Headache in Adolescents

a, b,1
Irene Patniyot, MD *, William Qubty, MD

KEYWORDS
Adolescent headache Adolescent migraine Onabotulinumtoxin A CGRP

KEY POINTS
Migraine is a common neurologic disorder in adolescents, causing significant disability.
Although NSAIDs and triptans are considered first-line therapies for short-term treatment
of migraine attacks, clinical trials are evaluating the safety and efficacy of gepant use in the
adolescent population.
Several migraine preventive therapies are available, including calcitonin gene-related pep-
tide (CGRP)-targeted therapies.
Accompanying treatments include behavioral therapies, neuromodulation devices, and
procedures for when symptoms are not improving.

INTRODUCTION

Migraine is a common neurologic disease that affects about 18% of women and 6% of
men.1 Prevalence increases with age, and by adolescence it affects 8% to 22% of in-
dividuals.2 Although the degree to which migraine interferes with an individual’s life
varies, it is the second leading cause of years lived with disability (YLD) worldwide3
and the leading cause of YLD in those aged 15 to 49 years.4 It is therefore paramount
to identify and address migraine symptoms in adolescence, in an effort to prevent
escalation of symptoms in adulthood. In recent years there have been several ad-
vances in the areas of short-term and preventive medication treatments, behavioral
therapies, and neuromodulation devices, which have provided more hope for treating
migraine and reducing migraine-related disability. This article discusses headache
classification, in addition to outpatient headache management strategies for meeting
the needs of adolescent patients. Although the World Health Organization (WHO) con-
siders years 10 to 19 as the period of adolescence,5 in clinical practice the adolescent
age group typically encompasses ages 12 to 17 years.

a
Section of Neurology and Developmental Neuroscience, Department of Pediatrics, Texas
Children’s Hospital Pediatric Headache Clinic, Baylor College of Medicine, Houston, TX, USA;
b
Division of Child Neurology, Minneapolis Clinic of Neurology, Minneapolis, MN, USA
1
Present address: 9645 Grove Circle North Suite 100, Maple Grove, MN 55369.
* Corresponding author. Texas Children’s Hospital, West Campus, 18200 Katy Freeway, Suite
360, Houston, TX 77094.
E-mail address: [email protected]

Neurol Clin 41 (2023) 177–192

https://doi.org/10.1016/j.ncl.2022.08.001 neurologic.theclinics.com
0733-8619/23/ª 2022 Elsevier Inc. All rights reserved.
178 Patniyot & Qubty

HEADACHE CLASSIFICATION

The most common headache disorders in adolescence include tension-type head-

ache (TTH), migraine, primary stabbing headache, new daily persistent headache
(NDPH), and posttraumatic headache (PTH). The trigeminal autonomic cephalalgias
(TACs) are quite uncommon in this population as a primary headache disorder. The
frequency and features of these headache disorders in adolescents compared with
the adult population may vary, and these differences are highlighted.
History taking is of particular importance in this age group. The adolescent develop-
mental stage produces a wide range of behaviors, some of which results in vague,
equivocal, or indifferent responses to the clinician’s queries. Building rapport and
asking questions in a variety of ways is crucial for obtaining the necessary history.
The history should be directed toward the patient, although on rare occasion it may
be necessary to rely more heavily on the parent/guardian.

Tension-Type Headache
TTH in adolescents is not significantly different from the adult presentation except that
in the authors’ experience, the bandlike sensation around the head is less common
than a mid- to bifrontal pressure headache. The diagnostic criteria are found in
Box 1. There are 4 variations of TTH based on headache frequency: infrequent
episodic (<1 d/mo), frequent episodic (1–14 d/mo), chronic (>14 d/mo), and probable
based on not meeting all the diagnostic criteria for TTH.

