Management of headaches in
children and adolescents
Debra M. O’Donnell, MD,a,* and Anastazia Agin, MDb
Pediatric headache impacts up to 80% of children, many recur-
rently, by the time they are 15 years old. Preventing the pro-
gression of episodic to chronic headache results in less truancy,
staying current with schoolwork and improves children’s quality
of life. Lifestyle choices can play an important role in headache
treatment. Early effective treatment of episodic headache can
prevent transformation into a chronic form. While details of a
child’s headache are critical for making a proper diagnosis;
patient education is critical and effective rescue and preventive
treatment strategies enable patients to focus on enjoying
Introduction
ediatric and adolescent headache carries signif-
P icant physical, psychological and economic
burden. Multiple individual studies and
reviews documented the incidence and prevalence of
headaches in children, most studies suggest that at
least 20-40% of children experience headache com-
plaints by the age of 7 years1 3 with the prevalence of
headache by age 15 years increasing to 60-80%.3 7
Migraine impacts up to 4% of children under age
8 years and 10% or more of children aged 5-
15 years.1 3,8 Migraine prevalence approaches adult
levels by late teens.
Diagnosing and treating pediatric headache
patients requires a thorough yet focused approach.
Classical history-taking and examination of the
patient are critically important to initiate an appro-
priate therapy.
Evaluation must include identification of any
patient with secondary headache so that the child
can be referred for urgent imaging or intervention.
Secondary headaches can be caused by serious
underlying pathology such as vascular
From the aPediatric Neurologist, Dayton Children’s Hospital, Division of
Neurology, OH, United States; and bPediatrician and Headache Specialist,
Dayton Children’s Hospital, Division of Neurology, OH, United States.
*Corresponding author.
E-mail: ODonnellD@childrensdayton.org
Curr Probl Pediatr Adolesc Health Care 2021;51:101034
1538-5442/$ - see front matter
Ó 2021 Elsevier Inc. All rights reserved.
https://doi.org/10.1016/j.cppeds.2021.101034
Curr Probl Pediatr Adolesc Health Care, July 2021
activities of daily living. Recognizing “red flags” that may sug-
gest a serious underlying etiology is critical in the early stages
of diagnosing and preparing to treat children with headaches.
Finally directing patients to manage their headaches at home
and when to proceed to an emergency department, urgent
care or infusion unit can lower the economic burden of acute
headache management.
Curr Probl Pediatr Adolesc Health Care 2021; 51:101034
malformations or neoplasia but may also be due to
more readily treatable conditions such as sinus dis-
ease. While considered less serious, primary head-
aches can, however, have a serious impact on
quality of life.5 Headaches may disrupt the child’s
ability to perform well in school or engage in
enjoyable activities. Patient well-being hinges on
our ability to diagnose headache type and develop
an effective treatment strategy.
From the initial presentation of the child with
headaches to the successful management of the
problem, an orderly approach facilitates the most
thorough, safe and effective care of each individual
patient. Fig. 1 outlines an algorithm that highlights
appropriately ordered steps to evaluate a patient
with headache.9 Under the direction of the Clini-
cally Integrated Network of Dayton Children’s Hos-
pital, members of our neurology department and
select primary care clinicians along with institu-
tional educators and other principles developed the
algorithm for distribution to Miami Valley Clini-
cians. The objective of the algorithm is to foster a
collaborative and consistent approach to the child
with headaches as well as better utilization of avail-
able resources.9 The recognition of the limited num-
ber of patients who need urgent evaluation in the
emergency department (ED) and the development
of an effective strategy to initiate outpatient treat-
ment in the majority who do not, will cost effec-
tively enable the delivery of appropriate care, in the
right place at the right time.
1
 Fig. 1. Headache Co-Management Algorithm.

Diagnosis
Diagnosing common primary headaches in any child
and differentiating it from a more serious secondary
headache is important for designing an appropriate
diagnostic assessment and effective treatment plan.
While many over the counter agents (OTC) can reduce
varying types of pain, more specific therapeutic inter-
ventions can sometimes be facilitated by identifying
the type of headache a child has and educating the
family. This approach builds trust and a foundation
for shared decision-making when recommending
treatment.
Correct diagnosis in migraine is often not difficult
since about 50% of children who have 1 parent with a
diagnosis of migraine will develop migraine them-
selves. While this number is often quoted and gener-
ally true, the genetics of migraine transmission are
rather complicated and vary based on the type of
migraine.10 There is evidence that a family history of
migraine is common in children who present at a
younger age.11 Family history of migraine may also
influence whether a child will develop migraine fol-
lowing a concussion, this is often seen by pediatric
neurologists.12 Individual presentation with respect to
age of onset, associated features and response to treat-
ment can vary, but knowledge of migraine in the fam-
ily can help reduce concern that something more
serious is occurring. The parent’s personal experience

2 Curr Probl Pediatr Adolesc Health Care, July 2021

may facilitate devising a proper treatment plan for
their child.
Migraine is often associated with unilateral head
pain (although this is not necessarily true in children),
pounding/throbbing/pulsing character, the need to
retreat from activities and sleep, and variable combi-
nations of nausea, vomiting, photo- and phono- pho-
bia. Tension type headaches are more regularly
holocephalic or bilateral and described as tight or
squeezing. The specific criteria for Migraine with or
without aura and Tension-Type Headache were most
recently published in 2018 by the International Head-
ache Society.14 Criteria established for migraine and
tension-type headache among others are outlined in
the International Classification of Headache Disor-
ders, 3rd Edition (ICHD-3).13 See Tables 1, 2 and 3.
There are diagnostic differences among these entities
in children and adults. The most notable difference is
the duration of migraine in children versus adults. To
meet criteria for migraine, in adults, qualifying head-
aches last 4-72 h. For children under 18 years of age,
attacks may last from two to 72 h.13
The term “chronic daily headache” is not part of the
ICHD-3. While the ICD-9 code of 784.0 and ICD-10
code R51.9 can be used for headache, unspecified; a
child with a daily headache ought to be able to provide
enough detail to lend itself to be sorted into one of the
categories outlined in the ICHD-3. Patients may have
different types of headaches at different times and
may have mixed features during any individual head-
ache. Multiple codes may be applicable to any indi-
vidual patient at any given time. This is discussed in
detail in the publication outlining the ICHD-3.13 New
daily persistent headache is a reasonable coding
option (ICD-10/ICD-9: G44.52/339.42) if details are
not forthcoming. In this instance requesting the child/
parent keep a headache diary to facilitate diagnosis is
wise and a more specific code may be applied during
a follow up visit. The collected information should
include pain location, character, duration and associ-
ated features. Triggers, attempted treatment and fre-
quency are important details to review. Several tools
have been developed to assist in headache tracking
including a number of apps that enable the child to
track his/her headaches and symptoms on a cellular
device.
