Pediatric and Adolescent Migraine: Update on Treatment Options

September 8, 2017

If the goal of headache therapy for adolescent migraineurs is a pain-free adult life, here's a road map.

[[{"type":"media","view_mode":"media_crop","fid":"63140","attributes":{"alt":"","class":"media-image media-image-right","id":"media_crop_8210064788622","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"8052","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"height: 282px; width: 300px; float: right;","title":"©Lightspring/Shutterstock.com","typeof":"foaf:Image"}}]]If headaches are one of mankind’s most prevalent and impactful infirmities-it is estimated that 1 out of 2 people worldwide has had a headache in the past year-then the sheer number of children and adolescents affected by headaches must be absolutely jaw dropping. As of July 2016, an astonishing 33% of the world’s population was younger than age 19.1 This translates into nearly 2.5 billion children who must suffer what many adults consider to be excruciating episodes of pain and debility often lasting hours or days.

Indeed, Bille and colleagues2 concluded that as many as 75% of children experience a significant headache by age 15, and that 28% of these headaches fulfill the International Classification of Headache Disorders 2 (ICHD2) criteria for migraine headaches.3,4 Affected children can be on a collision course with a number of comorbid conditions, such as depression and anxiety, as well as compromised interpersonal relationships with family and friends. Children who suffer from headaches often withdraw from social groups and activities-likely, in part, from their fear of being stricken with “the next big headache.”5 Their cephalalgic condition can follow them into adulthood, when they may experience major difficulties coping with a chronic unrelenting sickness from which there appears to be no escape.

In this article, I will cover some of the more common and successful pharmacological options available to the pediatric and adolescent migraine populations-especially for those aged 15 and older.

First: Therapeutic Goals


 

THERAPEUTIC GOALS

One of the most immediate goals in migraine therapy for the pediatric population is to return each affected child to normal activities as quickly as possible while keeping an eye on the child’s predisposition and tendency to relapse (episodic headaches). If a child has frequent headaches (usually greater than 1 to 2 episodes biweekly), then a prophylactic strategy must be considered.

No physician relishes the thought of placing an adolescent on daily medication. But it is entirely appropriate and necessary to recognize when headaches are truly episodic and when they have-or are ready to-burst into the next most detrimental level of frequency, when they often transition to chronic headaches. No specific number of headaches clearly defines a point at which prophylactic therapy should be instituted. Adult thresholds that warrant prevention tend to be slightly greater (ie, 1 to 2 severe headaches weekly) than those for children.

No physician relishes the thought of placing an adolescent on daily medication.

Although a discussion of biobehavioral or cognitive behavioral modifications is beyond the scope of this article, suffice it to say that this important intervention for episodic or chronic headaches should be considered in every patient. Once the decision has been made as to whether a child should receive either episodic or prophylactic therapy, then the work of addressing lifestyle, nutritional, and exercise as well as how to integrate these changes into a child’s neurocognitive and neurobehavioral domains must be undertaken as soon as possible.

A detailed treatise of the Headache Diary is for another day’s discussion. I emphasize, however, that it is one of the most reliable and effective tools with which to teach an adolescent or teenager how to quickly and accurately identify headaches such as migraines. We spend significant time in our clinic teaching patients the importance of bringing an updated and accurate diary with them to each visit. We believe it is the clinician’s obligation to review this log and identify problems a young patient may have with filling in its parameters, such as start and stop times, potential triggers, associated symptoms, and sleep habits.

Next: Abortive Therapies



 

ABORTIVE THERAPIES

Successful abortive therapeutics rely on a patient (or parent’s) ability to recognize when a migraine attack is imminent or in progress. Timing of administration of these abortive medications can make the difference between success and failure.6

The following medications are commonly used as first-line agents when treating migraine headaches in the adolescent age group (Table 1):

Table 1. Acute migraine therapy options for pediatric patients

Drug classCaveats
NSAIDSRisk of medication overuse headache
Aspirin, in migraine-specific formulationsCaffeine combination for improved efficacy. Caution for Reye syndrome.
AcetaminophenNo more than

FDA approved: rizatriptan, almotriptan, zolmitriptan nasal spray, naproxen sodium/sumatriptan

NSAIDs (ibuprofen, naproxen, diclofenac) Pediatric dosing guidelines in the 15 and older age group on a mg/kg scale tend not to be strictly adhered to, and dosages commonly suggested are those for adults. Labeled instructions are typically adequate when it comes to initial recommendations; however, care should be taken to instruct patients to take these medications with food or beverage, and there should be a strict limit on frequency of use. Standards of abortive therapy generally call for no more than 2-3 treatment regimens/week with no more than 2 doses within a 24-hour period. Doses higher than 400-600mg per administration may be considered, but benefits must be weighed against risks.

