SummaryFewer than 10% of people state that they have never had a headache.1 A recent UK survey identified 7.6% of males and 18.3% of females with migraine within the preceding year.2 Prevalence of migraine was shown to vary with age, rising through early adult life and declining in the late 40s and early 50s. Migraineurs reported at least one migraine attack per month on average, and most experienced interference with daily activities in at least 50% of their attacks.
Fewer than 10% of people state that they have never had a headache.1 A recent UK survey identified 7.6% of males and 18.3% of females with migraine within the preceding year.2 Prevalence of migraine was shown to vary with age, rising through early adult life and declining in the late 40s and early 50s. Migraineurs reported at least one migraine attack per month on average, and most experienced interference with daily activities in at least 50% of their attacks. On average, an estimated 5.7 working days were lost per year for every working or student migraineur, although the most disabled 10% of patients accounted for 85% of the total days lost. Based on these findings, an estimated 5.85 million people aged 16–65 years experience 190,000 migraine attacks every day and lose 25 million days from work or school each year as a direct result. The cost to the economy of lost work time and impaired working effectiveness as a consequence of migraine is thought to be in the region of £1.5 billion per annum. Hence, migraine represents an immense socioeconomic burden.
Despite these estimates, migraine remains under diagnosed and under treated. Although it is often presumed that those who do not consult do not need to consult, the figures tell a different story: substantial disability occurs in over two-thirds of those who never consulted, never received a correct medical diagnosis or who self-treated only with over-the-counter medication.3
The World Health Organization (WHO) has also recognised the impact of headache on health – its statistics suggest that migraine alone ranks nineteenth amongst all causes of years lived with disability, whilst in women it ranks twelfth.4
For a long time the pharmaceutical industry largely ignored migraine as a diagnosis, until 1973, when following up on observations implicating serotonin in the pathophysiology of migraine, a selective serotonin agonist was developed. The launch of sumatriptan in 1991 heralded a revolution in migraine management. Suddenly patients could take a treatment that enabled them to continue to work or return to work. This had rarely been possible with ergotamine because of its narrow therapeutic window. Side-effects of feelings of warmth, heaviness or pressure were rarely a problem and the familiar ‘funny feeling up the back of my neck’ was a welcome sign to many patients that the drug was taking effect.
However, it was soon noticed that headache relapse within the same migraine attack was a problem, particularly for migraine attacks with a longer duration. Debate continues as to how best to manage relapse, but it fuelled the fire for development of the ‘me too’ triptans – almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan and zolmitriptan. These second-generation triptans have all attempted to improve on sumatriptan. In practice, although there may be reasons to recommend one triptan over another in different situations, in general the differences between these compounds are subtle rather than dramatic.
The development of new drugs has not just led to better treatment; we now also have a better understanding of the pathophysiology of migraine. Whilst vasoconstriction and vasodilation was a long-held theory, the attack is now thought to be generated within the central nervous system (CNS). Evidence of activation of brainstem nuclei – including the raphe nuclei, the locus coeruleus and the periaqueductal grey matter – during migraine supports the theory of a ‘migraine generator’. Sumatriptan taken during the attack relieves the headache but does not affect the brain stem activity and may explain why relapse occurs.5
The efficacy of neuromodulators on CNS activity in migraine has sparked a resurgence in prophylaxis but many patients still prefer symptomatic agents. Unfortunately, drugs based on the theory of neurogenic inflammation were a backwards step but research into nitric oxide is a definite advance. Results of early clinical trials suggest that nitric oxide synthetase inhibitors, together with calcitonin gene-related peptide (CGRP) antagonists, may have a bright future in migraine management.
Whilst new drugs jostle for a place amongst the old, it will still be some years before the triptans are ousted from pole position. As safety becomes established, the next advance needs to be a greater ease of access to triptans. How ever effective a treatment is, its benefits are limited if access is restricted. As doctors conclude the safety of over-the-counter triptans,6 we are one step closer to reducing migraine-related disability in 3 million non-consulters.
1 Rasmussen BK. Epidemiology of headache. Cephalalgia 1995; 15: 45–68.
2 Steiner TJ, Scher AI, Stewart WF, Kolodner K, Liberman J, Lipton RB. The prevalence and disability burden of adult migraine in England and their relationships to age, gender and ethnicity. Cephalalgia 2003; 23: 519–27.
3 Lipton RB, Scher AI, Steiner TJ et al. Patterns of health care utilization for migraine in England and in the United States. Neurology 2003; 60: 441–8.
4 World Health Organization. Mental Health: New Understanding, New Hope. Geneva: WHO, 2001.
5 Weiller C, May A, Limmroth V et al. Brainstem activation in spontaneous human migraine attacks. Nat Med 1995; 1: 658–660.
6 Dodick D, Lipton RB, Martin V et al. Consensus statement: cardiovascular safety profile of triptans (5-HT1B/1D Agonists) in the acute treatment of migraine. Headache 2004; 44: 414–25.
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This Editorial has been written by the specialist opinion leader, Dr Anne MacGregor
Director of Clinical Research,The City of London Migraine Clinic and published in the latest issue of the serial publication, Drugs in Context.
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