The Pathophysiological and Pharmacological Basis of Current Drug Treatment of Migraine Headache

Doodipala Samba Reddy

Disclosures

Expert Rev Clin Pharmacol. 2013;6(3):271-288. 

In This Article

Abstract and Introduction

Abstract

Migraine is a common neurological syndrome that affects approximately 10–20% of the population. The pathophysiology of migraine is unclear. 5-hydroxytriptamine is a key mediator in the pathogenesis of migraine and thus 5-HT1-receptor agonists are the principal drugs for acute migraine therapy. There are three classes of drugs for migraine: over-the-counter analgesics and nonsteroidal anti-inflammatory drugs for acute mild migraine, specific prescription drugs (triptans and ergot alkaloids) for acute severe migraine and pharmacological agents for prophylaxis of migraine. Sumatriptan, naratriptan and others, referred to as 'triptans', are the mainstay for acute treatment of migraine. Ergot alkaloids (ergotamine, dihydroergotamine) are used in patients with frequent, moderate migraine, but are less effective than triptans. There are several agents for prevention of migraine occurrence in patients with frequent or severe disabling migraine attacks. New drugs with improved efficacy and reduced side effects are needed for effective treatment and prevention of migraine.

Introduction

Migraine headaches are a common neurological condition with a prevalence of 10–20% of the population. The typical manifestations of migraine headache are the debilitating throbbing pain around the eyes and temples lasting for hours, nausea and heightened sensitivity to light and sound (see Box 1). Many patients experience auras (telltale period) as a very concrete sign of discomfort to come. According to the American Migraine Study, migraine affects approximately 30 million people in the USA.[1] Migraines affect people during their productive years (25–50 years of age) and are three-times more common in women than men.[2–6] Approximately 80% of patients report having a family history of migraines, with heritability estimates as high as 50%.[7–12] The diagnosis and treatment of migraine is a frequent activity for primary care physicians. Migraine headaches have a significant impact on quality of life. It is estimated that US$13 billion dollars are lost in productivity each year due to migraine burden in the USA.[2] Medical costs are thought to approach US$2 billion per year. Migraine is ranked by the WHO as number 19 among all diseases worldwide causing disability.[7]

According to the International Headache Society's International Classification of Headache Disorders, migraine is classified into two major clinical subtypes: migraine with aura (MA) and migraine without aura (MO).[13] The migraine subtype classification is described in Table 1.

MA, which occurs in about 20% of migraine cases, is always associated with a 'prodrome' (aura) and is unilateral. It is preceded by 10–30 min of neurological symptoms, called an aura. Prodrome and aura are, in fact, separate (and variable) phases of migraine attack. Premonitory aura may begin as long as 24 h before the onset of pain and is often accompanied by photophobia, phonophobia, polyuria and diarrhea, and by disturbances of mood and appetite. In MA, the premonitory symptoms, such as difficulty with speech and reading, increased emotional sensitivity and sensory hypersensitivity, are highly predictive of the migraine attack. The auras include fully reversible visual symptoms of positive (teichopsia, rockets, bright stars or spots) or negative (black spots, hemianopsia or quadrantanopsia) diplopia or total loss of vision, hemiparesis, hemisensory loss, dysphasia (receptive or expressive), confusion, vertigo or loss of consciousness as the most common. These may occur before or during the headache or even without headache (International Headache Classifcation 2nd edition, 1.2.3 – typical aura without headache).[14,15]

MO, which occurs in approximately 80% of migraine cases, is not preceded by an aura, but could begin with premonitory symptoms. It may involve an array of vague symptoms preceding the attack, such as mental fuzziness, mood changes and fatigue. A migraine attack may last for hours or days and be followed by prolonged pain-free intervals. The frequency of migraine attacks is extremely variable, usually ranging from 1 to 4 per month or year. There is evidence that in the period between attacks, many patients show abnormalities or hypersensitivity to sensory stimuli[8,10,14]

This article describes the pathophysiological mechanisms underlying migraines and the pharmacological basis of drug treatment of acute migraine. It also describes drugs used for prophylactic treatment of migraine and emerging new treatment approaches for migraine.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....