Pediatric anxiety

An update for primary care NPs

Abstract

New guidelines for identifying anxiety in pediatric patients constitute important changes in screening for primary care providers, including primary care NPs. This article seeks to guide NPs in both following the screening guidelines and providing strategic care for patients and their families.

In Brief

New guidelines for identifying anxiety in pediatric patients constitute important changes in screening for primary care providers, including primary care NPs. This article seeks to guide NPs in both following the screening guidelines and providing strategic care for patients and their families.

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Anxiety disorder screening for children has come to the forefront in the US as the new United States Preventive Services Task Force (USPSTF) recommendation statement advises screening children for anxiety starting at age 8.¹ Although the American Academy of Pediatrics (AAP) had previously recommended mental health screenings, the USPSTF recently adopted this recommendation as a routine measure for children.^1,2 Prior USPSTF recommendations included screening for depression in children age 12 and older but did not include guidelines for younger children or anxiety. In recent years, the world has seen increased anxiety across the lifespan: the World Health Organization estimates a 25% increase in the prevalence of anxiety and depression worldwide, secondary to the COVID-19 pandemic.³ Anxiety is present and diagnosed in about 6 million children from ages 3 to 18.⁴ In the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), anxiety in children includes generalized anxiety disorder (GAD), social anxiety disorder, panic disorder, agoraphobia, specific phobias, separation anxiety disorder, and selective mutism.⁵ Anxiety can lead to poor school performance, relationship challenges, and functional impairment: ideally, these should be addressed early to help build skills and reduce long-term effects, including any on neurobiological pathways. Estimates indicate that 80% of children with a diagnosable anxiety disorder are not receiving treatment.⁶

As the primary care setting is the foundation and gateway for care, most family and pediatric NPs will see pediatric patients at least annually for well-child visits and occasionally for sick or episodic care. Early identification can lead to early referral and actions toward therapy. As the rates of anxiety have increased and the need for early intervention is clear, NPs in pediatric primary care play a key role in identifying mental health concerns and working collaboratively with mental health providers to introduce a comprehensive collaborative care approach to the child with anxiety.

This article is intended to provide guidance for primary care providers reflecting the new recommendation. It discusses screening for anxiety in 8- to 17-year-old pediatric patients, with emphasis on the new provision for inclusion of younger patients in screening.

Risk factors and prevalence

Risk for childhood anxiety disorders seems to be multifactorial, constituting a complex yet not fully understood interplay among environmental, biological, and developmental components. The emotional theory developed in the early 2000s suggests that the development of anxiety is a combination of a genetic sensitivity, formative early experiences, and an environment that supports development of anxious behaviors.⁷ Early separation and institutionalization, such as foster care and juvenile detention, increase the risk of developing an anxiety disorder. Certain parenting styles (for example, overprotective parenting) may increase the risk of behavioral inhibition, thus increasing the likelihood of developing anxiety later. Parents' accommodation of children in avoiding anxiety-inducing stimuli has been shown to potentiate and reinforce the anxiety.⁸ Behavioral and social-emotional patterns in the family home may correlate with differences in anterior cingulate cortex and prefrontal cortex activation, thus linking and reinforcing the biobehavioral factors.⁹ Having a parent with GAD, childhood separation events (death of a parent and parental separation or divorce), and family dysfunction (reflected by a higher McMaster Family Assessment Device score, which assesses the family's ability to solve problems and communicate) increase the risk of developing GAD.⁹

Anxiety disorders vary in typical age of onset. Specific phobias are among the earliest to emerge, often manifesting in children around the age of 6.^10,11 Separation anxiety disorders typically arise around the age of 8 (affecting 7.6% of US youth).^9,11,12 Separation anxiety is a normal part of an infant's development and usually presents itself at 7-8 months of age. Under normal conditions, children become upset and anxious when their primary caregivers leave but are calmed upon the caregivers' return. However, some children exhibit insecure attachment styles (and are not reassured by the return of their caregivers) as early as 12 months of age; these children are at increased risk of developing anxiety disorders.⁹ The onset of social anxiety disorders typically occurs around age 12 and affects approximately 9% of adolescents, with an increased prevalence in females versus males (11.2% versus 7%).¹¹ The occurrence of GAD is twice as common in females as in males (3% versus 1.5%); overall, 2.2% of adolescents ages 13-18 have this disorder.¹¹ Panic disorder typically develops at a later age than other anxiety disorders. Prevalence increases with age, affecting 1.8% of 13 to 14 year olds, 2.3% of 15 to 16 year olds, and 3.3% of 17 to 18 year olds.¹³