Tension type and migraine headaches make up the
majority of the diagnoses in children presenting with
headaches.1 3,8 There are of course a great number of
secondary headaches that may be the result of illness,
Curr Probl Pediatr Adolesc Health Care, July 2021
infection, vascular etiologies, neoplasia, endocrino-
logic or sleep disorder, trauma, substance use or with-
drawal and psychiatric disorders. Proper diagnosis, of
course is necessary to select effective treatment. An
extensive list of secondary headaches is part of the
ICHD-3 criteria and can be accessed online or in the
publication referenced here.13
Red flags
Identifying patients with potentially serious etiolo-
gies for their headaches is not a separate process but a
concomitant activity. At the outset of presentation
there is often a sense of immediacy/urgency on the
family’s part or sometimes a lack of urgency because
the parents are unaware of serious signs and symp-
toms. Children who present with recent trauma, fever,
neurologic deficits and/or persistent vomiting require
a more focused effort to identify serious and treatable
conditions that if left undiagnosed could lead to seri-
ous complications and/or death. Historical informa-
tion gathered from the family/child are critical to
identify concerning symptoms and an expedient,
directed physical examination for specific abnormal
signs is necessary. This type of evaluation requires
prompt, hands on, in person evaluation. Some symp-
toms identified by phone triage can be concerning
enough to direct the child/family immediately to the
emergency department. These “red flags” are
reviewed in detail in a later section. While a thorough
history is required to gather as much necessary detail
as possible in evaluating any headache patient
(Table 4), critical information can be more
TABLE 1. ICHD-3 Criteria for Migraine Without Aura
Migraine without Aura
A. At least five attacks fulfilling criteria B-D
B. Headache attacks lasting 2-72 h* (untreated or unsuccessfully
treated)
C. Headache has at least two of the following four characteristics
-unilateral location
-pulsating quality
-moderate to severe pain intensity
-aggravation by/causing avoidance of routine physical activity (eg,
walking, climbing stairs)
D. During headache at least one of the following:
-nausea and/or vomiting
-photophobia and phonophobia
E. Not better accounted for by another ICHD-3 diagnosis
*in children, 4-72 h in adults.
3
TABLE 2. ICHD-3 Criteria for Migraine With Aura.
Migraine with Aura
A. At leasttwo attacks fulfilling criteria B and C
B. One or more of the following fully reversible aura symptoms:
-visual
-sensory
-speech and/or language
-motor
-brainstem
-retinal
C. At least three of the following six characteristics
-at least one aura symptom spreads gradually over greater than or
equal to 5 min
-two or more aura symptoms occur in succession
-each individual aura symptom last 5-60 min
-at least one aura symptom is unilateral
-at least one aura symptom is positive
-the aura is accompanied or followed within 60 min by headache
D. Not better accounted for by another ICHD-3 diagnosis
Typical Aura Symptoms: fully reversible visual, sensory and/or
speech/language symptoms; no motor, brainstem or retinal
symptoms
Brainstem Aura Symptoms: no motor or retinal symptoms and at least
two of the following: dysarthria, vertigo, tinnitus, hypacusis, diplo-
pia, ataxia not attributable to sensory deficit, decreased level of
consciousness
expeditiously obtained if symptoms listed in Table 5
are identified. An urgent situation may also be
revealed with a targeted physical exam. This includes
a good fundoscopic exam and search for any neuro-
logic asymmetry amongst other findings listed in
Table 6. The identification of asymmetry or other fea-
tures listed in Table 7 may warrant an expedited eval-
uation in an emergency department. This is often the
best approach to expeditiously obtain additional diag-
nostic evaluation such as neuroimaging and/or lumbar
puncture. The level of urgency in any individual situa-
tion may vary, but expedient referral to the ED can
hasten completion of imaging and/or other diagnostics
that rapidly move the patient into appropriate diagno-
sis or treatment.
Urgent imaging
Magnetic Resonance Imaging (MRI) provides the
best resolution of parenchymal abnormalities and
smaller lesions but requires a cooperative, relatively
motionless, patient. Obtaining high quality images
with MRI takes longer when compared to computed
tomography (CT) and is more sensitive to motion
4 Curr Probl Pediatr Adolesc Health Care, July 2021
TABLE 3. ICHD-3 Criteria for Tension-Type Headache.
Tension-Type Headache
Infrequent Episodic Tension-Type Headache (<12 days/year)
10 episodes of headache occurring on <1 day/month on
A. At least
average, fulfilling B-D
B. Lasting from 30 min to 7 days
C. At least two or the following four characteristics
-bilateral location
-pressing or tightening (non-pulsating) quality
-mild or moderate intensity
-not aggravated by routine physical activity such as walking or
climbing stairs
D. Both of the following:
-no nausea or vomiting
-no more than one of the following: photophobia or phonophobia
E. Not better accounted for by another ICHD-3 diagnosis
Frequent Episodic Tension-Type Headache: above criteria 1-14 day-
s/month for > 3 months
Chronic Episodic Tension-Type Headache: above criteria 15 day-
s/month or more for > 3 months
TABLE 4. Important historical information to gather when eval-
uating a headache patient.
History
location/description/character
frequency/duration
precipitated by: _____ improved by: _____
current medications including over the counter therapies
sleep history including electronic use
meals/hydration
physical/social activities
known triggers
psychosocial factors: relationships, grades, substance use
artifact. This can be difficult to accomplish in a pediat-
ric patient, particularly one that may be frightened, in
pain or both. MRI remains the recommended tool
when assessing for potential tumors and posterior
fossa lesions, but it is not always readily available,
and sedation may not be easily accomplished in a
more urgent situation. On the other hand, CT scanning
can often be accomplished without sedation and can
usually provide adequate resolution of large masses,
hydrocephalus, acute bleeding, skull fracture or tissue
injury in a child with recent trauma or concerns for
possible intracranial bleeding.15 Rapid progression or
severe worsening of headaches, focal neurologic defi-
cits, vomiting associated with any of the above are
indications of the need for urgent neuroimaging.14 16
There is a significantly higher percentage of occipi-
tal lobe tumors in younger children.16,17 In one
review, 50% of posterior fossa tumors occurred in
children under 5 years of age while only 15 % Use of any medication can create analgesia rebound
occurred 11 15-year olds.18 headache now referred to as med-
Being knowledgeable about ication overuse headache.22,23
Being knowledgeable about
“red flags” in the history and Failure of an acute treatment
physical exam can help identify “red flags” in the history and strategy can lead to repeated dos-
patients at greater risk for seri- physical exam can help identify ing. This can occur with
ous etiologies more quickly and patients at greater risk for seri- increased frequency and when
minimize routine overuse of ous etiologies more quickly and coupled with lack of insight into
neuroimaging. the contribution of unhealthy life-
minimize routine overuse of style choices, episodic headache
neuroimaging. can rapidly progress to fulfilling
Conversion to chronic criteria for chronic headache.
headache This transformation to chronic
headaches reinforces the importance of a good acute
A discussion of diagnostic criteria would be incom-
treatment strategy backed up by an effective preventive
plete without attention to the increased incidence of
strategy if headaches are frequent and persist.19 23 There
developing chronicity in migraine.19,20 Chronic
are many options to choose from when devising an acute
migraine and tension type headaches are defined in
13 and/or preventive treatment strategy.
