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Internal Medicine Journal 2003; 33: 436–442

CLINICAL PERSPECTIVES
Migraine: diagnosis and management
P. J. GOADSBY
Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, United Kingdom

Abstract migraine (ergotamine and the triptans). The triptans –
Migraine is the most common form of disabling primary sumatriptan, naratriptan, rizatriptan, zolmitriptan,
headache and affects approximately 12% of studied almotriptan, eletriptan and frovatriptan – are potent
Caucasian populations. Non-pharmacological manage- serotonin, 5-HT1B/1D, receptor agonists which represent
ment of migraine largely consists of lifestyle advice to a major advance in the treatment of acute migraine.
help sufferers avoid situations in which attacks will be Chronic daily headache in association with analgesic
triggered. Preventive treatments for migraine should overuse is probably the major avoidable cause of head-
usually be considered on the basis of attack frequency, ache disability in the developed world. (Intern Med J
particularly its trend to change with time, and tract- 2003; 33: 436–442)
ability to acute care. Acute care treatments for migraine
can be divided into non-specific treatments (general
analgesics, such as aspirin or non-steroidal anti- Key words: headache, treatment, serotonin agonist,
inflammatory drugs) and treatments relatively specific to brainstem.

INTRODUCTION Migraine should be considered as an inherited,
episodic disorder of sensory modulation; a brain disorder
Headache is one of the most common human maladies that results from dysfunction of brainstem9–11 or dien-
and books have been devoted to the subject.1–3 Migraine cephalic structures that normally regulate sensory traffic.
is the commonest of the disabling primary headache Migraine is not primarily a vascular headache, nor is it
syndromes (Table 1). The World Health Organization simply a pain problem. Certainly, part of its patho-
rates a day with severe migraine to be as disabling as a physiology may involve nerve-driven vascular change;
day spent quadriplegic.4 The neurobiology of migraine is neurovascular effects that are completely non-specific to
as well understood now as any of the major neurological headache type.12 Migraine is probably, at its core, a
illnesses, and interested readers are referred to a recent disorder of the central nervous system synchrony
review.5 The key to the clinical approach to migraine is mechanisms13 and is best understood and managed as a
to understand its biology; this drives diagnosis and neurological condition.
management, while allowing the clinician to provide a
useful explanation to patients who seek information or
disease control, or both. I will first deal with traditional DIAGNOSIS
migraine, by which I mean ‘episodic migraine’, as The production of the International Headache Society
defined by the International Headache Society (IHS) IHS classification,6 and its widespread acceptance in the
Classification Committee (see Table 2).6 In the closing headache community, must rank as one of the great
section I will deal specifically with the recalcitrant steps of the twentieth century in the field of headache. A
problem of frequent headache, and the migrainous simplified version of the diagnostic criteria is listed in
version of this, which will be called ‘chronic migraine’ Table 2. The IHS classification codifies what most clini-
when the IHS classification is revised to its second cians had considered from first principles, that migraine
edition.7 It deserves special mention, as clinicians will is a collection of symptoms, some more important than
realize, because frequent (daily) headache is a burden for others, but none really dominating. So while unilateral,
the sufferer,8 and a significant challenge for the treating throbbing, severe pain with nausea is clearly migrainous,
clinician. it is also true that bilateral throbbing pain may be part of
the migrainous spectrum. The IHS classification simply
and very neatly accommodates this view.
Correspondence to: P. J. Goadsby, Institute of Neurology, Queen Square, Migraine manifesting as an episodic disorder
London, WC1N 3BG, United Kingdom. Email: peterg@ion.ucl.ac.uk
A fundamental principle of migraine is that it is episodic
Received 5 September 2002; accepted 14 April 2003. in terms of its typical clinical presentation. I would
Funding: The work of P. J. Goadsby was supported by the Wellcome suggest that this is more or less universal, but that the
Trust and the Migraine Trust. time constant of the disorder varies widely. The IHS
Conflicts of interest: None classification captures the great majority of migraine in
Diagnosis & treatment of migraine 437

