Naomi B. Swiezy

Bio: Naomi B. Swiezy is an academic researcher from Indiana University. The author has contributed to research in topics: Autism & Risperidone. The author has an hindex of 29, co-authored 53 publications receiving 4579 citations. Previous affiliations of Naomi B. Swiezy include Kennedy Krieger Institute & Indiana University – Purdue University Indianapolis.

Risperidone in Children with Autism and Serious Behavioral Problems

Abstract: 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). Treat...

Randomized, controlled, crossover trial of methylphenidate in pervasive developmental disorders with hyperactivity

Abstract: CONTEXT Hyperactivity and inattention are common symptoms in children with autistic disorder and related pervasive developmental disorders, but studies of stimulants in these conditions have been inconclusive. OBJECTIVES To determine the efficacy and safety of methylphenidate hydrochloride in children with pervasive developmental disorders and hyperactivity. DESIGN Double-blind, placebo-controlled, crossover trial followed by open-label continuation. SETTING Five academic outpatient clinics. PARTICIPANTS Seventy-two drug-free children, aged 5 to 14 years, with pervasive developmental disorders accompanied by moderate to severe hyperactivity. INTERVENTIONS Prior to randomization, subjects entered a 1-week test-dose phase in which each subject received placebo for 1 day followed by increasing doses of methylphenidate (low, medium, and high doses) that were each given for 2 days. The low, medium, and high doses of methylphenidate hydrochloride were based on weight, and they ranged from 7.5 mg/d to 50.0 mg/d in divided doses. Subjects who tolerated the test dose (n = 66) were assigned to receive placebo for 1 week and then 3 methylphenidate doses in random order during a double-blind, crossover phase. Children responding to methylphenidate then entered 8 weeks of open-label treatment at the individually determined best dose. MAIN OUTCOME MEASURES The primary outcome measure was the teacher-rated hyperactivity subscale of the Aberrant Behavior Checklist. Response was defined as \"much improved\" or \"very much improved\" on the Clinical Global Impressions Improvement item coupled with considerable reductions in the parent-rated and/or teacher-rated Aberrant Behavior Checklist hyperactivity subscale score. RESULTS Methylphenidate was superior to placebo on the primary outcome measure, with effect sizes ranging from 0.20 to 0.54 depending on dose and rater. Thirty-five (49%) of 72 enrolled subjects were classified as methylphenidate responders. Adverse effects led to the discontinuation of study medication in 13 (18%) of 72 subjects. CONCLUSIONS Methylphenidate was often efficacious in treating hyperactivity associated with pervasive developmental disorders, but the magnitude of response was less than that seen in typically developing children with attention-deficit/hyperactivity disorder. Adverse effects were more frequent.

Risperidone for the core symptom domains of autism: results from the study by the autism network of the research units on pediatric psychopharmacology.

Abstract: OBJECTIVE: Risperidone has been found efficacious for decreasing severe tantrums, aggression, and self-injurious behavior in children and adolescents with autistic disorder (autism). The authors report on whether risperidone improves the core symptoms of autism, social and communication impairment and repetitive and stereotyped behavior. METHOD: The database from an 8-week double-blind, placebo-controlled trial (N=101) and 16-week open-label continuation study (N=63) of risperidone for children and adolescents with autism was used to test for drug effects on secondary outcome measures: scores on the Ritvo-Freeman Real Life Rating Scale, the Children’s Yale-Brown Obsessive Compulsive Scale, and the maladaptive behavior domain of the Vineland Adaptive Behavior Scales. RESULTS: Compared to placebo, risperidone led to a significantly greater reduction in the overall score on the Ritvo-Freeman Real Life Rating Scale, as well as the scores on the subscales for sensory motor behaviors (subscale I), affectual rea...

Effect of Parent Training vs Parent Education on Behavioral Problems in Children With Autism Spectrum Disorder: A Randomized Clinical Trial

Abstract: RESULTS At week 24, the Aberrant Behavior Checklist–Irritability subscale declined 47.7% in parent training (from 23.7 to 12.4) compared with 31.8% for parent education (23.9 to 16.3) (treatment effect, −3.9; 95% CI, −6.2 to −1.7; P < .001, standardized effect size = 0.62). The Home Situations Questionnaire–Autism Spectrum Disorder declined 55% (from 4.0 to 1.8) compared with 34.2% in parent education (3.8 to 2.5) (treatment effect, −0.7; 95% CI, −1.1 to −0.3; P < .001, standardized effect size = 0.45). Neither measure met the prespecified minimal clinically important difference. The proportions with a positive response on the Clinical Global Impression– Improvement scale were 68.5% for parent training vs 39.6% for parent education (P < .001). CONCLUSIONS AND RELEVANCE For children with autism spectrum disorder, a 24-week parent training program was superior to parent education for reducing disruptive behavior on parent-reported outcomes, although the clinical significance of the improvement is unclear. The rate of positive response judged by a blinded clinician was greater for parent training vs parent education.

Medication and Parent Training in Children with Pervasive Developmental Disorders and Serious Behavior Problems: Results from a Randomized Clinical Trial.

Abstract: 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.