One of the most common complications associated with these medications (aside from the side effect profile itself) is medication overuse headache (MOH). This should be avoided at all cost. Patients and parents should be thoroughly educated and invested in preventing excessive use of abortive medications, which can result in additional burdens of headache according to current ICHD standards.3

Aspirin, in migraine-specific formulations, is generally well-tolerated and efficacious, when taken according to labeling instructions. In general, however, 1-2 tablets of brand name or generic varieties can be taken with the intent of clearing the headache completely over a maximum 2-hour limit. It is acceptable to repeat the dose of 1-2 tablets within 60 to 90 minutes if the headache has not entirely subsided. In our practice, we reserve aspirin as a second or third tier agent from the NSAID family in order to lower the risk of aspirin-induced Reye syndrome. When taken with caffeine, there appears to be enhancement of the cyclooxygenase (COX enzyme) inhibitory effects believed to halt inflammatory processes surrounding meningeal blood vessels, thereby reducing pain and associated symptoms.

Acetaminophen was tested in head-to-head trials and found to be inferior to ibuprofen at both the 60 and 120-minute mark in terms of pain-free relief. However, it was superior to placebo at the 2-hour mark.7

Acetaminophen was . . .found to be inferior to ibuprofen in terms of pain-free relief. However, it was superior to placebo at the 2-hour mark.

We commonly recommend 1 gram per dose for a migraine attack and repeat this regimen in 60-90 minutes if headache and all associated symptoms have not fully vanished. Newer dosing guidelines now call for a total daily reduction in acetaminophen from 4g to 3g (package labeling). We limit pediatric and adolescent migraineurs to a maximum of 2g (in divided doses) per 24 hours and restrict the number of dosing administrations to no more than 2-3/week depending upon clinical circumstances.

Triptans have become significantly more available to pediatric patients than when they were first marketed owing to the number of studies performed since the first trials and the FDA approval of sumatriptan. Here are the currently approved triptans for use in patients under age 18:

   ► Rizatriptan (ages 6-17)

  ► Almotriptan (ages 12+)

  ► Zolmitriptan nasal spray (ages 12+)

  ► Naproxen sodium/sumatriptan (ages 12+)

In the pediatric population, exclusion criteria are typically the same as those for the adult population. These include coronary ischemic syndromes, TIAs, hemiplegic/basilar migraines, ischemic bowel syndromes, and uncontrolled hypertension. Patients with these or other important conditions should not take a triptan unless benefits clearly outweigh risks. And even then, our clinic tends to use test doses at half recommended administration to observe effects before titrating to a full adult dose.

Our clinic tends to use test doses [of triptans] at half recommended administration to observe effects before titrating to a full adult dose.

Next: Prophylactic Therapy


 

PROPHYLACTIC THERAPY

When headache frequency in the pediatric/adolescent population exceeds 3 to 4 episodes/month, then preventative or prophylactic therapy should be strongly considered. This requires medications that must be taken daily and compliantly to have the best odds at noticeable improvements in either frequency reduction, symptom reduction, or both.

As noted earlier, a Headache Diary is one of the most helpful tools a teenager can be encouraged to keep. It can guide the clinician’s choice toward the most effective, and safest therapy.

If a period of time-generally 3 to 4 weeks-has elapsed without any significant improvements, then consideration must be given to changing the regimen (eg, a new drug, new dosing, adding adjunct). The following medications are commonly used in this population (Table 2):

Table 2. Prophylactic migraine therapy options for pediatric patients

Drug classCaveats
Beta blockersPropranolol may be most efficacious; best dosed as TID or QID regimen
Anti-epilepticsTopiramate (gold standard)
Tricyclic antidepressantsAmitryptyline is prototycial drug from the class; anticholinergic side effects, eg, dry mouth/eyes, dizziness, limit their use.

Not FDA approved for <18 years; may use for chronic migraines when benefits outweight risks

 

Beta blockers (propranolol, metoprolol, atenolol, timolol, nadolol) have been widely used for migraine prophylaxis in adults but are limited in children, and data are limited regarding their absolute efficacy.8

They can exacerbate and even precipitate exercise-induced asthma, can cause somnolence, hypotension, dizziness, and pre-syncope, and can also contribute to depressive mood symptoms.

Propranolol, nadolol, and metopropol are at least 3 options to consider in the pediatric population.9 From an efficacy perspective, we have seen the most success from propranolol. Titration of propranolol should be done slowly, starting at 10mg. Daily and over 6 to 8 weeks, the dosage should be incrementally raised such that the patient will be taking the drug at least three times daily or even as often as four times a day. Once-daily preparations have poor efficacy and should not be substituted because of convenience for more efficacious multi-dosing regimens.

Anti-epileptics(AEDs) such as topiramate and valproic acid (VPA) are approved for adult migraine prophylaxis and can be used successfully to treat pediatric/adolescent migraines. Dosing is generally that of adults’, where increments of either 125mg or 250mg in a TID or QID regimen are targeted over a 3 to 4-week period. 

