Pharmacotherapy of Autism Spectrum Disorder: Results from the Randomized BAART Clinical Trial.

The objective of this trial, Biomarkers in Autism of Aripiprazole and Risperidone Treatment (BAART), was to provide support and guidance for an evidence-based approach for the selection and monitoring of initial pharmacotherapy in patients with autism by assessing predictors of efficacy, tolerability, and safety. This randomized double-blind parallel-group study was conducted in three academic medical centers and a single private pediatric practice. Eighty children or adolescents (aged 6-17 yrs) with autistic disorder were enrolled, and 61 patients were randomized to the study drug. Of those patients, 51 completed the 10-week trial, and 31 completed an optional 12-week blinded extension phase. All patients were treated with 2 weeks of placebo before random assignment to receive aripiprazole (31 patients) or risperidone (30 patients) for 10 weeks. Sixteen placebo responders (20%) were excluded from further analysis. Drug dosing followed U.S. Food and Drug Administration (FDA) labeling, and weekly dosage adjustments were allowed until week 4; patients were then maintained on a fixed dose for 6 additional weeks. Safety, physical, and psychological assessments were recorded weekly or every 2 weeks. No significant differences in severity of illness between the aripiprazole and risperidone groups were noted at baseline. All patients significantly improved on the Aberrant Behavior Checklist-Irritability subscale after 1 week and continued for the remaining 9 weeks and the extension phase. Improvement was greatest in the risperidone group at every assessment period and was statistically significantly better than that in the aripiprazole group at weeks 3 and 6 (p<0.05). No dose-limiting adverse events occurred during the dose-titration period. Mean weight gain in the aripiprazole group was significantly less than that in the risperidone group at week 4 (0.62 vs 1.38 kg, p=0.033) and week 10 (1.61 vs 3.31 kg, p<0.001), but the difference became nonsignificant for the 31 patients completing the 3-month extension phase (4.36 vs 5.55 kg, p=0.26). Pharmacotherapy of patients with autism spectrum disorder resulted in behavioral improvement within 1 week and lasted at least 22 weeks. Weight gain occurred to a greater degree with risperidone than aripiprazole initially, but the differences became nonsignificant by the end of the trial. Our trial supports previous results of drug efficacy and safety in patients with autism spectrum disorder from other trials and extends the evidence-based support for choosing an FDA-approved drug for initial pharmacotherapy for autism spectrum disorder.

Difference in age at regression in children with autism with and without Down syndrome.

OBJECTIVE: Autism occurs more frequently in individuals with Down syndrome than it does in the general population. Among children with autism and Down syndrome, regression is reported to occur in up to 50%. The aim of this study was to characterize and compare regression in children with autism with and without Down syndrome. METHODS: In this case-control study, children with Down syndrome and autism characterized by a history of developmental regression (n = 12) were compared to children with autism with regression who did not have Down syndrome, matched for chronologic age and gender. Comparisons were made on age at acquisition of language and age at loss of language and other skills as measured by the Autism Diagnostic Interview-Revised (ADI-R). RESULTS: The mean age at acquisition of meaningful use of single words was 40.6 months (SD = 38.0) in children with Down syndrome and autism compared to 14.9 months (SD = 8.5) in children with autism without Down syndrome (p = .005). The mean age at language loss in children with autism with Down syndrome was 61.8 months (SD = 22.9) compared to 19.7 months (SD = 5.8) for those with autism without Down syndrome (p = .01). The mean age at other skill loss was 46.2 months (SD = 19.1) and 19.5 months (SD = 5.6), respectively (p = .006). CONCLUSIONS: When regression occurs in children with autism and Down syndrome it is, on average, much later than is typically seen in children with autism without Down syndrome.

Improving Early Identification and Intervention for Children at Risk for Autism Spectrum Disorder.

