Which medications in the drug class Serotonin 5-HT-Receptor Agonists are used in the treatment of Pediatric Headache?

Updated: Jan 02, 2019
  • Author: J Ivan Lopez, MD, FAAN, FAHS; Chief Editor: George I Jallo, MD  more...
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Answer

Serotonin 5-HT-Receptor Agonists

The pathophysiology of vasoconstrictors is uncertain. A reduction in regional cerebral blood flow during the aura and early headache phases of migraine has been demonstrated.

Therapeutic activity of the serotonin 5-HT1 receptor agonists (ie, triptans) in migraine is most likely attributed to agonist effects at 5-HT1B/1D receptors. These specific receptor subtypes act on the extracerebral, intracranial blood vessels that become dilated during a migraine attack and on nerve terminals in the trigeminal system. Almotriptan (Axert) and zolmitriptan (Zomig Nasal Spray) have been approved by the FDA for use in adolescents aged 12-17 years, and rizatriptan has received FDA approval for migraine relief in children aged 6-17 years. [48, 49]

The profile of naratriptan is different from all other triptans, as it has a long half-life with a slow onset and prolonged duration of action. Differences between the other drugs (eg, oral sumatriptan, zolmitriptan, rizatriptan, almotriptan, frovatriptan, eletriptan) are modest. Rizatriptan is available in orally disintegrating tablets and zolmitriptan as a nasal spray that are convenient for the pediatric patient.

The American Academy of Neurology quality standards subcommittee and the practice committee of the Child Neurology Society have provided guidelines for treating migraine headaches in children and adolescents. [43]

Naproxen/sumatriptan (Treximet)

This combination product indicated for the acute treatment of migraine attacks with or without aura in adolescents aged 12 y or older. Naproxen inhibits synthesis of prostaglandins in body tissues by inhibiting at least 2 cyclooxygenase (COX) isoenzymes, COX-1 and COX-2; may inhibit chemotaxis, alter lymphocyte activity, and decreases proinflammatory cytokine activity. Sumatriptan is a selective 5-HT1B and 5-HT1D receptor agonist in cranial arteries. It elicits vasoconstrictive and anti-inflammatory effects. It is associated with antidromic neuronal transmission and is used for relief of migraine headache.

Rizatriptan (Maxalt, Maxalt-MLT)

Rizatriptan is a selective agonist for serotonin 5-HT1 receptors in cranial arteries and suppresses the inflammation associated with migraine headaches. It has a high affinity for 5-HT1D and 5-HT1B receptor subtypes. Rizatriptan has been approved by the FDA for migraine relief in children aged 6-17 years. [48, 49]

A randomized, controlled trial by Winner et al found the drug to be no better than placebo in adolescents. However, an open-label, long-term investigation by Visser et al seemed to indicate a small advantage over standard care (pain relief at 2 hours 77% for 5 mg ,vs 64 % for placebo). [59, 60]

Another open-label, long-term study (mean duration, 292 days), by Hewitt et al, also found rizatriptan to be effective in pediatric patients, as well as generally safe for and well tolerated during acute, long-term migraine treatment, with a consistent treatment effect revealed over time. The study included 606 migraineurs aged 12-17 years who were treated with rizatriptan, with 583 patients (weighing 40 kg or more) given 10 mg doses and 23 patients (weighing less than 40 kg) given 5 mg doses. [61]

Almotriptan (Axert)

Almotriptan is used to treat acute migraine. It is a selective 5-HT1B/1D/1F receptor agonist that causes cranial vessel constriction, inhibition of neuropeptide release, and reduced pain transmission in trigeminal pathways. Almotriptan has received FDA approval to be used in children aged 12-17 years.

Zolmitriptan (Zomig Nasal Spray)

Zolmitriptan is used for the symptomatic relief of headache. It is a selective serotonin (5-HT1) receptor agonist in cranial arteries. This agent elicits vasoconstriction and reduces inflammation associated with antidromic neuronal transmission in chronic headache. Zolmitriptan has a high affinity for 5-HT1D and 5-HT1B receptor subtypes and can reduce the severity of headache within 15 minutes. The intranasal spray is approved by the FDA for use in adolescents aged >12 y; however, the oral dosage forms are not approved for use in children or adolescents.

Naratriptan (Amerge)

Naratriptan is a selective 5-HT1 agonist with a long half-life and a high affinity for the 5-HT1D receptor subtype. The drug has a duration of action of up to 24 hours, with a low rate of headache recurrence. It is useful for patients with slow-onset, prolonged migraine, such as menstrual migraine. Naratriptan has had no formal FDA approval for use in headache relief for children.

Frovatriptan (Frova)

Frovatriptan is a selective 5-HT1 agonist with a long half-life (26-30 h). It has a high affinity for 5-HT1D and 5-HT1B receptor subtypes. Its duration of action is as long as 24 hours, with a low rate of headache recurrence. Frovatriptan is useful for patients with slow-onset, prolonged migraine, such as menstrual migraine. It has had no formal FDA approval for use in headache relief for children.

Eletriptan (Relpax)

Eletriptan is a selective serotonin agonist. It specifically acts at 5-HT1B/1D/1F receptors on intracranial blood vessels and sensory nerve endings to relieve pain associated with acute migraine. As of now, it has had no formal FDA approval for use in headache relief for children.


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