US Pharm. 2014;39(3):56-60.

ABSTRACT: Migraines are common in the pediatric population, but they are often overlooked or misdiagnosed. Children can exhibit a variable array of symptoms that are atypical of the symptoms that occur with adult migraines. Nonpharmacologic strategies, such as rest and sleep, are the preferred therapies for mild-to-moderate migraines in children. Numerous classes of drugs are available to treat acute migraine attacks. Prophylactic therapy is recommended for children whose migraines are frequent and severe. Pharmacists can provide guidance on product selection and counsel parents and adolescents on the proper use, dosing, and side effects of medications in order to maximize the effectiveness of these treatments.

Migraines are chronic headaches that occur in individuals of all ages. Symptoms associated with migraine can vary in severity and duration, making it difficult for the patient to identify the appropriate treatment. In children, the identification of migraines can be particularly problematic, since symptoms can present in a variety of ways that differ considerably from those occurring in adults with migraines. Children may have difficulty expressing the location and extent of the pain caused by the migraine. Over time, a clearer understanding of migraine etiology has developed, and parents are now better equipped to care for their child’s chronic disorder. It is common for parents whose child is in pain to try nonprescription treatments before seeking professional support. Pharmacists, as the most accessible health specialists, have a unique opportunity to assist parents by identifying possible migraine indicators and assisting in the formulation of a suitable treatment plan for the child.

EPIDEMIOLOGY

Migraine occurs frequently in the pediatric population. Prevalence differs among age groups, but increases with age. The prevalence of migraines in children aged 2 to 7 years is 3%; prevalence in those aged 7 to 11 years is 4% to 11%; and that in individuals aged 11 to 21 years is 8% to 23%. Migraine onset typically occurs at an earlier age in boys than in girls, at 7.2 years and 10.9 years, respectively. At the onset of puberty, girls are three times more likely than boys to have migraines. It is estimated that about one-fourth of children suffering from migraines will no longer have symptoms at age 25 years.¹

Headaches, one of the top five health problems in children, rank third in emergency room visits.¹ The prevalence of migraine has been increasing recently, owing in part to improved diagnostic procedures.^2,3 With the rising prevalence in the pediatric population comes a growing concern about the physical pain and psychological effects experienced by children, especially when the migraines go untreated.

ETIOLOGY

The basic mechanism behind migraine involves profound sympathetic nervous system activation and subsequent overcompensation, with dilation of extracranial and intracranial arteries.⁴ The pain associated with migraine can be attributed to the magnitude of arterial dilation. Migraines can be triggered by a variety of environmental, psychological, and physiological factors (TABLE 1). Environmental triggers, examples of which include lighting, strong odors, high altitude, and quick changes in ambient temperature, may be the most easily addressed and modified. Psychological triggers, while important catalysts, may be more difficult to avoid. Depression, stress, and anxiety are all factors that can incur headaches. Lastly, physiological triggers also can contribute to migraines, but are often overlooked. These include fatigue, travel, illness, lack of sleep, and skipping a meal.⁵

CLINICAL PRESENTATION AND DIAGNOSIS

The diagnosis of migraine in children is difficult because of the variability of symptoms children may exhibit during an attack. In general, migraines are characterized by severe, pulsating headaches located in the temple area. Migraines in younger children manifest in a bilateral fashion, concentrated in the frontal or temporal regions. In contrast, older children usually exhibit unilateral headaches located in the temporal area. Migraines in all pediatric age groups can occur with or without aura; however, migraine with aura presents in only 20% of children.⁵

There are several indicators of aura, although children often have difficulty identifying and expressing the sensations they feel during these occurrences. The most common type of aura in children is visual aura, which has been described as the appearance of zigzag lines, size distortion, blurry vision, black dots, and kaleidoscopic color patterns. Other types of aura include dizziness, attention deficit, confusion, one-sided body weakness, loss of coordination, and agitation. The aura typically appears 30 minutes before the headache begins and lasts up to 20 minutes.⁵

Migraine headaches in children typically last less than 4 hours, but can range anywhere from 10 minutes to 72 hours.^2,5 Following the throbbing headache, the child may experience either a boost of energy or a bout of exhaustion that can last up to several days.

