CHAPTER 34

Treatment of Children and Adolescents

Margery R. Johnson, M.D

Nicholas M. Hatzis, M.D.

Mina K. Dulcan, M.D.

Glen C. Crawford, M.D.

Stephen J. Cozza, M.D.

In this chapter we focus on psychiatric treatments for children and adolescents and how they differ from treatment of adults. Expanding research has led to more specific empirically tested interventions for youth. Childhood psychopathology and disorder-specific treatments are discussed in Part II (see, e.g., Chapter 8, "Neurodevelopmental Disorders"). Throughout this chapter, unless otherwise stated, the terms child and children include adolescents. Parent is used for the parent, guardian, or responsible adult. The goals of all treatments are to reduce symptoms, to improve emotional and behavioral functioning, to remedy skill deficits, and to remove obstacles to normal development. In contrast to the treatment of adults, a child is usually brought by someone else, and in each case there are at least two clients, the parent and the child, whose perceptions of the problem and goals for treatment often conflict. Compared with adults, children are more dependent on others for meeting their basic needs, they have fewer choices of residence or activities, and they are required to attend school.

Evaluation

The psychiatric treatment of children should be preceded by a comprehensive clinical assessment and formulation of a biopsychosocial treatment plan. Clinicians must have a clear understanding of normal development and its variations in order to distinguish normal from pathological states. Interview adaptations such as drawing or symbolic play, including a parent until the child is comfortable, or the use of simpler language may be required.

Information from the school is always useful and is essential when there is concern about learning or behavior in school or peer functioning. With parental consent, the clinician talks with the teacher; obtains records of testing, grades, and attendance; and requests completion of a standardized checklist, such as the Teacher Report Form of the Child Behavior Checklist (www.aseba.org), the Child Symptom Inventory (www.checkmateplus.com/product/csi-4.htm), or the Vanderbilt ADHD Rating Scale (Wolraich et al. 1998). Even better, if feasible, is a visit to the school to observe the youngster with peers in the classroom and on the playground and to talk with teachers and counselors.

A referral to another specialist such as a pediatrician, pediatric neurologist, child psychologist, or speech and language pathologist may be necessary to complete the assessment. Psychological evaluation, including an intelligence test and achievement tests, may be obtained when there are questions about learning or IQ, with additional testing as indicated.

In an emergency situation, treatment may need to be initiated following an expedited assessment of the child's medical and psychological status. A more thorough evaluation should be accomplished as soon as possible. Of course, the process of assessment does not end with the initiation of treatment but continues throughout.

Treatment Planning

Treatment planning takes into consideration psychiatric diagnosis, target emotional and behavioral symptoms, and the strengths and weaknesses of the patient and family. Resources and risks in the school, neighborhood, and social support network as well as cultural factors such as ethnicity and religious group affiliation influence the selection and sequencing of treatment strategies.

Treatments not in the repertoire of the clinician or those requiring additional staff or a different setting should be arranged by referral. Unfortunately, the practical realities of the quality and availability of community resources and the family's ability to pay for or attend treatment often force the clinician to make compromises to an ideal plan. The clinician must decide which treatment is likely to be the most efficient or to have the highest benefit-cost or risk ratio and whether treatments should be administered simultaneously or in sequence. The American Academy of Child and Adolescent Psychiatry (AACAP) has developed practice parameters as guides to the evaluation and treatment of specific disorders (published in the Journal of the American Academy of Child and Adolescent Psychiatry [http://www.jaacap.com]). AACAP practice parameters are also available at www.aacap.org.

Parents are best included in the choice of treatment strategies, with the strength of the clinician's recommendation depending on the clarity of the indications. The skilled clinician presents the probable course of the disorder if untreated, as well as the best estimate of benefits and risks of all available treatments for a particular child. The child patient is included in decision making as appropriate. The motivation and ability of the responsible adults to carry out the treatment should be considered because there is little chance of success without the cooperation of the family. Treatment planning is an ongoing process, with reevaluations done as interventions are attempted and their results observed and as additional information about the child and family comes to light.

Informed Consent

The implementation of any treatment plan requires carefully obtained informed consent from parents. Clinicians should also strive to obtain assent from child patients, being mindful of the cognitive capacities and developmental level of the patient. The discussion of consent should include the selected therapeutic modality its intended purpose, the availability of any alternative treatments (including no treatment), and the nature of possible adverse reactions. An open discussion and documentation of any questions or concerns not only meet the legal obligations of practice, but also can safeguard the therapeutic alliance should undesirable effects occur. Specific requirements for consent to hospitalization vary by state. Printed materials to supplement discussion in educating parents and children regarding medication treatments are available (Dulcan 2007). The Internet has become an important source of information about medications and treatments for consumers. Because the quality of information available is inconsistent, patients and their families benefit from guidance as to the best sources of information about mental health issues (see, for example, www.aacap.org).

Confidentiality

It is essential that the guidelines for confidentiality and for sharing information between parent and child be clear. Adolescents are usually more sensitive to this issue than younger children. Parents may have concerns about a therapist's keeping vital information about their child from them or indiscriminately revealing information to the child that was disclosed in confidence to the therapist. As a general rule, either party should be told when information from one party's session will be relayed to the other. When children are engaged in potentially dangerous activities or have serious thoughts of harming themselves or others, parents must be informed. Carefully planned family sessions in which the therapist coaches and supports a parent or child in sharing information may be useful.

Psychopharmacology

This section focuses on how medication treatment of children is different from that of adults. U.S. Food and Drug Administration (FDA) warnings have focused the attention of patients, parents, and prescribers on the potential risks of the use of medications in children. Two important general principles are that polypharmacy should be minimized and medication should rarely be used as the sole treatment.

Most disorders of children and adolescents that require medication are either chronic (e.g., attention-deficit/hyperactivity disorder [ADHD], autism spectrum disorder, Tourette's disorder) or likely to have recurrent episodes (e.g., mood disorders). It is important to educate the family regarding the disorder, its treatment, and changes with developmental stage. The clinician must consider the meaning of the prescription and administration of a medication to the child, the family, the school, and the child's peer group.

Special Issues for Children and Adolescents

Pharmacokinetics and Pharmacodynamics

Pharmacokinetics is the study of the movement of drugs into, around, and out of the body by the processes of absorption, distribution, metabolism, and elimination. For example, children differ from adults in the proportions of extracellular water volume and body fat. The proportion of extracellular water decreases substantially from birth through early adolescence, resulting in a relatively larger distribution volume for water-soluble drugs in younger children, who therefore require a relatively higher dose to achieve a comparable plasma concentration (Clein and Riddle 1996). By late infancy to early childhood, hepatic metabolic activity is at its peak. This substantially greater metabolic rate is related to the proportionally larger liver size of children compared with adults. Relative to body weight, the liver of a toddler is 40%-50% greater and that of a 6-year-old is 30% greater than the liver of an adult. This greater metabolic rate has been postulated as the principal factor contributing to decreased drug plasma concentration levels and decreased drug half-lives in children compared with adults (Clein and Riddle 1996). Children also may be more sensitive than adults to increases or decreases in drug metabolism due to interactions with the cytochrome P450 (CYP) enzyme system. Medication dose also is determined by pharmacodynamics, or how the biological system responds to the drug. Growth and development may affect receptor number, distribution, structure, function, and sensitivity. Ideally, medication doses in children should be derived from studies of children, but these are relatively rare. Generally, children are anticipated to require a higher weight-adjusted dose to achieve the same blood levels and therapeutic effects as adults. However, clinicians should remain alert to the possibility that such practice occasionally results in toxicity. It is thus wise to start medications at a low dose and titrate upward, being prepared for the possibility that the final dose may be relatively high, especially in larger adolescents.

Side Effects

Side effects are common in children being treated with psychiatric medications. Clinicians must actively look for adverse reactions, as children often will not report them and parents may not notice. Occasionally, a child will develop an atypical or paradoxical response to a particular medication. Parents are often understandably protective and may have great difficulty tolerating even the most minor side effects in their child. This may lead to premature discontinuation of a medication due to a mild side effect that would probably resolve with continued treatment. Good communication and support from the child psychiatrist can be important in getting beyond this stumbling block.

There may also be behavioral toxicity or exacerbations of the very symptom that is the target of treatment. This phenomenon is often difficult to distinguish from the natural fluctuations in symptoms of the disorder, especially in children with tics, autism spectrum disorder, or severe mood disorders. Having parents keep a mood or behavior chart or a tic log is helpful in tracking response to medication and possible side effects.

Measurement of Outcome

Effective medication management requires the identification and monitoring of target symptoms. The clinician must obtain emotional, behavioral, and physical data at baseline and periodically during treatment. Therapeutic effects can be assessed by parent and child interviews and rating scales, direct observation, collection of data from outside sources (e.g., teachers), or specific tests evaluating attention or learning.

In evaluating psychopharmacology research, it is important to distinguish between statistically significant effects and clinically significant ones and to know whether the target symptoms are reduced to near-normal levels or merely changed, and the clinical meaning of the change. The percentage of patients who improve may be more important than the mean change in a group. Some patients may improve and others worsen, resulting in non-significant group data. On the other hand, statistically significant group changes may translate into only modest changes in the symptoms of individual patients.

Developmentally Disabled Patients

Medication effects are even more difficult to assess in children and adolescents with intellectual disability or autism spectrum disorder. Their impaired ability to verbalize symptoms is relevant to diagnosis, measurement of efficacy, and detection of side effects. These individuals are at risk of idiosyncratic or paradoxical effects and/or smaller therapeutic effects in comparison with typically developing youth.

Adherence to Medication Regimen

Taking medication as directed requires the cooperation of parent(s) and child, and often school personnel as well. In a patient who has a recurrence of symptoms after an initial good response, gentle inquiry about medication adherence should be made prior to making a change in dose. In general pediatric practice, adherence to medication regimens is associated with degree of parental concern about the seriousness of the child's illness, severity of the child's symptoms, and prior adherence to treatment (Lewis 1995). Adherence appears to be inversely related to the complexity of the medication regimen (including the number of medicines used and the frequency of dosing). Adherence to treatment often relates to child and parental attitudes about taking medications for emotional or behavioral problems. Practically, use of a weekly pill organizer is often important for even simple medication regimens. A young child whose medication is dispensed by two parents may easily end up with either no medication or a double dose. Pill organizers may also help parents to check on adherence of an adolescent who is responsible for taking his or her own medication. Adolescents may need more supervision in taking medication than parents assume is needed.

Ethical Issues and "Off-Label" Prescribing

Physicians who treat children with pharmacotherapy face significant ethical challenges. Pharmaceutical companies often do not go to the expense and risk of testing drugs in children and adolescents, although a federal (U.S) law was passed in 1997 to encourage such testing by extending patent protection for 6 months on drugs studied in children. In 2000, the FDA released additional guidelines to encourage the clinical investigation of drugs for use in the pediatric population. Because few psychotropic medications have an approved FDA indication for young children, most drugs are used "off label" in this patient group. While FDA guidelines are not meant to restrict the clinical practice of physicians, the clinician is responsible for the careful use of these medications in young patients. The lack of knowledge of the potential effect of medications on the neural development of children further complicates the issue. A clinician must balance multiple factors: the risks of the untreated disorder, the anticipated and actual efficacy of medication, and potential adverse outcomes or unknowns of medication use.

The interaction between pharmacotherapy and the environment is even more important for children than for adult patients because their immature developmental status places them in the care of adults. There is a danger of misinterpreting the youngster's response to the family, school, or institutional milieu as an exacerbation requiring medication or as improvement due to a medication. Some adults may seek to use drugs to control or eliminate troublesome youth behavior rather than instituting more time-consuming and difficult therapeutic or behavioral management strategies. The clinician must therefore evaluate and monitor the environment as well as the patient, using all available information to make therapeutic decisions.

