in 30–60 minutes of oral administration (longer
Migraine
Rationale for drug use
Relief of headache and associated symptoms.
Prevention of recurrent migraine.
Before starting treatment
Exclude other causes of headache, particularly if
there is an abnormal neurological examination,
new onset in patients >50 years, or a substantial
change in headache pattern.
Drugs can cause headache: as an adverse effect,
following withdrawal, or secondary to overuse (see
Medication overuse headache p 651).
Consider the possibility that >1 type of headache is
involved.
Acute migraine
Non-drug treatment
Rest or sleep in a dark and quiet room; relaxation
techniques may help.
Drug choice
Overuse of all drugs (including aspirin and
paracetamol) used to treat migraine can cause
headache (see also Medication overuse
headache p 651).
First-line drug treatment for mild-to-moderate
migraine is usually an analgesic such as paraceta-
mol, aspirin or another NSAID. If these are consist-
ently ineffective (eg for 3 attacks) or if migraine is
severe, use a triptan or ergot alkaloid at the onset of
the attack. Alternative triptans or ergot alkaloids
may be tried over subsequent episodes to find the
most effective agent.
Consider adding an antiemetic for nausea and
vomiting and for those who do not respond to an
analgesic alone.
Analgesics
There are few studies of analgesics in migraine,
but aspirin (p 44) or other NSAIDs (p 617), eg
ibuprofen, naproxen, are beneficial in practice;
paracetamol (p 45) alone may be less effective.
Ensure analgesics are taken in sufficient dosage
early in the attack, when absorption is least
impaired by reduced GI motility; use soluble
products in preference.
Avoid opioids (including paracetamol or aspirin
with codeine or dextropropoxyphene) because
they aggravate GI symptoms, have a risk of
dependence, and there is little evidence for their
effectiveness in acute migraine.
Antiemetics
Oral metoclopramide (p 485) or domperidone
(p 484) may be used at the onset of symptoms
and then every 6–8 hours if needed. They reduce
nausea and vomiting, increase GI motility and
may improve absorption of analgesics.
When nausea or vomiting are prominent,
metoclopramide (IM/IV) or prochlorperazine
(IM/IV or rectally) may be used but there is a risk
of EPSE (eg acute dystonic reaction).
Triptans (5HT1 agonists)
Triptans (p 651) are effective in about two-thirds
of patients. They begin to relieve headache with-
AMH © 2011
with naratriptan); they also improve associated
symptoms such as nausea, vomiting, photo-
phobia and phonophobia. About one-third of
patients may have recurrence of headache, which
a second dose may relieve.
All are effective, well tolerated and safe. How-
ever, the response to each agent can vary consid-
erably between patients.
Triptans are most effective if taken when the
headache is beginning to develop, and not earlier
(eg during aura) or later (when headache is more
severe).
Sumatriptan is the most studied; there are limited
data comparing sumatriptan with other triptans.
Few trials compare triptans directly with analge-
sics or ergot alkaloids. Efficacy of oral sumatrip-
tan is similar to oral aspirin with or without
metoclopramide. Efficacy of sumatriptan and
ergot alkaloids seem similar via the SC or rectal
route but adverse effects are more common with
the latter.
Ergot alkaloids
Use of ergot alkaloids (p 680) is limited by
adverse effects (eg peripheral vasoconstriction)
and lack of evidence regarding effective doses;
also associated with high risk of overuse synd-
romes and rebound headaches.
Ergotamine is used rectally and dihydroergot-
amine is given SC or IM. They should be taken at
the onset of a migraine attack. Do not use with
triptans.
Prevention of migraine
Non-drug treatment
Self-management is the key. Identify and manage
trigger factors if possible, eg missing meals, stress,
irregular sleep habits, alcohol, bright lights, over-
work. Often there is no obvious cause. Relaxation
and behavioural therapy may help, and there is
limited evidence for the effectiveness of acupunc-
ture but more studies are needed.
Drug choice
Consider drug treatment if the person has 2 or
3 severe migraine attacks each month that
significantly impair quality of life and do not
respond well to treatment taken at the start of
attacks. Take patient preference into account, as
compliance with these drugs is often low.
