Triptans are FDA approved and the first-line agents for the treatment of acute migraine episodes with or without aura.[1][2] There are seven triptans available in the United States in a variety of dosage forms: sumatriptan, naratriptan, zolmitriptan, rizatriptan, almotriptan, frovatriptan, and eletriptan.[3] Sumatriptan, in the subcutaneous formulation, is also approved for the treatment of cluster headaches.[1] Almotriptan is the only triptan with an FDA indication for use in adolescents to treat migraines lasting at least 4 hours.[4] Zolmitriptan nasal spray is FDA approved for children 12 years or older; the use of other triptans for children is off-label.[5][4] Frovatriptan and naratriptan have an off-label indication for the prevention of menstrual migraine.[6]

Triptans act as antimigraine agents by selectively binding to the serotonin receptors 5-HT1B and 5-HT1D. Triptan binding to the vascular 5-HT1B receptors leads to vasoconstriction of the cranial arteries, which painfully dilate during a migraine attack. When triptans bind to the neurogenic and central 5-HT1D receptors, they prevent the release of vasoactive neuropeptides by inhibiting the activation of trigeminal nerves and also block the transmission of pain signals to the brain.[7]

Triptans should be taken at the first onset of the headache phase of a migraine attack; they are not effective if taken during the aura phase before the start of the headache.[8] The patient may repeat the dose after 2 hours if needed, but no more than twice a week. "Triptan-overuse headache" is a type of rebound headache, which can occur with the use of triptans of more than ten days per month.[9]

Triptans are available in multiple dosage forms such as oral tablets, orally disintegrating tablets, nasal sprays, and subcutaneous injections. [3] Formulations, other than oral tablets, make a good alternative for patients with difficulty swallowing. Furthermore, the nasal spray and subcutaneous injection dosage forms are an option for patients who experience nausea and possibly vomiting before the orally administered medication is absorbed.[10] The choice of agent should be an individualized therapy. If a patient has no response to one of the triptans after three trials, increasing the dose, switching to a different dosage form of the same agent, or another triptan might work.[9] Taking a nonsteroidal anti-inflammatory drug (NSAID) with a triptan targets a different mechanism and may be more effective than a triptan alone. Sumatriptan is available as an oral tablet combined with the NSAID naproxen.[11]

During a migraine attack, patients may experience a decreased gastric motility, causing a delay in gastric emptying; this may affect the rate and extent of triptan absorption when administered orally. Metoclopramide, an antiemetic agent, exhibits prokinetic activity and is FDA approved for the treatment of gastric stasis. Metoclopramide can improve the inconsistent absorption of orally administered triptans when taken concomitantly. However, metoclopramide has a boxed warning because of the risk of adverse effects like extrapyramidal symptoms and hyperprolactinemia. Alternatively, an injectable or a nasal triptan formulation is an option, as these formulations bypass the gastrointestinal tract.[12]

For the prevention of menstrual migraine, patients may initiate frovatriptan and naratriptan two days before menses begin and continued for 5 to 7 days.[13]

Propranolol, which has a role in migraine prophylaxis, increases rizatriptan serum concentrations. Rizatriptan dose should not exceed 5 mg for patients using propranolol.[14]

Triptans may cause nausea, dizziness, and coronary vasoconstriction.[15] The most common side effects associated with triptans, such as paresthesia, flushing, tingling, neck pain, and chest tightness, are known as "triptan sensations." These side effects are most pronounced with subcutaneous triptan injections and may be less severe with different formulations. Cardiovascular adverse effects like arrhythmias, myocardial infarctions, and strokes are rare, occurring in less than 1 % of patients on triptans.[3] The severity of adverse effects may differ among triptans.[16]

Triptans can cause vasoconstriction of the coronary and limb arteries; therefore, they are contraindicated in patients with a history of myocardial infarction, coronary artery disease, cerebrovascular accidents, hemiplegic migraines, uncontrolled hypertension, or peripheral vascular disease.[2] Other contraindications include severe hepatic or renal failure, as well as the age of 65 years or more. All triptans, except for sumatriptan, are contraindicated in pregnancy and breastfeeding.[3] Based on data from pregnancy registries, sumatriptan is safe during pregnancy and breastfeeding.[17]

Triptans should not be administered with ergot alkaloids or monoamine oxidase inhibitors.[6]

There is not enough evidence that the triptans increase the risk of serotonin syndrome either as monotherapy or in patients taking a selective serotonin reuptake inhibitor (SSRI) or a selective serotonin-norepinephrine reuptake inhibitor (SNRI).[18]