Pediatric Headache Medication

Updated: Jan 06, 2017
  • Author: J Ivan Lopez, MD, FAAN, FAHS; Chief Editor: Amy Kao, MD  more...
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Medication

Medication Summary

If the diagnosis for a patient with headache is not a surgical condition that requires immediate operative treatment, the emphasis of headache therapy should be to provide analgesia and to treat the headache’s underlying cause. In patients with migraine, tension-type, or posttraumatic headache, the goals of therapy are to relieve pain, alleviate nausea, and promote sleep.

Pharmacologic treatment of migraine may be abortive or prophylactic. Abortive agents include the following:

  • Selective agonists for serotonin 5-HT1 receptors - These include sumatriptan, naratriptan, zolmitriptan, rizatriptan, almotriptan, frovatriptan, and eletriptan
  • Ergotamines
  • Analgesics such as acetaminophen and NSAIDs

Prophylactic agents include the following:

  • Beta-blockers - Propranolol and nadolol
  • Tricyclics - Amitriptyline
  • Antiepileptic drugs - Valproic acid, topiramate, and zonisamide
  • Verapamil

Abortive therapies should be used selectively. If possible, they should be used no more than 4 days in a month, per month, according to Termine et al, but they should be used early on in the course of the attack. [56]

Prophylactic agents can and should be used for daily headache, and they can be considered for over 4 attacks per month for more than 2 months. This has to be addressed clearly with the parents, since it requires a level of commitment.

It must be emphasized that the placebo effect for headache treatment in children is very high, reaching 55% for prophylactic agents and 69% for abortive ones. [57, 58]

Additional agents

Drugs exist that can be considered individually but cannot be recommended on a routine basis because either (1) they have not been studied specifically or used regularly in the pediatric population, or (2) they are not available in the United States. These medications are migraine preventatives; they include flunarizine, a calcium channel blocker; gabapentin; riboflavin; and metoprolol . (This list is not comprehensive.)

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Analgesics, Other

Class Summary

Analgesics are indicated for the treatment of mild to moderate pain and headache. They are the mainstays of headache treatment. Analgesics ensure patient comfort, promote pulmonary toilet, and have sedating properties, which are beneficial for patients in pain.

Aspirin (Bayer Aspirin, Ecotrin, Tri-Buffered Aspirin)

Aspirin is used to treat mild to moderate pain. It inhibits prostaglandin synthesis, which prevents the formation of platelet-aggregating thromboxane A2.

Acetaminophen (Tylenol, FeverAll, Acephen, Little Fevers, Mapap)

Acetaminophen is the drug of choice for pain in patients with documented hypersensitivity to aspirin or NSAIDs, upper GI disease, or current oral anticoagulant use.

It can be used for symptomatic relief in migraine and tension-type headaches, although its efficacy in relieving tension-type headache is modest. Acetaminophen is fairly effective in migraine attack termination, especially when it is combined with an antiemetic.

Combinations with pseudoephedrine (Sudafed) or caffeine (Excedrin Migraine) can be considered but should not be used regularly short of a risk of rebound withdrawal headache.

Acetaminophen 15 mg/kg was slightly less effective than ibuprofen 10 mg/kg at 2 hours, but was equally effective at 1 hour, in a randomized, controlled trial by Hamalainen et al. There were no serious adverse events. [58]

Morphine (Duramorph, Avinza, Kadian, MS Contin, Oramorph)

Morphine is the drug of choice for analgesia because of its reliable and predictable effects, safety profile, and ease of reversibility with naloxone. It is the most potent of the opiate agonists and is useful for the acute management of headache due to migraine. Various IV doses are used and are commonly titrated until the desired effect is obtained. Its use is cautioned in conditions with raised intracranial pressure. Opiates should be used with a great deal of caution in the pediatric population.

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Sedative/Hypnotics

Class Summary

Chloral hydrate promotes sleep in children with migraine headache.

Chloral hydrate (Somnote)

Chloral hydrate is a CNS depressant. Its mechanism of action is unknown.