Prophylactic drugs are relatively non-specific, with
moderate efficacy at best, and are associated with 16
significant adverse effects. Some are not approved
for this indication.
First-line drugs are beta-blockers and amitriptyline;
valproate and topiramate are second line. Other
drugs are used but either evidence for their efficacy
is limited (eg gabapentin) or they have adverse
effects that limit their use (eg methysergide, pizo-
tifen).
The choice of treatment involves balancing clinical
response and tolerability and considering coexist-
ing diseases for which the drug may also be of
benefit (eg beta-blockers for migraine and angina or
hypertension).
Treatment for acute attacks is still required as
preventive therapy only reduces frequency and
 severity of attacks; this must be explained to
patients. It may take 1–3 months for the full effect
to be seen.
Use only 1 preventive agent at a time. Start at a low
dose and increase gradually to the lowest effective
dose. If the drug is effective, continue for
4–6 months and then, to establish if it is still
required, gradually withdraw over 2–3 weeks
(rebound headaches may occur with rapid with-
drawal). Long-term prophylaxis may be necessary
in some patients, but evidence of benefit is weak.
Beta-blockers
Beta-blockers (p 263) with no intrinsic sympa-
thomimetic activity can decrease the frequency
of migraine attacks.
Propranolol has the most evidence of efficacy.
Metoprolol is also approved for migraine
prevention and atenolol (not approved) is
frequently used. Although evidence is more
limited, both are effective in preventing
migraine.
Failure of one beta-blocker does not predict
response to another, so consecutive trials of
different drugs may be appropriate.
Antidepressants
Amitriptyline (p 745): although not marketed for
this indication, amitriptyline is effective
(evidence for the efficacy of other TCAs is
lacking). It may be particularly useful in patients
with associated tension headache. Start with a
low dosage at bedtime, and gradually increase.
Venlafaxine (p 751) may be effective but evidence
is limited; it is not marketed for migraine pre-
vention.
Antiepileptics
Topiramate (p 664): limited studies suggest it is
more effective than placebo, as effective as
valproate, and possibly as effective as propran-
olol, in reducing frequency of migraine. Adverse
effects, eg cognitive dysfunction, are common. It
may be considered second-line for migraine
prevention.
Valproate (p 665) reduces migraine frequency but
is not marketed for this indication. Its use in
women is limited by the risks associated with
use during pregnancy (see Pregnancy p 650 in
Epilepsy).
Gabapentin may have modest efficacy, but
16 evidence is limited.
Methysergide
Methysergide (p 683) is considered the most
effective preventive agent, but its use is limited
by a high incidence of adverse effects. Reserve it
for prevention of severe recurrent migraine
attacks or cluster headache unresponsive to
other treatments.
Other drugs
Pizotifen may be effective, but is poorly tolerated
with a high rate of withdrawal due to adverse
effects, particularly drowsiness and weight gain.
Cyproheptadine and clonidine are still marketed for
prevention of migraine but are rarely used.
Evidence for the efficacy of cyproheptadine is
lacking and clonidine has been shown to be
ineffective.
Special cases
Children
Management is similar to that in adults but fewer
drugs are approved for treatment of migraine in
children.
Acute attacks
Paracetamol or an NSAID is usually effective;
nasal sumatriptan can relieve migraine in
adolescents aged 12–17 years. Avoid aspirin in
children <12 years and in those aged 12–16 years
with, or recovering from, chickenpox, influenza
or fever. Although antiemetics (eg prochlor-
perazine, promethazine) may be used to reduce
nausea and vomiting, evidence regarding their
efficacy in paediatric migraine is lacking and
EPSE (eg acute dystonia) are more common in
children.
Behavioural therapy, particularly biofeedback
with or without progressive muscle relaxation,
may be useful.
Prevention
Evidence for efficacy in children is conflicting
for propranolol, and limited for drugs such as
amitriptyline, topiramate and valproate.
Pizotifen appears to be ineffective.
Cluster headache
Cluster headache is rare and debilitating. Each
attack is short-lived but multiple attacks may occur
each day. Prevention is the main treatment;
abortive agents are used for breakthrough head-
ache; seek specialist advice. Avoid alcohol during
active cluster periods.