the published criteria of the ICHD-3. Headaches
that occur for greater than or equal to 15 days/month
for greater than three months are deemed chronic. Headache management
This annualizes to more than or equal to 180 headache The management of primary headaches in children
days per year.13 A recent review of data from several (the majority being migraine or tension-type) should
nations by Youssef and Mack be customized to each patient
revealed that conversion to depending on type, frequency
chronic headache has been Conversion to chronic headache and severity of the headaches
globally observed in roughly is more likely in individuals with as well as the child’s comorbid
2% of children evaluated for stressful life events, anxiety, medical conditions and thera-
headache. Conversion to
chronic headache is more likely
depression, history of head pies. Treatment focuses on life-
in individuals with stressful life injury, excessive caffeine use, style modifications, acute
headache treatment and preven-
events, anxiety, depression, his- sleep difficulties, allodynia, tive management of more
tory of head injury, excessive allergic rhinitis and lack of an chronic headaches.
caffeine use, sleep difficulties,
allodynia, allergic rhinitis and
optimized acute treatment Often, poor lifestyle habits
strategy. contribute to headache disabil-
lack of an optimized acute ity in children and
treatment strategy. 19 21 adolescents.19 23 Thus, non-
pharmacologic lifestyle modifications can often be
TABLE 5. Items of history that may indicate need for urgent
intervention.
beneficial to young patients. Patients should be
History RED FLAGS
TABLE 6. Important physical exam features to assess when evaluating a
headache present every morning or awakening from sleep with headache patient.
headache
positional or worse with exertion Physical Exam
accelerating course (increasing frequency or severity) blood pressure
any new neurologic deficits/focal weakness cutaneous abnormalities
confusion, impaired consciousness fundoscopic exam
sudden, complete loss of vision complete neurologic exam
diplopia -extraocular movements
personality changes -deep tendon reflexes
loss of balance -motor strength/pronator drift
abrupt decline in school performance -tandem (heel to toe) gait
ANY OF THE ABOVE associated with vomiting -Romberg

Curr Probl Pediatr Adolesc Health Care, July 2021 5

advised to drink adequate amounts of water, limit caf- standard tablet (5 or 10 mg each) has been approved
feine use, eat on a regular schedule (without skipping for use in children 6 years and older. Other forms,
meals) and exercise regularly. Screen time should be such as sumatriptan (25, 50, or 100 mg tablets; 6 mg
limited as well, especially before bedtime. Alterations packaged in a subcutaneous autoinjector; 5 or 20 mg
in sleep patterns can lead to inadequate sleep and, in packaged as a nasal spray), almotriptan (6.25 or
turn, more headaches. Making sure children have a 12.5 mg tablets), and zolmitriptan (2.5 or 5 mg stan-
regular sleep schedule from day to day in addition to dard or orally disintegrating tablets; 2.5 or 5 mg NS)
getting the proper amount of sleep is an important part are FDA approved for patients twelve years and older
of headache control.19 21 but may be cautiously used off label by some special-
Educating parents and patients about healthy life- ists in younger patients. It is important to advise chil-
style choices can lead to striking improvement when dren and their families that triptans are most effective
advice is heeded. If such advice when given at the onset of a
is ignored, pharmacologic inter-
vention may be useless.
Educating parents and patients migraine when the pain is mild.
If given too late in the migraine
about healthy lifestyle choices cycle, the medication may fail
can lead to striking improve- to relieve or only partially
Acute therapy ment when advice is heeded. If relieve headache and associated
symptoms. However, if a child
For headaches that occur less such advice is ignored, pharma- truly fails to respond to one
than once a week, acute medi- cologic intervention may be triptan, he/she may respond to a
cal management is usually suf- useless. different triptan so the child
ficient. Milder to moderate should be offered an alternative
headaches may be treated with triptan. Those triptan medica-
over the counter (OTC) analge- tions available in intranasal sprays or injectable for-
sics, such as acetaminophen, ibuprofen, or naproxen mulations may be the best option for children with
(see Table 8). Caution, however, should be advised to intense, headache onset, nausea and vomiting associ-
limit such use to no more than two to three times per ated with their migraines or for children whose
week to avoid medication overuse headaches and the migraines peak quickly after headache onset. As with
potential of developing a more chronic headache OTC analgesics, clinicians should caution patients to
pattern.19 23 limit triptan use to no more than two doses in twenty-
Children with moderate to severe migraine head- four hours and four doses per week to avoid acute
aches not relieved by over-the-counter analgesics excessive vasoconstriction or the development of
should be offered a triptan for abortive therapy.24,25 chronic medication overuse headache.19 23
These medications can be prescribed to children as
young as six years of age in some instances, down to
age 12 years in others. Rizatriptan, which is available Preventive therapy
in both an orally disintegrating tablet (ODT) or When headaches start occurring more than once a
week on average and are persistently bothersome to
TABLE 7. Physical findings that may indicate need for urgent the child’s life, a preventive medication may be con-
intervention. sidered after any lifestyle issues have been addressed.
Physical Exam RED FLAGS It should be noted, however, that most preventive
papilledema headache medications are used “off-label” in the pedi-
increased BMI with papilledema atric population and not approved by the FDA26 29
meningeal signs
evidence of recent head trauma (See Table 9).
ANY neurologic deficits: For children three years of age and older, cyprohep-
-brainstem or cerebellar signs like ocular paralysis or nystagmus tadine (0.2-0.4 mg/kg/d, max 12 mg/d) is often an
-ataxia
-hemiplegia or other focal finding
effective choice with minimal side effects. It may
-slurred speech cause some drowsiness and increased appetite, mak-
-pronator drift ing nightly dosing ideal.29 Typically, this is more effi-
-altered mental status
cacious in smaller children, but there is no particular

6 Curr Probl Pediatr Adolesc Health Care, July 2021

Curr Probl Pediatr Adolesc Health Care, July 2021
TABLE 8. Rescue Medication for Headache Treatment
Rescue Medications (Start with a medication that has the least amount of side effects. Use no more than 2 times per week.)
Over the counter medications
Medication Drug Class Age Dosage Form Dose Side Effects/comments
Ibuprofen (Motrin, Anti-inflammatory 6 months & older Liquid: 100 mg/5ml Tablet: 10 mg/kg/dose (Max 400 mg/dose) every 4 to 6 h; at Dyspepsia, renal dysfunction, decreased platelet
Advil) 100, 200, 400, 600, 800 mg onset of headache; may repeat once in 3 h. Max 40 mg/kg/ function
Chewable: 50, 100 mg day or 2400 mg/day, whichever is less
Naproxen sodium Anti-inflammatory 12 years & older Liquid: 125 mg/5ml Tablet: 5 to 7 mg/kg/dose every 12 h; max 1000 mg/day Dyspepsia, renal dysfunction. decreased platelet
(Aleve, Naprosyn) 250 mg function
Acetaminophen Analgesic all ages Liquid: 160 mg/5ml Tablet: 10-15 mg/kg/dose; max: 650 mg - 1 gram per dose every Liver dysfunction
(Tylenol) 325, 500 mg 6 h; max 75 mg/kg/day not to exceed 3,750 in those <
50 kg or 4000 mg/day if  50 kg.
