Pediatric Migraine: Epidemiology, Clinical Presentation, Diagnosis, Management, Psychological Impact, and Non-Pharmacological Treatments

Abstract

Migraine, a debilitating primary headache disorder, represents a significant yet often underrecognized and undertreated health challenge within the pediatric and adolescent populations. This comprehensive review aims to provide an exhaustive analysis of pediatric migraine, delineating its intricate epidemiology, diverse clinical manifestations, and the inherent complexities associated with its diagnosis. Furthermore, it delves into the established management strategies, encompassing both acute abortive and preventive pharmacological interventions, prior to the widespread advent of calcitonin gene-related peptide (CGRP) inhibitors. Critical attention is also given to the profound psychological and social impacts experienced by affected children and adolescents, alongside an in-depth exploration of the efficacy and mechanisms of various non-pharmacological treatments, including lifestyle modifications, behavioral therapies, and emerging non-invasive neuromodulation techniques. This detailed exposition offers a foundational understanding of the multifaceted landscape of pediatric migraine, emphasizing the necessity of a holistic, multidisciplinary approach to care.

Many thanks to our sponsor Esdebe who helped us prepare this research report.

1. Introduction

Migraine, far from being solely an adult affliction, constitutes a pervasive and profoundly disabling primary headache disorder affecting a substantial proportion of children and adolescents globally. It is characterized by recurrent episodes of moderate to severe head pain, frequently accompanied by an array of autonomic and neurological symptoms, including nausea, vomiting, photophobia, and phonophobia. Unlike the often stereotyped presentation in adults, pediatric migraine exhibits distinct features and a broader spectrum of symptomatic expression, frequently complicating its early recognition and accurate diagnosis. The burden extends beyond the physical pain, encompassing significant impairment in academic performance, social interaction, and overall quality of life, leading to substantial psychosocial morbidity. Despite its high prevalence and significant impact, pediatric migraine continues to be a largely underdiagnosed and undertreated condition, contributing to prolonged suffering and increased healthcare utilization. This necessitates a thorough and nuanced understanding of its complex epidemiology, varied clinical presentations, inherent diagnostic challenges, and the comprehensive range of management strategies available before the transformative introduction of CGRP-targeted therapies. Such an understanding is crucial for clinicians, researchers, and families alike, facilitating improved patient outcomes and enhancing the quality of life for these vulnerable young individuals.

Many thanks to our sponsor Esdebe who helped us prepare this research report.

2. Epidemiology

The epidemiological profile of pediatric migraine underscores its status as a highly prevalent neurological disorder, with its incidence and prevalence demonstrating dynamic shifts across different age groups and genders. Understanding these patterns is fundamental to appreciating the scope of the condition and informing public health strategies.

2.1 Prevalence and Incidence

Migraine affects approximately 3-10% of children aged 5-15 years, with a notable increase in prevalence during adolescence, reaching 8-23% among adolescents aged 12-17 years. The prevalence rates are generally lower in prepubertal children, with an approximate equal distribution between boys and girls, or even a slight male predominance in some younger cohorts [Ref 1]. However, a significant epidemiological shift occurs around puberty, where there is a marked increase in prevalence among females. Post-puberty, the female-to-male ratio can be as high as 2:1 or even 3:1, mirroring the pattern observed in adult populations [Ref 2, 3]. This pronounced gender disparity strongly suggests a pivotal role for hormonal influences, particularly fluctuating estrogen levels, in the pathogenesis of migraine susceptibility and expression. Longitudinal studies indicate that migraine often tracks into adulthood, with a significant proportion of children experiencing chronic migraine continuing to have chronic or high-frequency episodic migraine as adults [Ref 2]. The observed variations in prevalence figures across different studies can be attributed to several factors, including diverse methodologies, differing age cohorts, and the specific diagnostic criteria applied, highlighting the need for standardized epidemiological approaches.

2.2 Age of Onset

The typical age of onset for pediatric migraine ranges broadly, usually occurring between the ages of 5 and 15 years, with a discernible peak during early adolescence, typically around 11 to 13 years [Ref 2, 4]. While rarer, migraine can manifest in preschool children, and even in infants, often presenting as migraine equivalents or episodic syndromes, such as benign paroxysmal vertigo of childhood or cyclic vomiting syndrome. An earlier age of onset is generally associated with a higher likelihood of migraine persisting into adulthood, potentially indicating a more severe phenotype or a stronger genetic predisposition [Ref 4]. Conversely, migraine onset in late adolescence may share more similarities with adult-onset migraine, both in terms of clinical characteristics and prognostic implications. Recognizing the age of onset is crucial for anticipating disease trajectory and tailoring long-term management strategies.

2.3 Risk Factors

The etiology of pediatric migraine is multifactorial, arising from a complex interplay of genetic predispositions and various environmental, physiological, and psychological factors. These risk factors often modulate an individual’s susceptibility and contribute to the frequency and severity of migraine attacks.

2.3.1 Genetic Predisposition

Genetic factors play an undeniable and substantial role in the susceptibility to migraine. A positive family history of migraine is present in a remarkable 70-80% of affected children and adolescents, often with a clear autosomal dominant inheritance pattern [Ref 4]. Studies have identified several genes associated with monogenic forms of migraine, most notably Familial Hemiplegic Migraine (FHM). FHM, a rare subtype, is linked to mutations in ion channel genes such as CACNA1A (FHM1), ATP1A2 (FHM2), and SCN1A (FHM3), which encode for calcium, sodium-potassium ATPase, and sodium channels, respectively. These mutations lead to neuronal hyperexcitability and altered cortical spreading depression (CSD) thresholds, which is believed to be the underlying neurophysiological event of aura and potentially the migraine headache itself [Ref 5].

