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[diagnosis and treatment of migraine]

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Migraine is the most common neurological The management of migraine in Primary
condition in the world and the most Care can be quite challenging, largely due to
frequently seen disabling headache in the widespread variability in clinical
primary care. In Ireland, approximately 10- presentation, impact and response to
15% of the population suffer from migraine, treatments. Nevertheless, the vast majority
indicating that there are over 400,000 of patients presenting with migraine can be
sufferers in the country. Only about half of diagnosed and managed through Primary
these people are managing their migraine Care. Only a minority need referral to
adequately. specialist services such as the Headache/
Migraine Clinics in Cork and Dublin.
The introduction of the 5-HT1B/1D agonists
(Triptans) in the 1990’s has revolutionised Migraine
the treatment of migraine and lessened the Migraine is a neurological disorder
heavy burden for thousands of people characterised by episodic attacks of
across the country. However, migraine is still disabling headache often with associated
an extensively underdiagnosed and autonomic and neurological symptoms.
undertreated condition and the impact that Attacks vary in their frequency, duration,
it can have on the individuals quality of life severity and number of associated
can be huge. symptoms.

It is this impact that distinguishes migraine


from other headache disorders. It is common
for patients to say that the condition has
taken control of their lives. Many claim that
at its height, migraine is the worst pain they
have ever experienced.

Migraine is estimated to cost the Irish Economy €45 million in lost productivity per annum

Minimum of 200,000 days are lost from work per annum in Ireland due to Migraine

Average migraineur loses 3-5 days per annum and the equivalent of
another 4 days in reduced effectiveness
The World Health Organisation recently classified Migraine as the 19th leading cause of
disability worldwide and the 12th leading cause of disability among women.

1
Epidemiology of Migraine average sufferer gets 1-2 attacks per month
Migraine affects 10 – 15% of the adult and up to 10% of sufferers get 1 attack per
population. About 11% of children are week. See FIG 2.
affected with it being equally common in
boys and girls. At puberty, there is a rapid FIG. 2 Average Frequency of
Migraine Attacks.
rise in incidence among women with adult
women being three times more commonly 10%
affected. Its peak prevalence occurs at
17%
around 40 years (see FIG 1). 25% of people
with migraine will have experienced their
first attack before the age of 10 and over 40%
32%
90% will have experienced their first attack
before the age of 40. It is rare for new cases
to occur after the age of 40. In post-
< 1 month 2-4 month
menopausal women and beyond middle age
1/month > 1/week
in men, the prevalence of migraine
Adapted from
decreases so that by the age of 60 it has Stewart WF; Shechter A, Lipton RB. Migraine heterogeneity
- Disability, Pain intensity and attack frequency and duration.
frequently disappeared. For a minority Neurology 1994; 44 (Suppl 4) 24-39
however, it can continue into old age.
The frequency at which migraine attacks Diagnosis of Migraine
In 1988, The International Headache Society
FIG. 1
published diagnostic guidelines for migraine
30
Migraine prevalence (%)

and other types of headache. It proposed 7


25
major subcategories (see below).
20 Of these subcategories, Migraine with Aura
15 Females and Migraine without Aura account for
10 almost all patients.
5 1.1 Migraine without Aura
Males
1.2 Migraine with Aura
0
0 20 30 40 50 60 70 80 90 1.3 Opthalmoplegic Migraine
Age (years) 1.4 Retinal Migraine
Staffa JA, Lipton RB, Stewart WF, Rev Contemp Pharmacother
1994;5:241-252. 1.5 Childhood Periodic Syndromes
1.6 Complications of Migraine
occur varies enormously. Some patients 1.7 Migrainous disorders not fulfiling
experience 1-2 attacks per year, whilst the the above criteria