Prescription
Medication Drug Class Age Dosage Form Dose Side Effects/comments
Almotriptan* Triptan 12 year and older Tablet: 6.25, 12.5 mg 6.25 - 12.5 mg as single dose; may repeat once in two Reduce dose with CYP3A4 inhibitor. Dizziness, nausea,
(Axert) hours. Max daily dose 25 mg. drowsiness, xerostomia
Rizatriptan* Triptan 6 years & older Tablet: 5, 10 mg ODT: 5, 10 mg < 40 kg: 5 mg as a single dose If also taking propranolol: < 40 kg: do not use rizatrip-
(Maxalt)  40 kg: 10 mg as a single dose, may repeat once in 2 h. tan;  40 kg: 5 mg as a single dose. max dose over
Max daily dose = 20 mg 40kg is 5 mg/day
Sumatriptan* Triptan 6 years & older Tablet: 25, 50, 100 mg 25 to 100 mg by mouth at onset of migraine symptoms; Injection site reaction (SQ use) paresthesia hot or cold
(Imitrex) repeat if no relief in 2 h; max 200 mg/day. sensation malaise/fatigue chest pain/pressure/tight-
SQ: autoinjector 6 mg, vial 3-6 mg in single dose (0.06 mg/kg/dose); max 12 mg/day ness neck pain/pressure/tightness throat pain/pres-
6 mg/0.5ml sure/tightness jaw pain/pressure/tightness dizziness/
Intranasal solution: 5 mg per 5 mg, 10 mg or 20 mg administered in one nostril as single vertigo flushing (SC use) weakness (SQ use) drowsi-
actuation, 20 mg per actuation dose; May repeat once after 2 h. Max 40 mg/day. Weight- ness/sedation (SQ use) diaphoresis (SQ use)
based dose: 20 to 39 mg: 10 mg; >40kg, 20 mg. Can
repeat the dose in 2 h; max 40 mg/day
Zolmitriptan* Triptan 18 years & older Tablet: 2.5, 5 mg ODT: 2.5, Oral: 1.25 to 2.5 mg; max single dose 5 mg, Max daily dose Can use for menstrual migraines 6 years & older off
(Zomig) 5 mg Intranasal spray: 2.5 mg 10 mg. Intranasal: 2.5 mg, may repeat in 2 h. Max daily label. Start 2 days prior to expected onset of menses
per actuation, 5 mg per dose 10 mg. and continued on to 5 days after menses
actuation
12 -18 years Intranasal spray: 2.5 mg per 2.5 mg/dose; repeat if no relief in 2 h; max 10 mg/day
actuation
Ondansetron Antiemetic under 12 years Liquid: 4 mg/5ml Tablet: 4 mg 0.15 mg/kg up to 4 mg given up to 3 times Rare, but can cause headache in which case consider
(Zofran) Max 25 mg/day different antiemetic, blurred vision, dizziness, anxiety
12 years & older Tablet: 8 mg 8 mg up to 3 times a day; Max 40 mg/day
Diphenhydramine Antihistamine 2 years & older Liquid: 12.5 mg/5 ml Tablets: 0.5 - 1 mg/kg/dose every 6 h. Max per dose - 50 mg Nausea, blurred vision, xerostomia
(Benadryl) 25, 50 mg
Prochlorprerazine Antiemetic  8 years Liquid: 4 mg/5ml Tablets: 5, 18-39 kg: 2.5 mg every 8 h or 5 mg every 12 h.  39 kg: 5- Blurred vision, akathisia, dystonic reaction
(Compazine) 10, 25 mg 10 mg every 6-8 h. Max 40 mg/day
Dihydro-egotamine Ergot alkaloid 12 years & older Intranasal spray: 4 mg/ml; One spray (0.5 mg) into each nostril; if needed repeat within Black box warning: Avoid with potent CYP 3A4 inhibitors
(Migranal) 0.5 mg per spray 15 min, up to a total of 4 sprays (2 mg). Max daily dose: 6 such as protease inhibitors, azole antifungals, and
sprays (3 mg per24 h period). Max weekly dose: 8 sprays macrolide antibiotics due to risk of vasospasm and
(4 mg per week). cerebral ischemia. May cause nausea, dizziness,
drowsiness, taste disorder
Ketorolac (formerly Anti-inflammatory 8 years & older Tablet: 10 mg 10 mg tablet every 6 h; max 30 mg/day; limit to 2 day- Headache, nausea, abdominal pain, dyspepsia
known as Toradol) s/week 1 mg/kg IM, single dose; max 30 mg
*No more than 2 doses each day or 4 doses each week.
7
age or weight “cut off” per se. It is available in both
oral solution and tablet formulations. Amitriptyline
can be used at age nine years and up (0.25-1 mg/kg/d
given nightly).30 An EKG should be considered if dos-
ing more than 25 mg/d or in a child with a personal or
family history of syncope or cardiac disease. Another
option for prevention is topiramate29 32 for children
twelve years and older. Dosing should start at 25 mg
nightly or twice daily and may be increased to a max
dose of 200 mg/d. This choice may be especially ben-
eficial in overweight patients due to the side effect
of decreased appetite (when dosed twice daily);
however, clinicians should also be cognizant of the
other potential unwanted side effects. Users may
experience cognitive slowing as well as transient
paresthesias in the hands and feet; these may vary
from mild to intolerable. Topiramate may also be
given nightly to reduce side effects. If prescribing
topiramate to a young woman of childbearing age,
the clinician must discuss the decreased efficacy of
hormonal contraceptives and the potential harm to
the fetus should that patient become pregnant while
taking topiramate. Beta-blockers, such as proprano-
lol (0.5 -3 mg/kg/d divided twice to three times
daily with a max of 120 mg/d), can be used in
non-asthmatic patients and may more be helpful in
patients with comorbid hypertension. Beta blockers
are strictly contraindicated in patients with reactive
airway disease since it may cause bronchoconstric-
tion. Gabapentin33,34 can improve sleep mainte-
nance, decrease restlessness and reduce migraine
headaches; often with fewer side effects, particu-
larly if dosed only at night. Dosing begins with
5 mg/kg/dose initially followed by titrating up to
10-40 mg/kg/day with a maximum dose of
2400 mg. Some headache prevention medications
such as propranolol and topiramate are available as
extended-release forms that can be used once a
day. These features can sometimes help improve
compliance.
Other potential preventive medications that may be
prescribed by headache specialists include, but are not
limited to valproate, verapamil, some SSRIs/SNRIs,
and the newer CGRP (calcitonin gene-related peptide)
antagonist agents (for adolescents/young adults eigh-
teen years and older).
Some children and families prefer more natural ther-
apies for headache prevention (see Table 10). In addi-
tion to lifestyle modifications, clinicians may
recommend some OTC supplements that have shown
8 Curr Probl Pediatr Adolesc Health Care, July 2021
some benefit in headache control.35,36 Magnesium
(250 500 mg/d) may be offered as preventive option
for frequent, mild to moderate headaches.35,36 It can
be readily found in most grocery stores and pharma-
cies in numerous formulations. Riboflavin (50-
400 mg/d), or vitamin B2, can be harder to find OTC,
but may be prescribed, usually divided twice daily.
Often, magnesium and riboflavin are given together
for better prevention than either offers as monother-
apy.35 CoQ10 (10-20 mg/kg/d) is growing in popular-
ity as it theoretically reduces CGRP levels, a
mechanism of action similar to the newest chronic
migraine medications on the market.