Migraine
Diagnosing migraine in adolescents is generally similar to that in adults with a few
notable exceptions. Migraine in adolescents may be of shorter duration, lasting as little
as 2 hours untreated versus 4 hours in adults. Also, the location of the headache is
more likely to be bilateral instead of unilateral. It is the authors’ opinion that the com-
plete migraine diagnostic features early in the development of migraine may not all be
present and that over time they may fully develop. Headache disability can be
assessed using the validated pediatric migraine disability assessment (PedMIDAS)

Box 1
Tension-type headache diagnostic criteria

A. At least 10 episodes of headache occurring on aday(s)/month on average and fulfilling

criteria B to D
B. Lasting from 30 minutes to 7 days
C. At least 2 of the following 4 characteristics:
1. Bilateral location
2. Pressing or tightening (nonpulsating) quality
3. Mild or moderate intensity
4. Not aggravated by routine physical activity such as walking or climbing stairs
D. Both of the following:
1. No nausea or vomiting
2. No more than 1 of photophobia or phonophobia
a
Options are less than 1, 1 to 14, and greater than 14.

From Vincent M, Wang S. Headache Classification Committee of the International Headache

Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia.
2018;38(1):1-211. https://doi.org/10.1177/0333102417738202; with permission.
Headache in Adolescents 179

survey.6 This screening tool uses 6 questions to assess the level of disability at school,
home, and activities for the prior 3 months. The PedMIDAS may, however, underrepre-
sent disability during the summer months and holiday breaks when adolescents are
out of school (Box 2).

New Daily Persistent Headache

NDPH is more common in children and adolescents than adults.7 NDPH is defined as
a clearly recalled, new-onset persistent headache, lasting at least 3 months, in pa-
tients without a notable prior headache history (Box 3). The onset of headache may
be preceded by illness such as Epstein-Barr virus, Valsalva,8 or a stressful event. A
retrospective NDPH study of school-aged children found that 39% of cases began
in either September or January, correlating with school onset.9 Headache character-
istics of this disorder commonly overlap with migraine features and may be quite re-
fractory to treatment.10

Trigeminal Autonomic Cephalagias

TACs such as cluster headache and hemicrania continua are rarely encountered in ad-
olescents, but when they are, consideration for secondary intracranial pathology must
be excluded. A recent review of 1788 pediatric, primary TAC publications found 86
studies that met their basic inclusion criteria.11 Fifty-six of those studies focused on
cluster headache. For pediatric cluster headache, the review found they can typically
fulfill the adult criteria except for maximum of 6 instead of 8 attacks per day. Also, cra-
nial autonomic features, number of attacks, and restlessness occurred at lower rates
than in adults.

ABORTIVE THERAPIES

During a severe migraine attack, the goal of short-term treatment is to provide rapid
relief of symptoms with minimal side effects. Adolescents should be advised to take
their rescue medications earlier in the migraine attack, because short-term migraine

Box 2
Pediatric Migraine Without Aura Diagnostic Criteria

A. At least 5 attacks fulfilling criteria B to D

B. Headache attacks lasting 2 (instead of 4) to 72 hours (when untreated or unsuccessfully
treated)
C. Headache has at least 2 of the following 4 characteristics:
1. Bilateral (instead of unilateral) location
2. Pulsating quality
3. Moderate or severe pain intensity
4. Aggravation by or causing avoidance of routine physical activity (eg, walking or climbing
stairs)
D. During headache at least 1 of the following:
1. Nausea and/or vomiting
2. Photophobia and phonophobia
E. Not better accounted for by another International Classification of Headache Disorders
(ICHD)-3 diagnosis.

From Vincent M, Wang S. Headache Classification Committee of the International Headache

Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia.
2018;38(1):1-211. https://doi.org/10.1177/0333102417738202; with permission.
180 Patniyot & Qubty

Box 3
New Daily Persistent Headache Diagnostic Criteria

A. Persistent headache fulfilling criteria B and C

B. Distinct and clearly remembered onset, with pain becoming continuous and unremitting
within 24 hours
C. Present for greater than 3 months
D. Not better accounted for by another ICHD-3 diagnosis

From Vincent M, Wang S. Headache Classification Committee of the International Headache

Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia.
2018;38(1):1-211. https://doi.org/10.1177/0333102417738202; with permission.

treatments are more effective when the pain is still mild. The American Academy
of Neurology provided updated guidelines in 2019 on short-term treatment of
migraine in children and adolescents, which found that ibuprofen, acetaminophen,
almotriptan, rizatriptan, sumatriptan/naproxen, sumatriptan, and zolmitriptan nasal
sprays exhibited pain improvement or 2-hour pain freedom in placebo-controlled pe-
diatric trials.12 Other major treatment recommendations include coupling triptans with
ibuprofen or naproxen if a migraine is incompletely responsive, administering a sec-
ond dose of a short-term migraine medication within a 24-hour period, treating
migraine-associated nausea, and avoiding medication overuse by limiting use of
ibuprofen or acetaminophen to 14 or fewer days per month, and triptans to 9 or fewer
days per month.13 The ensuing discussion on short-term treatments will focus on the
most commonly studied classes of medications for acute migraine treatment: over-
the-counter analgesics, triptans, and dopamine receptor antagonists.

