Stephen R. Schroeder

Weight Gain in a Controlled Study of Risperidone in Children, Adolescents and Adults with Mental Retardation and Autism

As part of an ongoing, prospective, ABA design, double-blind crossover study of risperidone versus placebo for the treatment of aggressive, destructive and self-injurious behavior in persons aged 6-65 years with mental retardation (MR) and autism, we measured the weight of 19 subjects at each study visit. We compared mean weight gain during the 16-week acute phase and 24-week open maintenance phase with that during the initial and middle placebo phases statistically, using a linear mixed model procedure. Results of the linear mixed model analysis showed that relative weight gain observed during the acute and maintenance drug phases was significantly greater than that observed during the initial and middle placebo phases respectively (p = .0001 and p = .0001). Over approximately a year, children aged 8-12 (n = 5) gained a mean of 8.2 kg (range = 2.7-17.7 kg); adolescents (n = 6) aged 13-16 gained a mean of 8.4 kg (range 3.6-15.5 kg); adults aged 21-51 (n = 8) gained a mean of 5.4 kg (range 0-9.5 kg). Weight gain observed in this controlled study of risperidone treatment in children, adolescents, and adults with MR and autism was significant. It may be greater in this population than in others reported and in this study was not limited to an acute effect only. Rate of weight gain diminished rapidly on tapering and stopping the drug. Further studies are urgently needed, including those incorporating diet and exercise programming.

Effects of risperidone on Aberrant behavior of persons with developmental disabilities: I. A double-blind crossover study using multiple measures

The efficacy of the atypical antipsychotic risperidone was evaluated in the treatment of aberrant behavior (e.g., aggression, self-injury) in 20 individuals with developmental disabilities. A double-blind, crossover design was used to compare risperidone with placebo in a 22-week trial with a 6-month follow-up phase. Based on a 50% reduction in mean Aberrant Behavior Checklist--Community total scores, 50% of the participants were identified as responders. Naturalistic observations of a subset of five individuals showed that for 4 out of 5 participants, risperidone was effective in reducing aberrant behavior. Side effects included weight gain (84% of participants) and sedation (40% of participants). The advantages of conducting a comprehensive analysis of the effects of medication on aberrant behavior are discussed.

Effects of risperidone on destructive behavior of persons with developmental disabilities: III. Functional analysis.

Functional analyses were conducted during a double-blind, placebo-controlled study of the atypical antipsychotic medication risperidone with 13 individuals. Risperidone was effective in reducing destructive behavior (compared to placebo) for 10 participants. For 7 of these responders, an undifferentiated pattern of responding occurred across their baseline functional analysis conditions (i.e., a similar rate of responding across conditions), and risperidone treatment produced nonspecific reductions of their destructive behavior across functional analysis conditions. For the remaining 3 responders, a differentiated pattern of responding occurred across their baseline functional analysis conditions (i.e., an elevated rate of responding occurred in a specific condition), and risperidone treatment produced function-specific reductions of their destructive behavior.

Use of Functional Analysis Methodology in the Evaluation of Medication Effects

The atypical antipsychotic medication risperidone was evaluated using a double-blind, placebo-controlled design in the treatment of destructive behavior in two individuals with autism. Premedication functional analyses indicated that destructive behavior was maintained by escape from demands, attention, or access to tangible items. For both individuals, destructive behavior during the demand condition was significantly reduced during the medication phases, whereas destructive behavior continued to occur to obtain tangible items (Reggie) and attention (Sean). In addition, there appeared to be a differential effect of the medication on self-injurious behavior (SIB) versus aggression for Sean. Results of the study demonstrate how functional analysis may provide information on those conditions and behaviors that are most likely to be affected by a specific medication.

Cognitive and Motor Components of Bilateral Transfer

Right-handed college students practiced pursuit tracking in a clockwise or counter-clockwise direction for 5 or 25 trials with the left hand. Subjects then switched to the right hand for 25 trials, half tracking in the same direction as originally and half in the opposite direction. Two additional groups practiced with the right hand for 50 trials. Transfer to the opposite direction was found to be greater after 25 trials of original practice than after 5 trials of original practice.