Beyond these rare monogenic forms, common forms of migraine are considered polygenic, involving multiple genes with small additive effects. Genome-wide association studies (GWAS) have identified numerous single nucleotide polymorphisms (SNPs) associated with common migraine, implicating genes involved in neuronal excitability, neurotransmitter regulation (e.g., glutamatergic, serotonergic pathways), vascular function, and pain processing [Ref 6]. These genetic predispositions create a neurobiological vulnerability, where individuals are inherently more sensitive to various internal and external triggers that can precipitate a migraine attack.

2.3.2 Environmental and Lifestyle Triggers

While genetics lay the groundwork, environmental and lifestyle factors frequently act as precipitating triggers for migraine attacks in predisposed individuals. Identifying and managing these triggers is a cornerstone of non-pharmacological migraine management.

• Stress: Psychological stress is one of the most commonly reported migraine triggers in children and adolescents, affecting up to 80% of sufferers [Ref 7]. Academic pressures, peer relationships, family conflicts, and even excitement or anticipation of events can induce stress. The physiological response to stress involves activation of the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system, leading to the release of stress hormones (e.g., cortisol, adrenaline) and inflammatory mediators, which can lower the migraine threshold [Ref 7].
• Sleep Disturbances: Both insufficient sleep and excessive sleep, as well as irregular sleep patterns (e.g., weekend lie-ins), are significant triggers. Sleep deprivation can disrupt homeostatic processes, alter neurotransmitter balance, and increase brain excitability. There is a bidirectional relationship between sleep and migraine, where poor sleep can trigger attacks, and migraine pain itself can disrupt sleep architecture, leading to a vicious cycle [Ref 8]. Insomnia, sleep apnea, and restless legs syndrome are common comorbidities that can exacerbate migraine.
• Dietary Factors: While highly individual, certain dietary factors are frequently implicated. Skipping meals can lead to hypoglycemia, a common trigger. Specific food items include aged cheeses, processed meats (containing nitrites), chocolate, caffeine (both excessive intake and withdrawal), artificial sweeteners (aspartame), monosodium glutamate (MSG), and certain food additives [Ref 9]. Dehydration is also a significant and often overlooked trigger, emphasizing the importance of adequate fluid intake.
• Hormonal Changes: Fluctuations in hormone levels, particularly estrogen, are prominent triggers, especially in adolescent females. Menarche often marks the onset or exacerbation of migraine, and attacks frequently cluster around menstruation (menstrual migraine). Oral contraceptive use can also influence migraine frequency and severity, though effects are variable [Ref 3].
• Environmental Stimuli: Sensory overload can precipitate attacks. This includes bright or flickering lights (photophobia), loud noises (phonophobia), strong odors (osmophobia) such as perfumes, smoke, or certain chemicals, and weather changes (barometric pressure changes, storms) [Ref 10].
• Physical Exertion: Intense or prolonged physical activity, especially in individuals unaccustomed to it, can sometimes trigger a migraine attack, though regular, moderate exercise is generally protective.
• Head Trauma: While not a direct trigger for episodic migraine, a history of mild traumatic brain injury (concussion) can sometimes lead to the development or exacerbation of post-traumatic headaches, which can resemble migraine.
• Medication Overuse: Chronic use of acute migraine medications (e.g., NSAIDs, triptans, opioids) can paradoxically lead to medication overuse headache (MOH), also known as rebound headache, transforming episodic migraine into a chronic daily or near-daily headache pattern [Ref 11].

2.3.3 Comorbidities

Pediatric migraine frequently co-occurs with other medical and psychiatric conditions, which can act as aggravating factors or complicate management. These include anxiety disorders, depression, attention-deficit/hyperactivity disorder (ADHD), obesity, asthma, allergic rhinitis, and epilepsy. The presence of these comorbidities often necessitates a more integrated and multidisciplinary approach to care [Ref 12].

Many thanks to our sponsor Esdebe who helped us prepare this research report.

3. Clinical Presentation

The clinical presentation of migraine in children and adolescents shares core features with adult migraine but also exhibits unique characteristics, often making diagnosis challenging due to developmental differences in symptom expression and reporting.

3.1 Headache Characteristics

In children, migraine headaches often present with distinct features that differ from the classic adult presentation. While adult migraine is typically unilateral and pulsating, pediatric migraines frequently present as bilateral, frontal, or temporal headaches in younger children, evolving to a more unilateral pattern as they age [Ref 1]. The pain character is often described as throbbing or pulsating, reflecting the vascular component of the migraine process. The intensity is typically moderate to severe, meaning it significantly interferes with or prevents normal daily activities, such as school attendance or play. Children may express pain by crying, irritability, withdrawal, or refusal to engage in activities they usually enjoy. Pain scales appropriate for age, such as Faces Pain Scale-Revised (FPS-R) or visual analog scales, are crucial for objective assessment of intensity.

Pediatric migraine attacks are generally shorter in duration than in adults, lasting from 2 to 72 hours [Ref 1]. In younger children, attacks can be even briefer, sometimes only lasting 1-2 hours, which can be easily overlooked or misattributed. If left untreated or ineffectively treated, the headache can persist for the full 72 hours, leading to significant functional impairment.

Beyond the headache phase, children may experience prodromal symptoms hours or even days before the headache onset. These premonitory symptoms, though often difficult for younger children to articulate, can include mood changes (irritability, euphoria), fatigue, difficulty concentrating, neck stiffness, excessive yawning, food cravings, or increased urination. The postdromal phase, often referred to as the ‘migraine hangover,’ follows the resolution of the headache and can last for several hours to a day. During this phase, children may feel fatigued, have difficulty concentrating, experience muscle soreness, or feel generally unwell [Ref 13]. Recognizing these phases is vital for a comprehensive understanding of the child’s migraine experience and for timely intervention.

3.2 Associated Symptoms

Migraine attacks in children are almost invariably accompanied by a constellation of non-headache symptoms that significantly contribute to the overall burden of the condition.

