Medication Summary
Acute treatment (symptomatic therapy) terminates the migraine variant episode. Prophylactic treatment prevents episodes or reduces their number or severity. Medications used to treat or abort attacks include antiemetics, ergot alkaloids, serotonin agonists, and nonsteroidal anti-inflammatory drugs (NSAIDs).
Minor analgesics, with or without antiemetics or caffeine, are useful in most children. Avoid narcotics and sedatives in most patients. Some of the prophylactic medications that are effective in some patients with migraine variants include low-dose aspirin, beta blockers, low-dose tricyclic antidepressants (TCAs), cyproheptadine, calcium channel blockers, and low-dose anticonvulsants, including valproic acid and topiramate. Acetazolamide (Diamox) is useful for selected patients with hemiplegic migraine due to specific channelopathies.
Antiemetic Agents
Class Summary
Antiemetics may be administered (orally, rectally, or intravenously [IV]) if nausea or vomiting is prominent.
Promethazine HCl (Phenergan, Phenadoz, Promethegan)
Promethazine is an antiemetic and sedative that is available in oral, rectal, and parenteral preparations. It blocks postsynaptic mesolimbic dopaminergic receptors in the brain and reduces stimuli to the brainstem reticular system.
Metoclopramide (Reglan, Metozolv)
Metoclopramide blocks dopamine receptors in the chemoreceptor trigger zone of the central nervous system (CNS). It is indicated for migraine-associated nausea.
Ergot Derivatives
Class Summary
Ergotamine preparations (alone or combined with caffeine) are direct vasoconstrictors of smooth muscle in cranial blood vessels. Their activity depends on the CNS vascular tone at administration. They also help establish the diagnosis. Ergot alkaloids should never be used to treat hemiplegic migraine.
Ergotamine (Ergomar)
Ergotamine is an alpha-adrenergic antagonist and serotonin antagonist that causes constriction of the peripheral and cranial blood vessels. Its effects are enhanced by caffeine. It is available as sublingual tab.
Dihydroergotamine (DHE-45, Migranal)
Dihydroergotamine is an alpha-adrenergic blocking agent that has a direct stimulating effect on the smooth muscle of peripheral and cranial blood vessels and depresses central vasomotor centers. Its mechanism of action is similar to that of ergotamine; it is a nonselective 5-HT1 agonist with a wide spectrum of receptor affinities outside the 5-HT1 system, and it also binds to dopamine. Thus, dihydroergotamine has alpha-adrenergic antagonist and serotonin antagonist effects.
Dihydroergotamine is indicated for aborting or preventing vascular headache when rapid control is needed or when other routes of administration are not feasible. It is not approved by the US Food and Drug Administration (FDA) for use in children.
Dihydroergotamine is usually administered in conjunction with antiemetics such as metoclopramide (a 5-HT3 receptor antagonist and a dopamine antagonist) to treat migraine-associated nausea. Dihydroergotamine is available in IV or intranasal preparations, and it tends to cause less arterial vasoconstriction than ergotamine tartrate does.
Antidepressants, SSRIs
Class Summary
Sumatriptan and other serotonin agonists stimulate serotonin 5-HT1 receptors, producing a direct vasoconstrictive effect. Serotonin agonists help establish the diagnosis, but they never should be used for hemiplegic migraine. Some triptans have slightly different pharmacokinetics or adverse effect profiles, but all have substantially the same mechanism as sumatriptan. None has been adequately evaluated in children.
Sumatriptan succinate (Imitrex, Alsuma, Sumavel DosePro)
Sumatriptan is the first of the antimigraine agents that directly affect 5-HT1 receptors. A selective agonist for serotonin 5-HT1 receptors in cranial arteries, it suppresses inflammation associated with migraine headaches. The nasal form has been demonstrated to have some efficacy in adolescents with migraine; other forms have no proven efficacy in children, though uncontrolled reports suggest some efficacy.
Nonsteroidal Anti-inflammatory Agents (NSAIDs)
Class Summary
NSAIDs are most commonly used to relieve mild to moderate pain. Although their efficacy in treating pain tends to be patient-specific, ibuprofen is usually the drug of choice for initial therapy. Ibuprofen, sodium naproxen, or other NSAIDs, particularly if combined with or preceded by an antiemetic, may abort acute episodes.
Ibuprofen (Ibuprin, Advil, Motrin)
Ibuprofen inhibits pain, probably by decreasing the activity of the enzyme cyclooxygenase, thereby inhibiting prostaglandin synthesis. In randomized trials, ibuprofen is one of the only agents with proven efficacy in pediatric migraine.
Indomethacin (Indocin)
Inhibition of prostaglandin synthesis reduces the delivery of solute to distal tubules, reducing urine volume and increasing urine osmolality. Indomethacin is usually used in nephrogenic diabetes insipidus.
Naproxen (Anaprox, Naprelan, Naprosyn)
Naproxen is well-absorbed orally and is not usually associated with rebound headaches. It is used for the relief of mild to moderate pain. Naproxen inhibits inflammatory reactions and pain by decreasing the activity of cyclo-oxygenase, which is responsible for prostaglandin synthesis. It is inexpensive and can be purchased over the counter.