2
1.1 Migraine without Aura
To arrive at a diagnosis of Migraine without 3. No aura symptom lasts longer than 60
minutes, but if more than one aura
Aura, the I.H.S. lists the following criteria:e
symptom is present, the duration is
A. At least five headaches fulfiling B-D proportionately increased.
B. The headaches last for 4-72 hours 4. The Headache follows the aura with a
(treated or untreated), patients being symptom-free interval of less than 60
symptom free between attacks minutes, but may also begin before or
C. The headaches have at least 2 of the simultaneously with the aura.
Headache classification Committee of the International
following features: Headache Society. Classification and Diagnostic criteria for
1. Unilateral location Headache disorders, Cranial Neuralgias and Facial Pain.
2. Pulsating in nature Cephalalgia 1988;8(suppl 7);19-28
3. Moderate to severe intensity
4. Aggravation by movement or
routine physical activity No single headache feature and no single
D. During the headache, at least
non-headache symptom are absolutely
one of the following is present
1. Nausea or Vomiting required for diagnosis. Migraine diagnosis
2. Photophobia using the criteria is quite flexible and
3. Phonophobia
subjective. In addition to the above inclusive
Headache classification Committee of the International features, a process of exclusion should also
Headache Society. Classification and Diagnostic criteria for
Headache disorders, Cranial Neuralgias and Facial Pain. take place prior to diagnosis to rule out
Cephalalgia 1988;8(suppl 7);19-28 potential secondary headaches. CT scanning
of the brain is indicated when secondary
1.2 Migraine with Aura:
causes are suspected based on the patients
The diagnosis of Migraine with Aura is based
history or any abnormality on neurological
on the aura and not on the headache.
examination.
(See also Page 7)
The following criteria are defined.
There are a number of distinguishable
A At least 2 attacks fulfiling B subcategories of Migraine with aura. These
B. At least 3 of the following characteristics include:
are present
1. One or more fully reversible aura
symptoms indicating focal Familial Hemiplegic Migraine (FHM)
cerebrocortical or brainstem FHM is a rare condition of recurrent
dysfunction.
headaches associated with hemiparesis. An
2. At least one symptom develops
gradually over more than 4 minutes or additional prerequisite for diagnosis of FHM
two or more symptoms occur in is that that at least one first degree relative
succession.
is affected as well. Hemiplegic Migraine may
also occur in non-familial (sporadic) form.
3
Basilar Artery Migraine (BAM) 1.4 Retinal Migraine
BAM is another rare form of migraine in Consists of repeated reversible attacks of
which the aura symptoms originate from the monocular scotoma or blindness lasting less
brainstem, giving rise to diplopia, ataxia, than 60 minutes and associated with
dysarthria, vertigo, tinnitus and/or changes headache. The headache usually follows the
in consciousness and cognition attack but can be simultaneous or absent. It
is the eye, rather than the visual field that is
Migraine Aura without headache affected. Ischaemic, embolic disease and
This is a relatively common condition in other organic causes must be ruled out
which aura symptoms such as fortification before diagnosis.
spectra, scotomas, paraesthesiae,
dysphasia and other symptoms of cortical or 1.5 Childhood Periodic Syndromes
brain stem origin may occur without any (Childhood Migraine)
subsequent headache. In older patients, this Studies show that about 11% of children
needs to be distinguished from Transient experience migraine. It is frequently of
Ischaemic Attacks which carry a higher risk shorter duration and less severe.
of subsequent vascular disease. Gastrointestinal symptoms, abdominal
discomfort, motion sickness, and fatigue are
1.3 Opthalmoplegic Migraine commonly more eminent than headache
About 1 in 5000 people with migraine suffer symptoms. Children often experience one or
from Ophthalmoplegic migraine. The more “Migraine equivalents”- symptoms of
condition is associated with acute attacks of nausea, vomiting, mood changes,
oculomotor nerve palsy with accompanying photophobia and phonophobia that are
dilation of the pupil. Ptosis and Diplopia are unaccompanied by headache. If these
common features. In this setting, the symptoms are occuring in children without
differential diagnosis includes an an organic explanation, then that is a strong
intracranial aneurysm or chronic sinusitis indication of Abdominal Migraine. It has
complicated by a mucocele. The been linked to migraine because of its
ophthalmoplegia normally outlasts the functional nature, its simultaneous
headache by days or weeks. The condition occurrence with migraine or migraine
occurs more commonly in children, occurring elsewhere in the family. In
especially boys. addition, Abdominal Migraine often
precedes the onset of typical migraine, so is
considered to be a migraine forerunner.