Neurobiological factors

Hallmarks of anxiety disorders include responses to stimuli greater in intensity and duration than expected. From a neurobiological perspective, there is often an exchange among the hippocampus, amygdala, and cortical regions.¹⁴ In response to a fear- or anxiety-provoking stimulus, the amygdala is triggered, activating the autonomic, adrenocortical, and reticular activating systems which in turn intensifies the cortical perception of those emotions.¹⁴ Under normal conditions, the ventromedial prefrontal cortex allows for modulation, thereby decreasing the hyperreactivity of the amygdala.¹⁵

Adolescence is a time for rapid change in the growth and development of the brain, and anxiety disorders often emerge during this time. Fear conditioning may be related to maturation of connectivity of the prefrontal cortex with the amygdala and other subcortical structures.¹⁵ Overall, among children at risk for developing anxiety, there seems to be a vulnerability of brain systems to govern the internal and external environments of the individual.⁹

Twin study heritability estimates of anxiety-related traits from a 2013 study ranged from 50% to 60%; heritability is believed to be related to multiple genetic variants rather than a specific single nucleotide polymorphism.¹⁶ This contradicts prior theories on a link between inhibited temperament and increased risk for panic and phobia-related disorders and a gene variant in the coding region of the corticotropin-releasing hormone.¹⁷ Essentially, the data confirming genetic heritability are inconclusive. A 2015 study suggested that direct environmental transmission, not genetic factors, affects development of anxious behaviors and anxiety.¹⁸ This is contrasted by a much larger 2019 United Kingdom study, with 5,000 twin pairs who were studied for 57 psychological traits; results indicated that all factors were genetically influenced, and average heritability was 34%.¹⁹

Evaluation and screening tools

Patient history and physical exam will yield information contributing to the differential diagnosis, but standardized tools can improve visibility of otherwise ambiguous symptoms. Physical assessment and routine labs (thyroid panel, basic metabolic panel, complete blood cell count, and urinalysis) can help exclude medical diagnoses that may mimic the signs and symptoms of anxiety. Medical conditions with overlapping symptoms include hyperthyroidism, cardiac anomalies, glycemic disorders, migraines, seizures, central nervous system disorders, autoimmune conditions, and history of head trauma.²⁰ A medication reconciliation is recommended as certain medications, including antihistamines, bronchodilators, steroids, stimulant attention-deficit/hyperactivity disorder medications, selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), sympathomimetics, supplements, caffeine, and illicit drugs, can cause anxiety.²⁰

The novel recommendation by the USPSTF is to begin screening all children at age 8 for anxiety disorders. The USPSTF states that its recommendation applies to children and adolescents who do not have a diagnosed anxiety disorder or are not showing recognized signs or symptoms of anxiety.¹ NPs should be aware of common symptoms that can occur in pediatric patients with anxiety, including abdominal pain, nervousness, fear, refusal to attend school or other activities, excessive worrying, avoidance behaviors, tantrums, and low self-esteem.²¹ GAD specifically may present in the pediatric population as an inability to control worry, irritability, difficulty with concentration, fatigue, and/or muscle tension/pain.²² Typical red flags indicating a need to screen for anxiety include disruption of behavior and/or inability to participate in routine activities.

There are a variety of screening tools to consider for use (see Selected pediatric anxiety screening tools). Some tools screen for a specific disorder, while others screen for several.¹ It is important to remember that these are screening, not diagnostic, tools. Some tools, including Patient Health Questionnaire-9 (PHQ-9) modified for Adolescents (PHQ-A) and the social phobia inventory, have been a part of clinical practice for years but may not be structured to match DSM-5 criteria for specific diagnoses or for pediatric anxiety specifically. Other tools, such as the Level 1 Cross-Cutting Symptom Measure, exist for parents or adolescents to complete at home.²⁰ Other tools include Pediatric Anxiety Rating Scale (PARS), Youth Anxiety Measure for DSM-5 (YAM-5), Screen for Child Anxiety-Related Emotional Disorders (SCARED), and the Spence Children's Anxiety Scale (SCAS). The PARS tool has confirmed validity and reliability.^23,24 The YAM-5, an updated tool in alignment with the DSM-5, requires parent and child reports.²⁵ The YAM-5 was tested for face validity in two phases by expert clinicians and has confirmed reliability.²⁵ The SCARED survey is a validated 2-part tool (entailing parent and child questionnaires) in a long (41-item) or short (5-item) format, and it has good internal consistency, discriminant validity, and test-retest reliability.^26,27 The SCAS has a child self-report version with 44 items and a parent-report version with 39 items.²⁸ Additionally, the GAD-7, teen/adult version, has been noted to have acceptable psychometric properties.²⁰ Results from these screening tools can help score effectiveness of treatment.^27,29