Diclofenac (Voltaren, Cataflam XR, Zipsor, Cambia)
Diclofenac inhibits prostaglandin synthesis by decreasing cyclo-oxygenase activity, which, in turn, decreases the formation of prostaglandin precursors.
Ketoprofen
Ketoprofen is used for relief of mild to moderate pain and inflammation. Small dosages are indicated initially in small patients, elderly patients, and patients with renal or liver disease. Doses higher than 75 mg do not increase the therapeutic effects. Administer high doses with caution, and closely observe the patient's response.
Ketorolac (Sprix)
Ketorolac is indicated for short-term (up to 5 d) management of moderate to moderately severe pain. The bioavailability of a 31.5-mg intranasal dose (2 sprays) is approximately 60% of 30-mg IM dose. Intranasal spray delivers 15.75 mg per 100-µL spray; each 1.7-g bottle contains 8 sprays.
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)
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.
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. Efficacy in prophylactic therapy is 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. Efficacy in prophylactic therapy is 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. Efficacy in prophylactic therapy is presumably by blocking vasodilators, decreasing platelet adhesiveness and aggregation, stabilizing membranes, or increasing the release of oxygen to tissues.
Tricyclic Antidepressants
Class Summary
In low doses, TCAs (eg, amitriptyline, imipramine, and nortriptyline) are useful in preventing migraines, particularly in patients with cyclic vomiting syndrome. These agents 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 activity of such diverse agents as histamine, 5-HT, and acetylcholine. When administered at a low dose, it may be particularly effective against cyclic vomiting of childhood.
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.
Nortriptyline (Pamelor)
Nortriptyline has efficacy for migraine prophylaxis that is independent of its antidepressant effect. Its mechanism of action is unknown, but it inhibits activity of such diverse agents as histamine, 5-HT, and acetylcholine.
Protriptyline (Vivactil)
Protriptyline has efficacy for migraine prophylaxis that is independent of its antidepressant effect. It inhibits activity of such diverse agents as histamine, 5-HT, and acetylcholine.
Anticonvulsants
Class Summary
When given in doses lower than those generally used for preventing seizures, valproic acid, topiramate, phenobarbital, and phenytoin usually have antimigraine activity. Only divalproex sodium is approved specifically for migraine prophylaxis. Topiramate has been reported to reduce migraine attacks in adults but is not yet approved for migraine prophylaxis in children.
Valproic acid (Depakote)
Divalproex sodium is a stable coordination compound comprising sodium valproate and valproic acid in a 1:1 molar relationship; it is approved by the FDA for prevention of migraine. 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).
Gabapentin (Neurontin, Gralise)
Gabapentin is used for migraine headache prophylaxis. It has shown efficacy in migraine and transformed migraine.
Topiramate (Topamax)
Migraine prophylaxis in adults is a labeled indication for topiramate. Studies of this use of the drug in adolescents and children are under way. Topiramate is sedating and causes cognitive slowing if the dose is advanced rapidly or the starting dose is high.
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 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 basilar migraine. Verapamil has not been FDA-approved for use in migraine.
Metabolic Support
Class Summary
Metabolic support to prevent catabolic state is indicated in migrainelike episodes caused by suspected mitochondrial cytopathies. IV glucose and, occasionally, carnitine supplementation may be useful.
Dextrose
Dextrose is administered with the goal of preventing dehydration and a catabolic state in mitochondrial cytopathies.
Levocarnitine (Carnitor)
Levocarnitine is a vitaminlike substance that is necessary for transport of fatty acids into mitochondria; it is a cofactor in mitochondrial energy production. Levocarnitine can be deficient in organic acidurias or mitochondrial dysfunction and can be depleted by the administration of valproic acid. Supplementation with levocarnitine may be helpful in mitochondrial cytopathies to prevent severe metabolic collapse and encephalopathy. Supplementation may be useful in cyclic vomiting or atypical migraine syndromes caused by mitochondrial dysfunction.
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 (Periactin)
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.
Water-Soluble Vitamins
Class Summary
Riboflavin, with or without magnesium supplements and with or without herbs (eg, feverfew), has been used as prophylaxis for migraine headaches. For adults, the dosage ranges from 200-400 mg/day; no pediatric dose has been established. The only side effect is bright yellow-green discoloration of the urine. Patients should be warned about this harmless effect so that they do not become unduly alarmed.
Riboflavin (Riobi)
Riboflavin is essential in the activation of pyridoxine and the conversion of tryptophan to niacin. It is a component of flavoprotein enzymes, which are necessary for tissue respiration.
Electrolyte Supplements
Class Summary
Magnesium salts, typically magnesium oxide, are combined in a commercial over-the-counter preparation for migraine prophylaxis (MigreLief). Excess dosing may produce diarrhea.
Magnesium oxide (Mag-Ox)
Magnesium oxide is used in migraine prophylaxis.
