Medical Treatment of Migraine in Children and Adolescents

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Medical Treatment of Migraine

The American Academy of Neurology established useful practice guidelines for the management of migraine as follows: • Reduction of headache frequency, severity, duration, and disability • Reduction of reliance on poorly tolerated, ineffective, or unwanted acute pharmacotherapies • Improvement in quality of life • Avoidance of acute headache medication escalation • Education and enabling of patients to manage their disease to enhance personal control of their migraine • Reduction of headache-related distress and psychological symptoms To accomplish these goals, three components need to be incorporated into the treatment plan: (1) An acute treatment strategy should be developed for stopping a headache attack on a consistent basis with return to function as soon as possible, with the goal being 2 hr maximum; (2) a preventive treatment strategy should be considered when the headaches are frequent (one or more per week) and disabling; and (3) biobehavioral therapy should be started, including a discussion of adherence, elimination of barriers to treatment, and healthy habit management.

Acute Treatment

Management of an acute attack is to provide headache freedom as quickly as possible with return to normal function. This mainly includes two groups of medicines: nonsteroidal antiinflammatory drugs (NSAIDs) and triptans. Most migraine headaches in children will respond to appropriate doses of NSAIDs when they are administered at the onset of the headache attack. Ibuprofen has been well documented to be effective at a dose of 7.5-10.0 mg/kg and is often preferred; however, acetaminophen (15 mg/kg) can be effective in those with a contraindication to NSAIDs. Special concern for the use of ibuprofen or other NSAIDs includes ensuring that the children can recognize and respond to onset of the headache. This means discussing with the child the importance of telling the teacher when the headache starts at school and ensuring that proper dosing guidelines and permission have been provided to the school. In addition, overuse needs to be avoided, limiting the NSAID (or any combination of nonprescription analgesics) to not more than 2-3 times per week. The limitation of any analgesic to not more than three headaches a week is necessary to prevent the transformation of the migraines into medication-overuse headaches. If a patient has maximized the weekly allowance of analgesics, the patient's next step is to only use hydrating fluids for the rest of the week as an abortive approach. If ibuprofen is not effective, naproxen sodium also may be tried in similar doses. Aspirin is also a reasonable option but is usually reserved for older children (>16 yr). Use of other NSAIDs has yet to be studied in pediatric migraine. The goal of the primary acute medication should be headache relief within 1 hr with return to function in 10 of 10 headaches. When a migraine is especially severe, NSAIDs alone may not be sufficient. In this case, a triptan may be considered. Multiple studies have demonstrated their effectiveness and tolerability. There are currently three triptans that are approved by the United States (U.S.) Food and Drug Administration (FDA) for the treatment of episodic migraine in the pediatric population. Almotriptan is approved for the treatment of acute migraine in adolescents (ages 12-17 yr). Rizatriptan is approved for the treatment of migraine in children as young as age 6 yr. The intranasal formulation of zolmitriptan was recently approved by the FDA in the United States for use in children ages 12 and over. Several studies have shown it to provide rapid and effective relief, and it has been demonstrated to be well tolerated for treatment of acute migraine in patients 12 yr and older. Zolmitriptan nasal spray may be of particular benefit to those with nausea and in patients who have difficulty swallowing tablets. The combination of naproxen sodium and sumatriptan has been studied and may be effective in children. Controlled clinical trials demonstrate that intranasal sumatriptan is safe and effective in children older than age 8 yr with moderate to severe migraine. At present, pediatric studies showing the effectiveness of oral sumatriptan are lacking, and there is insufficient evidence to support the use of subcutaneous sumatriptan in children. For most adolescents, dosing is the same as for adults; a reduction in dose is made for children weighing less than 40 kg. The triptans vary by rapidity of onset and biologic half-life. This is related to both their variable lipophilicity and dose. Clinically, 60–70% of patients respond to the first triptan tried, with 60–70% of the patients who did not respond to the first triptan responding to the next triptan. Therefore, in the patient who does not respond to the first triptan in the desired way (rapid reproducible response without relapse or side effects), it is worthwhile to try a different triptan. The most common side effects of the triptans are caused by their mechanism of action—tightness in the jaw, chest, and fingers as a result of vascular constriction and a subsequent feeling of grogginess and fatigue from the central serotonin effect. The vascular constriction symptoms can be alleviated through adequate fluid hydration during an attack. The most effective way to administer acute treatment is with the recognition that NSAIDs and triptans have different mechanisms of action. NSAIDs are used for all headaches, mild to severe, with their use being restricted to fewer than two to three attacks per week; the triptans are added for moderate to severe headaches, with their use being restricted to not more than four to six attacks per month. For an acute attack, the NSAIDs can be repeated once in 3-4 hr, if needed for that specific attack, and the triptans can be repeated once in 2 hr if needed. It is important to consider the various formulations available, and these options should be discussed with pediatric patients and their parents, especially if a child is unable to swallow pills or take an oral dose because of nausea. Because vascular dilation is a common feature of migraine that may be responsible for some of the facial flushing, followed by paleness and the lightheaded feeling accompanying the attacks, fluid hydration should be integrated into the acute treatment plan. For oral hydration, this can include the sports drinks that combine electrolytes and sugar to provide the intravascular rehydration. Antiemetics were used for acute treatment of the nausea and vomiting. Further study has identified that their unique mechanism of effectiveness in headache treatment is related to their antagonism of dopaminergic neurotransmission. Therefore, the antiemetics with the most robust dopamine antagonism (i.e., prochlorperazine and metoclopramide) have the best efficacy. These can be very effective for status migrainosus or a migraine that is unresponsive to the NSAIDs and triptans. They require intravenous administration because other forms of administration of these drugs are less effective than the NSAIDs or triptans. When combined with ketorolac and intravenous fluids in the emergency department or an acute infusion center, intravenous antiemetics can be very effective. When they are not effective, further inpatient treatment may be required using dihydroergotamine (DHE), which will mean an admission to an inpatient unit for more aggressive therapy of an intractable attack.

