Anxiety Disorders

Anxiety, defined as dread or apprehension, is not considered pathologic, is seen across the life span, and can be adaptive (e.g., the anxiety one might feel during an automobile crash). Anxiety has both a cognitive-behavioral component, expressed in worrying and wariness, and a physiologic component, mediated by the autonomic nervous system. Anxiety disorders are characterized by pathologic anxiety, in which anxiety becomes disabling, interfering with social interactions, development, and achievement of goals or quality of life, and can lead to low self-esteem, social withdrawal, and academic underachievement. The average age of onset of anxiety disorder is 11 yr. Diagnosis of a particular anxiety disorder in a child requires significant interference in the child's psychosocial and academic or occupational functioning, which can occur even with subthreshold symptoms that do not meet criteria in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Anxiety may have physical manifestations such as weight loss, pallor, tachycardia, tremors, muscle cramps, paresthesias, hyperhidrosis, flushing, hyperreflexia, and abdominal tenderness.

Separation anxiety disorder (SAD), childhood-onset social phobia or social anxiety disorder, generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), phobias, posttraumatic stress disorder (PTSD), and panic disorder (PD) are all defined by the occurrence of either diffuse or specific anxiety, often related to predictable situations or cues. Anxiety disorders are the most common psychiatric disorders of childhood, occurring in 5–18% of all children and adolescents, prevalence rates comparable to physical disorders such as asthma and diabetes. Anxiety disorders are often comorbid with other psychiatric and medical disorders (including a second anxiety disorder); significant impairment in day-to-day functioning is common. High levels of fear in adolescence are also a significant risk factor for experiencing later episodes of major depression in adulthood. Anxiety and depressive disorder in adolescence predict increased risk of anxiety and depressive symptoms (including suicide attempts) in adulthood, underscoring the need to diagnose and treat these underreported, yet prevalent, conditions early.

Because anxiety is both a normal phenomenon and, when highly activated, strongly associated with impairment, the pediatrician must be able to differentiate normal anxiety from abnormal anxiety across development ( Fig. 38.1 and Table 38.1 ). Anxiety has an identifiable developmental progression for most children; most infants exhibit stranger wariness or anxiety beginning at 7-9 mo of age. Behavioral inhibition to the unfamiliar (withdrawal or fearfulness to novel stimuli associated with physiologic arousal) is evident in approximately 10–15% of the population at 12 mo of age and is moderately stable. Most children who show behavioral inhibition do not develop impairing levels of anxiety. A family history of anxiety disorders and maternal overinvolvement or enmeshment predicts later clinically significant anxiety in behaviorally inhibited infants. The infant who is excessively clingy and difficult to calm during pediatric visits should be followed for signs of increasing levels of anxiety.

Open full size image

Normative fears throughout childhood and adolescence.

(From Craske MG, Stein MB: Anxiety. Lancet 388:3048–3058, 2016.)

Preschoolers typically have specific fears related to the dark, animals, and imaginary situations, in addition to normative separation anxiety. Preoccupation with orderliness and routines ( just right phenomena) often takes on a quality of anxiety for preschool children. Parents' reassurance is usually sufficient to help the child through this period. Although most school-age children abandon the imaginary fears of early childhood, some replace them with fears of bodily harm or other worries ( Table 38.2 ). In adolescence, general worrying about school performance and worrying about social competence are common and remit as the teen matures.

Genetic or temperamental factors contribute more to the development of some anxiety disorders, whereas environmental factors are closely linked to the cause of others. Specifically, behavioral inhibition appears to be a heritable tendency and is linked with social phobia, generalized anxiety, and selective mutism. OCD and other disorders associated with OCD-like behaviors, such as Tourette syndrome and other tic disorders, tend to have high genetic risk as well (see Chapter 37.1 ). Environmental factors, such as parent–infant attachment and exposure to trauma, contribute more to SAD and PTSD. Parental anxiety disorder is associated with an increased risk of anxiety disorder in offspring. Differences in the size of the amygdala and hippocampus are noted in patients with anxiety symptoms.

