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.

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, Asperger's 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 Children's 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 methylphenidate's efficacy in relieving ADHD symptoms in some children with PDD. Optimal dose analyses suggested significant interindividual variability in dose response.

Children's Yale-Brown Obsessive Compulsive Scale modified for pervasive developmental disorders.

OBJECTIVE: To examine the psychometric properties of the Children's Yale-Brown Obsessive Compulsive Scales (CYBOCS) modified for pervasive developmental disorders (PDDs). METHOD: Raters from five Research Units on Pediatric Psychopharmacology (RUPP) Autism Network were trained to reliability. The modified scale (CYBOCS-PDD), which contains only the five Compulsion severity items (range 0-20), was administered to 172 medication-free children (mean 8.2 +/- 2.6 years) with PDD (autistic disorder, n = 152; Asperger's disorder, n = 6; PDD not otherwise specified, n = 14) participating in RUPP clinical trials. Reliability was assessed by intraclass correlation coefficient (ICC) and internal consistency by Cronbach's alpha coefficient. Correlations with ratings of repetitive behavior and disruptive behavior were examined for validity. RESULTS: Eleven raters showed excellent reliability (ICC = 0.97). The mean CYBOCS score was 14.4 (+/- 3.86) with excellent internal consistency (alpha = .85). Correlations with other measures of repetitive behavior ranged from r = 0.11 to r = 0.28 and were similar to correlations with measures of irritability (r = 0.24) and hyperactivity (r = 0.25). Children with higher scores on the CYBOCS-PDD had higher levels of maladaptive behaviors and lower adaptive functioning. CONCLUSIONS: The five-item CYBOCS-PDD is reliable, distinct from other measures of repetitive behavior, and sensitive to change.

Validity of the autism diagnostic interview-revised.

The factor structure, internal consistency, and convergent validity of the Autism Diagnostic Interview-Revised (ADI-R) algorithm items were examined in a sample of 226 youngsters with pervasive developmental disabilities. Exploratory factor analyses indicated a three-factor solution closely resembling the original algorithm and explaining 38% of the variance, with one significant discrepancy: Unlike the algorithm, all nonverbal communication items were associated with the Social factor. Internal consistencies of domain scores ranged from .54 to .84. Correlations between ADI-R domain and total scores and instruments assessing adaptive behavior, psychopathology, and autism were examined. They indicated some similarities between constructs, but also that the ADI-R measures autism in a unique fashion.

Risperidone and adaptive behavior in children with autism.

OBJECTIVE: To evaluate the impact of risperidone on adaptive behavior in children with autistic disorder who have serious behavior problems and to examine different methods of scoring the Vineland Adaptive Behavior Scales to measure change. METHOD: Forty-eight children (5 years to 16 years, 5 months) who showed behavioral improvement during acute treatment with risperidone were followed for 6 months and assessed with the Vineland Scales. RESULTS: Raw scores, age-equivalents, and special norm percentile scores all showed significant increases in adaptive behavior in the areas of communication, daily living skills, and socialization (p <.01). During a period of 6 to 8 months, children gained an average of 7.8 age-equivalent months in the area of socialization, a > 6% improvement beyond what would be expected based on baseline growth rates. CONCLUSIONS: Although limited by the absence of a control group, these results suggest that risperidone may improve adaptive skills in children with autistic disorder accompanied by serious behavioral problems. Vineland age-equivalent scores appear to be most useful in assessing change with treatment over time.

Parent-defined target symptoms respond to risperidone in RUPP autism study: customer approach to clinical trials.

OBJECTIVE: A consumer-oriented efficacy assessment in clinical trials should measure changes in chief complaint and consumer request (symptoms of most concern to patient/caregiver), which may be diluted in change scores of multisymptom scales. METHOD: In the Research Units on Pediatric Psychopharmacology (RUPP) Autism Network 8-week double-blind trial of risperidone versus placebo, the chief concerns of parents were collected at 0, 4, and 8 weeks (endpoint), in addition to standardized primary measures. Blinded clinical judges rated change from baseline to 4 and 8 weeks on a 9-point scale (1 = normalized, 5 = unchanged, 9 = disastrous); 94 participants had usable data. RESULTS: The most common symptoms identified by parents were tantrums, aggression, and hyperactivity. Interrater reliability was excellent. Mean ratings at endpoint were 2.8 +/- 1.2 on risperidone and 4.5 +/- 1.3 on placebo (p <.001). Ratings were collinear with Clinical Global Impression-Improvement and Aberrant Behavior Checklist Irritability subscale (primary dimensional measure). Effect size d was 1.4, compared to 1.2 on the Aberrant Behavior Checklist Irritability subscale. Effect sizes varied twofold by symptom category, largest for self-injury (2.11) and tantrums (1.95). CONCLUSIONS: Risperidone was superior to placebo in reducing symptoms of most concern to parents of autistic children with irritable behavior. Rating individualized participant-chosen target symptoms seems a reliable, sensitive, efficient, and consumer-friendly way to assess treatment effect and might have clinical application.