Stimulants

This category of medications is the most studied and most used in pediatric psychopharmacology. Medication, primarily stimulants, is the most effective treatment for core symptoms of ADHD (Sonuga-Barke et al. 2013). A variety of distinct preparations of methylphenidate and amphetamine are available (Table 34-1). Contrary to earlier beliefs, hyperactive boys, typical boys, and healthy adults have similar cognitive and behavioral responses to comparable doses of stimulants. Stimulants do not have a "paradoxical" effect in ADHD. The therapeutic effect of stimulants is related to augmentation of dopaminergic and noradrenergic activity in key areas of the brain related to attention, motivation, and impulse control.

Indications and Efficacy

There is extensive empirical support for the short-term efficacy and safety of stimulant medications in the treatment of ADHD and comorbid oppositional defiant disorder (ODD) in boys and girls from preschool age through adolescence. Up to 96% of hyperactive children improve behaviorally in response to methylphenidate, dextroamphetamine, or both (Elia et al. 1991). Stimulant effects on various domains (cognitive, behavioral, and social) are variable within and among individuals. A dose that produces improvement in one domain may have no effect or may even lead to worsening in another. The response may differ between measures (e.g., math and reading), even in the same domain. Therapeutic effects typically seen in stimulant responders include improved sustained attention and short-term memory, reduced impulsivity and excessive motor behavior, improved classroom behavior and work completion, reduced impulsive aggression, and improved interactions with parents, teachers, and peers.

The long-term therapeutic effect of stimulant medication is observed clinically but difficult to demonstrate in research, and most studies have been of relatively short duration. The National Institute of Mental Health (NIMH) Collaborative Multisite Multimodal Treatment Study of ADHD (MTA) found after 14 months of treatment that optimally titrated stimulant treatment with supportive therapy (MTA Medication) was more effective for core ADHD symptoms than very intensive behavioral therapy without medication (MTA Cooperative Group 1999). Intensive behavioral treatment added only modestly to MTA Medication (primarily in improving comorbid anxiety social skills, and academic performance). All of the MTA treatments were more effective than treatment as usual in the community, which typically consisted of stimulant medication administered at lower dosages and fewer doses per day, for a shorter period, and with less careful monitoring than MTA Medication. The NIMH Preschool ADHD Treatment Study (PATS) (Greenhill et al. 2006) found methylphenidate to be safe and effective in preschool children, although improvement was less and side effects (especially sadness, irritability, clinging, insomnia, anorexia and repetitive behaviors) were somewhat greater than in school-age children.

Note. All of the above medications are Drug Enforcement Administration Schedule II controlled substances. IR=short-acting (immediate release); LA=long-acting.

^a =scored.

^b =double-scored.

Despite a positive response to stimulant medication, many youth with ADHD continue to have impairment due to learning disabilities, gaps in knowledge and skills, poor social skills, and/or family problems. Adding focused behavioral treatment may augment the stimulant effect or allow for a lower dose of medication to be used. Unfortunately, behavioral treatment is difficult to implement and sustain and does not generalize from one setting to another. Specific skills remediation (e.g., tutoring or coaching) may also be needed.

Stimulant treatment can be useful in reducing the impact of symptoms in comorbid conditions. In ADHD plus ODD, stimulants can reduce defiance, negativism, and impulsive verbal and physical aggression. In children with intellectual disability, stimulants are effective in treating ADHD target symptoms, although therapeutic effect is less robust and side effects are more common than in those of normal intelligence. Stimulants may also be useful in reducing symptoms of inattention, impulsivity and hyperactivity in some children with autism spectrum disorder. In a multicenter double-blind placebo-controlled crossover study of children with autism and hyperactivity (Aman et al. 2005), methylphenidate was superior to placebo, although less effective and with more side effects than in children with ADHD alone.

The use of stimulants in patients with tics or Tourette's disorder is supported by clinical trials. Patients with Tourette's disorder are often far more disabled by their inattention, impulsivity, low frustration tolerance, and oppositional behavior than by the tics. The Tourette's Syndrome Study Group (2002) trial comparing methylphenidate, clonidine, and their combination versus placebo in children with ADHD plus a chronic tic disorder found that methylphenidate was no more likely than clonidine or placebo to increase the frequency of tics. Observed increase in tics, previously attributed to stimulant treatment, may be due to the natural waxing and waning nature of tics. Nevertheless, monitoring for tics during stimulant use is advised.

Initiation and Maintenance

The decision to medicate a child or adolescent with ADHD is based on the child's inattention, impulsivity, and often hyperactivity that are not due to another treatable cause are sufficiently severe to cause impairment at school and usually also at home and with peers. Parents must be willing to monitor medication and to attend appointments. In preschool children, other interventions are generally implemented first, unless severe impulsivity and noncompliance create an emergency situation. An important part of treatment is education of the child, family, and teacher, including explicitly debunking common myths about stimulant treatment. Stimulants do not have a paradoxical sedative effect, do not lead to drug abuse, and do continue to be effective after puberty. There are no evidence-based predictors of which stimulant medication or formulation would be most effective for a specific patient. Neither neurological soft signs, EEG, brain scans nor neurochemical measures have been found to predict stimulant response. Multiple outcome measures that use more than one source and setting are essential to evaluate the effect of a medication regimen. Parent and teacher rating scales (such as the Vanderbilt or the ADHD Rating Scale IV) should be used at baseline and during titration and maintenance treatment. The clinician should work closely with parents on dose adjustments and obtain regular reports from teachers and the results of annual academic testing done by the school.

Prior to starting a stimulant medication, a complete patient and family cardiovascular history should be obtained, including structural cardiac abnormalities, chest pain, palpitations, unexplained fainting, arrhythmias, and family history of early cardiac death or sudden unexplained death. In the absence of cardiovascular indications on history or in the physical examination, an electrocardiogram (ECG) is not indicated prior to stimulant treatment (Perrin et al. 2008).

The variety of available preparations of stimulant medications (see Table 34-1) gives flexibility in addressing the clinical needs of an individual child. Although methylphenidate is the most commonly used and best studied, both methylphenidate and amphetamine may need to be tried. The Texas Children's Medication Algorithm Project (CMAP) for ADHD (Pliszka et al. 2006) provides guidance to clinicians in approaching the pharmacological management of ADHD, as well as the treatment of ADHD with other co-morbid disorders. In brief, the algorithm recommends starting with one of the stimulant medications (methylphenidate or amphetamine). If the treatment response is suboptimal or if side effects or other circumstances warrant, the next step would be the use of the other stimulant. Weight is used only as a rough guide to dosage range (0.3-0.7 mg/kg/dose). Optimal titration assesses therapeutic and side effects at a range of doses: 5,10, 15, and 20 mg dose of methylphenidate (doses of amphetamine and dexmethylphenidate are half those of methylphenidate). If symptoms are significant in multiple settings, dosing three times a day 7 days a week (or daily use of a long-acting formulation) is indicated for full symptom coverage. Daytrana is a transdermal form of methylphenidate. Dexmethylphenidate is the chenantiomer of racemic d,l-threo-methylphemdate (the usual form). Adderall is a racemic mixture of four amphetamine salts, and is dosed the same as dextroamphetamine. Vyvanse (lisdexamfetamine dimesylate) is a prodrug of dextroamphetamine. A therapeutically inactive molecule consisting of dextroamphetamine bound to L-lysine, lisdexamfetamine releases dextroamphetamine after ingestion when the amino acid is cleaved by liver enzymes.

Stimulant medication should be started at a low dose and titrated up (within the recommended range) every week or two according to response and side effects. When children reach 3 years of age, their absorption, distribution, protein binding, and metabolism of stimulants are similar to those of an adult (Coffey et al. 1983), although adults often have more side effects than children do at the same mg/kg dose. Giving medication after meals minimizes anorexia. Pre-school-age children or patients with ADHD predominantly inattentive type, intellectual disability, or autism spectrum disorder may benefit from (and have fewer side effects with) doses lower than are used in school-age patients with ADHD who are very hyperactive and impulsive. Starting with only a morning dose may be useful in assessing drug effect by comparing morning and afternoon school performance. The need for an after-school dose or medication on weekends should be individually determined according to the patient's target symptoms. Although some children who experience sleep or appetite disturbance but a good clinical response to stimulants may benefit from a suspension of medication on weekends and school holidays, those who are actively involved in sports or peer activities or evening or weekend academic projects require consistent daily medication (although a lower dose may be sufficient in some settings outside of the classroom). Results from the MTA study suggest that most children continue to benefit from maintenance medication doses that are similar to the initial titration dose. However, adjustments to dose are often required, reinforcing the need for ongoing monitoring of treatment response and active management of medication formulation, dose, and timing (Vitiello et al. 2001). MTA study results support the superiority of full-day, 7-day-per-week stimulant coverage in children with combined type ADHD.

If symptoms are not severe outside of the school setting, children may have an annual medication-free trial in the summer, lasting at least 2 weeks, but longer if possible. If school behavior and academic performance are stable, a carefully monitored trial off medication during the school year (but not at the beginning) will provide data on whether medication is still needed.

Tolerance is reported anecdotally, but adherence is often irregular and should be the first possibility considered when medication appears to be ineffective. Children should not be held responsible for taking their medication because these youngsters are impulsive and forgetful at best, and most dislike the idea of taking medication, even when they can verbalize its positive effects and cannot identify any side effects. They will often avoid, "forget," or simply refuse medication. Lower efficacy of a generic preparation may be another possibility when tolerance is suspected. Decreased drug effect also may be a reaction to a change at home or school. Greenhill (1995) used the term pseudo-tolerance to define circumstances in which increased symptoms are inaccurately ascribed to decreased medication efficacy (instead of some other factor, such as decreased adherence or life stress). True tolerance is very rare, but might be more likely with the long-acting formulations (Birmaher et al. 1989); if it occurs, the other stimulant may be substituted.

Risks and Side Effects

Most side effects are similar for all stimulants (Table 34-2). Giving medication after meals and offering evening snacks reduce effects of appetite suppression. Insomnia may be due to drug effect, ADHD or ODD symptoms, separation anxiety, rebound, or a preexisting sleep problem. Stimulants may worsen or improve irritable mood. Black male adolescents who take stimulants may be at higher risk for elevated blood pressure (Brown and Sexson 1989). Although alarms were raised regarding a possible association between stimulant treatment for ADHD and sudden death, subsequent studies using very large data bases (Cooper et al. 2011; Olfson et al. 2012; Schelleman et al. 2011) have found no increased risk for serious cardiovascular events in youth prescribed stimulant medications compared with unmedicated youth (Hammemess et al. 2011).

Amphetamine preparations carry a "black box" warning regarding their potential for abuse and the possibility of sudden death and serious cardiovascular events if misused. They should also be avoided in patients with structural cardiac defects. Abuse is possible, but research has not found serious cardiovascular risk when amphetamines are used as prescribed.

The possibility of stimulant-induced growth retardation remains a concern. The magnitude is dose related and appears to be greater with amphetamine than with methylphenidate. Weight loss or slowed velocity of weight gain is common. Slowing of height growth has been found in some studies, but findings are variable and some youth with ADHD are above average in size prior to stimulant treatment. Measurement of height and weight at the initiation of treatment and at regular intervals throughout is recommended.

Rebound effects, consisting of increased excitability, activity, talkativeness, irritability, and insomnia, beginning 4-15 hours after a dose, may be seen as the last dose of the day wears off or for up to several days after sudden withdrawal of high daily doses of stimulants. This effect may resemble a worsening of the original symptoms, but also may simply be the return of original symptoms when the medication effect wanes or a result of environmental influences in the late afternoon and evening.

If there is a concern regarding abuse or diversion of medication by the patient, family, or peers, use of Concerta, Vyvanse, or Daytrana is recommended. These formulations do not produce a "high" because they cannot be snorted or injected.