its limits of 4–72 h, and provides well-defined cases for contrast, tension-type headache, in the pure sense, is a
research purposes. However, this does not stop paedi- pain problem without other sensory-system involvement.
atric migraine from often being shorter and less distinct, So for a simple, yet biologically plausible rule, ‘headache
nor does it preclude longer attacks. Indeed if one plus’ is migraine, and ‘headache full-stop’ is tension-type
considers patients with chronic migraine to have very headache.
long time constants (in years) for the exacerbations of
their disease processes, then the principle of episodicity
is never violated.
MANAGEMENT OF MIGRAINE
The management of migraine begins with an explanation
Migraine and tension-type headache of certain things to the patient, notably:
The most challenging part of the diagnosis of primary
headache is the differentiation between migraine and • Migraine is an inherited tendency to cerebral
tension-type headache. Clinically, if one takes a history dysfunction, and cannot be cured
that is vaguely suspicious of secondary headache, or if • Migraine can be modified and controlled by life-
there are any abnormal neurological signs, imaging is so style adjustment and the use of medicines
accessible that a brain scan will be done. Brain scans, • Migraine is neither life threatening nor associated
however, more often reveal findings that are unrelated to with serious illness, with the exception of females
the underlying primary headache.14 Suffice to say that who smoke and are on the oestrogenic oral contra-
the clinical problem for most neurologists will be the ceptives who are at increased risk for stroke, however
patient complaining of headache, with a normal neuro- migraine can and often does make life a misery
logical, and relevant general physical examination • Migraine management takes time and co-operation
(including blood pressure), and a normal brain scan.
when information, such as that from a headache
Furthermore, given how common migraine and tension-
type headache are (Table 1), one of these is highly likely diary, has to be collected.
to be the diagnosis.
As a rule – and I think it is reliable and will be shown Non-pharmacological management
to be biologically sound – migraine is headache with Put very simply, non-pharmacological management of
features of sensory sensitivity, sensitivity to light, sound, migraine helps the patient identify things that make the
smells and head movement, and with throbbing (effec- problem worse and encourages them to modify these. It
tively movement of blood vessels), whereas tension-type is important to explain to the patient that the tendency
headache is headache without any of those features. It is to suffer an attack probably varies because of some
likely that migraine is a disorder of the brainstem, cycling changes in the brain that are not well under-
probably the aminergic systems that normally regulate stood. This is why avoiding things on some days will
sensory information and the pathways required for prevent attacks and, perversely, enjoying the same things
attention; a disorder in effect of hypersynchrony.13 In on other days produces no headache. The crucial piece

Table 1 Common causes of headache†

Primary headache Secondary headache
Type Lifetime prevalence (%) Type Lifetime prevalence (%)

Migraine 16.0 Systemic infection 63.0
Tension-type 69.0 Head injury 4.0
Cluster headache 0.4 Sub-arachnoid haemorrhage <1.0
Idiopathic stabbing 2.0 Vascular disorders 1.0
Exertional 1.0 Brain tumour 0.1
†Table adapted from Rassmussen.47

Table 2 Modified† International Headache Society diagnostic criteria for migraine 6

Migraine-episodic attacks of headache lasting 4-72 h
With two of the following With one of the following
Unilateral Nausea/vomiting
Throbbing Photophobia and phonophobia
Aggravated by movement
Moderate/severe intensity of pain
†Table adapted from Goadsby et al.48