Prevention
There is limited evidence from trials for the
efficacy of drug treatments. Verapamil is a
reasonable first choice; it may initially be
combined with short-term high-dose oral
corticosteroids (usually prednisolone). Other
drugs, eg methysergide, pizotifen and lithium,
may be effective but more research is needed.
Start treatment at the first sign of an attack and
continue for 2 weeks after the last attack before
tapering dosage gradually and stopping until
the next attack.
Breakthrough treatment
Inhaling oxygen (7–12 L/minute for 10–15 min-
utes) at the onset of symptoms relieves pain in
about 70–80% of people within 15 minutes. SC
sumatriptan is similarly effective. Sumatriptan
nasal spray is also used and may improve or
abolish headache within 30 minutes.
Ergotamine and dihydroergotamine are market-
ed for use in acute attacks but evidence for their
efficacy is lacking.
Menstrual migraine
Triggered by reduction in oestrogen concentration
and occurs regularly within 1–2 days of the start of
a period.
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Acute treatment is the same as for other types of
migraine. Prevention includes taking an NSAID for
the duration of the period and/or use of oestrogen
supplements for 7 days, starting 3 days before
menstruation.
Medication overuse headache
Associated with all drugs (including paracetamol
and NSAIDs) used for treating acute migraine and
can occur in adults and children. Risk increases
with regular use of medication on >2 days/week.
Diagnosis is more likely with headache occurring
on >15 days/month and regular use of:
– paracetamol and/or NSAIDs on >14 days per
month for >3 months or
– triptans, ergot alkaloids, opioids or com-
bination analgesics on >9 days/month for
>3 months.
Management
Withdraw the overused drugs (may require
specialist referral). Withdrawal symptoms last
2–10 days, but complete resolution may take
months and relapse is common.
Reduce need for acute treatment by using ade-
quate preventive therapy to manage frequent
headaches. See Prevention of migraine p 649.
Practice points
• ask the patient to keep a diary recording drugs
and dosages used, and response to treatment,
including adverse effects
• in addition to medication overuse headache,
overuse of triptans, ergot alkaloids or opioids
(including combinations of paracetamol or
aspirin with codeine or dextropropoxyphene)
may be associated with dependence and
subsequent withdrawal syndrome
• migraine is associated with an increased risk of
depressive and anxiety disorders, which may
require treatment
• there is limited evidence for combining NSAIDs
or metoclopramide with triptans; consider this if
a triptan alone is ineffective
Triptans
See also Migraine p 649
For drug interactions see Triptans p 928
Also known as 5HT1 agonists.
Eletriptan p 652
Naratriptan p 652
Rizatriptan p 652
Sumatriptan p 652
Zolmitriptan p 653
Mode of action
Constrict cranial vessels by acting selectively at
5HT1B/1D receptors; also thought to inhibit the
abnormal activation of trigeminal nociceptors.
Indications
Acute relief of migraine
Precautions
Cerebro- or cardiovascular disease
Contraindicated in uncontrolled hypertension and
peripheral vascular disease, and if there is a history
of MI, ischaemic heart disease, coronary vaso-
AMH © 2011
spasm (eg Prinzmetal’s angina), cerebrovascular
accident or TIA.
Patients with risk factors for ischaemic heart
disease are at higher risk of cardiovascular adverse
effects.
Adolescents
Consider an intranasal product; efficacy of oral
triptans has not been established in people aged
12–17 years.
Elderly
Limited data; use not recommended due to
potential increased risk of cardiovascular adverse
effects.
Pregnancy
Limited data; appear acceptable; all Australian
category B3 except eletriptan and rizatriptan
(Australian category B1).
Breastfeeding
Contact one of the pregnancy drug information
centres (p 944); sumatriptan may be safe to use.
Adverse effects
Dependence may occur with overuse resulting in
recurrent and/or rebound headaches and with-
drawal syndrome.
Common
sensations of tingling, heat, pain, heaviness or
tightness in any part of the body including chest
and throat, flushing, dizziness, feeling of weak-
ness, drowsiness, fatigue, nausea, vomiting, dry
mouth, transient increase in BP
Infrequent
rash
Rare
angina, MI and death, arrhythmias, stroke,
seizures, ischaemic colitis, hypersensitivity
reactions including anaphylaxis
Comparative information
There is no evidence that any triptan is safer than
another, although the response to each agent can
vary considerably between patients. The same
individual may also respond quite differently to
different triptans.
