Clinical Approach to Headache in Children and Preventive Therapy of Migraine

CLINICAL MEDICINE
JIACM 2005; 6(1): 23-32
Clinical Approach to Headache in Children and
Preventive Therapy of Migraine
KK Sinha*
Headache is an ancient disorder and has been well
described in literature from the earliest time. All physicians
who do take care of children, know that headache is the
most common neurological disorder after epilepsy in
children. One population-based study estimated that 90%
of men and 95% of women had unprovoked headache
annually1, and according to another study 10% of children
between age 5 to 15 have migraine, and about 1% have
chronic tension headache2. Even non-organic headache
can be a major problem as it may result in missing school
days and lead to severe interruption in learning and
education. If the headache is chronic, it might lead to
developmental regression, depression, other behavioural
problems, and can severely affect a child’s daily day
activities and future life. But most parents want medical
attention for a child with headache, not so much for relief
of pain as wanting to know if the child has a serious
disease of the head such as a brain tumour or meningitis.
And if this is the purpose, the prime objective is to assure
the parents that the headache in a given child is not a
symptom of a major intracranial illness, because all
headache do not necessarily mean an underlying serious
structural disease of the brain. Every headache in a child
may not be explained, but evaluation of a child’s headache
is important in order to arrive at the proper diagnosis and,
if necessary, start appropriate treatment.
Headache has been classified in different ways over the
years, but in children what one usually encounters is a
migraine-like headache, or a chronic tension-type
headache (chronic, non-progressive headache). Most
neurologists however, have the fear that they are going
to miss headache that heralds some serious disease.
Why one gets headache is not entirely clear, because the
brain itself is insensitive to pain and it can be said that
“brain does not cry”. The reason for headache is the
sensitivity to painful stimuli of extracerebral structures
such as the blood vessels and the meninges; structures
that are supplied by fifth, ninth, and tenth cranial nerves.
It is usually possible, often by history and physical
examination alone, to differentiate headache that is only
pain problems from those that are serious and may need
various diagnostic tests.
The proper evaluation of the headache patient begins
with a carefully taken history, general examination, and a
thorough neurological examination. Once the history and
physical examination are over, the physician should
formulate a differential diagnosis particularly focussing
on the most likely aetiology and the severity of the illness.
If an organic aetiology is suspected, appropriate
diagnostic tests may be necessary to confirm the
diagnosis and exclude serious or life-threatening causes.
Most children with headache will also need monitoring
the subsequent clinical course of the illness, to make sure
that: (i) the initial diagnosis was correct; (ii) the child does
not have any other illness to account for his headache;
(iii) the treatment suggested was appropriate, effective,
and free from adverse effects.
History taking in a child with headache
History is the most important part in the evaluation of
headache to determine the correct diagnosis. When a child
with headache comes in the examination room of the
physician, it is advisable that he begins talking to the child
asking him questions that would help him in the diagnosis.
These questions need to be addressed to the child rather
than to the parents. Children are “little adults” and can
provide very useful information, if questions are asked
appropriately. Even young children may give a good
description of many characteristics of their headache;
although it is important to realise that younger the child,
less specific will be his response. Children of different ages
also respond to pain differently. Whereas younger children
* Neurologist, Mansarovar, Booty Road, Bariatu, Ranchi - 834 009, Jharkhand.
react to pain by crying and rocking their head if headache
is severe, older children may simply complain of severe
headache and close their eyes. An older child or
adolescent can also describe the pain better and localise
it well. The physician may ask the questions in any way he
wants, but one suggested order is the following3-6:
a. Does the child have one or more than one type of
headache ?
Because some patients may have more than one type
of headache, it is important to find out the different
types of headache the patient has, and inquiry should
be made about each type separately. This may be
done by asking the patient whether all headache are
similar or whether they vary in type and severity. We
all have experience of patients who have a mild
headache almost every day with superimposed more
severe headache which is often associated with
nausea, vomiting, vertigo, photophobia, and
phonophobia.
b. When and how did the headache start ?
While many patients are vague about the onset of
their headache, some can easily recall their first
headache and can also describe the factors that
started it. Such features might be physical such as a
head trauma or even an emotionally stressful
situation.
c.
