MIGRAINE

What is migraine?

Migraine is a severe form of headache which can last from a few hours to 72 hours or longer. Symptoms are very variable, but five stages are recognised:

• the prodrome, when there may be mood variations, neck stiffness and changes in gut activity
• the aura - a short period of visual or sensory disturbances such as patterns of flickering lights
• severe headache, aggravated by light and sound, that may be accompanied by nausea or vomiting
• resolution, as the headache declines, and deep sleep may occur
• the postdrome, when the patient feels fatigued and lethargic.

Between two main forms of migraine are recognised: those with and those without aura. 10-30 per cent of people with migraine experience migraine with aura (also known as classical migraine).

A wide range of factors can precipitate an attack, such as certain foods, menstruation, disturbed sleep pattern, stress, and smoking. There have been many theories proposed to provide an explanation for how migraine arises, mostly involving some aspect of blood flow or brain activity.

Who does migraine affect and what does it cost?

Migraine headaches are thought to affect almost six million people in the UK, with more than twice as many women affected as men. Many migraine sufferers treat themselves with over-the-counter pain medications such as aspirin, so that in these cases the cost does not fall on the NHS. Migraine has been estimated to cause the loss of 25 million days of work/education per year in the UK.

Present treatments and shortcomings

Many products are available for migraine, some for prevention (prophylaxis) and others to treat an attack. Prophylactic agents include Beta-blockers (metoprolol, from AstraZeneca/Novartis, or propranolol, nadolol, timolol, from AstraZeneca, sanofi-aventis and Valeant respectively), 5HT-antagonists such as pizotifen and methysergide (Novartis), Merck Sharp & Dohme's cyproheptadine, and the central alpha-agonist clonidine (Boehringer-Ingelheim). More recently, the anti-epileptic medication topiramate (Topamax, Janssen-Cilag) has also been made available for the prevention of migraine. Though useful, some of these prophylactic agents have side effects such as sedation, abdominal cramps, nausea, dizziness and so on.

Therapy for an acute attack most often involves painkillers for mild to moderate attacks, or ergotamine for more severe attacks, perhaps combined with an anti-emetic for feelings of nausea. However, in recent years, selective serotonin receptor agonists, known as 'triptans' have been introduced and have quickly taken a leading position in migraine therapy. The first of these, sumatriptan (Imigran, GlaxoSmithKline) was originally given by injection, but is now available in oral and nasal spray forms . Other triptans available in the UK are almotriptan (Almogran, Organon), naratriptan (Naramig, GSK), zolmitriptan (Zomig, AstraZeneca), rizatriptan (Maxalt, Merck Sharp & Dohme), eletriptan (Relpax, Pfizer) and frovatriptan (Migard, Menarini). Non-tablet forms of zolmitriptan and rizatriptan that dissolve rapidly in the mouth without water are also available and zolmitriptan is also available as a nasal spray. Frovatriptan has a longer duration of action than other triptans. The triptans are thought to act by shrinking dilated blood vessels in the brain, but may also constrict the coronary arteries and are therefore not suitable for people with high blood pressure, coronary heart disease or kidney or liver problems.

What's in the development pipeline?

Although some further development of triptans is still going on, such as Merck Sharp & Dohme's studies of rizatriptan in menstrual migraine and for the treatment of migraine-associated nausea, new medicines in development mainly act in different ways from triptans.

Migraine prophylaxis
Several companies are conducting trials in the prevention of migraine with medicines that have already been indicated for other uses. Takeda has ramelteon in trial for the prevention of migraine and Allergan is studying botulinum toxin (Botox) for this purpose. At Phase 2, Lilly is trialling olanzapine (Zyprexa; indicated in the UK for treating schizophrenia and mania in bipolar disorder) and Eisai is studying the anti-convulsant E-2007. Also new is tonabersat (Minster Pharmaceuticals), which has started Phase 2 trials for the prevention of migraine with and without aura.

Migraine treatment
A neuropeptide called calcitonin gene-related peptide (CGRP) found in the brain is believed to play a key role in migraine. Boehringer-Ingelheim is conducting Phase 2 trials of BIBN 4096BS (olcegepant), a selective CGRP antagonist that has already been reported in preliminary trials to show evidence of activity in counteracting acute pain and decreasing headache recurrence. Other agents for acute migraine treatment in Phase 2 trial include GlaxoSmithKline's GSK 274150, MK-0974 (Merck Sharp & Dohme), a glutamate receptor antagonist from Eli Lilly and a metered-dose inhaler compound (Marinol; Solvay/Nektar).

FOR FURTHER INFORMATION CONTACT:

THE MIGRAINE ACTION ASSOCIATION
Unit 6, Oakley Hay Lodge Business Park, Great Folds Road
Great Oakley
Northants, NN18 9AS
Phone: 0870 050 5898 (Helpline)
Website: www.migraine.org.uk

THE MIGRAINE TRUST
2nd floor, 55-56 Russell Square
London, WC1B 4HP
Phone: 020 7436 1336 (Helpline)
Website: www.migrainetrust.org