A notable complication in demonstrating efficacy in
clinical trials is the fact that the placebo responder
rate is so high. Efficacy of placebo is up to 50% in
children enrolled in treatment trials for migraine med-
ication. The “active” responder rate may be as low as
60% (or as high as 85%).30,37 Migraine based treat-
ments in children have often been anecdotal or based
on “experience”. In the clinical setting, engaging in a
convincing discussion with the patient during the
office visit could result in an improved response. The
assurance that prescribed treatment identified in this
section has been “very helpful to others” is neither
false nor misleading and encouragement can be thera-
peutic.
The biopsychosocial approach to
headache treatment
A discussion of headache treatment would be
incomplete without addressing the impact chronic ill-
ness has on the mental health of our patients. Even
episodic migraine can result in missing school and
recreational activities leading to an accumulation of
make-up school work and a deficit in the much-needed
enjoyable social interactions that keep each of us
healthy. Migraine and mood abnormalities have a
notable relationship and a very recent paper explores
the situation in detail. Gazerani38 notes that mood in
migraine patients can be impacted prior to, during and
after the migraine itself. Much of this may occur in
the “prodromal phase” lending itself to be used as a
predictor of headache onset and potential signal for
initiation of treatment at the earliest possible opportu-
nity. She notes “A multidisciplinary intervention has
been recommended to reduce migraine disability,
improve coping strategies, and reduce chronification
Curr Probl Pediatr Adolesc Health Care, July 2021
TABLE 9. Preventive Medication for Headache Treatment.
Preventive Headache Medications (Start with a medication that has the least amount of side effects. It can take 6 to 8 weeks at the target dose, not the starting dose, to know if the medication will be effective.)
Prescription
Medication Drug Class Age Dosage Form Dose Side Effects/comments
Cyproheptadine Antihistamine 2 years & older Liquid: 2 mg/5ml Tablet: 4 mg Starting dose 0.2 mg/kg (2-4 mg q hs); increase by 2-4 mg Sedation, weight gain not as effective if >80lbs used
(Periactin) each week. Maintenance dose; 0.2 to 0.4 mg/kg (4-8 mg q mostly in children 6 years and younger and 30kg or less
hs). Max dose: < 7 years: 12 mg/day,  7 years: 16 mg/
day
Gabapentin Antiseizure  6 years Liquid: 50mg/ml Tablet: 600, 5 mg/kg/dose titrate up to 10-40 mg/kg/day. Max dose Weight gain, behavior changes can improve REM sleep
(Neurontin) 800 mg Capsule: 100, 300, 2400 mg/day. Given at bedtime
400 mg
Topiramate Antiseizure 12 years & older Tablet: 25, 50, 100, 200 mg Given at bedtime. Start with 1 to 3 mg/kg/dose (top start- Weight loss, cognitive slowing, renal stones. Must rec-
(Topamax) Sprinkle capsule: 15, 25 mg ing dose 25 mg) and increase slowly to maintenance dose ommend daily folic acid supplementation to patients of
of 5 to 9 mg/kg/day.; if giving more than 25 mg, divide into childbearing potential
2 doses/day; max dose 200 mg/24 h; usually effective at
less than or equal to 100 mg/day divided BID
Valproate Antiseizure  7 years Liquid: 250 mg/5 ml Start with 10-15 mg/kg/day divided BID; Max initial dose Somnolence, skin rash, weight gain, tremor, drowsi-
(Depakote) Tablet ER: 250, 500 mg Cap- 250 mg; Increase in increments over 4 to 6 weeks to max ness, hematological or liver function abnormalities.
sule: 250 mg Capsule DR sprin- 45 mg/kg/day in two divided doses. Max daily Must recommend daily folic acid supplementation to
kles: 125 mg dose = 1000 mg/day patients of childbearing potential
Verapamil (Calan) Calcium channel 12 years and older Tablet (immediate release): 40, Start with 40 mg TID; increase by 40 mg weekly. Mainte- For prevention of cluster headaches Constipation, hypo-
blocker 80, 120 mg nance dose 40-80 mg TID; Max dose 480 mg/day (up to tension, nausea, AV block, weight gain. Obtain EKG
160 mg TID) before starting and 1 week after dosing changes
Amitriptyline (Elavil) Antidepressant TCA 9 years & older Tablet: 10, 25, 50, 75, 100, Start with 0.1 to 0.25 mg/kg/dose at bedtime; increase by dizziness, sleepiness, dry mouth, palpitations, can pro-
150 mg 0.25 mg/kg/day every 2 weeks to 1 mg/kg/day. Max long QT (caution or alternative with patient or family his-
2 mg/kg or 75 mg daily. If giving over 25 mg/24 h, monitor tory of arrythmia)
cardiac status/EKG
Propranolol Beta blocker  7 years Liquid: 20 mg/5ml, 40 mg/5ml 0.5 - 3 mg/kg/day in 2-3 divided doses; Max 120 mg/day Cough, dizziness, light headedness, anxiety, sleep
(Inderal) Tablet: 10, 20, 40, 60, 80 mg problems do not use with asthma can exacerbate
depression use with caution in diabetics
Venlafaxine SNRI 8-17 years Tablet: 25, 37.5, 50, 75, Major depressive disorder: immediate release 8-12 years: Case specific Black Box Warning Serious reactions: sui-
(Effexor) 100 mg Tablet ER: 37.5, 75, Start 12.5 mg QD x3 days, increase to 12.5 mg BID cidality depression exacerbation hypomania/mania
150, 225 mg Capsule ER: 37.5, x3 days, then increase to 12.5 mg TID; max 75 mg/day; serotonin syndrome Common reactions: headache nau-
75, 150 mg give with food; taper dose over 2 weeks to discontinue sea insomnia dizziness anorexia somnolence
Immediate release 13-17 years: Start 25 mg QD x3 days,
increase to 25 mg BID x3 days, then increase to 25 mg TID;
max 75 mg/day; give with food; taper dose over 2 weeks to
discontinue Extended release 7-17 years: Start 37.5 mg ER
QD, increase by 37.5 mg/day ER Q4-7 days; give with food;
may open ER cap but do not cut/crush/chew/dissolve con-
tents; do not cut/crush/chew/dissolve ER tab; taper dose
by no more than 75 mg/week to discontinue Generalized
anxiety disorder 7-17 years: Start 37.5 mg ER QD, increase
by 37.5 mg/day ER Q4-7 days; give with food; may open ER
cap but do not cut/crush/chew/dissolve contents; do not
cut/crush/chew/dissolve ER tab; taper dose by no more
than 75 mg/week to discontinue
9
TABLE 10. Naturopathic Options for Headache Treatment
Preventive Headache Medications (Start with a medication that has the least amount of side effects. It can take 6 to 8 weeks at the target dose,
not the starting dose, to know if the medication will be effective.)