Brief report: reliability and validity of instruments for assessing psychotropic medication effects on self-injurious behavior in mental retardation

Treatment of self-injurious behavior (SIB), a devastating behavior disorder among individuals with severe/profound retardation and in autism, has become the target of renewed interest. Prevalence estimates vary greatly depending on circumstances of the respective studies (Rojahn, 1994), but a prudent estimate would be that SIB occurs in approximately 5 to 10% of the population with mental retardation, and in about twice as many among persons with autism. Chronic severe SIB has been found to be extremely difficult to treat. So far the most successful approach has been the behavioral technology based on operant principles of learning. The behavioral technology, how-

The effect of clozapine on self-injurious behavior

Traditional neuroleptic drugs like thioridazine and haloperidol have not proven to be systematically effective with the treatment of self-injurious behavior (SIB). These drugs may be ineffective because they primarily block D2 dopamine receptors. Based on research with humans and other animals, it appears that another dopamine receptor, D1, may be responsible for mediating some SIB. Clozapine, a neuroleptic recently introduced in the United States, has proven effective in treatment of refractory cases of schizophrenia and is known to have an affinity for blocking D1 receptors. The drug was used to complete a 93-week double-blind crossover trial with a client displaying chronic SIB. Though clozapine is known to affect other neurotransmitter systems, the successful treatment of the participant is consistent with the D1 hypothesis of self-injurious behavior and suggests the possibility that clozapine could be an effective pharmacological intervention for some cases of SIB.

Risk Factors for Self-Injury, Aggression, and Stereotyped Behavior Among Young Children At Risk for Intellectual and Developmental Disabilities

Before the 1990s, research on the early identification and prevention of severe behavior disorders (SBDs), such as aggression, self-injury, and stereotyped behavior, among young children with intellectual and developmental disabilities (IDD), was mostly done with children 3 years or older. More recent work suggests that signs of SBDs may occur as early as 6 months in some infants. The present study combined a cross-sectional and longitudinal approach to examine SBDs in 180 young children aged 4-48 months recruited through mass screening, then receiving an interdisciplinary evaluation and six-month follow-ups for one year. Twelve potential risk factors related to SBDs were examined. Eight of these risk factors, including age, gender, diagnosis, intellectual and communication levels, visual impairment, parent education, family income, were differentially related to scores for Aggression, SIB, and Stereotyped Behavior subscales on the Behavior Problems Inventory (BPI-01) at initial interdisciplinary evaluation. BPI-01 scores decreased over the year for 57% of the children and increased for 43%. The amount of decrease on each BPI-01 subscale varied with age, gender, and diagnosis.

Brief Report: Effects of Clozapine on Self-Injurious Behavior of Two Risperidone Nonresponders with Mental Retardation

A typical antipsychotic medications for self-injurious behavior (SIB), aggression, and destruction among people with mental retardation and development disabilities are becoming increasingly accepted. Most studies are on risperidone and fewer have been conducted on clozapine. The present single-blind study reports marked reductions in SIB and aggression of two persons with profound mental retardation who were nonresponsive to all other behavioral and psychopharmacological interventions, including risperidone. The most effective dose was 200 mg/day. Side effects were mild and the drug was tolerated well.

Cross-sensitization between footshock stress and apomorphine on self-injurious behavior and neostriatal catecholamines in a rat model of Lesch-Nyhan syndrome

The effects of footshock sensitization (priming), apomorphine (APO) priming and their combination on behavior and neostriatal and cortical catecholamines were examined in adult rats which had neonatally received bilateral intracerebroventricular injections with 6-hydroxydopamine (6-OHDA; a model of Lesch-Nyhan syndrome (LNS)) or vehicle (unlesioned rats). Lesioned (6-OHDA-treated) rats displayed self-biting (SB; 7/20 rats) and self-injurious behavior (SIB; 1/20 rats) during APO priming, but not during footshock priming. During subsequent acute cumulative APO dosing, 20-30% of lesioned rats primed with APO alone or footshock alone displayed SB and SIB. However, SB and SIB incidence in APO+footshock-primed lesioned rats was nearly tripled. Dopamine (DA) synthesis, metabolism and extracellular concentrations (disposition) in unlesioned rats and in cortices of lesioned animals were unaffected by priming. In lesioned rats primed with APO alone or footshock alone, only neostriatal 3-methoxytyramine (3-MT) was significantly increased. However, neostriatal DA and metabolite concentrations (and norepinephrine (NE)) were all significantly elevated in lesioned rats primed with both APO and footshock. These results confirm that neonatal 6-OHDA-induced neostriatal catecholamine depletion can be antagonized by experiential change, suggest that behavioral and neurochemical cross-sensitization between APO and footshock in such rats is unidirectional and support the view that stress can exacerbate the incidence of SIB in LNS.