Generalized anxiety disorder (GAD) is one of the most common mental health disorders among children, affecting an estimated 2% to 10%.1–3 Despite this high prevalence, few affected children are properly diagnosed or receive adequate mental health care.4 Although GAD in children may remit spontaneously, it also can cause severe social, academic, and emotional impairment or distress.4 Anxiety disorders early in life can increase a child's risk of comorbid psychiatric disorders in adolescence and adulthood, such as panic attacks, conduct disorder, attention-deficit hyperactivity disorder, depression, alcohol or substance use disorder, and suicidality.5 Untreated anxiety disorders also are associated with poor outcomes in long-term functioning and general health as well as difficulties with interpersonal relationships.6 In children, anxiety disorders are associated with school absenteeism and poor academic performance, which can strain their socioeconomic trajectory, leading to financial difficulties later in life.6 The significant disease burden associated with pediatric anxiety disorders means that early identification in the primary care setting and effective management are essential to reducing negative effects and improving patient outcomes.4
Anxiety activates the brain's “fight or flight” response to dangerous stimuli, causing patients to actively confront or to avoid the perceived threat in order to survive.2 This basic and necessary response is present in infancy and childhood but typically is not pathologic. Studies have only recently begun to examine the neurobiology of anxiety disorders in children, so the exact pathogenesis is still uncertain. Patients with GAD have overwhelmingly demonstrated increased activation of the amygdala-based networks throughout the prefrontal cortex. Recent functional MRI studies of children with GAD also have implicated dysfunction in the ventrolateral prefrontal cortex.7 This area of the brain is thought to be involved in fear conditioning and responds in conjunction with the amygdala to emotional stimuli.
Despite the recent discoveries made by neuroimaging studies, the relationship between the neurocircuitry and symptomatology in pediatric anxiety disorders remains complex. The functional activity in the amygdala-prefrontal networks, however, has been shown to be a successful target for psychopharmacologic treatment and cognitive behavioral therapy (CBT).2 Furthermore, numerous brain pathways involving various neurotransmitters in the amygdala also are responsible for the expression of anxiety. The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) is central to the regulation of anxiety, and is the target for benzodiazepines, which have been used to treat anxiety disorders.7 Other neurotransmitters implicated in anxiety regulation include serotonin, opioid peptides, and oxytocin. Because anxiety disorders have a broad effect on patient function, further studies of the neurobiology underlying these conditions are critical for the development of early intervention strategies.
Multiple risk factors for anxiety disorders have been identified in children, including genetic and environmental factors.
- Sex. Girls have a greater risk of developing anxiety disorders than boys.8 Sex differences are smaller at younger ages but with adolescents and adults, the female-to-male ratio of anxiety prevalence increases noticeably from 2:1 to 3:1.8
- Genetics. Research has revealed a genetic factor to anxiety, with higher rates of anxiety found among children of parents with anxiety.3 Genes controlling temperament, personality, and cognitive vulnerabilities also have been linked to the development of anxiety disorders.3
- Personality traits. A behavioral inhibition temperament, defined by heightened physiologic arousal to stimuli, puts a child at increased risk for an anxiety disorder.3 Neuroticism, shyness, and emotionality are personality traits that have been associated with anxiety disorders.3
- Family dynamics. Study findings suggest that certain parent–child bonds can lead to a greater risk of anxiety disorders. For instance, children with insecure and ambivalent attachment have higher levels of anxiety, and parenting characteristics such as being overly critical, overly controlling, parental rejection, and parental stress and anxiety can be predictors of pediatric anxiety.3 Family practices such as family accommodation (the ways in which family members take part in avoiding anxiety-provoking situations) can lead to more severe clinical presentations and functional impairment.3 In addition, issues in the family environment, including family conflict, marital strain, domestic violence, and divorce, have been associated with higher levels of childhood anxiety.3
- Environmental factors. Low socioeconomic status is associated with a higher prevalence of anxiety disorders.4
CLINICAL PRESENTATION AND DIAGNOSIS
Children with anxiety disorders usually present with excessive worry or apprehension that they do not recognize as unreasonable. They commonly have somatic complaints such as headache and gastrointestinal complaints. In patients age 12 years and younger, crying, irritability, and angry outbursts can be misinterpreted as disobedience. Clinicians and parents must realize that this behavior, although seemingly oppositional in nature, may represent the child's effort to avoid stimuli that provoke distress or excessive worry. GAD in particular is characterized by chronic and excessive worry in areas such as school, social interactions, family, health and safety, and natural disasters. In other words, children with GAD display excessive worry about a broad range of stimuli rather than a specific object or situation. These children often are perfectionists who display reassurance-seeking behavior, as reflected in the diagnostic criteria for pediatric GAD in the Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-5).9
The DSM-5 defines GAD as excessive anxiety or worry on most days for at least 6 months that causes clinically significant functional impairment and distress not attributable to substance use or another medical condition.9 Clinicians must distinguish developmentally normal anxiety from an abnormal level of anxiety that the patient has difficulty controlling and that causes excessive distress and impairs function. In conjunction with this abnormal anxiety, to fully meet the DSM-5 criteria, children also must experience at least one additional symptom, such as restlessness, fatigue, difficulty concentrating, sleep disturbance, muscle tension, or irritability. Recognizing excessive, abnormal anxiety can be difficult in children because they manifest fears and anxieties as a part of normal development.8 This can be particularly challenging in younger children because they cannot adequately communicate the cognition, emotions, and avoidance behaviors that clinicians need in order to apply the diagnostic criteria. As a result, self-reports from patients age 12 years and younger are insufficient to identify those in need of treatment.