Migraine symptoms in children include nausea, vomiting, abdominal cramps, sleep disorders, hypersomnia, and sensitivity to light and sound. Sleep disturbances due to migraine can decrease total sleep time, delay sleep onset, increase nighttime awakenings, and heighten daytime sleepiness (P <.0001).⁶ Frequently, parents do not realize that a child is experiencing a migraine because the wide variety of symptoms makes it difficult to recognize that they signal a migraine attack. Consequently, migraines often go unnoticed and untreated, with a direct effect on a child’s quality of life.

In studies using the Pediatric Migraine Disability Assessment questionnaire, quality-of-life scores in children with migraines were comparable to those in children with cancer or rheumatoid conditions.⁷ Children with migraines had higher social and physical operational levels than children with cancer and other conditions, but lower emotional and school-functioning levels.⁷ The unpredictability of migraines, which can interrupt a child’s school schedule, may contribute to the self-reports of lower school-functioning levels.

The diagnosis of migraine in children is accomplished primarily by obtaining a patient’s medical history and performing a physical examination while applying clinical judgment. Clinical judgment also plays a role in determining the necessity of additional laboratory evaluations, such as imaging studies. Radiologic tests are not typically performed unless the patient has head trauma, a history of seizures, or substantial instability of headaches.⁵

Migraine classification is contingent upon the frequency of attacks and the symptoms present. Migraines can be identified as either acute or chronic. Migraines occurring up to 14 times a month are categorized as acute episodic, whereas those occurring 15 or more times a month are considered chronic. Chronic migraines generally persist for three consecutive months and account for approximately 60% of migraine cases.⁵

Some types of migraine present differently from typical migraines. Migraine-associated cyclic vomiting syndrome includes abdominal pain, nausea, retching, photophobia, phonophobia, and headache.⁵ Cyclic vomiting, which may resolve by adulthood, can cause severe fluid and electrolyte imbalances and warrants vigorous treatment.

There are also several less common categories of migraine. Acute confusional migraine occurs after head trauma and includes periods of amnesia, confusion, and dysphagia. This type of migraine usually lasts only a few hours, but children may experience persistent episodes.⁵ Acephalgic migraine is classified as aura without the headache. These visual disturbances occur more frequently in girls and commonly include a family history of migraine.⁵

Certain types of migraine do not present with a headache. Abdominal migraine occurs in 1% to 4% of children, with onset at approximately age 7 to 12 years.⁸ This type of migraine, which is more common in girls, consists of acute episodes of abdominal pain followed by severe periumbilical pain that lasts for an hour or more. Abdominal migraines are often overlooked or misdiagnosed by parents, since the child does not usually experience headache as part of the migraine.

TREATMENT

Nonpharmacologic

For children with occasional mild migraines, nonpharmacologic treatment strategies are preferred and offer the advantage of avoiding side effects. These methods include sleep, biofeedback, relaxation techniques, and avoidance of all types of triggers (TABLE 1). Sleep and rest are simple, effective ways to alleviate the pain of acute migraine headaches. The child should have a quiet, dark, and cool environment in which to lie down and sleep.⁹

Relaxation techniques such as self-hypnosis and abdominal breathing exercises are helpful for aborting headaches. Thermal biofeedback, another alternative to medication therapy, involves raising the temperature of a body part, such as a finger, with confirmation from a thermometer.⁹ These methods are believed to impede the preliminary sympathetic activation that begins the migraine process.⁴ Additionally, the autonomic system is “trained” to be less reactive.⁴

Research has suggested that nonpharmacologic treatment can be effective in children, although results vary from person to person.^4,9 These strategies can be implemented before or in combination with medication therapy.

Pharmacologic

Although nonpharmacologic methods can help reduce migraine frequency, medication still may be necessary to alleviate discomfort. The two main treatment approaches are symptomatic (abortive) therapy (TABLE 2) and prophylactic therapy. Because a number of drugs are off-label for use in treating migraines in children and adolescents and their safety and efficacy have not been established, most  dosages listed in TABLE 2 are based on recommendations found in the literature. There is not clear agreement on which drugs and dosages should be used in this population.