Attention is required to avoid possible indirect and inadvertent cognitive and social consequences of medication, such as lower self-esteem and self-efficacy; attribution by child, parents, and teachers of both success and failure to the medication rather than to the child's effort; stigmatization by peers; and dependence by parents and teachers on medication rather than making needed changes in the environment (Whalen and Henker 1991). Both patients and relevant adults can be instructed that medication enables the child to accomplish what he/she wishes to do; it does not make him/her do anything. Children should be given full credit for improvement and helped to take an appropriate amount of responsibility for problems.

Although there is a commonly held notion that stimulants lower the seizure threshold, there is no evidence that stimulants produce an increase in seizure activity. Addiction has not been found to result from the prescription of stimulants for ADHD.

Alpha₂-Noradrenergic Agonists

Clonidine and guanfacine are α₂-noradrenergic agonists developed for the treatment of hypertension. The shortacting forms (Catapres and Tenex) have been used for some time to treat ADHD, with modest empirical support. A long-acting formulation of each (Kapvay and Intuniv) is now FDA-approved for the treatment of ADHD, alone or in combination with a stimulant medication (for a review, see Sallee et al. 2013).

Indications and Efficacy

Attention-Deficit/Hyperactivity Disorder

Clonidine is useful in modulating mood and activity level and in improving cooperation and frustration tolerance in a subgroup of children with ADHD, especially those who are highly aroused, hyperactive, impulsive, defiant, and labile. Children with ADHD and comorbid tics may have a more positive response to clonidine than children who have ADHD without tics (Steingard et al. 1993). A randomized controlled trial in children with both ADHD and a chronic tic disorder found significant improvements in all treatment groups (clonidine, methylphenidate, and the combination) (Tourette's Syndrome Study Group 2002). The greatest benefit compared with placebo was seen in the combination medication group. While clonidine and methylphenidate individually were both noted to be effective for symptoms of ADHD, methylphenidate appeared more beneficial for the inattention symptoms, while clonidine appeared more beneficial for the impulsivity and hyperactivity symptoms. A similar trial in patients with ADHD alone did not find clonidine to be very helpful with ADHD symptoms.

In a study that examined the addition of either clonidine or placebo to the treatment of children with ADHD and comorbid conduct disorder or ODD who were already taking a stimulant, after about 5 weeks of treatment clonidine was modestly superior to placebo (Hazell and Stuart 2003). This study suggests that 4-6 weeks of treatment with clonidine may be necessary before its benefits can be adequately assessed.

Two large controlled trials have demonstrated efficacy of extended-release clonidine (Kapvay) in the treatment of children and adolescents with ADHD. In the first, extended-release clonidine at 0.2 mg/day or 0.4 mg/day was superior to placebo, with significant improvement at 5 weeks (Jain et al. 2011). In the second, youth with ADHD combined or hyperactive subtypes who had a partial response to a stimulant were randomly assigned to stimulant plus placebo or extended-release clonidine. Extended-release clonidine was superior to placebo in improvement of inattention and hyperactivity (Kollins et al. 2011). Common adverse effects were somnolence, headache, and fatigue.

Immediate-release guanfacine has been demonstrated to be more effective than placebo in a controlled trial in children with comorbid ADHD and tic disorders (Scahill et al. 2001). Extended-release guanfacine (Intuniv) has been shown to be effective monotherapy in the treatment of ADHD. In two large controlled trials, extended-release guanfacine was superior to placebo for symptoms of hyperactivity, impulsivity, and inattention as well as for oppositional symptoms (Biederman et al. 2008; Sallee et al. 2009). More recently, extended-release guanfacine once a day in morning or evening has been shown to be effective in reducing symptoms of ADHD when added to a stimulant medication (Wilens et al. 2012).

Tic Disorders

Efficacy of clonidine in reducing tics in youth who do not also have ADHD has not been consistently demonstrated. Clonidine appears to be most useful in reducing subjective distress and the behavioral symptoms of hyperactivity and impulsivity that often accompany Tourette's disorder. As mentioned above, guanfacine may be useful in treating tics (Scahill et al. 2001).

Initiation and Maintenance

Blood pressure and pulse should be measured before treatment and at regular intervals thereafter. An ECG may be considered in preschoolers and in those with a patient or family history of cardiovascular symptoms. Baseline laboratory blood studies (especially fasting glucose) may be considered if patient or family history suggests increased risk. Shortacting clonidine is started at 0.05 mg at bedtime. This low dose and timing convert the side effect of initial sedation into a benefit. An alternate strategy is to begin with 0.025 mg qid. Either way, the dose is then titrated gradually over several weeks to 0.15-0.30 mg/day (0.003-0.01 mg/kg/day) in three or optimally four divided doses. Young children (ages 5-7 years) may require even lower initial and maintenance doses. The transdermal form (skin patch) may be useful to avoid swallowing pills and to reduce variability in blood levels. It lasts only 5 days in children (compared with 7 days in adults). Once the daily dose has been determined using pills, an equivalent-size patch may be substituted (0.1, 0.2, 0.3 mg/day). Patches should not be cut to adjust the dose, as this may damage the delivery membrane, potentially causing an increase in the delivered dose of cloni-dine. Unfortunately, patches do not adhere well in hot, humid weather. Cloni-dine extended-release is started at 0.1 mg/day divided into two doses and increased by 0.1 mg/day each week to a target of 0.4 mg/day divided into two doses (every 12 hours).

For guanfacine, doses range from 0.5 to 4.0 mg/day, in three divided doses per day. A recommended starting regimen is 0.5 mg once or twice daily in children and 1 mg once or twice daily in adolescents, to be increased every 3 or 4 days until therapeutic effect is noted. Intuniv is started at 1 mg/day, increasing weekly by 1 mg/day to the maximum of 4.0 mg/day. This extended-release form is given only once a day, and is not mg-to-mg equivalent with the immediate-release form.

One mg of guanfacine is equivalent to 0.1 mg of clonidine. They can be gradually cross-tapered to switch between them. When clonidine or guanfacine is discontinued, it should be tapered gradually, rather than stopped suddenly, to avoid a withdrawal syndrome consisting of increased motor restlessness, headache, agitation, elevated blood pressure and pulse rate, and (in patients with Tourette's disorder) exacerbation of tics.

Risks and Side Effects

Sedation and irritability are troublesome side effects of clonidine, although these tend to decrease after several weeks. Dry mouth, nausea, and photophobia have been reported, with hypotension and dizziness possible at high doses. The cloni-dine skin patch often causes local pruritic dermatitis; daily rotation of the patch site or use of a steroid cream may minimize this. Glucose tolerance may decrease, especially in patients at risk for diabetes. Although guanfacine is less sedating and less hypotensive than clonidine, it shares many of the other side effects. Small mean decreases in pulse and blood pressure without clinical significance have been noted with extended-release guanfacine treatment, and headache and sedation are common.

Although there were past anecdotal reports suggesting serious adverse drug reactions (including sudden death) in children treated with clonidine, alone or in combination with methylphenidate, more recent studies (Hazell and Stuart 2003; Tourette's Syndrome Study Group 2002) have found benefits without acute cardiovascular risk. Manic symptoms that resolved upon medication discontinuation have been reported in a small number of children treated with guanfacine (Horrigan and Barnhill 1999).

Atomoxetine

Atomoxetine, a norepinephrine reuptake inhibitor, is a nonstimulant medication approved for the treatment of ADHD in children and adults.

Indications and Efficacy

The efficacy of atomoxetine in the treatment of ADHD in preschoolers through adolescents has been demonstrated (Kelsey et al. 2004; Kratochvil et al. 2011; Michelson et al. 2001; Weiss et al. 2005). In controlled trials, approximately half of the atomoxetine-treated subjects are "much improved" (Newcom et al. 2009). A meta-analysis of 13 studies of atomoxetine in 6- and 7-year-old children concluded that atomoxetine maintained its efficacy and tolerability for up to 2 years (Kratochvil et al. 2006). Atomoxetine is beneficial in children with comorbid ADHD and ODD, although higher doses (1.8 mg/kg/day) are required (Newcorn et al. 2005). A controlled pilot trial found efficacy and safety of atomoxetine in the treatment of ADHD symptoms in children with autism spectrum disorder (Arnold et al. 2006).

Studies of ADHD treatment suggest that atomoxetine has a smaller effect size compared with stimulants (Wigal et al. 2005). Atomoxetine is considered a second-line treatment for ADHD. The Texas CMAP (Pliszka et al. 2006) recommends the use of atomoxetine only after trials of both stimulants, unless severe side effects from stimulants or contraindications to their use require that atomoxetine be used preferentially. Clinical experience and small trials suggest that atomoxetine and a stimulant can be safely used together.

Initiation and Maintenance

Atomoxetine is started at 0.3 mg/kg/day in a single dose in the morning. If the patient is sedated, the dose can be moved to bedtime. If there are gastrointestinal side effects, the dose can be divided into morning and evening and given with food. Over 1-3 weeks, the total daily dose is increased to the initial target dose of 1.2 mg/kg/day. The total daily dose in children and adolescents weighing less than 70 kg should not exceed 1.4 mg/kg/day or 100 mg, whichever is less. For patients who weigh over 70 kg, the maximum daily dose is 100 mg. Doses up to 1.8 mg/kg/day do not result in increased benefit, with the exception of youth with comorbid ODD. The maximum response to a given dose may be delayed for several weeks or even months.

Risks and Side Effects

Atomoxetine is generally well tolerated. The most common side effects include abdominal pain, headache, irritability or mood lability, dizziness, somnolence or fatigue, decreased appetite, and nausea and vomiting. Modest dose-related increases in pulse and blood pressure have also been noted. Most side effects appear to subside over time and only rarely result in discontinuation of treatment. A meta-analysis found only minimal effects on height and weight over a 2-year treatment period, compared with expected growth rates (Spencer et al. 2005). The capsules should not be opened, as the contents are caustic to the eyes. There are two FDA bolded warnings: one for extremely rare severe liver injury and one (based on limited evidence) for increased hostility and aggression or suicidal ideation. No routine liver function tests are recommended, but parents should be instructed that if the patient develops jaundice; unexplained decreased appetite, nausea or vomiting; pruritus; dark urine; or abdominal tenderness the medication should be stopped and the physician called immediately to obtain liver function tests.

Atomoxetine is metabolized primarily through the hepatic CYP 2D6 pathway, although it is not itself an inhibitor of this enzyme. Genetically slow metabolizers are not at increased risk of side effects, and genotyping is not indicated. Atomoxetine does not increase tics (Allen et al. 2006), lower the seizure threshold, or cause QTc prolongation and has a large margin of safety in overdose.

Selective Serotonin Reuptake Inhibitors

Controversy Surrounding SSRI Use in Children

In 2003, the Medicines and Healthcare products Regulatory Agency (MHRA) of the United Kingdom issued a statement reporting the receipt of new data from clinical trials of paroxetine that did not demonstrate efficacy in depressive illness in children. Moreover, the studies showed an increase in suicidality and suicidal behavior in children taking paroxetine, relative to placebo. The MHRA issued warnings that paroxetine or venlafaxine not be used in children to treat depressive illness. That same year, the MHRA issued an advisory stating that, with the exception of fluoxetine, the use of any SSRI for the treatment of depression in children is contraindicated.

