Chapter 38

Anxiety Disorders

David R. Rosenberg, Jennifer A. Chiriboga

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.

Fig. 38.1 Normative fears throughout childhood and adolescence. (From Craske MG, Stein MB: Anxiety. Lancet 388:3048–3058, 2016.)

Table 38.1

Differential Diagnosis of Anxiety Disorders

Shyness
Substance use
Substance use withdrawal
Hyperthyroidism
Arrhythmias
Pheochromocytoma
Mast cell disorders
Carcinoid syndrome
Anaphylaxis
Hereditary angioedema
Lupus
Autoimmune encephalitis
Body dysmorphic disorder
Autism spectrum disorder
Major depressive disorder
Delusional disorder
Oppositional defiant disorder
Embarrassing medical condition

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.

Table 38.2

DSM-5 Diagnostic Criteria for Specific Phobia

A. Marked fear or anxiety about a specific object or situation (e.g., flying, heights, animals, receiving an injection, seeing blood).
Note: In children, the fear or anxiety may be expressed by crying, tantrums, freezing, or clinging.
B. The phobic object or situation almost always provokes immediate fear or anxiety.
C. The phobic object or situation is actively avoided or endured with intense fear or anxiety.
D. The fear or anxiety is out of proportion to the actual danger posed by the specific object or situation and to the sociocultural context.
E. The fear, anxiety, or avoidance is persistent, typically lasting for 6 mo or more.
F. The fear, anxiety, or avoidance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.
G. The disturbance is not better explained by the symptoms of another mental disorder, including fear, anxiety and avoidance or situations associated with panic-like symptoms or other incapacitating symptoms (as in agoraphobia); objects or situations related to obsessions (as in obsessive-compulsive disorder); remainders of traumatic events (as in posttraumatic stress disorder); separation from home or attachment figures (as in separation anxiety disorder); or social situations (as in social anxiety disorder).
Specify if:
Code based on the phobic stimulus:
- Animal (e.g., spiders, insects, dogs).
- Natural environment (e.g., heights, storms, water).
- Blood-injection-injury (e.g., needles, invasive medical procedures).
- Situational (e.g., airplanes, elevators, enclosed places).
- Other (e.g., situations that may lead to choking or vomiting; in children, e.g., loud sounds or costumed characters).

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.

Table 38.3

DSM-5 Diagnostic Criteria for Social Anxiety Disorder (Social Phobia)

A. Marked fear or anxiety about 1 or more social situations in which the individual is exposed to possible scrutiny by others. Examples include social interactions (e.g., having a conversation, meeting unfamiliar people), being observed (e.g., eating or drinking), and performing in front of others (e.g., giving a speech).
B. The individual fears that he or she will act in a way or show anxiety symptoms that will be negatively evaluated (i.e., will be humiliating or embarrassing; will lead to rejection or offend others).
C. The social situations almost always provoke fear or anxiety.
Note: In children, the fear or anxiety may be expressed by crying, tantrums, freezing, clinging, shrinking, or failing to speak in social situations.
D. The social situations are avoided or endured with intense fear or anxiety.
E. The fear or anxiety is out of proportion to the actual threat posed by the social situation and to the sociocultural context.
F. The fear, anxiety, or avoidance is persistent, typically lasting for 6 mo or more.
G. The fear, anxiety, or avoidance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.
H. The fear, anxiety, or avoidance is not attributable to the physiologic effects of a substance (e.g., a drug of abuse, a medication) or another medical condition.
I. The fear, anxiety, or avoidance is not better explained by the symptoms of another mental disorder, such as panic disorder, body dysmorphic disorder, or autism spectrum disorder.
J. If another medical condition (e.g., Parkinson disease, obesity, disfigurement from burns or injury) is present, the anxiety or avoidance is clearly unrelated or is excessive.
Specify if:
Performance only: If the fear is restricted to speaking or performing in public.

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 ).