Symptomatic treatment centers on providing rapid relief. The mainstay of treatment for acute migraine  involves the use of analgesics, anti-inflammatories, and antiemetics.

Nonprescription Treatment: Nonprescription medications such as ibuprofen and acetaminophen are commonly used as first-line treatment since they are proven safe and generally effective in the treatment of headache. Ibuprofen, the analgesic of choice, is effective in many children, including those with episodic or chronic tension-type headaches, and it has been found to be more effective than acetaminophen for treating migraine. Acetaminophen is usually recommended for children with episodic or chronic tension-type headaches. Naproxen sodium is another nonprescription anti-inflammatory medication that has been shown to be effective for acute treatment of migraine, although safety and efficacy in children and adolescents have not been established. Safety is always a concern, especially with medication use in young children.² Aspirin is not commonly used to treat migraines in children because it has been associated with Reye syndrome when given to those with viral infections.³

The pharmacist should counsel the parent or patient that excessive use of prescription and nonprescription analgesics can cause rebound headaches. To prevent rebound headaches, treatment should be limited to the lowest dosage and the minimum frequency that will provide effective relief.¹⁰ Parents should also be advised that if the headache does not subside or is unbearable, medical attention should be sought.

Prescription Treatment: If insufficient relief is obtained from nonprescription therapies, prescription medication may be required. Several classes of prescription drugs are used for children with migraines: 5-hydroxytryptamine 1 (5-HT1) agonists (triptans), dopamine antagonists, and dihydroergotamine.

Triptans are serotonin agonists that specifically target migraines. They are considered safe and effective, although the FDA has not yet identified exact safe and effective dosages for children under the age of 12. Clinical trials indicate that almotriptan 12.5 mg is an optimal dosage and is more effective than placebo for acute migraine relief. Rizatriptan may be used for acute treatment of migraines, with evidence supporting its effectiveness in children aged 6 years and older. Rizatriptan appears to be well tolerated in children and displays adverse effects that are similar to those in adults. Currently, however, almotriptan is the only triptan FDA-approved to treat pediatric migraine (in patients aged 12 years and older). The main adverse effects with oral triptan use are nausea, fatigue, drowsiness, and dry mouth.³

Triptans are available in other formulations, such as oral disintegrating tablets and nasal sprays. These formulations may be useful if treatment with oral agents is not feasible owing to nausea, risk of choking, or difficulty swallowing. Sumatriptan nasal spray has been found effective for treatment of moderate-to-severe migraines and has the advantage of a quicker onset of action compared with oral tablets.¹¹ Taste alteration is the most common side effect reported for nasal sumatriptan.³ In one study, sumatriptan nasal spray was effective in children and adolescents who experienced multiple headaches.¹¹ Parents and adolescents should be counseled to avoid using triptans for more than six headaches per month.¹¹

Dihydroergotamine is usually reserved for patients who have already failed other treatments. Although the FDA-approved dosage is limited to a second dose in 1 hour, children should experience an improvement in migraine symptoms after about five doses, and the regimen should be continued until the headache dissipates, up to a maximum of 20 doses.³ The harsh side-effect profile of dihydroergotamines (i.e., nausea, vomiting, hypertension, anxiety) can be problematic for many children and adolescents, however.³

In addition to headache, nausea and vomiting are often associated with migraines. Dopamine antagonists have demonstrated efficacy in treating migraine-associated nausea and vomiting in the pediatric population. Two of the most common dopamine antagonists used for migraines are metoclopramide and prochlorperazine. Prochlorperazine is more effective than metoclopramide in reducing nausea and vomiting in acute migraine.³ Extrapyramidal side effects, such as involuntary movements, uncontrollable speech, and severe restlessness, are the main concerns with dopamine antagonists.