Over the counter
Medication Age Dosage Form
Magnesium oxide* 8-21 years Capsule: 250, 400 mg
Magnesium citrate* 8-21 years Capsule: 125, 250 mg
Magnesium glycinate* 8-21 years Capsule: 100, 200, 400 mg
Vitamin B2 (riboflavin) 8-21 years Tablet: 50, 100 mg
Melatonin 8-21 years Tablet: 1, 3, 5 mg
* In general, lower doses of magnesium cause less diarrhea. Titrate to migraine benefit and least side effects.
risks in children with migraine. Pharmacological and
non-pharmacological strategies are both available and
effective. Biofeedback, relaxation, and cognitive-
behavioral therapy yield positive outcomes in pediat-
ric migraine. Developing healthy lifestyle habits (diet,
exercise, sleep) also seems to improve migraine in
this population.”38
Research into the impact of cognitive behavior ther-
apy (CBT) combined with amitriptyline versus head-
ache education combined with amitriptyline revealed
a convincing difference in outcomes.39 Education
included non-specific support/sharing of headache-
related educational materials. The CBT group were
paced through evidence-based coping skill protocols
for pediatric pain management that included biofeed-
back monitoring of thermal and electromyographic
responses involved in relaxation.39 The reduction in
headache days for the CBT group was almost twice
that of the “education group” (headaches were down
by 11.5 days in the CBT group versus 6.8 days in the
education group over a 20-week trial period). In fol-
low-up patients with higher baseline depression and
those from lower income households had poorer
prognosis.40
Even brief psychological intervention can facilitate
some degree of improvement in anxiety in patients
with chronic illness. In one review of 12 randomized
controlled trials, interventions lasting less than 6 total
hours over less than 10 sessions were found to be of
benefit. Techniques included CBT, parenting interven-
tions, family/systemic therapy, music therapy,
10
Dose Side Effects & Comments
400 mg caps once a day 250 mg Least readily absorbed, therefore
caps twice a day theoretically may be least likely to
assist systemic functions including
those of the CNS. May be best for
constipation.*
125 mg or 250 mg caps, 1-2 caps Much better absorption, can still be
once or twice a day used for constipation (usually in liq-
uid form).*
100 mg caps, 1-3 times a day Good absorption. Least likely to
200 mg caps, once or twice a day cause.*
400 mg caps, once a day
50 mg to 100 mg twice a day Transient diarrhea, GI upset, bright
yellow urine
3 to 6 mg; 20 min prior to sleep Nightmares
massage therapy, hypnosis and biofeedback among
others.41 Preventive treatment for headache should
include strategies that promote psychological well-
being. This not only reduces the psychological impact
of chronic illness, but also facilitates reduction in the
financial burden created when providing care to
chronically ill children.42
Subsequent treatment opportunities
When headache does not lend itself to acute inter-
vention and efforts to manage the situation at home
have failed, some patients are able to gain relief with
more aggressive treatment in the ED25,43,44 or an infu-
sion center.44 Combinations of ketorolac, diphenhy-
dramine and prochlorperazine, promethazine or
metoclopramide administered intravenously along
with a normal saline fluid bolus,25,43,44 can result in
headache resolution in some instances admission to
provide several doses may be necessary.45 Intravenous
administration of valproate or magnesium sulfate may
also provide relief. Inpatient treatment can include all
of the above and/or dihydroergotamine (DHE).43 45
Caution must be exercised when patients have used a
triptan. DHE should not be given within 24 h of the
administration of a triptan and vice versa.46 Children
who are unable to remain hydrated or retain medica-
tion prescribed due to vomiting can receive intrave-
nous rescue treatment to minimize physical suffering
and added psychological strain from missing school
and other activities.3 5,20,30,45
Curr Probl Pediatr Adolesc Health Care, July 2021
 When headaches fail to respond to preventive meas- Transition from debilitating to disabling can be avoided
ures and persist despite the child and family being edu- through proper diagnosis, education and a multidisciplin-
cated about healthy lifestyle choices and being ary approach to children who do not respond quickly to
prescribed appropriate acute and preventive medication intervention. Engaging our psychology colleagues in the
strategies, referral to a neurologist and psychologist may care of children with headaches can be crucial to improv-
be helpful. The reiteration of the need for healthy ing their headaches and overall well-being. Appropriate
choices, attention to regular meals, a proper amount of diagnosis facilitates effective treatment and education of
sleep and managing stress is likely to occur in the neu- the child and family regarding lifestyle choices is neces-
rology office, reinforcing what has been said in the pri- sary since pharmacologic treatment can be rendered use-
mary care office. Pursuing more novel strategies less in a child who is not eating or sleeping well.
including the recently developed CGRP antagonists47,48 Economic costs shrink when children with headaches are
mentioned above or neuromodulation therapy available provided with appropriate options and an understanding
with approved devices such as NerivioÒ 49,50 and of when to pursue more aggressive/expensive options.
CefalyÒ 51,52 may follow. Some clinicians are adept at Preemptive identification of serious causes for headache
occipital nerve blocks43,53,54 (in addition to supraorbital before patients are in acute distress can be simultaneously
and auriculotemporal blocks) as well as onabotulimtox- accomplished when performing a focused but thorough
inA.55,56 These interventions are not uniformly approved history and physical examination. Classification and treat-
for use in children, but trials for the CGRP agents are ment strategies will continue to evolve with time. Morbid-
underway and some insurance companies approve use in ity and disability from childhood headaches can be
Ò
teens who meet specific criteria. Nerivio is now reduced when primary care clinicians master these con-
approved for use in adolescents 12 years of age and cepts.
above.50 This device provides relief via conditioned pain
modulation and is worn on the arm. The device provides
a non-painful stimulation that travels along C-fibers to
Declaration of Competing Interest
the trigeminal ganglion in an effort to disrupt the pro- None of the authors have any conflicts of interest.
cesses involved in the pain pathway during migraine.
The CefalyÒ device is approved for use in adults, oper-
ates through similar technology and is applied to the
Acknowledgements
forehead. It is being used both as an acute therapy51 and Gogi Kumar MD, Pediatric Neurologist, Dayton
a preventive treatment.52 Advanced therapies such as Children’s Hospital, Division Chief, Division of
use of nerve blocks, Botox injec- Neurology
tions, neuromodulation and Daniel Lacey MD, Pediatric
CGRP antagonists can be facili- Neurologist, Dayton Children’s
tated through referral to a neurol- Hospital, Division of
ogist when more standard Neurology
approaches fail. Advanced therapies such as use Judene Thome MD, Pediatri-
of nerve blocks, Botox injec- cian, PriMed Pediatrics
Summary tions, neuromodulation and Rebecca Dandoy MD, Pedia-
CGRP antagonists can be facili- trician, Premier Health
Migraine and tension-type Sarah MacDonald RN, Clini-
headache in addition to other
tated through referral to a neu- cal Care Coordinator, Dayton
headache types are common in rologist when more standard Children’s Hospital, Division
children and adolescents. The approaches fail. of Neurology
physical, psychological and eco- Angela Eberhart CNP, Man-
nomic burden is significant and ager Population Health and
can become quite difficult for children with chronic head- Quality Improvement, Dayton
aches. Prevention of overuse of acute medication, trans- Children’s Hospital, Clinically Integrated Network
formation to a chronic state, school absences and the Sandy Spoltman, Manager Population Health and
ensuing need to complete missed work are important Data Analytics, Dayton Children’s Hospital, Clini-
goals when caring for children who experience migraine. cally Integrated Network

Curr Probl Pediatr Adolesc Health Care, July 2021 11

 References
1. Raieli V, D'Amico A, Piro E. Migraine in children under
7 years of age: a review. Curr Pain Headache Rep 2020;24
(12):79 https://doi.org/10.1007/s11916-020-00912-5.