Internal Medicine Journal 2003; 33: 436–442
438 Goadsby

of the puzzle is what the brain is doing and this is the probably do not provide candidates for prevention. The
subject of intense study. Rather than make a long list of other part of the equation relates to the natural history.
things to avoid, patients should first be encouraged to If a patient diary shows a clear trend for increased
have regular habits and not to exceed their limits. frequency it is probably better to get in early with
Regular sleep, exercise, meals, work habits, and some prevention than wait for the problem to become intrac-
time for relaxation will be very rewarding in terms of table. A simple rule for frequency might be that: (i) for
reducing headache frequency. Avoiding what regularly one or two headaches per month there is usually no need
triggers attacks (and not being disturbed when the long to start a preventive, (ii) for three or four headaches per
list of advice in the magazine is not useful) is good month it may be needed, but not necessarily and (iii) for
general advice for migraineurs. Migraineurs are individ- five or more headaches per month prevention should
uals; encourage them to individualize their trigger definitely be on the agenda for discussion. Options avail-
avoidance. Extensive and exclusive dietary advice is able for preventive treatment are included in Table 3.
rarely useful, and often seems to punish patients for their The most notable addition in recent times is topiramate,
poor choice of parents. with clear evidence of efficacy in large, placebo-
In the non-pharmacological arena it is remarkable that controlled, randomized clinical trials.21 These studies
certain disciplines – such as reflexology, osteopathy and are convincing from what I have seen, albeit only
chiropractic – pursue the treatment of migraine without abstracted as yet. Topiramate should be started at low
controlled evidence. Consider the pathophysiology of dose and slowly titrated to clinical response and side-
acute migraine with activation of trigeminocervical effects. The principles are common to neurological ther-
afferents15 and the referral of pain to the occipital and apeutics; start low, go slow and warn the patient of
upper-cervical region that can be well demonstrated in potential side-effects.
animal studies.16 It is logical, indeed expected, that
during migraine there may be neck discomfort and stiff- Acute attack therapies for migraine
ness, with perhaps over-activity of muscles such as Acute attack treatments for migraine can be usefully
trapezius. This is part of the attack, not evidence of neck divided into: (i) disease non-specific treatments, such as
disease requiring re-alignment of structures that are analgesics and non-steroidal anti-inflammatory drugs
bystanders to the pathophysiology of migraine. It is (NSAIDs) and (ii) relatively disease-specific treatments,
worth reviewing the spinal manipulation literature here, such as ergot-related compounds and triptans
because I am sure many readers are confronted with (Table 4). It must be emphasized that most acute attack
anecdote on this issue. A recent meta-analysis of spinal medications seem to have a propensity to aggravate
manipulation in migraine 17 listed three studies under headache frequency and induce a state of refractory
Chronic Migraine (which is an incorrect use of that daily or near-daily headache; ‘analgesic-associated
nomenclature but I will use it in this instance for discus- chronic daily headache (CDH)’. Codeine-containing
sion). Of these three studies, two were old, low-quality compound analgesics are a particular problem because
and did not use clear clinical definitions (i.e. non-IHS opioid receptor agonists produce troublesome with-
classification).6 The one that is modern was given a drawal symptoms and require careful monitoring. Not
rather generous run by the peer-reviewers.18 First, there all patients who stop taking regular analgesics will have
was no control group. Second, there was no differenti- a miracle cure of their headache, but almost all feel in
ation of spinal manipulation from amitriptyline. If the some way better and will be easier to treat with standard
authors used amitriptyline as an active control, assuming preventives (Table 3).
it works, then their study provides no evidence whatso- One simple approach to treatment is described as
ever for an effect of spinal manipulation. One might ‘stepped care’. In this model all patients are treated,
observe that the evidence for amitriptyline is weak,19 but assuming no contraindications, with the simplest treat-
that provides cold comfort. One study of high quality ment, such as aspirin with an antiemetic. This is an
used a clear case definition, migraine by the IHS classi- effective strategy proven by double-blind controlled
fication, and a control group.20 However, it was single- clinical trials.22 The alternative strategy is known as
blinded, in the sense that the operators knew what they ‘stratified care’, by which the physician determines, or
were doing and thus knew who was in the active group stratifies, treatment at the start based on likelihood of
and who was in the placebo group. In short, there is no response to levels of care. Lipton and Stewart have
single, well-conducted, placebo-controlled, double-blind proposed the Migraine Disability Assessment Scale
study demonstrating a positive effect for chiropractic (MIDAS)23 and have demonstrated that patients with
treatment of migraine. greater disability (high MIDAS scores) may be better off
having earlier access to triptans.24 The MIDAS scale is
Preventive treatments for migraine easy to use and freely available. Somewhere in between
The decision to start a patient on a preventive drug these two treatment strategies is ‘stepped-care with
requires input from both doctor and patient. The basis clinical modification’, which seems reasonably rational
for considering preventive treatment from a medical to the author (Table 5).
viewpoint is a combination of acute attack frequency and Simple things, such as aspirin (900 mg) and para-
attack tractability. Attacks that are unresponsive to acute cetamol (1000 mg), are cheap, can be very effective
attack medications are easily considered for prevention and are usefully employed in many patients. The
at almost any frequency, whereas simply treated attacks addition of domperidone (10 mg p.o.) or metaclopramide