Separation anxiety disorder is one of the most common childhood anxiety disorders, with a prevalence of 3.5–5.4%. Approximately 30% of children presenting to an outpatient anxiety disorder clinic have SAD as a primary diagnosis. Separation anxiety is developmentally normal when it begins about 10 mo of age and tapers off by 18 mo. By 3 yr of age, most children can accept the temporary absence of their mother or primary caregiver.

SAD is more common in prepubertal children, with an average age of onset of 7.5 yr. Girls are more frequently affected than boys. SAD is characterized by unrealistic and persistent worries about separation from the home or a major attachment figure. Concerns include possible harm befalling the affected child or the child's primary caregivers, reluctance to go to school or to sleep without being near the parents, persistent avoidance of being alone, nightmares involving themes of separation, numerous somatic symptoms, and complaints of subjective distress. The first clinical sign might not appear until 3rd or 4th grade, typically after a holiday or a period where the child has been home because of illness, or when the stability of the family structure has been threatened by illness, divorce, or other psychosocial stressors.

Symptoms vary depending on the child's age: Children <8 yr often have associated school refusal and excessive fear that harm will come to a parent; children 9-12 yr have excessive distress when separated from a parent; and those 13-16 yr often have school refusal and physical complaints. SAD may be more likely to develop in children with lower levels of psychosocial maturity. Parents are often unable to be assertive in returning the child to school. Mothers of children with SAD often have a history of an anxiety disorder. In these cases the pediatrician should screen for parental depression or anxiety. Often, referral for parental treatment or family therapy is necessary before SAD and concomitant school refusal can be successfully treated.

Comorbidity is common in SAD. In children with comorbid tic disorders and anxiety, SAD is especially associated with tic severity. SAD is a predictor for early onset of PD. Children with SAD compared to those without SAD are 3 times more likely to develop PD in adolescence.

When a child reports recurring acute severe anxiety, antidepressant or anxiolytic medication is often necessary. Controlled studies of tricyclic antidepressants (TCAs, imipramine) and benzodiazepines (clonazepam) show that these agents are not generally effective. Data support the use of cognitive-behavioral therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs) (see Chapter 33 , Table 33.4 ). Adverse events with SSRI treatment, including suicidal and homicidal ideation, are uncommon. CBT alone is associated with less insomnia, fatigue, sedation, and restlessness than SSRIs. Combining SSRIs with CBT may be the best approach to achieving a positive response; long-term SSRI treatment can provide additional benefit.

Childhood-onset social phobia (social anxiety disorder) is characterized by excessive anxiety in social settings (including the presence of unfamiliar peers, or unfamiliar adults) or performance situations, leading to social isolation, and is associated with social scrutiny and fear of doing something embarrassing ( Table 38.3 ). Fear of social settings can also occur in other disorders, such as GAD. Avoidance or escape from the situation usually dissipates anxiety in social phobia (SP), unlike GAD, where worry persists.

Children and adolescents with SP often maintain the desire for involvement with family and familiar peers. When severe, the anxiety can manifest as a panic attack. SP is associated with a decreased quality of life, with increased likelihood of having failed at least 1 grade, and a 38% likelihood of not graduating from high school. Its onset is typically during or before adolescence and is more common in girls. A family history of SP or extreme shyness is common. Approximately 70–80% of patients with SP have at least 1 comorbid psychiatric disorder. Most shy patients do not have SP.

Social effectiveness therapy for children (SET-C), alone or with SSRIs, is considered the treatment of choice for SP (see Table 33.4 ). SSRI and SET-C are superior to placebo in reducing social distress and behavioral avoidance and increasing general functioning. SET-C may be better than SSRI in reducing these symptoms. SET-C, but not SSRI, may be superior to placebo in improving social skills, decreasing anxiety in specific social interactions, and enhancing social competence. SSRIs have a maximum effect by 8 wk; SET-C provides continued improvement through 12 wk. A combination of SSRI and CBT is superior to either treatment alone in reducing severity of anxiety in children with SP and other anxiety disorders. β-Adrenergic blocking agents are used to treat SP, particularly the subtype with performance anxiety and stage fright. β-Blockers are not approved by the U.S. Food and Drug Administration (FDA) for SP.