4
Other established migraine forerunners are: Migraine in children goes into remission in
Cyclic Vomiting Syndrome about 60% of cases, though it can recur in
later life in about 20% of these. The earlier
Characterised by recurrent, prolonged
the onset of migraine in childhood, then the
attacks of severe nausea, vomiting and
increased likelihood of it continuing or re-
prostration with no apparent cause.
emerging in adult life.
Vomiting occurs at frequent intervals ( 5-10
times an hour at the peak) for a few hours 1.6 Complications of Migraine
to 10 days (1-4 days most commonly). The There are 2 recognised sub-types of
episodes tend to be similar to each other in migraine that fall under this category. Status
symptoms and duration. It is most common Migrainosus occurs when a patient fulfills
from the ages of 3-7 years. the criteria for Migraine with or without aura,
but when the headache lasts for longer than
Benign Paroxysmal Vertigo
72 hours. Headache free periods of ≤ 4 hours
Benign paroxysmal vertigo of childhood
may occur. Migrainous Infarction
consists of sudden vertigo and dizziness
(Complicated Migraine) is a migraine attack
spells without hearing loss or tinnitus. The
complicated by ischaemic stroke, leading to
spells last minutes to hours. Nausea,
aura symptoms which are not fully reversible
vomiting, flushing, and visual disturbances
within 7 days.
can also occur. It is most commonly seen in
children between 1 and 4 years old. Many
Chronic Daily Headache (CDH)
children develop more typical migraine in
Chronic daily headache is an umbrella term
their teens.
referring to a group of headache disorders
Paroxysmal Torticollis
characterised by headaches that occur more
Paroxysmal torticollis of infancy consists of than 15 days a month, with an average
head-tilt spells that may be associated with untreated duration of more than 4 hours a
nausea, vomiting, pallor, agitation, and day and existing for at least 6 months.
ataxia. There is no hearing loss or tinnitus.
Alternating Hemiplegia of Childhood The condition develops insidiously over time
Infantile attacks of hemiplegia, affecting and patients frequently have a past medical
each side alternately. The nature of the history of migraine or other primary
disorder is unclear, though a relationship headache. Patients may also have a
with migraine is suggested on clinical possible history of neck or head injury.
grounds. Co-morbid conditions include stress, anxiety
states and depression and are important
predisposing risk factors.
5
The overuse of analgesics, particularly the Prophylactic therapies: Low-dose tricyclic
paracetamol/ codeine preparations can lead antidepressants are the first line choices.
to the development of dependence. Other preventative options include sodium
Clinically these headaches are generalised, valproate, beta-blockers, calcium
non-throbbing and mild to moderate in antagonists, and more recently the S.S.R.I.’s.
severity. Patients with a past history of The objective is to raise the threshold for
migraine may continue to experience full pain at central brainstem locations by
blown episodic migraine attacks. actions on the adrenergic and nonadrenergic
Because CDH is resistant to treatment, it can receptor sites.
be a difficult condition to manage. Guiding Physical Measures such as physiotherapy of
principles involve: the neck may be beneficial if head or neck
Investigations: Some patients will require a injury is involved.
CT scan because the changed pattern and Diagnostic Screening Model
increased frequency of
FIG. 3 Patient presenting with headache Exclude sinister
headaches will require
Question 1 headache (<1%)
secondary causes to be ruled Acute tension-
out. type headache What is the impact of the
(ATTH)(40-60%) headache on the sufferer's
Detoxification: Many patients LOW daily life?
consume in excess of 40-50 HIGH

paracetamol / codeine tablets Migraine/Chronic daily headache (CDH)


or other analgesics weekly. In
Consider short-lasting Question 2
patients with rebound
headache (<1%) How many days of
headache attributable to headache does the patient
>15 have every month? <15
medication overuse, a
detoxification programme can
be implemented, aiming at a CDH (5%) Migraine (10-12%)
10% weekly reduction in the Question 3 Question 4
consumption of the For patients with chronic daily For patients with migraine, does
headache, on how many days per the patient experience reversible
medication. Initially the week does the patient take sensory symptoms associated
headaches may worsen due to analgesic medications? with their attacks?
<2 >2 YES NO
the rebound phenomenon and
Figure 3. New MIPCA screening
patients need to be warned of Not analgesic Analgesic questionnaire for the differential Without
dependent dependent With aura
this possibility. The use of diagnosis of migraine aura
AJ Dowson, S Lipscombe, J Sender et al. New guidelines for the
analgesics should be limited management of migraine in primary care. Curr Med Res Opin. 2002.
to twice per week. Long-acting
N.S.A.I.D.s are an alternative analgesic. 6
FIG. 4

Headache
Clinical Features of Migraine
rexia/nausea vomiting vomiting
ano
Migraine is a clinical syndrome e t ite craving sleepy/yawning deep sl
eep
l i mi t e d f
o o d t o l e ra n
a p p ning ce appetite
p t ired/yaw h o tophobia photophobia tired
characterised by four distinct awake/as l e e p a w a k e / a s l eep
c e ho n ophobia phonophobia fee ling
an heightened p
phases: light toler opho b ia osmophobia hig
light tolerance
n m h
noise perceptio os or low n o is e
1) The prodromal phase. noise n smell
e f l u i d retentio diuresis
nc
2) The aura phase. fluid bala fluid balance

resolution

recovery
headache
prodrome
normal

normal
aura
3) The headache phase
4) The postdromal phase.
see FIG 4 the 5 phases of a migrane attack

symptom is visual (99%) consisting of


fortification spectra, flashing lights, zig-zag
The prodromal or premonitory symptoms lines and scotoma. In addition 33% of aura
are experienced by approximately 50% of patients experience unilateral sensory
patients, and precede the headache by a parasthesia, often following the visual aura.
number of hours. These symptoms include This usually begins as numbness in the hand
alteration in mood, tiredness, difficulty in and migrates up the arm and jumps across
concentration, yawning, cravings for certain to involve the face, lips and tongue. Less
foods, fluid retention, altered perception of frequent aura symptoms are dysphasia and
heat and cold, and loss of appetite. These motor weakness.
symptoms give the patient a subjective The headache phase is the most disabling
insight towards an impending attack, though feature of a migraine attack and is the most
some patients are not always aware of these common reason for consultation. There is
symptoms or may mistake them for migraine huge variability in the severity and duration
‘triggers’ of the headache. The duration ranges from
The aura is a transient complexity of 4-72 hours and may be described as either
reversible, focal neurological symptoms that moderate or severe in nature. The pain is
affects 10-30% of migraineurs. Not all usually gradual in onset and frequently is
patients with Migraine with Aura will present on awakening in the morning. At
experience aura symptoms with all attacks. onset the headache may be bilateral but as
Aura symptoms develop over 5-20 minutes it progresses it becomes unilateral in 70-
but can last up to 1 hour. They usually 80% of patients, and can extend from the
precede the headache, but may coincide periorbital and frontal areas backwards to
with or continue into the early stages of the the temporo-parietal and occipital regions
headache phase. The most common aura and can even extend to the shoulder area.

