Sumatriptan is FDA approved as an abortive treatment for migraine attacks with or without aura in adults. Acute treatment of cluster headache episodes can be relieved by the administration of subcutaneous treatment. According to the clinical studies, sumatriptan is an effective and well-tolerated treatment for a migraine when given intravenously, subcutaneously, or orally. It relieves photophobia, nausea, headache, and functional disability. Non-FDA-approved indications of sumatriptan include the treatment of migraine in children and adolescents.[1][2][3]

Serotonin (5-hydroxytryptamine) has a central role in the pathophysiology of a migraine. Its metabolism is abnormal in patients with a migraine, and intravenous administration of 5-hydroxytryptamine can alleviate migraine attacks. Antimigraine drugs share the ability to activate 5-hydroxytryptamine receptors. Headaches, a prominent feature of a migraine, are believed to result from the following: excessive dilatation of extracerebral cranial (dural or meningeal) arteries, arteriovenous shunts, or both; neurogenic dural plasma extravasation; or a combination of these mechanisms. Sumatriptan (3-[2-(dimethylamino)ethyl]-N-methylindole-5-methanesulfonamide) is a selective agonist of 5-hydroxytryptamine1-like receptors that block plasma leakage from the dura and venous sinuses, stimulated by perivascular trigeminal fibers that release substance P, calcitonin G-related peptide, and neurokinin A. This pain mechanism may provide the final common pathway for other cephalgias and migraines, which explains the overlap and similarities between different headache syndromes. Subcutaneous administration of sumatriptan, however, results in the rapid attainment of peak plasma levels.

Sumatriptan 5-HT1B/1D receptor agonist leads to vasoconstriction in the basilar artery and the blood vessels of the dura mater. It decreases peripheral nociception either by selective cranial vasoconstriction or an effect on trigeminovascular nerves. The blocking effect of sumatriptan indicated a peripheral effect on trigeminal vascular nerves in neurogenically mediated plasma extravasation. Sumatriptan inhibits the presynaptic terminal of the trigeminal nucleus caudalis, which leads to the reversal of facial allodynia. Triptans not only decrease transmission of the pain impulses to the trigeminal nucleus caudalis but also release inflammatory mediators from trigeminal nerves, therefore reducing calcitonin gene-related peptide-mediated vasodilation. Migraine pain is associated with middle cerebral artery dilatation, which leads to a lower velocity of regional cerebral blood flow. Sumatriptan reverses the dilatation of MCA, which suggests that the 5-HT receptor system has a role in the pathogenesis of a migraine.[4][5][6][7]

An acute dose of sumatriptan (100 micrograms/kg) decreases the 5-HT synthesis rate in many brain regions, including the dorsal raphe nucleus. Chronically, sumatriptan (300 micrograms/kg per day) induced significant increases in the 5-HT synthesis rate in many projection areas but did not affect the dorsal raphe nucleus.

Sumatriptan can be administered orally, intranasally, via subcutaneous injection, rectally, and more recently, as a transdermal patch. The sumatriptan nasal powder system has faster improvement in migraine-related disability and migraine pain intensity at early time points as compared to the oral sumatriptan. Sumatriptan (25 mg) administered rectally is an effective treatment for acute migraine attacks and leads to a significant reduction in symptoms within two hours. Individuals with nausea and vomiting can receive a subcutaneous injection as compared to oral; however, subcutaneous administration correlates with increased adverse events. Subcutaneous administration also has been considered the most efficacious treatment in the acute phase of a migraine, both on pain as well as on associated autonomic symptoms.

Oral sumatriptan has demonstrated effectiveness in the treatment of a single acute attack of a migraine. The absorption of sumatriptan is rapid after oral and subcutaneous administration. However, the bioavailability of oral sumatriptan is just 14% as compared to the subcutaneous administration, which is nearly 100%. The elimination of sumatriptan is primarily by metabolism to a nonactive indoleacetic acid analog. The pharmacokinetic and pharmacodynamic variables of sumatriptan are not altered by the presence of alcohol, food, prophylactic migraine treatments, or dihydroergotamine.

Sumatriptan can cause adverse central nervous system events outside migraine attacks. It can cause mild sedative effects such as sleepiness or fatigue. It also causes a significant increase in the EEG alpha power as compared with the placebo. In a study measured by the Yale-Brown Scale, sumatriptan worsened the symptoms of patients with obsessive-compulsive disorder (OCD).  Sumatriptan also can cause a transient rise in blood pressure, but the increase in blood pressure is the same as would be anticipated during moderate exercise.

Subcutaneous injection administered by the physician results in transient stinging at the site of injection in most subjects; however, toleration is better when the subjects use the auto-injector. Sumatriptan can induce angle-closure glaucoma, but this is a rare event and should receive correct and prompt treatment to prevent visual loss. A common adverse drug reaction of subcutaneous sumatriptan includes injection site reaction (bleeding, bruising, erythema). Intranasal sumatriptan leads to dysgeusia and nasal discomfort.

Sumatriptan works earlier and more completely as compared to a combination of caffeine and ergotamine, but sumatriptan is associated with a higher rate of recurrent headaches. Rothner et al. reported a case of facial nerve palsy in a teenager using sumatriptan nasal spray. Hossein et al. described a recurrent paresis of the superior division of the oculomotor nerve occurring after subcutaneous administration of the drug. A thorough evaluation is necessary for the patients who present with acute onset of a severe headache, and sumatriptan requires careful administration since it could precipitate RCVS (reversible cerebral vasoconstriction syndrome) or aggravate cerebral vasoconstriction. Vascular imaging should be performed after several days if sumatriptan-induced reversible vasoconstriction syndrome is suspected.

Oral, intranasal, and subcutaneous routes of sumatriptan administration are contraindicated in patients with severe hepatic treatment. It is also contradicted in patients receiving concurrent MAO type A inhibitors or within two weeks of discontinuing an MAO type A inhibitor. Patients with signs and symptoms of ischemic heart disease are relatively C/I. Ischemic heart disease includes coronary artery vasospasm, MI, Prinzmetal angina, and Angina pectoris. Sumatriptan also is contraindicated in patients who use ergotamine and another 5-HT1 agonist concurrently. Patients with peripheral vascular disease (also, ischemic bowel disease), cerebrovascular syndromes, or uncontrolled hypertension have a contraindication to Sumatriptan as well.