Manual of Psychiatric Therapeutics: Practical Psychopharmacology and Psychiatry (Little, Browns Paperback Book Series)

Editors: Shader, Richard I.

Title: Manual of Psychiatric Therapeutics, 3rd Edition

Copyright 2003 Lippincott Williams & Wilkins

> Table of Contents > 21 - Approaches to the Psychopharmacologic Treatment of Children and Youth

21

Approaches to the Psychopharmacologic Treatment of Children and Youth

Jessica R. Oesterheld

Richard I. Shader

Dean X. Parmelee

Aradhana Bela Sood

The initial psychiatric evaluation of youth is often more complex and time-consuming than is the evaluation of adults. The following three sources of information must be tapped: parents (e.g., reason for referral, child's current and past functioning, child's past developmental and medical history, family functioning, and psychiatric history), teachers (e.g., child's cognitive functioning, learning style, symptoms present in school, and peer relations), and the youth (e.g., current and past symptoms and concerns, responses to important life events, and world view). Younger children may reveal information about themselves through their play and drawings. Most clinicians who evaluate children use a variety of standardized rating scales during the assessment process.

Parents and teachers may disagree on their views of the child because of bias or because children may behave differently in different settings (e.g., mild oppositional behavior may be evident only at home; bullying other children may be evident only on the playground). The clinician-evaluator must integrate all data and must place the information into a developmental, familial, cultural, and gender perspective to generate a differential diagnosis and to initiate a comprehensive treatment plan.

A modest research base for informing the development of psychologic and pharmacologic treatment plans for youth has hobbled clinicians. Because the United States Food and Drug Administration (FDA) and the National Institutes of Health have required or supported more research in pediatric psychopharmacology since 1995, a meaningful increase has occurred in studies and publications in this field. This has included the establishment of multicenter Research Units for Pediatric Psychopharmacology, which have begun to tackle questions about the efficacy of medications in youth for conditions such as anxiety disorders that have long been answered in adults. Disorders of childhood, such as Tourette disorder and attention deficit hyperactivity disorder (ADHD), are considered separately in Chapters 7 and 22. In this chapter, schizophrenia; autism; and disorders of conduct, mood, and anxiety are reviewed. Only issues of diagnosis and treatment specific to youth are included; the reader is referred to the appropriate general chapters for a more in-depth presentation of each disorder.

I. Major Depressive Disorder

Major depressive disorder (MDD) is a common psychiatric condition in youth that has been shown to be increasing in prevalence in each generation since the 1940s and that is developing in successively younger individuals (a cohort effect). Several decades ago, the diagnosis of MDD in youth was controversial because psychoanalytic theory precluded the possibility of the development of depression until the superego was formed. Although accurate diagnosis requires that the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), are met (see Chapter 18), important, recognizable, developmentally based differences are evident in the presentation of depression symptoms in children and teenagers. Children are more likely to have concomitant anxiety (phobias, separation anxiety), somatic complaints (headaches and stomachaches), auditory hallucinations, irritability, frustration, temper tantrums, and behavioral problems. Adolescents show more irritability, sleep and appetite disturbances (e.g., hypersomnia and hyperphagia), delusions, and suicidal ideation and attempts. Recent research suggests that MDD may be chronic, familial, and recurrent. Childhood depression often persists into adulthood, and it is

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Suicide prevention (see Chapter 17) is the highest goal for assessing and treating any child or adolescent with depression. Population studies suggest MDD prevalence rates of 0.4% to 2.5% for depression in children and 4% to 8% for adolescents. The lifetime prevalence rate of MDD for adolescents is about 15%, which is similar to the estimated adult prevalence rate of about 17%. The comparable figures for dysthymic disorder (DD) are 0.6% to 1.7% for children and 1.6% to 8% for adolescents. Although MDD in childhood occurs equally in boys and girls, adolescent girls over age 14 are affected at almost twice the rate of adolescent boys. This trend persists through the reproductive years, suggesting that hormonal and other developmental factors appearing during puberty may have an important etiologic role in this disorder.

In youth, a typical untreated episode lasts between 7 and 9 months. Relapse is common, and recurrence rates may be as high as 50% after 1 to 2 years and 70% after 5 years. Chronicity is evident in only 10% of first-episode cases. Youth with chronic depression have an earlier onset, a greater number and severity of prior episodes, poor compliance, psychosocial adversity, parental psychiatric illness, and adverse life events. For the diagnosis of DD, the child or adolescent must have had a 1-year period of dysphoric mood, wherein the signs and symptoms are quite similar to those of MDD but are fewer and less severe. Recent evidence shows that DD may have a chronic course and that it commonly acts as a gateway to the development of MDD. The clinician should remember that not all youth who show symptoms of depression develop a mood disorder.

Children and teens with MDD commonly have comorbid diagnoses (e.g., DD, anxiety disorders, substance abuse, disruptive behaviors, somatoform disorders, and personality traits), and the presence of comorbidity impacts the risk for recurrent depression, the duration of an episode, suicidal behaviors, poor psychosocial and/or academic function, and the benefits from treatment interventions. For example, youth with double depression (MDD plus DD) tend to have longer and more severe depressive episodes, increased suicidality, and poorer overall functioning. These youth are often significantly more impaired socially and less competent than their peers with either MDD or DD alone. Youth with co-occurring anxiety and MDD may also have poor outcomes.

A. Diagnosis, Etiology, and Assessment

Depression in a child or adolescent is the result of a confluence of biologic and environmental factors. Numerous twin and adoption studies have demonstrated that genetic factors account for at least 50% of the variance in the transmission of mood disorders for the adult population, and genetic studies have further indicated that environmental factors play a significant role in the onset, duration, and course of depression. Family aggregation studies have suggested that children of depressed parents are much more likely to have a lifetime episode of MDD, and the first-degree relatives of children with depression have lifetime prevalence rates of depression that range from 20% to 46%. Children appear to be highly sensitive to environmental events in both the development and the maintenance of depressive symptoms (e.g., children's depressive symptoms may relent when hospitalized for a short stay). Environmental factors that may predate the onset of signs and symptoms of a depressive disorder in a child or adolescent include adverse life events, such as loss or separation of a parent or other caregiver, the loss of a romantic relationship, change in peer group and/or school because of a family move, parental discord, and psychiatric illness in one or both parents. Studies suggest that depressed children may have cognitive styles that differ from nondepressed children in that they see the world more negatively. Many depressed children believe that they have less control over

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The most effective approach for the treatment of a child or adolescent who is depressed begins with a comprehensive assessment (Table 21.1). The clinical interview is the starting point for the evaluation of any child or adolescent with a possible depressive disorder. A careful assessment can reduce tension in the family; improve the bond between parents and child; reduce the risk of suicidal behaviors; and create a working alliance with the physician, which is necessary for treatment compliance. The parents and others who are important in the child's life serve as sources of information about changes in the child's mood and behavior. Although a careful detailed history from the parents is vital, the frequency of parents' lack of awareness of their children's suicidal thoughts or actions, hallucinations, delusions, or substance abuse is surprising. Children must therefore be afforded the opportunity to speak privately and must be given enough time to enable the clinician to explore the circumstances surrounding, and the progression of, mood and affect changes. Developmentally sensitive questioning about symptoms is essential. A series of pictures of different facial expressions may be used to initiate a conversation about feelings with younger children as follows:

• What feeling does this face show?

• After the identification of happy, sad, scared, angry, ask Do you ever feel happy?

• When do you feel happy?

• Do you ever feel sad?

• When do you feel sad?

At times, clinicians may use a mood thermometer, a ranking from 0 to 10 that indicates sad to increasingly happier faces.

• If 0 is I wish I were dead and 10 is I am feeling really, really happy, what number are you right now?

• What is the highest number you ever feel?

• When do you feel that way?

• What is the lowest number you ever feel?

• When did you feel that way?

• Have you ever felt like a 0?

Children may prefer to interact with play or drawing materials as a way of displacing their feelings, or they may simply be more comfortable talking with an adult if they are allowed to engage in familiar activities such as drawing. Clinicians should be alert to any anhedonic quality and themes of death and destruction in the play of a depressed child. Several clinician and self-administered rating scales can be helpful in screening for depressive symptoms.

Medical conditions may first present with signs and symptoms of depression in children and adolescents, and they must be considered when evaluating for depression (e.g., hepatitis, influenza, infectious mononucleosis, acquired immunodeficiency syndrome, Cushing disease, hypothyroidism,

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B. Treatment

• Psychoeducational approaches. As outcome studies of schizophrenia and depression in adults have shown (see Chapters 18 and 20), patients and families benefit from learning about their illnesses. Children and adolescents and their families are often relieved to learn that they have a treatable or understandable illness. Furthermore, in describing the illness, the clinician can build rapport, enlist compliance with the treatment recommendations, and encourage patience with a prolonged treatment process. When the parents themselves suffer from depressive disorders, the appropriate referral should be initiated.

• Psychotherapy. This approach has benefit for depressed children or adolescents who have mild or moderate forms of depression (some evidence for efficacy is also seen in severe depression). Individual and group cognitive-behavior therapy (CBT), interpersonal therapy, and psychodynamic psychotherapy have all shown benefit when tailored to the specific needs of the child or adolescent and his or her family. Dialectic behavioral therapy may be useful for teens with suicidal behaviors. The use of one or more of these psychotherapeutic approaches is important for more severely depressed children or adolescents and for those whose family backgrounds and situations (e.g., psychiatric and/or drug-dependent illness in parents, contentious divorce) place them at greater risk for chronic depression and suicidal behaviors.

• Pharmacotherapy. Medication is not usually first-line treatment, except in certain contexts (e.g., unwillingness to participate in psychotherapy, a previously adequate but ineffective psychotherapeutic trial, a high suicidal risk, the presence of severe or psychotic symptoms). In contrast to adults, a limited number of double-blind, placebo-controlled studies demonstrate the efficacy of selective serotonin reuptake inhibitors (SSRIs) in the treatment of depression in children and adolescents. Fluoxetine is approved for use in youth 7 years of age and older. No similar studies of bupropion, venlafaxine, mirtazapine, or nefazodone nor of augmentation strategies have been conducted for treatment-resistant depression in youth. Tricyclic antidepressants (TCAs) are rarely used as an initial treatment in these age groups because no proven benefit over a placebo has been found in many drug trials. TCAs may have untoward side effects, especially cardiovascular ones; they may be lethal in overdose.