Internal Medicine Journal 2003; 33: 436–442
Diagnosis & treatment of migraine 439

Table 3 Preventative therapy for migraine†5

Drug Dose Selected side-effects

Proven or very well accepted treatments2
-adrenergic receptor antagonists
Propranolol 40–120 mg b.i.d. Reduced energy, tiredness, postural symptoms
Metoprolol 100–200 mg/day Contraindicated in asthma.
Tricyclic antidepressants
Amitriptyline 25–75 mg nocte Drowsiness (Note: some patients are very sensitive and may
only need a total dose of 10 mg, although often 1 mg/kg
body weight is required for a response)
Pizotifen 0.5–3 mg/day Drowiness, weight gain
Valproate 400–600 mg bid Drowsiness, weight gain, tremor, hair loss, fetal
abnormalities, haematological and liver abnormalities
Topiramate21,49 25–200 mg/day Cognitive impairment, parasthesiae, weight loss
Flunarizine 5–15 mg/day Tiredness, weight gain, depression, Parkinsonism
Methysergide 1–6 mg/day Drowsiness, leg cramps, hair loss, retroperitoneal fibrosis
(a 1-month ‘drug holiday’ is required every 6 months)
Widely used with poor evidence§
Verapamil 160–320 mg/day Constipation, leg swelling and atrioventricular conduction
disturbances such as fluoxetine
SSRIs
Promising‡
Gabapentin50,51 900–2400 mg/day Tiredness, dizziness

SSRI, selective serotonin reuptake inhibitor. †Commonly used preventives are listed with reasonable doses and common side-effects. Local
prescribing information should be consulted before use. ‡Positive placebo-controlled studies but more data are required. §Compounds listed here
are widely used but the evidence for benefit is very poor.

Table 4 Oral acute migraine treatments required. Whereas ergotamine remains a useful anti-
migraine compound, its place as the first-choice has
Non-specific treatments† Specific treatments slipped in recent years and this trend is likely to
continue. There are particular situations in which ergot-
Aspirin (900 mg) Ergot derivatives amine is very useful, however its use must be strictly
Paracetamol (1000 mg) Ergotamine (1–2 mg) controlled because ergotamine overuse produces
NSAIDs Triptans dreadful headache in addition to a host of vascular prob-
Naproxen (500–1000 mg) Sumatriptan (50 or 100 mg) lems.26 The triptans have revolutionized the lives of
Ibuprofen (400–800 mg) Zolmitriptan (2.5 or 5 mg) many patients with migraine and are clearly the most
Tolfenamic acid (200 mg) Naratriptan (2.5 mg) powerful option available to stop a migraine attack. They
Rizatriptan (5 or 10 mg)‡ can be rationally applied by considering their pharmaco-
Almotriptan (12.5 mg)‡ logical, physicochemical and pharmacokinetic features,
Eletriptan (40 or 80 mg)‡ as well as the formulations that are available.27 Some
Frovatriptan (2.5 mg)‡,§ suggested situations in which particular triptans are
†Often used with antiemetic/prokinetics, such as domperidone (10 mg) helpful are detailed in Table 5, and a recent meta-
or metaclopramide (10 mg). ‡Not launched in Australia at the time of analysis compares the clinical trial data from 53
writing. §Not yet widely enough used in clinical practice, nor with controlled trials.28
enough published studies to make clear recommendations. NSAIDs,
non-steroidal anti-inflammatory drugs.
CHRONIC DAILY HEADACHE
(10 mg p.o.) can be very helpful. NSAIDs can be very Perhaps no clinical issue in headache provides as much
useful when tolerated. Their success is often limited by controversy nor as substantive a medical load as that of
inappropriate dosing: naproxen (500–1000 mg p.o. or daily headache. CDH is not one thing, but a collection
p.r. with an antiemetic), ibuprofen (400–800 mg p.o.) or of very different problems with different management
tolfenamic acid (200 mg p.o.) can be extremely effective. strategies. CDH is simply headache on 15 days per
Tolfenamic acid has been shown in a double-blind, month; certainly not all daily headache is tension-type
placebo-controlled study to have comparable efficacy to headache (Table 6). Population-based estimates of daily
sumatriptan 100 mg, 25 a result that reinforces the headache are remarkable, demonstrating that nearly 5%
general clinical view that NSAIDs can be very useful of people in developed countries such as Spain, 29
compounds in migraine. France30 and the USA31 are affected. Daily headache
When simple measures fail, or more aggressive treat- may again be primary or secondary, and it seems clini-
ment is required, the relatively specific treatments are cally useful to consider the possibilities in this way when

