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Acute treatment of migraine in children

Acute treatment of migraine in children
Literature review current through: Jan 2024.
This topic last updated: May 08, 2023.

INTRODUCTION — Migraine is the most common acute and recurrent headache syndrome in children. It is characterized by episodes of severe headache often accompanied by nausea, vomiting, photophobia, phonophobia, and abdominal pain and is relieved by sleep.

The acute treatment of migraine in children is reviewed here. Other aspects of pediatric migraine are discussed separately. (See "Types of migraine and related syndromes in children" and "Pathophysiology, clinical features, and diagnosis of migraine in children" and "Preventive treatment of migraine in children".)

APPROACH TO TREATMENT — The goals of acute migraine treatment are to obtain consistent, effective relief of migraine symptoms with minimal side effects and to promote a rapid return to normal function, including participation in school and social activities [1]. The management of migraine consists of general measures, acute treatment, and preventive treatment [2-4]. An individual patient may need all three approaches. The management of pediatric migraine headache varies among clinicians. The sections that follow describe one potential approach for different clinical situations.

General measures for all patients — When migraine symptoms develop, the child should rest or sleep in a dark, quiet room with a cool cloth applied to the forehead if possible.

Educating the child and caregivers about migraine headache is an important aspect of care. A headache calendar (diary) may identify triggering factors, clarify features of the attacks, and help evaluate the effectiveness of treatment [2,5]. Precipitating factors (eg, stress, poor sleep habits, irregular meals, odors, weather changes, specific foods, menstrual cycles), if identified, should be addressed. A headache diary suitable for children can be used, such as this example from Boston Children’s Hospital.

Step-wise selection of medications for most patients — Early use of medication during the migraine attack, when the headache pain is still mild, is an important principle of acute migraine treatment [2,4]. Medications useful for the acute treatment of migraine range from analgesics such as nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen to triptans and antiemetics. A trial of several medications may be needed to find treatments that are most effective for individual patients. Our suggested hierarchy for selecting and sequencing pharmacologic agents for acute migraine treatment is divided into tiers (1 to 3) and provides choices for treating migraine attacks of increasing severity and/or refractory responsiveness.

Tier 1 (analgesics) — The initial treatment of migraine attacks in children and adolescents usually involves a simple analgesic and may include an antiemetic. For treatment-naïve children and adolescents with migraine, we suggest initial acute treatment with either acetaminophen or ibuprofen. If the patient does not respond to one, the other can be tried. Naproxen is an alternative.

Acetaminophen, 15 mg/kg per dose as an oral solution, melt (oral disintegrating tablet), tablet, or rectal suppository, with a maximum single dose of 1000 mg. This dose may be repeated in two to four hours if symptoms persist but should not exceed three doses in 24 hours.

Ibuprofen, 10 mg/kg per dose as an oral solution or tablet. This dose may be repeated in four to six hours if needed. No more than four doses should be given in 24 hours (maximum daily dose 40 mg/kg).

Naproxen, 5 mg/kg per dose as an oral solution or tablet. This dose may be repeated in 8 to 12 hours if symptoms persist (maximum daily dose 1000 mg).

To prevent the development of medication overuse headache, analgesics should not be used more than 14 days per month. (See 'Avoiding medication overuse' below.)

Analgesics are reviewed in greater detail below. (See 'Analgesics' below.)

Tier 2 (triptans) — For children at least six years of age who have moderate to severe migraine attacks or who have acute migraine of any severity that is refractory to analgesics, we suggest treatment with a triptan. The choice of triptan, route of administration, and dose depends upon several factors, including the child's age, weight, ability to swallow pills, and whether the migraine attacks are associated with nausea and vomiting. It is reasonable to offer an alternate triptan if one triptan does not provide sufficient relief [2].

For children who are unable to swallow pills and for children who have migraine attacks associated with significant nausea and vomiting, rizatriptan and zolmitriptan are available as orally disintegrating tablets and/or films, and sumatriptan and zolmitriptan are available as nasal sprays. A nonoral route of delivery may be preferred for patients when headache pain rapidly reaches maximum severity, is accompanied by nausea or vomiting, or is unresponsive to oral formulations [2,4].

Triptan dosing varies by body weight and age.