Over-the-Counter Analgesics
Most individuals with migraine use over-the-counter analgesics, including acetamino-
phen, ibuprofen, naproxen, and combination containing analgesics, as first-line ther-
apy. Nonsteroidal anti-inflammatory drugs (NSAIDs) are typical mainstays of therapy,
and there is limited evidence in the pediatric and adolescent population showing su-
periority of ibuprofen over acetaminophen and placebo.14 Longer-acting NSAIDs such
as naproxen can also be considered as first-line short-term treatment, especially if
other over-the-counter analgesics have been ineffective. Other NSAIDs include diclo-
fenac and etodolac, and more recently a liquid formulation of celecoxib has shown
effectiveness in adults for short-term treatment of episodic migraine.15 There is evi-
dence in adults with chronic migraine that when naproxen is used frequently over a
period of 3 months it can lead to a substantial reduction in migraine frequency,
providing a prophylactic benefit.16 It is the authors’ experience that twice daily nap-
roxen can be used for a few days up to 1 month as “bridging therapy” when migraine
frequency is high. For example, it can be used in this manner concurrent with initiation
of a new migraine preventive, viral illness, perimenstrually, with mild head injury, or
during final examination time. Patients can be advised to take naproxen with food
to prevent stomach upset, and revert to using it fewer than 15 days per month after
the bridging period has ended to prevent medication side effects and concern for
medication-overuse headache with frequent long-term use.

Triptans
Triptans are 5-hydroxytryptamine (5-HT1B/1D) receptor agonists and were the
first medication class designed specifically for acute migraine management. Since
Headache in Adolescents 181

sumatriptan’s US Food and Drug Administration (FDA) approval in 1991, 6 more trip-
tans with varying routes of administration have been developed. There are 3 triptans
and 1 triptan/NSAID combination currently approved by the FDA for use in the pedi-
atric and adolescent populations. These medications include rizatriptan for ages 6
to 17 years, and almotriptan, zolmitriptan nasal spray, and sumatriptan/naproxen so-
dium for ages 12 to 17 years (Table 1).
Triptans are generally well tolerated, and are more effective if taken when the pain is
still mild. Although they may not shorten visual or sensory aura duration, in one-third of
people triptans are effective in aborting a migraine attack within 2 hours of administra-
tion.17 If triptan side effects occur, which include fatigue, dizziness, nausea, sensation
of feeling hot, or chest or jaw tightness, consideration can be given to switching to a
triptan with a lower side effect profile (ie, frovatriptan or naratriptan). Triptan contrain-
dications include cardiovascular disease, uncontrolled hypertension, stroke, and
pregnancy, which are not usual health concerns in the adolescent population.
Although the FDA has not yet updated its guidelines advising against use of triptans
in hemiplegic migraine or migraine with brainstem aura, triptans continue to be used
with caution in adolescents with these aura symptoms if symptoms are instead due
to stroke.
When choosing a triptan the provider can consider FDA approval status in the
adolescent population, which may be more easily covered by insurance. If the
pain escalates quickly or there are associated symptoms of nausea or emesis, a
nasal spray formulation (sumatriptan, zolmitriptan) or injection (sumatriptan) can
be considered. Providers should also take into consideration prescribing an appro-
priate initial dose, especially if the patient has previously required repeat dosing after
2 hours. Other considerations include combining the triptan with an NSAID for
improved effect, in addition to avoiding use of triptans and dihydroergotamine within
24 hours of each other.

