Use of Functional Behavioral Assessments to Evaluate Stereotypy and Repetitive Behaviors in a Double-blind, Placebo Controlled Trials of Various Medications Used to Treat Children With Autism.
Condition: Autism
MeSH terms: Autistic Disorder
Study type: Observational

Summary: 
      Autism, originally described by Kanner (1943), is among the most severe of neuropsychiatric
      disorders. It is a pervasive developmental disorder affecting social, communicative, and
      compulsive/repetitive behaviors characterized by stereotypic complex hand and body movements,
      craving for sameness, and narrow repetitive interests. Individuals with autism spectrum
      disorders (ASD) are characteristically heterogeneous and show marked variability in their
      response to interventions. Studies of behavioral and psychopharmacological interventions
      document approximately 1/3 of ASD participants fail to respond to targeted treatments.
      Efforts to evaluate the specificity of treatment effects are important to inform
      conceptualizations about the disorder, identify behavioral phenotypes, and to aide clinical
      decision making.

      The goal of this study is to evaluate the use of clinical behavioral pharmacology methods,
      functional behavioral assessments (FBA), in assessing the treatment effects of pediatric
      medications in children with ASD. The present study of FBA procedures in pharmacological
      treatment will be conducted as a separate, but parallel study within IRB approved, federally
      funded, double-masked, placebo controlled medication trials of citalopram (GCO # 01-1295
      PS*), an SSRI hypothesized to reduce stereotyped and repetitive behaviors in ASD and
      divalproex sodium (GCO # 01-0294), a medication recently found to reduce repetitive behaviors
      in ASD (Hollander et al., in press). This study will focus on the use of FBAs in
      distinguishing responders vs. nonresponders on the basis of behavior function, in evaluating
      functional patterns for stereotypy, aggression, and impulsivity, and in using descriptive
      FBAs as outcome measures in clinical trials.

      FBAs are behavioral assessment methods used to hypothesize about the function of maladaptive
      behaviors. FBAs are conducted either through experimental manipulations known as functional
      analyses or through descriptive analyses procedures, which involve structured observations
      and parent/caregiver interviews. Descriptive analyses will be conducted with all participants
      (n=24). The more rigorous, functional analyses will be conducted with a sub-set of the sample
      (n=6) to corroborate the findings of the descriptive analyses. Data from the FBAs will be
      collected using videotaped recordings of behavior and coded by trained raters for both the
      descriptive and experimental analyses.

      Our pilot data and other published data suggest that certain medications such as citalopram
      (celexa) and divalproex sodium (Depakote) may improve global functioning in autistic patients
      and repetitive/compulsive behaviors and social deficits. The addition of FBA methods to
      evaluate outcome are an important step in extending the research and knowledge of the
      conditions associated with good and poor treatment response to pediatric medications in
      children with autism.
    

Detailed description: 
      Research geared towards increasing knowledge of the variables contributing to treatment
      response is critical to advancing intervention studies in ASD. Literature in the growing
      field of clinical behavioral pharmacology suggests functional behavioral assessments (FBA),
      when integrated into clinical trials of medication, can be important tools in elucidating the
      specificity of treatment effects (Mace & Mauk, 1995, Northup & Gully, 2001). The goal of this
      study is to evaluate the use of clinical behavioral pharmacology methods, primarily
      descriptive functional behavioral assessments (FBA), in a double-masked, placebo controlled
      trial of medications used to treat children with autism. These medications are hypothesized
      to reduce the stereotyped and repetitive behaviors in ASD. This study will focus on the use
      of descriptive FBAs in distinguishing responders vs. non-responders on the basis of behavior
      function, in evaluating functional patterns for stereotypy, and in using descriptive FBAs as
      outcome measures in clinical trials.

      This study is accordance with CAN research priorities in its focus on improving
      methodological approaches in clinical trials (Hollander, et al., 2004). This study is also
      consistent with recent NIMH recommendations for clinical research. The recommendations
      identify the integration of behavioral research methods with traditional methods of clinical
      research (i.e. group designs) as important aims for ASD treatment research (CPEA/STAART
      working group, 2004). As such, this study fills significant gaps in two research areas:
      treatments for repetitive behaviors and research methodology in treatment trials for
      individuals with ASD.

      The bio-behavioral methods proposed for use in this evaluation have been previously used to
      stratify and match treatments for self-injurious behavior in adults with developmental
      disabilities (Mace & Mauk, 1995), identify specific treatment effects of methylphenidate in
      children with ADHD (Northup & Gully, 2001), and more recently in evaluating the specificity
      of risperidone's effects on destructive behaviors in individuals with autism (Crosland, et
      al, 2003).