Older children and adolescents – Children who are older than 12 years of age and weigh more than 40 kg often tolerate adult doses of the triptans; options include:

Almotriptan 12.5 mg tablet

Rizatriptan 10 mg tablet or melt (the dose should be decreased in patients taking concomitant propranolol)

Rizatriptan 10 mg oral film

Sumatriptan 50 mg tablet

Sumatriptan 10 mg nasal spray

Zolmitriptan 5 mg tablet, melt, or nasal spray

Younger children – Children between 6 and 11 years of age and who weigh less than 40 kg should begin with the smallest available dose of triptan in order to minimize the chance of adverse effects. For children who weigh less than 40 kg (generally 6 to 12 years of age), options include:

Almotriptan 6.25 mg oral tablet

Rizatriptan 5 mg oral tablet (decrease the dose with concomitant propranolol)

Sumatriptan 25 mg oral tablet

Sumatriptan 5 mg nasal spray

Zolmitriptan 2.5 mg tablet, melt, or nasal spray

To prevent the development of medication overuse headache, triptans should not be used more than nine days per month. (See 'Avoiding medication overuse' below.)

Triptans are reviewed in greater detail below. (See 'Triptans' below.)

Tier 3 (combination) — For children (age ≥6 years) and adolescents who have acute migraine attacks that are refractory to monotherapy with other acute migraine medications, we suggest treatment with a triptan taken together with an analgesic medication (eg, a triptan taken with naproxen 5 mg/kg per dose, or the proprietary combination drug sumatriptan-naproxen) [4]. Another option is promethazine 0.25 to 0.5 mg/kg per dose, typically used as adjunct therapy with a triptan or with a triptan plus naproxen. (See 'Combined sumatriptan and naproxen' below and 'Antiemetics' below.)

The combination drug acetaminophen-isometheptene-dichloralphenazone was once commonly used to treat migraine for adolescents and children older than eight years of age. However, supporting data are limited to studies in adults [6-9]. This drug is not widely available in all countries.

Clinical factors that impact medication selection — Specific features of the headache may be used to guide medication selection and hasten relief. These include severity and duration of symptoms, the presence of associated nausea and vomiting, and responsiveness to prior medications used. In addition, treatment may vary by setting and patient-level factors such as children at school, those in emergency department settings, and patients who are pregnant.

Attack severity

Mild attacks – Although the distinction is subjective, a mild migraine attack may be considered one that is nondisabling; the child or adolescent can continue to participate in activities without functional impairment. A moderate or severe migraine attack causes some degree of functional impairment that interferes with the ability to fully participate in usual activities at school, home, or outdoors.

For migraine attacks with mild pain and minimal disability, over the counter analgesics (NSAIDs, acetaminophen) are first-choice agents because they are generally effective, less expensive, and less likely to cause adverse effects than migraine-specific agents such as triptans.

For children and adolescents with acute mild migraine headache, we suggest initial treatment with an analgesic, either acetaminophen or ibuprofen, both of which have efficacy for migraine in children in a randomized controlled trial. The choice depends upon individual preference. If the patient does not respond to one, the other can be tried. Naproxen is an alternative analgesic in this setting.

Variable attacks – Many patients with migraine have attacks that vary in severity, time of onset, and association with vomiting and nausea [10]. These patients may require two or more options for the management of acute migraine, including oral medications for mild attacks and nonoral medications (eg, subcutaneous or nasal triptans) for more severe attacks or those associated with vomiting or severe nausea.

Severe attacks – For migraine attacks with moderate to severe headache pain or disability, analgesics may still be effective, and migraine-specific agents (triptans) can be tried if the migraine attack does not respond to simple analgesics.

Patients who present with migraine in emergency settings generally have unusually severe or long-lasting attacks, and in many cases their customary acute migraine treatment has failed to provide relief [11-13]. The treatment of migraine attacks in the emergency department or other urgent care settings follows the same principles as treatment in nonurgent settings outlined above, with the obvious difference that parenteral medications are available.

For children who present in emergency or urgent care settings and fail to improve with analgesics, we suggest the following:

The most effective treatment in our clinical experience is intravenous (IV) fluid therapy, such as 20 mL/kg of normal saline, given with IV prochlorperazine (0.15 mg/kg to a maximum dose of 10 mg) followed by IV ketorolac (0.5 mg/kg up to a maximum of 30 mg). Pretreatment with diphenhydramine may prevent potential dystonic reactions associated with prochlorperazine. (See 'Antiemetics' below.)

Reasonable alternatives include:

-Sumatriptan 3 to 6 mg administered by subcutaneous injection. (See 'Subcutaneous sumatriptan' below.)

-Metoclopramide 0.2 mg/kg by IV administration to a maximum dose of 10 mg. (See 'Antiemetics' below.)