How long has the headache been going on ?
Many children or their parents can easily tell how
long the headache has been present; whether for
days, weeks, months or years. This is prognostically
an important question. If the headache has been
going on for a long time without ever giving rise
to signs of raised intracranial pressure or
progressive neurological decline, then obviously,
it is unlikely to be serious in nature. Episodic
migraine in children typically has its onset in the
first decade, whereas the chronic non progressive
daily headache (tension headache) usually appears
after 10 years of age.
To know the temporal pattern and course of headache,
the next question is important.
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d. Is the headache intermittent, or progressive, or
non-progressive ?
Whatever the headache type, one of the first things
to be inquired about and to be identified is its
temporal pattern. If the pattern suggests that the
headache is intermittent and comes in attacks such
as one, two, or more times in a month; and if it is also
associated with nausea, vomiting, photophobia, or
phonophobia, then migraine is the most likely
diagnosis. On the other hand, if it is becoming more
severe over time, and is also associated with the
appearance of new neurological features, an organic
cause should be strongly suspected. For example, in
an older child with a tumour, the headache gradually
increases over time, but this is not what one sees in a
younger child, in whom the headache is often
biphasic. Such younger children begin with bad
headache that awaken them from sleep and then they
vomit; but they begin to feel better as the day
progresses and the headache then comes back in 2
to 3 days or more, and at this point, the suspicion of a
brain tumour becomes much stronger. The reason for
this biphasic headache is that in very young children
the skull can expand by separation of sutures and
therefore can accommodate the raised intracranial
pressure for a sufficient length of time. The child with
migraine has a temporal progression which follows
quite a different pattern. As said earlier, they have
headache that comes and goes with periods in which
there is no headache at all. A headache-free period is
necessary to make a diagnosis of migraine in a child.
If the headache occurs daily or almost daily from the
time the patient awakens until the time he or she goes
to sleep, and if it has been present for 4 months to
years, and if new neurologic features have not
appeared, the diagnosis most likely is a chronic daily
non-progressive headache (chronic tension-type
headache, also called “muscle contraction headache”).
Here, headache is fairly consistent, although it may
have undulations, and headache is present almost
every day. Many-a-time, one sees a combination of
migraine and tension headache; the so called “mixed”
headache. Such children may tell that they have
headache every day, but they have “valleys” of less
severe headache with interspersed “peaks” of severe
Journal, Indian Academy of Clinical Medicine
Vol. 6, No. 1
January-March, 2005
headache. These children with mixed headache with
coincidental migraine and tension headache are often
difficult to sort out.
watch children who are doing poorly in school and
because of their substandard performance they are
only “acting out”. Such headache has “adolescence”
related adjustment problems and needs
psychological evaluation and attention. But these may
also sometimes indicate gradually developing serious
problems which the parents did not take notice of
initially; so it is important to remember that a
combination of changes in behaviour and school
performance and headache might suggest organic
disease.
e. How frequent is each type of attack in a particular
patient ?
The frequency of headache is often very helpful in
the diagnosis. For example, migraine occurs in attacks
about 2 to 4 times every month. Typical migraine does
not occur daily, unless it gets converted into what is
now called a “transformed migraine pattern” over the
years. Cluster headache also typically occurs
episodically in clusters of attacks, about 2 or 3 times
every day for several months, then they might
disappear for several months or even years. On the
other hand, chronic, non-progressive headache
(chronic, tension-type headache) occurs almost daily
or five to seven times each week or atleast 215 days
in a month. This might continue for months or years.
The quality of headache is not very helpful in the
diagnosis in younger children. One will rarely find a
child who describes a pulsating quality of a migraine
headache as one sees in adults. It is also important to
see whether or not the frequency, or the pattern, or
quality, of a particular type is changing. For example,
intermittent relapsing headache might become more
frequent with each attack, coming closer to the next
and then might even become a daily headache, as
happens when a typical intermittent migraine
headache converts into a chronic, daily migraine.
