Targeting Neuropeptides Could Be Future For Migraine Treatment

Main Category: Headache / Migraine
Also Included In: Neurology / Neuroscience
Article Date: 20 Oct 2008 - 3:00 PDT

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Targeting a system which utilises peptides in the brain during a migraine could be the future of treatment for this debilitating condition. The future and recent developments in the field of migraine are discussed in a Comment in this week's edition of The Lancet, written by Dr Stephen D Silberstein, Thomas Jefferson University, Philadelphia, PA, USA.

Recent US studies have confirmed that prevalence of migraine among men (6%) and women (18%) has remained stable over the past 15 years. Migraine with aura (sensory phenomena that occur before the migraine itself, eg, visual flashes) roughly doubles the risk of heart attack, increases the risk of angina by 71%, and more than doubles the risk death from ischaemic cardiovascular disease. People with migrane also have an increased risk of having a poor cholesterol profile and high blood pressure, and a parental history of early heart attack. One study also found that some 38% of patients with migraine with aura have a patent foramen ovale (PFO). A PFO is a defect in the wall between the two upper (atrial) chambers of the heart, and is present in everyone before birth but seals shut in about 80 percent of people. It was believed that PFO closure would produce migraine relief, but a well designed trial failed to show this.

Migraine aura is probably due to 'cortical spreading depression', caused by enhanced neuronal excitation during the migraine attack, and the author notes a study which shows that, if given chronically rather than acutely, drugs to prevent migraine block cortical spreading depression. He also notes a study from Schoonman and colleagues that showed migraine is not, as was originally thought, associated increased blood flow in the brain or the lining of the brain.

Co-ordinated headache treatment does make a difference. An active intervention consisting of headache education, diagnosis and treatment by a headache specialist, and active follow-up by case-worker improved patients' scores on the Migraine Disability Assessment (MIDAS) scale by an average of 7•0 points compared with controls. Quality of life and treatment satisfaction also improved. Drug treatment can be acute or preventive, and patients may need both. The author and his colleagues investigated use of sumatriptan and naproxen used within one hour of headache onset, and found that at 2 hours more than half patients given the treatment were pain free compared with around just one in six of those given placebo. The author also refers to a study on preventive (prophylactic treatment) which showed that patients had fewer migraine-days per four-week period when continuing on the prophylactic treatment topiramate, compared with placebo.

The future of migraine treatment is currently focused on drugs which target calcitonin gene-related peptide (CGRP), a peptide released in the brain during migraine attacks.

Using olcegepant, an intravenous CGRP antagonist (a drug which competes for the same active sites on neurons as CGRP), gave a 2 h headache response rate of 66%, compared with 27% for placebo. And treatment with another CGRP antagonist, telcagepant, this time taken orally, showed at a dose of 300 mg it was as effective at reducing pain than the conventional migraine treatment zolmitriptan, and considerably better than placebo. The author concludes: "Telcagepant was effective and generally well tolerated for acute migraine treatment. Phase III trials are positive with results similar to those with zolmitriptan (5 mg) and an adverse-event profile similar to that for placebo and lower than that with zolmitriptan."

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