Table 38.4

DSM-5 Diagnostic Criteria for Panic Disorder

A. Recurrent unexpected panic attacks. A panic attack is an abrupt surge of intense fear or intense discomfort that reaches a peak within minutes, and during which time 4 (or more) of the following symptoms occur:
Note: The abrupt surge can occur from a calm state or an anxious state.
1. 1. Palpitations, pounding heart, or accelerated heart rate.
2. 2. Sweating.
3. 3. Trembling or shaking.
4. 4. Sensations of shortness of breath or smothering.
5. 5. Feelings of choking.
6. 6. Chest pain or discomfort.
7. 7. Nausea or abdominal distress.
8. 8. Feeling dizzy, unsteady, light-headed, or faint.
9. 9. Chills or heart sensations.
10. 10. Paresthesias (numbness or tingling sensations).
11. 11. Derealizations (feeling or unreality) or depersonalization (being detached from one-self).
12. 12. Fear of losing control or “going crazy.”
13. 13. Fear of dying.
Note: Culture-specific symptoms (e.g., tinnitus, neck soreness, headache, uncontrollable screaming or crying) may be seen. Such symptoms should not count as 1 of the 4 required symptoms.
B. At least 1 of the attacks has been followed by 1 mo (or more) of 1 or both of the following:
1. 1. Persistent concern or worry about additional panic attacks or their consequences (e.g., losing control, having a heart attack, “going crazy”).
2. 2. A significant maladaptive change in behavior related to the attacks (e.g., behaviors designed to avoid having panic attacks, such as avoidance of exercise or unfamiliar situations).
C. The disturbance is not attributable to the physiologic effects of a substance (e.g., a drug of abuse, a medication) or another medical condition (e.g., hyperthyroidism, cardiopulmonary disorders).
D. The disturbance is not better explained by another mental disorder (e.g., the panic attacks do not occur only in response to feared social situations, as in social anxiety disorder; in response to circumscribed phobic objects or situations, as in specific phobia; in response to obsessions, as in obsessive-compulsive disorder; or in response to reminders of traumatic events, as in posttraumatic stress disorder; or in response to separation from attachment figures, as in separation anxiety disorder).

Table 38.5

DSM-5 Diagnostic Criteria for Agoraphobia

A. Marked fear or anxiety about 2 (or more) if the following 5 situations:
1. 1. Using public transportation (e.g., automobiles, buses, trains, ships, planes).
2. 2. Being in open spaces (e.g., parking lots, marketplaces, bridges).
3. 3. Being in enclosed places (e.g., shops, theaters, cinemas).
4. 4. Standing in line or being in a crowd.
5. 5. Being outside of the home alone.
B. The individual fears or avoids these situations because of thoughts that escape might be difficult or help might not be available in the event of a developing panic-like symptoms or other incapacitating or embarrassing symptoms (e.g., fear or falling in the elderly, fear of incontinence).
C. The agoraphobic situations almost always provoke fear or anxiety.
D. The agoraphobic situations are actively avoided, require the presence of a companion, or are endured with intense fear or anxiety.
E. The fear or anxiety is out of proportion to the actual danger posed by the agoraphobic situations and to the sociocultural context.
F. The fear, anxiety, or avoidance is persistent, typically lasting for 6 mo or more.
G. The fear, anxiety, or avoidance causes clinically significant distress or impairment in social, occupational, or other important area of functioning.
H. If another medical condition (e.g., inflammatory bowel disease, Parkinson disease) is present, the fear, anxiety, or avoidance is clearly excessive.
I. The fear, anxiety, or avoidance is not better explained by the symptoms or another mental disorder—for example, the symptoms are not confined to specific phobia, situational type; do not involve only social situations (as in social anxiety disorder); and are not related exclusively to obsessions (as in obsessive-compulsive disorder), reminders or traumatic events (as in posttraumatic stress disorder), or fear of separation (as in separation anxiety disorder).
Note: Agoraphobia is diagnosed irrespective of the presence of panic disorder. If an individual's presentation meets criteria for panic disorder and agoraphobia, both diagnoses should be assigned.

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 ).

