Overview

An occasional headache for most people is easily remedied by a couple of aspirin or ibuprofen pills and a glass of water. However, for many people, headaches are unremitting, severe, and recurring. The International Headache Society divides headache disorders into two large groups. The first group, primary headache disorders, includes cluster, migraine, and tension headaches. The characteristics and management of these three types of headaches, which together account for about 95% of all headaches, are compared in Table 29-1. The second group, secondary headache disorders, consists of headaches that arise from organic disorders (e.g., hemorrhage, infection, neuropathy, stroke, and tumor). In patients with secondary headaches, management focuses on treating the underlying disorder.

Because migraine is the most serious and common type of headache in patients with a headache disorder, it is the main focus of the discussion. The chapter closes with a brief review of treatment options for cluster and tension headaches.

Characteristics and Pathogenesis of Migraine Headaches

In the United States, approximately 24 million people experience migraine headaches (Box 29-1). The pathophysiologic mechanisms of migraines are not completely understood, but migraine headaches appear to result from neurovascular dysfunction caused by an imbalance between excitatory and inhibitory neuronal activity at various levels in the central nervous system (CNS). This imbalance can be triggered by hormones, stress, fatigue, hunger, diet, or drugs.

About 15% of patients who have migraine headache disorder report that they experience an aura that precedes each headache attack and lasts for about 15 to 20 minutes. A visual aura can take the form of brightly flashing lights or rippling images that spread from the corner of the visual field (teichopsia). A sensory aura can take the form of paresthesias that involves the arm and face and tends to march sequentially from the fingers to the hand and then to the body. Auras are believed to result from the cerebral vasoconstriction and ischemia that precipitate migraine attacks. A migraine without an aura (previously known as a common migraine) is often accompanied by an attack of photophobia, phonophobia, nausea, or vomiting.

Each migraine attack has two phases. The first phase is characterized by cerebral vasoconstriction and ischemia. The release of serotonin from CNS neurons and circulating platelets contributes to this first phase. Hence, antiplatelet drugs and serotonin receptor antagonists are efficacious in the prevention of migraine headaches. The second phase, which is longer than the first one, is characterized by cerebral vasodilation and pain. The trigeminal neurovascular system appears to play a central role in the second phase. Neurons in the trigeminal complex release vasoactive peptides, including substance P and calcitonin gene-related peptide (CGRP). These peptides trigger vasodilation and inflammation of pial and dural vessels, which in turn stimulate nociceptive fibers of the trigeminal nerve and cause pain. Figure 29-1 depicts these events and the mechanisms of drugs that are used to terminate migraine headaches.

Drugs for Migraine Headaches

The drugs used to manage patients with migraine headaches can be classified as prophylactic drugs and abortive (symptomatic) drugs. Many prophylactic drugs act by preventing the vasoconstrictive phase of the disorder, whereas abortive drugs reverse the vasodilative phase of migraine or relieve pain and inflammation.

Several drugs for migraine are antagonists or agonists at specific types of serotonin receptors. These receptors have been classified into four main types, 5-HT₁ through 5-HT₄.

The 5-HT₂ receptors are widely distributed in the CNS, smooth muscle, and platelets, where they mediate vasoconstriction and platelet aggregation. Drugs that block 5-HT₂ receptors, such as methysergide, can prevent the vasoconstrictive phase of migraine and are used as migraine prophylactics.

The 5-HT₁ receptors are the predominant serotonin receptors in the CNS, and many of them function as presynaptic autoreceptors whose activation inhibits the release of serotonin and other neurotransmitters. The 5-HT₁ receptors also mediate cerebral vasoconstriction. Drugs that activate these receptors, such as sumatriptan, are used to terminate a migraine attack.