Journal 7

CLINICAL REPORT

Management of Children With Autism Spectrum Disorders Scott M. Myers, MD, Chris Plauché Johnson, MD, MEd, the Council on Children With Disabilities

ABSTRACT Pediatricians have an important role not only in early recognition and evaluation of autism spectrum disorders but also in chronic management of these disorders. The primary goals of treatment are to maximize the child’s ultimate functional independence and quality of life by minimizing the core autism spectrum disorder features, facilitating development and learning, promoting socialization, reducing maladaptive behaviors, and educating and supporting families. To assist pediatri- cians in educating families and guiding them toward empirically supported inter- ventions for their children, this report reviews the educational strategies and associated therapies that are the primary treatments for children with autism spectrum disorders. Optimization of health care is likely to have a positive effect on habilitative progress, functional outcome, and quality of life; therefore, important issues, such as management of associated medical problems, pharmacologic and nonpharmacologic intervention for challenging behaviors or coexisting mental health conditions, and use of complementary and alternative medical treatments, are also addressed.

INTRODUCTION The term autism spectrum disorders (ASDs) has been used to include the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR)1

diagnostic categories autistic disorder, Asperger disorder, and pervasive develop- mental disorder–not otherwise specified.2 Recent estimates of the prevalence of ASDs are in the range of 6.5 to 6.6 per 1000, and pediatricians, therefore, are likely to care for children and adolescents with these diagnoses.3–5 In the companion document to this clinical report,2 the American Academy of Pediatrics has sum- marized pertinent background information on ASDs and emphasized the impor- tance of surveillance and screening as well as other potential physician roles in the diagnostic process. However, the role of the primary health care professional extends beyond recognizing signs of ASDs, referring for diagnostic evaluation, conducting an etiologic investigation, providing genetic counseling, and educating caregivers about ASDs and includes ongoing care and management.

ASDs, similar to other neurodevelopmental disabilities, are generally not “cur- able,” and chronic management is required. Although outcomes are variable and specific behavioral characteristics change over time, most children with ASDs remain within the spectrum as adults and, regardless of their intellectual func- tioning, continue to experience problems with independent living, employment, social relationships, and mental health.6–8 The primary goals of treatment are to minimize the core features and associated deficits, maximize functional indepen-

www.pediatrics.org/cgi/doi/10.1542/ peds.2007-2362

doi:10.1542/peds.2007-2362

All clinical reports from the American Academy of Pediatrics automatically expire 5 years after publication unless reaffirmed, revised, or retired at or before that time.

The guidance in this report does not indicate an exclusive course of treatment or serve as a standard of medical care. Variations, taking into account individual circumstances, may be appropriate.

KeyWords autism, autism spectrum disorders, Asperger syndrome, pervasive developmental disorders, complementary and alternative medicine, early intervention

Abbreviations ASD—autism spectrum disorder TEACCH—Treatment and Education of Autistic and Related Communication Handicapped Children ABA—applied behavior analysis DTT—discrete trial training DIR—developmental, individual- difference, relationship-based RDI—relationship-development intervention RT—responsive teaching SI—sensory integration EEG—electroencephalography SSRI—selective serotonin-reuptake inhibitor CAM—complementary and alternative medicine

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). Copyright © 2007 by the American Academy of Pediatrics

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Guidance for the Clinician in Rendering Pediatric Care

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dence and quality of life, and alleviate family distress. Facilitating development and learning, promoting social- ization, reducing maladaptive behaviors, and educating and supporting families can help accomplish these goals. Ideally, interventions should help mitigate the core fea- tures of ASDs, which include impairment in social reci- procity, deficits in communication, and restricted, repet- itive behavioral repertoire.

Educational interventions, including behavioral strat- egies and habilitative therapies, are the cornerstones of management of ASDs. These interventions address com- munication, social skills, daily-living skills, play and lei- sure skills, academic achievement, and maladaptive be- haviors.

Optimization of medical care is also likely to have a positive impact on habilitative progress and quality of life. In addition to routine preventive care and treatment of acute illnesses, management of sleep dysfunction, coexisting challenging behaviors or psychiatric condi- tions, and associated medical problems, such as seizures, may be particularly important. Medications have not been proven to correct the core deficits of ASDs and are not the primary treatment. However, associated mal- adaptive behaviors or psychiatric comorbidities may in- terfere with educational progress, socialization, health or safety, and quality of life. These behaviors may be ame- nable to psychopharmacologic intervention or, in some cases, treatment of underlying medical conditions that are causing or exacerbating the behaviors. Effective medical management may allow a child with an ASD to benefit more optimally from educational interventions.

EDUCATIONAL INTERVENTIONS Education has been defined as the fostering of acquisi- tion of skills and knowledge to assist a child to develop independence and personal responsibility; it encom- passes not only academic learning but also socialization, adaptive skills, communication, amelioration of interfer- ing behaviors, and generalization of abilities across mul- tiple environments.9 Physicians and other clinicians are often in a position to guide families to empirically sup- ported practices and help them evaluate the appropri- ateness of the educational services that are being offered.

Comprehensive Programs for Young Children In the last 2 decades, research and program development in the area of educational intervention have focused largely on very young children with ASDs because of earlier identification and evidence that early intensive intervention may result in substantially better out- comes.9,10 Model early childhood educational programs for children with ASDs have been described in thorough reviews.9,11,12 These model programs are often catego- rized as behavior analytic, developmental, or structured teaching on the basis of the primary philosophical ori- entation. Although the approaches have important dif-

ferences, they also overlap. For example, contemporary comprehensive behavioral curricula borrow from devel- opmental or cognitive approaches (such as addressing joint attention, reciprocal imitation, symbolic play, and theory of mind and using indirect language stimulation and contingent imitation techniques), and some devel- opmental models (eg, the Denver model) and the struc- tured teaching approach of the Treatment and Education of Autistic and Related Communication Handicapped Children (TEACCH) program use behavioral techniques to fulfill their curriculum goals.10,13

Although programs may differ in philosophy and rel- ative emphasis on particular strategies, they share many common goals, and there is a growing consensus that important principles and components of effective early childhood intervention for children with ASDs include the following9,10,14–16:

● entry into intervention as soon as an ASD diagnosis is seriously considered rather than deferring until a de- finitive diagnosis is made;

● provision of intensive intervention, with active en- gagement of the child at least 25 hours per week, 12 months per year, in systematically planned, develop- mentally appropriate educational activities designed to address identified objectives;

● low student-to-teacher ratio to allow sufficient amounts of 1-on-1 time and small-group instruction to meet specific individualized goals;

● inclusion of a family component (including parent training as indicated);

● promotion of opportunities for interaction with typi- cally developing peers to the extent that these oppor- tunities are helpful in addressing specified educational goals;

● ongoing measurement and documentation of the in- dividual child’s progress toward educational objec- tives, resulting in adjustments in programming when indicated;

● incorporation of a high degree of structure through elements such as predictable routine, visual activity schedules, and clear physical boundaries to minimize distractions;

● implementation of strategies to apply learned skills to new environments and situations (generalization) and to maintain functional use of these skills; and

● use of assessment-based curricula that address:

● functional, spontaneous communication;

● social skills, including joint attention, imitation, re- ciprocal interaction, initiation, and self-manage- ment;

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● functional adaptive skills that prepare the child for increased responsibility and independence;

● reduction of disruptive or maladaptive behavior by using empirically supported strategies, including functional assessment;

● cognitive skills, such as symbolic play and perspec- tive taking; and

● traditional readiness skills and academic skills as de- velopmentally indicated.