OBJECTIVES: To provide an example of a successful, novel statewide effort to increase early identification of young children at risk for autism spectrum disorder (ASD) using a 2-tiered screening process with enhanced quality assessment, interagency policy collaboration and coordination. METHODS: The South Carolina Act Early Team (SCAET) provided focused collaboration among leaders representing state agencies, universities, health care systems, private organizations, and families to improve quality of life for children with ASD. Specific focus was on implementing policy changes and training to result in earlier identification and home-based behavioral intervention for young children at risk for ASD. RESULTS: Policy changes, training, and modified state agency practices were accomplished. Presumptive eligibility, on the basis of a 2-tiered screening process was implemented by BabyNet (South Carolina's Early Intervention Program) in collaboration with the lead agency for developmental disability services. There was a fivefold increase in children eligible for early intensive behavioral intervention without waiting for a diagnosis of ASD, avoiding long waits for diagnostic evaluations. Only 16 children (2.5%) were later found not to have ASD from a comprehensive evaluation. CONCLUSIONS: Improvements in early identification and intervention are feasible through collaborative policy change. The South Carolina Act Early Team and its key stakeholders committed to improving outcomes for this population used existing tools and methods in new ways to improve early identification of children with ASD and to make available evidence-based intervention services. This example should be replicable in other states with key stakeholders working collaboratively for the benefit of young children with ASD.

Training the Motor Aspects of Pre-driving Skills of Young Adults With and Without Autism Spectrum Disorder.

The purpose of this study was to investigate the utility of using a driving simulator to address the motor aspects of pre-driving skills with young adults with Autism Spectrum Disorder (ASD). A group of neurotypical control participants and ten participants with ASD completed 18 interactive steering and pedal exercises with the goal to achieve error-free performance. Most participants were able to achieve this goal within five trials for all exercises except for the two most difficult ones. Minimal performance differences were observed between the two groups. Participants with ASD needed more time to complete the tasks. Overall, the interactive exercises and the process used worked well to address motor related aspects of pre-driving skills in young adults with ASD.

Examining treatment adherence among parents of children with autism spectrum disorder.

BACKGROUND: Children with Autism Spectrum Disorder (ASD) participate in a variety of treatments, including medication, behavioral, alternative and developmental treatments. Parent adherence to these treatments is crucial for positive child outcomes. OBJECTIVE: The current study: 1) Explored patterns of parent adherence across the full range of treatments that are prescribed to children with ASD and, 2) Examined whether parent demographics, parent treatment attitudes, and child ASD severity contribute to parents' adherence across ASD treatments. METHOD: Questionnaires were distributed to parents of children with ASD in a southeastern state. Parents (N = 274) were included if they were parenting a child with ASD who was receiving treatment for ASD symptoms. Paired t-tests and multiple linear regression were used to assess the study aims. RESULTS: Adherence to medication treatment was significantly greater than adherence to behavioral, developmental, or alternative treatments (adjusted p-values 0.0006, 0.0030, 0.0006 respectively). Perceived family burden of a treatment was associated with lower adherence to medication, developmental, and alternative treatments. Finally, greater ASD severity was associated with lower adherence to alternative treatments. CONCLUSION: Overall, the independent variables accounted for more variance in adherence to medication and alternative treatments than in behavioral and developmental treatments. Parents' adherence to ASD treatment differs significantly by treatment type and is influenced by parental perceptions of the burden of treatment on the family. These findings highlight the importance of understanding and addressing the impact of ASD treatment regimens on family life.

Lack of benefit of intravenous synthetic human secretin in the treatment of autism.

The objective of this study was to determine if an intravenous infusion of synthetic human secretin improves language and behavioral symptoms in children with autism. Forty-two children with the diagnosis of autism were randomized to one of two groups in this double-blind cross-over trial. One group received 2 IU/kg of intravenous synthetic human secretin at the first visit, followed by an equal volume of intravenous saline placebo at week 6. The other group received treatments in the reverse order. All children were evaluated at weeks 1, 3, 6, 9, and 12 with standardized assessments of language, behavior, and autism symptomatology. There were no significant differences in the mean scores on any measure of language, behavior, or autism symptom severity after treatment with secretin compared to treatment with placebo. The results of this study do not support secretin as a treatment for autism.