School refusal , which occurs in approximately 1–2% of children, is associated with anxiety in 40–50% of cases, depression in 50–60% of cases, and oppositional behavior in 50% of cases. Younger anxious children who refuse to attend school are more likely to have SAD, whereas older anxious children usually refuse to attend school because of SP. Somatic symptoms, especially abdominal pain and headaches, are common. There may be increasing tension in the parent–child relationship or other indicators of family disruption (domestic violence, divorce, or other major stressors) contributing to school refusal.

Management of school refusal typically requires parent management training and family therapy. Working with school personnel is always indicated; anxious children often require special attention from teachers, counselors, or school nurses. Parents who are coached to calmly send the child to school and to reward the child for each completed day of school are usually successful. In cases of ongoing school refusal, referral to a child and adolescent psychiatrist and psychologist is indicated. SSRI treatment may be helpful. Young children with affective symptoms have a good prognosis, whereas adolescents with more insidious onset or with significant somatic complaints have a more guarded prognosis.

Selective mutism is conceptualized as a disorder that overlaps with SP. Children with selective mutism talk almost exclusively at home, although they are reticent in other settings, such as school, daycare, or even relatives' homes. The mutism must be present for ≥1 mo. Often, one or more stressors, such as a new classroom or conflicts with parents or siblings, drive an already shy child to become reluctant to speak. It may be helpful to obtain history of normal language use in at least one situation to rule out any communication disorder (fluency disorder), neurologic disorder, or pervasive developmental disorder (autism, schizophrenia) as a cause of mutism. Fluoxetine in combination with behavioral therapy is effective for children whose school performance is severely limited by their symptoms (see Chapter 52 ). Other SSRIs may also be effective.

Panic disorder is a syndrome of recurrent, discrete episodes of marked fear or discomfort in which patients experience abrupt onset of physical and psychological symptoms called panic attacks ( Table 38.4 ). Physical symptoms can include palpitations, sweating, shaking, shortness of breath, dizziness, chest pain, and nausea. Children can present with acute respiratory distress but without fever, wheezing, or stridor, ruling out organic causes of the distress. The associated psychological symptoms include fear of death, impending doom, loss of control, persistent concerns about having future attacks, and avoidance of settings where attacks have occurred (agoraphobia, Table 38.5 ).

PD is uncommon before adolescence, with the peak age of onset at 15-19 yr, occurring more often in girls. The postadolescence prevalence of PD is 1–2%. Early-onset PD and adult-onset PD do not differ in symptom severity or social functioning. Early-onset PD is associated with greater comorbidity, which can result from greater familial loading for anxiety disorders in the early-onset subtype. Children of parents with PD are much more likely to develop PD. A predisposition to react to autonomic arousal with anxiety may be a specific risk factor leading to PD. Twin studies suggest that 30–40% of the variance is attributed to genetics. The increasing rates of panic attack are also directly related to earlier sexual maturity. Cued panic attacks can be present in other anxiety disorders and differ from the uncued “out-of-the-blue” attacks in PD.

No randomized controlled trials (RCTs) have evaluated the effectiveness of antidepressant medication in youth with PD. Open-label studies with SSRIs appear to show effectiveness in the treatment of adolescents (see Table 33.4 ). CBT may also be helpful. The recovery rate is approximately 70%.