Table 1
Triptans

Weight
Route of Weight £ ‡ 40 kg
Medication Administration 40 kg (mg) (mg)
Almotriptanb Oral 6.25 12.5
Eletriptan Oral 20 40–80
Rizatriptana Oral 5 10
ODT 5 10
Sumatriptan Oral 25 50–100
Nasal 5 20
Subcutaneous 0.06 mg/kg 4,6
Sumatriptan/naproxen sodiumb Oral N/A 10/60
85/500
Zolmitriptanb Oral 2.5 5
Nasal N/A 5
Naratriptan Oral 1 2.5
Frovatriptan Oral 1.25 2.5

Abbreviations: N/A, not applicable; ODT, oral disintegrating tablet.

a
FDA approved in children aged 6 to 17 years.
b
FDA approved in children aged 12 to 17 years.
182 Patniyot & Qubty

Dopamine Receptor Antagonists

Dopamine receptor antagonists are often used as migraine abortive therapy in emer-
gency centers in intravenous (IV) form; however, they can also be prescribed for home
use in the oral form. Dopamine receptor agonists can be considered as a rescue ther-
apy in those in whom triptans have either not worked or are contraindicated and pro-
vide a good option before sending patients to the emergency room for IV therapy.
Various prospective and retrospective trials in the pediatric and adolescent population
have found that the phenothiazines, prochlorperazine and chlorpromazine in IV form,
are effective in either reducing headache intensity by 50% or more18–20 or preventing
the need for further rescue therapy, hospitalization, or return within 48 hours.21,22 A
more recent randomized, double-blind controlled trial in adults found that both IV pro-
chlorperazine and IV chlorpromazine reduced headache severity scores, without su-
periority in efficacy of one agent over the other.23 Metoclopramide is also used for
acute migraine treatment, and antagonizes both dopamine and 5-HT3 receptors. In
adults metoclopramide has level B evidence that it is probably effective for acute
migraine treatment24; however, in adult studies have shown inferiority to prochlorper-
azine at comparable doses.25,26
Extrapyramidal side effects such as akathisia and a dystonic reaction can occur
with this class of medication and can be mitigated in some individuals with diphenhy-
dramine premedication. Chlorpromazine can cause worsening of hypotension, and
this medication class as a whole can cause sedation. Caution should also be used
with patients taking other QTc prolonging medications such as some antipsychotics.

Ditans and Gepants

Ditans are a newer class of medications developed for acute migraine treatment that
cross the blood-brain barrier and target the 5-HT1F receptors found in the peripheral
and central trigeminovascular system. Ditans do not cause the vasoconstriction that
triptans do and may be a suitable alternative in those with cardiac or vascular disease.
Lasmiditan was FDA approved in October 2019 for use in ages 18 and more based on
phase 3 trial results showing superiority over placebo in achieving 2-hour pain
freedom (200 mg dosing: 38.8% vs 21.3%; odds ratio [OR], 2.3; 95% confidence in-
terval [CI] 1.8–3.1; P<.001).27 Side effects can include dizziness, somnolence, nausea,
and paresthesias, and patients should avoid driving for 8 hours following
administration.
Gepants are another class of small molecule calcitonin gene related peptide (CGRP)
antagonists that cross the blood-brain barrier and are FDA approved in those aged 18
years and older for short-term and/or preventive therapies. Rimegepant is the only
drug in this class showing efficacy as both short-term and preventive therapy, and
in February 2020 it was approved by the FDA for short-term use in those aged 18 years
and older based on multicenter, randomized, double-blind placebo-controlled trial
findings that pain freedom with rimegepant 75 mg oral disintegrating tablet occurred
in 21% of patients compared with 11% placebo (P<.0001).28 Ubrogepant is another
medication in this class approved by the FDA in December 2019 for acute migraine
use in those aged 18 years and more, following results of a phase 3, randomized,
placebo-controlled trial revealing pain freedom for the 100 mg dose (21.2%,
P 5 .002), 50 mg dose (19.2%, P<.001), and placebo (11.8%).29 Zavegepant is the first
third-generation gepant being studied in oral, subcutaneous, and intranasal formula-
tions and has shown efficacy with the intranasal formulation. Although gepants are not
approved for use in adolescents younger than 18 years, there are phase 3 randomized
controlled trials in the pediatric and adolescent populations currently underway.
Headache in Adolescents 183

LIFESTYLE FACTORS

Addressing lifestyle factors that may be contributing to headache burden are an

important part of headache education and management. These factors include sleep,
diet, hydration, physical activity, caffeine, and mood. When discussing these healthy
habits, expectations should be relayed to the patient that although these interventions
support general health and may lead to a reduction in headache burden, there is no
guarantee that this will happen. In addition, there may be external or internal circum-
stances making it difficult for adolescents to follow a routine, and blaming the patient
may lead to further internalized stigma.