• Nausea and Vomiting: These are among the most common and distressing associated symptoms, occurring in a high proportion of pediatric migraineurs. Nausea can be severe enough to prevent oral medication intake, while vomiting can lead to dehydration and further discomfort. Abdominal pain frequently accompanies nausea, particularly in younger children, sometimes mimicking gastrointestinal illnesses [Ref 1].
• Photophobia and Phonophobia: Sensitivity to light (photophobia) and sound (phonophobia) are hallmark features. Children with photophobia will often seek out a dark room, pull curtains, or complain about bright lights. Phonophobia manifests as a desire for quiet, irritability with noises, or covering their ears. Both symptoms contribute to the child’s withdrawal from normal activities during an attack [Ref 1].
• Osmophobia: While less frequently discussed than photophobia and phonophobia, an increased sensitivity to smells (osmophobia) is also reported by some children during migraine attacks, contributing to their sensory aversion.
• Allodynia: Cutaneous allodynia, where normally non-painful stimuli (e.g., light touch of hair or skin, wearing clothing) become painful, can occur in pediatric migraine, signaling central sensitization and often associated with more severe attacks [Ref 14].
• Aura: Migraine with aura occurs in about one-third of older children and adolescents, though it is less common in younger children. Auras are transient neurological symptoms that typically precede or sometimes accompany the headache, developing gradually over 5-20 minutes and lasting up to 60 minutes. The most common type is visual aura, characterized by flickering lights, spots, lines (scintillating scotomas), or even temporary partial or complete loss of vision [Ref 1]. Other types of aura include:
  • Sensory aura: Tingling, numbness, or pins and needles sensations that spread gradually over a limb or one side of the face.
  • Speech aura (dysphasic aura): Difficulty with word finding, slurred speech, or misunderstanding spoken words.
  • Motor aura (seen in hemiplegic migraine): Unilateral weakness, ranging from mild clumsiness to complete paralysis, which can be alarming and necessitates careful differentiation from stroke or other neurological emergencies [Ref 15].
  • Brainstem aura (formerly Basilar-type Migraine): Symptoms include vertigo, dysarthria (slurred speech), tinnitus, diplopia (double vision), and bilateral paresthesias, often without motor weakness. These symptoms indicate involvement of the brainstem structures [Ref 15].

3.3 Migraine Variants (Episodic Syndromes that may be Associated with Migraine)

Children may experience certain ‘migraine variant’ syndromes, now classified as ‘episodic syndromes that may be associated with migraine’ by the International Classification of Headache Disorders (ICHD-3). These conditions often precede or co-occur with migraine later in life, and their recognition is crucial for early diagnosis and appropriate management.

• Abdominal Migraine: Predominantly seen in school-aged children, abdominal migraine is characterized by recurrent episodes of acute, moderate to severe, midline abdominal pain, typically around the navel. These attacks are usually accompanied by nausea, vomiting, pallor, and anorexia, often lasting from 1 to 72 hours. There are symptom-free intervals between attacks. A strong family history of migraine is common, and many children with abdominal migraine eventually develop typical migraine headaches [Ref 4]. The diagnosis is based on clinical criteria and exclusion of gastrointestinal pathology.
• Cyclic Vomiting Syndrome (CVS): CVS involves recurrent, stereotypical episodes of intense nausea and intractable vomiting, often occurring with a predictable pattern and separated by symptom-free intervals lasting weeks to months. The vomiting is severe, frequent, and debilitating, leading to significant dehydration and requiring hospitalization for intravenous fluids. Accompanying symptoms often include abdominal pain, pallor, lethargy, and photophobia/phonophobia. CVS is considered a migraine equivalent due to its strong association with migraine in patients and their families, and its response to migraine therapies [Ref 4].
• Benign Paroxysmal Vertigo of Childhood (BPV): BPV is characterized by sudden, brief, recurrent episodes of vertigo in otherwise healthy children, often occurring without warning. During an attack, the child may appear dizzy, lose balance, stumble, or hold onto objects for support. Nystagmus (involuntary eye movements) and vomiting can occur. Attacks are usually brief, lasting seconds to minutes, and resolve spontaneously. Like abdominal migraine, BPV is often a precursor to later typical migraine headaches [Ref 4].
• Benign Paroxysmal Torticollis of Infancy (BPTI): Seen in infants, BPTI involves recurrent episodes of head tilt (torticollis) that typically last for hours or days, spontaneously resolving. Episodes may be accompanied by pallor, vomiting, or irritability. It is considered an early life manifestation of migraine susceptibility [Ref 16].
• Acute Confusional Migraine: A rare but dramatic variant, acute confusional migraine presents with transient episodes of confusion, disorientation, memory loss, agitation, and speech difficulties, often following minor head trauma or extreme exertion. These symptoms typically resolve within hours, followed by a severe headache. It is important to differentiate from seizures or other acute neurological conditions [Ref 17].

Many thanks to our sponsor Esdebe who helped us prepare this research report.

4. Diagnosis

The diagnosis of pediatric migraine is primarily clinical, relying heavily on a detailed history obtained from the child and parents, a thorough physical examination, and the application of standardized diagnostic criteria. Challenges in diagnosis stem from developmental factors and the need to differentiate migraine from other headache types, including potentially serious secondary causes.

4.1 Diagnostic Criteria

Diagnosis of migraine in children and adolescents is guided by the International Classification of Headache Disorders, 3rd edition (ICHD-3 Beta criteria) [Ref 18]. The ICHD-3 provides specific criteria for both migraine without aura and migraine with aura, tailored to the pediatric population acknowledging the unique features:

For Migraine Without Aura (A1.1):

• A. At least 5 attacks fulfilling criteria B-D.
• B. Headache lasting 2-72 hours (untreated or unsuccessfully treated). In children, attacks may last 1-72 hours.
• C. Headache has at least two of the following four characteristics:
  • 1. Bilateral location (often frontal/temporal) in children, evolving to unilateral in adolescents/adults.
  • 1. Pulsating quality.
  • 1. Moderate or severe pain intensity.
  • 1. Aggravation by or causing avoidance of routine physical activity (e.g., walking, climbing stairs).
• D. During the headache, at least one of the following:
  • 1. Nausea and/or vomiting.
  • 1. Photophobia and phonophobia (or just one of these in younger children).
• E. Not better accounted for by another ICHD-3 diagnosis.

