stands out as the initial
preferred choice for migraine prophylaxis
d) If one prophylactic medication is ineffective,
rather than withdrawing this agent, a
second prophylactic agent should be added
8. Which TWO statements about
prophylactic treatments for migraine are
correct?
a) Selective beta blockers are the mainstay of
migraine prophylaxis with beta blockade
b) Nortriptyline is the most favoured
antidepressant used as a migraine
prophylactic
c) Anti-epileptics should be avoided as
migraine prophylaxis if pregnancy is
possible
d) Pizotifen may be useful in migraine patients
with vestibular auras
9. Which TWO statements about other
agents used in migraine prophylaxis are
correct?
a) Methysergide is a potent migraine
prophylactic but has been associated with
pleural, pericardial and retroperitoneal fibrosis
b) The calcium-channel blocker, verapamil, is a
first-choice migraine prophylactic agent
c) NSAIDs can be used for prophylaxis of
migraine, particularly when associated with
menstruation
d) Topical oestradiol gel has not been found to
be useful for prophylactic treatment of
menstrual-associated migraine
10. Which TWO statements about
medication-overuse headache are correct?
a) In medication-overuse headache, the
headaches often recur in the early morning
b) Medication-overuse headache should be
suspected if mixed analgesics are used for
five or more days a month
c) Patients with medication-overuse headache
can be reassured their headaches will
immediately improve upon stopping the
offending medication
d) Prophylactic medication should usually be
introduced before the weaning process
begins
CPD QUIZ UPDATE
The RACGP now requires that a brief GP evaluation form be completed with every quiz to obtain category 2 CPD or PDP points for the 2008-10 triennium. You
can complete this online along with the quiz at www.australiandoctor.com.au. Because this is a requirement, we are no longer able to accept the quiz by post
or fax. However, we have included the quiz questions here for those who like to prepare the answers before completing the quiz online.
HOW TO TREAT Editor: Dr Wendy Morgan
Co-ordinator: Julian McAllan
Quiz: Dr Wendy Morgan
NEXT WEEK Some drugs are more likely to cause certain rashes, and some rashes are more likely to be caused by certain drugs. Some are allergy-like, others mimic common skin diseases. Some are mild
while others can be life-threatening. The next How To Treat takes a look at recognising, diagnosing and managing drug eruptions. The author is Dr James Young Joon Choi, consultant clinical immunologist
and dermatologist, VMO, Westmead Hospital and Concord Hospital, and in private practice in North Parramatta, Rhodes and Miranda, NSW.
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