Internal Medicine Journal 2003; 33: 436–442
440 Goadsby

making management decisions. It should be said that and paroxysmal hemicrania – have chronic varieties,6 the
results from population-based studies support evidence question of frequent migraine is only now being system-
from clinical practice and a large group of refractory atically addressed. Few headache authorities would
daily headache patients overuse various over-the-counter argue that migraine can never, ever be chronic in terms of
preparations. frequency. However, the question of whether patients
with frequent headache, which fulfils some of standard
Chronic daily headache and migraine criteria for migraine, and some standard criteria tension-
Whereas it is widely accepted that some of the primary type headache, have a single migrainous problem in
headaches – tension-type headache, cluster headache biological terms is vexed.

Table 5 Clinical stratification of acute specific migraine treatments

Clinical situation Treatment options

Failed analgesics/NSAIDs Rapid effects
– Sumatriptan 50 mg or 100 mg po
– Rizatriptan 10 mg p.o.
– Zolmitriptan 2.5 mg p.o.
– Almotriptan 12.5 mg p.o.
– Eletriptan 40 mg p.o.
Slower effect/better tolerability
– Naratriptan 2.5 mg
– Frovatriptan 2.5 mg
Infrequent headache
– Ergotamine 1–2 mg p.o.†
Early nausea or problem taking tablets Nasal route
– Sumatriptan 20 mg nasal spray
– Zolmitriptan 5 mg nasal spray
Oral: rapidly dissolving
– Rizatriptan 10 mg MLT wafer
– Zolmitriptan (RapiMelt) 2.5 mg
Headache recurrence Ergotamine (perhaps most effective p.r.)
Eletriptan 80 mg p.o.
Naratriptan 2.5 mg p.o.
Tolerating acute treatments poorly Naratriptan 2.5 mg
Almotriptan 12.5 mg
Frovatriptan 2.5 mg
Early vomiting Sumatriptan 25 mg p.r. (available in Europe)
Sumatriptan 6 mg s.c.
Menstrually related headache Prevention
– Consider tri-cycling oral contraceptive to reduce menstrual attacks
– Ergotamine p.o. nocte
– Oestrogen patches
Treatment
– Triptans
Very rapidly developing symptoms Sumatriptan 6 mg s.c.
Dihydroergotamine 1 mg i.m.i.
†Expert consensus suggests there are now very few first-line uses for ergotamine in migraineurs.26 NSAIDs, non-steroidal anti-inflammatory drugs.

Table 6 Daily or near-daily headache†

Primary daily headache Secondary daily headache

Chronic migraine Chronic headache with intracranial pathology, such as subdural, brain tumour
Chronic tension-type headache Inflammatory disease, such as giant cell arteritis
Chronic cluster headache Chronic headache after dural irritation, such as postinfectious or postbleed
Chronic paroxysmal hemicrania Chronic headache after trauma, such as blunt head trauma or neurosurgical procedures
Primary new daily persistent headache52 Chronic headache with cerebrospinal fluid pressure abnormalities, such as low or raised
pressure
†Daily as used in this terminology implies headache on 15 days per month. 45

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Diagnosis & treatment of migraine 441

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