Ronald L. Lindsay

Dietary status and impact of risperidone on nutritional balance in children with autism: a pilot study.

Abstract Background Risperidone may be effective in improving tantrums, aggression, or self‐injurious behaviour in children with autism, but often leads to weight gain. Method Using a quantitative Food Frequency Questionnaire (FFQ), we prospectively examined the nutritional intake of 20 children with autism participating in a randomised placebo‐controlled trial of risperidone for disruptive behaviours. Results At baseline, the mean intakes for macronutrients, vitamins and minerals exceeded Dietary Reference Intakes (DRIs). However there was substantial inter‐participant variability, with individual deficiencies (<80% of DRI) in the intake of calcium (9 of 20 participants), pantothenic acid (6 of 20), vitamin D (5 of 20) and vitamin K (8 of 20). For the participants for whom FFQs were available, there was an increase in weight and an increase in vitamin K intake after 2 months of risperidone treatment (n = 9) compared to placebo (n = 8). An additional 4 months of risperidone treatment (n = 8) did not result in significant changes in reported nutritional balance. Conclusion These pilot data suggest that treatment with risperidone did not significantly affect the nutritional balance of this small group of children.

Methodological Issues in Designing a Multisite Trial of Risperidone in Children and Adolescents with Autism

OBJECTIVE To describe the methodological challenges and decisions made in developing a multisite, controlled study of risperidone in children and adolescents with autism. METHODS Review the design considerations for clinical trials in children with autistic disorder accompanied by severe tantrums, aggressive and/or self-injurious behaviors. These design considerations include the definition of inclusion criteria that are relevant to clinical practice and matching study design to the goal of evaluating short- and long-term effects. Additional ethical and scientific issues concern the length of trial and sample size. RESULTS We undertook a short-term, placebo-controlled study to evaluate the efficacy and safety of risperidone in children and adolescents with autistic disorder. This trial design was followed by an extended open-label maintenance on risperidone to confirm durability of treatment effects and to monitor safety. Finally, a placebo-controlled discontinuation study tested the need for continuous treatment. CONCLUSIONS In the absence of standard pharmacological treatment for children with autistic disorder, a placebo-controlled study remains the most appropriate method of testing efficacy and safety. The clinical relevance of this study is enhanced by the addition of an extended maintenance phase followed by a placebo discontinuation.

Treating attention-deficit/hyperactivity disorder with a stimulant transdermal patch: the clinical art.

Stimulant medications (amphetamine and methylphenidate) are the best-documented treatments for attention-deficit/hyperactivity disorder, but their short pharmacokinetic and behavioral half-lives have historically produced irksome time-course effects. New drug-delivery systems designed to eliminate the need for frequent dosing include the methylphenidate transdermal system, in which the matrix acts as both the drug reservoir and the skin adhesive. The methylphenidate transdermal system patch, in contrast to long-acting oral preparations, requires a paradigmatic shift in clinical thinking, as well as refinement of clinical management skills. For dosing with the methylphenidate transdermal system patch, clinicians must think in terms of a retrievable form of drug delivery (in milligrams per hour) rather than a fixed nonretrievable dose (in milligrams per dose or milligrams per day). Clinicians and patients can determine the optimal clinical dose by controlling 2 variables: (1) patch size (controlling milligrams per hour) and (2) duration of patch wear. The new paradigm is worth learning, because the patch offers several advantages over oral preparations for some patients, chiefly individualized control over effect duration (determined by when the patch is applied in the morning and removed in the afternoon/evening). Taking full advantage of this treatment option requires educating the patient and parents regarding practical elements of daily use. These elements include patch-site selection, application techniques, management of wear time to optimize the daily time course of clinical benefits, and skin hygiene. This article summarizes clinical principles that physicians may find useful in managing this new addition to the attention-deficit/hyperactivity disorder treatment armamentarium.