For Migraine With Aura (A1.2):

• A. At least two attacks fulfilling criteria B and C.
• B. Aura consisting of at least one of the following fully reversible symptoms:
  • 1. Visual (e.g., flickering lights, spots, lines).
  • 1. Sensory (e.g., tingling, numbness).
  • 1. Speech and/or language (dysphasia).
  • 1. Motor (weakness – usually indicating hemiplegic migraine).
  • 1. Brainstem (e.g., vertigo, dysarthria, tinnitus, diplopia).
  • 1. Retinal (monocular visual disturbance).
• C. At least two of the following four characteristics:
  • 1. At least one aura symptom spreads gradually over >= 5 minutes, and/or two or more symptoms occur in succession.
  • 1. Each individual aura symptom lasts 5-60 minutes. (If motor aura is present, it may last longer, up to 72 hours).
  • 1. At least one aura symptom is unilateral (except for brainstem aura, which can be bilateral).
  • 1. The aura is accompanied or followed within 60 minutes by headache.
• D. Not better accounted for by another ICHD-3 diagnosis.

A comprehensive history remains the cornerstone of diagnosis. This includes asking about headache frequency, duration, intensity, character, location, associated symptoms, triggers, relieving factors, impact on daily life (school, social activities), previous treatments, and family history of headaches. A headache diary can be invaluable for tracking these details over time. A thorough physical and neurological examination is essential to rule out secondary causes of headache. This includes assessing vital signs, head circumference, fundoscopy (for papilledema), cranial nerve function, motor and sensory systems, reflexes, coordination, and gait. Neuroimaging (MRI or CT) is generally not required for typical migraine presentations but is indicated if there are ‘red flags’ suggestive of a secondary headache, such as abnormal neurological exam findings, sudden onset of severe headache, headache worsening over time, or associated systemic symptoms [Ref 19].

4.2 Challenges

Diagnosing pediatric migraine presents several challenges that necessitate careful clinical acumen and a comprehensive approach.

• Developmental Considerations: Younger children may struggle to articulate their symptoms accurately. Instead of describing a ‘throbbing’ headache, they might express pain through irritability, crying, withdrawal from play, or changes in sleep patterns. Parents’ observations are therefore critical, though their interpretations can sometimes be subjective [Ref 20]. As children mature, their ability to describe symptoms improves, aligning more closely with adult descriptions.
• Overlapping Symptoms: Differentiating migraine from other primary headache disorders, particularly tension-type headaches (TTH), can be challenging due to overlapping symptoms. While migraine tends to be more severe, throbbing, and associated with nausea and sensory sensitivities, TTH is typically milder, pressing/tightening, and not aggravated by routine physical activity. However, mixed presentations can occur, and some children with frequent TTH may also experience episodic migraine [Ref 19].
• Ruling Out Secondary Headaches (‘Red Flags’): The paramount challenge is to exclude secondary headaches caused by underlying structural, infectious, or systemic conditions. Clinicians must be vigilant for ‘red flags’ that suggest a more serious etiology, often remembered by the SNOOP mnemonic (adapted for pediatrics):
  • Systemic symptoms (fever, weight loss, rash, malaise) or Secondary risk factors (e.g., cancer, immunocompromise).
  • Neurological symptoms or signs (e.g., focal weakness, numbness, papilledema, seizures, altered mental status, changes in gait) not typical of migraine aura.
  • Onset: new, sudden, severe headache (‘thunderclap’), or onset after age 6-8 (for new migraine-like headaches) or under 3 years.
  • Other associated conditions: head trauma, illicit drug use, medication overuse.
  • Previous headache history: change in pattern, increasing frequency/severity [Ref 19].
    Conditions to consider include brain tumors, hydrocephalus, central nervous system infections (meningitis, encephalitis), idiopathic intracranial hypertension, cerebral venous thrombosis, sinusitis, post-concussion syndrome, and medication overuse headache. Timely neuroimaging (MRI preferred over CT due to radiation exposure) is crucial if red flags are present.
• Comorbidity with Psychiatric Disorders: The high comorbidity rates between pediatric migraine and psychiatric conditions such as anxiety and depression can complicate diagnosis. Migraine symptoms can mimic or exacerbate psychological distress, and vice-versa. This necessitates careful assessment to distinguish primary headache symptoms from those influenced by mood disorders [Ref 12].
• Lack of Objective Biomarkers: Unlike many medical conditions, migraine diagnosis currently relies entirely on clinical criteria, as there are no specific blood tests or imaging findings that definitively diagnose migraine. This lack of objective markers can sometimes lead to diagnostic delays or misdiagnoses, especially in cases with atypical presentations or in very young children.

Many thanks to our sponsor Esdebe who helped us prepare this research report.

5. Management

Effective management of pediatric migraine requires a comprehensive and individualized approach that integrates acute symptom relief with preventive strategies, coupled with robust patient and family education. The primary goals are to reduce pain and associated symptoms, minimize disability, prevent headache recurrence, and improve overall quality of life.

5.1 Acute Treatment

The cornerstone of acute migraine management is early intervention, ideally within the first 15-30 minutes of headache onset, to prevent the progression of central sensitization and improve treatment efficacy. The choice of acute medication depends on headache severity, associated symptoms, and patient preference [Ref 21].

5.1.1 Non-Pharmacological Measures (Acute)

Before or alongside medication, simple non-pharmacological measures can provide immediate relief:

• Rest: Encouraging the child to rest in a quiet, dark room away from light, noise, and screens.
• Cold Compress: Applying a cold compress or ice pack to the forehead or back of the neck.
• Hydration: Ensuring adequate fluid intake, especially if vomiting is present.
• Sleep: For some children, falling asleep can significantly alleviate the headache.