7
As the headache intensifies, patients The postdromal or resolution phase follows
describe it as throbbing, pounding or the headache. Typically, the sufferer
pulsating in character and is exacerbated by continues to complain of symptoms of
physical activity or simple head movement. tiredness, sore muscles, food intolerance,
The headache can alternate from one side to malaise, alteration in mood, and decreased
the other in different attacks. The headache energy and requires a period of rest until
is almost always accompanied by other recovery is complete. Immediately after an
symptoms, which generally intensify in attack, a minority of sufferers feel energised,
tandem with the headache. Nausea euphoric and can return to normal activities
accompanies the headache in 70-90% and at once. The Postdromal phase may last for
leads to vomiting in 20-50%. Vomiting may up to 48 hours.
occur early or late in the headache phase
and when it occurs after the headache is well Causes of Migraine
established, it may result in a precipitious In recent years, the causes of migraine have
easing of the headache. Some migraineurs become clearer, though they are still not
are aware of this and will induce vomiting to completely understood. A number of factors
gain relief. Other associated symptoms are are involved:
photophobia, phonophobia and
osmophobia. See FIG 5. 1. Genetic Factors
Migraine has been long observed to run in
FIG. 5
100 Migraine Associated Symptoms families and studies have shown that 60% of
Adapted from the
'American Migraine Study II - A ten year report card' patients have a positive family history with
90 Stewart, Lipton et al Headache, 2001; 41:638-57
the mother being the most commonly
80 80% affected relative. If both parents suffer from
75%
70 73% migraine, each off-spring has a 70% risk of
inheriting the condition and a 45% risk if one
60
parent suffers.
50

40 Migraine with aura seems to be strongly


30 30%
associated with genetic factors, while
29%
Migraine without aura is determined by a
20
combination of genetic and environmental
10 factors.
1%
ra

e
ea

ng
ia

ch
bi

au
ob
us

ti
o

da
mi
ph
na

ph

a
vo
no

he
oto

no
ph

ph

8
COMMON TRIGGER FACTORS
Dietary Factors
– e.g. chocolate, cheese, red wine, citrus fruits, MSG etc.
– Lack of food; irregular meals
Recent evidence has shown that a mutation – Caffeine withdrawal

in the gene for the voltage-dependent Sleep Related


– Sleep deprivation or disturbance
calcium ion channel on Chromosome 19 is – Irregular patterns
implicated in hemiplegic migraine and this – Excessive sleep

has led to further research into genetic Emotional triggers


– Anxiety
factors. – Stress
– Relaxation after stress
– Excitement
2. Trigger Factors
Physical triggers
Internal or external precipitating (or trigger)
– Over-exertion
factors are implicated in 30-40% of attacks. – Travel
– Change of routine
A wide range of potential trigger factors – Too much/ too little exercise
exist. The most common are listed on the – Smoking/ Passive smoking

d
FIG. 6 Threshold Theory of Migraine
ere
igg
tr
Medications c k
ta
Threshold raised/lowered by at Attack Threshold
Genetic Factors
rs
to e.g. red wine
Pre-disposing
Fac
risk factors e r e.g. missed meal
g
Trig e.g. late night
of
e.g. stress at work
up
i ld e.g. menstruation
Bu
Adapted from MacGregor EA 1996 -Menstrual Migraine: towards a definition, Cephalalgia 16:11-21

right. Identifying trigger factors for migraine Hormonal Factors


– Menstrual Cycle (±2 days of menstruation; around
is through association and recognising a
ovulation)
cause/effect relationship between the – Oral Contraceptives
– Menopause
trigger and the subsequent development of – HRT
an attack. The individual, with the aid of a
Environmental Factors
migraine diary (included in pack) should be – Flickering lights
– Sunlight/ Bright lights
able to identify trigger factors when present. – Heat
Frequently it is a combination of triggers that – High altitude
– Loud noise
will result in the patient crossing the – TV/ VDU screens
– Strong smells
‘threshold’. See FIG 6. – Meterological changes
– Barometric Changes