It is important that when one is dealing with headache
in children, one has to ask the patient and the parents
again and again, and go through the history again in
subsequent interviews, because some points in the
history and physical examination may not strike the
patient, the parents, and the physician, at the first
interview. This is also true for many other similarlooking repetitive neurological syndromes such as
epilepsy.
f.
How long does the headache attack last ?
The answer to this question could help make a
diagnosis. For example, migraine in young children
lasts from a few minutes to about 3 hours and only
uncommonly for longer periods. On the other hand,
migraine in an adolescent may last much longer and
can also be more severe. Attacks of cluster headache
do not usually last longer than 30 to 40 minutes,
although they might come back in a few hours.
Chronic, daily, non-progressive headache may last all
day or several days.
g. Does the headache occur in any special situation?
Most children, adolescents, and parents are able to
recognise specific situations, which cause headache.
For example a car ride may sometimes, provoke a
migraine attack; or, return to school on a monday
morning or after a vacation or holiday, or domestic
tension, or death of a friend or a dear one, may
percipitate tension headache. However, a headache
that awakens a child from sleep often heralds a serious
problem.
h. Is headache induced by certain specific food,
medicine, or activity ?
There could be some patients who are able to
identify specific food or medicine or
environmental situations such as excessive heat or
exertion or exposure to sun that induce headache.
Headache that gets worse on straining during a
bowel movement, usually suggests some
important illnessas its cause, such as a raised
Change in the pattern of headache is important, but
change in behaviour and school performance are
equally important. These are very sensitive indicators
of structural disease of the brain. However, one must
Journal, Indian Academy of Clinical Medicine
Vol. 6, No. 1
January-March, 2005
25
intracranial pressure, or a vascular anomaly.
i.
frequently located in the malar region, or above
the eye, or below the eyes, or between the eyes.
Sphenoidal sinusitis headache may be referred to
the vertex. Pain in cluster headache is unilateral,
usually either in the orbit or around it. In chronic
paroxysmal hemicrania, headache is always
unilateral and does not change sides as it might,
in hemicrania of migraine. Headache due to muscle
contraction is bifrontal or bitemporal, or has a
band-like feeling encircling the head. Episodic
occipital headache may be observed in basilar
artery migraine, or occipital neuralgia, or craniocervical junction lesions.
Does the patient have warning symptoms ?
Some children can describe the prodrome that might
herald their headache several minutes before the
attack. They may get a warning signal that the
headache may be coming on. And parents who are
keen observers may notice that the child develops
certain prodromal features such as he might become
quiet, or his skin colour might change, or there is a
change in his behaviour.
j.
Does the headache appear at a particular time of
the day ?
The time of the day when the headache appears, is
important. For example, if it occurs first thing in the
morning, or if it wakes the child from sleep, or if it tends
to occur in the afternoon. It is important here to find
out if the headache wakes him up from sleep as it
may eventually turn out to be a serious illness. Also,
make sure that it is not the child who wants simply to
stay in bed – which usually means tension headache.
k. What is the site of headache ?
Usually the localisation of headache is non-specific;
sometimes, however, it can be diagnostically
important. If the child always localises his pain on
the same spot of the head and takes his pointed
finger to exactly where his head hurts, the
physician must pay attention. It might be hurting,
because he may have an eroded bone from a
dermoid or a brain tumour, or an arterio-venous
malformation, or some other structural disease.
Pain of otitis media or mastoiditis is frequently
localised to the affected ear or a particular region
around the ear. Pain of optic neuritis and glaucoma,
or cluster headache, is located to one eye and the
pain of temporomandibular arthritis is localised to
the ipsilateral joint or infra-aural region. Migraine
in the young is usually bifrontal or bitemporal, and
the typical hemicranial headache seen in adults is
not common in them; but it does become more
frequent and more localised as they enter into
adolescence. Pain of maxillary sinusitis is
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l.
Are there other symptoms associated with
headache ?
This is a very important question and needs to be
asked to every patient. Gastrointestinal symptoms
such as anorexia, nausea, vomiting, abdominal pain
are frequent accompanying features of migraine.