Specific Strategies A variety of specific methodologies are used in educa- tional programs for children with ASDs. Detailed re- views of intervention strategies to enhance communica- tion,9,17–20 teach social skills,21–24 and reduce interfering maladaptive behaviors21,25,26 have been published in re- cent years. Brief descriptions of selected methodologies are provided below.

Applied Behavior Analysis Applied behavior analysis (ABA) is the process of apply- ing interventions that are based on the principles of learning derived from experimental psychology research to systematically change behavior and to demonstrate that the interventions used are responsible for the ob- servable improvement in behavior. ABA methods are used to increase and maintain desirable adaptive behav- iors, reduce interfering maladaptive behaviors or narrow the conditions under which they occur, teach new skills, and generalize behaviors to new environments or situ- ations. ABA focuses on the reliable measurement and objective evaluation of observable behavior within rele- vant settings including the home, school, and commu- nity. The effectiveness of ABA-based intervention in ASDs has been well documented through 5 decades of research by using single-subject methodology21,25,27,28 and in controlled studies of comprehensive early intensive behavioral intervention programs in university and community settings.29–40 Children who receive early in- tensive behavioral treatment have been shown to make substantial, sustained gains in IQ, language, academic performance, and adaptive behavior as well as some measures of social behavior, and their outcomes have been significantly better than those of children in control groups.31–40

Highly structured comprehensive early intervention programs for children with ASDs, such as the Young Autism Project developed by Lovaas35,41 at the University of California Los Angeles, rely heavily on discrete trial training (DTT) methodology, but this is only one of many techniques used within the realm of ABA. DTT methods are useful in establishing learning readiness by teaching foundation skills such as attention, compliance, imitation, and discrimination learning, as well as a vari- ety of other skills. However, DTT has been criticized

because of problems with generalization of learned be- haviors to spontaneous use in natural environments and because the highly structured teaching environment is not representative of natural adult-child interactions. Traditional ABA techniques have been modified to ad- dress these issues. Naturalistic behavioral interventions, such as incidental teaching and natural language para- digm/pivotal response training, may enhance generali- zation of skills.13

Functional behavior analysis, or functional assess- ment, is an important aspect of behaviorally based treat- ment of unwanted behaviors. Most problem behaviors serve an adaptive function of some type and are rein- forced by their consequences, such as attainment of (1) adult attention, (2) a desired object, activity, or sensa- tion, or (3) escape from an undesired situation or de- mand. Functional assessment is a rigorous, empirically based method of gathering information that can be used to maximize the effectiveness and efficiency of behav- ioral support interventions.42 It includes formulating a clear description of the problem behavior (including fre- quency and intensity); identifying the antecedents, con- sequences, and other environmental factors that main- tain the behavior; developing hypotheses that specify the motivating function of the behavior; and collecting direct observational data to test the hypothesis. Func- tional analysis also is useful in identifying antecedents and consequences that are associated with increased frequency of desirable behaviors so that they can be used to evoke new adaptive behaviors.

Structured Teaching The TEACCH method, developed by Schopler and col- leagues,43 emphasizes structure and has come to be called “structured teaching.” Important elements of structured teaching include organization of the physical environment, predictable sequence of activities, visual schedules, routines with flexibility, structured work/ac- tivity systems, and visually structured activities.43 There is an emphasis on both improving skills of individuals with ASDs and modifying the environment to accom- modate their deficits. Several reports have documented progress in children who have received TEACCH ser- vices as well as parent satisfaction and improvement in parent teaching skills, but these reports were not from controlled studies of treatment outcomes.44–49 In a con- trolled trial, Ozonoff and Cathcart50 found that children treated with a TEACCH-based home program for 4 months in addition to their local day treatment programs improved significantly more than children in the control group who received local day treatment services only.

Developmental Models Developmental models are based on use of developmen- tal theory to organize hypotheses regarding the funda- mental nature of ASDs and design approaches to address

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the deficits. The Denver model, for example, is based largely on remediating key deficits in imitation, emotion sharing, theory of mind, and social perception by using play, interpersonal relationships, and activities to foster symbolic thought and teach the power of communica- tion.12 This program has shifted from a center-based treatment unit to service delivery in homes and inclusive school environments. Several studies have demon- strated improvements in cognitive, motor, play, and so- cial skills beyond what would be expected on the basis of initial developmental rates in children who are treated according to the Denver model, but controlled trials are lacking.51–54

Relationship-focused early intervention models in- clude Greenspan and Wieder’s developmental, indi- vidual-difference, relationship-based (DIR) model,55

Gutstein and Sheely’s relationship-development inter- vention (RDI),56 and the responsive-teaching (RT) cur- riculum developed by Mahoney et al.57,58 The DIR ap- proach focuses on (1) “floor-time” play sessions and other strategies that are purported to enhance relation- ships and emotional and social interactions to facilitate emotional and cognitive growth and development and (2) therapies to remediate “biologically based processing capacities,” such as auditory processing and language, motor planning and sequencing, sensory modulation, and visual-spatial processing. Published evidence of the efficacy of the DIR model is limited to an unblinded review of case records (with significant methodologic flaws, including inadequate documentation of the inter- vention, comparison to a suboptimal control group, and lack of documentation of treatment integrity and how outcomes were assessed by informal procedures55) and a descriptive follow-up study of a small subset (8%) of the original group of patients.59 RDI focuses on activities that elicit interactive behaviors with the goal of engaging the child in a social relationship so that he or she discovers the value of positive interpersonal activity and becomes more motivated to learn the skills necessary to sustain these relationships.56 Some reviewers have praised the face validity of this model, which targets the core im- pairment in social reciprocity. However, the evidence of efficacy of RDI is anecdotal; published empirical scien- tific research is lacking at this time. One study reported beneficial effects of RT on young children with ASDs or other developmental disabilities.58 Parents were taught to use RT strategies to encourage their children to ac- quire and use pivotal developmental behaviors (atten- tion, persistence, interest, initiation, cooperation, joint attention, and affect). Children in both groups improved significantly on nonstandardized play-based measures of cognition and communication and standardized parent ratings of socioemotional functioning. Although a con- trol group was lacking and the potential role of concur- rent educational services was unclear, the improvements

were beyond what the authors expected from matura- tional factors alone.58

Speech and Language Therapy A variety of approaches have been reported to be effec- tive in producing gains in communication skills in chil- dren with ASDs.9,17,20 Didactic and naturalistic behavioral methodologies (eg, DTT, verbal behavior, natural lan- guage paradigm, pivotal response training, milieu teach- ing) have been studied most thoroughly, but there is also some empirical support for developmental-pragmatic approaches (eg, Social Communication Emotional Reg- ulation Transactional Support, Denver model, RDI, Hanen model).

