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 pediatricians in educating families and guiding them toward empirically supported interventions 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.

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Management of Children With Autism Spectrum Disorders

Autism spectrum disorder is characterized by patterns of delay and deviance in the development of social, communicative, and cognitive skills that arise in the first years of life. Although frequently associated with intellectual disability, this condition is distinctive in its course, impact, and treatment. Autism spectrum disorder has a wide range of syndrome expression and its management presents particular challenges for clinicians. Individuals with an autism spectrum disorder can present for clinical care at any point in development. The multiple developmental and behavioral problems associated with this condition necessitate multidisciplinary care, coordination of services, and advocacy for individuals and their families. Early, sustained intervention and the use of multiple treatment modalities are indicated. J. Am. Acad. Child Adolesc. Psychiatry, 2014;53(2):237–257. Key Words: autism, Practice Parameters, guidelines, developmental disorders, pervasive developmental disorders

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Practice Parameter for the Assessment and Treatment of Children and Adolescents With Autism Spectrum Disorder

Recent reviews highlight limitations in the evidence base for early interventions for children with autism. We conducted a systematic review of controlled studies of early intensive behavioral interventions (EIBI) for young children with autism. Eleven studies met inclusion criteria (including two randomized controlled trials). At group level, EIBI resulted in improved outcomes (primarily measured by IQ) compared to comparison groups. At an individual level, however, there was considerable variability in outcome, with some evidence that initial IQ (but not age) was related to progress. This review provides evidence for the effectiveness of EIBI for some, but not all, preschool children with autism.

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Systematic review of early intensive behavioral interventions for children with autism

* Abbreviations:
 RCT — : randomized controlled trial
 SSRI — : selective serotonin reuptake inhibitor

It has long been an axiom in clinical pediatrics that “children are not just little adults.” It has also been recognized that there are many changes from birth through childhood and the adolescent years. However, the full implications of pediatric age groupings for health care and research are still not adequately understood. There is still much to be discovered about children’s biological and psychological development and how these processes affect the effectiveness and efficacy of interventions. Trial design that accounts for age differences and promotes consistency in reporting of age-related data is essential to ensure the validity and clinical usefulness of pediatric trial data.

A recent study highlighted variable treatment efficacy in children versus adults. In this study, 128 meta-analyses from Cochrane reviews, containing data on at least 1 adult and 1 pediatric randomized controlled trial (RCT) with a binary primary efficacy outcome, were reviewed.1 The authors found that in all except 1 case, the 95% confidence intervals could not exclude a relative difference in treatment efficacy between adults and children of >20%; in two-thirds of these cases, the relative difference in observed point estimates was >50%. The study also highlighted the paucity of RCTs in pediatrics; the median number of children per meta-analysis was 2.5 times smaller than the number of adults.

Children and adults seem to have distinctive responses to treatments. For example, administration of phenobarbitones is useful for adults with cerebral malaria and is associated with decreased convulsions. However, in children, this drug is associated with increased 6-month mortality. Similarly, corticosteroids may offer survival benefit for adults with bacterial meningitis but not for children with the same condition. In acute traumatic brain injury, corticosteroids did not decrease mortality in adults, but there was a trend for increased mortality in children.1 In asthma, long-acting β2-agonists decreased … 

Address correspondence to Martin Offringa, MD, PhD, Senior Scientist and Program Head, Child Health Evaluative Sciences, Research Institute, The Hospital for Sick Children, 555 University Ave, Toronto, Ontario, Canada M5G 1X8. E-mail: martin.offringa{at}sickkids.ca

Standard 6: Age Groups for Pediatric Trials

Background
Autism spectrum disorders (ASD) are characterised by abnormalities in social interaction and communication skills, as well as stereotypic behaviours and restricted activities and interests. Selective serotonin reuptake inhibitors (SSRIs) are prescribed for the treatment of conditions often comorbid with ASD such as depression, anxiety and obsessive-compulsive behaviours.

Objectives
To determine if treatment with an SSRI:
1. improves the core features of autism (social interaction, communication and behavioural problems);
2. improves other non-core aspects of behaviour or function such as self-injurious behaviour;
3. improves the quality of life of adults or children and their carers;
4. has short- and long-term effects on outcome;
5. causes harm.