With the exception of naratriptan, the oral triptans
relieve headache within 30–60 minutes.
Eletriptan and naratriptan are the only triptans that
are not substrates of MAO-A so these are the best
options in patients taking MAOIs.
Naratriptan has a slower onset of action and is less 16
effective in improving headache than sumatriptan,
but has a lower relapse rate and fewer adverse
effects.
Rizatriptan may be useful in nauseous patients as
the wafers can be taken without water. It has similar
efficacy to sumatriptan.
Sumatriptan is also available as an injection and as a
nasal spray; may be useful in people with nausea
and vomiting.
Eletriptan and zolmitriptan have similar efficacy and
adverse effects to sumatriptan.
Counselling
This medication is most effective if taken when the
headache is beginning to develop, and not earlier
(eg during aura) or later (when headache more
severe).
 This medicine may make you feel drowsy or dizzy;
if you are affected, do not drive or operate
machinery.
If there is no improvement with the first dose, do
not repeat.
Eletriptan
For additional information see Triptans p 651
For drug interactions see Triptans p 928, Eletriptan
p 928
Indications
Acute relief of migraine
Precautions
Other drugs
Manufacturer contraindicates use within 24 hours
of an ergot alkaloid or methysergide and within
48 hours of the CYP3A4 inhibitors ketoconazole,
itraconazole, erythromycin, clarithromycin, fosam-
prenavir, ritonavir, indinavir and saquinavir.
Renal
Effect on BP may be greater in renal impairment;
reduce maximum dose.
Hepatic
Contraindicated in severe impairment (no data).
Dosage
Adult >17 years, 40 mg as soon as possible after
onset of headache. Dose may be repeated after at
least 2 hours if migraine recurs. Maximum single
dose 80 mg; maximum daily dose 160 mg (but see
Practice points below).
CrCl <50 mL/minute, 20–40 mg; maximum daily
dose 40 mg.
Practice points
• the incidence of adverse effects (including chest
pain) is higher with the 80 mg dose; the maxi-
mum daily dose in the Australian approved
product information (160 mg) is double that
approved in the UK and the USA (80 mg)
tab, 40 mg (orange), 2, 4, 6, Relpax (PF), PBS-A[4]1
tab, 80 mg (orange), 2, 4, 6, Relpax (PF), PBS-A[4]1
1 help it to be absorbed more quickly). It may take
migraine usually unresponsive to analgesics
Naratriptan
For additional information see Triptans p 651
For drug interactions see Triptans p 928
Indications
16 Acute relief of migraine
Precautions
Treatment with ergot alkaloids or methysergide—may
increase risk of vasospasm; avoid combination.
Renal
Contraindicated if CrCl <15 mL/minute; reduce
maximum daily dose if CrCl 15–50 mL/minute.
Hepatic
Contraindicated in severe impairment; reduce
maximum daily dose in mild-to-moderate
impairment.
Dosage
Adult, 2.5 mg as soon as possible after onset of
headache. Dose may be repeated after at least
4 hours if migraine recurs. Maximum daily dose
5 mg.
Renal or hepatic impairment
Maximum daily dose 2.5 mg in mild-to-moderate
hepatic impairment or if CrCl 15–50 mL/minute.
tab, 2.5 mg (green), 2, 4, 6, Naramig (GK), PBS-A[4]1,2
1 migraine usually unresponsive to analgesics
2 indication as for footnote 1 and when other PBS-listed
drugs are unsatisfactory, see PBS
Rizatriptan
For additional information see Triptans p 651
For drug interactions see Triptans p 928, Rizatriptan
p 928
Indications
Acute relief of migraine
Precautions
Phenylketonuria—wafers contain phenylalanine.
Other drugs
Propranolol increases rizatriptan concentration;
reduce rizatriptan dose.
Manufacturer contraindicates use with, or within
14 days of stopping, a MAOI. Use within 6 hours of
an ergot alkaloid or methysergide is not recom-
mended.