There may also be autonomic symptoms such as
pallor, chills, flushing, fever, dizziness, syncope, or
behavioural changes. Vertigo may also be a prominent
accompanying feature of migraine headache.
Temporary or permanent neurologic dysfunction
such aphasia, hemiparesis, confusion, unilateral
blindness, hemianopsia, ophthalmoplegia, or loss of
consciousness are rare associated features of
migraine; but if they are present, an organic aetiology
must be sought. Questions regarding symptoms that
might suggest raised intracranial pressure or a
progressive neurological disease are asked at this
point. For example, are symptoms such as lethargy or
personality changes, nausea, vomiting, visual
difficulties, focal signs or gait disturbance, gradual
mental decline, and changing pattern of headache
present? Or are there any symptoms that could
specifically suggest raised intracranial pressure?
m. What does the child do when he has a headache ?
This is also an important question and may give a clue
to the diagnosis. If a migraine headache occurs when
the child is in school, he may simply put his head on
the desk or he may want to go home. In migraine
attacks associated with nausea, vomiting, or vertigo,
Journal, Indian Academy of Clinical Medicine
Vol. 6, No. 1
January-March, 2005
children want to go home and want to lie in a dark,
quiet place with curtains drawn. With severe, chronic,
non-progressive headache, children do not want to
go to school and miss classes.
q. Is there a history of headache in the family ?
Migraine is supposed to have a genetic basis, and it
tends to occur in clusters in the family. It is important
to ask if parents, siblings, or grandparents, or other
first degree or second degree relatives have a history
of headache either currently or in the past. This usually
points to the diagnosis of migraine, particularly if the
headache is associated with nausea and vomiting, or
vertigo. Chronic, non-progressive headache usually
does not have a family history.
n. What improves their headache ?
Most children in a severe migraine attack want to lie
in bed quietly in the dark, or take a pain-killing tablet
to treat their headache. Mothers may apply cold
compresses, or give them a sleeping tablet which is
many-a-time beneficial, but not always. Children and
adolescents with chronic tension type headache do
not usually find relief with any medicine, but often a
sleeping tablet helps them.
r.
Is there anything important in the social and
emotional history and school performance, and
the pressure to obtain high grades from peers,
teachers, and parents ?
o. Is there anything that makes the headache
worse ?
It is important to observe factors that make a
headache worse. Patients with migraine try to avoid
activities, movements, and exposure to sun, because
these usually make their headache worse. In both
chronic tension type headache and migraine,
headache gets worse with bright light, noise, or
strenuous activity. Cluster headache patients do not
find relief even with rest in bed; they are often restless.
Another question that needs to be asked is, whether
the headache increases with any act that involves
valsalva-like manoeuvre such as sneezing or straining
at stool. If that is so, it often reflects increase in the
intracranial pressure. Such children usually do not
have simple tension-type headache; they may have
something more serious that causes a rise in
intracranial pressure.
p. Do associated symptoms continue even when
headache is gone ?
If associated symptoms continue even when the
headache has disappeared, it usually means
presence of an organic cause for headache such
as raised intracranial pressure, or a mass lesion.
When symptoms such as personality changes,
forgetfulness, lethargy, visual problems, nausea,
vomiting, and gait imbalance persist, physicians
need to get alerted.
Journal, Indian Academy of Clinical Medicine
This is a very important aspect of history and must
be inquired of, in every case of headache in a child.
General and neurological examination
The physical and neurological examination of such
children should be done while keeping in mind such
diseases that come in the immediate differential diagnosis
during history taking. The vital signs including blood
pressure, temperature, and organomegaly should be
recorded.
The gait should be examined to see if there is any evidence
of subtle hemiparesis, ataxia, or hysterical gait. They should
be examined for Romberg’s sign and for proximal and
distal weakness.
The head should be examined for size, and if it is large, it
might suggest macrocephaly, hydrocephalus, or
neurofibromatosis. Head should also be auscultated,
looking for a possible machinery-like murmur that might
indicate intracranial vascular anomaly such as an
arteriovenous malformation or a caroticocavernous
fistula.