People with ASDs have deficits in social communica- tion, and treatment by a speech-language pathologist usually is appropriate. Most children with ASDs can develop useful speech, and chronologic age, lack of typ- ical prerequisite skills, failure to benefit from previous language intervention, and lack of discrepancy between language and IQ scores should not exclude a child from receiving speech-language services.60 However, tradi- tional, low-intensity pull-out service delivery models often are ineffective, and speech-language pathologists are likely to be most effective when they train and work in close collaboration with teachers, support personnel, families, and the child’s peers to promote functional communication in natural settings throughout the day.60

The use of augmentative and alternative communi- cation modalities, including gestures, sign language, and picture communication programs, often is effective in enhancing communication.17,20,61 The Picture Exchange Communication System (PECS)62,63 is used widely. The PECS method incorporates ABA and developmental- pragmatic principles, and the child is taught to initiate a picture request and persist with the communication un- til the partner responds. Some nonverbal people with ASDs may benefit from the use of voice-output commu- nication aids, but published evidence for these aids is scant.20,64 Introduction of augmentative and alternative communication systems to nonverbal children with ASDs does not keep them from learning to talk, and there is some evidence that they may be more stimu- lated to learn speech if they already understand some- thing about symbolic communication.61,62,65

Social Skills Instruction There is some objective evidence to support traditional and newer naturalistic behavioral strategies and other approaches to teaching social skills.22–24,66–68 Joint atten- tion training may be especially beneficial in young, preverbal children with ASDs, because joint attention behaviors precede and predict social language develop- ment.69,70 A recent randomized, controlled trial demon- strated that joint attention and symbolic play skills can be taught and that these skills generalize to different

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settings and people.71 Families can facilitate joint atten- tion and other reciprocal social interaction experiences throughout the day in the child’s regular activities. Ex- amples of these techniques are described in the Ameri- can Academy of Pediatrics parent booklet “Understanding Autism Spectrum Disorders.”72

A social skills curriculum should target responding to the social overtures of other children and adults, initiat- ing social behavior, minimizing stereotyped persevera- tive behavior while using a flexible and varied repertoire of responses, and self-managing new and established skills.10 Social skills groups, social stories, visual cueing, social games, video modeling, scripts, peer-mediated techniques, and play and leisure curricula are supported primarily by descriptive and anecdotal literature, but the quantity and quality of research is increasing.10,15,73 A number of social skills curricula and guidelines are avail- able for use in school programs and at home.10,66,74,75

Occupational Therapy and Sensory Integration Therapy Traditional occupational therapy often is provided to promote development of self-care skills (eg, dressing, manipulating fasteners, using utensils, personal hy- giene) and academic skills (eg, cutting with scissors, writing). Occupational therapists also may assist in pro- moting development of play skills, modifying classroom materials and routines to improve attention and organi- zation, and providing prevocational training. However, research regarding the efficacy of occupational therapy in ASDs is lacking. Sensory integration (SI) therapy of- ten is used alone or as part of a broader program of occupational therapy for children with ASDs. The goal of SI therapy is not to teach specific skills or behaviors but to remediate deficits in neurologic processing and inte- gration of sensory information to allow the child to interact with the environment in a more adaptive fash- ion. Unusual sensory responses are common in children with ASDs, but there is not good evidence that these symptoms differentiate ASDs from other developmental disorders, and the efficacy of SI therapy has not been demonstrated objectively.76–78 Available studies are plagued by methodologic limitations, but proponents of SI note that higher-quality SI research is forthcoming.79

“Sensory” activities may be helpful as part of an overall program that uses desired sensory experiences to calm the child, reinforce a desired behavior, or help with transitions between activities.

Comparative Efficacy of Educational Interventions for Young Children All treatments, including educational interventions, should be based on sound theoretical constructs, rigor- ous methodologies, and empirical studies of efficacy.15

Proponents of behavior analytic approaches have been the most active in using scientific methods to evaluate their work, and most studies of comprehensive treat-

ment programs that meet minimal scientific standards involve treatment of preschoolers using behavioral ap- proaches.16,38 However, there is still a need for additional research, including large controlled studies with ran- domization and assessment of treatment fidelity. Empir- ical scientific support for developmental models and other interventions is more limited, and well-controlled systematic studies of efficacy are needed.

Most educational programs available to young chil- dren with ASDs are based in their communities, and often, an “eclectic” treatment approach is used, which draws on a combination of methods including applied behavior analytic methods such as DTT; structured teaching procedures; speech-language therapy, with or without picture communication or related augmentative or alternative communication strategies; SI therapy; and typical preschool activities. Three studies that compared intensive ABA programs (25–40 hours/week) to equally intensive eclectic approaches have suggested that ABA programs were significantly more effective.31,32,34 An- other study that involved children with ASDs and global developmental delay/mental retardation retrospectively compared a less intensive ABA program (mean: 12 hours) to a comparably intensive eclectic approach and found statistically significant but clinically modest out- comes that favored those in the ABA group.33 Although the groups of children were similar on key dependent measures before treatment began, these studies were limited because of parent-determined rather than ran- dom assignment to treatment group. Additional studies to evaluate and compare educational treatment ap- proaches are warranted.

Programs for Older Children and Adolescents Some model programs provide programming through- out childhood and into adulthood.11 More commonly, the focus of specialized programs is on early childhood, and published research evaluating comprehensive edu- cational programs for older children and adolescents with ASDs is lacking. However, there is empirical sup- port for the use of certain educational strategies, partic- ularly those that are based on ABA, across all age groups to increase and maintain desirable adaptive behaviors, reduce interfering maladaptive behaviors or narrow the conditions under which they occur, teach new skills, and generalize behaviors to new environments or situa- tions.13,21,28

When children with ASDs move beyond preschool and early elementary programs, educational interven- tion continues to involve assessment of existing skills, formulation of individualized goals and objectives, selec- tion and implementation of appropriate intervention strategies and supports, assessment of progress, and ad- aptation of teaching strategies as necessary to enable students to acquire target skills. The focus on achieving social communication competence, emotional and be-

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havioral regulation, and functional adaptive skills nec- essary for independence continues. Educational pro- grams should be individualized to address the specific impairments and needed supports while capitalizing on the child’s assets rather than being based on a particular diagnostic label.

Specific goals and objectives and the supports that are required to achieve them are listed in a child’s individ- ualized education plan and should be the driving force behind decisions regarding the most appropriate, least restrictive classroom placement. Appropriate settings may range from self-contained special education class- rooms to full inclusion in regular classrooms. Often, a mix of specialized and inclusive experience is appropri- ate. Even highly functioning students with ASDs often require accommodations and other supports such as pro- vision of explicit directions, modification of classroom and homework assignments, organizational supports, access to a computer and word-processing software for writing tasks, and social communication skills training. When a paraprofessional aide is assigned, it is important that there be an infrastructure of expertise and support for the child beyond the immediate presence of the aide.80 The specific duties of the aide should be outlined, the strategies to be used should be defined, and the aide should receive adequate training.

In adolescence, the term “transition” is used to de- scribe the movement from child-centered activities to adult-oriented activities. The major transitions are from the school environment to the workplace and from home to community living. In schools, transition-plan- ning activities may begin at as early as 14 years of age, and by 16 years of age, the individualized education plan should include an individualized transition plan. The emphasis may shift from academic to vocational services and from remediating deficits to fostering abilities. A vocational assessment is often conducted to evaluate the adolescent’s interests and strengths and to determine the services and supports needed to promote independence in the workplace and in the community. Comprehensive transition planning involves the student, parents, teach- ers, the medical home, and representatives from all con- cerned community agencies. Depending on the individ- ual’s cognitive level, social skills, health condition, work habits, and behavioral challenges, preparation for com- petitive, supported, or sheltered employment is targeted. Regardless of the type of employment, attention to skill development should never stop. Skills necessary for in- dependent living should be taught to the degree possible given the abilities of the person. Sexuality education instruction should be included, and there is a growing body of literature that has addressed the topic.81–83

MEDICALMANAGEMENT Children with ASDs have the same basic health care needs as children without disabilities and benefit from

the same health-promotion and disease-prevention ac- tivities, including immunizations. In addition, they may have unique health care needs that relate to underlying etiologic conditions, such as fragile X syndrome or tu- berous sclerosis, or to other conditions, such as epilepsy, that often are associated with ASDs. Those with pica or persistent mouthing of fingers or objects should be mon- itored for elevated blood lead concentrations, particu- larly if the history suggests potential for environmental exposure.84 These health care needs are most appropri- ately met within the context of a medical home.85,86