-Dihydroergotamine (DHE) 0.5 mg over three minutes by IV administration for children who are <25 kg or age ≤9 years and 1 mg over three minutes for children age ≥10 years. DHE administration should be preceded by the use of an antiemetic 20 minutes before the first DHE dose. (See 'Dihydroergotamine' below.)

Status migrainosus – Children presenting with untreated status migrainosus (ie, a debilitating migraine attack lasting for more than 72 hours) can be treated initially with parenteral therapies given for severe attacks of shorter duration such as prochlorperazine and ketorolac, a triptan, metoclopramide, or DHE. However, many children with prolonged migraine symptoms may be unresponsive to initial parenteral dosing and require further treatment in the inpatient setting.

For most children, we suggest a regimen consisting of repetitive IV DHE [14]. All females of childbearing age should first have a negative pregnancy test. For children age 10 years and older, the dose of DHE is 1 mg IV over three minutes every eight hours, with a maximum of 20 doses. For children <25 kg or age 9 years and younger, the dose is 0.5 mg IV every eight hours. Prior to being treated with DHE, all patients should receive a test dose of DHE (one-half the initial dose appropriate for age and weight) to see if the patient is particularly susceptible to adverse events such as nausea, anxiety, or dyskinesia. Patients should also receive pretreatment with an antiemetic (prochlorperazine or metoclopramide) 30 minutes prior to each DHE dose for the first three doses, followed by ondansetron as needed for remaining doses (to prevent the extrapyramidal side effects that can occur with the antidopaminergic drugs).

Alternative options for children who do not respond or have a contraindication to DHE include:

-Valproate sodium – A retrospective series of 83 children with status migrainosus unresponsive to initial abortive treatments and who received an intravenous valproate sodium infusion reported a favorable response (resolution of pain) in 66 percent [15]. Loading dose in this series was 20 mg/kg followed by continuous infusion at 1 mg/kg per hour to achieve a sustained serum level of 80 to 100 mcg/mL. More than 75 percent of responders improved within 24 hours, after which the intravenous infusion switched to oral extended-release valproic acid for preventive therapy.

Valproate may cause teratogenicity and should be avoided in pregnancy wherever possible. Other common adverse effects include nausea, weight gain, and insulin resistance.

-Peripheral nerve block (PNB) – In a retrospective single-center cohort of children with status migrainosus who were unresponsive to initial acute migraine treatments, 77 children were treated in a single session with PNB using bupivacaine administered to the bilateral occipital, superior orbital, and auriculotemporal nerves [16]. A favorable response (≥50 percent improvement) was reported in 49 percent (38 patients) as well as an additional 40 percent of patients who received PNB after nonresponsiveness to treatment with DHE.

Patients with associated nausea and vomiting — Early use of an antiemetic may relieve symptoms and facilitate sleep if nausea and vomiting are prominent. For children with acute migraine attacks who have nausea and vomiting, we suggest oral or rectal promethazine in a single dose of 0.25 to 0.5 mg/kg as needed at intervals of four to six hours, in conjunction with simple or combination analgesics.

Oral analgesics and triptan medications may be ineffective because of poor absorption secondary to migraine-induced gastric stasis. Thus, a nonoral route of administration (ie, rectal, nasal spray, or injection) may be better for some children whose migraines present with significant nausea or vomiting.

Special populations

Young children – Early use of medication during the headache episode is an important principle of acute treatment. This may be difficult in young children, who often do not report a migraine until symptoms are severe. The younger the child, the more challenging it is to treat migraine effectively with an acute medication. Therefore, the treatment plan should be straightforward and safe. The parents typically decide when treatment is indicated and when to administer medication.

In general, young children are not able to medicate themselves and often are unable to swallow pills; in such cases, a liquid analgesic preparation is required but may not be tolerated because of nausea and vomiting. For children age 5 years and older, we suggest a trial of sumatriptan nasal spray due to its proven efficacy in randomized controlled trials in adolescents. In addition, it is generally better tolerated by children than an injection. Sumatriptan nasal spray can be started with a 5 mg dose and repeated once. Older children can use a dose of 20 mg. One drawback to nasal sumatriptan is the associated bad taste, which limits its acceptability in children. This problem can be mitigated by having children suck on a piece of hard candy.

Children in school – In the school-age child, a school nurse or other professional must administer medicine. The directions from the clinician and parents should include specific guidelines for the school. Often the school requires the parents to sign a permission form to treat.

