Autism is a neurodevelopmental disorder characterized by dysfunction in three core behavioral domains: repetitive behaviors, social deficits, and language abnormalities. There is evidence that abnormalities exist in peptide systems, particularly the oxytocin system, in autism spectrum patients. Furthermore, oxytocin and the closely related peptide vasopressin are known to play a role in social and repetitive behaviors. This study examined the impact of oxytocin on repetitive behaviors in 15 adults with autism or Asperger's disorder via randomized double-blind oxytocin and placebo challenges. The primary outcome measure was an instrument rating six repetitive behaviors: need to know, repeating, ordering, need to tell/ask, self-injury, and touching. Patients with autism spectrum disorders showed a significant reduction in repetitive behaviors following oxytocin infusion in comparison to placebo infusion. Repetitive behavior in autism spectrum disorders may be related to abnormalities in the oxytocin system, and may be partially ameliorated by synthetic oxytocin infusion.

Repetitive behaviors are a core symptom domain in autism that has been linked to alterations in the serotonin system. While the selective serotonin-receptive inhibitor fluvoxamine has been shown to be effective in adults with autism, as yet no published placebo controlled trials with these agents document safety and efficacy in children with autism. This study examines the selective serotonin reuptake inhibitor liquid fluoxetine in the treatment of repetitive behaviors in childhood and adolescent autism spectrum disorders (ASDs). In total, 45 child or adolescent patients with ASD were randomized into two acute 8-week phases in a double-blind placebocontrolled crossover study of liquid fluoxetine. Study design included two randomized 8-week fluoxetine and placebo phases separated by a 4-week washout phase. Outcome measures included measures of repetitive behaviors and global improvement. Low-dose liquid fluoxetine (mean final dose: 9.974.35 mg/day) was superior to placebo in the treatment of repetitive behaviors by CY-BOCS compulsion scale. The effect size was in the moderate to large range, and the doses used were low. Liquid fluoxetine was only slightly, and not significantly, superior to placebo on CGI autism score partially due to a phase order effect. However, fluoxetine was marginally superior to placebo on a composite measure of global effectiveness. Liquid fluoxetine did not significantly differ from placebo on treatment emergent side effects. Liquid fluoxetine in low doses is more effective than placebo in the treatment of repetitive behaviors in childhood autism. Limitations include small sample size and the crossover design of the study. Further replication and long-term maintenance trials are needed.

No abstract

Atypical antipsychotics have been shown to improve disruptive and repetitive behaviors in pervasive developmental disorders (PDDs), but they require assessment of potential side effects. This is the first placebo-controlled trial of olanzapine in the treatment of children and adolescents with PDD. Eleven patients with a diagnosis of either autism, Asperger's syndrome, or PDD not otherwise specified (PDD-NOS) and aged 6-14 years were randomized into an 8-week double-blind, placebo-controlled, parallel treatment study with olanzapine. There was a significant linear trend x group interaction on the Clinical Global Impressions- Improvement (CGI-I) and 50% on olanzapine versus 20% on placebo were responders. Olanzapine was associated with significant weight gain (7.5 +/- 4.8 lbs vs. 1.5 +/- 1.5 lbs on placebo). Olanzapine may be a promising treatment for improving global functioning of PDDs, but the risk of significant weight gain remains a concern. Additional studies are needed to determine the efficacy and safety of olanzapine in the treatment of children with PDD.

This paper identifies instruments and measures that may be appropriate for randomized clinical trials in participants with autism spectrum disorders (ASDs HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author Manuscript scale was recommended for all randomized clinical trials. At this point, however, there is no "perfect" choice of outcome measure for core features of autism, although we will discuss five measures of potential utility. Several communication instruments are recommended, based in part on suitability across the age range. In trials where the intention is to alter core features of ASDs, adaptive behavior scales are also worthy of consideration. Several "behavior complexes" common to ASDs are identified, and instruments are recommended for assessment of these. Given the prevalence of cognitive impairment in ASDs, it is important to assess any cognitive effects, although cognitive data from ASD randomized clinical trials, thus far, are minimal. Guidance from trials in related pharmacologic areas and behavioral pharmacology may be helpful. We recommend routine elicitation of side effects, height and weight, vital signs, and (in the case of antipsychotics) extrapyramidal side-effects assessment. It is often appropriate to include laboratory tests and assessments for continence and sleep pattern.