Cranium should be examined for areas of tenderness or
skeletal defect. Fundoscopic examination is very
important, and the fundus should be looked at searching
for papilloedema, other optic head changes and
haemorrhages. Ocular movements and examination of
pupil should be done next. A sixth nerve weakness is a
Vol. 6, No. 1
January-March, 2005
27
common non-specific finding in raised intracranial
pressure. A combination of cranial nerve signs, with ataxia
and dysarthria suggests a posterior fossa or brainstem
lesion.
At the end of history taking and physical examination, the
suspected specific headache type should be categorised
into one of the known patterns of headache which
include: (a) an acute, first time headache pattern; (b) a
recurrent, acute headache pattern; (c) chronic headache
with progressive decline in neurological status; (d) a
chronic, non-progressive headache; and (e) a mixed
headache . If it falls into one of these well-known headache
patterns, one should try to find what may be the probable
aetiology.
Diagnostic tests
The majority of patients with migraine or with chronic
non-progressive headache with absence of other
symptoms and signs will not need diagnostic testing.
Laboratory tests are however required in some and should
be done in a rational manner with the aim of establishing
the final diagnosis. Routine tests are rarely helpful. But if
the history, or physical, or neurological examination
suggests an organic cause, one needs to order certain
diagnostic tests of which there are two main classes: (a)
neuroimaging; and (b) laboratory investigations.
Neuroimaging : CT Scan, MRI, and MR angiography have
revolutionised the diagnosis of space occupying lesions
of the intracranial space, and have been extremely
valuable in the diagnosis of a wide variety of other
diseases including congenital malformations, intracranial
infections and their sequelae, head trauma and its
sequelae, degenerative and vascular diseases. In many
acute situations, it can be a life saving procedure. Of all
the neuroimaging methods, it is the MRI which is most
valuable in a headache patient. Although it costs more,
takes a longer time, and may require sedation, it
demonstrates lesions much earlier and much more clearly
and accurately, particularly the sellar and parasellar lesions,
craniocervical junction lesions, white matter diseases and
congenital anomalies, than the CT scanning does.
In such patients, where the history is suggestive of a
vascular problem, MR angiography may be necessary at
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the same time as the MRI. No contrast is needed in MR
angiography. It is a non-invasive procedure and if it is done
on a high resolution machine, the images are very clear
and informative. Where one suspects a venous occlusion
or primary intracranial hypertension, MR venography with
MRI can be diagnostic.
Laboratory tests: Some of these patients will need
specialised laboratory tests but the choice of the test
will depend on the differential diagnosis the physician
has made on the basis of the history, physical, and
neurological examination. Routine blood rests in
patients without any sign of progressive disease or
normal examination are not helpful. If however, the
patient is acutely ill, several of these tests are valuable
and the selection of the specific tests will depend upon
the illness one suspects. EEG which is commonly
ordered by physicians, is of practically no value in the
diagnosis of an average case of headache which has
no evidence of an organic disease. On the other hand,
physicians may also be misled by nonspecific
abnormalities reported in many of these records in
children who are otherwise normal. And if a focal
generalised slowing is discovered, neuroimaging will
be necessary to establish the diagnosis, in any case.
Lumbar puncture is useful in determining the presence
of an infective process affecting the brain and
meninges. However, it is contraindicated in a case of
headache caused by intracranial space occupying
lesion, because it may cause brain herniation; and in
such cases, if it is indicated, it must be done very
cautiously, only after neuroimaging. If an acute
infective process such as an acute bacterial meningitis
or a chronic meningitis such as tuberculous meningitis
is suspected, and if there is no papilloedema,it may
sometime become necessary to perform lumbar
puncture without waiting for the CT or MRI. In a case
where one suspects primary intracranial hypertension,
it may be very important to measure CSF pressure for
diagnosis, and CSF drainage through lumbar puncture
may be needed as a form of treatment.
Preventive treatment of childhood migraine
After the diagnosis of migraine is established, or when it
is strongly suspected, one may initiate the treatment. After
Journal, Indian Academy of Clinical Medicine
Vol. 6, No. 1
January-March, 2005
starting treatment, patients need to report for follow-up
as well, every 4 to 6 weeks at least initially. All patients are
first asked to avoid any provoking agents or situations as
best as possible. Over-the-counter (OTC) medications
need to be avoided, unless they are really necessary.