To deliver appropriate and effective medical care, the history, approach to the patient, physical evaluation, and treatment options must be considered in the context of the patient’s ASD.87,88 Familiarizing the patient with the office setting and staff, allowing ample time while talking before touching the patient, allowing the child to manipulate instruments and materials, keeping instruc- tions simple, using visual cues and supports, slowing down the pace, exaggerating social cues, and having family and/or familiar staff available may be helpful in reducing the obstacles to health care provision presented by patients’ difficulties with social interaction, commu- nication, and accepting novelty.88 Often, more time is required for outpatient appointments. In a nationally representative sample, it was found that children with ASDs spent twice as much time with the physician per outpatient visit compared with children in control groups.89

Associated Morbidity and Mortality Health care utilization and costs are substantially higher for children and adolescents with ASDs compared with children without ASDs,89–91 and available data suggest that mortality is increased as well (standardized mortal- ity ratio: 2.4–2.6).92,93 The increased mortality in ASDs is thought to be largely, but not completely, accounted for by the increased mortality associated with mental retar- dation and epilepsy. Cases of suicide in higher-function- ing individuals have been reported.6

Seizures The reported prevalence of epilepsy among people with ASDs ranges from 11% to 39%.94 Comorbid severe global developmental delay/mental retardation and mo- tor deficits are associated with a high prevalence of seizures (42%),95 whereas the prevalence of seizures is only 6% to 8% in children with ASDs without severe mental retardation, a motor deficit, an associated etio- logic medical disorder, or a positive family history of epilepsy.95,96 The prevalence of epilepsy also was higher in studies that included adolescents and young adults, because the onset of epilepsy in ASDs has 2 peaks: 1 before 5 years of age and another in adolescence.97 An- ticonvulsant treatment in children with ASDs is based on the same criteria that are used for other children with

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epilepsy, including accurate diagnosis of the particular seizure type.98

Epileptiform abnormalities on electroencephalogra- phy (EEG) are common in children with ASDs, with reported frequencies ranging from 10% to 72%.99 Some studies have suggested that epileptiform abnormalities on EEG100 and/or epilepsy101 are more common in the subgroup of children with ASDs who have a history of regression, whereas other studies have not demon- strated this association.102,103 Autistic regression with ep- ileptiform abnormalities on EEG has been compared by analogy with Landau-Kleffner syndrome and electrical status epilepticus in sleep, but there are important dif- ferences between these conditions, and the treatment implications are unclear.94,104 Whether subclinical sei- zures have adverse effects on language, cognition, and behavior is debated, and there is no evidence-based rec- ommendation for the treatment of children with ASDs and epileptiform abnormalities on EEG, with or without regression.104 Universal screening of patients with ASDs by EEG in the absence of a clinical indication is not currently supported.2,99 However, because of the in- creased prevalence of seizures in this population, a high index of clinical suspicion should be maintained, and EEG should be considered when there are clinical spells that might represent seizures.

Gastrointestinal Problems The relationship between gastrointestinal problems and ASDs is unclear, because most studies have not exam- ined representative groups of children with ASDs com- pared with appropriate controls.105,106 Surveys published in the gastroenterology literature have stated that gas- trointestinal problems, such as chronic constipation or diarrhea, occur in 46% to 85% of children with ASDs.107–109

Lower rates in the range of 17% to 24% have been reported in other population-based studies,110–112 and a nested case-control study in the United Kingdom found that only 9% of children with ASDs and the same per- centage of controls had a history of gastrointestinal com- plaints.113 However, in a recent cross-sectional study that used structured interviews and matched control groups, a lifetime history of gastrointestinal symptoms (includ- ing abnormal stool pattern, frequent constipation, fre- quent vomiting, and frequent abdominal pain) was elic- ited in 70% of the children with ASDs, compared with 42% of the children with other developmental disabili- ties (P � .03) and 28% of the children without devel- opmental disabilities (P � .001).114

In children with ASDs undergoing endoscopy, who may or may not be representative of the general popu- lation of children with ASDs, high rates of lymphoid nodular hyperplasia and, often, histologically subtle esophagitis, gastritis, duodenitis, and colitis have been described, and preliminary evidence suggests that some immunohistochemical features may be unique to in-

flammation associated with ASDs.105,115,116 The existing literature does not support routine specialized gastroen- terological testing for asymptomatic children with ASDs.105 However, if a child with an ASD presents with symptoms such as chronic or recurrent abdominal pain, vomiting, diarrhea, or constipation, it is reasonable to evaluate the gastrointestinal tract. Occult gastrointesti- nal discomfort also should be considered in a child who presents with a change in behavior, such as outbursts of aggression or self-injury. Radiographic evidence of con- stipation has been found to be more common in children with ASDs than in controls with abdominal pain (36% vs 10%),117 and effective management may provide global benefit.

Sleep Disturbance Sleep problems are common in children and adolescents with ASDs at all levels of cognitive functioning.118–122

Sleep problems correlate with family distress and may have significant effects on daytime functioning and qual- ity of life of children with ASDs.123–125 In some cases, there may be an identifiable etiology such as obstructive sleep apnea or gastroesophageal reflux; assessment and treatment are guided by history and physical examina- tion. When there is not an identifiable medical cause, behavioral interventions including sleep-hygiene mea- sures, restriction of daytime sleep, positive bedtime rou- tines, and extinction procedures often are effective.118,126–129

Relatively little empirical information is available re- garding pharmacologic management of sleep problems in children with ASDs or other developmental disabili- ties. Recommendations typically are based on case re- ports and open-label trials, extrapolation from the adult literature, and expert consensus (Table 1).128 There is some evidence of abnormality of melatonin regulation in children with ASDs,125,130 and melatonin may be effective for improving sleep onset in children with ASDs as well as children with other developmental disabilities131–134

and otherwise healthy children with sleep/wake disor- ders.135 A recent open-label study suggested that con- trolled-release melatonin improved sleep in a group of 25 children with ASDs and that treatment gains were maintained at 1- and 2-year follow-up,136 but random- ized, double-blind, placebo-controlled studies are needed. Recently, a child and a young adult with ASDs with significant insomnia were reported to have re- sponded well, with no apparent adverse effects, to open- label treatment with the high-affinity melatonin recep- tor agonist ramelteon.137 Antihistamines, �2-agonists, benzodiazepines, chloral hydrate, trazodone, and newer nonbenzodiazepine hypnotic agents, such as zolpidem and zaleplon, sometimes are used to treat pediatric in- somnia.128 In some cases, other conditions or symptoms, such as epilepsy, depression, anxiety, or aggressive out- bursts, warrant pharmacologic treatment, and an agent that also may assist with sleep can be chosen.118

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Evaluation of Challenging Behaviors Problematic emotional reactions and behaviors such as aggression and self-injury are common in children and adolescents with ASDs. In some cases, medical factors may cause or exacerbate maladaptive behaviors, and recognition and treatment of medical conditions may

eliminate the need for psychopharmacologic agents. For example, in the case of an acute onset or exacerbation of aggressive or self-injurious behavior, a source of pain or discomfort may be identified and treated.138 Sources of discomfort may include otitis media, otitis externa, phar- yngitis, sinusitis, dental abscess, constipation, urinary