Psychiatric disorders in children with autism spectrum disorders: Prevalence, comorbidity, and associated factors in a population-derived sample

Abstract: Objective Autism spectrum disorders are now recognized to occur in up to 1% of the population and to be a major public health concern because of their early onset, lifelong persistence, and high levels of associated impairment. Little is known about the associated psychiatric disorders that may contribute to impairment. We identify the rates and type of psychiatric comorbidity associated with ASDs and explore the associations with variables identified as risk factors for child psychiatric disorders. Method A subgroup of 112 ten- to 14-year old children from a population-derived cohort was assessed for other child psychiatric disorders (3 months' prevalence) through parent interview using the Child and Adolescent Psychiatric Assessment. DSM-IV diagnoses for childhood anxiety disorders, depressive disorders, oppositional defiant and conduct disorders, attention-deficit/hyperactivity disorder, tic disorders, trichotillomania, enuresis, and encopresis were identified. Results Seventy percent of participants had at least one comorbid disorder and 41% had two or more. The most common diagnoses were social anxiety disorder (29.2%, 95% confidence interval [Cl)] 13.2-45.1), attention-deficit/hyperactivity disorder (28.2%, 95% Cl 13.3-43.0), and oppositional defiant disorder (28.1 %, 95% Cl 13.9-42.2). Of those with attention-deficit/hyperactivity disorder, 84% received a second comorbid diagnosis. There were few associations between putative risk factors and psychiatric disorder. Conclusions Psychiatric disorders are common and frequently multiple in children with autism spectrum disorders. They may provide targets for intervention and should be routinely evaluated in the clinical assessment of this group. J. Am. Acad. Child Adolesc. Psychiatry , 2008;47(8):921-929.

Comorbid Psychiatric Disorders in Children with Autism: Interview Development and Rates of Disorders

Abstract: The Kiddie Schedule for Affective Disorders and Schizophrenia was modified for use in children and adolescents with autism by developing additional screening questions and coding options that reflect the presentation of psychiatric disorders in autism spectrum disorders. The modified instrument, the Autism Comorbidity Interview-Present and Lifetime Version (ACI-PL), was piloted and frequently diagnosed disorders, depression, ADHD, and OCD, were tested for reliability and validity. The ACI-PL provides reliable DSM diagnoses that are valid based on clinical psychiatric diagnosis and treatment history. The sample demonstrated a high prevalence of specific phobia, obsessive compulsive disorder, and ADHD. The rates of psychiatric disorder in autism are high and are associated with functional impairment.

Second-Generation (Atypical) Antipsychotics and Metabolic Effects: A Comprehensive Literature Review.

Abstract: Increasing numbers of reports concerning diabetes, ketoacidosis, hyperglycaemia and lipid dysregulation in patients treated with second-generation (or atypical) antipsychotics have raised concerns about a possible association between these metabolic effects and treatment with these medications. This comprehensive literature review considers the evidence for and against an association between glucose or lipid dysregulation and eight separate second-generation antipsychotics currently available in the US and/or Europe, specifically clozapine, olanzapine, risperi-done, quetiapine, zotepine, amisulpride, ziprasidone and aripiprazole. This review also includes an assessment of the potential contributory role of treatment-induced weight gain in conferring risk for hyperglycaemia and dyslipidaemia during treatment with different antipsychotic medications. Substantial evidence from a variety of human populations, including some recent confirmatory evidence in treated psychiatric patients, indicates that increased adiposity is associated with a variety of adverse physiological effects, including decreases in insulin sensitivity and changes in plasma glucose and lipid levels. Comparison of mean weight changes and relative percentages of patients experiencing specific levels of weight increase from controlled, randomised clinical trials indicates that weight gain liability varies significantly across the different second-generation antipsychotic agents. Clozapine and olanzapine treatment are associated with the greatest risk of clinically significant weight gain, with other agents producing relatively lower levels of risk. Risperidone, quetiapine, amisulpride and zotepine generally show low to moderate levels of mean weight gain and a modest risk of clinically significant increases in weight. Ziprasidone and aripiprazole treatment are generally associated with minimal mean weight gain and the lowest risk of more significant increases. Published studies including uncontrolled observations, large retrospective database analyses and controlled experimental studies, including randomised clinical trials, indicate that the different second-generation antipsychotics are associated with differing effects on glucose and lipid metabolism. These studies offer generally consistent evidence that clozapine and olanzapine treatment are associated with an increased risk of diabetes mellitus and dyslipidaemia. Inconsistent results, and a generally smaller effect in studies where an effect is reported, suggest limited if any increased risk for treatment-induced diabetes mellitus and dyslipidaemia during risperidone treatment, despite a comparable volume of published data. A similarly smaller and inconsistent signal suggests limited if any increased risk of diabetes or dyslipidaemia during quetiapine treatment, but this is based on less published data than is available for risperidone. The absence of retrospective database studies, and little or no relevant published data from clinical trials, makes it difficult to draw conclusions concerning risk for zotepine or amisulpride, although amisulpride appears to have less risk of treatment-emergent dyslipidaemia in comparison to olanzapine. With increasing data from clinical trials but little or no currently published data from large retrospective database analyses, there is no evidence at this time to suggest that ziprasidone and aripiprazole treatment are associated with an increase in risk for diabetes, dyslipidaemia or other adverse effects on glucose or lipid metabolism. In general, the rank order of risk observed for the second-generation antipsychotic medications suggests that the differing weight gain liability of atypical agents contributes to the differing relative risk of insulin resistance, dyslipidaemia and hyperglycaemia. This would be consistent with effects observed in nonpsychiatric samples, where risk for adverse metabolic changes tends to increase with increasing adiposity. From this perspective, a possible increase in risk would be predicted to occur in association with any treatment that produces increases in weight and adiposity. However, case reports tentatively suggest that substantial weight gain or obesity may not be a factor in up to one-quarter of cases of new-onset diabetes that occur during treatment. Pending further testing from preclinical and clinical studies, limited controlled studies support the hypothesis that clozapine and olanzapine may have a direct effect on glucose regulation independent of adiposity. The results of studies in this area are relevant to primary and secondary prevention efforts that aim to address the multiple factors that contribute to increased prevalence of type 2 diabetes mellitus and cardiovascular disease in populations that are often treated with second-generation antipsychotic medications.

Risperidone in Children with Autism and Serious Behavioral Problems

Abstract: 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). Treat...