Chapter 23 Anxiety Disorders

Anxiety, defined as dread or apprehension, is a normal phenomenon. Anxiety by itself is not considered pathologic, is seen across the lifespan, and can be adaptive (e.g., the anxiety one might feel during an automobile crash). Anxiety has both a physiologic component, mediated by the autonomic nervous system, and a cognitive and behavioral component, expressed in worrying and wariness. 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. Diagnosis of a particular anxiety disorder in a child requires significant interference in the child’s psychosocial and/or 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, Fourth Edition (DSM-IV).

Separation anxiety disorder (SAD), childhood-onset social phobia or social anxiety disorder, generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), phobias, post-traumatic stress disorder (PTSD), and panic disorder 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; they occur 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 disorders (including a 2nd 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. 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.

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-aged children abandon the imaginary fears of early childhood, some replace them with fears of bodily harm or other worries (Table 23-1). 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 (Chapter 590.4). 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 (SAD) 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 commonly 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 his or her 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 1st 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 stressor.

Symptoms vary depending on the child’s age: Children younger than 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 panic disorder. Children with SAD compared to those without SAD are 3 times more likely to develop panic disorder in adolescence.

When a child reports recurring acute severe anxiety, antidepressant or anxiolytic medication is often necessary. Controlled studies of tricyclic antidepressants (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 Table 19-4). One controlled trial of 488 children, 7-17 yr, which included children with a primary diagnosis of SAD, compared 12 wk of treatment with CBT, the SSRI, sertraline, their combination, and placebo. Nearly 81% of those treated with combination therapy improved, 55% for SSRI alone, 60% for CBT. All treatments were superior to placebo (24% response rate). The SSRI was well tolerated and had few side effects; adverse events, including suicidal and homicidal ideation, did not differ between the SSRI and placebo groups. There was no attempted suicide among the 488 children. CBT was associated with less insomnia, fatigue, sedation, and restlessness than SSRI. Combining SSRI 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 (Table 23-2) and is associated with social scrutiny and fear of doing something embarrassing. 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 38% of SP patients not graduating from high school. SP is associated with increased likelihood of having failed at least one grade. Its onset is typically during or before adolescence and is more common in girls. A family history of SP or extreme shyness is common. About 70-80% of patients with SP have at least one comorbid psychiatric disorder.

Social effectiveness therapy for children (SET-C), alone or with SSRIs, is considered the treatment of choice for SP (see Table 19-4). 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 FDA approved 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/or 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 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. 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, neurologic disorder, or pervasive developmental disorder as a cause of mutism. Fluoxetine in combination with behavioral therapy is effective for children whose school performance is severely limited by their symptoms (Chapter 32).

Panic disorder is a syndrome of recurrent, discrete episodes of marked fear or discomfort in which patients experience abrupt onset of physical and psychologic symptoms called panic attacks (Tables 23-3 and 23-4). 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 psychologic 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 23-5).

Table 23-3 CRITERIA FOR DIAGNOSIS OF PANIC DISORDER

Table 23-4 CRITERIA FOR DIAGNOSIS OF A PANIC ATTACK

Table 23-5 CRITERIA FOR DIAGNOSIS OF AGORAPHOBIA

Panic disorder is uncommon before adolescence, with the peak age of onset at 15-19 yr of age, occurring more often in girls. The postadolescence prevalence of panic disorder is 1-2%. Early-onset panic disorder and adult-onset panic disorder do not differ in symptom severity or social functioning. Early-onset panic disorder is associated with greater comorbidity, which can result from greater familial loading for anxiety disorders in the early-onset subtype. Children of parents with panic disorder are much more likely to develop panic disorder. A predisposition to react to autonomic arousal with anxiety may be a specific risk factor leading to panic disorder. 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 panic disorder.

SSRIs have shown effectiveness in the treatment of adolescents (see Table 19-4). CBT may also be helpful. The recovery rate is approximately 70%.