Although unstructured interviews offer an approachable, nonthreatening style, they are associated with missed diagnoses, as compared with standardized structured interviews, which tend to be more accurate.³⁰

The new USPSTF guidelines do not indicate the frequency of screening, but the AAP recommends screening at least annually.¹ The authors of this article additionally recommend screening when symptoms, behavior, or stressors indicate increased risk for anxiety.⁶

- Selected pediatric anxiety screening tools^23-29

Screening tool	Notes
GAD-7	Self-reporting; appropriate for adolescents; 7 questions
PHQ-A	Depression screening tool; adapted for adolescents
DSM-5-TR Parent/Guardian-Rated Level 1 Cross-Cutting Symptom Measure—Child Age 6-17	To be completed by parent(s); aligned with DSM-5
DSM-5-TR Self-Rated Level 1 Cross-Cutting Symptom Measure—Child Age 11-17	To be completed by child; aligned with DSM-5
PARS	Ages 6-17; aligned with DSM-IV; 50 items; clinician-administered
SCARED	Ages 8-18; aligned with DSM-IV
YAM-5	Ages 8-18; aligned with DSM-5
SCAS - Child	To be completed by child; ages 8-15
SCAS - Parent	To be completed by parent(s); ages 6-18

Abbreviations: GAD-7, general anxiety disorder-7; PHQ-A, Patient Health Questionnaire-9 modified for Adolescents; DSM-5-TR, Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), Text Revision; PARS, Pediatric Anxiety Rating Scale; SCARED, Screen for Child Anxiety-Related Emotional Disorders; YAM-5, Youth Anxiety Measure for the DSM-5; SCAS, Spence Children's Anxiety Scale.

Best-practice strategies

Psychotherapy. Cognitive behavioral therapy (CBT) has historically been the mainstay of treatment for anxiety disorders, as it works to diminish heightened responses to anxiety-producing stimuli, increase coping skills, and abate autonomic activation. CBT for the pediatric population involves relaxation training; cognitive restructuring; exposure practice; and education on symptoms, triggers, and causes.⁹ CBT is recommended by the American Academy of Child and Adolescent Psychiatry (AACAP) for pediatric patients ages 6 to 18 with social anxiety, GAD, separation anxiety, specific phobias, or panic disorder.²⁰ For the very young (ages 3 to 9), a combination of parent and child CBT could be efficacious, as evidenced by a 10-week randomized controlled trial.³¹

Pharmacotherapy. Additionally, the AACAP recommends pharmacologic therapy, specifically SSRIs, as a treatment for children ages 6 to 18 with social anxiety, GAD, separation anxiety, or panic disorder.²⁰ It is important to note that use of SSRIs for treatment of pediatric anxiety is off-label. Of the SSRIs used in the pediatric population, sertraline, fluoxetine, fluvoxamine, and paroxetine have been the most well studied. A common adverse reaction of SSRIs in children and adolescents is behavioral activation/agitation, specifically irritability, impulsivity, hyperactivity, and disinhibition; these effects may be linked to serotonergic neurotransmission. Other adverse reactions of SSRIs include headache, gastrointestinal complaints, and insomnia. SNRIs are another medication option in certain cases. Duloxetine is the only medication with an FDA indication for the treatment of any pediatric anxiety: it is approved for the treatment of GAD for patients age 7 years or older.²⁰

The key mantra for implementation of pediatric anxiolytic medications is “start low, go slow, and check often.” When starting a medication for anxiety, increased frequency of routine follow-up with slow titration is recommended. The US FDA recommends weekly visits for at least the first 4 weeks, followed by visits every 2 weeks for 4 weeks, and then finally monthly visits after starting an antidepressant. The FDA's boxed warning for increased risk of suicidality in children, adolescents, and young adults on drug labeling of antidepressants including SSRIs, based on studies linking suicidal thoughts to antidepressant treatment in youth, remains an important consideration and should not be taken lightly when considering initiation of medication in pediatric patients. The increased risk of suicidality mandates a different approach to prescribing for the pediatric population versus the adult.³² Potential signs and symptoms of an increased risk of suicidality can include worsening mood, increased irritability, increased sadness, or sudden calm.³² After a pediatric patient has had anxiety symptoms well controlled with medication for more than a year, medication reduction should be attempted during a low-stress time, such as vacation, and if the patient experiences a relapse, medication should be restarted.³³