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Serotonin 5-HT-Receptor Agonists

Class Summary

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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Antiemetic Agents

Class Summary

Antiemetics are useful in the treatment of symptomatic nausea. Interestingly, sometimes the GI symptoms of migraine, as opposed to the pain, are at the forefront of the clinical picture and require the most attention. This can significantly differ from the management of adults with migraine. Delayed gastric peristalsis can hinder medication absorption. [59]

Promethazine (Phenergan, Promethegan, Phenadoz)

Promethazine blocks the postsynaptic mesolimbic dopaminergic receptors in the brain and reduces stimuli to the brain-stem reticular system. It has antiemetic and antihistaminic actions that alleviate nausea and vomiting and promote sleep. Because of its antidopamine action, promethazine also has a direct antimigraine effect. It is usually well tolerated.

Metoclopramide (Reglan, Metozolv ODT)

Metoclopramide promotes gastric emptying and has antiemetic effects, which are useful for treating the nausea and vomiting associated with migraine.

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Beta-Blockers

Class Summary

Beta-blockers are effective in migraine prophylactic therapy, possibly by blocking vasodilators, decreasing platelet adhesiveness and aggregation, stabilizing membranes, or increasing the release of oxygen to tissues.

Propranolol (Inderal, InnoPran XL)

Taken long-term, beta-blockers such as propranolol are frequently effective in reducing the number and severity of attacks. When administering this medication, start with the lowest dose and increase the dose gradually (usually at monthly intervals) to allow each dose level to exert its maximum effect. The ideal dosage will reduce the heart rate by about 20%.

Propranolol is extensively used in migraine prevention in adults and children. Its mechanism of action in migraine prevention is supposed to be a reduction of central noradrenergic activity.

Timolol

Timolol is FDA approved for migraine prophylaxis, although there is less scientific evidence of efficacy for timolol than for propranolol.

Metoprolol (Lopressor, Toprol XL)

Metoprolol is not FDA approved for migraine prevention. It achieves efficacy in prophylactic therapy presumably by blocking vasodilators, decreasing platelet adhesiveness and aggregation, stabilizing membranes, or increasing the release of oxygen to tissues.

Nadolol (Corgard)

Nadolol is not FDA approved for migraine prevention. It achieves efficacy in prophylactic therapy presumably by blocking vasodilators, decreasing platelet adhesiveness and aggregation, stabilizing membranes, or increasing the release of oxygen to tissues.

Atenolol (Tenormin)

Atenolol is not FDA approved for migraine prevention. It achieves efficacy in prophylactic therapy presumably by blocking vasodilators, decreasing platelet adhesiveness and aggregation, stabilizing membranes, or increasing the release of oxygen to tissues.

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Tricyclic Antidepressants

Class Summary

In low doses, tricyclic antidepressants (eg, amitriptyline) are useful in preventing migraines, particularly in patients with cyclic vomiting syndrome. They appear to exert their antimigraine effect independent of their effect on depression.

Amitriptyline

Amitriptyline has efficacy for migraine prophylaxis that is independent of its antidepressant effect. Its mechanism of action is unknown, but it inhibits the activity of such diverse agents as histamine, 5-HT, and acetylcholine. Its mechanism of action may also be central serotonin enhancement, but this has never been proven. When amitriptyline is administered at a low dose, it may be particularly effective against cyclic vomiting of childhood. The drug also has been used for long-term prophylactic treatment of chronic tension-type headache. It cannot be formally recommended for individuals under 12 years.

Doxepin

Doxepin has efficacy for migraine prophylaxis that is independent of its antidepressant effect. Its mechanism of action is unknown, but it increases the concentration of serotonin and norepinephrine in the CNS by inhibiting their reuptake by the presynaptic neuronal membrane. It also inhibits histamine and acetylcholine activity.

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Anticonvulsants

Class Summary

When given in doses lower than those generally used for preventing seizures, valproic acid and topiramate usually have antimigraine activity; divalproex sodium (which contains valproic acid) and topiramate have been approved by the FDA for migraine prophylaxis.