Table 38.6

DSM-5 Diagnostic Criteria for Generalized Anxiety Disorder

A. Excessive anxiety and worry (apprehensive expectation), occurring more days than not for at least 6 mo, about a number of events or activities (such as work or school performance).
B. The individual finds it difficult to control the worry.
C. The anxiety and worry are associated with 3 (or more) of the following 6 symptoms (with at least some symptoms having been present for more days than not for the past 6 mo):
Note: Only 1 item is required in children.
1. 1. Restlessness or feeling keyed up or on edge.
2. 2. Being easily fatigued.
3. 3. Difficulty concentrating or mind going blank.
4. 4. Irritability.
5. 5. Muscle tension.
6. 6. Sleep disturbance (difficulty falling or staying asleep, or restless, unsatisfying sleep).
D. The anxiety, worry, or physical symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.
E. The disturbance is not attributable to the physiologic effects of a substance (e.g., a drug of abuse, a medication) or other medical condition (e.g., hyperthyroidism).
F. The disturbance is not better explained by another mental disorder (e.g., anxiety or worry about having panic attacks in panic disorder, negative evaluation in social anxiety disorder [social phobia], contamination or other obsessions in obsessive-compulsive disorder, separation from attachment figures in separation anxiety disorder, remainders of traumatic events in posttraumatic stress disorder, gaining weight in anorexia nervosa, physical complaints in somatic symptom disorder, perceived appearance flaws in body dysmorphic disorder, having a serious illness in illness anxiety disorder, or the content of delusional beliefs in schizophrenia or delusional disorder).

Fig. 38.2 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.

Table 38.7

DSM-5 Diagnostic Criteria for Obsessive-Compulsive Disorder

A. Presence of obsessions, compulsions, or both:
Obsessions are defined by (1) and (2):
1. 1. Recurrent and persistent thoughts, urges, or images that are experienced, at some time during the disturbance, as intrusive and unwanted, and that in most individuals cause marked anxiety or distress.
2. 2. The individual attempts to ignore or suppress such thoughts, urges, or images, or to neutralize them with some other thought or action (i.e., by performing a compulsion).
Compulsions are defined by (1) and (2):
1. 1. Repetitive behaviors (e.g., hand washing, ordering, checking) or mental acts (e.g., praying, counting, repeating words silently) that the individual feels driven to perform in response to an obsession or according to rules that must be applied rigidly.
2. 2. The behaviors or mental acts are aimed at preventing or reducing anxiety or distress, or preventing some dreaded event or situation; however, these behaviors or mental acts are not connected in a realistic way with what they are designed to neutralize or prevent, or are clearly excessive.
B. The obsessions or compulsions are time-consuming (e.g., take more than 1 hr per day) or cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.
C. The obsessive-compulsive symptoms are not attributable to the physiologic effects of a substance (e.g., a drug of abuse, a medication) or another medical condition.
D. The disturbance is not better explained by the symptoms of another mental disorder (e.g., excessive worries, as in generalized anxiety disorder; preoccupation with appearance, as in body dysmorphic disorder; difficulty discarding or parting with possessions, as in hoarding disorder; hair pulling, as in trichotillomania [hair-pulling disorder]; skin picking, as in excoriation [skin-picking] disorder; stereotypies, as in stereotypic movement disorder; ritualized eating disorder, as in eating disorders; preoccupation with substances or gambling, as in substance-related and addictive disorders; preoccupation with having an illness, as in illness anxiety disorder; sexual urges or fantasies, as in paraphilic disorders; impulses, as in disruptive, impulse-control, and conduct disorders; guilty ruminations, as in schizophrenia spectrum and other psychotic disorders; or repetitive patterns of behavior, as in autism spectrum disorder).
Specify if:
With good or fair insight: The individual recognizes that obsessive-compulsive disorder beliefs are definitely or probably not true or that they may or may not be true.
With poor insight: The individual thinks obsessive-compulsive disorder beliefs are probably true.
With absent insight/delusional beliefs: The individual is completely convinced that obsessive-compulsive disorder beliefs are true.
Specify if:
Tic-related: The individual has a current or past history of a tic disorder.

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.