A meta-analysis examined the efficacy and tolerability of SNRIs, SSRIs, 5-HT_1A receptor agonists (buspirone), benzodiazepines, alpha 2 agonists, and tricyclic antidepressants (TCAs) against placebo for anxiety among pediatric patients.³⁴ According to the study, SSRIs were the most effective and most tolerable, with SNRIs a close second.³⁴ The study findings also indicate that 5-HT_1A agonists were the least efficacious, and TCAs and alpha 2 agonists were the least tolerable.³⁴ Treatment-emergent suicidality was significantly higher in paroxetine-treated patients compared with those receiving sertraline.³⁴ Serotonin helps to modulate glutamate, an excitatory neurotransmitter that often plays a role in anxiety response. The serotonergic system matures earlier than the noradrenergic system, which could explain the differences in efficacy of antidepressants largely targeting the norepinephrine system (such as SNRIs and TCAs) when compared with antidepressants primarily targeting the serotonin system (SSRIs) in youth.³⁵

Off-label use of buspirone for treatment of pediatric anxiety has been studied little to date, but most existing completed studies show no difference or minimal difference between buspirone and placebo.³⁶ Benzodiazepines, which also do not have an FDA indication for the treatment of pediatric anxiety, remain controversial: a recent study found an association between benzodiazepines and suicidality, with suicidal adverse events—defined as new or worsening suicidal ideation, a suicidal threat, or a suicide attempt within the first 12 weeks of the trial—present in 60% of the subset of adolescents adjunctively treated with benzodiazepines versus 13% of adolescents who were not adjunctively treated with benzodiazepines.³⁷ Additionally, benzodiazepines have a boxed warning for risks of abuse, misuse, and addiction; for risks of dependence and withdrawal reactions; and for risks from concomitant use with opioids.³⁸

Combination therapy. There is a consensus that combined CBT and use of SSRIs may be best for the treatment of pediatric anxiety. In the large Child/Adolescent Anxiety Multimodal Study (CAMS), the percentage of children who experienced improved anxiety severity (rated as very much or much improved on the Clinical Global Impression-Improvement scale) on sertraline alone was 55%, and the percentage who experienced improvement with CBT alone was 60%, while combined CBT and sertraline benefited 81%.^39,40 All were statistically superior to placebo.^39,40 Additionally, in a study using data from the CAMS, researchers discovered that remission rates after 12 weeks of treatment were highest with combination treatment of sertraline plus CBT.⁴¹ A long-term recommendation from this study is the extension of treatment beyond 12 weeks for children experiencing residual symptoms, even if their anxiety has improved during treatment.⁴¹

Telemedicine. Telemedicine has become an established and often preferred modality for adult medicine, and evidence supports its use in pediatric mental health as well.⁴² Online commercial resources for mental health, such as BetterHelp, Cerebral, and Talkspace, address mental health issues for those over age 18 but do not provide services for minors. According to an evidence review, multiple studies suggested general efficacy of telehealth interventions in a variety of pediatric mental health conditions; many interventions were pilot studies, indicating that further research might be warranted.⁴² Updated resources regarding telehealth during the COVID-19 pandemic are available online.^43,44

Conclusion

Mental health care is a complicated but necessary piece of overall healthcare for the pediatric population. A worldwide increase in the prevalence of anxiety supports the recommendation for universal screening of the pediatric population and other related practice changes. The current climate of increased anxiety makes this an area of research ripe for update, especially in the face of newer treatment modalities such as telemedicine. It is hoped that the new recommendation statement from the USPSTF will increase secondary prevention measures and identify more patients with anxiety. The benefit of increased screening is the increased likelihood of early treatment and diagnosis. Inclusion of the family in therapy choices and conservative approaches to medication use remain the recommended course of action for this population. The COVID-19 pandemic has caused an increase in anxiety, somatic complaints, and behavioral issues in the pediatric population; parents and providers need to be equipped to recognize symptoms and respond accordingly.⁴⁵ Proper screening, recommendations, and evidence-based treatment can help NPs to equip parents and families with the tools they need to effectively address pediatric anxiety.