Divalproex sodium (Depakote)

Divalproex sodium is a stable coordination compound composed of sodium valproate and valproic acid in a 1:1 molar relationship; it has been approved by the FDA for prevention of migraine in children older than 12 years. It is likely that all forms of valproic acid have similar efficacy. Preparations that can be used include 250 mg tablets, 125 mg sprinkle capsules, and 250 mg/5 mL liquid formulations (US preparations). The mechanism of action in migraine is unknown, but it is reported to act through the inhibitory neurotransmitter gamma-aminobutyric acid in the treatment of epilepsy.

Valproic acid (Stavzor)

Valproic acid has been approved by the FDA for the prevention of migraine in children older than 12 years. The mechanism of action in migraine is unknown, but it is reported to act through the inhibitory neurotransmitter gamma-aminobutyric acid in the treatment of epilepsy.

Gabapentin (Neurontin, Gralise)

Gabapentin is used for migraine headache prophylaxis.

Topiramate (Topamax)

Migraine prophylaxis in adults is a labeled indication for topiramate. Although studies of the use of the drug in adolescents and children are under way, in 2014 the FDA approved the use of topiramate for the prevention of headaches in migraine patients aged 12-17 years. Topiramate is sedating and causes cognitive slowing if the dose is advanced rapidly or the starting dose is high.

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Calcium Channel Blockers

Class Summary

Migraine prophylaxis has been reported with various calcium channel blockers, including verapamil, nifedipine, and others. The calcium channel blocker with the highest evidence of efficacy is flunarizine, which is not available in the United States. Results are not entirely predictable, and the dosage must be individualized. Some patients experience exacerbation of migraine with these agents.

Verapamil (Calan, Calan SR, Covera-HS, Verelan)

Verapamil relaxes smooth muscles and increases oxygen delivery during vasospasms. It is used in children for migraine with aura and for basilar migraine. Verapamil has not been FDA approved for use in migraine.

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Antihistamines

Class Summary

Cyproheptadine is occasionally useful for migraine prophylaxis, probably because of its serotonergic (as opposed to antihistaminic) effects. Other antihistamines generally are not useful for migraine prophylaxis.

Cyproheptadine

Cyproheptadine is an antihistamine that has been used for migraine prevention in children more than it has in adults. It is usually well tolerated. The mechanism by which cyproheptadine acts has not been clarified; hypotheses include antihistaminic and anti-5-HT2 effects. There is no solid scientific evidence that this medication has any value in migraine prevention, but it is used by many physicians.

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Corticosteroids

Class Summary

Steroid therapy may decrease intracranial pressure in benign intracranial hypertension.

Prednisone

Prednisolone is not used as often as it once was, but it should still be part of the armamentarium. It should be emphasized that the treatment of benign intracranial hypertension ought to be left to a neurology/neurosurgery specialist. Prednisolone should be part of an integrated treatment approach that includes decompressive procedures.

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Carbonic Anhydrase Inhibitors

Class Summary

These agents are used for the treatment of idiopathic intracranial hypertension.

Acetazolamide (Diamox)

Acetazolamide decreases the production of CSF and has diuretic effects. It has not been formally recommended for pediatric use and should be reserved for consultation.

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Ergot Derivatives

Class Summary

Ergot derivatives are not approved for children and off-label use requires close monitoring. The risk ergotism (intense vasoconstriction) may result and is typically associated with overdosage or prolonged use. Causes constriction of peripheral and central vasculature.

Dihydroergotamine (Migranal, D.H.E. 45)

Ergot derivatives include ergotamine and dihydroergotamine. Ergotamine comes only in oral form and has significant adverse effects, including vomiting, which makes it far less suitable than other drugs for the treatment of migraine.

Dihydroergotamine is used parenterally for severe migraine attacks in the adult patient and can be considered in some instances in children.

Ergotamine (Ergomar)

Ergotamine is an alpha-adrenergic and serotonin (5-HT1) antagonist and partial agonist (depending on the receptor site). It causes constriction of peripheral and cranial blood vessels. This agent works best when it is used in the early stages of migraine. Significant nausea and vomiting have been associated with its use.

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