Naomi B. Swiezy

Medication and Parent Training in Children With Pervasive Developmental Disorders and Serious Behavior Problems: Results From a Randomized Clinical Trial

OBJECTIVE Many children with pervasive developmental disorders (PDDs) have serious, functionally impairing behavioral problems. We tested whether combined treatment (COMB) with risperidone and parent training (PT) in behavior management is superior to medication alone (MED) in improving severe behavioral problems in children with PDDs. METHOD This 24-week, three-site, randomized, parallel-groups clinical trial enrolled 124 children, aged 4 through 13 years, with PDDs, accompanied by frequent tantrums, self-injury, and aggression. The children were randomized 3:2 to COMB (n = 75) or MED (n = 49). The participants received risperidone monotherapy from 0.5 to 3.5 mg/day (with switch to aripiprazole if risperidone was ineffective). Parents in the COMB group (n = 75; 60.5%) received a mean of 10.9 PT sessions. The primary measure of compliance was the Home Situations Questionnaire (HSQ) score. RESULTS Primary: intent-to-treat random effects regression showed that COMB was superior to MED on HSQ (p = .006) [effect size at week 24 (d) = 0.34]. The HSQ score declined from 4.31 (± 1.67) to 1.23 (± 1.36) for COMB compared with 4.16 (± 1.47) to 1.68 (± 1.36) for MED. Secondary: groups did not differ on Clinical Global Impressions-Improvement scores at endpoint; compared with MED, COMB showed significant reductions on Aberrant Behavior Checklist Irritability (d = 0.48; p = .01), Stereotypic Behavior (d = 0.23; p = .04), and Hyperactivity/Noncompliance subscales (d = 0.55; p = .04). Final risperidone mean dose for MED was 2.26 mg/day (0.071 mg/kg), compared with 1.98 mg/day for COMB (0.066 mg/kg) (p = .04). CONCLUSIONS Medication plus PT resulted in greater reduction of serious maladaptive behavior than MED in children with PDDs, with a lower risperidone dose.

Assessment in Multisite Randomized Clinical Trials of Patients with Autistic Disorder: The Autism RUPP Network

Assessment of autistic disorder (autism) symptoms, primary and secondary, poses more challenging problems than ordinarily found in multisite randomized clinical trial (RCT) assessments. For example, subjects may be uncommunicative and extremely heterogeneous in problem presentation, and current pharmacological treatments are not likely to alter most core features of autism. The Autism Research Units on Pediatric Psychopharmacology (RUPP Autism Network) resolved some of these problems during the design of a risperidone RCT in children/adolescents. The inappropriateness of the usual anchors for a Clinical Global Impression of Severity (CGI-S) was resolved by defining uncomplicated autism without secondary symptoms as a CGI-S of 3, mildly ill. The communication problems, compromising use of the patient as an informant, were addressed by several strategies, including careful questioning of care providers, rating scales, laboratory tests, and physical exams. The broad subject heterogeneity requires outcome measures sensitive to individual change over a wide spectrum of treatment response and side effects. The problems of neuropsychologically testing nonverbal, lower functioning, sometimes noncompliant subjects requires careful instrument selection/adaptation and flexible administration techniques. The problems of assessing low-end IQs, neglected by most standardized test developers, was resolved by an algorithm of test hierarchy. Scarcity of other autism-adapted cognitive and neuropsychological tests and lack of standardization required development of a new, specially adapted battery. Reliability on the Autism Diagnostic Interview (currently the most valid diagnostic instrument) and other clinician instruments required extensive cross-site training (in-person, videotape, and teleconference sessions). Definition of a treatment responder required focus on individually relevant target symptoms, synthesis of possible modest improvements in many domains, and acceptance of attainable though imperfect goals. The assessment strategy developed is implemented in a RCT of risperidone (McDougle et al., 2000) for which the design and other methodological challenges are described elsewhere (Scahill et al., 2000). Some of these problems and solutions are partially shared with RCTs of other treatments and other disorders.