Physiological Factors
9 – Neck/ Back injury
– Head trauma
– High Blood pressure
3. Predisposing factors trigeminovascular system is activated. On
Research has shown that migraineurs can activation, there is depolarisation of the
have certain metabolic abnormalities that trigeminal ganglion which gives rise to a
may predispose them to migraine. Some of central transmission of painful information
the factors identified include dysfunction and a retrograde release of vasocative
and instability in the autonomic nervous neuro-peptides (C.G.R.P., neurokinin and
system; changes in ovarian hormone levels substance P) from the perivascular nerve
and changes to platelet structure and terminals of the ophthalmic division of the
function. trigeminal nerve. Centrally, the painful
sensory information is transmitted upwards
Pathophysiology of Migraine to the thalamus by second order neurones
At least 3 mechanisms are involved in the and onwards to the higher centres where
pathogenesis of migraine. pain is perceived. Peripherally, the
• Extracranial arterial vasodilation neuropeptides have local vascular effects.
• Extracranial neurogenic inflammation Vasodilatation and plasma extravasation are
• Lowered inhibition of central mediated via C.G.R.P. and neurokinin/
pain transmission substance P respectively.
On reaching the Migraine threshold, a wave
of depolarization spreads across the Migraine patients have low circulating levels
cerebral cortex from occipital to frontal of plasma 5-HT in between attacks and
regions at a rate of 2-3 mm/min, resulting in during an attack there is a release of
brain ion dysfunction and secondary endogenous 5-HT from platelets. This is
vasoconstrictor vascular events. These confirmed by increased levels of the
changes account for the progression and breakdown product, 5 Hydroxyindolacetic acid
variety of symptoms that occur during these in the urine.
phases.

The pain sensitive structures responsible for In the absence of a cure for migraine, the aims of
headache are the extracranial arteries, the migraine management at Primary care level are:
proximal parts of the intracranial The successful treatment of the migraineurs acute attack.

extracerebral arteries, the pial vessels, the The prevention and limitation of future attacks.

meninges, and the large dural venous To encourage migraine sufferers to continue with
their care.
sinuses. The sensory innervation is from the
The identification and referral of the minority of
ophthalmic division of the trigeminal nerve patients who need specialist services.
and the upper segments of the cervical cord
(C2-C3). During the headache phase the
10
FIG. 7 The new MIPCA algorithm for the management of migraine in primary care

• Detailed history, patient education and buy-in


• Diagnostic screening and differential diagnosis

Initial consultation
• Assess illness severity
• tack frequencyAt and duration
• erityPain sev
• Impact (MIDAS or HIT questionnaires)
• Non-headache symptoms
• Patient history and preferences

Intermittent Intermittent
mild-to-moderate moderate-to-severe
migraine (+/- aura) migraine (+/- aura)

Behavioural/alternative
therapies

Initial treatment
Aspirin/NSAID (large dose)
Aspirin/paracetamol Oral triptan
plus anti-emetic Rescue

Nasal spray/subcutaneous
Rescue
triptan

If initial treatment unsuccessful


Alternative oral triptan
Oral triptan Nasal spray/subcutaneous
Rescue triptan

Follow-up treatment
Consider prophylaxis +
Frequent headache acute treatment for
(i.e.>4 attacks per month) breakthrough migraine
Migraine attacks

Chronic daily Consider referral


headache (CDH)?
If management
unsuccessful
AJ Dowson, S Lipscombe, J Sender et al. New guidelines for the management of migraine in primary care.
Curr Med Res Opin. 2002.

11
Migraine Management in Primary Care The Migraine Diary
In recent years, the traditional stepped care The diagnosis of migraine will sometimes
model of managing migraine has been require more than one consultation. The use
largely superceded by evidence based, of a headache/ migraine diary (enclosed in
individualised criteria such as the Migraine pack) is now standard practice for both
in Primary Care Advisors (MIPCA) guidelines diagnosis and management.
from the UK (see FIG 7) as the approach of The diary will yield vital information on the
choice in the management of migraine. pattern of the headache and associated
The main features of this model are: symptoms from one attack to the next.
• Patient reassurance and an explanation of It also gives important information on the
the condition should be provided and the identification of trigger factors and the
patient encouraged to buy into the severity, duration and impact of attacks.
management of their own migraine. The diary is a useful tool for encouraging
People with headache disorders are often patients to become actively involved in the
motivated to understand their condition. management of their migraine.
They should be made aware that although Finally the diary monitors on-going
primary headache cannot be cured, it can treatment changes, in both the acute and
be effectively managed. preventative approaches.

• A careful history assessment and Additional diaries can be obtained free of


diagnosis should be conducted. charge by calling the Association on
1850 200 378 or downloaded from our
• The impact that migraine has on the
website at www.migraine.ie
patient should be considered when
evaluating the patient.
Non Pharmacological treatments
• Each patient should have an individual Self-Management
treatment plan, based on factors such as Migraineurs should be encouraged to
headache frequency, duration and assume responsibility for the management
severity, non-headache symptoms, the of their own condition. Part of this involves
impact it has on the patients life and the recognising that drug treatments can be
patients own history and preference. augmented by self-help approaches. The
• Migraine specific treatments should be identification and subsequent avoidance of
provided from the start if necessary. trigger factors has been shown to decrease
Rescue medication is recommended in the frequency at which migraine attacks
case the initial therapy fails. occur.