Sleep
The American Academy of Sleep Medicine (AASM) recommends that adolescents get
8 to 10 hours of sleep per night.30 Teenagers have a physiologically delayed sleep
phase that predisposes them to go to bed later and wake up later,31 which can lead
to shorter overall sleep duration during the school week. In addition to physiology,
use of electronic devices often interferes with sleep schedules. In one study, most ad-
olescents reported using 1 or more electronic devices in the hour before bedtime. A
dose-response relationship was observed between sleep duration and use of elec-
tronic devices, such that a total screen time greater than 4 hours was associated
with an increased risk of less than 5 hours of sleep (OR, 3.64; 95% CI, 3.06–4.33).32
In addition to electronic content contributing to mental and bodily arousal, light expo-
sure from electronic devices can affect circadian rhythms by reducing or delaying the
release of the sleep-potentiating hormone melatonin from the pineal gland.33
Addressing sleep disruption has the potential to improve headache symptoms.
Counseling can include putting away electronic devices at least 30 minutes to
1 hour before bedtime. If that is not possible due to academic or psychosocial factors,
families can consider the use of blue blocking glasses to minimize the impact of blue
light interference with sleep. Families can be informed that there are differences in the
quality of blue-blocking glasses, and those with specific FL-41 tint filters can also be
helpful for individuals who have light and screen sensitivity. Natural sleep-promoting
therapies can also include herbal teas, cherry juice,34 mindfulness exercises, and
melatonin. If headache burden is high and interfering with high school or college per-
formance, accommodations can be sought to adjust the patient’s academic schedule
accordingly.

Diet
Counseling on eating regular, healthy meals with snacks is a typical part of a headache
visit. Although this practice stems from a belief that disruptions in routine can be a
trigger for migraine attacks, it is unclear whether and to what degree skipping meals
may contribute to migraine frequency. In addition, comorbid symptoms such as
nausea or delayed gastric emptying may interfere with eating regular meals. Studies
in the adult and adolescent populations have found that skipping meals, breakfast
in particular, is common in individuals with migraine35–37; however, the association be-
tween skipping a meal and triggering a migraine attack has not been as consistently
made.
Patients with migraine often ask about migraine food triggers. In the hours before
the headache phase of migraine, there is a premonitory phase involving hypothalamic
changes, which can cause symptoms of increased yawning, irritability, fatigue, neck
pain, increased urination, and also food cravings.38–40 If an individual craves a certain
food such as chocolate or a carbohydrate-rich snack during this time, they may
184 Patniyot & Qubty

associate that food with triggering a migraine attack, when in fact migraine-related
brain changes result in the food craving. Providers can encourage the adolescent to
eat regular healthy meals as a good practice for overall health and explain that certain
identified food triggers may actually be hypothalamic-driven food cravings attributed
to the premonitory phase of migraine.