Emergency Department Treatments for Intractable Headaches

When an acute migraine attack does not respond to the recommended outpatient regimen and the headache is disabling, more aggressive therapeutic approaches are available and may be necessary to prevent further increase in the duration as well as the frequency of headaches. These migraines fall into the classification of status migrainosus and patients may need to be referred to an infusion center, the emergency room, or an inpatient unit. Available specific treatments for migraine headache in an emergency room setting include the following: antidopaminergic medications such as prochlorperazine and metoclopramide; NSAIDs such as ketorolac; vasoconstrictor medications such as DHE; and antiepileptic drugs such as sodium valproate.

Antidopaminergic Drugs: Prochlorperazine and Metoclopramide

The use of antidopaminergic medications is not limited to controlling the nausea and vomiting often present during a migraine headache. Their potential pharmacologic effect may be a result of their antidopamine property and the underlying pathologic process involving the dopaminergic system during a migraine attack. Prochlorperazine is very effective in aborting an attack in the emergency room when given intravenously with a bolus of intravenous fluid. Results show a 75% improvement with 50% headache freedom at 1 hr and 95% improvement with 60% headache freedom at 3 hr. Prochlorperazine may be more effective than metoclopramide. The average dose of metoclopramide is 0.13-0.15 mg/kg, with a maximum dose of 10 mg given intravenously over 15 min. The average dose of prochlorperazine is 0.15 mg/kg, with a maximum dose of 10 mg. These medications are usually well-tolerated, but extrapyramidal reactions are more frequent in children than older persons. An acute extrapyramidal reaction can be controlled in the emergency room with 25-50 mg of diphenhydramine given intravenously. There is no need for premedication with diphenhydramine to prevent side effects. Diphenhydramine should only be used if needed when side effects are present.

Nonsteroidal Antiinflammatory Drugs: Ketorolac

It is known that an aseptic inflammation occurs in the central nervous system as a result of the effect of multiple reactive peptides in patients with migraines. Ketorolac is often used in the emergency department as monotherapy for a migraine attack or in combination with other drugs. In monotherapy, the response to ketorolac is 55.2% improvement. When the ketorolac is combined with prochlorperazine, the response rate jumps to 93%.

Antiepileptic Drugs: Sodium Valproate

Antiepileptic drugs have been used as prophylactic treatment for migraine headache for years with adequate double-blinded, controlled studies on their efficacy in adults. The mechanism in which sodium valproate acutely aborts migraine headaches is not well understood. Sodium valproate is given as a bolus of 15-20 mg/kg push (over 10 min). This intravenous load is followed by an oral dose (15-20 mg/day) in the 4 hr after the injection. Patients may benefit from a short-term preventive treatment with an extended-release form after discharge from the emergency room. Sodium valproate is usually well tolerated. Patients should be receiving a fluid load during the procedure to prevent a possible hypotensive episode.