When assessing children age 12 years and younger, clinicians generally need to obtain collateral information from parents and teachers. In addition, clinicians should be alert for certain associated behaviors, including frequent physical complaints, impaired sleeping patterns (insomnia, repeated visits to parents' room), changes in eating habits, avoidance of outdoor or interpersonal activities, excessive need for reassurance, inattention and poor academic performance, and explosive outbursts. In adolescents (ages 13 through 17 years), diagnostic decisions can be made on information provided primarily by the patient. Validated screening and assessment tools, such as the Self-Report for Childhood Anxiety Related Emotional Disorders, Spence Children's Anxiety Scale, and Children's Yale-Brown Obsessive-Compulsive Scale (Table 1), all available free online, have been developed to help clinicians identify anxiety symptoms, accurately diagnose anxiety disorders, and monitor treatment.
Because symptoms overlap, distinguishing GAD from other psychiatric disorders can be challenging. Conditions that can mimic GAD symptoms, such as thyroid dysfunction and substance use, should be ruled out with the appropriate laboratory tests; however, avoid excessive laboratory testing for somatic complaints. The differential diagnosis for pediatric GAD includes:
- Separation anxiety disorder, or excessive anxiety related primarily to the child's separation from the home or a significant attachment figure, regardless of the length of time involved. Fear or worry is persistent and lasts at least 4 weeks. Concerns about death and dying are common features. Children with separation anxiety disorder often are demanding, intrusive, and in constant need of attention, which can lead to parental frustration and family conflict.
- Social phobia, also called social anxiety, and defined by marked and persistent apprehension of social or performance situations that could result in patient embarrassment. The DSM-5 requires that patients under age 18 years have these recurrent symptoms for at least 6 months to establish the diagnosis. This disorder is distinct from GAD in that social phobia specifically emphasizes shyness and fear of embarrassment in front of others.
- Panic disorder, which often is comorbid with GAD. According to the DSM-5, the patient must experience recurrent, unexpected panic attacks and be persistently worried about having more panic attacks.9 A panic attack is an abrupt surge of intense fear and intense physical discomfort characterized most often by tachycardia, sweating, shortness of breath, feelings of choking, chest pain, dizziness, paresthesias, and/or trembling.
- Obsessive-compulsive disorder (OCD), characterized by recurring obsessions, intrusive unwanted thoughts, compulsions, and repetitive excessive actions that interfere with the patient's daily functioning. Clinicians must distinguish anxiety disorders from OCD because growing evidence has shown that patients with these disorders have distinctly different neurocircuitry and need different treatments.10 Children with OCD try to neutralize obsessive thoughts by performing compulsive and repetitive actions such as washing, counting, lining up objects, or reading the same passage over and over again. If this compulsive behavior is disrupted, the child may become upset and oppositional. The diagnostic tool of choice for pediatric OCD is the Children's Yale-Brown Obsessive-Compulsive Scale.11
- Child abuse and/or neglect, which should be considered in patients presenting with discrepancies in medical history and excessive anxiety or fear in the context of physical injury. Abusers commonly inflict injury on areas of the child's body that are obscure or hidden, such as the back or buttocks. Victims of child abuse may present with a history of a fall; however, the injury usually is inconsistent with the mechanism or explanation. Other explanations that are concerning for child abuse include no explanation or a vague explanation for significant injury, an important detail of the explanation that changes dramatically, or markedly different explanations for the injury from different witnesses. Multiple injuries in various stages of healing also point to possible child abuse.
Different forms of therapy for GAD include CBT, mindfulness-based therapies, and psychodynamic therapies. CBT has been the most widely used and most effective among nonpharmacologic therapies for anxiety disorders. CBT involves several elements including relaxation techniques, anxiety management skills, exposure therapy to anxiety-provoking situations, and general education of the child and parents about GAD. In 2014, the Child/Adolescent Anxiety Multimodal Study (CAMS), a large-scale multimodal study, compared the efficacy of CBT alone, sertraline therapy alone, and a combination therapy of CBT plus sertraline in 488 patients ages 7 to 17 years.12 The study patients met DSM-IV criteria for GAD, separation anxiety disorder, or social anxiety disorder and were studied over a 12-week acute treatment phase and 6-month maintenance phase.