Table 38.8

DSM-5 Diagnostic Criteria for Posttraumatic Stress Disorder

Posttraumatic Stress Disorder

Note: The following criteria apply to adults, adolescents, and children older than 6 yr. For children 6 yr and younger, see corresponding criteria below.
A. Exposure to actual or threatened death, serious injury, or sexual violence in 1 (or more) of the following ways:
1. 1. Directly experiencing the traumatic event(s).
2. 2. Witnessing, in person, the event(s) as it occurred to others.
3. 3. Learning that the traumatic event(s) occurred to a close family member or close friend. In cases of actual or threatened death of a family member or friend, the event(s) must have been violent or accidental.
4. 4. Experiencing repeated or extreme exposure to aversive details of the traumatic event(s) (e.g., 1st responders collecting human remains; police officers repeatedly exposed to details of child abuse).
Note: Criterion A4 does not apply to exposure through electronic media, television, movies, or pictures, unless this exposure is work related.
B. Presence of 1 (or more) of the following intrusion symptoms associated with the traumatic event(s), beginning after the traumatic event(s) occurred:
1. 1. Recurrent, involuntary, and intrusive distressing memories of the traumatic event(s).
Note: In children older than 6 yr, repetitive play may occur in which themes or aspects of the traumatic event(s) are expressed.
1. 2. Recurrent distressing dreams in which the content and/or effect of the dream are related to the traumatic event(s).
Note: In children, there may be frightening dreams without recognizable content.
1. 3. Dissociative reactions (e.g., flashbacks) in which the individual feels or acts as if the traumatic event(s) were recurring. (Such reactions may occur on a continuum, with the more extreme expression being a complete loss or awareness of present surroundings.)
Note: In children, trauma-specific reenactment may occur in play.
1. 4. Intense or prolonged psychological distress at exposure to internal or external cues that symbolize or resemble an aspect of the traumatic event(s).
2. 5. Marked physiologic reactions to internal or external cues that symbolize or resemble an aspect of the traumatic event(s).
C. Persistent avoidance of stimuli associated with the traumatic event(s), beginning after the traumatic event(s) occurred, as evidenced by 1 or both of the following:
1. 1. Avoidance of or efforts to avoid distressing memories, thoughts, or feelings about or closely associated with the traumatic event(s).
2. 2. Avoidance of or efforts to avoid external reminders (people, places, conversations, activities, objects, situations) that arouse distressing memories, thoughts, or feelings about or closely associated with the traumatic event(s).
D. Negative alterations in cognitions and mood associated with the traumatic event(s), beginning or worsening after the traumatic event(s) occurred, as evidenced by 2 (or more) of the following:
1. 1. Inability to remember an important aspect of the traumatic event(s) (typically due to dissociative amnesia and not to other factors such as head injury, alcohol, or drugs).
2. 2. Persistent and exaggerated negative beliefs or expectations about oneself, others, or the world (e.g., “I am bad,” “No one can be trusted,” “The world is completely dangerous,” “My whole nervous system is permanently ruined”).
3. 3. Persistent, distorted cognitions about the cause or consequences of the traumatic event(s) that lead the individual to blame himself/herself or others.
4. 4. Persistent negative emotional state (e.g., fear, horror, anger, guilt, or shame).
5. 5. Markedly diminished interest or participation in significant activities.
6. 6. Feelings of detachment or estrangement from others.
7. 7. Persistent inability to experience positive emotions (e.g., inability to experience happiness, satisfaction, or loving feelings).
E. Marked alterations in arousal and reactivity associated with the traumatic event(s), beginning or worsening after the traumatic event(s) occurred, as evidenced by 2 (or more) of the following:
1. 1. Irritable behavior and angry outbursts (with little or no provocation) typically expressed by verbal or physical aggression toward people or objects.
2. 2. Reckless or self-destructive behavior.
3. 3. Hypervigilance.
4. 4. Exaggerated startle response.
5. 5. Problems with concentration.
6. 6. Sleep disturbance (e.g., difficulty falling or staying asleep or restless sleep).
F. Duration of the disturbance (Criteria B, C, D, and E) is more than 1 mo.
G. The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.
H. The disturbance is not attributable to the physiologic effects of a substance (e.g., medication, alcohol) or another medical condition.
Specify whether:
With dissociative symptoms: The individual's symptoms meet the criteria for posttraumatic stress disorder, and in addition, in response to the stressor, the individual experiences persistent or recurrent symptoms of either of the following:
1. 1. Depersonalization: Persistent or recurrent experiences of feeling detached from, and as if one were an outside observer of, one's mental processes or body (e.g., feeling as though one were in a dream; feeling a sense of unreality of self or body or of time moving slowly).
2. 2. Derealization: Persistent or recurrent experiences of unreality of surroundings (e.g., the world around the individual is experienced as unreal, dreamlike, distant, or distorted).
Note: To use this subtype, the dissociative symptoms must not be attributable to the physiologic effects of a substance (e.g., blackouts, behavior during alcohol intoxication) or another medical condition (e.g., complex partial seizures).
Specify if:
With delayed expression: If the full diagnostic criteria are not met until at least 6 mo after the event (although the onset and expression of some symptoms may be immediate).