Effects of risperidone on cognitive-motor performance and motor movements in chronically medicated children

This study was designed to explore the placebo-controlled effects of risperidone on cognitive-motor processes, dyskinetic movements, and behavior in children receiving maintenance risperidone therapy. Sixteen children aged 4-14 years with disruptive behavior were randomly assigned to drug order in a crossover study of risperidone and placebo for 2 weeks each. Dependent measures included tests of sustained attention, memory, visual matching, tremor, seat activity, abnormal movements, and parent behavior ratings. Results were compared by repeated measures ANOVA. Fourteen boys and 2 girls with disruptive behavior and IQ</=84 all completed the protocol. Risperidone was superior to placebo on response time (p=0.01, eta(P)(2)=0.43) and seat movement (p<0.05, eta(P)(2)=0.29) on a short-term memory task, and on a measure of static tremor (p=0.05, eta(P)(2)=0.28). There was not a significant difference between treatment conditions on the Abnormal Involuntary Movement scale. Risperidone was superior to placebo on three subscales of the Nisonger Child Behavior Rating Form [Overly Sensitive (p<0.01, eta(P)(2)=0.44), Conduct Problem (p=0.02, eta(P)(2)=0.36), Hyperactivity (p=0.03, eta(P)(2)=0.32)] and on the Hyperactivity/Noncompliance subscale of the Aberrant Behavior Checklist (p=0.01, eta(P)(2)=0.41). Significant increases in heart rate (p=0.05, eta(P)(2)=0.27) and weight (p=0.02, eta(P)(2)=0.36) occurred in the risperidone condition. The findings suggest a beneficial effect of risperidone after several months of treatment on efficiency of responding, activity level, static tremor, and aspects of behavior.

Impact of attentional dysfunction in dyscalculia

Ronald L Lindsay* MD, Nisonger Center UAP, The Ohio State University, Columbus, OH; Terry Tomazic PhD, Department of Research Methodology, St Louis University, St Louis, MO; Melvin D Levine MD, Clinical Center for the Study of Development and Learning, University of North Carolina, Chapel Hill, NC; Pasquale J Accardo MD, Westchester Institute for Human Development, New York Medical College, Valhalla, NY, USA.

Discontinuation of Risperidone and Reversibility of Weight Gain in Children with Disruptive Behavior Disorders

Although atypical antipsychotics generally have a good side effect profile and are clinically very effective, weight gain and associated problems accompany their use. The authors followed up 14 subjects who were in studies of risperidone for management of disruptive behavior disorders. The subjects exited after a mean exposure of 8.9 months because of excessive weight gain, or excessive appetite, or insufficient clinical response. Weight was monitored for the full cohort before risperidone treatment, at termination, and (for various subgroups) at 3, 9-12, and 24 months after termination. Analysis of standardized weight scores in relation to standardized BMI scores suggested marked similarity between them at all time points. Comparison of standardized weights at time of drug termination with 3, 9-12, and 24 months after termination indicated that weight gain during risperidone treatment is reversible (i.e., significantly less weight after risperidone was discontinued) at all time points after termination. Furthermore, standardized weight at 12 and 24 months after discontinuation of risperidone was not distinguishable from standardized weight before risperidone. The prospect of reversibility may provide some comfort for clinicians and parents alike, but far more data are needed before an assumption can be made that this is the case for all children. The authors provide several recommendations for clinicians and researchers working with atypical antipsychotics.

Early Ear Problems and Developmental Problems at School Age

Retrospective history of middle ear disease was compared with developmental diagnosis in 507 consecutively referred school-age children. History of major ear problems was positively associated with discrepancies between the performance and verbal IQ on the WISC-R. History of major ear problems was positively associated with the presence of articulation disorders for children in the low social class, hyperactivity in the middle social class, and language problems in the high social class. A history of significant middle ear disease in early childhood should raise concerns for articulation difficulties and possible language problems in children presenting to clinicians with school problems.