Generalized anxiety disorder occurs in children who often experience unrealistic worries about different events or activities for at least 6 mo with at least 1 somatic complaint ( Table 38.6 ). The diffuse nature of the anxiety symptoms differentiates it from other anxiety disorders. Worries in children with GAD usually center around concerns about competence and performance in school and athletics. GAD often manifests with somatic symptoms, including restlessness, fatigue, problems concentrating, irritability, muscle tension, and sleep disturbance. Given the somatic symptoms characteristic of GAD, the differential diagnosis must consider other medical causes. Excessive use of caffeine or other stimulants in adolescence is common and should be determined with a careful history. When the history or physical examination is suggestive, the pediatrician should rule out hyperthyroidism, hypoglycemia, lupus, pheochromocytoma, and other disorders (see Table 38.1 ; Fig. 38.2 ).

Open full size image

Evaluation of worry, fear, and panic.

PANDAS , Pediatric autoimmune neuropsychiatric disorders associated with Streptococcus pyogenes .

(From Kliegman RM, Lye PS, Bordini B, et al, editors: Nelson pediatric symptom-based diagnosis, Philadelphia, 2018, Elsevier, p 429).

Children with GAD are extremely self-conscious and perfectionistic and struggle with more intense distress than is evident to parents or others around them. They often have other anxiety disorders, such as simple phobia and PD. Onset may be gradual or sudden, although GAD seldom manifests until puberty. Boys and girls are equally affected before puberty, when GAD becomes more prevalent in girls. The prevalence of GAD ranges from 2.5–6% of children. Hypermetabolism in frontal precortical area and increased blood flow in the right dorsolateral prefrontal cortex may be present.

Children with GAD are good candidates for CBT, an SSRI, or their combination (see Table 33.4 ). Buspirone may be used as an adjunct to SSRI therapy. The combination of CBT and SSRI often results in a superior response in pediatric patients with anxiety disorders, including GAD. The recovery rate is approximately 80%.

It is important to distinguish children with GAD from those who present with specific repetitive thoughts that invade consciousness ( obsessions ) or repetitive rituals or movements that are driven by anxiety ( compulsions ). The most common obsessions are concerned with bodily wastes and secretions, the fear that something calamitous will happen, or the need for sameness. The most common compulsions are handwashing, continual checking of locks, and touching. At times of stress (bedtime, preparing for school), some children touch certain objects, say certain words, or wash their hands repeatedly.

Obsessive-compulsive disorder is diagnosed when the thoughts or rituals cause distress, consume time, or interfere with occupational or social functioning ( Table 38.7 ). In the DSM-5, OCD and related disorders, such as trichotillomania, excoriation, body dysmorphic disorder, and hoarding, are listed separately and are no longer included under anxiety disorders.

OCD is a chronically disabling illness characterized by repetitive, ritualistic behaviors over which the patient has little or no control. OCD has a lifetime prevalence of 1–3% worldwide, and as many as 80% of all cases have their onset in childhood and adolescence. Common obsessions include contamination (35%) and thoughts of harming loved ones or oneself (30%). Washing and cleaning compulsions are common in children (75%), as are checking (40%) and straightening (35%). Many children are observed to have visuospatial irregularities, memory problems, and attention deficits, causing academic problems not explained by OCD symptoms alone.

The Children's Yale-Brown Obsessive-Compulsive Scale (C-YBOCS) and the Anxiety Disorders Interview Schedule for Children (ADIS-C) are reliable and valid methods for identifying children with OCD. The C-YBOCS is helpful in following the progression of symptoms with treatment. The Leyton Obsessional Inventory (LOI) is a self-report measure of OCD symptoms that is quite sensitive. Patients with OCD have consistently identified abnormalities in the frontostriatal-thalamic circuitry associated with severity of illness and treatment response. Comorbidity is common in OCD, with 30% of patients having comorbid tic disorders, 26% comorbid major depression, and 24% comorbid developmental disorders.

Consensus guidelines recommend that children and adolescents with OCD begin treatment with either CBT alone or CBT in combination with SSRI, when symptoms are moderate to severe (YBOCS >21). In OCD patients with comorbid tics, SSRIs are no more effective than placebo, and the combination of CBT and SSRI is superior to CBT; CBT alone is superior to placebo. Pediatric OCD patients with comorbid tics should begin treatment with CBT alone or combined CBT and SSRI. Pediatric patients with OCD who have a family history of OCD may be significantly less responsive to CBT alone than patients without a family history.