VPA possesses the unhappy side effect of causing weight gain. Patients and parents should be warned of this possibility and counseled about the need for more daily exercise or for other nutritional activities/restrictions. This can help avoid distress over increases in weight, which can then potentially trigger noncompliance and lead to other health concerns, such as obesity and its related comorbidities.

Tricyclic antidepressants (TCAs) such as amitriptyline-the most widely used and prototypical drug from the class-are quite effective in reducing headaches aggressively and relatively quickly. However, their anticholinergic side effects, including as dry eyes, dizziness, reduced gastric emptying, vague abdominal discomfort, and especially dry mouth, limit their use.

We have found nortriptyline to be as effective as amitriptyline in reducing headache frequency and, in some cases, intensity with a more tolerable side effect profile.

TCAs are also titrated slowly, on the basis of no more than 10mg weekly. Dosing is strictly nocturnal and escalated generally to a maximum daily dose of 50mg. We have achieved doses as high as 150-200mg/d, which are tolerated by many patients if titrated and monitored carefully.

BOTOX is currently not approved for use in patients under age 18. For patients with chronic migraines (15 or more headaches/month), however, it is possible to offer BOTOX off-label to patients when benefits outweigh risks.10 Conditions that rule out this option are those that could result in complications such as breathing disorders (asthma), UTI, or local infection in the areas where injections are to be given.

It is possible to offer BOTOX off-label to patients [under age 18] when benefits outweigh risks.

Because BOTOX now carries a black box warning, it is always considered prudent to get written parental/guardian permission to administer the drug and to explicitly explain the risks associated with respiratory complications (especially if giving higher numbers of units to the patient (>100u in one sitting).

In our practice, when injecting BOTOX into adolescents we are partial to finding the minimum number of injection sites necessary to control symptoms. Therefore, we start the process by staging the first set of injections to include no more than the frontalis and/or temporalis muscles bilaterally (typically 9 to 17 injection sites). We observe the patient in the office for 15 to 30 minutes after the injections (offering a cold pack for the face if minor swelling were to occur. And we have the patient return in 4 weeks for a posterior head and neck set of injections if needed. At that time, we apply BOTOX into the occipitalis, paracervical, and trapezius muscles or some combination thereof, depending on the patient and how they reacted to the previous set of injections.

THE BOTTOM LINE

The foregoing is offered in the hopes that clinicians recognize the unquestionably important role they play in accurately identifying both at-risk patients as well as those who suffer from pediatric/adolescent migraine headaches and how to offer treatment options that truly work. The pharmacological options presented here are not exhaustive, but rather the most common and efficacious.

Migraines are extremely painful and debilitating. We should not allow young patients to evolve alongside their headaches with the mistaken belief that there is no better treatment for their condition than simple OTC medications, ice packs on their heads, or sleeping in a dark, quiet room for half a day or more. We want to encourage our children to share their pains and symptoms and to become part of a proactive health care team whose mission is to bring their physical ailment under control, give it a name, and potentially find its underlying cause(s). We want them to learn the utility of scrutinizing their bodies, their symptoms, and how to relay to us what they do to get better and what seems to make things worse. And we want our young patients to learn the discipline of compliance, patience, and persistence when it comes to headache therapy-ultimately leading them to pain-free free lives as they become adults.

Please click on the link below for the next topic in the Patient Care "What's New In Migraine" Special Report for PCPs:

Hormones and Migraine: A Case Study

For previous articles:

Introduction and Pre-test

 

References:

1. World Demographics Profile 2017.
2. Bille BO. Migraine in school children. Acta Paediatr.1962;51(Suppl. 136):16–151.
3. The International Classification of Headache Disorders 3rd Edition (Beta Version)- https://www.ichd-3.org/
4. Kabbouche MA, Gilman D. Management of migraine in adolescents. Neuropsychiatr Dis Treat. 2008;4:535-548.
5. Headache disorders. Fact Sheet. Updated 2016. World Health Organization.
6. Kacperski J, Hershey AD. Newly approved agents for the treatment and prevention of pediatric migraine. CNS Drugs. 2016;30:837-844.
7. Hamalainen ML, Hoppu K, Valkeila F, Santavuori P. Ibuprofen or acetaminophen for the acute treatment of migraine in children: a double-blind, randomized, placebo-controlled, crossover study.Neurology. 1997;48:103-107.
8. Lewis D, Ashwal S, Hershey A, et al. Practice Parameter: Pharmacological reatment of migraine headache in children and adolescents. Report of the American Academy of Neurology Quality Standards Subcommittee and the Practice Committee of the Child Neurology Society. Neurology. 2004;63:22152224.
9. Brenner M, Lewis D. The treatment of migraine headaches in children and adolescents. J Pediatr Pharmacol Ther. 2008;13:17–24.
10. Pediatric and adolescent migraine. Headache Toolbox. American Headache Society. Headache.