  A few pharmacokinetic studies of youth have been completed, but dosing of the SSRIs in children is generally initiated in lower doses than in those seen with adolescents and adults because weight-corrected plasma levels in children are generally higher than they are in teens or adults. A typical regimen would be to initiate fluoxetine (5 to 10 mg per day orally) and to increase the dose up to 20 mg as tolerated after 2 to 3 weeks once evidence of at least minimal clinical improvement is seen (Table 21.2). Antidepressant dosing regimens of adolescents are similar to those for adults.

  As in adults, adverse effects have been reported with all the SSRIs (see Chapter 18). Slight decreases in growth have been observed in youth on fluoxetine. Compared with adults, an increased rate of akathisia and behavioral activation may occur when these drugs (especially with higher doses of fluoxetine) are initiated in youth. (Note: Activation is not diagnostic of bipolar vulnerability.) Because some have suggested that as many as one-fourth of youth with depression develop manic symptoms, clinicians should be alert to frank manic symptoms that emerge later in the course of treatment after the depressive symptoms have relented.

  TABLE 21.2. DOSING OF SELECTIVE SEROTONIN REUPTAKE INHIBITORS IN YOUTH
  Drug Usual dosage range (mg) in children less than 12 years of age Citalopram 10 20 Fluvoxamine 25 200 Fluoxetine 5 20 Paroxetine 5 20 Sertraline 25 150

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  An increasing number of reports have been made of childhood central serotonin syndrome, which is now known as toxic serotonin syndrome (e.g., altered consciousness, hyperreflexia, myoclonus), after the initiation or a dosage increase of SSRIs or with the addition of other proserotonergic drugs (e.g., clomipramine [CMI], lithium, and meperidine) (see also Chapters 3 and 29). After successful treatment with SSRIs (or other antidepressants), some youth who have been socially withdrawn or apathetic begin to demonstrate new-onset oppositional behavior. Amotivational syndrome, epistaxis, and easy bruising are rarely reported. Sexual symptoms should be investigated sensitively. Clinicians should obtain a careful drug history of all prescription drugs, over-the-counter medications, herbals and dietary supplements, and illicit drugs because all the newer antidepressants are cytochrome P-450 substrates and most inhibit P-450 cytochromes to varying degrees. Clinicians must be cognizant of possible drug interactions when SSRIs are combined with psychotropic or nonpsychotropic agents. For example, if fluvoxamine was added to CMI, a child could develop profound sedation secondary to an increased concentration of CMI. If fluvoxamine was then abruptly discontinued, the child could develop a flu-like syndrome from the abruptly reduced concentrations of CMI. Similar discontinuation symptoms may also occur when SSRIs are abruptly withdrawn, and they may be more common with paroxetine and fluvoxamine, but all SSRIs except fluoxetine should be gradually tapered.

  If only some improvement is seen after administering the agent at full doses for 2 to 3 weeks, the clinician may augment the agent with lithium or buspirone. When no clinical improvement is seen or intolerable side effects have developed in 4 to 6 weeks, switching to another SSRI is common. Moving to a TCA (see Chapter 18), venlafaxine, nefazodone, bupropion, or mirtazapine may be indicated if the child or adolescent either fails to respond well to separate trials of two SSRIs or has a particularly adverse response to these agents. See Table 21.3 for dosing recommendations for these non-SSRI antidepressants.

  TABLE 21.3. USUAL DOSING OF SELECTED ANTIDEPRESSANTS IN YOUTHS
  Drug Usual dosage range in children less than 12 years of age Bupropion IR 3 6 mg/kg/d in t.i.d. dosing (no higher than 150 mg in a single dose) Bupropion SR 150 300 mg/d in b.i.d. dosing Mirtazapine 7.5 30 mg/d q.d. Nefazodone 50 300 mg/d in b.i.d. dosing Venlafaxine 1 3 mg/kg/d in b.i.d. or t.i.d. dosing Abbreviations: b.i.d., twice a day; q.d., every day; t.i.d., three times a day.

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  Children or adolescents who do not substantially improve with any of these recommendations can be treated as if they were treatment-resistant adults (see Chapter 18). Electroconvulsive therapy (see Chapter 24) can and should be used in those youth who do not respond to a well-considered set of medication trials or whose level of sustained suicidal intent precludes the protracted time required for medication treatments. (Note: State laws rarely permit the administration of electroconvulsive therapy to children younger than the age of 14.) When psychotic features accompany MDD in a child or adolescent, adding one of the newer atypical antipsychotic medications to the antidepressant regimen can be considered (with careful attention to possible drug interactions). Unless the family support situation is particularly strong, inpatient hospitalization is likely indicated for the psychotically depressed child or adolescent.

  A child or adolescent undergoing medication treatment for MDD should be seen weekly by the physician or another licensed and qualified clinician until clear signs of improvement are observed. The systematic use of one of the depression rating scales provides some objective information for the treating clinician, as well as for the patient and family. Once clinical improvement occurs (and the family feels better about the child), continuation of medication is recommended for at least 6 to 12 months. Visits to the treating clinician do not need to be as frequent unless ongoing psychotherapy with the child or family is being provided on a weekly basis. Because longitudinal studies show that MDD or DD starting in childhood or adolescence often persists into young adulthood (or recurs if it remits), plans should be made for regular follow-up visits for several years.

II. Bipolar Disorder

As in adults, youth who develop bipolar disorder (BD) can present initially with either depression or classic signs of mania, and one estimate is that 70% of individuals with teen-onset BD have an initial presentation of MDD. About one-third of prepubertal-onset children with depression and one-fifth of teenaged-onset depressives will develop mania. The mean onset of manic symptoms after MDD in the latter group is 4 years, and it occurs after two to four depressive episodes. Although prediction of a BD outcome in children with prepubertal-onset depression is correlated with parental and grandparental BD disease, only 12% to 15% of the offspring of parents with BD are diagnosed with BD, even in parents with early-onset BD or childhood ADHD.

Rarely children and more commonly those in their mid to late teens with BD present initially with hypomanic or full-blown manic symptoms. In community samples of teens, 6% to 13% have manic symptoms; however, when impairment and severity criteria are applied, less than 1% meet BD criteria. Youth with adolescent-onset BD have a prolonged course of mixed episodes and rapid cycling; psychotic features; an increased risk of suicide; comorbid substance abuse; and anxiety disorders, including panic disorder (PD), more often than do individuals with adult-onset BD. They may have other significant comorbid diagnoses, such as ADHD, CD, panic disorder, and Tourette disorder. The stability of a BD diagnosis of teen-onset BD has been shown through young adulthood, but the group of teens with some manic symptoms does not later develop BD.

Although individuals with teen-onset classic BD (especially those with comorbid childhood ADHD) are difficult to treat and they have high rates of relapse, no controversy is seen about their existence as a diagnostic entity. However, considerable controversy exists about whether the diagnosis of BD should be applied to a group of prepubertal children with chronic and nonepisodic disabling behaviors and emotions that have many similarities to adolescent and adult BD. In the early 1990s, clinician-investigators began to describe a group of children who were extremely troubled and unresponsive to treatment. The hallmark of these children was their labile and irritable moods, which were termed affective storms, that often occurred in combination with symptoms of impulsivity, hyperactivity, and distractibility. Hence, differentiating them from children with severe ADHD was difficult.

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Currently, some investigators who are supported by the National Institute of Mental Health (NIMH) are using the diagnosis BD, not otherwise specified (NOS), for these children. Studies are being conducted over time to determine whether these children progress into cyclothymia or true BD diagnostic categories or, as often happens to teens with some manic symptoms, the evolution into a BD diagnosis does not take place (see Additional Reading).

A. Diagnosis and Etiology

Unfortunately, the term BD in children and teens has become a fad diagnosis for psychiatrists, pediatricians, and family practitioners. This is because of recent attention devoted to this diagnosis by a variety of media and lay publications, as well as the pressures of practicing in an environment controlled by managed care, which requires a biologically based diagnosis to make a payment. Many children with ADHD or CD are inappropriately diagnosed as BD. Diagnosis must be based on supporting data and not on the previous clinical diagnosis or even the hospitalization diagnoses of BD because of the inaccuracy and overdiagnosis of this condition.

Diagnostic instruments provide a standard format for assessing and quantifying mood-related symptoms (e.g., the Young Mania Rating Scale). However, clinical experience, a knowledge of development, and an understanding of the differences from and similarities to the other severe forms of psychopathology in childhood create the strongest basis for making an accurate diagnosis. Clinicians must search for comorbid ADHD, CD, anxiety disorders, and substance abuse. The latter is commonly found in teens with BD, but the clinician must also distinguish the symptoms of true BD from the highs and crashes of amphetamine use or from hallucinations caused by hallucinogens. Distinguishing the hallucinations of schizophrenia from those of BD is particularly difficult because the classic display of mood-congruent hallucinations (e.g., I hear voices telling me that I am a bad person ) is not always present. The presence of affective disorders in multiple generations of relatives is suggestive of a diagnosis of BD rather than of schizophrenia; for many youth, only long-term follow-up clarifies the diagnosis. Clinicians must be vigilant to hints of suicidality in youth with BD and must act to prevent its occurrence (see Chapter 17).

B. Treatment

• Psychoeducational approaches. Families of youth with BD need education and psychologic support over time. Patients and parents must learn about the cyclical nature of this disorder, and they should be encouraged to create and maintain a life chart. This practice helps define precipitating stressors, as well as the outcome of specific therapeutic interventions. Appropriate residential placement can be a powerful remedial treatment, especially in youth with chaotic home environments that perpetuate their cyclic illness. Appropriate educational placements allow these youth to maximize their academic potential. Educating teachers and guidance counselors about the needs of youth with this disorder can facilitate a more positive attitude toward these youth, rather than viewing them merely as that problem child.