In the United States, the FDA issued its own advisory to clinicians recommending that paroxetine not be used in children for the treatment of depression, pending the outcome of a review of the data. In 2003, the FDA issued a Public Health Advisory alerting clinicians to reports of increased suicidal thinking in children taking antidepressants. The Advisory concluded that while "the data do not clearly establish an association between the use of these drugs and increased suicidal thoughts or actions by pediatric patients," such an association could not be ruled out. The FDA commissioned a team of experts to evaluate the available data and determine whether the adverse events as defined in the studies actually represented suicidality. The FDA held meetings of its Psychopharmacological Drugs and Pediatric Advisory Committees, during which input from the public was considered along with a review of an FDA meta-analysis of the data from both published and unpublished studies. The conclusion of this review was that the rate of "definite or possible" suicidality among children in the treatment group was twice that of the placebo group (Newman 2004). The FDA stopped short of contraindicating the use of antidepressants in youth but required a "black box" caution on all antidepressants, warning of increased risk of suicidality in pediatric patients. It is important to note that no completed suicides occurred in the more than 4,000 children included in the studies of SSRI use. In addition, methodological limitations in the studies made drawing conclusions regarding efficacy and side effects difficult (Brent and Birmaher 2004). Furthermore, studies of SSRI use in children with anxiety disorders have not shown any increase in suicidal ideation or behavior. The clinical consensus is that SSRIs are clearly beneficial for children with anxiety disorders and probably so for depression, but monitoring for suicidal ideation is important, especially in the first few weeks of treatment. Since the "black-box" warning, prescriptions of SSRIs for children have decreased. The adolescent suicide rate, which had been declining for about 15 years, began to rise. A reanalysis at the person-level of longitudinal data from all of the controlled trials of fluoxetine for pediatric depression found no evidence of increased suicidal thoughts and behaviors in youth randomly assigned to medication versus placebo (Gibbons et al. 2012).

Indications and Efficacy

Depressive Disorders

Fluoxetine has an FDA indication for the treatment of depression in children ages 8-17 years and escitalopram is FDA indicated for the treatment of major depression in youth age 12 and older. The efficacy of fluoxetine in treating pediatric depression has been demonstrated in two rigorous randomized controlled trials (Emslie et al. 2002). The NIMH Treatment for Adolescents with Depression Study (TADS) (March et al. 2006), a randomized controlled trial of 439 patients ages 12-17 years with major depressive disorder (MDD), compared the efficacy of fluoxetine (10-40 mg/day) and cognitive-behavioral therapy (CBT), either alone or in combination, with placebo over a 12-week period. At the conclusion of the study, fluoxetine plus CBT and fluoxetine alone were superior to both placebo and CBT alone. The results of studies of other SSRIs (sertraline, citalopram, and escitalopram) in pediatric depression have been inconsistent. In summary, although more study is needed of efficacy and safety, SSRIs can be effective in the treatment of depression in children. The results may be less predictable and less positive than with adults. With respect to pharmacologic treatment of pediatric depression, SSRIs are the first and second line choices.

Obsessive-Compulsive Disorder

Fluoxetine is FDA approved for the treatment of obsessive-compulsive disorder (OCD) in children ages 7-17 years. Other SSRIs with FDA indications for OCD in youth are fluvoxamine (8 years and older) and sertraline (6 years and older). A meta-analysis of controlled trials of treatment of pediatric OCD found that fluoxetine, fluvoxamine, paroxetine, and sertraline are equal in efficacy and all are superior to placebo (Geller et al. 2003).

The NIMH Pediatric OCD Treatment Study (POTS) (March et al. 2004) examined the use of sertraline, CBT, and their combination in a 12-week randomized controlled study of 112 children and adolescents with OCD. All active treatment conditions were significantly superior to placebo. The combination of CBT and sertraline was superior to monotherapy with either CBT or sertraline. The effect size of CBT monotherapy was greater than sertraline monotherapy, with more children achieving remission from CBT monotherapy, although the benefit over sertraline monotherapy did not reach statistical significance. The combination of CBT and medication for relatively severe OCD thus appears to be more effective and may also be more acceptable to patients and parents. When compared with medication alone, the addition of CBT includes techniques that can address subsequent relapses in OC symptoms that occur despite medication treatment or that happen after medication discontinuation.

Other Disorders

Studies have demonstrated the efficacy of SSRIs (e.g., fluvoxamine, sertraline, fluoxetine) in generalized anxiety disorder, separation anxiety disorder, selective mutism, panic disorder, and social phobia.

Initiation and Maintenance

Patients and parents should be cautioned regarding the "black box" warning of the potential for increased suicidality. The FDA recommends weekly monitoring of children during the first 4 weeks of treatment and additional monitoring at weeks 6,8, and 12, but the American Psychiatric Association and the AACAP suggest that monitoring be tailored to the individual patient and family (PhysiciansMedGuide n.d.). With responsible parents or a mature adolescent, phone check-ins with the physician or a nurse may be substituted for some weekly visits.

The guidelines from the Texas CMAP (Hughes et al. 2007) recommend fluoxetine, sertraline, or citalopram as first line medication for the treatment of pediatric MDD. Fluoxetine is the consensus conference panel's first choice, with sertraline and citalopram as alternates. Fluoxetine and citalopram maybe started at a dose of 5-10 mg/day, increased as needed to 20 mg/day. Although most children will respond to 20 mg/day or less of these medications, some children may require up to 40 mg/day (citalopram) or 60 mg/day (fluoxetine for OCD). Escitalopram doses are half those of citalopram. All three of these medications are available in a liquid formulation that may facilitate medication administration or dose titration.

Sertraline and fluvoxamine may be started at 25 mg/day and increased as necessary to 100-150 mg/day. The dose may be increased every few days, monitoring therapeutic and side effects. The shorter half-life of these drugs in children makes discontinuation syndrome more likely to occur, even after only one missed dose. It is therefore preferable to taper the medication over several days rather than discontinue it abruptly. Discontinuation syndrome is less likely when switching from one SSRI to another, but even then, close communication and monitoring for withdrawal symptoms can eliminate unnecessary suffering. Discontinuation syndrome is not usually observed with fluoxetine, because of its active metabolites and long half-life.

Risks and Side Effects

Children and adolescents usually tolerate this class of medication well, although they may experience similar side effects to adults, such as gastrointestinal complaints or headache. If medication is stopped abruptly, a discontinuation syndrome, consisting of malaise, myalgias, headache, and anxiety, may ensue. "Behavioral activation" or manic symptoms have been reported to appear within days to weeks of initiating treatment with an SSRI, even with no premorbid or family history of a cyclical mood disorder. These symptoms typically resolve within a few days of a dose reduction or cessation of medication. In some cases, treatment with a mood stabilizer is necessary. A systematic chart review of 82 children and adolescents treated with SSRIs for depression or OCD found that 22% experienced a "psychiatric adverse event," most commonly a disturbance in mood (Wilens et al. 2003). Behavioral activation with physical agitation and insomnia is often difficult to distinguish from emergent mania, but symptoms like grandiosity, increased goal-directed activity, and euphoric mood may be helpful in identifying the child with true mania or hypo-mania. Children being treated with an SSRI may also develop disinhibition or apathy and lack of motivation. These symptoms typically develop 6-8 weeks after initiation of treatment with an SSRI or an increase in dose and usually subside with a decrease in dose. While SSRIs do not consistently affect weight or appetite, weight loss or slowing of weight gain does occasionally happen, so it is wise to ask about this side effect and check weight for the first few months of treatment. Adolescents, like adults, may experience sexual dysfunction from SSRI treatment and this may affect adherence to treatment. Movement disorders, including dystonia, akathisia, and tics, have been reported rarely in children taking SSRIs. Serotonin syndrome is a rare but potentially fatal reaction that is more common when serotonergic agents are used in combination, but is possible after only one dose of a serotonergic agent. Signs of this syndrome include mental status changes, fever, tremor, diaphoresis, and agitation. Clinicians should be alert to the possibility and counsel patients and parents as appropriate. Treatment, as in adults, includes stopping the SSRI and providing supportive medical interventions.

Other Antidepressants

All antidepressants share the "black box" warning regarding increased suicidality. Bupropion and venlafaxine are used rarely to treat depression in youth. Bupropion has been demonstrated to be effective in treatment of pediatric ADHD in controlled trials (Barrickman et al. 1995; Conners et al. 1996) and is a third-line treatment for that disorder. Its use as an antidepressant is generally limited to adolescents who have failed one or more trials of an SSRI and have low energy and difficulty concentrating as symptoms of depression or who have comorbid ADHD. The most serious side effect is a decrease in the seizure threshold, seen most frequently in patients with an eating disorder. Other side effects in children include skin rash, perioral edema, nausea, increased appetite, agitation, and exacerbation of tics. Use of venlafaxine is generally limited to adolescents with major depression who have failed one or more trials of an SSRI. In the NIMH Treatment of Resistant Depression in Adolescents (TORDIA) study, after one failed trial of an SSRI, switching to another SSRI was as effective as switching to venlafaxine and venlafaxine produced more side effects (Brent et al. 2008).

Until the introduction of the SSRIs, tricyclic antidepressants (TCAs) were used in the pharmacological treatment of a variety of disorders in children and adolescents. However, the paucity of clinical studies demonstrating the efficacy of TCAs in pediatric depression, the cardiac side effects of this class of medication, and the availability of alternative medications have resulted in a shift away from using TCAs in youth, except for OCD (clomipramine), ADHD (imipramine or nortriptyline), and enuresis (imipramine), where they are third-line choices. Children metabolize TCAs more rapidly than adults do and are prone to swings in blood levels from ineffective to toxic, requiring monitoring of baseline and follow-up ECGs and divided doses to produce a more stable level. TCAs are extremely dangerous in overdose, either intentional or accidental, and parents should be advised to lock up or otherwise secure the medication for the safety of all household members.

Mood-Stabilizing Agents

Lithium has been approved for use in the United States since 1970 for the treatment of mania in patients 12 years of age and older. Antiepileptic drugs have been used for a variety of psychiatric indications, with varying degrees of empirical support in both adults and youth. Data on children and adolescents are far more limited than on adults, but side effect patterns appear to be similar. All of the mood stabilizers, particularly the anticonvulsants, have complex interactions with multiple other drugs. Wide variations in bioavailability and rate of absorption of generic products have led to recommendations that the brand name (or at least a single generic) product be prescribed.

Lithium

Indications and Efficacy

Controlled trials in pediatric bipolar disorder are few and difficult to carry out, but existing results support lithium efficacy (Findling et al. 2003). In a small controlled study of adolescents with bipolar disorder and a substance dependence disorder, Geller et al. (1998) found that lithium significantly improved global functioning and decreased substance use compared with placebo. Information on lithium augmentation of SSRIs in children is sparse. Lithium is not indicated for prophylaxis in bipolar disorder in children unless there is a well-documented history of recurrent episodes. A recent randomized controlled trial showed risperidone to be more effective in treating acute mania than either lithium or divalproex sodium (although at some sites lithium efficacy equaled that of risperidone) (Geller et al. 2012).

Initiation and Maintenance

Lithium should not be prescribed unless the family is willing and able to consistently administer multiple daily doses and obtain lithium blood levels. In addition to the usual medical history and physical examination, complete blood count (CBC) with differential, electrolytes, thyroid function studies, blood urea nitrogen (BUN), and creatinine should be determined before lithium is started. A urinalysis and ECG also should be obtained. A patient with a history suggesting increased risk of seizures warrants an EEG. Sexually active girls should have a pregnancy test. Height, weight, thyroid-stimulating hormone (TSH), creatinine, and morning urine specific gravity (or osmolality) should be obtained every 3-6 months.

Lithium levels, drawn 10-12 hours after the last dose, should be obtained twice weekly during initial dose adjustment and monthly thereafter. Three to four days are required to reach steady-state levels after a dose change. Therapeutic levels are the same as for adults, 0.6-1.2 mEq/L. The starting dose is 300 mg/day, gradually titrated upward in divided doses according to serum levels and clinical effects. Total daily therapeutic dose is typically between 900 and 1,200 mg per day. Because lithium excretion occurs primarily through the kidney, and most children have more efficient renal function than adults, they may require higher doses for body weight than do adults (Weller et al. 1986). More steady blood levels may be obtained by using a slow-release formulation. Lithium should be taken with food to minimize gastrointestinal distress. Given lithium's teratogenicity, the clinician should address this potential with female adolescent patients and consider contraception as appropriate.

