There can be variation in the licensing of
different medicines containing the same drug. Forms available
from special-order manufacturers include: oral solution
Tablet
CAUTIONARY AND ADVISORY LABELS 2
▶Pizotifen (Non-proprietary)
Pizotifen (as Pizotifen hydrogen malate)
500 microgram Pizotifen 500microgram tablets | 28 tablet P
£16.25 DT = £1.73
Pizotifen (as Pizotifen hydrogen malate) 1.5 mg Pizotifen 1.5mg
tablets | 28 tablet P £16.25 DT = £4.85
6.1a Migraine
Migraine
Description of condition
Migraine is a common type of primary headache disorder. It
occurs more commonly in women than in men, and is
characterised by recurrent attacks of typically moderate to
severe headaches that usually last between 4–72 hours. The
headache is usually unilateral, pulsating, aggravated by
routine physical activity, and may be severe enough to
impact or prevent daily activities. It is frequently
accompanied by nausea and vomiting, photophobia and
phonophobia, or both. Migraine is subdivided into migraine
with or without aura, and is defined as either episodic or
chronic.
Migraine with aura consists of visual symptoms (zigzag or
flickering lights, spots, lines, or loss of vision), sensory
symptoms (pins and needles, or numbness), or dysphasia,
which usually precede the onset of headache. Symptoms
usually develop gradually and resolve within 1 hour.
Episodic migraine is defined as headache which occurs on
less than 15 days per month, and can be further subdivided
into low frequency (1–9 days per month) and high frequency
(10–14 days per month). Chronic migraine is defined as
headache which occurs on at least 15 days per month and
has the characteristics of a migraine headache on at least
8 days per month for greater than 3 months.
In some women, the drop in oestrogen levels just before
menstruation is a trigger for migraine, with symptoms
generally occurring from two days before the start of
bleeding up until three days after.
Medication-overuse headache is a complication of
migraine; the frequent use of acute treatment for migraine
increases the frequency and intensity of headache, and can
become the cause of the headache.
Aims of treatment
Treatment of acute migraine aims to stop the attack, or to
significantly reduce the severity of the headache and other
associated symptoms. Preventative treatment aims to reduce
the frequency, severity and duration of migraine attacks, and
development of medication-overuse headache.
Nervous system
Lifestyle advice
g Patients should be encouraged to eat regular meals,
and to maintain adequate hydration, sleep and exercise. h
Other potential triggers include stress, relaxation after
stress, some foods and drinks, and bright lights. g Known
triggers should be avoided; keeping a headache diary may be
useful to identify potential triggers and should be continued
for a minimum of 8 weeks. h
Acute migraine treatment
g The choice of treatment for acute migraine should be
guided by the patient’s preference, response to previous
treatment, the severity and frequency of headache attacks,
other associated symptoms, and co-morbidities. Treatment
should ideally be restricted to 2 days per week and patients
should be advised of the risk of developing medication-
overuse headache.
Monotherapy, with either aspirin p. 130, ibuprofen
p. 1203, or a 5HT1-receptor agonist (‘triptan’) is
recommended as first-line treatment and should be taken as
soon as the patient knows that they are developing a
migraine (start of headache phase).
In patients who experience aura with their migraine, it is
recommended that 5HT1-receptor agonists are taken at the
start of the headache and not at the start of the aura (unless
the aura and headache start at the same time). Treatment
with a 5HT1-receptor agonist can be repeated after 2 hours
with the same or different drug if there has been an
inadequate response to the initial dose.
Based on its clinical efficacy and safety profile,
sumatriptan p. 503 is the 5HT1-receptor agonist of choice.
h Alternative 5HT1-receptor agonists include almotriptan
p. 500, eletriptan p. 501, frovatriptan p. 501, naratriptan
p. 502, rizatriptan p. 502, and zolmitriptan p. 504. g In
patients who do not respond to one 5HT1-receptor agonist, a
different 5HT1-receptor agonist should be tried as response
can be variable between patients. Subcutaneous sumatriptan
p. 503 or nasal zolmitriptan p. 504 can be given to patients
who present with early vomiting or who have severe
migraine attacks. h
g Other NSAIDs that may be used for the treatment of
acute migraine include, naproxen p. 1211 [unlicensed
indication], tolfenamic acid p. 497, and diclofenac potassium
p. 1197. In patients presenting with severe nausea and
vomiting, diclofenac sodium suppositories p. 1198
[unlicensed indication] may be an option. Mefenamic acid
p. 1208 [unlicensed indication] can also be used for
menstrual migraine in women already using it for other
indications such as dysmenorrhea, or menorrhagia. l
g Treatment with paracetamol p. 465 can be considered
in patients who are unable to take other acute treatment
options.
In patients who fail to respond to monotherapy,
combination therapy with sumatriptan p. 503 and naproxen
p. 1211 can be given.