Posttraumatic Stress Disorder for Children 6 Yr and Younger

A. In children 6 yr and younger, exposure to actual or threatened death, serious injury, or sexual violence in 1 (or more) of the following ways:
1. 1. Directly experiencing the traumatic event(s).
2. 2. Witnessing, in person, the event(s) as it occurred to others, especially primary caregivers.
Note: Witnessing does not include events that are only in electronic media, television, movies, or pictures.
1. 3. Learning that the traumatic event(s) occurred to a parent or caregiving figure.
B. Presence of 1 (or more) of the following intrusion symptoms associated with the traumatic event(s), beginning after the traumatic event(s) occurred:
1. 1. Recurrent, involuntary, and intrusive distressing memories of the traumatic event(s).
Note: Spontaneous and intrusive memories may not necessarily appear distressing and may be expressed as play reenactment.
1. 2. Recurrent distressing dreams in which the content and/or effect of the dream is related to the traumatic event(s).
Note: It may not be possible to ascertain that the frightening content is related to the traumatic event.
1. 3. Dissociative reactions (e.g., flashbacks) in which the child feels or acts as if the traumatic event(s) were recurring. (Such reactions may occur on a continuum, with the most extreme expression being a complete loss of awareness of present surroundings.) Such trauma-specific reenactment may occur in play.
2. 4. Intense or prolonged psychological distress at exposure to internal or external cues that symbolize or resemble an aspect of the traumatic event(s).
C. One (or more) of the following symptoms, representing either persistent avoidance of stimuli associated with the traumatic event(s) or negative alterations in cognitions and mood associated with the traumatic event(s), must be present, beginning after the event(s) or worsening after the event(s):
1. Persistent Avoidance of Stimuli
2. 1. Avoidance of or efforts to avoid activities, places, or physical reminders that arouse recollections or the traumatic event(s).
3. 2. Avoidance of or efforts to avoid people, conversations, or interpersonal situations that around recollections of the traumatic event(s).
4. Negative Alterations in Cognitions
5. 3. Substantially increased frequency of negative emotional states (e.g., fear, guilt, sadness, shame, confusion).
6. 4. Markedly diminished interest or participation in significant activities, including constriction of play.
7. 5. Socially withdrawn behavior.
8. 6. Persistent reduction in expression of positive emotions.
D. Alterations in arousal and reactivity associated with the traumatic event(s), beginning or worsening after the traumatic event(s) occurred, as evidenced by 2 (or more) of the following:
1. 1. Irritable behavior and angry outbursts (with little or no provocation), typically expressed as verbal and physical aggression toward people or objects (including extreme temper tantrums).
2. 2. Hypervigilance.
3. 3. Exaggerated startle response.
4. 4. Problems with concentration.
5. 5. Sleep disturbance (e.g., difficulty falling asleep or staying asleep or restless sleep).
E. The duration of the disturbance is more than 1 mo.
F. The disturbance causes clinically significant distress or impairment in relationships with parents, siblings, peers, or other caregivers or with school behavior.
G. The disturbance is not attributable to the physiologic effects of a substance (e.g., medication or alcohol) or another medical condition.
Specify whether:
With dissociative symptoms: The individual's symptoms meet the criteria for posttraumatic stress disorder, and the individual experiences persistent or recurrent symptoms of either of the following:
1. 1. Depersonalization: Persistent or recurrent experiences of feeling detached from, and as if one were an outside observer of, one's mental processes or body (e.g., feeling as though one were in a dream; feeling a sense of unreality of self or body or of time moving slowly).
2. 2. Derealization: Persistent or recurrent experiences of unreality of surroundings (e.g., the world around the individual is experienced as unreal, dreamlike, distant, or distorted).
Note: To use this subtype, the dissociative symptoms must not be attributable to the physiologic effects of a substance (e.g., blackouts, behavior during alcohol intoxication) or another medical condition (e.g., complex partial seizures).
Specify if:
With delayed expression: If the full diagnostic criteria are not met until at least 6 mo after the event (although the onset and expression of some symptoms may be immediate).