Search methods
We searched the following databases up until March 2013: CENTRAL, Ovid MEDLINE, Embase, CINAHL, PsycINFO, ERIC and Sociological Abstracts. We also searched ClinicalTrials.gov and the International Clinical Trials Registry Platform (ICTRP). This was supplemented by searching reference lists and contacting known experts in the field.

Selection criteria
Randomised controlled trials (RCTs) of any dose of oral SSRI compared with placebo, in people with ASD.

Data collection and analysis
Two authors independently selected studies for inclusion, extracted data and appraised each study's risk of bias.

Main results
Nine RCTs with a total of 320 participants were included. Four SSRIs were evaluated: fluoxetine (three studies), fluvoxamine (two studies), fenfluramine (two studies) and citalopram (two studies). Five studies included only children and four studies included only adults. Varying inclusion criteria were used with regard to diagnostic criteria and intelligence quotient of participants. Eighteen different outcome measures were reported. Although more than one study reported data for Clinical Global Impression (CGI) and obsessive-compulsive behaviour (OCB), different tool types or components of these outcomes were used in each study. As such, data were unsuitable for meta-analysis, except for one outcome (proportion improvement). One large, high-quality study in children showed no evidence of positive effect of citalopram. Three small studies in adults showed positive outcomes for CGI and OCB; one study showed improvements in aggression, and another in anxiety.

Authors' conclusions
There is no evidence of effect of SSRIs in children and emerging evidence of harm. There is limited evidence of the effectiveness of SSRIs in adults from small studies in which risk of bias is unclear.

Selective serotonin reuptake inhibitors (SSRIs) for autism spectrum disorders (ASD)

BACKGROUND\nSecretin is a gastro-intestinal hormone which has been presented as an effective treatment for autism based on anecdotal evidence.\n\n\nOBJECTIVES\nTo determine if intravenous secretin:1. improves the core features of autism (social interaction, communication and behaviour problems); 2. improves the non-core aspects of behaviour or function such as self injurious behaviour;3. improves the quality of life of affected individuals and their carers; 4. has short term and long term effects on outcome; 5. causes harm.\n\n\nSEARCH STRATEGY\nResults of electronic searches of CENTRAL, MEDLINE, EMBASE, PsycINFO, CINAHL, ERIC, HealthStar and Sociofile (1998 - March 2005) were independently examined by two authors. Reference lists of trials and reviews were searched; experts and trialists were contacted to find unpublished studies.\n\n\nSELECTION CRITERIA\nRandomised controlled trials of intravenous secretin comparing secretin with a placebo treatment in children or adults diagnosed with autism spectrum disorders, where at least one standardised outcome measure was reported.\n\n\nDATA COLLECTION AND ANALYSIS\nFourteen studies met inclusion criteria. All outcome data were continuous. Where trials used cross-over designs, analysis was conducted on results from first treatment phase, allowing combined analysis with parallel design trials. Where standardised assessment tools generated scores as outcome measures, comparisons were made between means of these scores. Where baseline means were reported, differences between treatment and control were determined to assess possible bias. Where mean change from baseline was reported, this was used in preference to post-treatment scores for meta-analyses or forest plots. As meta-analysis was possible for only one outcome (Childhood Autism Rating Scale), it was impossible to use sensitivity or subgroup analyses to assess impact of study quality, clinical differences in the intervention, or clinically relevant differences between groups, such as age or presence of gastrointestinal symptoms.\n\n\nMAIN RESULTS\nTwenty-five established standardised outcome measures were reported to assess core features of autism, communication, behaviour, visio-spatial skills, affect and adverse events within fourteen included studies. No more than four studies used any one outcome measure similarly. Outcomes were reported between three and six weeks. RCTs of efficacy of secretin in autism have not shown improvements for core features of autism.\n\n\nAUTHORS' CONCLUSIONS\nThere is no evidence that single or multiple dose intravenous secretin is effective and as such it should not currently be recommended or administered as a treatment for autism. Further experimental assessment of secretin's effectiveness for autism can only be justified if methodological problems of existing research can be overcome.

J. J. Wray

Papers

Intravenous secretin for autism spectrum disorder (Review)