2. Arruda MA, Guidetti V, Galli F, Albuquerque RC, Bigal ME.
Primary headaches in childhood A population-based study.
Cephalalgia 2010;30(9):1056–64. https://doi.org/10.1177/
0333102409361214.
3. Abu-Arefeh I, Russell G. Prevalence of headache and
migraine in schoolchildren. BMJ 1994;309(6957):765–9.
https://doi.org/10.1136/bmj.309.6957.765.
4. Nieswand V, Richter M, Gossrau G. Epidemiology of head-
ache in children and adolescents-another type of pandemia.
Curr Pain Headache Rep 2020;24(10):62 https://doi.org/
10.1007/s11916-020-00892-6.
5. Philipp J, Zeiler M, W€ober C, et al. Prevalence and burden of
headache in children and adolescents in Austria - a nationwide
study in a representative sample of pupils aged 10-18 years. J
Headache Pain 2019;20(1):101 https://doi.org/10.1186/
s10194-019-1050-8.
6. W€ober-Bing€ol Ç. Epidemiology of migraine and headache in
children and adolescents. Curr Pain Headache Rep
2013;17:341. https://doi.org/10.1007/s11916-013-0341-z.
7. Abu-Arafeh I, Razak S, Sivaraman B, Graham C. Prevalence
of headache and migraine in children and adolescents: a sys-
tematic review of population-based studies. Dev Med Child
Neurol 2010;52(12):1088–97. https://doi.org/10.1111/j.1469-
8749.2010.03793.x.
8. Abu-Arafeh I, Howells R. Primary headaches in children
under the age of 7 years. Curr Pain Headache Rep 2014;18
(3):401. https://doi.org/10.1007/s11916-013-0401-4.
9. Provided by Dayton Children’s Hospital and Dayton Child-
ren’s Health Partners
10. de Boer I, van den Maagdenberg AMJM, Terwindt GM.
Advance in genetics of migraine. Curr Opin Neurol 2019;32
(3):413–21. https://doi.org/10.1097/WCO.0000000000000687.
11. Eidlitz-Markus T, Haimi-Cohen Y, Zeharia A. Association of
age at onset of migraine with family history of migraine in
children attending a pediatric headache clinic: a retrospective
cohort study. Cephalalgia 2015;35(8):722–7. https://doi.org/
10.1177/0333102414554114.
12. Sufrinko A, McAllister-Deitrick J, Elbin RJ, Collins MW,
Kontos AP. Family history of migraine associated with post-
traumatic migraine symptoms following sport-related concus-
sion. J Head Trauma Rehabil 2018;33(1):7–14. https://doi.
org/10.1097/HTR.0000000000000315.
13. Headache Classification Committee of the International Head-
ache Society (IHS). The international classification of head-
ache disorders, 3rd edition. Cephalalgia 2018;38(1):1–211.
https://doi.org/10.1177/0333102417738202.
14. Trofimova A, Vey BL, Mullins ME, Wolf DS, Kadom N.
Imaging of children with nontraumatic headaches. AJR Am J
Roentgenol 2018;210(1):8–17. https://doi.org/10.2214/
AJR.17.18561.
15. Cain MR, Arkilo D, Linabery AM, Kharbanda AB. Emer-
gency department use of neuroimaging in children and adoles-
cents presenting with headache. J Pediatr 2018;201:196–201.
https://doi.org/10.1016/j.jpeds.2018.05.023.
12
16. Irwin SL, Gelfand AA. Occipital headaches and neuroimaging
in children. Curr Pain Headache Rep 2018;22(9):59 https://
doi.org/10.1007/s11916-018-0712-6.
17. Genizi J, Khourieh-Matar A, Assaf N, Chistyakov I, Srugo I.
Occipital headaches in children: are they a red flag?
J Child Neurol 2017;32(11):942–6. https://doi.org/10.1177/
0883073817723266.
18. Prasad KSV, Ravi D, Pallikonda V, Raman BVS. Clinico-
pathological study of pediatric posterior fossa tumors. J
Pediatr Neurosci 2017;12(3):245–50. https://doi.org/10.4103/
jpn.JPN_113_16.
19. Youssef PE, Mack KJ. Episodic and chronic migraine in chil-
dren. Dev Med Child Neurol 2020;62(1):34–41. https://doi.
org/10.1111/dmcn.14338.
20. Torres-Ferr us M, Ursitti F, Alpuente A, et al. From trans-
formation to chronification of migraine: pathophysiological
and clinical aspects. J Headache Pain 2020;21(1):42
https://doi.org/10.1186/s10194-020-01111-8.
21. Blumenfeld AM, Varon SF, Wilcox TK, et al. Disability,
HRQoL and resource use among chronic and episodic migrai-
neurs: results from the international burden of migraine study
(IBMS). Cephalalgia 2011;31(3):301–15. https://doi.org/
10.1177/0333102410381145.
22. Diener HC, Dodick D, Evers S, et al. Pathophysiology, pre-
vention, and treatment of medication overuse headache. Lan-
cet Neurol 2019;18(9):891–902. https://doi.org/10.1016/
S1474-4422(19)30146-2.
23. Abrams BM. Medication overuse headaches. Med Clin North Am
2013;97(2):337–52. https://doi.org/10.1016/j.mcna.2012.12.007.
24. Gelfand AA. Pediatric and adolescent headache. Continuum
(Minneap Minn) 2018;24:1108–36. https://doi.org/10.1212/
CON.0000000000000638:4, Headache.
25. Bachur R, et al. A comparison of acute treatment of regimens
for migraine in the emergency department. Pediatrics
2015;135(2):232–8.
26. Locher C, Kossowsky J, Koechlin H, et al. Efficacy, safety,
and acceptability of pharmacologic treatments for pediatric
migraine prophylaxis: a systematic review and network meta-
analysis. JAMA Pediatr 2020;174(4):341–9. https://doi.org/
10.1001/jamapediatrics.2019.5856.
27. Oskoui M, Pringsheim T, Holler-Managan Y, et al. Practice
guideline update summary: acute treatment of migraine in
children and adolescents: report of the guideline development,
dissemination, and implementation subcommittee of the
american academy of neurology and the american headache
society [published correction appears in neurology2020 Jan
7;94(1):50] Neurology 2019;93(11):487–99. https://doi.org/
10.1212/WNL.0000000000008095.
28. El-Chammas K, Keyes J, Thompson N, Vijayakumar J,
Becher D, Jackson JL. Pharmacologic treatment of pediatric
headaches: a meta-analysis. JAMA Pediatr 2013;167(3):250–
8. https://doi.org/10.1001/jamapediatrics.2013.508.
29. Eiland LS, Jenkins LS, Durham SH. Pediatric migraine: phar-
macologic agents for prophylaxis. Ann Pharmacother
2007;41(7):1181–90. https://doi.org/10.1345/aph.1K049.