Events that pose actual or threatened physical injury, harm, or death to the child, child's caregiver, or others close to the child, and that produce considerable stress, fear, or helplessness, are required to make the diagnosis of PTSD. Three clusters of symptoms are also essential for diagnosis: reexperiencing, avoidance, and hyperarousal. Persistent reexperiencing 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 usually observable in younger children, whereas older children may better describe reexperiencing 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, 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 the child's 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. Recent RCTs in children and adolescents with PTSD found no significant difference between SSRI and placebo. SSRIs may be considered in pediatric patients with PTSD who have comorbid conditions responsive to SSRIs, including depression, affective numbing, and anxiety (see Table 33.4 ). As for many other anxiety disorders, CBT is the psychotherapeutic intervention with the most empirical support.

Anxiety Associated With Medical Conditions

It is prudent to rule out organic conditions such as hyperthyroidism, caffeinism (carbonated beverages), hypoglycemia, central nervous system disorders (delirium, encephalopathy, brain tumors), migraine, asthma, lead poisoning, cardiac arrhythmias, and rarely, pulmonary embolism, hyperparathyroidism, systemic lupus erythematosus, anaphylaxis, porphyria, or pheochromocytoma, before making a diagnosis of an anxiety disorder (see Table 38.1 ). Some prescription drugs with side effects that can mimic anxiety include antiasthmatic agents, corticosteroids, sympathomimetics, SSRIs (initiation), anticholinergic agents, and antipsychotics. Nonprescription drugs causing anxiety include diet pills, antihistamines, stimulant drugs of abuse, drug withdrawal, and cold medicines.

Chronic illness is also an underlying cause of anxiety. Children are not often emotionally and cognitively competent to understand the implications of a serious and prolonged illness. In addition to the physiologic implications of illness, they must also attend to the hospitalizations, procedures, and medications that permeate their everyday schedule. This experience affects their schooling, friendships, activities, and dynamics of the nuclear family, including the experiences of their well siblings.

School issues surrounding both prolonged absences and school reentry following a medical condition can cause or reinforce and escalate existing anxiety. School is a foundation not only for learning, but it is central to children's social experiences and feelings of normalcy. It is often impeded and stunted by illness. Academic struggles can result from missing classes, medication use, and emotional status. Children with chronic conditions are also socially disadvantaged, with friendship networks hampered by unstable attendance or social rejection for being different. Consulting with the school psychologist can be beneficial in preparing teachers and classmates before the child returns to school. An agreement between the student and school staff should be implemented, outlining a plan for taking medication, needing rest, or consulting on other needs. If the child and family agree, an informational meeting with students and teachers can normalize the situation. Explaining the condition makes it less scary for children who catastrophize or worry about contagion. Classmates and teachers are a natural accessible resource and can be a valuable support community. Medication may also be warranted to supplement social supports.

The experiences of the siblings of children with chronic illness are often forgotten, with familial resources focused on medical-financial consequences and the emotional and physical functioning of the ill child. It is not uncommon for the siblings of ill children to experience depression and anxiety as well. Assessing their social support systems, communication opportunities with parents and emotional outlets are critical to maintaining healthy functioning. Maintaining a redefined schedule of after-school activities and social engagements are helpful in allowing siblings to continue in school.

Safety and Efficacy Concerns About SSRIs

No empirical evidence suggests the superiority of one SSRI over another. Data are limited on combining medications. SSRIs are usually well tolerated by most children and adolescents. The FDA issued a “black box” warning of increased agitation and suicidality among adolescents and children taking SSRIs. This warning was based on review of studies in children and adolescents with major depression and not anxiety disorders. Close monitoring is always warranted.