• Psychotherapy. CBT for children with BD is one of the preferred modalities of psychotherapy. A protocol has been formulated for the use of CBT with youth with BD (see Additional Reading) that helps them

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  learn to better manage the thoughts and behaviors that accentuate negative feelings and actions. Short-term, focused, insight-oriented psychotherapy may be useful for the management of poor medication compliance, especially among adolescents.

• Pharmacotherapy. Developing a firm alliance and continuity of care with these youth and their families is crucial because the disorder usually persists through adulthood. Medication nonadherence is often the biggest obstacle to a youth's stability; a recent research study showed a 31% noncompliance rate. Regularly scheduled visits are necessary, and frequency should be increased during stressful times (e.g., parental discord, drug and/or alcohol experimentation, transition to a new school). Comorbid conditions should be vigorously treated.

  The first multisite placebo-controlled study comparing lithium, valproate, and carbamazepine (CBZ) in these youth is underway. Several years are likely to pass before firm conclusions can be made about which drug is best for BD.

  • Lithium has FDA approval for the treatment of mania in children older than 12 years of age. It is the first line of treatment for classic mania, or it may be used as an add-on in valproate treatment-resistant or CBZ treatment-resistant mixed mania or rapid cycling. One double-blind, placebo-controlled study of adolescent-onset BD and concomitant substance abuse and of children with MDD with markers for future BD (i.e., delusions, TCA-induced mania, psychomotor retardation, family member with BD) reported an efficacy response of 43% to 46%.

    Weight-based dosing should be considered when initiating treatment (see Additional Reading). Trough blood levels, complete blood count, thyroid-stimulating hormone, creatinine, calcium, and phosphorous need to be tested before treatment and at regular intervals; a pretreatment and follow-up urinalysis are also indicated. The treating clinician must monitor lithium trough blood levels and must remain vigilant for symptoms and signs of lithium toxicity; children may require higher dosing to obtain lithium blood levels within a therapeutic range because of their increased glomerular filtration rate and total body water. Younger children and those with pervasive developmental disorder (PDD) may be more sensitive to the side effects of weight gain, nausea, vomiting, tremor, and urinary frequency. Because nocturnal enuresis may develop and since this may be particularly embarrassing for children, using a once a day dosing regimen in the morning may be useful. (Note: The clinician should remember that, when shifting from three times a day to once a day lithium dosing, the once a day dose should be reduced to about two-thirds of the total three times a day dosing to obtain comparable trough lithium levels.) When nausea or vomiting is a prominent side effect, longer-acting preparations may be used. The following are key considerations when using lithium:

    • Serum level of 0.8 to 1.2 mEq per L.

    • Onset of action: 7 to 14 days, full benefit at 6 to 8 weeks.

    • Side effects: nausea, diarrhea, tremor, enuresis, fatigue, ataxia, leukocytosis, malaise, acne, and weight gain.

    • Other adverse effects: renal abnormalities, generally polyuria and polydipsia; electrocardiographic changes; and rare hypothyroidism; a subgroup of children may develop cognitive impairment at normal lithium levels.

    • Importance of stable families to ensure medication adherence and to monitor levels.

    • Importance of long-term maintenance because those who discontinue it have higher relapse rates in clinical trials.

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  • Divalproate (DVP) is the current treatment of choice for mixed-episode presentations or rapid cycling. After liver function tests, complete blood count, and platelet count have been obtained, a loading dose of 7.5 mg per kg per day is tolerated by most youth. Alternatively, an initial oral dose of 250 mg twice a day can be gradually titrated upward. The following are key considerations when using DVP:

    • Serum level target of 50 to 125 mg per mL.

    • Onset of action: 4 to 10 days, full benefit at 6 to 8 weeks.

    • Side effects: nausea, vomiting, sedation, weight gain, transient hair loss, tremor, and transient elevation of liver function tests.

    • Other adverse effects: hepatotoxicity more likely in children under age 2 years treated with other anticonvulsants (note: findings from children with seizure disorders); high concentration of ammonia, blood dyscrasias, alopecia, and menstrual changes; rare cases of pancreatitis, benign hypothrombocytopenia, and decreased prothrombin times.

    • In children with seizures receiving DVP, polycystic ovary syndrome (i.e., obesity, hyperinsulinemia, lipid abnormalities, and hyperandrogenism) is uncommon, but this may occur in those who start DVP as peripubertal girls.

  • Carbamazepine is an alternative treatment for BD in youth. It may be added to either lithium or DVP in treatment-resistant cases. Clinicians should be cautious with the latter combination because CBZ may induce glucuronidation and DVP inhibits the formation of CBZ-10,11-epoxide (a metabolite that is active but is not routinely measured). No loading dose strategies are available, but treatment can be initiated with 100 mg per day; therapeutic levels are reached by adding 100 to 200 mg weekly. The usual dose is 10 to 20 mg per kg per day twice a day or three times a day, but blood levels need to be checked because CBZ induces CYP 3A4 and reduces its own blood levels. Induction occurs within the first 2 weeks after a dose increase. Pretreatment complete blood count and platelet count and periodic blood should be drawn for both therapeutic levels and for a hematologic profile. The following are key considerations when using CBZ:

    • Usual target dose of 200 to 600 mg per day for children; 400 to 1,200 mg per day for teens.

    • Serum level of 5 to 10 mg per mL.

    • Onset of action: 7 to 14 days, full benefit at 6 to 8 weeks.

    • Side effects: drowsiness, loss of coordination, vertigo.

    • Other adverse effects: leukopenia, aplastic anemia, thrombocytopenia, rashes, and drug drug interactions via induction.

    • In girls with seizures but without obesity, polycystic ovary syndrome rarely develops.

  • Other anticonvulsants with case reports of effectiveness for BD in youth include lamotrigine and topiramate. Children with seizures treated with lamotrigine have a higher incidence of rash than do adults, as well as a higher incidence of developing Stevens-Johnson syndrome or toxic epidermal necrolysis (1% versus 0.3%). These syndromes may be associated with a rapid titration of dosage and the concomitant usage of DVP in children with seizure disorders. A single case of cognitive impairment in a child with BD who was treated with topiramate has been reported, and a significant percentage of children with seizures who are treated with this drug have concentration and behavioral problems (14%). Concomitant usage of lamotrigine may be a predisposing factor. Weight loss in these children

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    was reported to occur only in the first 12 to 18 months of treatment. These drugs need further study in the pediatric population before they can be recommended for routine usage, particularly because of problems such as confusion and memory impairment. Metabolic acidosis has been described in children with convulsive disorders.

  • Atypical antipsychotic agents (AAPs) frequently need to be added to a mood stabilizer. These agents are useful in reducing aggression and the perceptual inaccuracies seen in these youth (see section IV). Clinical experience suggests that some AAPs may also have mood-stabilizing properties.

  • Psychostimulants should not be added until the mood disorder is treated and fully stabilized. This is important because many children with BD may also have ADHD.

  • Evidence suggests that antidepressants, such as SSRIs, improve the depressive episodes of BD, but, as in adults, SSRIs and TCAs may be associated with higher risks of mood destabilization. SSRI-treated children with BD may be at higher risk for induction of a manic switch and acceleration of an underlying BD illness than are teens who receive SSRIs. For treatment of BD depression, see Chapter 19.

  • Electroconvulsive therapy may be considered in situations of acute suicidality and life-threatening mania.

III. Conduct Disorder

CD behaviors violate either the basic rights of others or societal rules. In addition, they should not be solely a response to a negative family or social context. These youth must be distinguished from those with oppositional defiant disorder (ODD) who have a recurrent pattern of behavior towards authority figures that is negative, defiant, disobedient, and hostile and that persists for 6 months. In less severe forms of ODD, youth may demonstrate these behaviors only at home (Table 21.4).

Accounting for up to one-half of clinical referrals to child psychiatry treatment services for both boys and girls, CD is the most common diagnosis seen in youth psychiatric clinics. It is often a pervasive, complex, and disabling chronic disorder that acts as a gateway to antisocial personality disorder in adulthood. The term juvenile delinquent describes youth who have become involved with police and the courts, and it may represent some youth with the most severe CD symptoms. No single path to antisocial personality disorder exists. Many children with CD do not have preexisting ODD. A small subset of children with ADHD and ODD will develop CD, but less than 50% of these youth will go on to antisocial personality disorder in adulthood. Additionally, the co-occurrence of anxiety or mood disorders and substance abuse may complicate CD and may predispose these individuals to later antisocial personality disorder. Parents of these youth can have significant psychologic impairments (e.g., psychiatric disorders, marital strife) and social disadvantages that may significantly impact the development, persistence, and treatment of this disorder in their children.

Scant information about girls with CD is found. Because aggression is not a necessary criterion for CD (Table 21.4), the symptoms of CD in girls may be quite different from those of boys. Girls may be less overtly aggressive and more likely to violate rules or to engage in deceitfulness or theft. The fact that girls have a different presentation of CD symptoms may influence the prevalence figures for CD (under the age of 18 years, 2% to 9% of females and 6% to 16% of males meet criteria for CD). However, the risk of developing antisocial personality disorder for girls with CD appears to be equal to that of boys, and these girls are at risk for early pregnancy with antisocial partners and for developing sexually transmitted diseases and significant medical problems. When compared with boys with CD, girls also have higher rates of posttraumatic stress disorder (PTSD), depression, and suicidality.

The following two types of CD have been described: childhood onset and adolescent onset (Table 21.5). Although this distinction may have heuristic value, it may not predict the outcome of an individual youth.

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A. Diagnosis and Etiology

CD is a heterogeneous and complex disorder involving genetic, biologic, and environmental correlates. That as much as 50% of the variance for the development of CD may be genetic has been postulated. Some risk correlates in children that lead to CD include a difficult temperament; high novelty-seeking behaviors; chronic medical illness, especially that involving the central nervous system; co-occurring ADHD, especially with aggression, peer rejection, comorbid anxiety, depression, and substance abuse; and academic underachievement. Familial risk factors include parental antisocial personality disorder and substance abuse, exposure of children to parental discord, and inconsistent and harsh parental punishment. Low socioeconomic status and inner city residence are also associated with higher rates of CD. Physiologic correlates of youth with CD and aggressivity include underarousal demonstrated by a low resting heart rate and low hypothalamic pituitary adrenal axis activity (decreased morning cortisol level or a restricted low range or salivary cortisol). Studies showing these correlates have not always controlled for comorbid conditions, especially depression or PTSD.