12
It is a good starting point in tailoring a towards treatments and the ability to gain
treatment plan towards the individual control of symptoms. Behavioural
migraineur’s needs. Other useful general modifications include regular sleep, regular
tips a sufferer can employ include: exercise, regular meals, avoidance of trigger
factors, reduction of caffeine and alcohol
• Join the Migraine Association of Ireland intake and the introduction of a stress
• Learn about the condition
management programme.
• Try to control stress
• Use a migraine diary to assess the Feverfew: The herbal remedy feverfew
effectiveness of treatments (tanacetum parthenium) may be effective as
• Keep regular patterns of eating and sleeping
• Exercise regularly migraine prophylaxis, though its safety
• Learn to recognise trigger factors and profile needs to be evaluated further.
prodromal symptoms
• The appliance of heat, cold or light pressure to
Feverfew is contraindicated during
the head during an attack can ease the pain pregnancy.
• Be prepared for an attack

Pharmacotherapy for Migraine


Complementary treatments: Pharmacological treatment of migraine can
The use of complementary or alternative be given in 2 ways:
treatments is widespread among people • Acute treatment for symptomatic relief
with migraine. Individually, patients may • Prophylactic treatment to prevent future
respond to one or a combination of these attacks
therapies though there is little evidence
based medicine to support any statistical Because only a minority of migraineurs
benefit. The most beneficial non- suffer from frequent attacks, acute
pharmacological approaches observed in treatment is likely to be sufficient for most
clinical practice are: patients.
Relaxation / Biofeedback: Stress is a
common contributing factor and is in itself a Acute Treatment
trigger factor for migraine. These By the time patients consult their doctor,
techniques reduce the “fight/ flight” most will have already tried over-the-counter
response and limit the neurochemical preparations.
changes that occur in response to stress. Factors determining the doctor’s choice of
Behaviour / cognitive: This approach therapy will be influenced by:
relates to giving insight into the nature of • The effectiveness of previously tried or
headaches, altering negative feelings prescribed medication.

13
FIG. 8 Analgesics:
Up to a third of migraineurs effectively
Hypothalamus Trigger manage their attacks without needing to
Factors Cortex consult their G.P. The vast majority at some
time have self-medicated with over-the-
Thalamus
counter (O.T.C.) preparations. Preparations
Locus
Dura Mater coeruleus such a paracetamol, aspirin or ibuprofen can
Dorsal raphe be very effective particularly if taken early in
Nucleus
the headache phase. Although generally
well tolerated, frequent use can lead to the
Blood Trigeminal
vessel ganglion development of rebound headache which
Medulia
can ultimately lead to chronic daily
Anti-
inflammatory C1 headache.
Vasoconstriction
action
C2 Simple analgesics are often combined with
Triptans
other medications to improve their efficacy
Mechanism of action of triptan drugs
in migraine treatment. If nausea is a
Adapted from Goadsby PJ, Olesen J; Diagnosis and
Management of Migraine. Br Med J 1996; 312:1279-1283 symptom, then the concomitant use of the
pro-kinetic drugs Domperidone or
• The severity of an attack, whether it is
Metoclopramide will relieve the nausea and
mild-moderate or moderate-severe.
also prevent the gastric stasis associated
• The circumstances in which a migraine
with migraine which slows absorption.
attack occurs e.g. on the way out to work
Combined preparations such as
in the morning.
paracetamol/codeine preparations are
• Individual requirements of the patient.
effective for some, but there is an inherent
risk of developing codeine dependency.
In acute therapy the key concerns to be
Codeine is also a major cause of rebound
addressed from the patients perspective
headache.
are:

Triptans
• The efficacy of the treatment
The triptans are 5-HT1B/1D receptor
• The time to onset of action
agonists and are a refinement of the original
• The consistency of response from one
non-specific 5-HT, ergot preparations, which
attack to the next and
they have now largely replaced. They can be
• The tolerability of the medication
prescribed in patients (both those with and

14
Pharmacological Profile of the Triptans
Triptan Formulation Dosage Headache Tmax** Half Life Bioavailability
Relief * hrs hrs Percent
Percent

Almotriptan Oral 12.5 mg 64% 1.4 – 3.8 3.2 – 3.7 70

Frovatriptan Oral 2.5 mg 36-46% 2-4 25 24 – 30

(56-65% after 4 hrs)