TABLE 1 Selected Potential Medication Options for Common Target Symptoms or Coexisting Diagnoses in ChildrenWith ASDs

Target Symptom Cluster Potential Coexisting Diagnoses Selected Medication Considerations Selected References

Repetitive behavior, behavioral rigidity, obsessive-compulsive symptoms

Obsessive-compulsive disorder, stereotypic movement disorder

SSRIs (fluoxetine,a fluvoxamine,a

citalopram, escitalopram, paroxetine, sertraline)

McDougle et al,158,b Buchsbaum et al,180,b

Sugie et al,159,b Hollander et al,157,b Moore et al,160,c Namerow et al,181,d Owley et al182,d

Atypical antipsychotic agents (risperidone,a aripiprazole, olanzapine, quetiapine, ziprasidone)

McDougle et al164,b

Valproic acida Hollander et al183,b

Hyperactivity, impulsivity, inattention

Attention-deficit/hyperactivity disorder

Stimulants (methylphenidate,a

dextroamphetamine, mixed amphetamine salts)

Quintana et al,168,b Handen et al,169,b RUPP Autism Network170,b

�2-agonists (clonidine,a guanfacine) Fankhauser et al,172,b Jaselskis et al,173,b

Posey et al,175,d Scahill et al (RUPP Autism Network)174,d

Atomoxetinea Arnold et al,178,b Jou et al,176,d Posey et al177,d

Atypical antipsychotic agents (risperidone,a aripiprazole, olanzapine,a

quetiapine, ziprasidone)

McCracken et al,162,b Arnold et al,163,b Shea et al,165,b RUPP Autism Network,166,b

Troost et al167,d

Aggression, explosive outbursts, self-injury

Intermittent explosive disorder Atypical antipsychotic agents (risperidone,a aripiprazole, olanzapine, quetiapine, ziprasidone)

McCracken et al,162,b Arnold et al,163,b Shea et al,165,b RUPP Autism Network,166,b

Troost et al167,d

�2-agonists (clonidine,a guanfacine) Fankhauser et al,172,b Jaselskis et al,173,b

Posey et al175,d

Anticonvulsant mood stabilizers (levetiracetam, topiramate, valproic acid)

Hollander et al184,d, Rugino and Samsock185,d, Hardan et al186,d, Myers148,c, Myers and Challman149,c

SSRIs (fluoxetine,a fluvoxamine,a

citalopram, escitalopram, paroxetine, sertraline)

McDougle et al,158,b Moore et al,160,c

Namerow et al,181,d Owley et al182,d

�-blockers (propranolol, nadolol, metoprolol, pindolol)

Connor et al,187,d Ratey et al,188,d Myers and Challman149,c

Sleep dysfunction Circadian rhythm sleep disorder, dyssomnia–not otherwise specified

Melatonin Giannotti et al,136,d Jan and Freeman,131,c

Phillips and Appleton,133,c Turk,134,c

Owens et al128,c

Ramelteon Stigler et al137,e

Antihistamines (diphenhydramine, hydroxyzine)

Reed and Findling,189,c Owens et al128,c

�2-agonists (clonidine, guanfacine) Mehta et al,190,d Ingrassia and Turk,191,d

Posey et al,175,d Owens et al128,c

Mirtazapine Posey et al192,d

Anxiety Generalized anxiety disorder, anxiety disorder–not otherwise specified

SSRIs (fluoxetine,a fluvoxamine,a

citalopram, escitalopram, paroxetine, sertraline)

McDougle et al,158,b Buchsbaum et al,180,b

Sugie et al,159,b Hollander et al,157,b Moore et al,160,c Namerow et al,181,d Owley et al182,d

Buspirone Buitelaar et al193,d

Mirtazapine Posey et al192,d

Depressive phenotype (marked change from baseline including symptoms such as social withdrawal, irritability, sadness or crying spells, decreased energy, anorexia, weight loss, sleep dysfunction)

Major depressive disorder, depressive disorder–not otherwise specified

SSRIs (fluoxetine,a fluvoxamine,a

citalopram, escitalopram, paroxetine, sertraline)

McDougle et al,158,b Moore et al,160,c

Namerow et al,181,d Owley et al182,d

Mirtazapine Posey et al192,d

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tract infection, fracture, headache, esophagitis, gastritis, colitis, allergic rhinitis, and others. When behavioral deterioration is temporally related to menstrual cycles in an adolescent female,139 use of an analgesic or oral or injectable contraceptive may be helpful. Obstructive sleep apnea may contribute to behavioral deterioration and may be amenable to weight reduction, tonsillectomy and adenoidectomy, or continuous positive airway pres- sure.140 Extreme food selectivity has the potential to lead to protein-calorie malnutrition or specific vitamin or mineral deficiencies; however, most studies that evalu- ated nutritional status in children with ASDs have sug- gested that despite dietary selectivity, malnutrition is uncommon.105,141 Although the prevalence in children with ASDs is unknown, pica related to iron or zinc deficiency may respond to supplementation with the appropriate mineral. It should be noted that it is not clear how frequently medical factors cause or exacerbate se- rious maladaptive behaviors in children with ASDs, and the efficacy of these interventions is based on anecdotes, case reports, and conventional clinical practice rather than empirical support from clinical trials.

It is also important to consider environmental factors that may precipitate challenging behaviors. Parents, teachers, or other caregivers may inadvertently reinforce maladaptive behaviors, and in such cases, the most ap- propriate and effective interventions are behavioral. In some instances, a mismatch between educational or be- havioral expectations and cognitive ability of the child is responsible for disruptive behavior (eg, when the diag- nosis of mental retardation has not been recognized), and adjustment of expectations is the most appropriate intervention. In both situations, a functional analysis of behavior, completed by a behavior specialist in the set- tings in which the problems occur, will identify factors in the environment that exacerbate or maintain the prob- lematic behavior. A strategy for intervention through

behavioral techniques and environmental manipula- tions can then be formulated and tested.

Psychopharmacology Pharmacologic interventions may be considered for mal- adaptive behaviors such as aggression, self-injurious be- havior, repetitive behaviors (eg, perseveration, obses- sions, compulsions, and stereotypic movements), sleep disturbance, mood lability, irritability, anxiety, hyperac- tivity, inattention, destructive behavior, or other disrup- tive behaviors. After treatable medical causes and mod- ifiable environmental factors have been ruled out, a therapeutic trial of medication may be considered if the behavioral symptoms cause significant impairment in functioning and are suboptimally responsive to behav- ioral interventions. In some cases, the diagnosis of a comorbid disorder, such as major depression, bipolar disorder, or an anxiety disorder, can be made reasonably and the patient can be treated with medications that are useful for treating these conditions in otherwise typically developing children and adolescents. Modifications of diagnostic criteria may be necessary to account for clin- ical presentations of psychiatric conditions in individuals with developmental disabilities,142,143 and tools such as behavior checklists144 and structured interviews145 may be helpful. In other cases, clinicians opt to target specific interfering maladaptive behaviors or symptom clusters in the absence of a clear comorbid psychiatric diagnosis (a target-symptom approach).146–151

Recent surveys indicate that approximately 45% of children and adolescents152–154 and up to 75% of adults8,155 with ASDs are treated with psychotropic med- ication. Greater age, lower adaptive skills and social competence, and higher levels of challenging behavior are associated with the likelihood of medication use.154

The evidence regarding the efficacy of psychopharmaco- logic interventions in patients with ASDs has been de-

TABLE 1 Continued

Target Symptom Cluster Potential Coexisting Diagnoses Selected Medication Considerations Selected References

Bipolar phenotype (behavioral cycling with rages and euphoria, decreased need for sleep, manic-like hyperactivity, irritability, aggression, self- injury, sexual behaviors)

Bipolar I disorder, bipolar disorder–not otherwise specified

Anticonvulsant mood stabilizers (carbamazepine, gabapentin, lamotrigine, oxcarbazepine, topiramate, valproic acid)

Kowatch and DelBello,194,c Myers and Challman149,c

Atypical antipsychotic agents (risperidone, aripiprazole, olanzapine, quetiapine, ziprasidone)

Cheng-Shannon et al,195,c Kowatch and DelBello,194,c Myers,148,c Myers and Challman149,c

Lithium DeLong,196,e Kerbeshian et al,197,e Steingard and Biederman,198,e Myers,148,c Myers and Challman149,c

RUPP indicates Research Units on Pediatric Psychopharmacology. a At least 1 published double-blind, placebo-controlled trial supports use in patients with an ASD. b Double-blind, placebo-controlled trial. c Review article. d Open-label trial or retrospective chart study. e Case report.

