A Textbook of Clinical Pharmacology and Therapeutics

DRUGSUSED FORMIGRAINEPROPHYLAXIS 143

and zolmitriptan.Sumatriptan is also of value in cluster
headache. Importantly, they can cause vasoconstriction in other
vascular beds, notably the coronary and pulmonary vascula-
ture; they should therefore be avoided in patients with coronary
heart disease, cerebrovascular disease or peripheral arterial dis-
ease, and should also not be used in patients with significant
systemic or pulmonary hypertension. They should not be com-
bined with other serotoninergic drugs: ergotamine, MAOIs,
lithiumor selective serotonin reuptake inhibitors (SSRIs).
Sumatriptancan be given subcutaneously, by mouth or as a
nasal spray. Its bioavailability is only 14% when given orally due
to substantial presystemic hepatic metabolism. Rizatriptancan
be given orally, or as wafers to be dissolved on the tongue.
Zolmitriptancan be given orally or by intranasal spray. Both riza-
triptanandzolmitriptanhave 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 effec-
tive 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then withdrawn with monitoring of the frequency of attacks.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,metopro-

lol) 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 potenti-

ate the peripheral vasoconstriction caused by triptans or ergot-

amine, and these drugs should not be given concurrently.

Pizotifenis an appropriate choice for migraine prophy-

laxis, 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 stimula-

tion and weight gain. It potentiates the drowsiness and sed-

ation of sedatives, tranquillizers and antidepressants, and

should not be used with monoamine oxidase inhibitors.

The anti-epileptic drugs topiramateandsodium valproate

(see Chapter 22) also have good effectiveness in the prophy-

laxis of migraine. Topiramateshould only be initiated under

specialist supervision.

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?

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

2 or more attacks per month

Increasing frequency/severity

Incomplete relief by acute treatment

of attacks

Unable to take acute treatments

2 attacks per month

Stable in frequency and severity

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.