Clinical Pharmacology and Therapeutics

DRUGS USED FOR MIGRAINE PROPHYLAXIS 143
Assessment of migraine severity and frequency
Do attacks interfere significantly with the patient's life?
How frequent are attacks?
Are attacks increasing in frequency and/or severity?
2 attacks per month
Stable in frequency and severity
2 or more attacks per month
Increasing frequency/severity
Incomplete relief by acute treatment
of attacks
Unable to take acute treatments
Acute treatment strategy
Identify possible precipitants (stress;
irregular lifestyle, e.g. lack of sleep;
chemical triggers, e.g. alcohol, cheese,
chocolate, nitrates; combined oral
contraceptives) and avoid where possible
Treat as early as possible in attack
Treat with simple analgesia (aspirin,
paracetamol or NSAID) or triptan
Co-administer metoclopramide or
domperidone
Prophylactic treatment strategy
Identify possible precipitants
(stress; irregular lifestyle, e.g. lack
of sleep; chemical triggers, e.g.
alcohol, cheese, chocolate, nitrates;
combined oral contraceptives) and
avoid where possible
Treat with regular prophylactic drug:
Pizotifen
Beta blocker
Topiramate
Sodium valproate
Tricyclic antidepressant
(Cyproheptadine)
(Methysergide)
Treat acute attacks as for acute
treatment strategy
Figure 23.1: Scheme for the acute
treatment and prophylaxis of
migraine.
and zolmitriptan. Sumatriptan is also of value in cluster
headache. Importantly, they can cause vasoconstriction in other
vascular beds, notably the coronary and pulmonary vasculature;
they should therefore be avoided in patients with coronary
heart disease, cerebrovascular disease or peripheral arterial disease,
and should also not be used in patients with significant
systemic or pulmonary hypertension. They should not be combined
with other serotoninergic drugs: ergotamine, MAOIs,
lithium or selective serotonin reuptake inhibitors (SSRIs).
Sumatriptan can be given subcutaneously, by mouth or as a
nasal spray. Its bioavailability is only 14% when given orally due
to substantial presystemic hepatic metabolism. Rizatriptan can
be given orally, or as wafers to be dissolved on the tongue.
Zolmitriptan can be given orally or by intranasal spray. Both rizatriptan
and zolmitriptan have good oral bioavailability, but when
given parenterally have a quicker onset of action. These drugs can
be taken at any time during a migraine attack, but are most effective
if taken early, and relieve symptoms in 65–85% of attacks.
DRUGS USED FOR MIGRAINE
PROPHYLAXIS
Migraine prophylaxis should be considered in patients who:
• suffer at least two attacks a month;
• are experiencing an increasing frequency of headaches;
• are significantly symptomatic despite suitable treatment
for migraine attacks;
• cannot take suitable treatment for migraine attacks.
Due to the relapsing/remitting natural history of migraine,
prophylactic therapy should be given for four to six months and
then withdrawn with monitoring of the frequency of attacks.
β-Adrenoreceptor antagonists (e.g. propranolol, metoprolol)
have good prophylactic efficacy and can be given as a once
daily dose of a long-acting preparation. The mechanism of
action of the β-blockers in this regard is uncertain, but they may
act by opposing dilatation of extracranial vessels. They potentiate
the peripheral vasoconstriction caused by triptans or ergotamine,
and these drugs should not be given concurrently.
Pizotifen is an appropriate choice for migraine prophylaxis,
especially if β-blockers are contraindicated. It is related
to the tricyclic antidepressants. It is a 5HT 2 antagonist. It also
has mild antimuscarinic and antihistaminic activity. It affords
good prophylaxis, but can cause drowsiness, appetite stimulation
and weight gain. It potentiates the drowsiness and sedation
of sedatives, tranquillizers and antidepressants, and
should not be used with monoamine oxidase inhibitors.
The anti-epileptic drugs topiramate and sodium valproate
(see Chapter 22) also have good effectiveness in the prophylaxis
of migraine. Topiramate should only be initiated under
specialist supervision.