Risks and Side Effects

Although lithium is well tolerated by many youth, younger children are more prone to side effects. Children may experience side effects at serum levels that are lower than those in adults. Most common are weight gain, headache, nausea, tremor, and stomachache. Common early onset side effects, which seem to be related to rapid increase in serum level, include nausea, diarrhea, muscle weakness, thirst, urinary frequency, a dazed feeling, and hand tremor. Polydipsia and polyuria may result in enuresis and prevent attainment of a therapeutic level. In developing children, the consequences of hypothyroidism (which could resemble retarded depression) are potentially more severe than in adults. Lithium's tendency to aggravate acne may be especially significant for adolescents. Lithium's effects on glucose are controversial, but both hyperglycemia and exercise-induced hypoglycemia are possible. Managing any hypokalemia with dietary supplementation is preferable to using potassium tablets.

Toxicity is closely related to serum levels, and the therapeutic margin is narrow. Adequate salt and fluid intake is necessary to prevent levels from rising into the toxic range. The patient and the family should be instructed to stop the lithium and call the doctor immediately if the child develops a febrile or gastrointestinal illness, uses rigorous dieting to lose weight, or takes diuretics or nonsteroidal anti-inflammatory agents. The family should be instructed in the importance of preventing dehydration from heat or exercise. Erratic consumption of large amounts of salty snack foods may cause fluctuations in lithium levels. Symptoms of lithium toxicity include vomiting, drowsiness, hyperreflexia, sluggishness, slurred speech, ataxia, anorexia, convulsions, stupor, coma, and death.

Carbamazepine and Oxcarbazepine

The evidence suggesting a potential benefit of carbamazepine in the treatment of juvenile bipolar disorder or aggression is extremely limited. Carbamazepine has largely been replaced by other, more effective treatments for psychiatric indications. Use of oxcarbazepine instead of carbamazepine has been suggested, but a multicenter randomized controlled trial did not find efficacy of oxcarbazepine in pediatric mania (Wagner et al. 2006).

Divalproex Sodium

Indications and Efficacy

Research findings are inconsistent with regard to the efficacy of divalproex in pediatric bipolar disorder (DelBello et al. 2006; Findling et al. 2005; Kowatch et al. 2007; Wagner et al. 2009).

Initiation and Maintenance

CBC with differential and platelets and liver function tests should be measured before the patient begins taking valproate. Sexually active girls should have a pregnancy test. Liver function tests and CBC may be repeated weekly for the first month and then every 4-6 months. For children younger than age 10 years, monthly liver function tests are advisable. Valproate is typically started at 10-15 mg/kg/day in two or three divided doses and then titrated up gradually according to tolerance and response. Coadministration of guanfacine has been shown to increase plasma levels of valproate (Ambrosini and Sheikh 1998).

Risks and Side Effects

The most frequent adverse effects are nausea, vomiting, and gastrointestinal distress (which may be diminished by using enteric-coated divalproex sodium), sedation, weight gain, and tremor. A suggested causal relationship to menstrual disturbances and polycystic ovaries is controversial in the use of this drug for psychiatric indications (as opposed to epilepsy).

Other Anticonvulsants

There are limited data supporting the use of lamotrigine in pediatric bipolar disorder. Lamotrigine has the potential to induce a very rare but potentially life-threatening rash (Stevens-Johnson syndrome). Prompt discontinuation of treatment at the first signs of rash is necessary, although this may not prevent progression to the full syndrome. Very slow titration of this medication seems to reduce the potential for rash development.

Although retrospective reviews have suggested a possible role for topiramate in pediatric bipolar disorder, DelBello et al. (2005) cut short their double-blind, controlled study of topiramate monotherapy in pediatric bipolar I disorder after a negative trial of topiramate in adult bipolar disorder. Currently there are insufficient data to recommend topiramate for use in children.

Antipsychotic Medications

Indications and Efficacy

Antipsychotic medications are more fully discussed in Chapter 27, "Psychopharmacology/' In addition to their use in the treatment of schizophrenia and other psychotic disorders, antipsychotic medications have been used in the pediatric population to treat bipolar disorder, conduct and other aggressive disorders, Tourette's disorder, and the behavioral manifestations of autism spectrum disorders. The introduction of second-generation anti-psychotics (SGAs) or "atypical" antipsychotic medications greatly increased the use of these drugs in children. There are some pediatric data on the relatively older SGAs, but little or none on paliperidone, iloperidone, lurasidone, and asenapine. SGAs are often preferred over first-generation antipsychotics (FGAs) due to their decreased risk of inducing extrapyramidal side effects (EPS) and tardive dyskinesia, although they have a greater incidence of causing excessive weight gain and metabolic syndrome. Studies comparing the efficacy of first- and second-generation antipsychotics in children and adolescents are extremely limited.

Risperidone, quetiapine, and aripiprazole have pediatric FDA indications for bipolar disorder, manic (age 10 years and older) and schizophrenia (13 years and older). Olanzapine has an FDA indication for bipolar mania and schizophrenia in youth age 13 and older, with labeling that other drugs should be considered first (due to problems with weight gain and metabolic syndrome). Risperidone and aripiprazole have an FDA indication for irritability in autism (age 5-16 years and 6-17 years, respectively).

Psychotic Disorders

The few studies examining the efficacy of FGA medications in schizophrenic children and adolescents find that they are moderately effective in children and adolescents with schizophrenia, but side effects are significant, particularly sedation (with low-potency agents) and EPS (with high-potency agents). It appears that younger patients, especially males, are more prone to EPS. In the pediatric population, SGAs are generally considered to be preferable to the older antipsychotic drugs. Clozapine has consistently been demonstrated to be superior to haloperidol in adolescent patients with treatment-resistant childhood-onset schizophrenia (Kumra et al. 1996). Due to clozapine's serious side effects (agranulocytosis, cardiomyopathy, seizures, and significant weight gain), it is reserved for treatment of severely impaired patients who have failed to respond to trials of other antipsychotics.

There is research support for the effectiveness of risperidone, olanzapine, and quetiapine in schizophrenia spectrum and other psychotic disorders in youth but few data on aripiprazole and ziprasidone.

Mood Disorders

A controlled trial found quetiapine to be as effective as divalproex in treating acute manic symptoms (DelBello et al. 2006). Randomized controlled trials have demonstrated the efficacy of the "older" SGAs as monotherapy for mania in adolescents and for quetiapine (added to valproate) in bipolar disorder. As noted above, the NIMH Treatment of Early Age Mania (TEAM) study found risperidone to be more effective in treating acute pediatric mania than either lithium or divalproex sodium (Geller et al. 2012). Clinical experience suggests that an SGA may be used to augment antidepressant therapy in children with treatment-resistant MDD.

Autism Spectrum Disorders

Both short-term studies (McCracken et al. 2002; Shea at al. 2004) and longer-term studies (McCracken et al. 2005) have demonstrated the efficacy of risperidone in controlling aggression, self-injurious behavior, and tantrums in children with autism. The most significant side effect was weight gain. Data also support the use of aripiprazole in autistic patients. Effects of treatment with quetiapine are more variable, and side effects of ziprasidone (cardiac conduction problems) and olanzapine (weight gain) limit their usefulness.

Tourette's Disorder

Haloperidol and pimozide have established efficacy in the reduction of tics, but side effects are problematic. Randomized controlled trials have shown risperidone's efficacy in reducing symptom severity in children and adults with Tourette's disorder (Dion et al. 2002; Scahill et al. 2003). Some research supports the benefit of olanzapine, quetiapine, and ziprasidone.

Conduct Disorder and Aggression

Treatment Recommendations for the Use of Antipsychotics for Aggressive Youth (TRAAY) and Center for Education and Research on Mental Health Therapeutics Treatment of Maladaptive Aggression in Youth (CERT T-MAY) guidelines include both psychosocial and pharmacological interventions (Knapp et al. 2012; Pappadopulos et al. 2003; Schur et al. 2003; Scotto Rosato et al. 2012). Antipsychotic agents in general and SGAs in particular have some evidence of effectiveness in the treatment of aggression in selected pediatric populations. Studies have shown risperidone to be helpful at relatively low doses (approximately 1 mg/day) in reducing aggression and disruptive behaviors in youth with normal intelligence (Findling et al. 2000) and those with subaverage IQ (Aman et al. 2002; Snyder et al. 2002). Weight gain and sedation are problems, however.

Initiation and Maintenance

Before medication is initiated, a complete physical examination and baseline laboratory workup, including CBC with differential, serum chemistries including fasting glucose and liver-associated enzymes, thyroid function studies, lipid studies, and urinalysis, should be done. Weight and fasting glucose levels should be monitored. When using clozapine, a baseline EEG is recommended and a weekly white blood cell (WBC) count with differential is mandatory for at least the first 6 months. Both first- and second-generation antipsychotic agents have been shown to increase QT intervals on ECG, potentially leading to dysrhythmias and sudden death. Clinicians should consider ECG monitoring, when appropriate.

Doses must be titrated individually, with careful attention to positive and negative effects. The initial dose should be very low, with gradual increments no more than once or twice a week. It may require several weeks or months to reach full efficacy of a particular dose. Although divided doses are often used during titration, in most cases, once a therapeutic dose has been reached, a single daily dose (usually at bedtime) can be used. Dosing guidelines for the SGAs are presented in Table 34-3.

In the treatment of autism spectrum disorder, at 3- to 6-month intervals, consideration may be given to discontinuation of the drug to observe for withdrawal dyskinesias and to determine if continued treatment is still necessary. Risperidone may be effective at doses as low as 0.5-1.0 mg/day, with most patients responding to doses between 0.5 and 2 mg/day. Therapeutic doses for aripiprazole may range from 2 mg/day to 15 mg/day.

For patients with Tourette's disorder, careful initial monitoring for several months permits the clinician to establish a baseline of symptoms (which tend to wax and wane) and to assess the need for psychological and educational interventions. Risperidone doses in the range of 0.5-2.5 mg/day appear to be useful.

Risks and Side Effects

An excellent review of SGA side effects in children can be found in Correll et al. (2006).

Extrapyramidal Side Effects

Acute EPS, including dystonic reactions, parkinsonian tremor, rigidity, drooling, and akathisia, occur as in adults and may be induced by either first- or second-generation agents. Laryngeal dystonia is potentially fatal. Acute dystonia may be treated with oral or intramuscular diphenhydramine, 25 mg or 50 mg, or benztropine mesylate, 0.5-2.0 mg. Adolescent boys seem to be more vulnerable to acute dystonic reactions than are adult patients, so the physician may be more inclined to use prophylactic antiparkinsonian medication. For treatment or prevention of parkinsonian symptoms, adolescents may be given benztropine mesylate, 1-2 mg/day, in divided doses. For younger children, dose reduction is a preferred strategy, given the cognitive side effects of anticholinergic medications. Chronic parkinsonian symptoms are often drastically under recognized by clinicians and may impair age-appropriate activities and speech articulation.Akathisia may be especially difficult to identify in young patients or those with limited verbal abilities and may lead to nonadherence to treatment.

Tardive and Withdrawal Dyskinesias

Tardive or withdrawal dyskinesias, some transient but others irreversible, mandate caution regarding the use of these drugs for less severe indications. Tardive dyskinesia has been reported not only with the first-generation antipsychotic agents, but also in youths treated with SGAs (Kumra et al. 1998). In children with autism spectrum disorder or Tourette's disorder, it may be especially difficult to distinguish medication-induced movements from those characteristic of the disorder. Patients should be examined carefully for abnormal movements by using a scale such as the Abnormal Involuntary Movement Scale (AIMS 1988) before and at intervals while taking an antipsychotic medication. Parents and patients (as appropriate) should receive regular explanations of the risk of movement disorders.

