An Approach to the Diagnosis and Treatment of Chronic Headache Disorders in Children and Adolescents

By Hannah F Johnson, MD1 and Alyssa Lebel, MD2
1 Department of Child Neurology, Boston, Children’s Hospital; Harvard Medical School, Boston, Massachusetts
2 Division of Pain Medicine, Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital Boston; Harvard Medical School, Boston, Massachusetts

Introduction
Headache is a common cause of pain and disability in children and adolescents and is a major contributor to missed school days and activities.1,2 Chronic pediatric headache is difficult to manage due to the challenge of establishing a specific diagnosis, the lack of FDA-approved medications, and the relatively low effectiveness of the current therapies at improving pain. This paper reviews the diagnosis and treatment of two of the most common types of chronic headache: chronic migraine headache and chronic tension-type headache.

Establishing the Diagnosis of a Chronic Headache Disorder
Differentiating between types of chronic headache is challenging because there is significant overlap between symptoms of different headache disorders. In addition, different types of chronic headache are often considered part of the same continuum, as the same patient might experience features of different chronic headache types over time.3,4 Clinical history is the foundation of correctly diagnosing these disorders, but this can be difficult as the patients are often young and unable to describe the pain. The International Classification of Headache Disorders 3rd Edition (ICHD-3) was created to aid in diagnosis of headache disorders.

Chronic Migraine Headache
Migraine without aura is defined as at least five attacks described as moderate to severe, pulsating head pain that is oftentimes aggravated by routine physical activity.5 The headache is usually accompanied by nausea and/or vomiting, photophobia, and phonophobia. Migraine can also occur with aura. Aura symptoms can be visual, sensory, motor, speech/language, brainstem, or retinal. The aura tends to be unilateral and spreads gradually over five or more minutes. The symptoms tend to last between five and sixty minutes.5 It should be noted that about two thirds of children and adolescents have premonitory symptoms hours to days prior to a migraine headache attack, which is distinct from aura. The most frequently reported premonitory symptoms include fatigue, irritability/mood change, neck stiffness, and facial changes.6,7 There are two key differences between pediatric migraine and adult migraine. In children and adolescents, the head pain is more often bilateral in location, as opposed to unilateral, and the headache duration for pediatric patients, especially younger children, is typically shorter (1-48 hours) compared to adults (4-72 hours).8,9

The designation of chronic migraine is used when the headache has been present for at least 15 days per month over a period of three consecutive months.5 Chronic migraine headache typically starts in patients who have had episodic migraine headaches. Due to a number of factors including poorly treated acute migraine attacks,10 medication overuse,11 and genetics,12 some of these children and adolescents will develop chronic migraine. The prevalence of chronic migraine is 0.8-1.75% of adolescents ages 12-17 years and 0.6% of children ages 5-12 years.13,14

Chronic Tension-type Headache
Tension-type headache (TTH) is characterized by bilateral, non-pulsating headache that is mild to moderate in severity and is not aggravated by routine physical activity. There is no associated nausea or vomiting. Either photophobia or phonophobia may be present, but both are rarely present together.5 The distinction between TTH and migraine can be difficult to establish, but perhaps the most important distinction is that the pain is less severe in TTH compared to migraine. Similar to the designation of chronic migraine headache, the designation of chronic TTH is used when the headache has been present for at least 15 days per month over a period of three consecutive months.5 Also similar to migraine, TTH usually starts as episodic in nature and then progresses to chronic, likely due to similar factors that contribute to the development of chronic migraine. However, compared to their role in migraine, psychiatric comorbidities and stress likely play a larger role in transforming episodic TTH into chronic TTH.15 Chronic TTH has a similar prevalence compared to chronic migraine, with estimates between 0.9%-1.5% for children and adolescents ages 5-18 years.16

Management of Chronic Headache Disorders
Once the correct headache diagnosis is made, stepwise treatment involves a combination of self-care, nonpharmacological interventions, on- and off- label use of medications, and procedural injections. In the sections that follow, we review an evidenced-based approach to manage chronic headache. There is significant overlap in treatment strategies for chronic migraine and chronic TTH due to the paucity of research specifically in chronic TTH, the relative ineffectiveness of the treatments that are currently available for chronic headache, and the phenomenon whereby patients may have features of each headache type at different points in time. However, there are some important differences between treatment strategies for chronic migraine and chronic TTH that will be highlighted.