Analgesics and antiemetic compounds should however
be used whenever necessary, to suppress an acute attack.
It is important that both the child and the parent are
explained everything about the nature of the illness, the
correct use of medications, their dosage, potential for
misuse, and side effects.
At every follow-up visit, the course of the headache should
be reviewed, and if there is any suspicion of a change in
the pattern such as the headache becoming more severe,
more frequent, or there are new neurologic signs –
neuroimaging should be ordered and other tests
considered. If the child has been responsive to treatment
and general measures, he or she should then be followedup routinely every few months.
Use of drugs as prophylactic agents in
childhood and adolescent migraine
Several pharmacologic agents have been studied for
prevention of migraine in children and the list includes
propranolol7, timolol8, cyproheptadine9, naproxen10,
amitriptyline11, clonidine12, pizotifen13, nimodipine14,
trazodone hydrochloride 15, dihydroergotamine 16 ,
flunarizine17. But many of the studies on these drugs are
small, and involve only a few children, and therefore do
not reach the required statistical significance, to prove
their efficacy beyond doubt.
Gabapentin probably exerts its effect in migraine
prevention via a pathway other than GABA
neurotransmission, because although it is structurally
related to gamma aminobutyric acid (GABA), it does not
act at the GABA receptors, and is also not converted to
GABA. Baclofen has also been reported to be effective as
a migraine preventing agent, but the mechanism remains
unclear20.
There is a new experimental drug called Dotarizin, which
is a 5HT2 receptor agonist and has recently been reported
to be a good prophylactic drug 21. This is the first report of
a real designer drug for preventive treatment of migraine.
All this means that there are a host of agents available
from which the physician may choose a drug that he likes,
although the appropriate dosage for several of these are
still not known. There is always a scope of changing over
from one drug to another, if one is found ineffective or
toxic.
The ones that have been used most frequently include
beta blockers (mainly propranolol), antidepressants
(tricyclic antidepressants and serotonin selective reuptake inhibitors) antihistaminics (mainy
cyproheptadine), calcium channel blockers (mainly
flunarizine), anticonvulsants (mainly divalproex sodium)
non-steroidal anti-inflammatory agents (mainly naproxen
sodium).
1. Beta blocker: Propranolol
Although the evidence that propranolol is effective
in migraine prophylaxis is weak, it remains the
mainstay in the therapy of migraine headache in
children. Its dosing has also not been systematically
established. A commonly accepted starting dose of
propranolol is 1 mg/kg/day divided into twice daily
doses. The dose can be titrated by slowly increasing it
over succeeding two to four weeks to a maximum of
3 to 4 mg/kg/day if tolerated. Many adolescent
females may notice a drop in their blood pressure and
complain of feeling weak and dizzy. It can also reduce
stamina, and should therefore be used cautiously in
athletes. It is contraindicated in bronchial constricting
diseases, diabetes, and cardiac arrhythmias, and can
also lead to depression. Some children experience
nightmares and vivid dreams. Patients on propranolol
None of these drugs till date has been found to have a
known mechanism of action, and therefore it is unclear
how they provide any relief in headache whenever they
do. However, most of them are presumed to act through
one of the four main mechanisms: (a) 5HT2 antagonism;
(b) modulation of plasma extravasation; (c) modulation
of central aminergic control mechanism; and (d)
membrane stabilising effect, through voltage sensitive
channels18. Divalproex sodium has recently been shown
to be effective in migraine prophylaxis in adults, and it is
supposed to exert its effect by suppressing migraine
related cortical events19. Other new drugs that have been
used are, gabapentin, topiramate and baclofen.
Journal, Indian Academy of Clinical Medicine
Vol. 6, No. 1
January-March, 2005
29
should be evaluated every 2 to 3 months to see if it
has been effective and also well tolerated. It is also
important to remember that beta blockers may take
several weeks to have their full effect.
Other beta blockers have also been used for several
years, but their efficacy has not been established.