Psychiatric illness in a clinical sample of children with prenatal alcohol exposure.

The purpose of this study was to describe psychiatric disorders exhibited by children with prenatal alcohol exposure. Twenty-three children between the ages of 5 and 13 years who were referred to the UCLA Fetal Alcohol and Related Disorders Clinic because of heavy exposure to alcohol in utero were evaluated. Children with intelligence quotients of 70 and above and their families were interviewed by the study child psychiatrist and psychologist and psychiatric diagnoses were based upon DSM-IV diagnostic criteria. Inter-observer reliability of diagnosis was established comparing clinical diagnoses with diagnoses made using the "best-estimate" procedure. For the best estimate method, items from the Child Behavior Checklist, the Fetal Alcohol Behavior Scale, the Child Symptom Inventory-4, the Conners' Rating Scale, as well as information from historical records were reviewed by two experienced clinicians who were blind to the diagnostic and alcohol exposure status of the children. Approximately 87% of the sample met criteria for a psychiatric disorder. The majority of the children (61%) were assigned a mood disorder diagnosis. Twenty-six percent were diagnosed with major depressive disorder or adjustment disorder with depressed mood and 35% met criteria for bipolar disorder. Psychiatric disorders are common in children with prenatal alcohol exposure. In particular, these children seem to be highly vulnerable to mood disorders. There is a need for training in how to recognize the physical and behavioral phenotypes of children with prenatal alcohol exposure so that appropriate treatment can be initiated early.

Risperidone in children with autism and serious behavioral problems.

BACKGROUND: Atypical antipsychotic agents, which block postsynaptic dopamine and serotonin receptors, have advantages over traditional antipsychotic medications in the treatment of adults with schizophrenia and may be beneficial in children with autistic disorder who have serious behavioral disturbances. However, data on the safety and efficacy of atypical antipsychotic agents in children are limited. METHODS: We conducted a multisite, randomized, double-blind trial of risperidone as compared with placebo for the treatment of autistic disorder accompanied by severe tantrums, aggression, or self-injurious behavior in children 5 to 17 years old. The primary outcome measures were the score on the Irritability subscale of the Aberrant Behavior Checklist and the rating on the Clinical Global Impressions - Improvement (CGI-I) scale at eight weeks. RESULTS: A total of 101 children (82 boys and 19 girls; mean [+/-SD] age, 8.8+/-2.7 years) were randomly assigned to receive risperidone (49 children) or placebo (52). Treatment with risperidone for eight weeks (dose range, 0.5 to 3.5 mg per day) resulted in a 56.9 percent reduction in the Irritability score, as compared with a 14.1 percent decrease in the placebo group (P<0.001). The rate of a positive response, defined as at least a 25 percent decrease in the Irritability score and a rating of much improved or very much improved on the CGI-I scale, was 69 percent in the risperidone group (34 of 49 children had a positive response) and 12 percent in the placebo group (6 of 52, P<0.001). Risperidone therapy was associated with an average weight gain of 2.7+/-2.9 kg, as compared with 0.8+/-2.2 kg with placebo (P<0.001). Increased appetite, fatigue, drowsiness, dizziness, and drooling were more common in the risperidone group than in the placebo group (P<0.05 for each comparison). In two thirds of the children with a positive response to risperidone at eight weeks (23 of 34), the benefit was maintained at six months. CONCLUSIONS: Risperidone was effective and well tolerated for the treatment of tantrums, aggression, or self-injurious behavior in children with autistic disorder. The short period of this trial limits inferences about adverse effects such as tardive dyskinesia.