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tailed in recent reviews.148,150,151,156 Although most psych- otropic medications have been used in children with ASDs, there is currently insufficient literature to estab- lish consensus regarding an evidence-based approach to pharmacologic management. However, in recent years, there has been an increase in publication of randomized, double-blind, placebo-controlled clinical trials to guide clinical practice.

Surveys performed in the United States suggest that selective serotonin-reuptake inhibitors (SSRIs), atypical antipsychotic agents, stimulants, and �2-adrenergic ag- onist antihypertensive agents are the most commonly prescribed classes of psychotropic medications for chil- dren with ASDs.152,153 Double-blind, placebo-controlled trials have demonstrated efficacy of the SSRIs fluox- etine157 and fluvoxamine158,159 in the treatment of repet- itive and other maladaptive behaviors in patients with ASDs, and open-label trials of these and other SSRIs have shown improvements in target symptoms, includ- ing repetitive behaviors, irritability, depressive symp- toms, tantrums, anxiety, aggression, difficulty with tran- sitions, and aspects of social interaction and language.157–161

Potential adverse effects of SSRIs include but are not limited to nausea, drowsiness, sexual dysfunction, con- stipation, abdominal discomfort, fatigue, headache, diz- ziness, dry mouth, agitation, behavioral activation, hy- pomania or mania, apathy, suicidal ideation, and alteration of sleep.

Risperidone has become the first medication with US Food and Drug Administration–approved labeling for the symptomatic treatment of irritability (including ag- gressive behavior, deliberate self-injury, and temper tan- trums) in children and adolescents with ASDs. Two large, multisite, randomized, controlled trials have con- firmed the short-term efficacy of risperidone for these severe disruptive behaviors in youth with ASDs,162–165

and 2 open-label studies, each with a double-blind dis- continuation component, have suggested long-term benefits and tolerance.166,167 Potential adverse effects in- clude but are not limited to excessive appetite and weight gain, insulin resistance, dyslipidemia, hyperpro- lactinemia, extrapyramidal symptoms, tardive dyskine- sia, neuroleptic malignant syndrome, QTc prolongation, dry mouth, urinary retention, constipation, seizures, he- matologic abnormalities, and sedation.

Although early studies of the effects of stimulants yielded negative results, recent double-blind, placebo- controlled trials of methylphenidate have demonstrated improvement in hyperactivity, impulsivity, and inatten- tion in children with ASDs.168–170 Methylphenidate is effective in some children with ASDs, but the response rate is lower than that in children with isolated atten- tion-deficit/hyperactivity disorder, adverse effects are more frequent, and it is unclear whether the results can be generalized to other stimulants.170,171 Potential ad- verse effects of stimulant medications include but are not

limited to appetite reduction, inhibition of growth, de- layed sleep onset, jitteriness, exacerbation of tics, ab- dominal discomfort, increased blood pressure, increased heart rate, irritability, increased anxiety, and repetitive behaviors.

Two small double-blind, placebo-controlled trials have documented modest benefits of clonidine in reduc- ing hyperarousal symptoms including hyperactivity, irritability and outbursts, impulsivity, and repetitive be- haviors in children with ASDs.172,173 A prospective open- label trial174 and a retrospective record review175 have suggested that guanfacine was similarly effective in some patients. Potential adverse effects of these centrally act- ing �2-agonists include but are not limited to drowsiness, sedation, dry mouth, decreased blood pressure, dizzi- ness, constipation, and irritability, and these drugs can be dangerous in overdose. Recently, a retrospective study,176 an open-label trial,177 and a small double-blind, placebo-controlled crossover trial178 suggested that ato- moxetine may be effective for attention-deficit/hyperac- tivity disorder–like symptoms in children and adoles- cents with ASDs, and additional research is warranted. Appetite suppression, nausea, fatigue, mood swings, sui- cidal ideation, dizziness, and liver injury are among the potential adverse effects of atomoxetine.

A summary of selected target symptoms, potential psychiatric diagnoses, and medication options is pro- vided in Table 1. Pediatricians and other practitioners should only prescribe medications with which they have sufficient expertise, including knowledge of indications and contraindications, dosing, potential adverse effects, drug-drug interactions, and monitoring requirements. It will be important for future research to address the need for more rigorous evaluation of safety and efficacy of psychotropic agents in children with ASDs; the value of combining behavioral and medical interventions; the practice of polypharmacy; delineation of clinical and biological subgroups of patients who may be responsive to particular treatments; the role of drugs in treating deficits in language and nonlanguage cognition, social interaction, and behavioral rigidity; and the potential to alter the neural substrate during early critical periods to affect brain development and future function. Several multisite trials are underway, and others undoubtedly will be forthcoming.179

Principles to guide the approach to psychopharmaco- logic management of ASDs in clinical practice have been proposed by several authors in recent years, and an approach is outlined in Table 2.148–151 When medications are used, potential benefits and adverse effects should be explained, informed consent should be obtained, base- line data regarding behaviors and somatic complaints should be collected, and potential strategies for dealing with treatment failure or partial response should be reviewed. It is important to have some quantifiable means of assessing the efficacy of the medication and to

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obtain input from a variety of sources, such as parents, teachers, therapists, and aides. Consistent use of vali- dated, treatment-sensitive rating scales and medication adverse-effect scales is desirable. A wide variety of out- come measures have been used in research trials and in clinical practice to measure maladaptive behavior treat- ment effects.199 Among the most common are the Clin- ical Global Impression Scale, Aberrant Behavior Check- list, and Nisonger Child Behavior Rating Form.