Positive effects of methylphenidate on inattention and hyperactivity in pervasive developmental disorders : An analysis of secondary measures

BACKGROUND Methylphenidate has been shown elsewhere to improve hyperactivity in about half of treated children who have pervasive developmental disorders (PDD) and significant hyperactive-inattentive symptoms. We present secondary analyses to better define the scope of effects of methylphenidate on symptoms that define attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD), as well as the core autistic symptom domain of repetitive behavior. METHODS Sixty-six children (mean age 7.5 y) with autistic disorder, Aspergers disorder, and PDD not otherwise specified, were randomized to varying sequences of placebo and three different doses of methylphenidate during a 4-week blinded, crossover study. Methylphenidate doses used approximated .125, .25, and .5 mg/kg per dose, twice daily, with an additional half-dose in the late afternoon. Outcome measures included the Swanson, Nolan, and Pelham Questionnaire revised for DSM-IV (ADHD and ODD scales) and the Childrens Yale-Brown Obsessive Compulsive Scales for PDD. RESULTS Methylphenidate was associated with significant improvement that was most evident at the .25- and .5-mg/kg doses. Hyperactivity and impulsivity improved more than inattention. There were not significant effects on ODD or stereotyped and repetitive behavior. CONCLUSIONS Convergent evidence from different assessments and raters confirms methylphenidates efficacy in relieving ADHD symptoms in some children with PDD. Optimal dose analyses suggested significant interindividual variability in dose response.

Cognitive Effects of Risperidone in Children with Autism and Irritable Behavior

OBJECTIVE The objective of this research was to explore the effects of risperidone on cognitive processes in children with autism and irritable behavior. METHOD Thirty-eight children, ages 5-17 years with autism and severe behavioral disturbance, were randomly assigned to risperidone (0.5 to 3.5 mg/day) or placebo for 8 weeks. This sample of 38 was a subset of 101 subjects who participated in the clinical trial; 63 were unable to perform the cognitive tasks. A double-blind placebo-controlled parallel groups design was used. Dependent measures included tests of sustained attention, verbal learning, hand-eye coordination, and spatial memory assessed before, during, and after the 8-week treatment. Changes in performance were compared by repeated measures ANOVA. RESULTS Twenty-nine boys and 9 girls with autism and severe behavioral disturbance and a mental age >or=18 months completed the cognitive part of the study. No decline in performance occurred with risperidone. Performance on a cancellation task (number of correct detections) and a verbal learning task (word recognition) was better on risperidone than on placebo (without correction for multiplicity). Equivocal improvement also occurred on a spatial memory task. There were no significant differences between treatment conditions on the Purdue Pegboard (hand-eye coordination) task or the Analog Classroom Task (timed math test). CONCLUSION Risperidone given to children with autism at doses up to 3.5 mg for up to 8 weeks appears to have no detrimental effect on cognitive performance.

Skill acquisition in parents of children with developmental disabilities:: Interaction between skill type and instructional format

A variety of instructional formats have been used to teach parents of children with developmental disabilities how to implement treatments for problem behavior. Although several authors have suggested that the efficacy of various instructional methods might depend on the type of skill taught to parents, no studies have been designed to systematically explore this potential interaction. In this preliminary study, three parents who requested outpatient services for treatment of their childrens problem behavior were taught to implement multiple treatment components. Therapists employed the most cost-efficient method first (i.e., written and verbal instructions) to teach prescribed behavior management strategies (e.g., differential reinforcement). If the parents behavior failed to meet a performance criterion, feedback was included in training sessions. The efficacy of verbal and written instructions varied across different components of the childs treatment program.

Bridging for success in autism: training and collaboration across medical, educational, and community systems.

The basis for the need for improved training and collaboration models in the field of autism is supported through historical background and literature in related fields. Ultimately, training specific to autism spectrum disorders and related evidence-based practices is proposed as necessary for all care providers having influence on programming related to this special population. It is also posited that the most effective avenue for training is through models incorporating more intensive and interactive training processes such as hands-on learning activities with opportunities for coaching, modeling, practice and feedback. Effective collaboration across systems (including home, medical, educational, and community settings) is emphasized to facilitate consistency in implementation of strategies for ultimate program success.

Examination of aggression and self-injury in children with autism spectrum disorders and serious behavioral problems.

This study identified subtypes of aggression in a sample of 206 children with autism spectrum disorder (ASD) who participated in 2 risperidone trials. The narratives were derived from a parent interview about each childs 2 most pressing problems. Five subtypes of aggression emerged: hot aggression only, cold aggression only, self-injurious behavior (SIB) only, aggression and SIB, and nonaggressive. All groups showed a high rate of positive response to risperidone with no differences across subtypes. These study findings extend understanding of aggression in ASD and may be useful to guide further study on biological mechanisms and individualized treatment in ASD.