The purpose of the evaluation (e.g., forensic or treatment) and the role of the evaluator must be clarified by the clinician. If the psychiatric evaluation will be made available to the juvenile justice system, the clinician should tell the youth and the family before the start of the evaluation.

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Although interviews of parents or other caretakers, teachers, or juvenile justice workers is essential for making a diagnosis of CD, the clinician should be aware that parents may minimize their children's problems. When the clinician's attitude conveys I hear you have a tough reputation, the youth may volunteer a wealth of data, especially about covert acts unknown to the caretakers. The mental status examination is not useful in diagnosing CD, but a thorough and developmentally sensitive mental status examination is essential for assessing co-occurring mood disorders, anxiety disorders, ADHD, substance abuse, or PTSD. Youth with depression co-occurring with CD may have less severity of depressive symptoms, fewer anxiety symptoms, less guilt, and more self-injurious behaviors than do youth with MDD alone. Clinicians should be alert to any suggestion of neglect, abuse, traumatic brain injury, and seizure disorder; misperceptions that approach paranoia; or symptoms suggestive of mania. The clinician may use the parent or teacher-rated delinquency subscales of the Child Behavior Checklist or the Oregon Adolescent Depression Project Conduct Disorder Screener. Rating scales that may be clinically useful for aggressivity include the Overt Aggression Scale, the Children's Aggression Scale Parent Version, and the Brown-Goodwin Assessment for Lifetime History of Aggression. Other scales should also be employed to evaluate comorbid conditions. Laboratory paradigms that assess cheating, stealing, and property destruction, such as the Temptation Provocation Tasks, have research utility only because they do not assess actual behaviors. Cognitive and educational assessments are essential to evaluate cognitive ability and learning disabilities, (e.g., reading disabilities in boys). Because youth with CD may be socially disadvantaged, undiagnosed medical conditions should be sought. A thorough neurologic evaluation should be completed. Substance abuse history and screening and a sexual history should be obtained. Parental psychopathology, marital discord, and parenting style should be evaluated.

B. Treatment

The ideal treatment plan is a multimodal one that addresses the educational, medical, psychosocial, and psychiatric needs of the youth and his or her family; however, because most evaluations are completed only when juvenile justice is threatened or involved, this ideal is rarely achieved.

• Psychoeducational approaches. Parents of youth with CD and those with children at risk for the development of CD should receive detailed information about the risk correlates and treatment of CD.

• Psychotherapy. Three treatments are well documented to be effective in youth (mostly documented in boys) and their families with ODD and CD.

  • Parent management training. Although many treatment variants exist, general characteristics of these therapies include enhancing the quality of the parent child relationship, establishing consistent rules, and fostering positive rewards and negotiation. Consequently, parental consistency is increased, harsh punishment is reduced, and parent youth communication is improved. Dropout rates of 40% to 60% are common; these are associated with parental psychopathology and the parental perception of the difficulty and relevance of the therapy. Pretreatment parental psychoeducation, cultural sensitivity, and an understanding of resistance are crucial to improve compliance.

  • Youth cognitive problem-solving skills training (for youth at least 10 years of age). By learning to assess and seek prosocial solutions to interpersonal problems, a child may correct negative attributions and may reduce impulsive antisocial choices.

  • Multisystemic therapy. By using a home-based intensive model with many therapy modalities within the family, school, and community (e.g., parent management training, youth cognitive problem-solving skills training, marital therapy, contingency management),

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    families can improve cohesion, consistency, and nurturance; and youth can improve their investment in education and in relationships with peers with prosocial behaviors. No evidence indicates that jail tours or boot camps will prevent or ameliorate CD symptoms without psychologic interventions.

• Pharmacotherapy. No specific pharmacologic treatment exists for CD. The basis for pharmacotherapy is the treatment of comorbid disorders that may be related to the cause of the disruptive behavior (e.g., affective disorders, ADHD [note: psychostimulants have been shown to reduce aggression], anxiety disorder, PTSD, psychotic disorders, seizure disorder, traumatic brain injury). When aggression is a major problem in a youth with CD and the behavior does not respond to the psychologic therapies listed above or if the use of medication to treat a comorbid disorder has not improved aggressivity, the use of medication to treat aggressivity is warranted. Affective aggressivity associated with reactive impulsivity and lack of planning may be more responsive to psychotropic intervention than are planful or proactive aggression or covert aggression, such as lying and stealing. Although psychotropics are commonly used to treat aggression in this population, just a few placebo-controlled studies support the use of lithium, valproate, and risperidone. (Note: Nondrug factors may also contribute to reductions in aggressive behaviors in hospitalized youth.)

  • Antipsychotic agents (see section IV). Although only risperidone has been shown to be effective in aggressivity in teens with CD, in practice all AAPs can be used with youth. In childhood-onset CD, youth may have paranoid thinking that is not well defined or significant enough to warrant a diagnosis of a thought disorder, but these youth may improve with AAPs. The clinician must collaborate with the family and the youth to decide if the benefit from the use of these agents outweighs the side effects that make them problematic (e.g., weight gain, prolactinemia) and to use the lowest amount of medication that results in a clinical effect (e.g., risperidone, 0.25 to 2 mg twice daily). Meticulous evaluation for extrapyramidal syndrome effects should be conducted when using risperidone or olanzapine because both, at some threshold dose, may shift to produce the side-effect profiles seen with CAPs, as well as an increased likelihood of the development of extrapyramidal syndrome and tardive dyskinesia.

  • Mood-stabilizing anticonvulsants and lithium.

    • Lithium (see section II.B.3.a).

    • Anticonvulsants (see section II.B.3.b,II.B.3.c,II.B.3.d). CBZ has not been shown to be effective in children with CD and aggression. With sodium valproate, the least amount that will result in clinical effectiveness should be used. Blood levels are useful in monitoring compliance and preventing toxicity.

    • Other agents. A variety of other agents has been shown to have efficacy in youth with aggression and developmental disabilities in open studies, including -adrenergic receptor antagonists, buspirone, ₂-adrenergic receptor agonists, and trazodone.

IV. Schizophrenia

Investigators in the early 20th century, such as Kraeplin and de Sanctis, described schizophrenia occurring in childhood and adolescence as identical to that of adulthood. In the last mid-century, the term was expanded to include all severe childhood disorders. The term was further confused with autism after Kanner first described that syndrome in 1943. It was only after the studies of Kolvin and Rutter in the late 1960s and early 1970s that autism and schizophrenia in youth were differentiated. Now, the DSM-IV diagnostic criteria for schizophrenia in childhood and adolescence are identical to those of adult schizophrenia, except, in childhood, the definition of dysfunction is expanded to include

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The following two forms of schizophrenia in youth have been distinguished: childhood onset schizophrenia (COS), with onset occurring in youth less than 12 years of age, and early onset schizophrenia (EOS), with onset occurring in youth less than 18 years of age. Outcome studies of COS and EOS generally show stability of this diagnosis over time and a course that is indistinguishable from adult onset schizophrenia. Poor long-term outcomes for these youth have been demonstrated. (Note: Many of these are older studies, and youth had not received atypical antipsychotic agents and intensive treatment.) Unlike adults with schizophrenia, youth with schizophrenia show decreased intellectual functioning that continues after the onset of psychotic symptoms; this is related to hippocampal volume decreases that develop in the early stages of psychosis and that result in reduced information acquisition abilities. Schizophrenia in youth presents unique problems of diagnosis and treatment; this section focuses on these aspects only.

A. Diagnosis and Etiology

• Childhood onset schizophrenia. Hallucinations in latency-age children must be distinguished from normal childhood experiences of imaginary friends, belief in monsters or angels, hypnogogic or hypnopompic illusions, and other developmentally based phenomena. True hallucinations (usually auditory) are believed by the child to be outside his head and are either commenting, conversing, or commanding.

  Clinicians are often misled by the presence of childhood hallucinations because they may not be symptomatic of schizophrenia but rather they may be related to major depression, PTSD, psychosocial deprivation, or cultural beliefs. Asking parents whether the family believes in spirits or ghosts is important. The diagnosis of COS is sometimes made in children with hallucinations and speech and language deficits or PDDs who superficially may appear to meet the schizophrenic criteria of disorganized speech. Because of these factors and its extreme rarity (estimated to be 1 in 10,000), COS may be overdiagnosed by inexperienced clinicians.

  Patients with adult onset schizophrenia often have histories of abnormal language and motor development, low intelligence, or poor social development, but individuals who develop COS have even higher rates of these neurodevelopmental impairments. They may also have transient symptoms of PDD that precede the insidious development of frank psychotic symptoms (e.g., hand flapping, echolalia). Studies of offspring of schizophrenic parents support the presence of prodromal neurobehavioral deficits, especially in boys. Barbara Fish termed these traits pandysmaturation ; they may be markers of schizophrenic vulnerability. Most children with developmental delays will not develop COS. In most studies of youth with COS, boys predominate. Auditory hallucinations are as common as delusions, and both symptoms have a less complex content than those of adults. A family history of schizophrenia (usually with an early onset), avoidant personality disorder, or schizotypal disorder and physiologic evidence suggestive of increased genetic risk from both parents may be present.

  In the NIMH study of COS, a subgroup of children who had been referred as schizophrenic by community psychiatrists were identified as having multidimensionally impaired syndrome and, later, as psychotic disorder, NOS (Table 21.6).

  Children with psychotic disorder, NOS, share the neurodevelopmental, neuropsychologic, and neuroimaging abnormalities of youth with COS. Both groups of children have a higher incidence of sex chromosome abnormalities and chromosome 22q11 deletions (velocardiofacial syndrome).

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  That some of the children with psychotic disorder, NOS, fall within the category of schizophrenia spectrum disorder has been hypothesized, but longer term studies are necessary to establish this connection.