30. Hershey AD, Powers SW, Coffey CS, et al. Childhood and
adolescent migraine prevention (CHAMP) study: a double-
blinded, placebo-controlled, comparative effectiveness study
Curr Probl Pediatr Adolesc Health Care, July 2021
 of amitriptyline, topiramate, and placebo in the prevention of
childhood and adolescent migraine. Headache 2013;53
(5):799–816. https://doi.org/10.1111/head.12105.
31. Lewis D, Winner P, Saper J, et al. Randomized, double-blind,
placebo-controlled study to evaluate the efficacy and safety of
topiramate for migraine prevention in pediatric subjects 12 to
17 years of age. Pediatrics 2009;123(3):924–34. https://doi.
org/10.1542/peds.2008-0642.
32. Winner P, Pearlman EM, Linder SL, et al. Topiramate for
migraine prevention in children: a randomized, double-blind,
placebo-controlled trial. Headache 2005;45(10):1304–12.
https://doi.org/10.1111/j.1526-4610.2005.00262.x.
33. Belman A, et al. Gabapentin for migraine prophylaxis in chil-
dren (abstract). Ann Neurol 2001;50:S109.
34. Mathew NT, Rapoport A, Saper J, et al. Efficacy of gabapen-
tin in migraine prophylaxis. Headache 2001;41(2):119–28.
35. Orr SL. The evidence for the role of nutraceuticals in the man-
agement of pediatric migraine: a review. Curr Pain Headache
Rep 2018;22(5):37. https://doi.org/10.1007/s11916-018-0692-
6:Published 2018 Apr 4.
36. Wang F, Van Den Eeden SK, Ackerson LM, Salk SE, Reince
RH, Elin RJ. Oral magnesium oxide prophylaxis of frequent
migrainous headache in children: a randomized, double-blind,
placebo-controlled trial. Headache 2003;43(6):601–10.
https://doi.org/10.1046/j.1526-4610.2003.03102.x.
37. Lewis DW, Winner P, Wasiewski W. The placebo responder
rate in children and adolescents. Headache 2005;45(3):232–9.
https://doi.org/10.1111/j.1526-4610.2005.05050.x.
38. Gazerani P. Migraine and mood in children. Behav Sci (Basel)
2021;11(4):52. https://doi.org/10.3390/bs11040052:Published
2021 Apr 14.
39. Powers SW, Kashikar-Zuck SM, Allen JR, et al. Cognitive
behavioral therapy plus amitriptyline for chronic migraine
in children and adolescents: a randomized clinical trial.
JAMA 2013;310(24):2622–30. https://doi.org/10.1001/
jama.2013.282533.
40. Rettig EK, Ergun G, Warfield JR, et al. Predictors of Improve-
ment in pediatric chronic migraine: results from the cognitive-
behavioral therapy and amitriptyline trial [published online ahead
of print, 2021 May 24]. J Clin Psychol Med Settings 2021.
https://doi.org/10.1007/s10880-021-09782-4:10.1007/s10880-
021-09782-4.
41. Catanzano M, Bennett SD, Sanderson C, et al. Brief psycho-
logical interventions for psychiatric disorders in young people
with long term physical health conditions: a systematic review
and meta-analysis. J Psychosom Res 2020;136:110187.
https://doi.org/10.1016/j.jpsychores.2020.110187.
42. Cottrell D. Prevention and treatment of psychiatric disorders
in children with chronic physical illness. Arch Dis Child
2015;100(4):303–4. https://doi.org/10.1136/archdischild-
2014-307866.
43. Patniyot IR, Gelfand AA. Acute treatment therapies for pedi-
atric migraine: a qualitative systematic review. Headache
2016;56(1):49–70. https://doi.org/10.1111/head.12746.
Curr Probl Pediatr Adolesc Health Care, July 2021
44. Kabbouche M. Management of pediatric migraine headache in
the emergency room and infusion center [published correction
appears in headache. 2016 Apr;56(4):819]. Headache
2015;55(10):1365–70. https://doi.org/10.1111/head.12694.
45. Kabbouche M. Pediatric inchild headache therapy: what is
available. Headache 2015;55(10):1426–9. https://doi.org/
10.1111/head.12701.
46. Smith JH. Acute treatment of migraine in adults. In:
Swanson JW, Goddeau RP, (eds). UpToDate, Waltham, MA:
UpToDate Inc., 2021. https://www.uptodate.com/contents/
acute-treatment-of-migraine-in-adultsAccessed April 15.
47. Maasumi K, Michael RL, Rapoport AM. CGRP and migraine:
the role of blocking calcitonin gene-related peptide ligand and
receptor in the management of migraine. Drugs 2018;78
(9):913–28. https://doi.org/10.1007/s40265-018-0923-5.
48. Szperka CL, VanderPluym J, Orr SL, et al. Recommendations
on the use of anti-CGRP monoclonal antibodies in children
and adolescents. Headache 2018;58(10):1658–69. https://doi.
org/10.1111/head.13414.
49. Yarnitsky D, Dodick DW, Grosberg BM, et al. Remote Elec-
trical Neuromodulation (REN) relieves acute migraine: a ran-
domized, double-blind, placebo-controlled, multicenter trial.
Headache 2019;59(8):1240–52. https://doi.org/10.1111/
head.13551.
50. Hershey AD, Lin T, Gruper Y, et al. Remote electrical
neuromodulation for acute treatment of migraine in adoles-
cents. Headache 2021;61(2):310–7. https://doi.org/10.1111/
head.14042.
51. Chou DE, Shnayderman Yugrakh M, Winegarner D, Rowe V,
Kuruvilla D, Schoenen J. Acute migraine therapy with exter-
nal trigeminal neurostimulation (ACME): a randomized con-
trolled trial. Cephalalgia 2019;39(1):3–14. https://doi.org/
10.1177/0333102418811573.
52. Didier HA, Di Fiore P, Marchetti C, et al. Electromyography
data in chronic migraine patients by using neurostimulation
with the CefalyÒ device. Neurol Sci 2015;36(Suppl 1):115–9.
https://doi.org/10.1007/s10072-015-2154-9.
53. Szperka CL, Gelfand AA, Hershey AD. Patterns of use of
peripheral nerve blocks and trigger point injections for pediat-
ric headache: results of a survey of the American headache
society pediatric and adolescent section. Headache 2016;56
(10):1597–607. https://doi.org/10.1111/head.12939.
54. Dubrovsky AS. Nerve blocks in pediatric and adolescent
headache disorders. Curr Pain Headache Rep 2017;21
(12):50. https://doi.org/10.1007/s11916-017-0650-8.
55. Chan VW, McCabe EJ, MacGregor DL. Botox treatment for
migraine and chronic daily headache in adolescents. J Neuro-
sci Nurs 2009;41(5):235–43. https://doi.org/10.1097/
jnn.0b013e3181aaa98f.
56. Shah S, Calderon MD, Wu W, Grant J, Rinehart J. Onabotuli-
numtoxin a (BOTOXÒ ) for ProphylaCTIC treatment of pediatric
migraine: a retrospective longitudinal analysis. J Child Neurol
2018;33(9):580–6. https://doi.org/10.1177/0883073818776142.
13