Renal
Reduce dose and use with caution if CrCl <10 mL/
minute.
Dosage
Adult
10 mg as soon as possible after onset of headache;
repeat after at least 2 hours if migraine recurs.
Maximum daily dose 30 mg.
With propranolol, 5 mg taken as above; maximum
daily dose 15 mg.
CrCl <10 mL/minute, 5 mg taken as above;
maximum daily dose 15 mg.
Counselling
Put the wafer on top of your tongue and wait for it
to dissolve. You do not need to take it with any
liquid (but taking a glass of water afterwards may
longer to work if you take it after food.
wafer, 10 mg (white), 2, Maxalt (MK), PBS-A[4]1
1
migraine usually unresponsive to analgesics
Sumatriptan
For additional information see Triptans p 651
For drug interactions see Triptans p 928, Sumatriptan
p 928
Indications
Acute relief of migraine
Acute relief of cluster headache (injection)
Precautions
Other drugs—manufacturer contraindicates use
with, or within 14 days of stopping, a MAOI and
use with, or within 24 hours of stopping, an ergot
alkaloid or methysergide.
Adolescents
Intranasal, but not oral, sumatriptan is effective in
adolescents (12–17 years) in whom migraine
attacks are relatively short.
Hepatic
AMH © 2011
Contraindicated in severe hepatic impairment. Adverse effects
Adverse effects Rare
Common prolonged QT interval
transient pain at injection site; transient burning Dosage
sensation in the nose or throat, taste disturbance Adult, 2.5 mg as soon as possible after onset of
(nasal spray); dyspnoea headache. Dose may be repeated after at least
Rare
2 hours if migraine recurs; 5 mg may be given at
onset if lower dose tolerated but ineffective in
dystonia
previous attack. Maximum daily dose 10 mg.
Dosage
Severe hepatic impairment
Adult Maximum daily dose 5 mg.
Use as soon as possible after onset of headache.
Oral, 50–100 mg. Dose may be repeated after at tab, 2.5 mg (yellow), 2, Zomig (AP), PBS-A[4]1,2
1
least 2 hours if migraine recurs. Maximum daily migraine usually unresponsive to analgesics
2 indication as for footnote 1 and when other PBS-listed
dose 300 mg.
drugs are unsatisfactory, see PBS
SC, 6 mg. Dose may be repeated after at least
1 hour if migraine recurs. Maximum daily dose
12 mg.
Intranasal, 10–20 mg into 1 nostril. Dose may be
repeated after at least 2 hours if migraine recurs.
Maximum daily dose 40 mg.
Administration advice
Do not use IV (increased risk of coronary vaso-
spasm); give first SC injection under medical
supervision.
Practice points
• 100 mg oral dose is little better than 50 mg in
most people; it has more adverse effects, but can
be used if the lower dose is ineffective
Route of administration
• SC administration is more effective than oral but
there are more adverse effects and a higher
recurrence rate
• intranasal administration has a quicker onset of
action than oral
• if vomiting prevents oral use, SC route may be
preferred as absorption from the intranasal
route depends largely on ingestion
• the bitter taste of the nasal spray may be
unacceptable
tab, 50 mg (pink), 2, 4, Imigran (GK), Imigran FDT (GK),
Sumatab (AL), Sumatriptan (CR), PBS-A[4]1
tab, 50 mg (white), 4, Sumagran (SI), PBS-A1
tab, 100 mg (white), 2, Imigran (GK), Imigran FDT (GK),
Sumatab (AL)
nasal spray, 10 mg, 2, Imigran (GK)
nasal spray, 20 mg, 2, Imigran (GK), PBS-A1
inj, 12 mg/mL, 0.5 mL (kit for), 2, Imigran Mk II (GK)
inj, 12 mg/mL, 0.5 mL (cartridge), 2, Imigran Mk II Refill (GK)
1
migraine usually unresponsive to analgesics 16
Zolmitriptan
For additional information see Triptans p 651
For drug interactions see Triptans p 928, Zolmitriptan
p 928
Indications
Acute relief of migraine
Precautions
Treatment with ergot alkaloids or methysergide—
manufacturer contraindicates use.
Hepatic
Reduce maximum daily dose in severe
impairment.

AMH © 2011