  TABLE 21.6. CRITERIA FOR DIAGNOSIS OF MULTIDIMENSIONALLY IMPAIRED SYNDROME (MDIS) or PSYCHOTIC DISORDER, NOT OTHERWISE SPECIFIED (PD-NOS)

  Early onset of severe disturbance in boys Hallucinatory experiences that do not meet criteria for schizophrenia (e.g., brief hallucinations or distorted perceptions) Affective storms Poor social skills Excessive age-inappropriate fantasy or magical thinking (e.g., an 11-year-old who checks under sewer plates [covers] for Ninja Turtles) Borderline intelligence (by IQ testing) Comorbid ADHD Abbreviations: ADHD, attention deficit hyperactivity disorder; IQ, intelligence quotient. From Kumra S. Wiggs E, Bedwell J, et al. Neuropsychological deficits in pediatric patients with childhood-onset schizophrenia and psychotic disorder not otherwise specified. Schizophrenia Res 2000;42:135 144, with permission.

• Early onset schizophrenia. The clinical presentation of EOS is similar to that of adult onset schizophrenia. Symptoms may start at puberty, but they are more common after 15 years of age. As with adults, a first episode of psychosis in youth requires a thorough and complete psychiatric history from parents and other important adults, a thorough medical and neurologic assessment (see Chapter 20), and a meticulous mental status examination (see Chapter 2). Interviewing children for psychotic symptoms can be extremely challenging; children may need to be interviewed several times before the clinician is able to distinguish true hallucinations. Clinicians can begin this inquiry with the following questions:

  • Do you believe in spirits or ghosts or monsters?

  • Have you ever had any imaginary friends?

  • At night, most children see clothes or toys and think that they are something else. Has that happened to you?

  • Do you have any trouble with your ears or your eyes?

  • Have you seen or heard things and wondered if they were real?

  The developmental history should be reviewed, both to assess premorbid functioning and to document the existence of neurodevelopmental disabilities and symptoms suggestive of PDDs (see section VI). Review of collateral information (e.g., previous school records, intelligence quotient testing, speech and language evaluations) can corroborate parental information. Youth with dysmorphologic features or mental retardation should be reviewed for chromosomal syndromes (e.g., fragile X, velocardiofacial syndrome). Because psychotic manic symptoms may be indistinguishable from those of schizophrenia and a history of affective disorders can be present in some families of youth with schizophrenia, long-term follow-up is essential to clarify the diagnosis. The differential diagnosis of youth with suspected schizophrenia should include BD, drug intoxications (drug usage occurs in about 50% of teens with schizophrenia, and it may be associated with first psychotic episode), MDD with psychosis, complex partial seizures, side effects of other medications, and other organic causes of hallucinations and personality changes (e.g., delirium, central nervous system lesions, neurodegenerative disorders).

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  When appropriate or in preparation for a medication intervention, laboratory, neurologic, and neuroimaging studies should be conducted to rule out other diagnoses. Neuropsychologic testing may be used to assess cognitive deficits and to improve treatment planning. Clinicians should be cognizant that anxiety symptoms, social withdrawal, and antisocial behavior may accompany psychotic symptoms.

  Although the clinician is under pressure from managed care for rapid treatment, when possible, he or she should observe a youth over time before medication is initiated. The clinician should have an open mind about rediagnosis and drug-free reevaluations, because even the most rigorous of the diagnostic processes of the NIMH resulted in an almost 25% rediagnosis of youth with schizophrenia during a 4-week drug-free interval.

B. Treatment

• Psychoeducational approaches. Informing the patient and family about the nature of schizophrenia and the value of medication compliance is vital. Although computer-based information programs are untested in teens, it may be particularly suited to this population. Substance-abuse educational interventions should be provided. Appropriate psychiatric, educational, and vocational placements should be sought with an eye toward maximizing future independent living.

• Psychotherapy. Although few treatment studies of youth with schizophrenia have been conducted, clinicians can borrow treatment strategies from adults with schizophrenia, including family therapy, social skills training, and CBT.

• Pharmacotherapy. A few studies of conventional antipsychotic agents (CAPs) and a small group of short-term studies of AAPs, mostly open trials and case reports, show efficacy in this condition. Most pediatric clinicians use only atypical antipsychotics. Schizophrenia can be a phasic illness, and the pharmacotherapy should be appropriate to the stage. When using antipsychotic medication, the therapeutic effect must be weighed against the potential side effects in each phase of the illness. With short hospitalizations and pressure from managed care, clinicians may give larger than necessary dosing of antipsychotic agents through the acute phase, and outpatient clinicians may be reluctant to reduce dosing during recuperative or residual phases.

  Clinicians must have a flexible stance toward the long-term usage of antipsychotic agents in youth. The development of a strong alliance with youth and their families is crucial because decisions about medications involve negotiations over years. Many youth will discontinue treatment without warning, especially when clinicians are insensitive about issues of their autonomy. A planned trial of medication tapering with mutual observation for early warning signs of symptom return may be suggested as a preemptive strategy.

  Youth with COS and EOS may have an increased or unique side-effect burden compared with that of adults (see individual medications below). Using the smallest effective doses and observing carefully for side effects is crucial. Latency children have both therapeutic effects and side effects at lower antipsychotic plasma levels than do teens or adults. Cognitive and/or behavioral syndromes in youth on antipsychotic agents are common. Typical symptoms include cognitive blunting (apart from that induced by the disease itself), behavioral problems, avolitional difficulties, dysphoria, separation anxiety, and school refusal. Youth may also be at special risk for parkinsonian bradykinesia, acute dystonias, withdrawal and treatment-emergent dyskinesias, cognitive or behavioral symptoms, and lethality from neuroleptic malignant syndrome (see section IV.B.3.a.(7)). Because of the reduced incidence of some of these side effects with AAPs, more recently trained clinicians who have not worked with CAPs may overlook the development of important side effects in youth. That some of these symptoms may have a diurnal variation must

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  also be recalled, and clinicians should observe patients at different times of day.

  • Extrapyramidal syndrome in youth

    • Acute dystonia. Boys from the ages of 13 to 19 years with previous cocaine use and those with prior episodes of acute dystonia are at special risk. High potency CAPs (e.g., haloperidol) are more likely to precipitate acute dystonia, although this can occur with all antipsychotic agents, including but rarely clozapine. To reduce the incidence of acute dystonia, low initial dosing and slow upward titration of the antipsychotic agent are helpful, as is prophylaxis with a low-dose anticholinergic medication (e.g., benztropine, 0.5 to 1 mg three times a day, for 14 days in high-risk groups). When acute dystonia develops and the antipsychotic agent is discontinued, anticholinergic medication should continue for 4 to 5 days because of the extended duration of action of most antipsychotic agents and the possibility of renewed acute dystonia.

    • Parkinsonian symptoms. These may occur in about one-third of children receiving CAPs. Some prepubertal males may have atypical symptoms, and parkinsonism may be more common in older children with affective illness. Because these symptoms also may be associated with higher plasma concentrations of some AAPs, the clinician should be particularly vigilant in youth on combinations of other drugs and AAPs associated with cytochrome P-450 (CYP) based drug interactions (e.g., fluoxetine and risperidone, ciprofloxacin and olanzapine).

    • Akathisia. Akathisia may be less common in youth receiving antipsychotic agents compared with adults.

    • Withdrawal dyskinesias. These appear as the tardive dyskinesia-like symptoms associated with lowering the dose or stopping an antipsychotic agent, and they may be present in 20% to 30% of children on CAPs. The symptoms are usually transient, but this should be monitored carefully.

    • Treatment-emergent dyskinesias. These dyskinesias may occur in 12% to 15% of children on CAPs.

    • Tardive dyskinesia. The true incidence of tardive dyskinesia in children is not known, but two studies of youth receiving CAPs revealed the presence of tardive dyskinesia in 3 of 17 children and in 2 of 40 teens (with 5 of 40 having some symptoms).

    • Neuroleptic malignant syndrome. In youth, neuroleptic malignant syndrome may not be associated with a higher incidence of affective disorders, but it may have a higher incidence of fatal outcomes.

  • Atypical antipsychotic agents in youth. A careful physical examination and medical history should be completed before starting youth on these agents. Particular attention should be directed to a history of abnormalities in liver and renal function. See Tables 21.7, 21.8 and 21.9 for issues related to specific AAPs.

    Data exist for psychosis in children treated with clozapine. Because the FDA encourages clinicians to reserve clozapine for treatment-resistant schizophrenia, no dosing recommendations are provided here. Despite some good clinical responses, youth with treatment-resistant schizophrenia may not tolerate this medication because of seizures, neutropenia, sedation, drooling, tachycardia, transient increases in liver function tests, weight gain, significant risk for hyperglycemia, and akathisia. Other side effects may include hypotension, development of arrhythmias, and fever. As yet, no published trials covering the use of ziprasidone in youth with psychoses are available.

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V. Anxiety Disorders

Throughout the lifespan, some amount of anxiety is normative; it provides the impetus for change. In childhood, anxiety may emerge at developmental transitions, such as stranger anxiety at 8 to 10 months of age; separation anxieties during the toddler years; various fears of the dark, bodily injury or integrity, or death during latency; and social fears during adolescence. Childhood fears are extremely common. For example, nighttime fears are present in 75% of children from the ages of 4 to 12 years. Parents may be unaware of or may minimize childhood anxieties. Clinicians must distinguish developmentally adaptive or transient fears from those that are excessive and that interfere with development.

Diagnosis and treatment of children with anxiety disorders can be challenging. Assessment of children can be difficult because children under the ages of 8 to 9 years may lack the cognitive and language skills to describe their internal states to parents and clinicians. Rarely does a child meet criteria for a single DSM-IV anxiety diagnosis; 75% of these children have coexistent psychiatric conditions, usually depression. Gender, family, and culture can shape the clinical presentation. Anxiety disorders in youth are both a source of distress and impairment for children, and, untreated, they may be the gateway to lifelong symptoms of anxiety and depression. Although separation anxiety disorder and

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A. General Issues of Diagnosis of Anxiety in Youth

Rarely do parents bring children for the evaluation of anxiety but rather for anxiety avoidant or oppositional behaviors (e.g., children with separation anxiety disorder may not want to go to school, children with social phobias will not speak to peers in school). Only infrequently do children volunteer that they have subjective anxiety or fearfulness to parents or clinicians because they may not have attained the cognitive development to recognize their feelings as excessive or unusual. Children may only be aware of physical symptoms (e.g., headache, butterflies in the stomach ). Clinicians must interview parents and other adults to appreciate the degree of impairment in the child that is caused by the symptoms and must question the child to

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• If a T. Rex came in this room, how would you feel?