In addition to their use as antiemetics, metoclopramide
hydrochloride p. 452 [unlicensed indication] or
prochlorperazine p. 407 [unlicensed indication] can also be
given as a single dose at the onset of migraine symptoms for
the treatment of headache. They can be given orally or by
injection, depending on the severity of the patients’
symptoms and the setting. h
Antiemetics
g Metoclopramide hydrochloride p. 452 or
prochlorperazine p. 407 can be given orally or by injection to
relieve nausea or vomiting. Metoclopramide hydrochloride
p. 452 should not be used regularly due to the risk of
extrapyramidal side effects. h The MHRA and CHM (2013)
have released important safety information regarding the
Nervous system
use of metoclopramide and risk of neurological adverse
effects. See Important safety information for metoclopramide
hydrochloride p. 452.
g Domperidone p. 451 [unlicensed in those weighing
less than 35 kg] may be used as an alternative antiemetic.
l The MHRA and CHM (2019) have released important
safety information and restrictions regarding the use of
domperidone for nausea and vomiting in those weighing less
than 35 kg, and a reminder of contra-indications. For further
information, see Important safety information for
domperidone.
Preventative migraine treatment
g The decision to start prophylactic treatment should be
based on the impact of the migraine on the patient’s quality
of life. The choice of treatment depends on factors such as
patient preference, drug interactions, and other co-
morbidities. Treatment should be started at a low dose and
gradually increased to the maximum effective and tolerated
dose.
Propranolol hydrochloride p. 162 is recommended as first-
line preventative treatment in patients with episodic or
chronic migraine. hg For patients in whom propranolol
is unsuitable, other beta-blockers that can be considered are
metoprolol tartrate p. 166, atenolol p. 164 [unlicensed
indication], nadolol p. 161, and timolol maleate p. 163.
Bisoprolol fumarate p. 165 [unlicensed indication] may also
be considered, especially in patients already taking it for
cardiac reasons under the advice of their cardiologist.
lg Topiramate p. 348 can be given if a beta-blocker is
unsuitable, however in women of childbearing potential,
advice should be given on the associated risks during
pregnancy, the need to use highly effective contraception
and to seek further information if pregnant or planning a
pregnancy. h See Conception and contraception, and
Pregnancy in the topiramate p. 348 drug monograph for
further information.
g Amitriptyline hydrochloride p. 390 is effective for
migraine prophylaxis and should be considered for patients
with episodic or chronic migraine. A less sedative tricyclic
antidepressant can be used if amitriptyline hydrochloride
p. 390 is not tolerated.
Candesartan cilexetil p. 186 [unlicensed indication] can be
considered in patients with episodic or chronic migraine,
although there is limited evidence to support its use.
Sodium valproate p. 344 [unlicensed indication] can also
be considered in patients with episodic or chronic migraine.
h The MHRA has advised that sodium valproate must not
be used in women of childbearing potential unless the
conditions of the Pregnancy Prevention Programme are met
and alternative treatments are ineffective or not tolerated; it
must not be used during pregnancy for migraine prophylaxis.
For further information, see Important safety information,
Conception and contraception, and Pregnancy in the sodium
valproate p. 344 drug monograph.
g Flunarizine [unlicensed] can also be considered in
patients with episodic or chronic migraine (specialist use
only). Pizotifen p. 494 is used but evidence to recommend its
use is limited.
Preventative treatment should be tried for at least
3 months at the maximum tolerated dose, before deciding
whether or not it is effective. h A good response to
treatment is defined as a 50% reduction in the severity and
frequency of migraine attacks. g A review of ongoing
prophylaxis should be considered after 6–12 months;
treatment can be gradually withdrawn in many patients.
Patients should be referred to a neurology or specialist
headache clinic if trials with 3 or more drugs have been
unsuccessful.
Botulinum toxin type A p. 425 (specialist use only) is
recommended for prophylaxis of chronic migraine where
medication-overuse has been addressed and where 3 or more
oral prophylactic treatments have failed. h
Menstrual migraine prophylaxis
g Frovatriptan p. 501 [unlicensed indication] can be given
instead of, or in addition to, standard prophylactic treatment
in women with perimenstrual migraine. It is given from
2 days before until 3 days after menstruation starts.
Zolmitriptan p. 504 [unlicensed indication] or naratriptan
p. 502 [unlicensed indication] are suitable alternatives to
frovatriptan p. 501. In order for treatment to be effective, the
patient’s menstrual cycle must be regular.
Women with menstrual-related migraine who are using
5HT1-receptor agonists for both perimenstrual prophylaxis
and at other times in the month should be advised of the
increased risk of developing medication-overuse headache.
h
Medication-overuse headache
g Medication overuse should be addressed in patients
overusing acute treatments such as 5HT1-receptor agonists,
combination analgesics, ergots, or opioids for migraine. h
Withdrawing the overused medication can reduce the
frequency and intensity of headaches but is often associated
with transient worsening. Not all patients overusing acute
treatment will develop medication-overuse headache; in
some patients, continued headaches may be a sign of poorly
treated migraine.
Useful Resources
Pharmacological management of migraine. Scottish
Intercollegiate Guidelines Network. A national clinical
guideline 155. February 2018.
www.sign.ac.uk/assets/sign155.pdf
Other drugs used for Migraine Clonidine hydrochloride,
p. 156. Cyclizine, p. 449. Trifluoperazine, p. 408. Valproic
acid, p. 372
ANALGESICS › NON-OPIOID
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