Cardiovascular Side Effects

ECG monitoring at baseline and during dose titration of medications that are of higher risk is indicated. Antipsychotic medications have been associated with prolongation of the QTc interval, torsades de pointes, and sudden death. Thioridazine has a "black box" warning of risk of QTc prolongation and sudden death. Haloperidol has been associated with torsades de pointes. Ziprasidone can result in QTc prolongation that is greater than with most other antipsychotic agents and concerns remain regarding possible serious cardiac events. The use of clozapine has been associated with the development of cardiomyopathy, myocarditis, and pericarditis.

Metabolic Side Effects

Weight gain may be problematic with the use of SGAs, and it appears that children are more likely to be severely affected by this side effect than are adults. Weight gain appears to be greatest with olanzapine and least with ziprasidone, with others having variable and intermediate effects. Calculation of BMI helps distinguish weight gain due to antipsychotic use from normal growth-related weight gain and should be done before initiation of treatment with antipsychotic agents and at regular intervals thereafter.

Baseline measurement of fasting blood sugar, with occasional measurements thereafter, is recommended for patients treated with SGAs, because increases in fasting blood glucose and insulin resistance and development of type 2 diabetes may result. Prudence would suggest especially cautious use of these agents in children who are already overweight or who have a strong family history of diabetes. Because SGAs are associated with increases in cholesterol and triglycerides, blood lipids should be monitored throughout treatment, based on patient's baseline levels and family history. Given the chronic nature of the disorders treated with SGAs, it is appropriate to be concerned about the development of metabolic syndrome in patients who may have many years of treatment.

Other Side Effects

Hyperprolactinemia may occur with any antipsychotic agent, although this potential is theoretically lower with the SGAs. Hyperprolactinemia has been associated with galactorrhea, menstrual irregularities, sexual dysfunction, and osteoporosis. While SGAs, especially risperidone, usually elevate the prolactin level early in treatment, the level usually returns to normal or near-normal with prolonged treatment and it is only rarely associated with symptoms of hyperprolactinemia.

With first- or second-generation antipsychotic agents, behavioral drug toxicity can occur, manifested as worsening of preexisting symptoms or development of new symptoms such as hyperactivity or hypoactivity, irritability, apathy, withdrawal, stereotypies, or tics. Sedation can interfere with the patient's ability to benefit from school. Children may be at greater risk of antipsychotic-induced seizures than adults because of their immature nervous systems and the high prevalence of abnormal EEGs in seriously disturbed children.

Potentially fatal neuroleptic malignant syndrome has been reported in children and adolescents, with a presentation similar to that seen in adults. Anticholinergic side effects such as hypotension, dry mouth, constipation, nasal congestion, blurred vision, and urinary retention are most commonly experienced with low-potency first-generation antipsychotics and appear to be unusual in children.

Anxiolytics

Benzodiazepines

Little research has been done on the use of benzodiazepines for pediatric psychiatric conditions, but anxiety is usually more appropriately treated by therapy and/or an SSRI. Clonazepam (at 0.5-3.0 mg/day) may be useful in the treatment of panic disorder when symptoms are not adequately controlled by an SSRI. Adverse effects of these drugs include substance abuse, physical or psychological dependence, sedation, and cognitive dulling. Paradoxical or disinhibition reactions may occur, manifested by acute excitation, irritability, increased anxiety, hallucinations, and increased aggression and hostility.

Buspirone

Buspirone is a nonbenzodiazepine anxiolytic that is less sedating and has less risk of abuse or dependence than do the benzodiazepines. Reports on buspirone treatment of anxiety disorders in children are anecdotal and controlled trials have not been done.

Sedative-Hypnotics and Other Sleep Aids

While "behavioral insomnia" in children is very common and should be treated behaviorally and by attention to sleep hygiene, there are cases where pharmacological treatment, preferably short-term, is appropriate. The most commonly prescribed medication for insomnia in children is clonidine, presumably, at least in part, because so many children with ADHD have trouble falling asleep. This medication was discussed in an earlier section, "Alpha₂-Noradrenergic Agonists." When used for sleep, the immediate-release form is given at bedtime only.

Melatonin

Melatonin, available without a prescription, is frequently used for difficulty with sleep initiation in children, especially when a circadian rhythm disturbance results in late sleep onset and difficulty getting up in time for school. The fact that it is a natural hormone and does not result in tolerance or dependence makes it an appealing treatment to both the parents and the physician. It is also well tolerated and no significant side effects have been reported, although magnitude of effect is generally modest. The usual dose is 3 mg given approximately 30 minutes before the desired bedtime. Melatonin is sold as a non-FDA regulated supplement, so caution is needed to be sure that a high-quality brand is purchased to assure potency and absence of impurities.

Sedative-Hypnotics

The nonbenzodiazepine sedative-hypnotics eszopiclone, zaleplon, and zolpidem are occasionally used in the adolescent population. There is very little research on these medications in the pediatric population, and they are best used for short-term treatment and in conjunction with behavioral treatment, attention to sleep hygiene, and treatment of any underlying mood or anxiety problems.

Psychotherapy

Recent years have seen an increasing focus on empirical studies of the efficacy of psychotherapy. While psychotherapy for children has been shown to be effective when performed in a research setting (Kazdin 2000), the results are often less favorable in the usual clinical setting (Weisz and Jensen 2001). Compared with children seen in research environments, children seen in "real world" practice are often more symptomatic, have comorbid conditions, have more psycho-socially stressed families, and receive less structured forms of psychotherapy (Kazdin 2000). Challenges include accounting for the many influences in children's lives that affect treatment and functioning, as well as determining what (or who) should be the focus of change (e.g., parent, child, style of parenting).

Psychotherapies may be classified according to theoretical model, target of intervention, duration, or goals of treatment. There are more than 500 specific therapeutic techniques used in child and adolescent psychotherapy (Kazdin 2000). Data are emerging regarding the use and efficacy of specific forms of psychotherapy for particular disorders, especially depressive and anxiety disorders. The following sections describe, in very general terms, some of the more common forms of psychotherapy used in children. More thorough descriptions of models of psychotherapy as they are applied to youth and families may be found in specific treatment manuals.

In the treatment of children, it is essential to consider the patient's environment and family dynamics. In most cases, work with parents and school, and often pediatricians, welfare agencies, courts, or recreation leaders, must accompany individual therapy. The cooperation of parents, and often teachers, is required to maintain the child in treatment and to remove any secondary gain resulting from the symptoms. The therapist must be aware of a patient's level of physical, cognitive, and emotional development in order to understand the symptoms, set appropriate goals, and tailor effective interventions.

Communication With Children and Adolescents

Children are less able to use abstract language than are adults. They use play to express feelings, to narrate past events, to work through trauma, and to seek comfort. It is less threatening and anxiety provoking if the therapist uses the metaphor of the play and bases questions and comments on characters in the play rather than on the child (even if the connection is clear to the therapist). Effective communications are tailored to the child's stage of language, cognitive, and affective development. The therapist must be aware that the vocabulary of some bright and precocious children exceeds their emotional understanding of events and concepts. Dramatic play with dolls or puppets; drawing, painting, or modeling with clay; as well as questions about dreams, wishes, or favorite stories or movies, can provide access to children's fantasies, emotions, and concerns. Adolescents may prefer creative writing or more complex expressive art techniques.

The Uncooperative Child or Adolescent

It is not surprising that many children or adolescents do not cooperate in therapy, because most are brought to treatment by adults. These young patients often do not wish to change themselves or their behaviors and view their parents' and teachers' complaints as unreasonable or unfair. In addition, a child or adolescent may refuse to participate in or may attempt to sabotage therapy for a variety of psychological reasons. Effective interventions are tailored to the cause of the resistance.

A child who is feeling anxious or having difficulty separating from a parent may be helped by initially permitting the parent to remain in the therapy room. When a child or adolescent does not talk, whether from anxiety or opposition, the therapist may address this reluctance, either directly or through play. Long silences are not generally helpful and tend to increase anxiety or battles for control. Attractive play materials help to make therapy less threatening and to encourage participation while the therapist builds an alliance. However, the therapist must guard against the danger of sessions becoming mere play or recreation instead of therapy. A variety of techniques incorporate therapeutic activities with storytelling, drama, and game boards. Using behavioral contingencies in therapy also may improve motivation and cooperation.

Individual Psychotherapy

All individual therapies have certain common themes (Strupp 1973):

• Relationship with a therapist who is identified as a helping person and who has some degree of control and influence over the patient
• Instillation of hope and improved morale
• Use of attention, encouragement, and suggestion
• Goals of helping the patient to achieve greater control, competence, mastery, and/or autonomy; to improve coping skills; and to abandon or modify unrealistic expectations of himself or herself, others, and the environment

Supportive Therapy

The therapist provides support to the patient until a stressor resolves, a developmental crisis has passed, or the patient or environment changes sufficiently so that other adults can take on the supportive role. There is a real relationship with the therapist, who facilitates verbal expression of feelings and provides understanding and judicious advice.

Time-Limited Therapy

All of the models of time-limited therapy have in common a planned, relatively brief duration; a predominant focus on the presenting problem; a high degree of structure and attention to specific, limited goals; and active roles for both therapist and patient (Dulcan 1984; Dulcan and Piercy 1985). Length of treatment varies from several sessions to 6 months. The short duration is used to increase patient motivation, participation, and reliance on resources within the patient's world rather than on the therapist. Time-limited treatment has been recommended for both multi-problem families in crisis who are unlikely to persist in longer-term treatment and for well-functioning children and families who have circumscribed problems of relatively recent onset. Following a course of time-limited treatment, children or families may return to the therapist for an additional "round" of treatment if other problems or symptoms develop. Or, following planned termination of therapy, one or two "booster" sessions may be used to reinforce skills and maintain improvement.

Interpersonal Psychotherapy

A 12-week model of interpersonal psychotherapy for depressed adolescents (IPT-A) has been elaborated in a treatment manual (Mufson et al. 2004a) and has demonstrated efficacy in several controlled studies (Mufson et al. 2004b). IPT treatment focuses on improving interpersonal relationships in the lives of depressed adolescents through role clarification and enhanced communication.

Cognitive-Behavioral Therapy

CBT techniques adapted for children and adolescents have been shown in controlled trials to be efficacious in the treatment of anxiety disorders. Results in the treatment of depression are somewhat less consistent, but CBT is considered to be an important treatment option for depressed adolescents. Therapy manuals are available for treatment of anxiety or depression, adapted to the cognitive level of school-age children or adolescents (Chorpita 2007). The anxiety treatment programs are based on development of a hierarchy of fears, which are to be gradually faced and conquered. The depression treatments involve techniques such as examining and changing cognitive distortions regarding the world and relationships, social problem solving, behavioral activation, and goal-setting. All include significant psychoeducation for both the child and parents. Trauma-focused CBT is the preferred, empirically supported, treatment approach for youth suffering from PTSD (Cohen et al. 2006). Cognitive-behavioral treatment using exposure and response prevention (E/RP) is the first-line treatment for mild to moderate OCD in children and adolescents (March et al. 2004).

Caution is needed to ensure that CBT homework assignments are not perceived as aversive when added to homework assigned in school. Prepubertal children's more concrete cognitive processes may make this model impractical, although creative adaptations and the incorporation of behavioral techniques can render this approach feasible.

Dialectical Behavioral Therapy

Dialectical behavioral therapy (DBT) has been modified for treatment of adolescents, especially those with suicidal or self-injurious behaviors, and involves a combination of individual, group and family treatment (Miller et al. 2007). Key components are development of coping skills and self-soothing techniques to help such patients modulate unstable affective states and reduce impulsive destructive behaviors. Family members are also actively involved in the treatment to improve their own coping skills and learn how to help their teen put his or her coping skills to good use. The availability of a therapist on-call is an important feature of this treatment, to address crises.