5.1.2 First-Line Pharmacological Treatments

• Nonsteroidal Anti-inflammatory Drugs (NSAIDs): NSAIDs are often the first-line pharmacological treatment for mild to moderate migraine attacks, or as initial therapy for severe attacks. They work by inhibiting cyclooxygenase enzymes (COX-1 and COX-2), thereby reducing prostaglandin synthesis, which plays a role in pain and inflammation. Commonly used NSAIDs include:
  • Ibuprofen: Approved for children aged 6 months and older. Typical dosage is 10 mg/kg (max 400 mg) orally. It is generally well-tolerated with few side effects when used appropriately [Ref 21].
  • Naproxen: Also effective, often with a longer duration of action, making it suitable for longer-lasting attacks. Typical dosage is 5-7.5 mg/kg (max 500 mg) orally. It is generally indicated for children 12 years and older for migraine [Ref 21].
  • Potential side effects of NSAIDs include gastrointestinal upset, though these are less common with short-term, acute use.
• Acetaminophen (Paracetamol): While generally less effective for migraine than NSAIDs, acetaminophen (15 mg/kg, max 1000 mg) can be considered for mild attacks or when NSAIDs are contraindicated. Its efficacy is often limited for moderate to severe migraine [Ref 21].
• Triptans: For moderate to severe migraine attacks, or those unresponsive to NSAIDs, triptans are highly effective and are considered a cornerstone of acute treatment in adolescents. Triptans are selective serotonin 5-HT1B/1D receptor agonists that act by constricting intracranial blood vessels and inhibiting the release of pro-inflammatory neuropeptides from trigeminal nerve endings [Ref 22]. Several triptans are approved for pediatric use:
  • Rizatriptan: Oral disintegrating tablets (ODT) are approved for children aged 6-17 years (5 mg for 6-11 years, 10 mg for 12-17 years). ODT formulation is beneficial for children who struggle with pills or have accompanying nausea [Ref 21].
  • Zolmitriptan: Nasal spray is approved for adolescents aged 12-17 years (5 mg). The nasal formulation offers rapid absorption and bypasses the gastrointestinal tract, which is advantageous in the presence of nausea or vomiting [Ref 21].
  • Sumatriptan: Nasal spray (approved for 12-17 years) and oral tablets (approved for 18 years and older, but often used off-label in older adolescents) are available. Sumatriptan subcutaneous injection can be used for severe, refractory attacks in an emergency setting [Ref 21].
  • Almotriptan: Oral tablets are approved for adolescents aged 12-17 years. Similar to other triptans in efficacy and side effect profile [Ref 23].
  • Common triptan side effects, often termed ‘triptan sensations,’ can include chest tightness, throat tightness, tingling, and flushing, though these are generally mild and transient. Contraindications include uncontrolled hypertension, ischemic heart disease, and basilar or hemiplegic migraine due to theoretical vasoconstrictive risks [Ref 22].
• Antiemetics: For children experiencing significant nausea and vomiting, antiemetic medications like ondansetron (0.15 mg/kg orally or IV) can be administered to improve comfort and facilitate the absorption of oral analgesics [Ref 21].
• Rescue Medications: For severe, intractable migraine attacks or status migrainosus (migraine lasting >72 hours), rescue medications may be required in an emergency department setting. Intravenous dihydroergotamine (DHE) or glucocorticoids (e.g., dexamethasone) may be used to break the headache cycle, though DHE requires careful monitoring and is generally reserved for severe cases [Ref 24].

5.1.3 Medication Overuse Headache (MOH)

A critical consideration in acute treatment is the prevention of medication overuse headache (MOH). MOH can develop when acute headache medications are used too frequently (e.g., NSAIDs >15 days/month, triptans >10 days/month) over several months. It transforms episodic migraine into a chronic daily or near-daily headache pattern that is often refractory to treatment [Ref 11]. Educating families about the risks of MOH and promoting responsible use of acute medications is paramount. Management of MOH involves discontinuing the overused medication, which can lead to a temporary worsening of headaches before improvement.

5.2 Preventive Treatment

Preventive strategies are considered for children and adolescents with frequent, severe, or disabling migraine attacks that significantly impact their quality of life, despite adequate acute treatment. Indications for preventive therapy typically include more than 2-4 migraine attacks per month, prolonged attacks, significant school absenteeism or disability, medication overuse, or uncommon migraine types (e.g., hemiplegic migraine). The goal of preventive therapy is to reduce migraine frequency, severity, and duration by at least 50% [Ref 25].

Pharmacological prevention in the pre-CGRP era primarily relied on medications originally developed for other conditions but found to have efficacy in migraine prophylaxis. The choice of preventive medication is highly individualized, considering efficacy, side effect profile, comorbidities, and patient/family preferences. Most preventive medications are started at a low dose and gradually titrated up to a therapeutic dose to minimize side effects.