Pregnant patients – The acute treatment of migraine in pregnancy differs somewhat from that in others because of concerns about adverse fetal drug effects. This aspect of acute migraine care is reviewed separately. (See "Headache during pregnancy and postpartum", section on 'Acute migraine treatment'.)

Avoiding medication overuse — Medication overuse headache (MOH), also called analgesic rebound headache, is associated with significant morbidity. Acute symptomatic medications used to treat headaches have the potential for causing MOH. The risk for MOH appears to be highest with opioids, butalbital-containing combination analgesics, and triptans. The risk with triptans is considered intermediate by some experts but high by others. The risk is lowest with NSAIDs. (See "Medication overuse headache: Etiology, clinical features, and diagnosis", section on 'Causal medications'.)

The risk of MOH is minimized by educating patients and caregivers about this condition and by limiting the use of analgesics (eg, ibuprofen or acetaminophen) to no more than 14 days per month and triptans to no more than 9 days per month [2,4]. Any combination of triptans or analgesics should be limited to no more than 9 days per month for no more than three months [2]. Opioids should not be used to treat migraine in children.

Families and children should be encouraged to record the frequency and amount of analgesic used in a headache diary (log) or calendar. Preventive therapies should be used as the mainstay in patients with frequent headaches. (See "Preventive treatment of migraine in children".)

EFFICACY OF SPECIFIC DRUGS — The acute symptomatic therapy of migraine ranges from the use of simple over-the-counter analgesics such as nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen to triptans, antiemetics, or the less commonly used dihydroergotamine. However, there are limited data from high-quality randomized controlled trials regarding the treatment of migraine in children and adolescents [2,3]. Thus, many management recommendations are additionally based upon experience in adults as well as expert opinion.

Medications used for the preventive treatment of pediatric migraine are reviewed elsewhere. (See "Preventive treatment of migraine in children", section on 'Pharmacologic treatment'.)

Analgesics — Acetaminophen and NSAID often are effective treatment for migraine attacks in children, although supporting evidence is limited [2,17,18]. Early administration of acetaminophen, ibuprofen, or other NSAIDs may be helpful.

Opioids, barbiturates, and benzodiazepines should not be used to treat headache in children because they are habit-forming and have not been found to be effective [19,20]. Aspirin should be used only as a last resort because of concern about Reye syndrome. (See "Acute toxic-metabolic encephalopathy in children", section on 'Reye syndrome'.)

Acetaminophen — In a double-blind crossover study of 88 children, acetaminophen was effective for migraine relief [21]. Acetaminophen (paracetamol) is administered in an initial dose of 15 mg/kg as an oral solution or as one or two 325 mg tablets, with a maximum single dose of 1000 mg. A second dose of 15 mg/kg may be given in two to four hours if symptoms persist. Additional doses may be given at four- to six-hour intervals but should not exceed three doses in 24 hours. Acetaminophen is also available as a melt (oral disintegrating tablet) and rectal suppository.

When administered at appropriate doses, acetaminophen is relatively free of adverse effects [22,23]. Overdose of acetaminophen may cause acute liver failure.

Ibuprofen — In a double-blind crossover study of 88 children, aged 4 to 15.8 years, both acetaminophen and ibuprofen were effective for migraine relief, but ibuprofen provided faster relief [21]. Three attacks in each child were treated randomly with single oral doses of ibuprofen (10 mg/kg), acetaminophen (15 mg/kg), or placebo. Ibuprofen and acetaminophen were three and two times, respectively, more likely to reduce headache severity than was placebo. The headache was aborted within two hours twice as often with ibuprofen than with acetaminophen.

Ibuprofen is given in a dose of 10 mg/kg as an oral solution or tablet. This dose may be repeated in four to six hours if needed. No more than four doses should be given in 24 hours (maximum daily dose 40 mg/kg). Ibuprofen should be used with caution in patients with chronic abdominal pain or tinnitus. Adverse events associated with NSAID use include gastrointestinal bleeding and renal toxicity. (See "Nonselective NSAIDs: Overview of adverse effects".)

Others

Naproxen – There are few data for naproxen in pediatric migraine, but it is effective compared with placebo in the treatment of adults with acute migraine [24,25]. Naproxen, 5 mg/kg per dose, can be given up to three times per day at 8- to 12-hour intervals (maximum daily dose 1000 mg). Naproxen should be used with caution in patients with epigastric pain or worsening nausea. (See "Nonselective NSAIDs: Overview of adverse effects".)