• Some kids feel [whatever their word] in their body or their head.

• How would you know when you are [their word]?

• Does your heart go bunka-bunka or do you have trouble breathing or something else?

• When a symptom is elicited, ask When do you feel that way? When you are in bed at night?

• When you speak in front of class?

• What do you think about when you are lying in your bed at night?

• Are you a worrier?

Using self-report scales that children can complete or that parents or clinicians can read to them, such as the Multidimensional Anxiety Scale for Children and the Screen for Child Anxiety-Related Emotional Disorders-Revised, can be helpful. When parents have asked the questions of the child, rechecking of any endorsed symptoms by the clinician is crucial because children may not have understood the question. Clinician-driven rating scales, such as the Pediatric Anxiety Rating Scale, can provide a comprehensive diagnostic mini-interview.

B. General Issues of Treatment of Anxiety Disorders in Youth

Psychoeducation and CBT remain cornerstones of treatment in these conditions. Until recently, little research support existed for the use of pharmacotherapy in these conditions, although clinicians frequently used SSRIs or TCAs. The recent multicenter study of fluvoxamine in the treatment of social phobia, separation anxiety disorder, and GAD in children and teens and a double-blind study of sertraline in GAD have provided support for the pharmacotherapy of these conditions in youth

C. Separation Anxiety Disorder

School phobia is a general term that describes the clinical situation in which a youth avoids school. Children do not want to attend school for many reasons. These include the wish to avoid particular aspects of school or psychiatric symptoms that make attending difficult for them. Separation anxiety disorder is the most common psychiatric disorder causing school avoidance in prepubertal children. The cardinal feature of separation anxiety disorder is excessive anxiety engendered by separation from major attachment figures or the home environment that occurs for at least 4 weeks. Traits of separation anxiety disorder may continue to adulthood, but they are generally overshadowed by other psychiatric disorders, especially GAD, MDD, and PD. Indeed, separation anxiety disorder is a marker for the possible early onset of PD, and parental histories of PD or depression may be present.

• Treatment. Separation anxiety disorder can be a psychiatric emergency in childhood, and it should be treated vigorously.

  • Psychoeducational approaches. Parents need to have a clear understanding of the manifestations and treatment of this disorder. Clinicians must address parental collusion with children with separation anxiety disorder; this may include an inability to set clear expectations for school attendance.

  • Psychotherapy. Cognitive techniques can help a child learn to tolerate anxiety better. Behavioral plans or clear rules for school absences, scheduled phone calls, or beeper messages to parents each day from school are useful. Parents with psychiatric disorders, including anxiety disorders, should be offered treatment.

  • Pharmacotherapy. Although imipramine was used for many years as the primary medication treatment for separation anxiety disorder, SSRIs are now the first-line treatment (see section I.B.3).

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D. Shyness and Social Phobia (see Chapter 14)

Shyness is a trait with strong, but not immutable, continuity from childhood to adulthood. Behavioral inhibition is a research construct involving shyness; withdrawal avoidance; and fear of unfamiliar situations, objects, and people that can be shown to be present in a subgroup of children from the earliest months of infancy. This trait has only moderate stability over time; good parenting can change the outcome. Long-term follow-up reveals that some children with stable behavioral inhibition are at risk to develop social phobia (social anxiety disorder) in their teens. As in adults, the core symptoms for youth are blushing, trembling, palpitations, and sweating. For children, butterflies in the stomach may be experienced when speaking, writing, or eating at school or parties. The associated concern or fear of being scrutinized or evaluated by others may be lacking in young children.

The typical onset of symptoms of social phobia occurs in the mid-teens, with a higher prevalence in females. Of the two types of social phobia, the generalized form has an earlier onset than the specific form. The latter is most commonly a particular performance anxiety or fear of speaking. For youth with social phobia to seek treatment is highly uncommon; for them to resist treatment is quite common.

• Generalized type social phobia. Children with early onset generalized social phobia (less than 12 years of age) are apt to develop depression and substance abuse in their teen years, and they less often report fearful cognitions. Comorbidity is usual 10% have GAD, 10% have ADHD, 10% have specific phobias (injections, high places), and 8% have selective mutism. These children are lonely and generally fearful, with poor social skills. They are dysphoric but not depressed. As they grow older, they may develop depression and suicidality. Most youth with later onset generalized social phobia also have comorbid conditions, including other anxiety disorders, depression, and substance abuse. Both groups may have behavioral problems that arise out of their anticipation of their poor performance in social situations, and they may develop school difficulties and chronic symptoms of social phobia. Two groups that have increased rates of social phobia are first-degree relatives of children with autism and girls with fragile X syndrome.

• Specific type social phobia. This is more commonly associated with a traumatic event, and it usually develops in the late teens. Clinicians must distinguish these children from those with selective mutism. The latter fail to speak in certain social situations before the age of 5 years, and the syndrome usually comes to clinical attention when they fail to speak in school. It is more common in girls and in children with developmental delays, other anxiety disorders, encopresis, and enuresis. Whether this rare syndrome should be considered a subtype of social phobia or a separate anxiety disorder is not clear.

• Treatment. In addition to psychoeducation and CBT, youth with social phobia benefit from individual or group therapies that promote improved social skills and assertiveness. Particular value may be found in providing interventions in a school-based setting where graded exposures can be supplied. Similar strategies may be useful for children with selective mutism when family, teachers, and treaters have a firm expectation of speech and offer positive rewards for speech as well. Concomitant treatment with SSRIs is useful for youth who do not respond to these interventions and for youth with coexisting depression because they have a more malignant outcome than do those without depression.

E. Panic Disorder (see Chapter 14)

Although panic attacks are uncommon in school-aged children, they may be present in 15% of teens. However, less than 1% of teens meet criteria for PD, and the onset peaks in the mid-teen years. Prevalence of early onset PD may be higher in the children of parents with early onset PD, regardless of the presence of associated depression. Clinicians should be aware of the following

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• Psychoeducational approaches. Families and youth must understand how mislabeling the usual physiologic sensations of fear, panic, and the fear of fear can lead to these anxiety symptoms.

• Psychotherapy. CBT is the treatment of choice for all phases of PD anticipatory anxiety, panic attacks, and avoidance. Learning self-monitoring and cognitive restructuring techniques can be crucial in a successful treatment.

• Pharmacotherapy. Treatment of youth onset PD can be initiated with SSRIs (see section I.B.3) and ancillary high-potency benzodiazapines. Clinicians should be cautious about increasing dosages rapidly (as a way to avoid worsening of PD) with SSRIs and with benzodiazepines, as is the case with adults. Clonazepam with an initial dose of 0.25 mg twice a day can be useful in initiating treatment for PD while SSRIs are started and gradually titrated upward. Clinicians should be cautious with SSRIs that may increase the concentrations of benzodiazepines due to CYP interactions (e.g., fluvoxamine may increase alprazolam levels by up to 100%). After symptom relief is obtained, benzodiazepines may be tapered, if possible. TCAs are effective, but they are a second-line treatment because of their increased side-effect burden (see Chapter 18).

F. Specific Phobias

Specific phobias are more common in school-aged children (about 17%) than in teens (about 3%). Animal and natural environment phobias are the most common subtypes. More girls than boys receive the diagnosis of a specific phobia. Children rarely realize that their anxiety is excessive because they lack the cognitive abilities to assess their response compared with others. One-third of adolescents with specific phobias also have depressive and somatoform disorders. Although these teens may be significantly impaired, they rarely come to clinical attention. In vivo exposure is the best-studied intervention.

G. Generalized Anxiety Disorder (see Chapter 14)

Limited research data are available about GAD in youth. GAD is present in 3% to 4% of children and in 3.6% to 7.3% of teens. GAD symptoms in youth are believed to be similar to those in adults, but they may not be perceived as excessive by children. The focus of anxieties is success in school, sports, social, and child-related activities. Anxiety symptoms in children may result in an increased need for reassurance from parents. Teens more frequently resort to brooding. Once the diagnosis is made, almost one-half of youth with GAD continue to have the diagnosis more than 2 years later. As in adults, comorbid anxiety disorders, especially social anxiety disorder or PD, and depression are frequently present, and these predict more serious impairment.

• Diagnosis. Medical conditions (e.g., hyperthyroidism, pheochromocytoma) should be excluded by physical examination and appropriate laboratory testing. A higher incidence of GAD and MDD has been found in youth with insulin-dependent diabetes mellitus.

• Treatment. Education about the illness and parental support are necessary. CBT, including the recognition of anxiety and attendant cognitions and the development of coping treatment strategies (e.g., relaxation techniques), can be especially helpful. Fluvoxamine and sertraline have the best research support for efficacy in youth, and treatment with buspirone is supported by open studies. Buspirone may be used in three times a day dosing, up to 45 mg per day for children and 60 mg per day for teens. A single study supports the exclusion

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  of youth with BD from buspirone treatment because of an increase in agitation and aggressivity. TCAs and benzodiazepines remain options for treatment-resistant cases. Although paroxetine and venlafaxine are FDA approved for GAD in adults, insufficient experience with these exists to recommend their use in youth at this time.

H. Obsessive-Compulsive Disorder (see Chapter 6)

During preschool years, children may insist on sameness or symmetry, and latency-age children may develop rituals (e.g., avoiding cracks in sidewalks) or collecting behaviors (e.g., sorting baseball cards or spending hours dressing dolls). These normal developmental activities must be distinguished from the obsessions and compulsions characteristic of OCD (e.g., fear of dirt or contamination, fear of the death of a loved one or a terrible event, and washing or checking behaviors).

• Diagnosis. About half of the children with OCD will continue to be affected in adulthood, but some characteristics of childhood onset OCD distinguish this condition from OCD in adults. Although OCD has been documented in very young children, it most typically develops at 12 to 14 years of age. For clinicians to discern prior microepisodes of OCD symptoms or a waxing and waning course that is exacerbated by stressful events is often possible. Clinicians may use psychologic instruments, such as the Children's Leyton Inventory, the medication-sensitive Children's Yale-Brown Obsessive-Compulsive Scale, or the NIMH Obsessive-Compulsive Scale, to assist in diagnosing OCD in children. Most often, these children fit the poor insight type of OCD, according to DSM-IV criteria, because they may not recognize their activity or thought as senseless and they may not experience or link a fearful thought with a compulsion.