• Beta-blockers:
  • Propranolol: One of the most commonly used and best-studied preventive agents. It is thought to exert its effect through multiple mechanisms, including blockade of beta-adrenergic receptors, leading to central and peripheral vasoconstriction, and modulation of serotonin pathways. Dosage typically starts low (e.g., 10-20 mg/day) and is titrated up. Side effects can include fatigue, bradycardia, hypotension, and exacerbation of asthma. It is generally well-tolerated but requires monitoring of heart rate and blood pressure [Ref 25].
• Anticonvulsants:
  • Topiramate: Approved for migraine prevention in adults and adolescents (12 years and older). Its mechanism of action in migraine is complex, involving voltage-gated sodium channels, GABAergic enhancement, and glutamate receptor antagonism. Dosage starts low (e.g., 25 mg/day) and is slowly titrated. Common side effects include paresthesias (tingling), cognitive slowing (word-finding difficulties, memory issues), weight loss (often desired by adolescents), and less commonly, kidney stones or angle-closure glaucoma. Careful monitoring is required [Ref 25].
  • Valproic Acid (Divalproex Sodium): While effective in adult migraine prevention, its use in pediatric migraine is limited due to concerns regarding significant side effects, including weight gain, hair loss, tremor, and more serious risks such as liver toxicity (especially in younger children) and pancreatitis. It is generally reserved for refractory cases and used with caution, requiring regular liver function monitoring [Ref 25].
• Calcium Channel Blockers:
  • Flunarizine: While not available in the United States, flunarizine is widely used in Europe and Canada for pediatric migraine prevention and has a good evidence base. It acts by blocking calcium channels, thereby stabilizing neuronal membranes and preventing vasoconstriction. Side effects can include sedation, weight gain, and depression. It is generally considered effective and well-tolerated where available [Ref 26].
• Antidepressants:
  • Amitriptyline: A tricyclic antidepressant (TCA) used at low doses for migraine prevention, often administered at bedtime due to its sedating effects. Its antimigraine mechanism is independent of its antidepressant effect, involving modulation of serotonin and norepinephrine pathways and blocking of histamine and muscarinic receptors. Side effects include sedation, dry mouth, constipation, and weight gain. It is particularly useful for children with comorbid sleep disturbances or anxiety/depression [Ref 25].
• Other Agents:
  • Cyproheptadine: An antihistamine with serotonin-blocking properties, often considered for younger children due to its mild side effect profile and promotion of appetite/weight gain, which can be beneficial in underweight children. It can cause sedation [Ref 25].
  • NSAIDs: For predictable patterns like menstrual migraine, NSAIDs taken around the time of menstruation can be an effective preventive strategy [Ref 27].

Preventive therapy typically requires a trial of 2-3 months at an adequate dose to assess efficacy. If successful, the medication may be continued for 6-12 months and then gradually tapered, with the aim of achieving sustained remission. Patient and family education, adherence monitoring, and regular follow-up are critical for successful preventive management.

Many thanks to our sponsor Esdebe who helped us prepare this research report.

6. Psychological Impact

Pediatric migraine is far more than just a headache; it is a chronic illness that profoundly impacts the emotional, social, and academic well-being of affected children and adolescents, as well as their families. The intermittent yet often debilitating nature of migraine attacks can lead to significant psychosocial distress and functional impairment.

6.1 Emotional and Social Effects

• Anxiety and Depression: Children and adolescents with migraine have a significantly higher prevalence of anxiety and depressive disorders compared to their healthy peers [Ref 12, 28]. The chronic pain, unpredictability of attacks, fear of future attacks, and associated disability can lead to considerable emotional distress. Anxiety may manifest as generalized anxiety, separation anxiety (especially in younger children), or panic attacks, particularly related to school or social events. Depressive symptoms can include persistent sadness, loss of interest in activities, fatigue, sleep disturbances, and feelings of hopelessness [Ref 28]. This emotional burden can exacerbate pain perception and lower coping thresholds, creating a vicious cycle.
• Social Withdrawal and Isolation: Migraine attacks often necessitate withdrawal from social activities, such as school, sports, or peer gatherings. This can lead to feelings of isolation, loneliness, and a sense of being different from their peers. Repeated absences from school due to migraine attacks can result in academic underperformance, falling behind on coursework, and increased stress, further perpetuating the migraine cycle. They may miss out on important social developmental milestones and extracurricular opportunities [Ref 28].
• Reduced Quality of Life: The cumulative effect of pain, associated symptoms, emotional distress, and functional limitations significantly diminishes the overall quality of life for children with migraine. Quality of life scales (e.g., Pediatric Quality of Life Inventory – PedsQL) consistently show lower scores in physical, emotional, social, and school functioning domains compared to healthy controls. This impact extends to family quality of life, as parents often experience stress, worry, and disruption to their own routines and work schedules due to their child’s illness [Ref 29].
• Stigma: Children with chronic pain conditions like migraine may experience stigma from peers, teachers, and even family members who may not fully comprehend the invisible nature of their suffering or perceive their symptoms as exaggerated. This can lead to feelings of shame, misunderstanding, and reluctance to disclose their pain.

6.2 Comorbidities

The relationship between pediatric migraine and various comorbidities is complex and often bidirectional, meaning that migraine can predispose to these conditions, and vice versa. Understanding these associations is crucial for a holistic management approach.

• Psychiatric Comorbidities: As mentioned, anxiety disorders (e.g., Generalized Anxiety Disorder, Social Anxiety Disorder, Separation Anxiety Disorder) and Major Depressive Disorder are highly prevalent in children and adolescents with migraine [Ref 12]. Other psychiatric comorbidities include obsessive-compulsive disorder (OCD) and Attention-Deficit/Hyperactivity Disorder (ADHD). The shared neurobiological pathways involving neurotransmitters like serotonin, norepinephrine, and dopamine are thought to underlie these associations. Chronic pain itself can contribute to the development of mood disorders, and conversely, untreated anxiety or depression can lower pain thresholds and exacerbate migraine frequency and severity.
• Other Medical Comorbidities: Pediatric migraine is also frequently associated with other medical conditions, including:
  • Obesity: A clear association exists, with obese children having a higher prevalence of migraine and a greater likelihood of chronic daily headache. Obesity may contribute to chronic inflammation and altered pain processing [Ref 30].
  • Irritable Bowel Syndrome (IBS) and Functional Abdominal Pain: There is a significant overlap between migraine and functional gastrointestinal disorders, particularly abdominal migraine and IBS, suggesting shared underlying mechanisms such as visceral hypersensitivity and dysregulation of the gut-brain axis [Ref 32].
  • Sleep Disorders: Insomnia, sleep apnea, and restless legs syndrome are common in pediatric migraineurs, often contributing to and being exacerbated by the headaches. Addressing sleep hygiene and sleep disorders is critical for migraine management [Ref 8].
  • Epilepsy: A well-established comorbidity exists, with migraine being more common in individuals with epilepsy, and epilepsy more common in individuals with migraine. This link suggests shared mechanisms involving neuronal excitability and cortical spreading depression [Ref 31].
  • Asthma and Allergies: A less understood but observed association, possibly due to shared inflammatory pathways or immune system dysregulation.