Generalized anxiety disorder (GAD) occurs in children who often experience unrealistic worries about different events or activities for at least 6 mo (Table 23-6) with at least one somatic complaint. The diffuse nature of the anxiety symptoms differentiates it from other anxiety disorders. Worries in children with GAD commonly 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 exam is suggestive, the pediatrician should rule out hyperthyroidism, hypoglycemia, lupus, and pheochromocytoma.

Children with GAD are markedly 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 panic disorder. Onset may be gradual or sudden, although GAD does not often become manifest 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% to 6% of children. Hypermetabolism in frontal precortical area and increased blood flow in right the dorsolateral prefrontal cortex may be present.

Children with GAD are good candidates for CBT, an SSRI, or their combination (see Table 19-4). Buspirone may be used as an adjunct to SSRI therapy. 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 hand washing, 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. OCD is diagnosed when the thoughts or rituals cause distress, consume time, or interfere with occupational or social functioning (Table 23-7).

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 fronto-striatal-thalamic circuitry associated with severity of illness and treatment response. Comorbidity is common in OCD, with 30% of patients having comorbid tic disorders, 26% having comorbid major depression, and 24% having 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 (i.e., Y-BOCS >21). In OCD patients with comorbid tics, SSRI are no more effective than placebo, and 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 the combination of CBT and SSRI.

There are four FDA-approved medications for pediatric OCD: fluoxetine, sertraline, fluvoxamine, and clomipramine. Clomipramine, a heterocylic 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 critical role for glutamate in the pathogenesis and treatment response of OCD. The glutamate inhibitor riluzole (Rilutek) is FDA-approved for amyotrophic lateral sclerosis (Chapter 604.3) 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. 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 (GABHS) (Chapter 176). GABHS bacteria 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 disorders 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. The pediatrician should be aware of the infectious cause of some cases of tic disorders, attention-deficit disorder, and OCD and follow management guidelines (Chapter 22).

Children with phobias avoid specific objects or situations that reliably trigger physiologic arousal (e.g., dogs or spiders) (see Table 23-1). 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 0.5-2.0%.

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.

Post-traumatic stress disorder (PTSD; see Chapter 36) is typically precipitated by an extreme stressor. 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 23-8). Another diagnostic category, acute stress disorder, reflects the fact 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.

Life-threatening events that pose harm to the child or the caregiver and that produce considerable stress or fear are required to make the diagnosis of PTSD. Three clusters of symptoms are also essential for diagnosis: re-experiencing, avoidance, and hyperarousal. Persistent re-experiencing of the stressor through intrusive recollections, nightmares, and reenactment in play are typical responses in children. Persistent avoidance of reminders and numbing of emotional responsiveness, such as isolation, amnesia, and avoidance, constitute the 2nd cluster of behaviors. Symptoms of hyperarousal, such as hypervigilance, poor concentration, extreme startle responses, agitation, and sleep problems, complete the symptom profile of PTSD. Occasionally, children regress in some of their developmental milestones after a traumatic event. Avoidance symptoms are commonly observable in younger children, whereas older children may be more able to describe re-experiencing and hyperarousal symptoms. Repetitive play involving the event, psychosomatic symptoms, and nightmares may also be observed.

Initial interventions after a trauma should focus on reunification with a parent and attending to the child’s physical needs in a safe place. Aggressive treatment of pain might decrease the likelihood of PTSD, and facilitating a return to comforting routines, including regular sleep, is indicated. Long-term treatment may include individual, group, school-based, or family therapy, as well as pharmacotherapy, in selected cases. Individual treatment involves transforming the child’s concept of himself or herself as victim to that of survivor and can occur through play therapy, psychodynamic therapy, or CBT. Group work is also helpful for identifying which children might need more intensive assistance. Goals of family work include helping the child establish a sense of security, validating his or her emotions, and anticipating situations when the child will need more support from the family. Clonidine or guanfacine may be helpful for sleep disturbance, persistent arousal, and exaggerated startle response. Comorbid depression and affective numbing might respond to an SSRI (see Table 19-4). As for many other anxiety disorders, CBT is the psychotherapeutic intervention with the most empiric support.

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