Hydration and Physical Activity

Dehydration can exacerbate various headache disorders and is multifactorial.41 The
mechanisms by which this provocation occurs can include fasting from both food
and water, in addition to activation of central nervous system pain networks and
reduced pain threshold.42 Most children and adolescents are mildly dehydrated,43
and increasing water intake in adults can lead to decreased hours of headache,
migraine quality of life, and reduction in headache days.44,45 The Institute of Medicine
provides recommendations for adequate daily water intake based on age and sex,
which in 14- to 18-year-old adolescents ranges between 64 oz (girls) and 88 oz
(boys) of water per day. Both caffeinated and noncaffeinated beverages are thought
to contribute to total water intake.46 These recommendations are not absolute, and
consideration should be given to comorbid conditions such as orthostatic intolerance
and renal or cardiac disease, which alter these daily allowances.
Multiple studies have shown that routine physical activity can have a positive impact
on headache frequency, quality of life, and mood.47 Conversely, low levels of physical
activity and being overweight are associated with recurrent headaches in adoles-
cents.48 Obesity is also a known risk factor for progression from episodic to chronic
migraine,49 emphasizing the potential influence of diet and physical activity on pre-
venting escalation of headache burden. Studies have also shown that exercise may
be as effective as a daily migraine preventive. More specifically, migraine frequency
in individuals with episodic migraine decreased in all participants in a randomized trial
comparing topiramate alone, a relaxation program, or aerobic exercise 3 times per
week.50 Another study in individuals with chronic migraine randomized participants
to take amitriptyline 25 mg alone versus amitriptyline plus exercise involving fast
walking 3 times per week for 12 weeks. Although there was a substantial decrease
in both groups, the combined medication and exercise group experienced a greater
reduction, with a therapeutic gain of approximately 6 days.51
Adolescent patients can be given suggested water intake goals and encouraged to
drink water regularly throughout the day. They can also be encouraged to engage in
some form of exercise 3 days/wk. If aerobic exercise is a migraine trigger, lower-
intensity physical activity can be suggested in its place. Because there are sometimes
practical barriers to hydration such as school rules preventing drinks in the class or
limiting bathroom use, providing the patient with a school accommodation letter
can be a simple way to improve adherence.

PREVENTIVE THERAPIES

Adolescents with chronic and bothersome recurring headaches most commonly have
migraine. Thus, the following discussion focuses on pharmacologic and nonpharma-
cologic measures for migraine prevention. When the frequency of moderate to severe
headache reaches at least a weekly basis, consideration should be given for initiation
of a preventive treatment. Because FDA-approved headache treatments are rare in
adolescents, medications should be chosen based on side effect profiles, prior medi-
cation tolerability, adherence, and medical history. Common coexisting medical con-
ditions that may also influence medication options include depression, anxiety,
Headache in Adolescents 185

asthma, heart/vascular disease, and postural orthostatic tachycardia syndrome. Pa-

tients should be counseled on the time required for headache treatments to see
benefit, which is typically a minimum of 8 weeks. The level of benefit in the short
and long term should be discussed to provide realistic expectations; a typical goal
is to achieve at least a 50% reduction in the headache pattern. Adjunctive therapies
may be required for refractory cases, but increased caution should be used to assess
for medication interactions. Duration of preventive treatment depends on the duration
and severity of the headache presentation. A reasonable goal is 3 to 6 months of good
headache control before discussion of weaning preventive modalities.
The American Academy of Neurology in conjunction with the Child Neurology Soci-
ety updated their 2004 pediatric migraine treatment guidelines in August 2019.52 The
update involved a comprehensive literature search of nearly 2000 abstracts from 2003
through 2017. Inclusion criteria were trials of preventive therapy, with at least 90% of
participants aged 3 to 18 years, with a diagnosis of migraine, and treatment was
compared with placebo. Studies that had fewer than 20 participants were excluded.
Using these criteria, only 16 articles remained.
Anticonvulsants have long been used for migraine prevention. When looking at top-
iramate the guidelines concluded with moderate confidence that patients on topira-
mate were probably more likely than those taking placebo to have a reduction in
the frequency of migraine or headache days. Topiramate is the only FDA-approved
medication for migraine prevention in those aged 12 to 17 years. For extended-
release divalproex sodium, the guidelines concluded, with very low confidence, that
there was insufficient evidence to determine if it is more or less likely than placebo
to reduce headache frequency.
For antidepressants, only amitriptyline was discussed. The guidelines concluded,
with very low confidence, that there was insufficient evidence to determine if it is
more or less likely than placebo to reduce headache frequency or migraine disability.
However, there was high confidence to support amitriptyline use with cognitive behav-
ioral therapy (CBT) to reduce headache frequency and possibly disability.
Antihypertensives were also reviewed. For the beta-blocker propranolol, the guide-
lines concluded, with low confidence, that it is more likely than placebo to have at least
a 50% reduction in headache frequency. There was insufficient evidence for use of the
calcium channel blocker flunarizine, which is not available in the United States, or
nimodipine.
The CHAMP trial was a landmark multicenter pediatric and adolescent migraine
study that was included in the aforementioned guideline data.53 This study consisted
of 3 arms including treatment with topiramate, amitriptyline, and placebo. The trial was
stopped early due to futility because the intervention arms did not show benefit over
placebo and had increased adverse effects. Notably the placebo response rate was
61%. In light of these results, nonpharmacologic interventions and nutraceutical rec-
ommendations can strongly be considered as first-line treatment. Nutraceutical op-
tions with some evidence of migraine benefit include riboflavin,54 melatonin,55,56
coenzyme Q10,57 and possibly magnesium58 (Table 2). There is evidence to suggest
that treatments such as coenzyme Q10 and magnesium are more likely to have benefit
if there is associated deficiency.57,58
Not discussed in the 2019 guidelines are the newer anti-CGRP monoclonal anti-
bodies (mAbs), which include erenumab, galcanezumab, fremanezumab, and eptine-
zumab. These mAbs are not currently FDA approved for the treatment of migraine in
patients younger than 18 years. Expert opinion suggests that these agents may be
considered in adolescents with refractory migraine.59 Patient characteristics such
as age, weight, pubertal status, and medical comorbidities should be considered,
186 Patniyot & Qubty