The presence of these comorbidities necessitates an integrated management approach, often involving collaboration between neurologists, pain psychologists, psychiatrists, and other specialists, to address all facets of the child’s health and improve overall outcomes.

Many thanks to our sponsor Esdebe who helped us prepare this research report.

7. Non-Pharmacological Treatments

Non-pharmacological treatments are fundamental to the comprehensive management of pediatric migraine, serving as first-line interventions, adjuncts to medication, and crucial components of long-term prevention. They empower children and families with self-management skills, reduce reliance on medication, and minimize side effects.

7.1 Lifestyle Modifications (Headache Hygiene)

Establishing and maintaining consistent ‘headache hygiene’ is a cornerstone of migraine prevention. These lifestyle adjustments aim to minimize triggers and promote overall physiological stability.

• Regular Sleep Patterns: Consistency in bedtime and wake time, even on weekends, is paramount. Avoiding oversleeping, ensuring adequate sleep duration for age, and creating a conducive sleep environment (dark, quiet, cool room) are vital. Limiting screen time before bed helps improve sleep quality [Ref 33].
• Balanced Diet and Regular Meals: Skipping meals can lead to hypoglycemia, a common migraine trigger. Encouraging three balanced meals a day and healthy snacks helps maintain stable blood sugar levels. While specific food triggers are individual, keeping a food diary can help identify and then avoid potential culprits like caffeine, processed foods, artificial sweeteners, and certain aged products. However, overly restrictive diets should be avoided unless a clear trigger is identified [Ref 33].
• Hydration: Adequate fluid intake is essential, as dehydration is a common and easily modifiable trigger. Children should be encouraged to drink water throughout the day, especially during physical activity or hot weather [Ref 33].
• Stress Management: Given that stress is a major trigger, teaching children and adolescents effective stress-coping strategies is critical. This includes identifying stressors, practicing relaxation techniques (e.g., deep breathing exercises, progressive muscle relaxation), engaging in enjoyable hobbies, and ensuring a balance between academic demands and leisure time. Parental stress management also plays a role, as parental anxiety can exacerbate a child’s pain [Ref 33, 34].
• Regular Physical Activity: Engaging in moderate, regular physical activity (e.g., 30-60 minutes most days of the week) has been shown to reduce migraine frequency and severity. It promotes endorphin release, reduces stress, improves sleep, and helps maintain a healthy weight. Activities should be introduced gradually to avoid triggering headaches initially [Ref 33].
• Limiting Caffeine Intake: Excessive caffeine consumption, whether from sodas, energy drinks, or coffee, can trigger headaches and lead to caffeine withdrawal headaches. Reducing or eliminating caffeine, particularly in adolescents, is an important step [Ref 11].
• Avoiding Overuse of Acute Medications: This reiterates the importance of educating children and families on the risks of medication overuse headache (MOH) and adhering to prescribed acute medication limits. This is a crucial lifestyle modification to prevent chronic headache progression [Ref 11].

7.2 Behavioral Therapies

Behavioral therapies are highly effective, evidence-based non-pharmacological interventions for pediatric migraine, often recommended as first-line preventive treatments, either alone or in conjunction with medication. They teach children self-regulation skills and strategies to cope with pain and triggers.

• Cognitive-Behavioral Therapy (CBT): CBT is a structured, goal-oriented psychological therapy that helps children identify and change maladaptive thought patterns, feelings, and behaviors related to their pain. For migraine, CBT typically involves:
  • Psychoeducation: Teaching the child and family about migraine pathophysiology, triggers, and the pain cycle.
  • Cognitive Restructuring: Challenging negative or catastrophic thoughts about pain (e.g., ‘I can’t cope,’ ‘This pain will never go away’) and replacing them with more realistic and positive coping statements.
  • Relaxation Training: Teaching various relaxation techniques such as diaphragmatic breathing, progressive muscle relaxation (tensing and relaxing different muscle groups), and guided imagery (visualizing a peaceful scene) to reduce physiological arousal and muscle tension [Ref 34].
  • Stress Inoculation Training: Preparing the child to anticipate and manage stressors that might trigger headaches.
  • Problem-Solving Skills: Developing practical strategies for managing school, social, and family challenges related to migraine.
  • Behavioral Activation: Encouraging participation in enjoyable activities, even when feeling some pain, to prevent social withdrawal and improve mood. CBT is often delivered by a pain psychologist and involves active participation from parents, especially for younger children [Ref 34]. It has demonstrated significant efficacy in reducing headache frequency, intensity, and disability.
• Biofeedback: Biofeedback is a technique that teaches individuals to gain voluntary control over involuntary physiological responses (e.g., muscle tension, skin temperature, heart rate, brainwave activity) through real-time monitoring and feedback. For migraine, common types include:
  • Thermal Biofeedback: The child learns to increase peripheral skin temperature (e.g., in the fingers), which is often decreased during migraine, indicating sympathetic nervous system activation. This is thought to promote vasodilation and relaxation [Ref 35].
  • Electromyography (EMG) Biofeedback: Measures muscle tension (e.g., in the forehead or shoulders) and teaches the child to relax these muscles, as muscle tension can be a trigger or exacerbate headache [Ref 35].
  • Heart Rate Variability (HRV) Biofeedback: Teaches control over the variability in the time interval between heartbeats, reflecting autonomic nervous system balance. By increasing HRV, children can enhance their parasympathetic tone, promoting relaxation and stress reduction. Biofeedback can be a highly effective treatment, particularly for chronic migraine, by empowering children to self-regulate their physiological responses to stress and pain [Ref 35].
• Relaxation Techniques: Beyond those integrated into CBT, stand-alone relaxation techniques like mindfulness meditation, yoga, and tai chi can be beneficial. These practices focus on cultivating awareness of the present moment, reducing stress, and promoting a sense of calm.