  The attributions of some children with OCD may seem bizarre to adults (e.g., contamination from monster drool ), and they may incorrectly raise questions as to psychotic processes in less experienced clinicians. Unlike other anxiety disorders in childhood, boys can have a more severe or an earlier onset of symptoms of OCD, and they outnumber girls by 2 to 3 to 1 in prevalence of the disorder. Most children with OCD have other comorbid diagnoses, including depressive disorders, other anxiety disorders, motor tics, and learning disabilities. The child may hide his or her symptoms from the family for several months. Parents may inadvertently collude with their children by tacitly encouraging the carrying out of rituals in an attempt to avoid family conflict, or their own symptoms of anxiety may reinforce the child's attitudes toward his or her symptoms.

  Because an association may exist between group A -hemolytic streptococcal infections and the acute development of OCD, clinicians should document this association when it is present (this is termed PANDAS¹, see Chapter 7). Increases in the levels of antistreptococcal (ASO) titers and the nonhuman lymphocyte antigen DR-positive cell marker (D8/17) may be nonspecific markers of susceptibility to PANDAS. If documented by a positive throat culture, the vigorous treatment of future streptococcal pharyngitis should occur, but immunomodulatory treatments with plasmapheresis or intravenous immunoglobulin remain investigatory.

• Treatment. Therapy for this disorder in childhood may be challenging.

  • Psychoeducational approaches. Using these approaches with youth and family members is essential because this condition may be lifelong. Recognition and early identification of subsequent episodes is one goal, as is the disengagement of parental collusions with the child's rituals.

  • Psychotherapy. CBT techniques adapted for children, especially exposure and response prevention, habit reversal, and behavioral

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    rewards, are extremely useful. The addition of a CBT family component may be helpful.

  • Pharmacotherapy. As in adults, SSRIs are the first-line medication for treatment. Although CMI is one of a few pharmacologic treatments with sound research support in children, most clinicians reserve it for treatment-resistant cases because of its side-effect burden (e.g., decreased seizure threshold, QTc interval prolongation on electrocardiogram). Clinicians should initiate treatment with either drug class at a low dosage because rapid titration can worsen the OCD symptoms. Clinicians should wait a full 10 to 12 weeks before trying a second SSRI because obsessive-compulsive symptoms diminish slowly.

    Resistant cases can be treated with the addition of CMI at 25 mg per day to fluvoxamine because this combination preserves the higher CMI to desmethyl-CMI ratio best. Trough blood levels of CMI and desmethyl-CMI should be obtained after 3 weeks when the metabolite reaches steady state concentrations. Electrocardiograms should be obtained before and after treatment with CMI. The clinician can also try adding an AAP to any SSRI as long as he or she is mindful of possible drug interactions between these classes. If drug treatment is discontinued, this should be as a slow taper to prevent triggering a relapse. Regretfully, although a significant proportion of children's OCD symptoms may respond to treatment, these children may still meet the criteria for this disorder, even after pharmacotherapy.

I. Posttraumatic Stress Disorder

Youth are the victims of sexual and physical abuse, motor vehicle accidents, natural disasters, medical procedures, gang warfare, or other traumatic events. They may witness parental discord, and they see an estimated 10% of parental murders, rapes, and suicides. Of this potential pool of victims and witnesses, only about one-third of youth will develop symptoms that meet the full criteria of acute stress disorder or PTSD (see Chapters 14 and 27). Although the following are not absolutely related to the type, severity, or frequency of the traumatic event, possible risk factors for developing PTSD after a single event include the severity of the trauma and the distress of parents or caretakers. In community samples, 3% to 6% of school children have PTSD, whereas 12% to 36% of urban teens are affected.

• Diagnosis. The DSM-IV criteria for PTSD best fit adults who have experienced a single traumatic event. Teens are more likely to meet these criteria than are younger children. Table 21.10 highlights the differences of children's symptoms when compared with DSM-IV criteria. Many children who are either very young or who are victims of chronic physical or sexual abuse will meet only some of the criteria for PTSD. Especially, they may fail to meet the avoidance criteria.

  Many clinicians fail to ask youth about symptoms of PTSD because of a belief that children are too young to understand what they have seen or because of a wish to protect them. Psychiatric assessment of youth should always include questions about What bad things have happened to you? or Have you ever been hurt or ever seen anyone get hurt? A sensitive face to face interview must be conducted to assess PTSD symptoms. Details or clarifications may be elicited after the children have been allowed to tell their whole story. When particular PTSD symptoms have not been volunteered, the clinician should inquire about them. Estimates of both frequency and intensity should be elicited.

  Because children often recall traumatic events just before they go to sleep, the clinician can ask children what they think about at night. The interview should include questions about the child's ideas of how he or she could have stopped the event and any ideas about the future. Because childhood PTSD is highly comorbid, questions about new fears, grief, and depression should be included. Watching the child's play may be crucial to recognize posttraumatic play (i.e., joyless and relentless

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  repetition of the trauma with little disguise, such as when a child who witnessed his father drop his baby brother from a window repeatedly pretends during play that small figures are being dropped from heights and rescued by Superman). Clinicians should ask teens about coexistent depression, dissociative features, self-abuse, and substance abuse. If adults have also been involved in the trauma, they should also be interviewed if this is appropriate. The following inventories can be useful: the Children's PTSD Inventory delineates acute and chronic PTSD, and the Children's Impact of Traumatic Events Scale, revised, may be especially useful for sexually abused children. Children who fail to meet PTSD criteria but who are significantly impaired should nevertheless be considered for treatment.

• Treatment of single-event traumas

  • Psychoeducational approaches. Providing parents, guardians, teachers, and youth with an understanding of the nature and treatment of PTSD is essential, particularly with regard to educating caretakers to recognize and manage their children's everyday PTSD symptoms.

  • Psychotherapy. CBT interventions are the cornerstone of treatment. Identifying specific reminders of the trauma is crucial, and these are coupled with teaching techniques that reduce anxiety and promote a sense of mastery. Techniques of hierarchical imaginal exposure to reduce anxiety and exploration of cognitive attributions of the cause of the trauma and of how the future will be changed by the trauma can be helpful.

  • Pharmacotherapy. A few pharmacologic studies support the use of ₂-adrenergic receptor agonists (e.g., 0.05 to 0.3 mg per day of clonidine or 1 to 3 mg of guanfacine) or -adrenergic receptor antagonists (e.g., propanolol, 2 mg per kg per day) to help children's symptoms of hyperarousal, agitation, or sleep disturbance. Other psychotropic agents (e.g., trazodone, TCAs, mirtazapine) may be used as hypnotics. Because SSRIs or nefazodone have been shown to be effective in adults with PTSD, the clinician may borrow these findings as evidence to justify the use of these drugs in children. Although para-hallucinatory experiences may occur in youth with PTSD, atypical antipsychotics should be reserved for those with coexistent psychosis or serious aggression or self-injurious behaviors. Comorbid conditions should be diagnosed and appropriately treated.

• Treatment of multiple-event PTSD is more complex. Children may have long periods (e.g., months to years) of numbing symptoms that alternate with periods of reexperiencing symptoms. Children often have increased PTSD symptoms at times of the year when they were significantly abused, when they disclose their abuse, during legal processes, or in response to subtle cues (e.g., seeing a man who looks like their abuser, seeing a kitchen floor similar to that where parents fought). Pulsed therapies that either close down symptoms or open them up need to be used judiciously over the long-term course of this condition. Pharmacotherapy needs to be targeted to specific symptoms, and it should be withdrawn when symptoms relent.

VI. Pervasive Developmental Disorders

PDDs develop in early childhood; they are characterized by significant deviations in social interactive, language, and communicative skills. Additionally, children with these syndromes may have restrictions in interests or activities, and they may demonstrate repetitive behaviors. The use of the term pervasive is controversial because many children with one of these disorders have areas of normal functioning or areas of highly developed islets of abilities. However, the term is used because it does differentiate PDDs from one of the specific developmental disorders (e.g., expressive/receptive language disorder, reading disorder). The five PDD subtypes are autistic disorder (AD), PDD-NOS, Asperger disorder, Rett

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A. Autistic Disorder

AD has attracted much scientific investigation since its first naming in the mid-20th century. Over the past 50 years, much has been learned about its natural history. The medical community is better at diagnosing it, and it also has some evolving ideas about its cause(s), and some modest headway is being made in its treatment. Prevention remains a mystery.

Before 1988, the prevalence of AD was 4 to 5 cases per 10,000, but recent surveys have increased that number severalfold. When children with the presence of some symptoms or atypical presentation are included (i.e., PDD-NOS), the figure rises to 26 to 60 cases per 10,000. Although this term can be interpreted in several ways (see Cohen and Volkmar in Additional Reading), PDD-NOS is best understood as a lesser form of AD a condition in which a definite diagnosis of AD cannot be made because not all the sign and symptom criteria are met. Children with PDD-NOS may be less impaired than those with AD. The diagnostic process and treatment options are identical, however.

In AD, boys are more commonly affected than girls by a ratio of almost 5 to 1, but affected girls may be more seriously impaired than boys. Mental retardation is present in most individuals (75% to 80%) who receive an AD diagnosis. AD occurs with the same frequency in families of all socioeconomic levels, and a family that has one autistic child carries a small increased risk (4% to 5%) of having a second child with AD.