KetorolacKetorolac by intravenous (IV) administration may also be beneficial for pediatric migraine. A randomized trial comparing prochlorperazine with ketorolac found that IV ketorolac (0.5 mg/kg, maximum 30 mg) successfully treated migraine within 60 minutes in 55 percent of 29 children, with a 50 percent or greater reduction in the pain score [26]. However, IV prochlorperazine was more effective (with 85 percent of children responding), and the combination of prochlorperazine and ketorolac achieved the highest response rate. (See 'Antiemetics' below.)

Triptans — The triptans represent a significant advance in the abortive treatment of migraine. They are serotonin agonists with an affinity for 5-HT1B/1D receptors [27]. Triptans are thought to have multiple mechanisms of action. All of the triptans inhibit the release of vasoactive peptides, promote vasoconstriction, and block pain pathways in the brainstem [28].

Triptans inhibit transmission in the trigeminal nucleus caudalis, thereby blocking afferent input to second order neurons; this effect is probably mediated by reducing the levels of calcitonin gene-related peptide (CGRP) (see "Pathophysiology, clinical features, and diagnosis of migraine in children", section on 'Role of CGRP'). Triptans may also activate 5-HT1B/1D receptors in descending brainstem pain-modulating pathways and thereby inhibit dural nociception [29].

The US Food and Drug Administration (FDA) has approved the use of rizatriptan for children 6 to 17 years of age. For children 12 years of age and older, FDA-approved triptans are almotriptan, rizatriptan (tablet, oral disintegrating tablet or oral film), zolmitriptan nasal spray, and the combination of sumatriptan and naproxen. There is published experience with use of other triptans in the pediatric age range as well [2,4,17,30].

Triptans are contraindicated in children or adolescents with a history of ischemic vascular disease or arrhythmias associated with accessory conduction pathway disorders [4]. Triptans should be used with extreme caution in migraine with brainstem aura (see "Migraine with brainstem aura") and in hemiplegic migraine (see "Hemiplegic migraine") because of theoretical concerns about aggravating symptoms that may be caused by vasospasm.

Concerns have also been raised about the development of a serotonin syndrome (see "Serotonin syndrome (serotonin toxicity)") in patients who use triptans in combination with a selective serotonin reuptake inhibitor (SSRI) or a selective serotonin-norepinephrine reuptake inhibitor (SNRI) [31]. However, the risk of serotonin syndrome posed by the combined use of a triptan with an SSRI or SNRI appears to be very low [32,33].

Oral triptans — A placebo-controlled randomized trial of 866 patients showed that oral almotriptan was beneficial for relieving migraine in adolescents aged 12 to 17 [34]. Pain relief at two hours was greater with the 6.25 mg (72 percent), 12.5 mg (73 percent), and 25 mg doses (68 percent) compared with placebo (55 percent), although no differences were seen in the treatment groups for pain freedom at two hours compared with placebo.

A single randomized controlled trial of 267 adolescents failed to show efficacy of eletriptan 40 mg compared with placebo [35].

Early studies failed to show efficacy of 5 mg rizatriptan versus placebo in adolescents [36,37]. In a latter two-staged study designed to identify placebo nonresponders, a greater proportion of children ages 6 to 17 years taking 5 or 10 mg rizatriptan were pain free at two hours compared with those allocated to placebo (31 percent versus 22 percent) [38].

Data for oral sumatriptan in adolescent children include one randomized controlled trial of 144 adolescents from Japan [39] and another randomized trial of 23 children from Finland [40]. These trials found no benefit for oral sumatriptan compared with placebo. However, in our clinical experience, oral sumatriptan is effective and useful in some children and adolescents.

The initial dose of oral sumatriptan is 25 to 50 mg given as soon as possible after the onset of migraine headache. The dose should be adjusted on an individual basis to a maximum single dose of 50 mg for younger children and 100 mg for older adolescents. The dose may be repeated after two hours, with a maximum of 200 mg/day.

A 2019 guideline from the American Academy of Neurology (AAN) and the American Headache Society (AHS) did not identify any high-quality studies to support the effectiveness of oral zolmitriptan in children, although there is some positive experience noted in the medical literature [2,41-43].

Nasal triptans — For adolescents with acute migraine, sumatriptan nasal spray (20 mg) and zolmitriptan nasal spray (5 mg) are more effective than placebo

Nasal sumatriptan – Nasal sumatriptan is given to younger children in an initial dose of 5 mg. If this dose is ineffective, 10 mg can be tried. In adolescents, a dose of up to 20 mg can be given. The bad taste that may accompany use of the nasal spray can by lessened by tilting the head forward during administration and sucking on a flavored lozenge or piece of hard candy [44].