7.3 Non-Invasive Neuromodulation

In the years preceding the widespread clinical availability of CGRP inhibitors, several non-invasive neuromodulation devices emerged as promising options for both acute and preventive migraine management in children and adolescents, offering drug-free alternatives or adjuncts to traditional therapies. These devices modulate brain activity or nerve pathways involved in pain processing.

• Single-Pulse Transcranial Magnetic Stimulation (sTMS): This device (e.g., Spring TMS, now eNeura sTMS mini) delivers a brief magnetic pulse to the occipital cortex, inducing a localized electrical current that can modulate neuronal excitability. It has received FDA clearance for acute treatment of migraine with aura and later for prevention in adults and adolescents aged 12 years and older [Ref 36]. The precise mechanism is thought to involve inhibition of cortical spreading depression (CSD), the underlying neurophysiological event of aura and possibly the headache itself.
• Non-Invasive Vagal Nerve Stimulation (nVNS): This handheld device (e.g., gammaCore) delivers mild electrical stimulation to the vagus nerve in the neck through the skin. The vagus nerve plays a crucial role in modulating pain pathways, inflammation, and autonomic nervous system function. nVNS has been approved for acute and preventive treatment of episodic cluster headache, and later for acute and preventive treatment of migraine in adults and adolescents (12 years and older). It offers a non-pharmacological option with a favorable side effect profile, typically involving mild and transient local skin irritation or muscle twitching [Ref 37].
• External Trigeminal Nerve Stimulation (eTNS): This device (e.g., Cefaly) is placed on the forehead and delivers electrical impulses to stimulate the branches of the trigeminal nerve. The trigeminal nerve is central to migraine pathophysiology. eTNS is cleared for acute treatment of migraine attacks and for preventive treatment of episodic migraine in adults and adolescents (8 years and older for some models). It is thought to modulate pain processing within the trigeminal system. Common side effects are usually mild, such as a tingling sensation or local skin irritation [Ref 38].

These non-invasive neuromodulation devices represent important advancements, providing patients with new options, particularly for those who cannot tolerate or do not respond to conventional pharmacological treatments, and align well with the desire for drug-free options in pediatric care.

7.4 Nutritional Supplements and Complementary/Alternative Medicine

Certain nutritional supplements have garnered interest for migraine prevention, though evidence in children is often less robust than in adults. These typically have favorable safety profiles, making them attractive options for pediatric use.

• Magnesium: Magnesium deficiency has been implicated in migraine pathophysiology. Supplementation (e.g., magnesium oxide 400-600 mg/day) may help stabilize neuronal excitability and prevent CSD. It is generally well-tolerated, with diarrhea being the most common side effect [Ref 39].
• Riboflavin (Vitamin B2): High doses of riboflavin (e.g., 200-400 mg/day) are thought to improve mitochondrial energy metabolism, which may be dysfunctional in migraine. It is generally safe, with bright yellow urine as a harmless side effect [Ref 39].
• Coenzyme Q10 (CoQ10): Similar to riboflavin, CoQ10 (e.g., 100-300 mg/day) is an antioxidant and plays a role in mitochondrial function. It is considered safe and may be beneficial for some patients [Ref 39].

Other complementary approaches, such as acupuncture, have shown mixed but promising results in some studies for reducing migraine frequency and severity in adults, and its role in pediatric migraine is under investigation. Bio-psycho-social approaches, which integrate various non-pharmacological strategies into a holistic care plan, are increasingly recognized as the most effective long-term solutions for pediatric migraine management, particularly for chronic or highly disabling forms.

Many thanks to our sponsor Esdebe who helped us prepare this research report.

8. Conclusion

Pediatric migraine is a complex, pervasive, and often profoundly disabling neurological disorder that imposes significant burdens on affected children, adolescents, and their families. Despite its high prevalence, it remains a condition that is frequently underdiagnosed and undertreated, leading to prolonged suffering and substantial impairment in daily functioning, including academic performance, social interactions, and overall quality of life. The unique clinical presentations in children, the inherent challenges in differentiating migraine from other headache types, and the crucial need to exclude secondary causes necessitate a high degree of clinical vigilance and expertise.

Prior to the widespread integration of CGRP inhibitors, the comprehensive management of pediatric migraine relied on a multifaceted approach, strategically combining acute pharmacological interventions for symptom relief with sustained preventive pharmacological therapies. Crucially, a robust foundation of non-pharmacological treatments, including targeted lifestyle modifications, evidence-based behavioral therapies like Cognitive-Behavioral Therapy and biofeedback, and the emerging utility of non-invasive neuromodulation techniques, formed the bedrock of long-term care. These non-pharmacological strategies not only reduce medication reliance and side effects but also empower young patients with essential self-management skills, fostering resilience and improving their ability to cope with a chronic condition.

The profound psychological impact of migraine, manifesting as increased rates of anxiety, depression, and social withdrawal, underscores the critical importance of a holistic, multidisciplinary care model. This approach often integrates the expertise of neurologists, pain psychologists, and other specialists, addressing not only the physical symptoms but also the emotional and social well-being of the child and their family. Recognizing and managing comorbidities is equally vital for optimizing outcomes.

Continued research into the intricate pathophysiology of pediatric migraine, the identification of reliable biomarkers, and the development of even more targeted and child-friendly therapeutic options remain vital. Furthermore, enhanced public awareness and education are essential to improve early diagnosis, ensure equitable access to specialized care, and ultimately alleviate the considerable suffering associated with this challenging condition. By embracing a comprehensive and compassionate approach, clinicians can significantly improve outcomes and enhance the quality of life for children and adolescents living with migraine, enabling them to lead fuller, healthier lives.

Many thanks to our sponsor Esdebe who helped us prepare this research report.

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