Table 2
Nutraceuticals for migraine prevention

Nutraceutical Dosing (if At Least 40 kg)

Riboflavin 200 mg BID
Melatonin 3 mg 30 min before bedtime
Coenzyme Q10 1–3 mg/kg/d divided BID or 100 mg BID
Magnesium oxide 9 mg/kg/d divided BID to TID (maximum 600 mg/d)

Abbreviations: BID, twice daily; TID, 3 times per day.

and close follow-up is recommended. More specifically, adolescents with refractory

chronic primary headache, with significant headache disability, weighing at least
40 kg, are postpubertal, without significant bone disease, not pregnant or breastfeed-
ing, and without disrupted blood-brain barrier may be good candidates. A recent
multicenter retrospective study of CGRP mAbs in adolescents with refractory chronic
migraine, NDPH, or persistent PTH has shown at least some benefit in more than two-
thirds of patients treated.60 The side effect profile was similar to that of adult studies of
mAbs with only 5 of 112 patients discontinuing due to adverse effects.

ALTERNATIVE THERAPIES
Neuromodulation Therapies
Neuromodulatory devices modulate head pain by providing nonpharmacologic electric
current or magnetic stimulation to the central or peripheral nervous system, and can be
used as either individual or add-on therapies. There are 4 devices currently approved by
the FDA for acute (remote electrical neuromodulation [REN])61 or concurrent short-term
and preventive use (external trigeminal nerve stimulation [eTNS],62 noninvasive vagal
nerve stimulation,63 single-pulse transcranial magnetic stimulation [sTMS]64) in adoles-
cents ages 12 years and greater. The REN device delivers transcutaneous electrical
stimulation to the upper arm, which uses conditioned pain modulation to activate pain
inhibitory centers and exert a generalized analgesic effect.65 The eTNS device is now
available online without a prescription, whereas the other devices require a prescription.
The noninvasive vagus nerve stimulation is also approved by the FDA for short-term and
preventive treatment of cluster headache. These devices are generally well tolerated,
and can be beneficial for those who are either on multiple medications or have frequent
attacks placing them at risk of developing medication overuse headache.

Behavioral Therapies
Biobehavioral therapies have become very important therapies in teaching pain coping
mechanisms and regulation of autonomic arousal due to migraine. CBT, biofeedback,
and relaxation therapies have grade A evidence for use as preventive therapies for
migraine, and are increasingly being studied for short-term use.66 In the adolescent
population, CBT with a trained therapist can be extremely valuable in helping patients
acquire skills to make healthy changes in thoughts, feelings, physical sensations, and
behaviors, with the goal of improving pain and functioning.67 CBT was studied in a
20-week-long randomized controlled trial of 135 pediatric and adolescent patients
with chronic migraine concurrently taking amitriptyline, and it was found that 10 ses-
sions of 1-hour individual CBT was more effective than 10 headache education ses-
sions.68 This benefit was also sustained 12 months out,69 suggesting ongoing
benefits of this behavioral therapy especially when combined with pharmacotherapy.
Headache in Adolescents 187

Although biobehavioral therapies have traditionally been delivered in person, smart-

phone application formats have been developed for the adolescent70 and adult popu-
lation71 and can increase access to these beneficial therapies.