Self-care
For both chronic migraine and chronic TTH, the first intervention is addressing modifiable lifestyle factors. While childhood and adolescence are marked by frequent change, it is vital to educate families on the importance of lifestyle regularity for headache management. In the landmark study Childhood and Adolescent Migraine Prevention (CHAMP), a randomized controlled trial of preventative medications versus placebo for pediatric migraine, approximately 60% of patients in the placebo arm of the study had reduction in headache frequency.17 It is hypothesized that this exceptional response in the placebo group was due to the fact that lifestyle counseling was performed at monthly clinic visits.18 Patients should be counselled to keep a regular sleep schedule, to go to sleep and wake up at the same time each day (weekends included), and to achieve adequate sleep duration.19 Patients should be instructed to increase their fluid intake,20 eat regular meals,21 and exercise.22

Nonpharmacological Interventions
Nonpharmacological interventions include cognitive behavioral therapy (CBT), biofeedback, acupuncture, massage, and physical therapy.23 These can be used in both chronic migraine and chronic TTH. CBT focuses on mind and body relaxation skills including, but not limited to, deep breathing, progressive muscle relaxation, and activity pacing.24 Biofeedback is often incorporated into CBT by using visual cues to demonstrate changes in muscle tension and heart rate in response to relaxation techniques.25 In a randomized clinical trial in pediatric patients (ages 10-17) with chronic migraine, CBT used in conjunction with preventative medications resulted in a decrease in headache frequency and overall disability when compared to lifestyle education plus preventative medications.26  

Pharmacological Interventions
Abortive medications
Abortive medications are used for acute headache exacerbations in the setting of underlying chronic headache disorders. For episodes of both migraine- and tension-type headache exacerbations, acetaminophen, ibuprofen, and naproxen have been shown to have similar efficacy.27–29 Accordingly, these medications are considered first-line therapies for both types of headache. 
While the first-line therapies for both migraine- and tension-type headaches are identical, there are important differences in adjunctive abortive therapies. For migraine, antiemetics are often used in conjunction with the above interventions.

Prochlorperazine and metoclopramide not only help to reduce nausea associated with migraine, but also help to reduce head pain.30,31 These agents are generally safe but can cause extrapyramidal side effects including akathisia and dystonia.32,33 When exacerbations of migraine headache do not respond to first-line analgesics and antiemetics, triptans should be used as second-line therapy. Triptans are one of the only FDA-approved migraine-specific therapies for children and adolescents. Triptans should be given at headache onset, when the pain is still mild, in order to produce the greatest effect.34 While children and adolescents with episodic migraine respond more frequently to triptans than patients with chronic migraine, there is evidence that about 65% of pediatric patients with chronic migraine respond to triptans.35 Therefore, it is reasonable to trial triptans for migraine exacerbation in youth with chronic migraine. Triptans should not be used on more than 10 days per month to avoid medication overuse.5,36 There are currently seven triptans on the market; four (oral almotriptan, nasal zolmitriptan, rizatriptan melt, oral sumatriptan/naproxen) are FDA approved for adolescents age 12 and older and one (rizatriptan melt) is FDA approved for children age six and older.29,37–39 Failure of one triptan does not predict failure of others.