The 2019 AAN/AHS guideline concluded that sumatriptan 20 mg nasal spray was more likely than placebo to reduce migraine headache pain at one and two hours, but confidence in the evidence was low [2].

One trial of 738 adolescents (ages 12 to 17) compared placebo with 5 mg and 20 mg of nasal sumatriptan [45]. Sumatriptan nasal spray 20 mg provided greater headache relief than placebo at 30 minutes (42 versus 33 percent, respectively) and two hours (68 versus 58 percent) post-dose. Photophobia and phonophobia also improved with the 20 mg nasal sumatriptan. The 5 mg dose was no better than placebo.

In another trial, 653 adolescents (12 to 17 years old) with migraine were randomly assigned to one of three doses (5, 10, or 20 mg) of sumatriptan nasal spray or placebo [46]. Headache relief (ie, a reduction in pain severity) two hours after the 20 mg dose of sumatriptan occurred more often than with placebo (63 versus 53 percent), approaching significance, while complete relief two hours after the 20 mg dose was significantly greater with sumatriptan (36 versus 25 percent). Treatment also significantly reduced photophobia and phonophobia. Taste disturbance, the most frequently reported adverse event, occurred in 26, 30, 19, and 2 percent of patients treated with 20, 10, and 5 mg sumatriptan and placebo, respectively. No serious adverse events occurred.

In a trial that used 10 mg of nasal sumatriptan for children who weighed 20 to 39 kg and 20 mg nasal sumatriptan for children weighing ≥40 kg, both dosing groups had greater headache relief at one and two hours compared with placebo [47].

Nasal zolmitriptan – Results from randomized controlled trials suggest that nasal zolmitriptan is effective for acute treatment of migraine in adolescent children. In one randomized controlled trial of 798 adolescents (ages 12 to 17 years) with migraine, pain-free status at two hours after treatment was greater with zolmitriptan nasal spray 5 mg compared with placebo (30 versus 17 percent; odds ratio [OR] 2.18, 95% CI 1.40-3.39) [48]. Another trial enrolled 248 children (ages 12 to 17 years) with migraine (with or without aura) and employed a novel study design because of an anticipated high placebo response rate [49]. Each migraine attack was treated initially with placebo nasal spray (single blind) when the headache reached moderate or severe intensity. If the migraine intensity remained moderate to severe, patients were then randomly assigned (double blind) to zolmitriptan 5 mg nasal spray or placebo nasal spray. For headache improvement at one hour after treatment, the rate of response was higher for patients assigned to zolmitriptan nasal spray compared with placebo (58 versus 43 percent; OR 1.83, 95% CI 1.14-2.94).

In the clinical experience of some experts, patients may find that zolmitriptan nasal spray has a less objectionable taste than sumatriptan nasal spray.

Subcutaneous sumatriptan — Two small open-label studies suggest that subcutaneous sumatriptan may be an effective therapy for migraine [50,51]. In one of these reports, subcutaneous sumatriptan was evaluated in a series of 17 children, 6 to 16 years old, with severe migraine [50]. After a 6 mg dose, headache was relieved within one or two hours in 6 and 5 of 15 patients, respectively. Two smaller children had complete relief two hours after a 3 mg dose. In another study of 50 children, 6 to 18 years old, headache response was 78 percent overall, with 30, 60, and 60 to 120 minute response rates of 26, 46, and 6 percent [51].

Combined sumatriptan and naproxen — The combination drug sumatriptan-naproxen was superior to placebo for the treatment of moderate to severe acute migraine headache in a randomized controlled trial of 490 adolescents (ages 12 to 17 years) [52]. At two hours, adolescents assigned to three different doses of combination sumatriptan-naproxen tablets (10/60 mg, 30/180 mg, and 85/500 mg) had significantly higher pain-free rates (29, 27, and 24 percent, respectively) compared with those assigned to placebo (10 percent). All three doses of combination sumatriptan-naproxen were well tolerated. Efficacy was seen in other placebo-controlled randomized trials as well [53].

Antiemetics — Early use of an antiemetic may relieve symptoms and facilitate sleep, particularly if nausea and vomiting are prominent. Rectal administration may be preferable in a patient with nausea and vomiting who cannot easily take an oral medication.

