Over 43 million Americans regularly experience pain from headaches, including migraine, cluster, tension-type, and chronic migraine headache. Some 29.5 million Americans have migraines, which are characterized by throbbing head pain, usually on one side, often accompanied by nausea and sensitivity to light and/or sound. Cluster headaches are exceedingly rare, with less than 200,000 Americans affected. Cluster headaches are generally short in duration but involve excruciating pain on one side of the head, often localized in the eye region. Most cluster headaches are episodic, occurring in periods of several weeks or months and then disappearing completely for months or even years. The most common headaches are tension-type headaches, characterized by diffuse, intense pain on both sides of the head. About 78% of adults experience tension-type headaches at some point in their lives. Chronic daily headaches manifest characteristics of both tension-type and migraine headaches, and occur at least 180 days per year (15 days per month). Up to 12 million Americans suffer from chronic migraineheadaches. Migraine and chronic migraine headache have estimated market sizes of $4 billion and $5 billion, respectively. Cluster headache constitutes a much smaller market, approximately $50 million annually in the United States.
Current therapies for migraine, cluster, tension-type and chronic migraine headaches include a wide variety of over-the-counter and prescription medications, some of which are approved by the FDA for these headache indications, but many others are used off-label. The most widely used medications for abortive treatment of migraine headache are the serotonin (5-HT) agonists known as triptans. The NSAIDs have gastrointestinal side effects, which limit their use in migraine treatment, since larger than normal doses may be required to treat migraine attacks. Used chronically, they can also result in analgesic rebound that exacerbates the problem. Due to the severity of their migraines, some patients may use a narcotic analgesic, but such analgesics can result in addiction.
If patients have frequent migraine attacks, if the attacks do not respond consistently to migraine-specific acute treatments, or if migraine-specific medications are ineffective or contraindicated, then preventive medications for migraine headache may be given. FDA-approved drugs for migraine prevention include propranolol, timolol and divalproex sodium. Amitriptyline, other tricyclic antidepressants, and calcium channel blockers may also be effective in migraine prevention.
There are no approved medications for cluster headache prophylaxis. Off-label treatments include systemic corticosteroids, calcium channel blockers, and lithium. Abortive treatment of cluster headaches is difficult, because of the brief duration of an acute cluster attack. Injectable sumatriptan is the only FDA-approved medication indicated for acute cluster headache relief but includes warnings for use that make it less appropriate for many cluster headache patients. Oxygen inhalation by facial mask is also sometimes used in abortive treatment, and ergotamine preparations can be used immediately at the onset of a cluster attack.
Abortive medications for tension-type headaches include NSAIDs and other nonprescription pain relievers. Orally administered tricyclic antidepressants, such as amitriptyline (Elavil®) and Doxepin (Sinequan®), are considered the agents of choice in the prophylactic treatment of chronic migraine headache. However, the oral use of these tricyclic agents is accompanied by unacceptably high incidences of sedation and weight gain. Due to the complex nature of this syndrome, it is common to use combination therapy, involving a beta blocker, calcium channel antagonist, or antiepileptic drug in combination with each other or with an antidepressant. NSAIDs have been used successfully to abort individual acute headaches and are not associated with dependency problems, but their chronic use can result in analgesic rebound headaches.