Triptans

Subcutaneous sumatriptan (0.06 mg/kg) has an overall efficacy of 72% at 30 min and 78% at 2 hr, with a recurrence rate of 6%. Because children tend to have a shorter duration of headache, a recurrence rate of 6% would seem appropriate for this population. DHE, if recommended for the recurrences, should not be given in the 24 hr after triptan use. Triptans are contraindicated in patients treated with ergotamine within 24 hr and within 2 wk of treatment with monoamine oxidase inhibitors. Triptans may rarely produce a serotonin syndrome in patients taking a serotonin receptor reuptake inhibitor. Both triptans and ergotamine are contraindicated in hemiplegic migraines.

Dihydroergotamine (DHE)

DHE is an old migraine medication used as a vasoconstrictor to abort the vascular phase of migraine headache. The effectiveness is discussed in detail in the section Inpatient Management of Intractable Migraine and Status Migrainosus, below. One dose of DHE can be effective for abortive treatment in the emergency department. Emergency room treatment of migraine shows a recurrence rate of 29% at 48-72 hr, with 6% of patients needing even more aggressive therapy in an inpatient unit.

Inpatient Management of Intractable Migraine and Status Migrainosus

Six to 7% of patients fail acute treatment in the emergency department. These patients are usually admitted for 3-5 days and receive extensive parenteral treatment. A child should be admitted to the hospital for a primary headache when the child is in status migrainosus, has an exacerbation of a chronic severe headache, or has an analgesic overuse headache with an acute exacerbation. The goal of inpatient treatment is to control a headache that has been unresponsive to other abortive therapy and is disabling to the child. Treatment protocols include the use of DHE, antiemetics, sodium valproate, and other drugs.

Dihydroergotamine

Ergots are one of the oldest treatments for migraine headache. DHE is a parenteral form used for acute exacerbations. Its effect stems from the 5HT1A-1B- 1D-1F receptor agonist affinity and central vasoconstriction. DHE has a greater α- adrenergic antagonist activity and is less vasoconstrictive peripherally. Before initiation of an intravenous ergot protocol, a full history should be obtained and a neurologic examination performed. Females of childbearing age should be evaluated for pregnancy before ergots are administered. The DHE protocol consists of the following: Patients are premedicated with 0.13-0.15 mg/kg of prochlorperazine 30 min prior to the DHE dose (maximum of three prochlorperazine doses to prevent extrapyramidal syndrome; after 3 doses of prochlorperazine a non-dopamine antagonist antiemetic should be used, such as ondansetron). A dose of 0.5-1.0 mg of DHE is used (depending on age and tolerability) every 8 hr until headache freedom. The first dose should be divided into two half doses separated by 30 min; they are considered test doses. When the headache ceases, an extra dose is given in an attempt to prevent recurrence after discharge. The response to this protocol is a 97% improvement and 77% headache freedom. The response is noticeable by the fifth dose; the drug can reach its maximum effects after the tenth dose. Side effects of DHE include nausea, vomiting, abdominal discomfort, a flushed face, and increased blood pressure. The maximum dose used in this protocol is 15 mg total of DHE.

Sodium Valproate

Sodium valproate is used when DHE is contraindicated or has been ineffective. One adult study recommends the use of valproate sodium as follows: Bolus with 15 mg/kg (maximum of 1,000 mg), followed by 5 mg/kg every 8 hr until headache freedom or up to a maximum of ten doses. Always give an extra dose after headache ceases. This protocol was studied in adults with chronic daily headaches and showed an 80% improvement. It is well tolerated and is useful in children when DHE is ineffective, contraindicated, or not tolerated.

Other Inpatient Therapies

During an inpatient admission for status migrainosus, we highly recommend that other services, such as behavioral medicine and holistic medicine, become involved if they are available. The behavioral medicine staff can play a major role in talking to patients about their specific triggers and can also evaluate school, as well as home and social, stressors. The staff would also initiate some coping skills during the admission and evaluate the necessity for further outpatient follow-up for cognitive behavioral therapy, biofeedback, or treatment for other comorbidities. The holistic medicine staff, when consulted, can offer holistic approaches to pain control, including relaxation techniques, as well as medical massage and craniosacral therapy.

Medical Treatment of Migraine in Children and Adolescents