If outpatient abortive management of migraine headache exacerbation fails, inpatient management with dihydroergotamine (DHE) may be effective. DHE is considered first-line for inpatient management of refractory migraine. Although large, controlled trials are lacking, use of DHE in uncontrolled cohort studies in pediatric patients has been found to be safe and associated with a 63%-97% response rate to DHE. Response to DHE is defined as either headache freedom or significant improvement in head pain.40–42

It should be noted that opioids do not have a role in abortive headache management. There is no evidence that opioids are more effective then NSAIDs, anti-emetics, or triptans, and there is evidence that opioids reduce the effectiveness of triptans.43,44 Additionally, opioids are also thought to change the underlying physiology of the brain and contribute to transformation from episodic headache to chronic headache.11,45,46 Given these factors and the high risk of dependency, especially in an adolescent population, opioids should be avoided in all types of headache.

Preventative medications
In children, use of melatonin improved migraine headache disability and frequency compared to placebo.47 In adults, melatonin was more efficacious compared to placebo and equally efficacious compared to amitriptyline, but with a better side effect profile.48 Based on these data, melatonin may be a good option for preventative therapy in chronic migraine headache. Other nutraceuticals including magnesium, riboflavin, and butterbur have been efficacious in adults with migraine- or tension-type headache, but evidence of effectiveness in children and adolescents is lacking.49

Prescription preventative medications should be started at low doses and slowly up-titrated to achieve the desired effect. Since response to these medications may be delayed, incomplete, or even absent, patients should understand that these medications are not a quick fix.50 Given the lack of evidence in children and adolescents, choosing which preventative medication to try is oftentimes based on clinical experience, patient age, and medication side effect profile. For children less than ten years of age, cyproheptadine is often used as first-line.51,52 In older children, amitriptyline or nortriptyline is used frequently.53 Amitriptyline is a great option for those who struggle with sleep due to its sedating side effect.17 Propranolol can also be considered as a preventative treatment but should be avoided in patients with depression due to risk of worsening mood and suicidal ideation and in athletes due to decreased exercise tolerance.54 Topiramate is often used in patients who are overweight, as it is one of the only options without weight gain as a side effect and, in fact, weight loss is often seen.55

Procedural Interventions
Once a patient has failed two or more preventative options for chronic headache, children and adolescents can then trial peripheral nerve blocks and/or OnabotulinumtoxinonA (Botox) injections. These interventions are usually reserved for chronic migraine headache, as data for chronic TTH are lacking. There are data to support efficacy and safety of peripheral nerve blocks in pediatric patients.56 In a study analyzing the patterns of nerve block injections for pediatric patients, 100% of headache physicians targeted the greater occipital nerve and a majority (69%) also targeted the lesser occipital nerve.57 Most physicians injected bilaterally. All physicians used a local anesthetic, usually lidocaine and/or bupivacaine, though the concentrations varied. Approximately half of physicians added a corticosteroid to the injection. Peripheral nerve blocks are FDA approved for pediatric patients. Botox injections have been proven efficacious in adults.58 There are some data to suggest efficacy and safety in adolescents,59,60 but there are no prospective studies. Botox injections are not FDA approved for patients less than 18 years of age.

Novel Medications
In 2018, the FDA approved three calcitonin gene-related peptide (CGRP) receptor inhibitors for the prevention of migraine headache in adults: Erenumab-aooe (Aimovig), fremanezumab-vfrm (Ajovy), galcanezumab-gnlm (Emgality). These are the first migraine-specific—rather than off-label—preventative medications and have shown promising results.61 However, these have yet to be approved for use in children and adolescents.

Conclusion
Chronic headache in children and adolescents is common, disabling, and costly. Managing these pediatric patients involves a combination of therapies including self-care, nonpharmacological interventions, abortive medications, preventative medications, and procedural injections. While the general approach to treatment is the same regardless of chronic headache type, specific therapies for migraine - and tension-type headache exist and can be effective. Still, given that chronic headache is often refractory to current therapies, additional research is needed to determine novel interventions to reduce morbidity in children with chronic headache.

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