The case vignette in this week’s Clinical Therapeutics article, Triptan Therapy in Migraine, features an otherwise healthy 23-year-old woman who presents with a report of headaches and associated symptoms that occur twice a month. A diagnosis of migraine without aura is made.
Migraine is a genetically influenced chronic brain condition marked by paroxysmal attacks of moderate to severe throbbing headache with associated symptoms that may include nausea, vomiting, and photophobia or phonophobia. In up to a third of patients with migraine, the headaches are accompanied by focal neurologic symptoms (often visual) known as aura.
• What is the epidemiology of migraine?
Migraine is both more common and more severe in women than in men. Symptoms generally begin in adolescence or early adulthood. Disease activity peaks during the otherwise active years of middle life, with a lifetime cumulative incidence of 43% in women and 18% in men. Although migraine is not life-threatening, it is associated with an increased risk of other vascular complications, including ischemic stroke and pre-eclampsia.
• What is the mechanism of action of triptans?
Triptans are serotonin (5-hydroxytryptamine, or 5-HT) agonists with high affinity for 5-HT1B and 5-HT1D receptors. Triptans were originally thought to provide migraine relief by causing cranial vasoconstriction, most likely through action at postsynaptic 5-HT1B receptors on the smooth-muscle cells of blood vessels. It is now theorized that triptans also block the release of vasoactive peptides from the perivascular trigeminal neurons through their action at presynaptic 5-HT1D receptors on the nerve terminals. In addition, triptans bind to presynaptic 5-HT1D receptors in the dorsal horn, and this binding is thought to block the release of neurotransmitters that activate second-order neurons ascending to the thalamus. Triptans may also facilitate descending pain inhibitory systems.
Morning Report Questions
Q: How should triptans be used?
A: Triptans are first-line therapies for individual attacks of migraine in patients whose attacks do not reliably respond to simple or combination analgesics. A key advantage of triptans over most of these alternatives is their more favorable side-effect profile and more specific mechanism of action. Triptan therapy is most effective when provided rapidly in adequate doses, and when used early, while headache pain is still mild. The choice of which formulation to use depends on patient preference, headache characteristics, convenience, and cost; a generic formulation of sumatriptan is available. Most patients have a strong preference for oral treatment of migraine. Oral triptans are appropriate when nausea and vomiting are mild or absent at the time of treatment.
Q: How should a patient whose initial dose is ineffective at relieving headache be managed?
A: Triptan monotherapy does not provide relief from headache in about one third of patients. If the initial dose is ineffective, the dose should be increased within the approved limits. If an appropriate dose of a triptan is ineffective for two headache attacks, or produces an unacceptable level of side effects, a switch to a different triptan or triptan formulation should be considered. In particular, patients with headache that does not respond to an oral triptan should be encouraged to consider subcutaneous sumatriptan. If triptan monotherapy remains ineffective, triptans should be tried in combination with other drugs, especially antiemetics or nonsteroidal anti-inflammatory agents (NSAIDs).
Table 2. Characteristics of Triptans Commercially Available in the United States.