      Despite that stereotyped and repetitive behaviors are a core symptom domain of ASD,
      behavioral pharmacology approaches to date have only evaluated the correlated symptoms of
      aggression, self-injurious, and destructive behaviors in ASD. Repetitive behaviors in ASD
      include stereotypic movements, repetition of routine behaviors, repetitive play,
      perseverative speech, and over-focus on restricted interests. These repetitive movements may
      be associated with emotional distress, tension, or dysphoria and have significant impacts on
      daily life. It is believed that the methods used to elucidate and specify treatment effects
      in other medications and disorders will also be valuable to the understanding of SSRI effects
      in autism.

      Both behavioral and pharmacological treatments have been used to treat repetitive and
      stereotyped behaviors in autism. Behavioral treatments include the use of noncontingent
      reinforcement (Britton, et al., 2002) and alternative response training to maintain
      homeostasis (Johnson, Laarhoven, & Repp, 2002). Psychopharmacological approaches include the
      use of SSRIs given the similarity between repetitive behaviors in autism and OCD (McDougle,
      1995) and evidence for serotonin dysfunction in ASD (Hollander, 2000). To date, there are few
      controlled studies with any of the SSRIs in pediatric populations with ASD. Hollander &
      colleagues (Hollander, et al., in press) at Mt. Sinai recently completed a study suggesting
      the efficacy of low-dose liquid fluoxetine on reducing repetitive behaviors in a
      double-blind, placebo controlled crossover study of 45 children with ASD. This proposed FBA
      evaluation would occur within another SSRI trial at Mt. Sinai, which aims to extend previous
      findings in a large scale, multisite investigation of the safety and efficacy of liquid
      citalopram in children with ASD.

      Behavioral pharmacology methods Functional behavioral assessments (FBA) are the cornerstone
      of clinical behavioral pharmacology approaches. The goals of FBAs are to hypothesize and
      experimentally test the functions of maladaptive behaviors. Within the field of behavior
      analysis, determining the function of the maladaptive behavior is primary to developing
      effective interventions.

      FBAs involve both experimental and descriptive assessments of behavior functions.
      Experimental methods, also known as functional analyses (Iwata, et al., 1982/1994), have the
      advantage of using experimental manipulations and direct, continuous observations of
      behavior. The procedures outlined by Iwata, et al. (1982/1994) are considered the
      gold-standard for functional analyses. The procedure involves the use of multi-element,
      single-subject experimental design. During the functional analysis, consequences presented
      for a maladaptive behavior are varied. The experimental conditions outlined by Iwata, et al.
      (1982/1994) are labeled by the presumed function tested in a condition and include:
      escape/avoidance, attention, automatic reinforcement/self-stimulation, and control (i.e.
      preferred toys + social attention).

      Experimental methods provide valuable and reliable data on behavior functions, but involve
      significant time and expense for patients and experimenters. In contrast, descriptive methods
      are based on parent/caregiver-report, direct behavioral observations, and provide information
      on both consequent and antecedent predictors of behavior. Descriptive methods are strongly
      correlated with experimental analyses and have advantages because of the information provided
      on antecedent functions and in their relative cost-effectiveness (Horner, et al., 1997). This
      study will pilot the use of descriptive assessment methods as an outcome measure and use
      experimental FBAs to corroborate the results of the descriptive analyses.

      The methods and outcome of this investigation will be used to design an independent clinical
      trial using a multi-method approach, including descriptive and experimental FBAs as outcome
      measures, in medication studies of repetitive behaviors in ASD. Given this research has
      limited funding options outside of CAN, funding this project may be a critical, preliminary
      step in improving our treatment-specificity research and clinical research methods in ASD.

      Specific Aims

      The primary aim of this study is to determine the usability of functional behavioral
      assessment (FBA) procedures in predicting and measuring treatment response within a clinical
      trial of citalopram, an SSRI hypothesized to reduce repetitive behaviors in ASD. The specific
      aims of the study are as follows:

        1. To predict treatment response through results from descriptive FBAs.

        2. To evaluate functional patterns for stereotypy/repetitive behaviors in ASD.

        3. To evaluate the use of descriptive FBAs as outcome measures in SSRI trials in ASD and to
           correlate results from descriptive FBAs with standard global rating measures such as the
           Child Yale-Brown Obsessive Compulsive Scale (CYBOCS) and the Aberrant Behavior Checklist
           (ABC) for repetitive behaviors and stereotypy.
    

Intervention name(s): Behavioral Assessment
Intervention type(s): Behavioral
Intervention description(s): functional behavioral assessments are conducted at two separate visits for each subject.
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Subjects who are enrolled in the approved double-blind placebo controlled trial of
        citalopram in young children with autism.
      
Keywords: Autism; Functional Behavioral Assessment; Citalopram