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Headaches are a common chief complaint of patients seeking advice from a pharmacist. It is estimated that 18% of women and 6% of men experience migraine headache.1Prevalence is highest between the ages of 25 and 45 in both males and females.2 Migraines are considered to be one of the top 20 most disabling diseases worldwide by the World Health Organization.3 Tension headaches are the most common type of primary headaches with an estimated prevalence of 86% in women and 63% in men with the rates occurring highest between the ages of 20 and 50.4Cluster headaches may be relatively uncommon, with the prevalence estimated to be 56 to 401 per 100,000 with onset typically occurring over the age of 20.5

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The pathophysiologic and etiologic mechanisms of migraine are not completely known at this time. The sensory sensitivity may be due to a dysfunction of monoaminergic sensory control systems of the brainstem and thalamus. It is speculated that the trigeminovascular input from the meningeal vessels is a pathway for pain recognized in migraine headaches. There is a release of vasoactive neuropeptides, specifically calcitoningene-related peptide (CGRP), when the cells in the trigeminal nucleus are activated. There is a deficiency of serotonin levels in the plasma during a migraine attack. The use of serotonin agonists, triptans, in migraine therapy has demonstrated the role of serotonin in treatment, being potent agonists of 5-HT1B, 5-HT1D, and 5-HT1F. Dopamine may also play a role in migraine headaches as dopamine receptor antagonists are effective treatments administered as monotherapy or with other antimigraine medications; however, there is a lack of clinical data to support this theory.6

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The pathophysiology behind tension headache also remains unknown, but one hypothesis is that stress may be an important stimulus. Cluster headaches may be precipitated by hypothalamic- related changes in cortisol, prolactin, testosterone, growth hormone, luteinizing hormone, endorphins, or melatonin.7

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When considering the diagnosis of headaches, a comprehensive history of present illness and physical examination are critical. A thorough history will include time of onset, attack frequency, duration, aggravating and relieving factors, characteristics of pain, associated signs and symptoms, family history, social history, treatment history, and impact on daily living. Some history and physical examination findings that may be suggestive of a secondary headache disorder include, but are not limited to, the worst headache ever, increase in frequency or severity of usual headaches, head pain with exercise, increased head pain with sneezing or coughing, headache that wakes patient from sleep, signs of infection, ataxia or uncoordinated limbs, new headaches in a person ≥ age 40, history of head trauma, and changes in mental status.8 Headaches beginning after the age of 50 may suggest underlying issues such as a mass lesion or cerebrovascular disease. Any of these findings are considered "red flags" that warrant a referral to the physician.

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