The phenothiazines may have additional antimigraine properties, although few studies are available.

PromethazinePromethazine is the phenothiazine most commonly used in children because it is effective and has a low incidence of acute extrapyramidal reactions, such as oculogyric crisis. The dose is 0.25 to 0.5 mg/kg per dose orally, intramuscularly, or rectally; it should not be administered intravenously. Promethazine should not be given to children who are less than two years old because of the potential for severe and potentially fatal respiratory depression.

Prochlorperazine and chlorpromazineProchlorperazine and chlorpromazine also are effective, but they are used less commonly in children because of concerns about extrapyramidal reactions, although the frequency of this complication is uncertain [54]. A single randomized trial of 62 children presenting to the emergency department with migraine headaches compared IV ketorolac with IV prochlorperazine; successful treatment of migraine was defined as a 50 percent or greater reduction in pain score within 60 minutes [26]. Prochlorperazine was significantly more effective than ketorolac in achieving treatment success (85 and 55 percent, respectively) and in decreasing the mean pain score. In a retrospective study of 20 consecutive children seen in the emergency department for severe prolonged migraine, treatment with prochlorperazine (0.15 mg/kg intravenously) reduced pain severity in most patients; after three hours, 60 percent reported no pain [55]. No significant side effects were seen.

MetoclopramideMetoclopramide administered intravenously reduces nausea and vomiting associated with migraine. Its use in children usually is reserved for the emergency department and for protracted migraine [11,13,56]. It commonly is used prior to the administration of dihydroergotamine (see 'Dihydroergotamine' below). In one trial, adults with migraine seen in an emergency department were assigned randomly to treatment with metoclopramide with or without ibuprofen or placebo [57]. Metoclopramide resulted in significantly better relief of pain and nausea than ibuprofen or placebo. The effect of metoclopramide was similar with or without ibuprofen.

Acute dystonic reactions may occur with metoclopramide [58,59]. This complication is thought to occur more commonly in patients younger than 25 years of age. Thus, metoclopramide should be used with caution. Use of diphenhydramine can counteract some of these untoward effects.

Ondansetron – Limited retrospective data suggest that ondansetron is useful for treating children with acute migraine in the emergency department [60].

Ergots — A variety of sublingual, oral, and rectal ergot preparations, alone and in combination with caffeine and other analgesics, has been used to treat migraine attacks. However, with the exception of IV dihydroergotamine (see 'Dihydroergotamine' below), the triptans have replaced ergots for the acute treatment of migraine in children. The utility of ergots is limited by side effects, especially the potentiation of nausea and vomiting and vasospasm.

It is believed that ergot preparations should not be used to treat migraine with brainstem aura (see "Migraine with brainstem aura") or hemiplegic migraine (see "Hemiplegic migraine") since they may theoretically aggravate symptoms caused by vasospasm.

Combination drugs consisting of ergot derivatives, barbiturate, and belladonna are not recommended for children because they are potentially habit forming and predispose to medication overuse headache and the chronification of headache [61].

Dihydroergotamine — Dihydroergotamine (DHE) is available as a nasal spray and as a solution for IV injection. The IV preparation of DHE often is effective in the treatment of severe migraine [62]. This point is illustrated by findings from a retrospective report that reviewed the inpatient treatment of status migrainosus in 32 children (mean age 15 years) who were treated with IV DHE [63]. At time of discharge (mean length of stay three days), approximately 75 percent of the children were headache free. Treatment was well tolerated; nausea was the most frequent side effect. Dosing as used in this trial is described above. (See 'Attack severity' above.)

In an earlier study, 80 percent of children with migraine without aura who failed outpatient treatment responded to IV DHE plus oral metoclopramide [64]. Side effects were minimal but can include nausea and, in some patients, a worsening of their headache.

The use of IV DHE in children usually is restricted to the treatment of protracted migraine that has not responded to other therapies. It is administered in the emergency department or inpatient setting. (See 'Attack severity' above.)

Common side effects of DHE include nausea and anxiety; dyskinesia occurs infrequently. Patients should be pretreated with antiemetic medication (eg, prochlorperazine or metoclopramide) 30 minutes prior to each dose of DHE. With extended use of DHE, antidopaminergic drugs should be avoided and alternate antiemetic agents (eg, ondansetron) used instead.