PROPHYLAXIS

Children who experience frequent migraines (>3 per month) or severe, persistent migraine attacks (especially >2 hours in duration) and have failed to respond to abortive therapy are candidates for prophylactic therapy, the goal of which is to lessen the frequency and severity of the headaches.⁵ This is accomplished by having the child take a prophylactic medication daily without regard to migraine manifestations. Although several classes of medications are used for prophylactic treatment, there are currently no first-line agents preferred. Therapy is selected after the comorbidities and adverse-effect profiles of potential treatments have been considered. The only three medications found to be more effective than placebo in reducing episodic migraines are propranolol, trazodone, and topiramate.^12,13 Other medications used for prophylactic treatment include clonidine, amitriptyline (especially for migraine associated with anxiety, depression, and sleep disorders), cyproheptadine, divalproex sodium (although weight gain in adolescents can affect adherence), metoprolol, and magnesium oxide.¹³ Cyproheptadine is a safe first-line agent for children younger than 10 years.

PHARMACIST INVOLVEMENT

Since nonprescription drugs may be the starting point for pharmacologic treatment, pharmacists must be knowledgeable about the causes of and treatments for migraine in children. Pharmacists can educate parents and caregivers about key migraine triggers and advise avoidance of patient-specific indicators. This process may help reduce the frequency of migraine attacks in children. Pharmacists can also provide guidance on product selection and counsel parents and adolescents on the proper use, dosing, and side effects of nonprescription medications in order to maximize treatment effectiveness. This includes information on rebound headaches. When a patient receives prescription therapy, the pharmacist should monitor the patient’s pattern of medication use to ensure adequate symptom control without overuse of the medication. Lastly, it is important for pharmacists to counsel parents and patients on possible adverse reactions and assist in getting the medication changed if the side effects are unbearable. TABLE 3 lists resources for migraine in children.

CONCLUSION

Many treatments are available for children who suffer from migraines. It is common for children to experience the pain of a migraine without being able to express the symptoms clearly. Parents may have trouble interpreting their child’s symptoms, since the symptoms can differ from those for typical adult migraines and may mimic other childhood disorders. A variety of nonprescription and prescription medications are available for treatment. Pharmacists have the opportunity to ensure that children receive not only effective treatment, but also safe treatment that can be adjusted based upon disease progression or regression.

REFERENCES

1. Eiland LS, Hunt MO. The use of triptans for pediatric migraines. Paediatr Drugs. 2010;12:379-389.
2. Rosenblum RK, Fisher PG. A guide to children with acute and chronic headaches. J Pediatr Health Care. 2001;15:229-235.
3. O’Brien HL, Kabbouche MA, Hershey AD. Treatment of acute migraine in the pediatric population. Curr Treat Options Neurol. 2010;12:178-185.
4. Borins M. Biofeedback, relaxation techniques and attitudinal changes in adolescents with migraines: a feasibility study. Can Fam Physician. 1987;33:417-421.
5. Mack KJ. Episodic and chronic migraine in children. Semin Neurol. 2006;26:223-231.
6. Esposito M, Roccella M, Parisi L, et al. Hypersomnia in children affected by migraine without aura: a questionnaire-based case-control study. Neuropsychiatr Dis Treat. 2013;3:289-294.
7. Powers SW, Patton SR, Hommel KA, Hershey AD. Quality of life in childhood migraines: clinical impact and comparison to other chronic illnesses. Pediatrics. 2003;112:e1-e5.
8. Popovich DM, Schentrup DM, McAlhany AL. Recognizing and diagnosing abdominal migraines. J Pediatr Health Care. 2010;24:372-377.
9. Baumann RJ. Behavioral treatment of migraine in children and adolescents. Paediatr Drugs. 2002;4:555-561.
10. Cleveland Clinic. Rebound headaches. http://my.clevelandclinic.org/disorders/headaches/hic_rebound_headaches.aspx. Accessed January 17, 2014.
11. Hershey AD, Powers SW, LeCates S, Bentti AL. Effectiveness of nasal sumatriptan in 5- to 12-year-old children. Headache. 2001;41:693-697.
12. El-Chammas K, Keyes J, Thompson N, et al. Pharmacologic treatment of pediatric headaches: a meta-analysis. JAMA Pediatr. 2013;167:250-258.
13. Agency for Healthcare Research and Quality. Migraine in children: preventive pharmacologic treatments. Executive summary. Comparative Effectiveness Review. June 2013. AHRQ Publication No. 13-EHC065-EF.

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