Motivational Interviewing

Motivational interviewing (MI; Miller and Rollnick 2002) is appropriate for treatment of adolescents, especially those with drug or alcohol problems, who are poorly motivated to acknowledge their problems or try to change. MI is a semi-directive therapy that seeks to resolve the patient's ambivalence about changing his or her behavior. It is a non-judgmental, non-confrontational approach that attempts to increase the adolescent's awareness of the problems caused by and the consequences and risks of the behavior in question. The treatment also tries to help the teen see a more positive future and become more motivated to reach it. The three key elements of MI are collaboration, not confrontation; evocation or drawing out, rather than imposing ideas; and autonomy as opposed to authority. The teen becomes more motivated to change as he or she sees that current behaviors will interfere with the accomplishment of his or her goals.

Psychodynamic Psychotherapies

Psychoanalysis is an infrequently used treatment modality for children and adolescents due to the expense, frequency of sessions, length of treatment, and often lack of prompt symptom relief.

Psychodynamically oriented psychotherapy (American Academy of Child and Adolescent Psychiatry 2012) is grounded in psychoanalytic theory but is more flexible and emphasizes the real relationship with the therapist and the provision of a corrective emotional experience. Frequency is typically once or twice a week, most commonly over a period of 1-2 years, although shorter, time-limited dynamic psychotherapies are also available. There is active collaboration between the parents and the therapist. Goals of therapy include symptom resolution, change in behavior, and return to normal developmental process. The therapist forms an alliance with the child or adolescent, reassures, promotes controlled regression, identifies feelings, clarifies thoughts and events, makes interpretations, judiciously educates and advises, and acts as an advocate for the patient.

Dynamically oriented individual therapy is more likely to be effective for children and adolescents who are in emotional distress or who are struggling to deal with a stressor than for those children with behavior problems. Children and adolescents with attention-deficit, oppositional, or conduct disorders rarely acknowledge their problem behaviors and are usually better treated in family or group therapy, by parent training in behavior management, or in a structured milieu. Youngsters with ADHD have little insight into their behavior and its effect on others, and they maybe genuinely unable to report their problems or to reflect on them. However, insight-oriented therapy may be useful for some of these youngsters to address comorbid anxiety or depression or symptoms resulting from trauma.

Parent Counseling

Parent counseling or guidance is a psychoeducational intervention. It may be conducted with a single parent or couple, or in groups. Parents are taught about normal child and adolescent development. Efforts are made to help parents better understand their child and his or her problems and to modify practices that may be contributing to the current difficulties (whatever their original cause). It is essential that the therapist understand the parents' point of view and their hardships, including those that result from parenting a child with a psychiatric disorder. For some parents who have serious difficulties of their own, parent counseling may merge into or pave the way for individual treatment of the adult or conjoint couple therapy.

Virtually all parents of children with psychiatric or learning problems benefit from education in the nature of their children's disorders, support of their own emotional needs, and help in selecting treatments and managing difficult behaviors. Parents of children with chronic problems must become skilled advocates to ensure that their children receive the treatment and schooling they need. Carefully selected books and Web sites may be useful to parents.

Behavior Therapy

Behavior therapy is by far the most thoroughly evaluated psychological treatment for children. Maximally effective programs require home and school cooperation, focus on specific target behaviors, and ensure that contingencies follow behavior quickly and consistently. In behavior therapy, symptoms are viewed as resulting from bad habits, faulty learning, or inappropriate environmental responses to behavior. Behavioral approaches are characterized by detailed assessment of problematic emotional or behavioral responses and the environmental conditions that elicit and maintain them, the development of strategies to produce change in the environment and therefore in the patient's behavior, and repeated assessment to evaluate the success of the intervention. Behavior therapy is the most effective treatment for simple phobias, for enuresis and encopresis, and for the noncompliant behaviors seen in ODD and conduct disorder. For youngsters with ADHD, behavior modification can improve both academic achievement and behavior, if specifically targeted. Both punishment (time-out and response cost) and reward components are required. Behavior modification is more effective than medication in improving peer interactions, but skills may need to be taught first. Many youngsters require behavioral programs that are consistent, intensive, and prolonged (months to years). A wide variety of other childhood problems, such as motor and vocal tics, trichotillomania, and sleep problems, are treated by behavior modification, either alone or in combination with pharmacotherapy. Applied behavioral analysis (ABA) is indicated for most youth with autism spectrum disorders.

The greatest weaknesses of behavior therapy are lack of maintenance of improvement over time and failure of changes to generalize to situations other than the ones in which training occurred. Generalization and maintenance can be maximized by conducting training in the settings in which behavior change is desired, at multiple times and places, facilitating transfer to naturally occurring reinforcers, and gradually fading reinforcement on an intermittent schedule.

Parent Management Training

Effective training packages have been developed for parents of noncompliant, oppositional, and aggressive children (Barkley 2013; Forehand and Long 2002; McMahon and Forehand 2003) and delinquent adolescents. Parents are taught to give clear instructions, to positively reinforce good behavior, and to use punishment effectively. Time-out is a frequently used negative contingency for young children. The child is placed in a quiet, boring area where there is a "time-out" from attention or other positive reinforcement. Highly effective parent training programs combine instruction using multiple media with therapist modeling and coaching rehearsal of skills to be used. Families with low socioeconomic status, parental psychopathology (e.g., depression), marital conflict, and/or limited social support require maximally potent interventions, with attention to parental problems as necessary. Other families may be able to succeed with written materials only (see, for example, Green 2010; Kazdin 2009) or with manuals supplemented by group lectures.

Behavioral intervention can be done in the context of family therapy, in which the family learns how to negotiate and how to solve problems together. A key technique is parent-child contingency contracting, which entails a written social contract between parent and child to change behaviors in both parties, with specified contingencies (Blechman 1981).

Parent-Child Interaction Therapy (PCIT) has been shown to be effective in reducing disruptive behaviors in children up to 7 years old. PCIT is based on both social learning theory and attachment theory. The two phases of treatment are child directed interaction and parent directed interaction. In the first phase, the parents practice PRIDE skills, which include praising the child's appropriate behavior, reflecting on appropriate talk, imitating appropriate play, describing appropriate behavior, and being enthusiastic. The parent in this stage is also encouraged to avoid the use of commands, questions or criticisms and to ignore minor misconduct and to stop play for aggressive misconduct. In the next phase, the parent is taught how to give effective commands, such as emphasizing being specific, giving one command at a time, doing so in positive terms (telling child what to do as opposed to what not to do), using age-appropriate directions, being polite and respectful, and being direct (avoiding asking "can you" or "will you") (Brinkmeyer and Eyberg 2003). The therapist provides in vivo coaching, providing immediate reinforcement and feedback for the parent. Other empirically supported parental behavior training programs are Positive Parenting Program (Triple P) and Incredible Years.

Classroom Behavior Modification

Techniques for behavior modification in schools include token economies, class rules, and attention to positive behavior, as well as response cost programs in which reinforcers are withdrawn in response to undesirable behavior. Reinforcers such as positive recognition or stars on a chart may be dispensed by teachers or more tangible rewards or privileges by parents through the use of daily behavioral report cards. Even special education teachers rarely have sophisticated skills in behavior modification, and therapists may need to work closely with teachers and other school staff to develop appropriate programs. Effective programs for use in the classroom environment include the Academic and Behavioral Competencies (ABC) program (Pelham et al. 2005) and the Positive Behavior Support program (Sugai and Homer 2002).

Behavioral Treatment of Anxiety Disorders

Desensitization, in vivo or in fantasy, is the treatment of choice for simple phobias, often supplemented by modeling. The principles and techniques are essentially the same as those used with adults, with modification for developmental level. In vivo desensitization, often combined with contingency management and parent guidance, may be effective in the treatment of school avoidance (school phobia) resulting from separation anxiety disorder.

Family Treatment

Attempts to treat children and adolescents without considering their environment and relationships are unlikely to succeed. Any change in one family member, whether resulting from a psychiatric disorder, psychiatric treatment, a normal developmental process, or an outside event, is likely to affect family members and relationships. Family constellations vary widely, ranging from the traditional nuclear family to the single-parent family, a step-family, an adoptive or foster family, or a group home.

Evaluation of Families

Data should be gathered on each person living with the patient, as well as on others who may be important or have been so in the past (e.g., noncustodial parents, grandparents, siblings who are no longer living at home). It is often useful to have at least one session that includes all significant family members.

A family assessment includes identifying the stage of the family life cycle, whether the family is accomplishing the basic tasks needed for all families (Table 34-4), any problematic areas of family interaction that require intervention, and aspects of the child's development that may have been at risk due to impaired communication or poor role modeling by family members. Other goals of a family assessment are to define any areas of parental problem or psychopathology, identify vulnerable family members, and determine how the family may be either maintaining or compensating for a child's disorder. Family systems have become increasingly diverse, and extensive research describes variations in normal and dysfunctional family interactions (Walsh 2012).

Family Therapy

In the most general sense, family therapy is psychological treatment conducted with an identified patient and at least one biological or functional (e.g., by marriage, adoption) family member. Related techniques include therapy with an individual patient that takes a family systems perspective or therapy sessions with family members other than the identified patient, who is omitted due to refusal to participate, severity of illness, or other factors. There are an increasing number of empirically supported family-based treatments for child and adolescent emotional and behavioral problems (Sprenkle 2012). These include Patterson's (1975) behavioral family therapy, based on social learning theory, and Alexander's (1992) functional family therapy, both of which are used in the treatment of children and adolescents with conduct disorder. Multisystemic therapy includes energetic outreach into the home, neighborhood, and school and adds peer group and school-based interventions to family treatment of adolescent delinquents (Henggeler et al. 2009). Psychoeducational family therapy has been most extensively developed in the treatment of families of adult schizophrenic patients (Anderson et al. 1980), but it has been extended to a number of childhood disorders, such as ADHD, depression, and bipolar disorder.

Family therapy may be particularly useful when there are dysfunctional interactions or impaired communication within the family, especially when these appear to be related to the presenting problem. It also may be useful when symptoms seem to have been precipitated by difficulty with a developmental stage for an individual or the family or by a change in the family such as divorce or remarriage. If more than one family member is symptomatic, family therapy may be both more efficient and more effective than multiple individual treatments. Family therapy should be considered when one family member improves with treatment but another, not in treatment, worsens. In any case, the family must have, or be induced to have, sufficient motivation to participate. When the identified patient is relatively unmotivated to participate or to change, family therapy is likely to be more effective than individual therapy. Attention to family systems issues also may be useful when progress is blocked in individual therapy or in behavior therapy.

Source. Adapted from Fleck S: "A General Systems Approach to Severe Family Pathology." American Journal of Psychiatry 133:669-673, 1976.

If the family equilibrium is precarious or one or more family members are at serious risk of decompensation, family therapy may be useful in combination with other treatments, such as medication or hospitalization. Family sessions are not indicated when a parent has severe, intractable, or minimally relevant psychopathology or when the child strongly prefers individual treatment. Children should not be included in sessions in which parents persist (despite redirection) in criticizing the children or in sharing inappropriate information, when the most critical need is marital therapy, or when parents primarily need specific, concrete help with practical affairs.

Group Therapy

Group therapy offers opportunities for the clinician to model and facilitate practice of important skills. Interventions by peers may be far more acute and powerful in their effect than those by an adult therapist, especially in the treatment of adolescents with substance abuse or eating disorders. In addition, the therapist can observe in vivo behavior with peers. Target symptoms for group therapy include absent or conflictual peer relationships, anxiety, depression, and deficits in social interactive and problem-solving skills. These problems often are not accessible to intervention in individual therapy sessions.