There are 4 FDA-approved medications for pediatric OCD: fluoxetine, sertraline, fluvoxamine, and clomipramine. Clomipramine, a heterocyclic antidepressant and nonselective serotonin and norepinephrine reuptake inhibitor, is only indicated when a patient has failed 2 or more SSRI trials. There may be a role for glutamate-modulating medications in the treatment of OCD. The glutamate inhibitor riluzole (Rilutek) is FDA approved for amyotrophic lateral sclerosis (see Chapter 630.3 ) and has a good safety record. The most common adverse event with riluzole is transient increase in liver transaminases. Riluzole in children with treatment-resistant OCD may be beneficial and is well tolerated. Other glutamate-modulating agents, such as memantine, N -acetylcysteine, and d -cycloserine, have been used with some success in patients with OCD. Referral of patients with OCD to a mental health professional is always indicated.

In 10% of children with OCD, symptoms are triggered or exacerbated by group A β-hemolytic streptococcal infection (see Chapter 210 ). Group A β-hemolytic streptococci trigger antineuronal antibodies that cross-react with basal ganglia neural tissue in genetically susceptible hosts, leading to swelling of this region and resultant obsessions and compulsions. This subtype of OCD, called pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS), is characterized by sudden and dramatic onset or exacerbation of OCD or tic symptoms, associated neurologic findings, and a recent streptococcal infection. Increased antibody titers of antistreptolysin O and antideoxyribonuclease B correlates with increased basal ganglia volumes. Plasmapheresis is effective in reducing OCD symptoms in some patients with PANDAS and also decreasing enlarged basal ganglia volume. OCD has also followed episodes of acute disseminated encephalomyelitis (see Chapter 618.4 ) The pediatrician should be aware of the infectious cause of some cases of tic disorders, and OCD and follow management guidelines (see Chapter 37 ).

Children with phobias avoid specific objects or situations that reliably trigger physiologic arousal (e.g., dogs, spiders) (see Table 38.2 ). The fear is excessive and unreasonable and can be cued by the presence or anticipation of the feared trigger, with anxiety symptoms occurring immediately. Neither obsessions nor compulsions are associated with the fear response; phobias only rarely interfere with social, educational, or interpersonal functioning. Assault by a relative and verbal aggression between parents can influence the onset of specific phobias. The parents of phobic children should remain calm in the face of the child's anxiety or panic. Parents who become anxious themselves may reinforce their children's anxiety, and the pediatrician can usefully interrupt this cycle by calmly noting that phobias are not unusual and rarely cause impairment. The prevalence of specific phobias in childhood is 0.5–2%.

Systematic desensitization is a form of behavior therapy that gradually exposes the patient to the fear-inducing situation or object, while simultaneously teaching relaxation techniques for anxiety management. Successful repeated exposure leads to extinguishing anxiety for that stimulus. When phobias are particularly severe, SSRIs can be used with behavioral intervention. Low-dose SSRI treatment may be especially effective for some children with severe, refractory choking phobia.

Posttraumatic stress disorder is typically precipitated by an extreme stressor (see Chapter 14 ). PTSD is an anxiety disorder resulting from the long- and short-term effects of trauma that cause behavioral and physiologic sequelae in toddlers, children, and adolescents ( Table 38.8 ). Another diagnostic category, acute stress disorder , reflects that traumatic events often cause acute symptoms that may or may not resolve. Previous trauma exposure, a history of other psychopathology, and symptoms of PTSD in parents predict childhood-onset PTSD. Many adolescent and adult psychopathologic conditions, such as conduct disorder, depression, and some personality disorders, might relate to previous trauma. PTSD is also linked to mood disorders and disruptive behavior. Separation anxiety is common in children with PTSD. The lifetime prevalence of PTSD by age 18 yr is approximately 6%. Up to 40% show symptoms, but do not fulfill the diagnostic criteria.