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Continuing Education Activity

Triptans are a class of medications used in the treatment of migraines. This activity reviews the indications, action, and contraindications for triptans as valuable agents in migraine therapy. This activity will highlight the mechanism of action, adverse event profile, and other key factors (e.g., off-label uses, dosing, pharmacodynamics, pharmacokinetics, monitoring, relevant interactions) pertinent for the management team members of patients with migraine.


  • Identify the mechanism of action of triptans.
  • Describe the potential adverse effects of triptans.
  • Review the appropriate monitoring for patients on triptan therapy.
  • Summarize interprofessional team strategies for improving care coordination and communication to advance migraine therapy and improve outcomes.


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, naratriptan, and oral zolmitriptan have an off-label indication for the prevention of menstrual migraine.[6][7]

Mechanism of Action

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.[8]


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.[9] 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.[10]

Some of the most commonly prescribed triptan agents are:

  • Sumatriptan
  • Zolmitriptan
  • Frovatriptan
  • Eletriptan
  • Naratriptan

The above is not an exhaustive list.

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. The orally disintegrating tablets are a good option as long as the patient is not vomiting.[11] The nasal spray and subcutaneous injection dosage forms are options for patients who experience nausea and possibly vomiting before the orally administered medication is absorbed.[12] 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.[10] 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.[13]

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 to treat 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.[14]

For the prevention of menstrual migraine, patients may initiate frovatriptan and naratriptan two days before menses begin and continued for 5 to 7 days.[15]

Propranolol, which has a role in migraine prophylaxis, increases rizatriptan serum concentrations. Rizatriptan dose should not exceed 5 mg for patients using propranolol.[16]

Adverse Effects

Triptans may cause nausea, dizziness, and coronary vasoconstriction.[17] 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.[18]


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.[19]

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

There is not enough evidence that 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).[20]


Clinicians should monitor for triptan-associated cardiovascular adverse effects in patients taking propranolol. Propranolol is often used for migraine prevention and decreases the metabolism of some triptans like almotriptan and rizatriptan by inhibiting their metabolism via the monoamine oxidase A (MAO-A) pathway. For these patients, lowering the triptan dose or using a triptan that is not metabolized by the MAO-A pathway or other abortive migraine therapy is preferred.[21][16]

Other monitoring parameters include the degree of response to triptan therapy, migraine recurrence, and consistent response to the same triptan. Also, patients review monitoring for nausea, vomiting, and sensitivity to light and/or noise, which may occur during a migraine attack, and ultimately, improved ability to function.[6]


Analysis of triptan overdose cases from the National Poison Data System showed a low risk of death. Symptoms of triptan overdose include increased blood pressure, tachycardia, and drowsiness.[22]

Enhancing Healthcare Team Outcomes

A migraine is a common form of headache that can last for up to 72 hours if left untreated or when inappropriately treated. Nausea and/or vomiting may occur along with a migraine attack, thus affecting the patient's ability to function as usual.[23] 

Patient education is essential for successful migraine management plans.[6] It is essential to educate patients about migraine triggers, including stress, skipped meals, disrupted sleep, alcohol, certain types of foods, and menstruation. Keeping a migraine diary may help identify patient-specific triggers. Setting realistic expectations and goals of therapy with the patient is important, especially that migraine triggers may not always be avoidable.[24]

Some pharmacologic and non-pharmacologic therapies are available for migraine prophylaxis.[24] Prophylactic therapy reduces migraine frequency and severity. Patients should use abortive therapy when a migraine attack occurs. The indication for triptans is abortive migraine therapy.[6]

If the response to triptan therapy does not achieve the desired relief of symptoms, the interprofessional team should verify that the patient is taking the triptan as soon as the headache pain begins.[6] Other causes of triptan failure could be due to malabsorption or other patient-related factors. A trial of another triptan may be beneficial in these patients.[25]

Even though the risk of serotonin syndrome is low in patients taking triptans alone or even in combination with an SSRI or SNRI, health care providers should monitor for signs and symptoms of serotonin syndrome and are encouraged to report such cases to MedWatch.[20]

The interprofessional healthcare team should provide formal counseling to patients being prescribed triptans. Patients should understand to take the triptan as soon as the migraine starts for the best results.[26] The healthcare team should identify patients with headaches due to triptan overuse, defined as taking triptans on ten or more days per month. These patients should receive education to decrease the use of triptans for abortive therapy; they will likely benefit from prophylactic migraine therapy.[27]

Finally, a patient-centered approach is essential in migraine management for both prophylactic and abortive treatment. Treatment requires individualization, and the response to treatment is reassessed for the need for change in therapy.[28]

Appropriate use of triptans to treat migraines requires the efforts of an interprofessional healthcare team, including clinicians, specialists, mid-level practitioners, nurses, and pharmacists, all contributing from their specialized areas to enhance patient outcomes while limiting adverse events. [Level 5]

Article Details

Article Author

Samar Nicolas

Article Editor:

Diala Nicolas


10/13/2021 9:25:16 AM

PubMed Link:




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