Sumatriptan Oral 50 mg 50-61% 2.5 2.5 15

Oral 100 mg 56-62%

Nasal 20 mg 55-64%

Subcutaneous 6mg 81-82%

Zolmitriptan Oral 2.5 mg 62-65% 2 - 2.5 2.5 – 3 40 - 48

Oral 5 mg 59-67%

ODT 2.5 mg 63%

Nasal 5 mg 70%
* Headache relief is standardised to mean the percentage of patients who have gone from severe or moderate to mild or
absent pain within 2 hours
** Time to maximum concentration

without aura) between the ages of 18 - 65 their side effect profile and makes them well
years. In patients with moderate to severe tolerated. See TABLE 1.
migraine attacks the triptans are now
considered first line treatments, particularly The triptans have three sites of action:
if the circumstances of the attack imply an • They cause vasoconstriction of the dilated
inability to carry out routine activities or the meningeal, dural, extracerebral, and pial
cancellation of pre-arranged commitments. blood vessels by stimulating the 5-HT1B
There are four triptans currently available in receptors located on these blood vessels,
Ireland • They inhibit the release of C.G.R.P.,
• Almotriptan 12.5mg orally. substance P and neurokinin from the
• Frovatriptan 2.5mg orally periphereal end of the trigeminal nerve by
• Sumatriptan 100mg / 50mg orally; 20mg/ stimulating the 5-HT1D receptor sites
40mg intranasally; 6mg subcutaneously located on the pre-synaptic nerve
(on a named patient basis). terminals.
• Zolmitriptan 2.5mg orally (conventional • They have a high affinity for the 5-HT1D
and orally disintigrating formulation) located centrally in the region of the
trigeminal nucleus caudalis in the
The triptans have potent agonist activity at brainstem. This last site of action
the 1B/1D receptor sites. The specificity of modulates in-coming nociceptive or
these drugs to these receptor sites limits painful sensory information from the

15
periphery and inhibits its upward Evidence suggests that no one triptan is
transmission to the thalamus and higher substantially superior to another, especially
brain centres where pain is perceived. in oral format. The important question is not
which one is better relative to another, but
Clinical features of the Triptans which one will give headache relief to the
patient. Despite their advantages, triptans
All of the triptans share a number of do not respond in all patients and in clinical
clinical features: practice it is not possible to predict who will
• Effective for moderate to severe migraine. or will not respond. However, it has been
• Relief of both headache and shown that if a patient doesn’t respond to
non-headache symptoms without need for one triptan, they may still respond to an
an anti-emetic. alternative triptan. An evaluation of each
• When taken orally, efficacy starts within 1 patient as to his or her clinical needs should
hour and 60% or more of patients report drive the choice of triptan. Evaluation of
relief within 2 hours. When taken efficacy for a particular patient should be
intranasally or subcutaneously, onset of based over three consecutive attacks with
action may be as fast as 15 minutes. the aid of a migraine diary.
• Headache recurrance rate of about 30%
within 24 hours following an initial dose. Prophylactic drug therapies
When this occurs further doses of the Preventative or prophylactic treatment is
prescribed triptan should be repeated. indicated in patients that
• Well tolerated. Common adverse events • Experience 2 or more attacks per month
include nausea, drowsiness, fatigue, and are unresponsive to the acute
dizziness, parasthesia, and the sensation treatments.
of heaviness in the chest wall, throat and • Suffer from concomitant co-morbidities.
limbs. • Suffer from a medical illness precluding
• Contraindicated for patients with risk first line acute therapy.
factors for cardiovascular disease due to • Demonstrate regular patterns to their
the potential for vasoconstriction. attacks.
• Contraindicated in patients with
uncontrolled hypertension and pregnant The role of prevention is to achieve a
or lactating women. reduction in the frequency, severity and
• Triptans are contraindicated with lithium. duration of attacks. Effective prophylaxis
can achieve up to a 50% reduction in the
frequency in approximately 50% of