Intravenous valproate — The utility of IV valproate for the treatment of acute migraine in children is not established, and the existing evidence is limited and retrospective [11,65,66]. As an example, one study evaluated 31 adolescents who were treated with IV valproate (500 to 1000 mg infused at 50 mg/minute) one or more times for acute migraine [65]. Of 48 visits with adequate documentation of pain scores, headache relief considered major (51 to 80 percent pain reduction) or complete (81 to 100 percent pain reduction) was achieved in 47 percent of patients, with no or inadequate relief in 53 percent. The few prospective randomized trials evaluating IV valproate treatment for acute migraine in adults also suggest relatively low efficacy [67-69].

The use of valproic acid and its derivatives for migraine prophylaxis is discussed separately. (See "Preventive treatment of migraine in children", section on 'Valproate'.)

CGRP antagonists — Several oral or intranasal small molecule calcitonin gene-related peptide (CGRP) antagonists are available for the treatment of adults with migraine who are unresponsive to triptan medications. However, the safety and benefit of these agents in children are uncertain and none of these agents are approved for use in children. In addition, cost may be high and is not typically covered by medical insurance. Several clinical trials assessing the safety and efficacy of these agents in children and adolescents are underway [70-72].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Migraine and other primary headache disorders".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Migraines in children (The Basics)" and "Patient education: Headaches in children (The Basics)")

Beyond the Basics topic (see "Patient education: Headache in children (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

General measures for all patients – When migraine symptoms develop, have the child rest or sleep in a dark, quiet room. Educating the child and caregivers about migraine headache is an important aspect of care. A headache calendar can help identify triggering factors, clarify features of the attacks, and document response to treatment. Precipitating factors, if identified, should be managed. (See 'General measures for all patients' above.)

Initial medication selection – Early use of medication during the migraine attack, when the headache pain is still mild, is an important principle of acute migraine treatment. For children and adolescents with treatment-naïve acute migraine attacks, we suggest initial treatment with an analgesic, either acetaminophen or ibuprofen, rather than a triptan (Grade 2C). For migraine attacks that do not respond to one analgesic, it is reasonable to switch to another analgesic or, for older children (age ≥5 years), to a triptan. (See 'Tier 1 (analgesics)' above and 'Acetaminophen' above and 'Ibuprofen' above.)

Medication selection for patients with specific clinical features

Mild attacks – For children and adolescents with acute mild migraine headache, we suggest initial treatment with an analgesic, either acetaminophen or ibuprofen (Grade 2C). (See 'Attack severity' above.)

Severe attacks – For children (age ≥5 years) and adolescents in the ambulatory setting who have moderate to severe migraine attacks or who have acute migraine attacks of any severity that are refractory to analgesics, we suggest treatment with a triptan (Grade 2C). For children who are unable to swallow pills or have early nausea or vomiting, we prefer the orally disintegrating formulations of zolmitriptan and rizatriptan or nasal spray formulations of sumatriptan and zolmitriptan. (See 'Attack severity' above and 'Triptans' above.)

For children who present in emergency or urgent care settings and fail to improve with analgesics, we suggest intravenous (IV) fluid therapy, such as 20 mL/kg of normal saline, given with IV prochlorperazine (0.15 mg/kg to a maximum dose of 10 mg) followed by IV ketorolac (0.5 mg/kg up to a maximum of 30 mg) (Grade 2C). Reasonable alternatives include sumatriptan 3 to 6 mg by subcutaneous injection, metoclopramide 0.2 mg/kg IV to a maximum dose of 10 mg, or dihydroergotamine 0.5 mg IV given over three minutes. (See 'Attack severity' above and 'Antiemetics' above and 'Triptans' above and 'Dihydroergotamine' above.)

Severe nausea and vomiting – For children with acute migraine who have nausea and vomiting, we suggest oral or rectal promethazine in a single dose of 0.25 to 0.5 mg/kg as needed at intervals of four to six hours, in conjunction with analgesic, triptan, or combined acute migraine medication (Grade 2C). (See 'Patients with associated nausea and vomiting' above and 'Antiemetics' above.)

Patients with refractory headaches – For children (age ≥5 years) and adolescents who have acute migraine attacks that are refractory to monotherapy with other analgesics or triptans, we suggest treatment with a triptan taken together with an analgesic medication (eg, a triptan taken with naproxen, or the proprietary combination drug sumatriptan-naproxen) or taken with promethazine (Grade 2C). (See 'Tier 3 (combination)' above and 'Combined sumatriptan and naproxen' above and 'Antiemetics' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Robert P Cruse, DO, who contributed to earlier versions of this topic review.

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Topic 6168 Version 46.0

References

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