The wrath of math : deficiencies of mathematical mastery in the school child

Mastery of mathematics involves the interactions of multiple developmental pathways. Children with mathematics disabilities often experience profound feelings of intellectual inadequacy that can erode self-esteem and academic motivation. This article delineates 16 interactive subcomponents that students who underachieve in mathematics can encounter. The article also discusses assessment and management issues for children with mathematics disabilities.

Pharmacologic therapies aid treatment for autism.

In the absence of other guidelines, practitioners often prescribe by analogy with roles of psychotropic medicines in other psychiatric disorders (e.g., the ability of serotonergic antidepressants to reduce compulsive behavior). There is a slow but steady accumulation of data supporting the use of psychotropic medications to manage certain symptoms in children with autism. These data support the use of stimulant medications for attention/hyperactivity symptoms, with willingness to suspend such treatment if a trial is unsuccessful. Risperidone is supported for other disruptive behaviors, especially of an irritable/disruptive nature, but with attention to increases in appetite and weight. SSRIs and atypical antipsychotics may be helpful for a variety of perseverative behaviors, although one would seldom prescribe antipsychotic medication for mild perseverative behavior alone. SSRIs may be useful for anxiety. Again, there is no compelling evidence that existing pharmacologic treatments have a major role in treating the core symptoms of autism, especially the profound impairments in social interaction and communication. Further well-designed double-blind studies with significant numbers of subjects and defined target symptoms will provide the data that will guide therapeutic decisions in the future.

Gestational and postnatal tobacco smoke exposure as predictor of ADHD, comorbid ODD/CD, and treatment response in the MTA

Abstract Objective: To examine relationships among early smoke exposure (ESE), attention-deficit/hyperactivity disorder (ADHD), oppositional-defiant or conduct disorder (ODD/CD), and whether ESE affects symptom severity, comorbidity, and later treatment response. Study design: The Multimodal Treatment Study of Children with ADHD (MTA) had 468 children with ADHD and 279 others from the same classrooms (local normative comparison group, LNCG) with smoke-exposure data. We compared ESE as ‘gestational’ or ‘postnatal’ (ambient house smoke only, without gestational) between ADHD and LNCG, and tested its association with ADHD severity, comorbid ODD/CD, methylphenidate response, and differential treatment response to four randomly assigned treatments. Results: About 1/3 more ADHD than LNCG children had ESE (both types), but association with gestational smoke attenuated from P =0.024 to 0.094 when subjects with comorbid ODD/CD were excluded, although total smoke exposure retained significance ( P =0.006). In the MTA/ADHD participants, comorbid ODD/CD, and parent/teacher-rated ADHD and ODD symptom severity were not associated with gestational smoking, but severity of ODD was associated with postnatal smoke, and for boys only, ADHD severity at 14 months associated with postnatal smoke. When ODD and CD were ‘unbundled’, CD was associated ( P =0.005) with gestational smoke. Neither ESE moderated response to methylphenidate, optimal dose, 2-year growth slowing, or differential ODD symptom response to 14-months of 4 randomly assigned treatments. However, for ADHD symptoms, postnatal smoke moderated ( P =0.008) the 14-month advantage of behavioral treatment (Beh) over community-treated comparison (CC): postnatally exposed boys benefited relatively more from Beh ( d >0.5). ADHD symptom improvement also showed significant interaction of sex with gestational ( P =0.015) and postnatal ( P =0.044) smoke moderator effect for the contrast of MTA medication algorithm vs. Beh and CC: smoke-exposed girls did not show the usual algorithm superiority. Conclusions: These findings suggest possible moderating effects of postnatal ESE on the advantage of intensive behavioral treatment and sex-differential moderating effects of ESE on the advantage of intensive medication over behavioral treatment. This exploratory result requires replication. The findings do not convincingly support the hypothesis that the association of gestational smoking with offspring ADHD is accounted for by comorbid ODD/CD.