Complementary and Alternative Medicine Complementary and alternative medicine (CAM) is de- fined by the National Center for Complementary and Alternative Medicine as “a group of diverse medical and health care systems, practices, and products that are not presently considered to be part of conventional medi- cine.”200 The definition of CAM adopted by the Cochrane

Collaboration is “a broad domain of healing resources that encompasses all health systems, modalities, and practices and their accompanying theories and beliefs, other than those intrinsic to the politically dominant health systems of a particular society or culture in a given historical period.”201 Detailed reviews of CAM as related to developmental disabilities and ASD-specific CAM have been published recently.202–204

Use of CAM is common in children with ASDs.152,205–207

Levy et al206 reported that by the time their clinical population received a formal diagnostic evaluation for a suspected ASD, almost one third of the children already had received a complementary or alternative therapy, and a survey conducted in a predominantly white, mid- dle-to-upper socioeconomic-status private-practice pop- ulation found that 92% of parents who responded had used CAM therapies for their children with ASDs.205

TABLE 2 Clinical Approach to Psychopharmacologic Management

Identify and assess target behaviors Parent/caregiver interview Intensity Duration Exacerbating factors/triggers (time, setting/location, demand situations, denials, transitions, etc) Ameliorating factors and response to behavioral interventions Time trends (increasing, decreasing, stable) Degree of interference with functioning

Consider baseline behavior-rating scales and/or baseline performance measures/direct observational data Include input from school staff and other caregivers

Assess existing and available supports Behavioral services and supports Educational program, habilitative therapies Respite care, family psychosocial supports

Search for medical factors that may be causing or exacerbating target behavior(s) Consider sources of pain or discomfort (infectious, gastrointestinal, dental, allergic, etc) Consider other medical causes or contributors (sleep disorders, seizures, menstrual cycle, etc)

Complete any medical tests that may have a bearing on treatment choice Consider psychotropic medication on the basis of the presence of Evidence that the target symptoms are interfering substantially with learning/academic progress, socialization, health/safety (of the patient and/or others around him

or her), or quality of life Suboptimal response to available behavioral interventions and environmental modifications Research evidence that the target behavioral symptoms or coexisting psychiatric diagnoses are amenable to pharmacologic intervention

Choose a medication on the basis of Likely efficacy for the specific target symptoms Potential adverse effects Practical considerations such as formulations available, dosing schedule, cost, and requirement for laboratory or electrocardiographic monitoring Informed consent (verbal or written) from parent/guardian and, when possible, assent from the patient

Establish plan for monitoring of effects Identify outcome measures Discuss time course of expected effects Arrange follow-up telephone contact, completion of rating scales, reassessment of behavioral data, and visits accordingly Outline a plan regarding what might be tried next if there is a negative or suboptimal response or to address additional target symptoms Change to a different medication Add another medication to augment a partial or suboptimal therapeutic response to the initial medication (same target symptoms) Add a different medication to address additional target symptoms that remain problematic

Obtain baseline laboratory data if necessary for the drug being prescribed and plan appropriate follow-up monitoring Explore the reasonable dose range for a single medication for an adequate length of time before changing to or adding a different medication Monitor for adverse effects systematically Consider careful withdrawal of the medication after 6–12 mo of therapy to determine whether it is still needed

Adapted from Myers SM. The status of pharmacotherapy for autism spectrum disorders. Expert Opin Pharmacother. 2007;8:1579–1603; and Myers SM, Challman TD. Psychopharmacology: an approach tomanagement in autismand intellectual disabilities. In: AccardoPJ, ed.Capute&Accardo’s Neurodevelopmental Disabilities in Infancy andChildhood. 3rd ed. Baltimore,MD: Paul H. Brookes; 2007: In press.

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Another recent parent survey found that 52% of the children with an ASD had been treated with at least 1 CAM therapy, compared with 28% of a group of control children without disabilities.207 Surveys indicate that only 36% to 62% of caregivers who used CAM therapies for their children with ASDs had informed the child’s primary care physician,207,208 although more information on CAM is something that families indicate that they want from their child’s primary health care profession- als.209

It is important that health care professionals under- stand how to evaluate the evidence used to support all treatments, including CAM, psychopharmacologic, and other interventions. Ideally, the evidence supporting or refuting a treatment should include peer-reviewed stud- ies with appropriately diagnosed, well-defined homoge- neous study populations; a randomized, double-blind, placebo-controlled design; an adequate sample size to support the statistical analysis presented; control for con- founding factors; and use of appropriate, validated out- come measures. When evaluating the efficacy of studies, it is particularly important to keep in mind confounding factors, such as the placebo effect, and the natural his- tory of the disorder. Participation in a study may alter the way a parent interacts with a child and confound the perceived outcome,210 and improvements are expected with maturation and educational interventions. Only appropriately controlled studies are helpful in proving that an effect is attributable to the intervention being studied.

The practitioner should encourage families to seek additional information when they encounter the follow- ing claims or situations211:

● treatments that are based on overly simplified scien- tific theories;

● therapies that are claimed to be effective for multiple different, unrelated conditions or symptoms;

● claims that children will respond dramatically and some will be cured;

● use of case reports or anecdotal data rather than care- fully designed studies to support claims for treatment;

● lack of peer-reviewed references or denial of the need for controlled studies; or

● treatments that are said to have no potential or re- ported adverse effects.

To help to describe their proposed rationales and mechanisms, CAM therapies used to treat ASDs have been categorized as “nonbiological” or “biological.”204

Examples of nonbiological interventions include treat- ments such as auditory integration training, behavioral optometry, craniosacral manipulation, dolphin-assisted therapy, music therapy, and facilitated communication. Examples of biological therapies include immunoregu-

latory interventions (eg, dietary restriction of food aller- gens or administration of immunoglobulin or antiviral agents), detoxification therapies (eg, chelation), gastro- intestinal treatments (eg, digestive enzymes, antifungal agents, probiotics, “yeast-free diet,” gluten/casein-free diet, and vancomycin), and dietary supplement regi- mens that are purported to act by modulating neuro- transmission or through immune factors or epigenetic mechanisms (eg, vitamin A, vitamin C, vitamin B6 and magnesium, folic acid, folinic acid, vitamin B12, dimeth- ylglycine and trimethylglycine, carnosine, omega-3 fatty acids, inositol, various minerals, and others).203,204

For most of the aforementioned CAM interventions, there is not enough scientific evidence yet to support or refute their use as treatment for ASDs. However, evalu- ation of treatments is possible, and a few CAM treat- ments have been appropriately studied. For example, more than a dozen randomized, double-blind, placebo- controlled trials involving more than 700 patients have demonstrated that secretin (a biological treatment) is not an effective treatment for ASDs.212,213 Evaluation of non- biological treatments also is feasible. This has been dem- onstrated in the case of facilitated communication, a technique that uses a trained facilitator to provide phys- ical support to a nonverbal person’s hand or arm while that person uses a computer keyboard or other device to spell. Evidence suggests that the communications pro- duced actually originate from the facilitator214,215 and that facilitated communication is not a valid treatment for ASDs.216–218

Because of methodologic flaws, insufficient numbers of patients, or lack of replication, many CAM therapies have been inadequately evaluated; therefore, evidence- based recommendations for their use are not possible. The most recent and most appropriately designed trials have demonstrated no significant benefit of dimethyl- glycine,219,220 vitamin B6 and magnesium,221,222 or audi- tory integration training.223–225 Both positive226 and neg- ative227,228 results have been described for small, methodologically flawed studies of intravenous immu- noglobulin. A recent double-blind, placebo-controlled trial revealed no statistically significant differences on Aberrant Behavior Checklist subscale scores between small groups of children with ASDs who were given omega-3 fatty acids and those who were given place- bo.229 However, the investigators noted a trend toward superiority of omega-3 fatty acids over placebo for hy- peractivity, which suggests that further investigation may be warranted.229 The gluten/casein-free diet is based on a hypothesis of abnormal gut permeability and exog- enous opiate excess. Although use of the gluten/casein- free diet for children with ASDs is popular, there is little evidence to support or refute this intervention, and re- viewers have determined that meaningful conclusions cannot be drawn from the existing literature.230,231 Sub- sequent to these reviews, a randomized, double-blind

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pilot study demonstrated no significant benefit.232 Dou- ble-blind, placebo-controlled elimination and challenge studies are in progress, and it is anticipated that these studies will provide substantially more useful informa- tion regarding the efficacy of the gluten/casein-free di- et.204,230 Measurement of urinary peptides has not been proven to be clinically useful as a marker for ASDs or as a tool to determine if dietary restriction is warranted or would be effective.

