144 MIGRAINE
The tricyclic antidepressant amitriptyline(see Chapter 20)
is not licensed for this indication, but can afford good prophy-
lactic efficacy in some patients; it is given in a single dose at
night.
Cyproheptadineis an antihistamine with additional 5HT-
antagonist and calcium channel-antagonist activity. It can be
used for prophylaxis of migraine in refractory cases.
Methysergideis a semi-synthetic ergot alkaloid and 5HT 2
antagonist, which is sometimes used to counteract the effects
of secreted 5HT in the management of carcinoid syndrome. It
is highly effective as migraine prophylaxis in up to 80% of
patients. It is used for severe migraine or cluster headaches
refractory to other measures. It should only be used under
specialist hospital supervision because of its severe toxicity
(retroperitoneal fibrosis and fibrosis of the heart valves and
pleura). It is only indicated in patients who, despite other
attempts at control, experience such severe and frequent
migraine as to interfere substantially with their work or social
activities. The smallest dose that suppresses about 75% of the
headaches is used for the shortest period of time possible.
Key points
Migraine and its drug treatment- The clinical features of classical migraine consist of aura
followed by unilateral and then generalized throbbing
headache, photophobia and visual disturbances (e.g.
fortification spectra) with nausea and vomiting. - The pathophysiology of migraine is poorly understood.
5HT in particular, but also noradrenaline,
prostaglandins and kinins, have all been implicated.
Initial cranial vasoconstriction gives way to
vasodilatation, and spreading neuronal depression
occurs. - Attacks may be precipitated by relaxation after stress,
tyramine, caffeine or alcohol. Avoiding these and other
precipitants is worthwhile for individuals with a clear
history. - Up to 70% of acute attacks are aborted with simple
analgesics (e.g. paracetamol/aspirin), together with an
anti-emetic (e.g. metoclopramide/domperidone) if
necessary. - Unresponsive and disabling attacks merit more specific
therapy with 5HT1Dagonists (e.g. sumatriptan). - Preferred first-line drugs for prophylaxis are pizotifen
orβ-adrenoceptor antagonists. Topiramate, valproate,
tricyclic antidepressants, cyproheptadine and, in
exceptional cases only, methysergide may also be
effective.
Case history
A 29-year-old woman has suffered from migraine for many
years. Her attacks are normally ameliorated by oral Cafergot
tablets (containing ergotamine and caffeine) which she takes
up to two at a time. One evening she develops a particularly
severe headache and goes to lie down in a darkened room.
She takes two Cafergot tablets. Two hours later, there has
been no relief of her headache, and she takes some metoclo-
pramide 20 mg and two further Cafergot tablets, followed
about one hour later by another two Cafergot tablets as her
headache is unremitting. Approximately 30 minutes later, her
headache starts to improve, but she feels nauseated and
notices that her fingers are turning white (despite being
indoors) and are numb. She is seen in the local Accident and
Emergency Department where her headache has now disap-
peared, but the second and fifth fingers on her left hand are
now blue and she has lost sensation in the other fingers of
that hand.
Question
What is the problem and how would you treat her?
Answer
The problem is that the patient has inadvertently ingested
an overdose of Cafergot (ergotamine tartrate 1 mg and caf-
feine 100 mg). No more than four Cafergot tablets should be
taken during any 24-hour period (a maximum of eight
tablets per week). The major toxicity of ergotamine is
related to its potent α-agonist activity, which causes severe
vasoconstriction and potentially leads to digital and limb
ischaemia. Cardiac and cerebral ischaemia may also be pre-
cipitated or exacerbated. Treatment consists of keeping the
limb warm but not hot, together with a vasodilator – either
anα-blocker to antagonize the α 1 effects of ergotamine, or
another potent vasodilator such as a calcium-channel antag-
onist or nitroglycerin. Blood pressure must be monitored
carefully, as must blood flow to the affected limb/digits. The
dose of the vasodilating agents should be titrated, prefer-
ably in an intensive care unit.FURTHER READING
Arulmozhi DK, Veeranjaneyulu A, Bodhankar SL. Migraine: current
therapeutic targets and future avenues. Current Vascular
Pharmacology2006; 4 : 117–28.
Krymchantowski AV, Bigal ME. Polytherapy in the preventive and
acute treatment of migraine: fundamentals for changing the
approach. Expert Review of Neurotherapeutics2006; 6 : 283–9.