The CAMS found that 59.7% of participants receiving CBT monotherapy showed improvement in anxiety symptoms as indicated by positive or excellent treatment responses on the Clinical Global Impression-Improvement Scale (CGI-I) after the 12-week acute treatment phase.12 Nearly 81% of participants receiving combination therapy showed significant improvement of their anxiety but only 54.9% of participants receiving sertraline monotherapy showed improvement. The 6-month maintenance phase consisted of decreasing CBT visits to monthly meetings, maintenance of sertraline based on dosage at the end of the acute phase, and a combination of these two for the dual therapy arm. Two additional adjunctive services and attrition prevention panels (extra treatment sessions that address emergent conditions) were provided for patients in the monotherapy arms. At the end of the 6-month maintenance therapy, no one therapy exceeded the other in benefits.
Mindfulness therapies also have been useful in managing GAD. Two types have been commonly used: mindfulness-based stress reduction and mindfulness-based CBT.5 Meditation helps patients become more aware of their own thoughts, emotions, and triggers for anxiety, and to let those thoughts and emotions pass without judgment. A study from 2013 looked at the effect of an 8-week group intervention of mindfulness-based stress reduction compared with a stress management education program in 89 adults meeting DSM-IV criteria for primary GAD.13 Patients who completed at least one session of mindfulness-based stress reduction demonstrated significant anxiety reduction as indicated by the Hamilton Anxiety Scale (HAM-A), Beck Anxiety Inventory (BAI), Clinical Global Impression of Severity (CGI-S), and CGI-I scores. The mindfulness arm of the study showed that anxiety symptoms improved in 66% of patients, compared with 40% of the patients in the education.13 Further studies are needed to evaluate and confirm the benefit of mindfulness therapies in children.
Psychodynamic therapy for patients with GAD targets the underlying cause of the anxiety, with the therapist delving into the patient's emotions, distressing thoughts, and other recurring themes. In children, this is accomplished through play and other interactions. A recent study of 37 children ages 4 to 10 years who met DSM-IV criteria for anxiety disorder found that even short-term (20 to 25 sessions) psychodynamic child therapy significantly reduced symptoms of anxiety, as nearly 67% of the participants in this small study no longer met criteria for anxiety disorder after completing therapy.14 These results are comparable with CBT.
Antidepressants are used in conjunction with CBT or when CBT alone is insufficient to manage anxiety in children. Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) have been most widely studied and are viewed as more efficacious with fewer adverse reactions than other classes of antidepressants. In a 2016 randomized controlled study, Dobson and Strawn examined the efficacy and safety of SSRIs and SNRIs in children.1 Sertraline, fluoxetine, venlafaxine, and duloxetine all showed significant reduction in anxiety symptoms. The efficacy of these medications were determined by using the HAM-A, CGI-S, CGI-I, and Pediatric Anxiety Rating Scale (PARS). Anxiety symptoms improved in 55% of study participants taking sertraline, compared with 64% of those taking fluoxetine, 69% of those taking venlafaxine, and 50% of those taking duloxetine.1
Duloxetine is the only medication that is FDA-approved to treat GAD in children (specifically, those ages 7 to 17 years), although several SSRIs are FDA-approved for treating related pediatric anxiety disorders, such as social phobia and panic disorder. The initial dosage of duloxetine is 30 mg once a day for 2 weeks with a maximum dose of 120 mg once a day. The recommended dose range is 30 to 60 mg once a day; dosage increases should be in increments of 30 mg. Adverse reactions include dizziness, headache, abdominal pain, drowsiness, anorexia, oropharyngeal pain, cough, palpitations, and nausea. As with all antidepressants, duloxetine carries a black-box warning of an increased risk for suicidality; patients should be watched carefully for behaviors suggestive of this possibility.
Before the introduction of SSRIs and SNRIs, tricyclic antidepressants were used to treat anxiety disorders. However, the benefits of tricyclic antidepressants are outweighed by their anticholinergic adverse reactions, the need for continuous cardiac monitoring, and the risk of lethal overdose. Benzodiazepines commonly are used for treating adult anxiety disorders and were previously used to treat anxiety in children; they no longer are favored because randomized clinical trials have shown no statistically significant difference between benzodiazepine treatment and placebo.5 Benzodiazepines also can cause behavioral disinhibition in young children and long-term use is associated with dependence.5
Recent studies have found that combination therapy of nonpharmacologic and pharmacologic treatment is the most effective treatment for children with anxiety disorders. The CAMS showed that patients had the most significant response to combination therapy with CBT plus sertraline.12 At the end of the study's 6-month maintenance period, combination therapy, CBT monotherapy, and sertraline monotherapy were all similarly efficacious but combination therapy provided the most rapid improvement of GAD symptoms.12
Given its high prevalence, psychiatric comorbidities, and negative predictive outcomes for adulthood, GAD in children poses a significant public health concern. Estimates of the annual economic burden of mental health disorders among children in the United States reach a quarter of a trillion dollars.4 Prompt and proper recognition of GAD risk factors and symptoms, prompt diagnosis following DSM-5 guidelines, and proper management are necessary to reduce negative effects and improve outcomes in children. Nonpharmacologic and pharmacologic treatments are available and effective but combination therapy is most effective. Using CBT to prevent GAD in at-risk children is in early stages of research but preliminary results are promising.
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