Procedures
For adolescent migraine, greater occipital nerve (GON) blocks are relatively well
studied and generally well tolerated. There is significant provider variation whether
the blocks are done unilaterally or bilaterally; there are also variations in anesthetic
agents chosen such as lidocaine or bupivacaine as well as whether to add a steroid
such as methylprednisolone or dexamethasone.72 In a retrospective study of 40 pa-
tients younger than 18 years with a chronic primary headache disorder, 53% found
at least some benefit from a unilateral GON block with methylprednisolone acetate
and 2% lidocaine.73 There were no serious adverse effects in this study, although
common reactions include injection site pain and potential for localized infection.
Adults can usually easily tolerate 3 mL volume at an injection site. It is the authors’
recommendation that if there is a minimal amount of subcutaneous tissue at the
GON site, one should consider using less volume such as 2 mL to avoid tissue
injury.
Sphenopalatine ganglion (SPG) blocks have been used for decades for short-term
management of migraine and cluster headache, and newer intranasal devices can
offer higher tolerability.74 The anesthetics used include 2% lidocaine or 0.5% bupiva-
caine, which are injected via each nare into the pterygopalatine fossa while the patient
is laying supine with cervical spine extension. A double-blind, placebo-controlled
study of weekly SPG blocks over 6 weeks for short-term treatment of chronic migraine
in adults revealed significant reduction in numeric pain scores through 24 hours post-
procedure.75 The procedure is overall safe and well-tolerated,76 with a recent retro-
spective study in the pediatric and adolescent population demonstrating statistically
significant reduction in pain scores immediately postprocedure.77 A small prospective
case series of adolescents with chronic headache disorders unresponsive to standard
therapies found reduction in depressive symptoms and improvement in global impres-
sion of change scores following repetitive SPG blockade.78 Future studies are needed
to elucidate the long-term benefit of this procedure.
Using botulinum toxin injections for chronic migraine in adults has long been
approved by the FDA but still not approved in those younger than 18 years. Most pro-
viders use the standard 31 injections distributing 155 units of onabotulinumtoxin A
(BOTOX) with an interval of 3 months; this requires selecting patients who can tolerate
this regimen. High-quality evidence for BOTOX in the adolescent chronic migraine
population remains quite scant per a literature review,79 although 2 recent retrospec-
tive studies and 1 small placebo-controlled study have shown benefit in this popula-
tion.80–82 One study found that poorly controlled generalized anxiety disorder may be
a risk factor for lack of response to BOTOX therapy in adolescents.83

SUMMARY

Adolescents may be strongly impacted by chronic headache disorders resulting in

disability at home, school, and in maintaining peer relationships. Their headache char-
acteristics may share some but not all features of the same adult headache disorder.
Some headache disorders such as NDPH are more common in adolescents, whereas
others such as TACs are less prevalent.
Abortive therapy for adolescents with migraine has expanded to include the ditans,
gepants, minor procedures, as well as neuromodulation. Preventive therapy may
188 Patniyot & Qubty

initially rely on treatments with low risk for adverse effects such as CBT and nutraceut-
icals. For refractory adolescent migraine, monoclonal antibodies against CGRP are
starting to be used, but further high-quality evidence in adolescents is needed to
gain FDA approval.

CLINICS CARE POINTS

Migraine in children and adolescents can be of shorter duration and bilateral location
compared to adults, and is distinguishable from tension type headache by severity,
movement sensitivity, photophobia and phonophobia, and/or nausea.
Triptans are effective abortive medications to use in adolescents, and can have improved
effect when coupled with NSAID medications.
Treating migraine-associated nausea is important, and is part of the American Academy of
Neurology guidelines for short-term treatment of migraine in children and adolescents.
Non-pharmacologic lifestyle and behavioral interventions, nutraceutical medications, and
neuromodulation devices can be considered as first-line therapies for migraine prevention
in children and adolescents prior to prescription migraine preventive medications.

DISCLOSURE

Dr I. Patniyot has received institutional research support from Teva and Theranica Bio-
Electronics for multicenter trial participation. Dr W. Qubty has nothing to disclose.

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