Research Units of Pediatric Psychopharmacology (RUPP) Autism Network Randomized Clinical Trial of Parent Training and Medication: One-Year Follow-Up.

OBJECTIVE To follow up on a three-site, 24-week randomized clinical trial (N = 124) comparing antipsychotic medication alone (MED) with antipsychotic medication plus parent training in the behavior management (COMB) of children with autism spectrum disorders and severe behavior problems. The COMB treatment had shown a significant advantage for child behavioral noncompliance (p = .006, d = 0.34), irritability (p = .01, d = 0.48), and hyperactivity/noncompliance (p = .04, d = 0.55) with a lower medication dose. METHOD One year after each participants termination, the authors mailed an assessment packet with a return-addressed envelope; a telephone call alerted the family. Failure to return packets within 1 month elicited another contact and offers to resend. RESULTS Eighty-seven of 124 families (70.2%) participated in the follow-up. The improvement difference between treatments attenuated from after treatment to follow-up for noncompliance (d = 0.32 to 0.12) and irritability (d = 0.46 to 0.03). The follow-up differences were nonsignificant (the noncompliance difference also was nonsignificant after treatment for these 87 families). Sixty-seven percent of the COMB group and 53% of the MED group were still taking risperidone, the original study medication. Most needed dose adjustments or additional medication, and the COMB group no longer had a significantly lower dose. All COMB families but only 39% of MED families reported seeking parent training after treatment. Improvements in daily living skills during treatment predicted noncompliance improvement at follow-up for the COMB children, but noncompliance deterioration and especially hyperactivity/noncompliance deterioration for the MED children. CONCLUSIONS The study treatment experience/familiarity greatly influenced the follow-up treatment: those who had received parent training reported seeking it, whereas those who had not received it tended not to seek it. The superiority of COMB over MED after treatment attenuated by more than half at follow-up.

Factor structure and psychometric properties of the revised Home Situations Questionnaire for autism spectrum disorder: The Home Situations Questionnaire-Autism Spectrum Disorder:

Previously, we adapted the Home Situations Questionnaire to measure behavioral non-compliance in everyday settings in children with pervasive developmental disorders. In this study, we further revised this instrument for use in autism spectrum disorder and examined its psychometric properties (referred to as the Home Situations Questionnaire-Autism Spectrum Disorder). To cover a broader range of situations and improve reliability, we prepared seven new items describing situations in which children with autism spectrum disorder might display non-compliance. Parents completed ratings of 242 children with autism spectrum disorder with accompanying disruptive behaviors (ages 4–14 years) participating in one of two randomized clinical trials. Results from an exploratory factor analysis indicated that the Home Situations Questionnaire-Autism Spectrum Disorder consists of two 12-item factors: Socially Inflexible (α = 0.84) and Demand Specific (α = 0.89). One-to-two-week test–retest reliability was statistically significant for all scored items and also for subscale totals. The pattern of correspondence between the Home Situations Questionnaire-Autism Spectrum Disorder and parent-rated problem behavior, clinician-rated repetitive behavior, adaptive behavior, and IQ provided evidence for concurrent and divergent validity of the Home Situations Questionnaire-Autism Spectrum Disorder. Overall, the results suggest that the Home Situations Questionnaire-Autism Spectrum Disorder is an adequate measure for assessing non-compliance in a variety of situations in this population, and use of its two subscales will likely provide a more refined interpretation of ratings.

Predictors and moderators of parent training efficacy in a sample of children with autism spectrum disorders and serious behavioral problems.

The Research Units on Pediatric Psychopharmacology—Autism Network reported additional benefit when adding parent training (PT) to antipsychotic medication in children with autism spectrum disorders and serious behavior problems. The intent-to-treat analyses were rerun with putative predictors and moderators. The Home Situations Questionnaire (HSQ) and the Hyperactivity/Noncompliance subscale of the Aberrant Behavior Checklist were used as outcome measures. Candidate predictors and moderators included 21 demographics and baseline measures of behavior. Higher baseline HSQ scores predicted greater improvement on the HSQ regardless of treatment assignment, but no other predictors of outcome were observed. None of the variables measured in this study moderated response to PT. Antipsychotic medication plus PT appears to be equally effective for children with a wide range of demographic and behavioral characteristics.