• Diagnosis and etiology. The etiology of AD is likely heterogeneous, but little question remains that AD is genetic. Studies of twins demonstrate concordance rates of more than 50% in identical twins and a less than 3% concordance rate in nonidentical twins. Although the rate of mental retardation is not higher among nonautistic siblings of children with autism, both parents and siblings of children with AD are more likely to have social and cognitive deficits (e.g., awkward expressions and odd verbal interactions) than are the family members of nonautistic children. About 10% of children with AD also have tuberous sclerosis, neurofibromatosis, Angelman syndrome, intrauterine rubella infection, fragile X syndrome, M bius syndrome, and fetal valproate or thalidomide syndrome. Visual and hearing impairments occur at a higher rate in these children than they do in the general population. Retinopathy of prematurity is overrepresented in children with AD. Currently, evidence exists of an association between AD and chromosomes 7q, 13q, and 15q and perhaps with the serotonin transporter gene. An association is also found between unfavorable events during pregnancy and delivery in children with AD, but no evidence indicates that any particular difficulty during a mother's pregnancy or in the perinatal period leads to the onset of AD. Furthermore, none of the currently used childhood immunizations has been found to cause the disorder.

  Neuroimaging technology holds great promise for delineating the anatomic and metabolic abnormalities present in AD. Although studies of the brains of autistic individuals are relatively few in number, these do show evidence of abnormalities in limbic or cerebellar areas. More than 10% of individuals with AD have macrocephaly, especially in the occipital and parietal areas. Numerous neurochemical and neuroendocrine studies have been inconclusive, except for the discovery of hyperserotoninemia in as many as 30% of individuals with AD.

  The diagnosis of AD should be considered when significant deviations in a child's development are seen in the following areas:

  • Social relatedness: demonstrates little or no interest in either caregivers or peers; avoids eye contact with them; does not seek or give emotional or physical affection.

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  • Communication and play: demonstrates delayed or absent speech or nonverbal communications to express needs and wants; may have extremely idiosyncratic, repetitive, stereotypic speech; fails to respond to the communication of others, both verbal and nonverbal; does not use imaginative or make-believe play or engage in play with others or even with stuffed animals.

  • Restricted interests and activities: engages in repetitive stereotyped behaviors (e.g., twirling a small piece of string in front of his or her face, spinning, toe walking) or becomes extremely upset with any change in routine.

    Often the child with symptoms of AD who is under 3 years of age avoids eye contact and does not point to objects (e.g., toys, pets). Pretend play and communicative speech are not present. These children may not develop ritualistic, repetitive, stereotypic, and rigid behaviors until in their later preschool years. In the past, these children were often not diagnosed with AD until their school years. Because physicians, other professionals, and parents waited for more normal development to occur (i.e., he will grow out of it ), opportunities were missed to provide early intervention services that could possibly have changed the long-term outcome.

    As always, the process of assessment begins with the clinical history, the interview with the parents and child, and a careful observation of behaviors among the child, parent, and physician. Characteristically, these children will lack functional and imaginative play and will favor spinning or twisting toys. The medical history must consider the genetic disorders already noted, and the other possible disorders of the PDDs need to be systematically excluded. About 30% of children with AD develop a seizure disorder (usually peaks in early childhood and at puberty), compounding their disability. The Childhood Autism Rating Scale and, in 18-month-olds, the Checklist for Autism in Toddlers may be used as screening tools. The Autistic Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule-Generic are the most reliable and validated diagnostic instruments for the diagnosis of AD and PDD-NOS, although they do not differentiate specific PDDs particularly well.

• Treatment. The approach to children with autism must concentrate on the interrelated goals of improving communication, cognition, and social development.

  • Psychoeducational approaches. Every few months, reports are seen in the media of cures of AD with the use of some medication, hormone (e.g., secretin), special diet, megavitamin, allergy treatment, or some other new technique (e.g., facilitated communication). To date, none of those touted treatments or approaches has been found to make any sustained difference in the behaviors of these children. The clinician must play an active role in educating parents about the need for evidence that something new works and must help parents not to fall prey to false hope engendered by the publicity generated by the many charlatans who delight in the headlines of a cure for AD. Clinicians can realistically tell parents that their child's social interactions may improve over time with appropriate services. Clinicians need to help families select the validated interventions that best fit their child's needs. Parents can find information, support, and assistance from other parents through their state branch of the Autism Society of America (http://www.autism-society.org/).

  • Psychotherapy and education. Many useful approaches involve behavioral therapy or structured intensive education. Heflin and Simpson provide an excellent summary of approaches that may be recommended to parents (see Additional Reading). The earliest intervention was the Treatment and Education of Autistic and Related

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    Communication Handicapped Children program. This is a package of interventions for individuals with AD using visual cues, schedules, and workstations to promote skill acquisition. More recently, a specialized behavioral modification approach entitled discrete trial format training (Lovaas training), a method of applied behavioral analysis, has been found to be beneficial. Applied behavioral analysis is a one to one intervention, and parents and teachers and even peers can be trained in the techniques. Target behaviors (e.g., making eye contact, stopping self-stimulatory rituals, using words) can be enhanced by positive reinforcement or reduced by the absence of reinforcement or consequences. An essential element of Lovaas training is the constant evaluation of the child's performance to measure his or her progress. Other interventions that are more naturalistic (e.g., peer-initiated social interactions) may generalize better than one to one interventions do. A recent focus on developing techniques to target initiation of speech and nonverbal referential cues and then to fade them out systematically may improve outcomes. Other techniques may be used with older verbal children (e.g., increasing verbal responses through self-monitoring techniques, improving verbal interactions with scripted videotaped conversations or social stories, improving understanding of the affect of others through social skills groups). For children who are nonverbal, augmentative and alternative communication systems may be used (e.g., sign language, Picture Exchange Communication System, computer systems).

  • Pharmacotherapy. Although evaluating children with AD and PDD-NOS is sometimes challenging, clinicians must evaluate these children thoroughly. Psychiatric conditions (e.g., mood disorders, anxiety disorders) can develop, and treating these disorders with the same medications used in non-AD children is appropriate. However, because some children with AD or PDD-NOS may not communicate well, for the clinician to use one of the rating scales based on observation by parents and teachers to evaluate the medication effects objectively (e.g., Aberrant Behavior Checklist) is important.

    No specific pharmacologic treatments exist for AD. Behaviors that interfere with the acquisition of language and social skills and that fail to respond to behavioral techniques may be helped by psychotropic agents. Repetitive behaviors, aggression, hyperactivity, and self-injurious behaviors are the most common reasons for psychiatric consultation. In the past, low dosage haloperidol was well documented to reduce social withdrawal, repetitive behaviors, hyperactivity, and aggression in about 50% of children with AD. However, its side effects (e.g., sedation and subtle cognitive changes) interfered with learning, and more than one-third of the children developed withdrawal dyskinesias. Sixty percent of adults with AD show improvement in aggressivity, repetitive behaviors, and emotional lability with low dose risperidone. A controlled study by the Research Units for Pediatric Psychopharmacology Autism Network of the effectiveness and tolerability of risperidone in children with AD has shown efficacy for self-injurious behavior and aggression. AAPs may be used to improve the symptoms listed above (e.g., start with 0.25 to 0.5 mg per day of risperidone or others; see section IV.B.3).

    Fluvoxamine has been shown to be effective in ameliorating repetitive thoughts and/or behaviors, maladaptive behaviors, and aggression in about half of treated adults with AD. However, children with AD who were treated with the same drug failed to improve, and many developed behavioral activation or insomnia. Other SSRIs have not been sufficiently studied.

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    For the symptoms of hyperactivity often seen in children with AD, psychostimulants have been tried with some success. Because psychostimulants are known to worsen stereotypic movements in non-AD children sometimes, inventorying carefully and videotaping existing stereotypic movements before treatment are wise. Clinicians should also be alert for the side effects of dysphoria and aggression in these children. Clonidine may also be useful in selected cases (see Chapter 22). The symptom of inattention has not been well studied in this population.

B. Asperger Syndrome

Children with this disorder have social deficits but normal cognitive functioning and a history of normal language development. Their social deficits may include impaired nonverbal behaviors (e.g., eye contact, facial expressions, body postures, and gestures) and an inability to read social cues in others. Despite normal language development, they also have impaired speech (e.g., poor prosody and modulation of volume) and hyperverbosity about special areas of interest (e.g., clouds, clocks, a particular WWE wrestler). These interests may shift every few years. They have been dubbed little professors because of these traits. As a result, although they desperately want friends, they often fail to develop good peer relationships. Because they often have motor skill difficulties, they are clumsy and they have an awkward gait. They may be quite intelligent, and some individuals show high verbal intelligence and deficits in performance intelligence that are suggestive of a nonverbal learning disability. Exact epidemiologic figures for this disorder are lacking, but this condition is believed to be less common than is AD. Data about comorbidity of Asperger syndrome with other psychiatric conditions is just emerging: As many as 20% of these youth have OCD, ADHD, or MDD (seen especially in the teen years when they become aware of their deficits), and a percentage of children with Asperger syndrome also have Tourette disorder.

Treatment of children with Asperger syndrome should follow the principles used with children with AD, focusing on social awareness and social skills development. Psychopharmacologic interventions should be used to address specific comorbidities.

C. Rett Disorder

This very rare condition (1 in 10,000 to 15,000) continues to be included in the psychiatry nomenclature although almost all of its manifestations, except for autistic features, fall in the neurologic realm. Girls develop normally through their first 5 months. Then, their head circumference decelerates and their acquired hand skills are lost; later, stereotyped hand movements develop and social and communication skills atrophy. Classic Rett disorder is persistent and progressive. Occasionally, a girl with Rett disorder may have some modest developmental and social interaction gains in later childhood or adolescence; however, the deficits in communication and motor difficulties persist through life (e.g., by the third decade, as many as 80% will be nonambulatory). Usually, this condition is sporadic, but it is occasionally familial. Recently, mutations in the X-linked gene that codes methyl-CpG-binding protein-2 (MeCP2) have been identified in some children with Rett disorder. This protein is a transcriptional silencer that affects the normal development of other genes, including those regulating many neurotransmitters. In affected families, a broad range of phenotypes is present, extending from mildly learning disabled girls to those with the classic progressive encephalopathy. Although Rett disorder was believed to be present solely in girls because males had only a single affected gene, boys with the variants of this genetic abnormality and severe mental retardation have been identified.

D. Childhood Disintegration Disorder

Formerly called Heller syndrome, this extremely rare condition has a poor prognosis. It has two key features. First, during the first 2 years of life, normal verbal and nonverbal communication and social development are seen. Second, between the ages of 2 and 10 years, a loss of language, adaptive behavior,

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