Many popular interventions, such as chelation of heavy metals, antifungal agents to decrease presumed yeast overgrowth, and antiviral agents to modulate the immune system, have not yet been studied in people with ASDs; their popularity is based on unproven theo- ries and anecdotes or case reports. None of these inter- ventions can be endorsed as treatment for ASDs outside of well-designed and appropriately monitored clinical trials. Some treatments, such as intravenous chelation, may be particularly dangerous and should be discour- aged. One child with autism died as a result of chelation with edetate disodium (Na2EDTA) despite the facts that a causal association between mercury and ASDs has not been demonstrated, there is no scientific evidence that chelation is an effective treatment for ASDs, and the effectiveness of chelation therapy to improve nervous system symptoms of chronic mercury toxicity has not been established.233 Unless there is clear evidence of current heavy metal toxicity, chelation by any method is not indicated outside of monitored clinical trials.

In some cases, interesting findings await replication or further investigation. For example, in a double-blind, placebo-controlled trial of vitamin C, improvement was found in total and sensory motor scores on the Ritvo- Freeman Real Life Rating Scale,234 and several small studies have suggested that music therapy had some short-term benefit on communication skills but not on behavior problems of children with ASDs.235 Recently, a group of 20 children with ASDs were compared with children without ASDs and found to have an imbalance of methionine and homocysteine metabolism, which was interpreted to represent impaired capacity for meth- ylation and increased oxidative stress.236 Treatment with trimethylglycine, folinic acid, and methylcobalamin re- sulted in normalization of laboratory findings. The study did not measure clinical response to the intervention, but anecdotal improvements were noted. Interpretation of these preliminary findings awaits further investiga- tion.

Health care practitioners who diagnose and treat chil- dren with ASDs should recognize that many of their patients will use nonstandard therapies. The importance of becoming knowledgeable about CAM therapies, in- quiring about current and past CAM use, providing bal- anced information and advice about treatment options, identifying risks or potential harmful effects, avoiding becoming defensive or dismissing CAM in ways that

convey a lack of sensitivity or concern, maintaining open communication, and continuing to work with families even if there is disagreement about treatment choices has been emphasized.237 It also is essential to critically evaluate the scientific merits of specific therapies and share this information with families, educate families about how to evaluate information and recognize pseudoscience, and insist that studies that examine CAM be held to the same scientific and ethical standards as all clinical research.202,238

Parents of children with ASDs will understandably pursue interventions that they believe may present some hope of helping their child, particularly if the therapies are viewed as being unlikely to have any adverse effects. Unfortunately, families are often exposed to unsubstan- tiated, pseudoscientific theories and related clinical prac- tices that are, at best, ineffective and, at worst, compete with validated treatments or lead to physical, emotional, or financial harm. Time, effort, and financial resources expended on ineffective therapies can create an addi- tional burden on families. Health care professionals can help parents and other caregivers to distinguish empiri- cally validated treatment approaches from treatments that have been proven to be ineffective and those that are unproven and potentially ineffective and/or harm- ful.

FAMILY SUPPORT Management should focus not only on the child but also on the family. Although parents once were viewed er- roneously as the cause of a child’s ASD, it is now recog- nized that parents play a key role in effective treatment.9

Having a child with an ASD has a substantial effect on a family. Parents and siblings of children with ASDs expe- rience more stress and depression than those of children who are typically developing or even those who have other disabilities.239–243 Supporting the family and ensur- ing its emotional and physical health is an extremely important aspect of overall management of ASDs.

Physicians and other health care professionals can provide support to parents by educating them about ASDs; providing anticipatory guidance; training and in- volving them as cotherapists; assisting them in obtaining access to resources; providing emotional support through traditional strategies such as empathetic listen- ing and talking through problems; and assisting them in advocating for their child’s or sibling’s needs.244 In some cases, referral of parents for counseling or other appro- priate mental health services may be required. The need for support is longitudinal, although the specific needs may vary throughout the family life cycle.

One of the chief strategies for helping families raise children with ASDs is helping to provide them with access to needed ongoing supports and additional ser- vices during critical periods and/or crises. Natural sup- ports include spouses, extended family members, neigh-

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bors, religious institutions, and friends who can help with caregiving and who can provide psychological and emotional support. Informal supports include social net- works of other families of children with ASDs and com- munity agencies that provide training, respite, social events, and recreational activities. Formal supports in- clude publicly funded, state-administrated programs such as early intervention, special education, vocational and residential/living services, respite services, Medicaid, in-home and community-based waiver services, Supple- mental Security Income benefits, and other financial subsidies. The breadth and depth of services vary, even within the same state or region. Few services exist in many rural areas, and public programs may have long waiting lists.

Sibling support groups offer the opportunity to learn important information and skills while sharing experi- ences and connecting with other siblings of children with ASDs.244 Although the research on support groups for siblings of children with disabilities is difficult to interpret because of study-design problems and incon- sistent outcome effects on sibling adjustment, these groups generally have been evaluated positively by partic- ipating siblings and parents,244 and there is some evidence of beneficial effects for siblings of children with ASDs.245

Because each state has organized its services and ac- cess mechanisms differently, physicians and families must learn their own state’s unique rules to access sup- ports by contacting the state or county offices of the states’ Department of Health and Human Services or Mental Health and Mental Retardation or the state de- velopmental disabilities organization. In addition, local parent advocacy organizations, national autism and re- lated developmental disability organizations, early inter- vention administrators, and school district special edu- cation coordinators often are knowledgeable about various programs and their respective eligibility require- ments.

CONCLUSIONS ASDs are chronic conditions that affect nearly 1 of every 150 children and require ongoing medical and nonmed- ical intervention. There is a growing body of evidence that supports the efficacy of certain interventions in ameliorating symptoms and enhancing functioning, but much remains to be learned. In addition to their impor- tant roles in identifying ASDs through screening and surveillance, establishing the diagnosis, conducting an etiologic evaluation, and providing genetic counseling after a diagnosis is made,2 pediatricians and other pri- mary health care professionals are in a position to pro- vide important longitudinal medical care and to support and educate families and guide them to empirically sup- ported interventions for their children.

COUNCIL ON CHILDRENWITH DISABILITIES EXECUTIVE COMMITTEE,

2006–2007

Paul H. Lipkin, MD, Chairperson J. Daniel Cartwright, MD Larry W. Desch, MD John C. Duby, MD Ellen Roy Elias, MD Chris Plauché Johnson, MD, MEd Eric B. Levey, MD Gregory S. Liptak, MD Nancy A. Murphy, MD Scott M. Myers, MD Ann Henderson Tilton, MD

LIAISONS

Donald Lollar, EdD Centers for Disease Control and Prevention

Michelle Macias, MD Section on Developmental and Behavioral Pediatrics

Merle McPherson, MD, MPH Maternal and Child Health Bureau

Donna Gore Olson Family Voices

Bonnie Strickland, PhD Maternal and Child Health Bureau

STAFF

Stephanie Mucha Skipper, MPH Jill Ackermann, MS Mark Del Monte, JD

CONTRIBUTORS

Thomas D. Challman, MD Susan L. Hyman, MD Susan E. Levy, MD S. Andrew Spooner, MD

Partnership for Policy Implementation Marshalyn Yeargin-Allsopp, MD

REFERENCES 1. American Psychiatric Association. Diagnostic and Statistical

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