Inpatient and Residential Treatment

Inpatient or residential treatment is indicated only in emergencies or for youngsters who have not responded to outpatient treatment because of severity of the disorder, patient lack of motivation or refusal to cooperate with treatment, or inability of the patient and/or family to provide a structured environment for medication adherence.

Placement in a residential treatment center maybe indicated for children and adolescents with chronic behavior problems such as aggression, running away, truancy, substance abuse, school phobia, or self-destructive acts that the family, foster home, and/or community cannot manage or tolerate. Children for whom returning home is not advisable—because of factors in the patient, the family, or both—maybe referred to a residential treatment center following a hospital stay.

Short-term hospitalization (5-10 days) is typically an acute intervention, stemming from immediate physical danger to self or others; acute psychosis; a crisis in the environment that reduces the ability of the caregiving adults to cope with the child or adolescent; or the need for more intensive, systematic, and detailed evaluation and observation of the patient and family than is possible on an outpatient basis or in a day program. The typically brief hospital stay emphasizes rapid evaluation (including medical and neurological, when indicated), crisis intervention and stabilization, and development of a treatment plan to be implemented elsewhere. The goal is not to eliminate all psychopathology but to address the "focal problem" that precipitated hospitalization and then to discharge the patient to home, residential treatment, or foster placement, where he or she can receive ongoing outpatient or day treatment as part of a comprehensive treatment plan (Harper 1989).

Inpatient or residential treatment includes multiple interventions, set in a therapeutic milieu with a structured schedule for meals, sleep, school, recreation, and self-care activities. Most settings include a token economy or levels program, which also may be used for specific treatment or for management of behavior (e.g., encouraging a patient with anorexia nervosa to eat).

Hospitalization offers an ideal opportunity for systematic trials of medication in patients who have not responded to conventional treatment; whose illness is diagnostically puzzling; who have medical problems complicating pharmacotherapy; or whose parents are noncompliant, disorganized, or unreliable reporters of efficacy or side effects. In the hospital setting, the response to treatment can be constantly observed and side effects promptly managed. As-needed (i.e., prn) medications administered to control aggression or other behavior problems should be used only for brief periods until more effective, ongoing treatments are begun.

Regularly scheduled individual sessions with a therapist are essential in developing a more complete understanding of the patient's psychological, familial, and social dynamics and in assisting him or her to develop more adaptive methods of coping with strong emotions. In addition to general or special topic groups (e.g., twelve-step models, survivors of abuse), group therapy may include community meetings in which privileges and rules are decided, social skills are practiced, and patients learn to observe their own and others' behavior and to recognize the impact of their behavior on others. Work with families is an essential part of hospital treatment, including in vivo evaluation of family functioning and deciding where the child should reside. Interventions may include family therapy, parent counseling in behavior management, and education about child development and their child's disorder. Parents may require referral for marital therapy, individual medical or psychiatric assessment and treatment, or help with housing or income.

Virtually all children who require psychiatric hospitalization have had problems in school. The small classes and highly trained teachers of a hospital unit can provide a detailed evaluation of a youngster's academic strengths and weaknesses by direct observation of classroom behavior and learning. Educational strategies can be developed and tested.

Key elements of discharge planning are arranging for an appropriate educational placement and transitioning back to school.

Partial Hospitalization

Partial hospitalization (day treatment) may be best for the child who requires more intensive intervention than can be provided in outpatient visits but who is able to live at home. Partial hospitalization is less restrictive for the patient than inpatient treatment or residential placement. It can offer an opportunity for more intensive work with parents, who may attend the program on a regular basis. The daily transitions between home and the treatment program may enhance parent participation and home-based strategies. Partial hospitalization may be used as a "step-down" for a child who has been hospitalized or to avert a hospitalization.

Day treatment programs involve a full day, 5 days a week, and include a school or therapeutic nursery school program. Other programs, such as intensive outpatient (IOP) or "partial day" programs, may meet in the late afternoon and evening hours after patients attend community schools. It is desirable to offer the same treatment modalities as an inpatient unit.

Innovative, intensive summer treatment programs have been developed for children with ADHD and associated behavior and learning problems (Pelham et al. 2000). These programs provide positive social and recreational experiences for children who otherwise would not be able to participate in camp, while teaching parents behavior modification techniques, supplementing classroom work, and rigorously assessing medication efficacy and side effects.

Adjunctive Treatments

Parent Support Groups

Parents of children with psychiatric disorders, together with mental health professionals and teachers, have established groups that provide education and support for parents, as well as advocacy for services and fund-raising for research. National organizations with local chapters and extensive Web-based resources include Parents Anonymous, for abusive or potentially abusive parents; Autism Society; Children and Adults with Attention Deficit Hyperactivity Disorders (CHADD); the Learning Disabilities Association of America; and the National Alliance on Mental Illness (NAMI).

Special Education

Modified school programs range in intensity from tutoring or resource classrooms several hours a week to special classrooms in mainstream schools to public or private schools that serve only children with special educational needs and even therapeutic boarding schools. The federal Individuals with Disabilities Education Act (IDEA) requires that children who need them receive special services, provided in the least restrictive environment (i.e., as much in the mainstream with other children and adolescents as possible). An Individualized Education Program (IEP) is developed and describes the nature of the educational or developmental disability, the short-term and annual goals of treatment, and the specific educational or therapeutic interventions to be used. A 504 plan (named after Section 504 of the Rehabilitation Act of 1973, the first civil-rights statute for persons with disabilities) is another federally mandated option for obtaining accommodations in school for a child's disabilities.

Recreation

Learning a sport or skill and/or establishing a relationship with an adult such as a Big Brother or a YMCA counselor provides an opportunity in a supervised setting to improve peer relationships and self-esteem. A high school or college student may be employed to teach social and sports skills, provide structured time, and assist with homework. Day or overnight summer camps may be useful. Some youngsters can attend a regular camp, whereas others need a special program for children and adolescents with psychiatric or medical problems.

Foster Care

Placement in a foster home may be needed when parents are unwilling or unable to care for a child. Indications are clearest in cases of physical neglect or physical or sexual abuse. Other families may be unable to provide the appropriate emotional or physical environment. Court intervention is required for placement. Children with severe behavioral or physical problems or older adolescents who are difficult to place or maintain in foster or adoptive homes may be admitted to group homes. These homes vary in staffing and intensity of their programs. Some approach residential treatment, whereas others simply provide a supervised residence.

Dietary Treatments

Since the mid-1970s, advocates of dietary treatment of behavioral problems have been remarkably persistent, despite minimal scientific evidence. The Feingold Diet (which removes all foods containing natural salicylates, as well as a long list of additives) has been shown to have a small positive effect in a subset of young children with ADHD, but it is very difficult to maintain the diet. There are no scientific data to support dietary treatments for autism spectrum disorder.

Some parents and primary care practitioners find dietary treatment appealing because it is more "natural" than medication. However, special diets demand extra work and often additional expense from a family already disrupted by a child's behavior problems. Given the minimal evidence of efficacy and the extreme difficulty inducing children to comply with restricted diets, such diets should not be recommended. Families who insist on trying a diet should be permitted to do so, provided the diet is nutritionally sound, because initial attempts to dissuade them may disrupt the therapeutic alliance.

A thorough meta-analysis (Wolraich et al. 1995) put to rest the notion that dietary sugar contributes to hyperactivity. Caffeine, in the form of coffee or cola, has significant side effects and no demonstration of efficacy for the treatment of hyperactivity.

Integration of Multiple Modalities

Sophisticated simultaneous or sequential use of different techniques offers substantial promise of improved treatment outcome. There is often a need for more power and Wider coverage of symptoms than any single treatment alone provides. For many disorders, data support the potential synergistic effect of combining medication with psychotherapeutic interventions. For example, the combination of CBT and pharmacotherapy has been shown to be particularly effective in treating pediatric depression and OCD (March et al. 2004, 2006). Adding CBT improves the response rate in patients with OCD who have a partial response to a serotonin reuptake inhibitor (Franklin et al. 2011).

In the treatment of ADHD, combining medication management, behavioral interventions, parent management training, appropriate school placement and school-based interventions, and social skills training is often recommended for more severe cases and can be demonstrated to be effective in the short term. However, in the NIMH MTA study (MTA Cooperative Group 1999), the combination of protocol-based medication and intensive behavioral interventions was not significantly more beneficial for core ADHD symptoms than was protocol-based medication treatment alone. However, for children with ADHD who have comorbid anxiety or psychosocial impairments, supplementing pharmacotherapy with behavioral treatments appears to yield additive benefits (Jensen et al. 2000) as well as addressing symptoms not treatable by medication and perhaps permitting lower doses of medication to achieve the same positive effect.

Children with autism spectrum disorder require a comprehensive therapeutic plan that may include psychoeducation of the parents and family, special education placement, speech and language therapies, behavior modification (ABA), social skills training, and pharmacotherapy. Although families often request or implement complementary or alternative treatments, few such treatments have empirical support (Lofthouse et al. 2012).

Conclusion

The treatment of psychiatric disorders in children and adolescents is both an art and a science. Research on assessment and diagnosis, biological correlates of disorders, and outcome of traditional and newly developed techniques will continue to improve the specificity and outcome of treatment. However, a need always will exist for clinical skills in tailoring and applying therapeutic techniques to individual patients and their families.

Key Clinical Points

• Treatment of pediatric psychiatric patients requires expertise in psychiatric evaluation and case formulation, effective use of complex treatment strategies, and a respect for the principles of informed consent and confidentiality.
• An understanding of human development is key to the successful treatment of pediatric psychiatric patients, to include an appreciation of the differences between youngsters and adults as well as the developmental differences among children of all ages.
• Ideally, treatments identified specifically for children and adolescents should reflect evidence-based practices. However, many have been developed by applying known effective adult treatments to the pediatric population.
• Decisions regarding the use of psychoactive medications in children, as in adults, are best supported through double-blind, placebo-controlled efficacy trials and through the collection of longitudinal data regarding medication safety. Clinicians should avoid the routine use of medication in youngsters that is based solely on case reports or uncontrolled (open) drug trials.
• Parents should be carefully informed of the presence or absence of scientific evidence supporting the use of a specific medication in a child, as well as that medication's possible side effects and adverse effects.
• Stimulant medications are safe and effective as first-line treatment for ADHD.
• A variety of empirically supported psychotherapy models are now available for the treatment of disorders in child mental health.
• Although each psychotherapy is based on its own theoretical constructs and therapeutic principles, all psychotherapies share the importance of the relationship with the therapist, an emphasis on hopefulness, the use of therapist attention and suggestion, and the expectation of change in one or more realms—cognition, behavior, sense of self, or emotional experience.

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Suggested Readings

Barkley RA: Attention-Deficit Hyperactivity Disorder: A Handbook for Diagnosis and Treatment, 3rd Edition. New York, Guilford, 2006

Dulcan MK (ed): Helping Parents, Youth, and Teachers Understand Medications for Behavioral and Emotional Problems: A Resource Book of Medication Information Handouts, 3rd Edition. Washington, DC, American Psychiatric Publishing, 2007

Dulcan MK (ed): Dulcan's Textbook of Child and Adolescent Psychiatry. Washington, DC, American Psychiatric Publishing, 2010

Dulcan MK, Lake MB: Concise Guide to Child and Adolescent Psychiatry, 4th Edition. Washington, DC, American Psychiatric Publishing, 2012

Martin A, Scahill L, Kratochvil CJ (eds): Pediatric Psychopharmacology: Principles and Practice, 2nd Edition. New York, Oxford University Press, 2011

McVoy M, Findling RL (eds): Clinical Manual of Child and Adolescent Psychopharmacology, 2nd Edition. Washington, DC, American Psychiatric Publishing, 2013