2. Antidepressants: The ones that have been tried
most are amitriptyline,nontriptyline and SSRIs.
a. Amitriptyline: The tricyclic antidepressant
amitriptyline has been reported to reduce
headache frequency in children, but its efficacy
has not been studied in a placebo controlled
double blind trial. Moderate-to-excellent
improvement with amitriptyline has been
reported in one study22. The appropriate dose
of this drug has also not been determined, but
clinical experience suggests that a reasonable
starting dose of amitriptyline for a 5 to 10 years
old child could be 5 to 10 mg per day given at
bed time, and for an adolescent a 10 mg daily
dose is a reasonable starting dose. Children
may notice drowsiness in the early phases of
treatment, but it tends to disappear in 2 to 3
weeks. At the end of a six week period, the drug
dose can be titrated to reach higher efficacy
without side effects. Amitriptyline is a
potentially cardiotoxic drug and an ECG
examination may be necessary to monitor the
doses periodically.
b. Nortriptyline: This drug has also been widely
used as an alternative to amitriptyline in the
hope that there are fewer side effects. The
usual starting dose in a child in 10 mg per day
administered at bed time. Side effects are
similar to those of amitriptyline.
c. Serotonin selective re-uptake inhibitors
(SSRIs): These agents have been studied in
adults, but not in children. Since there are no
data to support their use in migraine
prevention in children, they should be used
with caution.
3. Cyproheptadine: This is an antihistaminic with
30
antiserotinergic properties and was one of the
earliest medications reported to be efficacious in
migraine prophylaxis23. Cyproheptadine can be
used as a single daily dose administered at bed
time. The starting dose is usually 2 to 4 mg per day.
The vast majority of patients respond to a dose
between 4 and 12 mg per day. But it can cause
sedation and weight gain.
4. Calcium channel blockers: Calcium channel
blockers have been used quite extensively in the
adult population.
Flunarizine, a calcium channel blocker has been
used quite extensively in India, over past 12 years.
It has been shown to be effective as a preventive
medication in some studies in children24,25. The
actual change in headache frequency is small, but
statistically significant. Side effects in adults
include depression, hypokinesia, nausea, weight
gain. But they are of limited usefulness in
prevention of childhood migraine and have not
been used much.
5. Anticonvulsants
Many anticonvulsants have been used for migraine
prevention including phenobarbital, carbamazepine,
phenytoin, divalproex sodium, gabapentin, and
topiramate, but it is the valproate which has received
maximum attention recently. Divalproex sodium has
been found to be effective in reducing headache
frequency in adults26,27 and it may be a good migraine
preventing drug agent in children as well. Clinical
experience suggests that a starting dose of 10 mg/
kg/day divided into twice daily doses may be a safe
starting dose. This can be increased in the second
week of treatment to 15 to 20 mg/kg/day, divided
either twice or thrice daily. A serum drug level
between 50 and 80 microgram/ml is considered to
be adequate to control migraine headache. It has
however the disadvantage of causing sedation,
increase in appetite, weight gain, and temporary hair
loss. Extended release preparations of divalproex
sodium are now available in India which can be given
as a single dose at bed time as a 250 mg tablet or 500
mg tablet.
Journal, Indian Academy of Clinical Medicine
Vol. 6, No. 1
January-March, 2005
6. Naproxen sodium
References
The non-steroidal anti-inflammatory agent,
naproxen sodium is well known as an effective
drug in the treatment of acute migraine headache
but has also been now reported to be effective as
a migraine preventive drug. Although the study has
been small, there has been significant reduction
in the frequency and severity of headache10. It is
given in a starting dose of 10 mg/kg/day twice
daily. Long-term use of this drug may not be
advisable because of its effect on the gut and renal
function, but in some patients this may be a
reasonable short-term alternative.
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Prevention of migraine, which is perhaps the most
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hopefully not in distant future – develop designer
drugs which are both safe and really effective.
Journal, Indian Academy of Clinical Medicine
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Vol. 6, No. 1
January-March, 2005
31
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Diamicron MR
32
Journal, Indian Academy of Clinical Medicine
Vol. 6, No. 1
January-March, 2005