16
migraineurs*. Patients should be started on on the severity or duration of attacks that
the lowest dose of a prophylactic medicine actually occur. Other Beta-Blockers known
and increased gradually if required. to confer benefit are atenolol and
Preventative therapies need to be taken metoprolol. Side effects include fatigue,
daily and often 8–12 weeks will elapse arterial hypotension, nightmares and
before a benefit is observed. Patients are depression.
maintained on preventatives for at least 6–9
months before reduction and gradual Pizotifen
withdrawal is considered. While on a course Pizotifen is a 5-HT2 antagonist and anti-
of prophlyactic treatment, patients still need histamine which has been shown to reduce
to have access to an effective acute attack frequency* by ≥50% in 35-50% of
treatment to deal with breakthrough patients. The dose is 0.5mg – 3mg and is
attacks. The preventative therapies are best taken as a single dose in the evening. It
thought to mediate their benefit by is frequently used in childhood and
antagonism of central serotonergic adolescent migraine. Side effects include
receptors, by regulation of calcium ion increased appetite with associated weight
channels, and by enhancement of central gain and drowsiness.
antinociceptive mechanisms. This results in
raising the threshold for both cortical Calcium Antagonists:
spreading depression and trigeminovascular Flunarizine is a calcium antagonist with a
activation. long half-life. It is a good alternative if
Beta-blockers are contraindicated. The dose
Beta-Blockers is 10mg daily at bedtime and is frequently
The Beta-Blockers have been used for prescribed for patients with prolonged aura
prophylaxis for more than 25 years and or for patients who frequently awaken with
continue today to be the drug of first choice migraine. Side effects can be severe and
unless contraindicated in patients with include sedation and Parkinsonian
asthma or peripheral vascular disease. It is symptoms after long-term use due to
believed that Beta-Blockers mode of action anti-dopaminergic actions. Verapramil is
is antagonism at the central 5-HT2 receptor. licensed in the U.S. for migraine prophylaxis
Propranolol 80mg (long acting) is the but it doesn’t have a licence in Ireland.
starting dose and can be titrated up to
320mg. Propranolol has been shown to lead Tricyclic Anti-Depressants:
to a ≥50% reduction in attack frequency* in Low dose tricyclic anti-depressants such as
35-60% of patients, though it has no impact amitriptyline are widely prescribed, though

17
not licensed, for migraine prophylaxis. They Management of Childhood Migraine
are most beneficial in those who suffer from Paracetamol with or without an anti-emetic
concurrent tension type or chronic daily is the recommended treatment for children.
headache and in those for whom migraine The prophylactic drug of choice is Pizotifen.
and depression are co-morbid. Side effects Non pharmacological interventions such as
include dry mouth, arterial hypotension and relaxation exercises, biofeedback, lifestyle
urinary retention. management and behavioural therapies can
also greatly reduce the frequency of
Anti-Convulsants children’s attacks.
Recent clinical trials have shown sodium
valproate to reduce attack frequency* by
≥50% in 45-50% of cases. It was also shown
The Combined Oral
to be generally well tolerated, with the most
Contraceptive & Migraine:
common side effects being mild to moderate The use of the Combined Oral
nausea, dyspepsia, dizziness and diarrhoea. Contraceptive is not contraindicated
Gabapentin may also be useful in clinical in migraine patients. However,
practice, especially in treating transformed Combined Oral Contraceptives often
migraine. Topiramate has been the subject aggravate migraine especially if it is
of recent clinical trials which also proved menstrually related. If, the
positive. frequency or the severity of attacks
increases, then the C.O.C.
* ‘Reduction in frequency’ is defined
(Combined Oral Contraceptive)
as a 50% or greater reduction in should be discontinued.
attack frequency
Smoking, particularly in migraine
Other prophylactic measures: with aura patients, is absolutely
Others agents used, though clinical trial contraindicated, in those patients
data is lacking, include magnesium seeking advice regarding the
supplementation and SSRI’s. Clonidine, the Combined Oral Contraceptive.
alpha-blocker, is now seldom used due to its These migraineurs are at increased
demonstrated lack of efficacy. In menstrual risk of stroke because of the
migraine, the use of N.S.A.I.D.s may be very synergistic effect of migraine with
effective when prescribed pre-emptively to aura, cigarette smoking and
prevent an attack. the C.O.C.

18
Headache/ Migraine Clinics The Migraine Association of Ireland
The Headache/ Migraine Clinic
The Migraine Association of Ireland
Beaumont Hospital
Dublin 9 was formed in 1994 with 3 main goals:
Ph: 01 8093342 1. To provide information, support and
reassurance to migraine sufferers in
Clinical Nurse Specialist in Ireland.
Headache/ Migraine (Beaumont 2. To raise awareness of the condition in the
Hospital)
general population and in the population
Esther Tomkins
Ph: 01 7979848 of the health profession.
3. To support research into the condition of
The Headache/ Migraine Clinic Migraine and seek out better treatments
Cork University Hospital for people with migraine.
Wilton
Cork Our patient services include:
Ph: 021 4922461
• Support & Reassurance available via our
Ethna Mitten Helpline
Clinical Nurse Specialist • Regular newsletter
in Neurology • Regular e-mail newsletter
Cork University Hospital • Information leaflets and publications
Ph: 021 454 6400 Bleep No: 595 • Advice available from the Specialist Migraine
nurse
• On-line information at www.migraine.ie.
• Public information seminars and awareness
campaigns.
• We also support research into migraine in
Ireland and we were the catalyst in the setting
up of Irelands two Headache/Migraine clinics.
Migraine Association of Ireland

HELPLINE
1850 200378
Senior House
All Hallows College
Your
‘Y No.1
resource for the
Gracepark Road
Drumcondra
Dublin 9
latest on
Tel: 01 8064121
Fax: 01 8064122
e-mail: info@migraine.ie
Migraine’
website: www.migraine.ie
19 Sources for data used in the publication of this
booklet are available upon request

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