346 research outputs found
Beta Blockers in Mental Retardation and Developmental Disorders
β-Adrenergic blockers appear to be effective in the management of verbal aggression, physical
aggression, or self-injurious behavior associated with mental retardation and other developmental disorders.
However, methodological limitations of the available studies make it difficult to judge the value of these
treatments. Optimal doses for treating patients with mental retardation or developmental disorders appear
lower than described in the general psychiatric literature, so low doses of β-blockers may be preferred in such
patients with abnormal brain development. Children and adolescents with mental retardation or
developmental disorders appear to respond to particularly low doses (e.g., below propranolol 150 mg daily).
Propranolol is recommended for central blockade, and nadolol is recommended for peripheral blockade.
Most β receptors in the brain (except cerebellum) seem to be β1 (cardiac type), but it is not clear that central
blockade is required for psychotropic effects. Interim suggestions for empirical trials are offered, and rating
scales and other measurement approaches are discussed. Since evidence supporting the efficacy of
β-blockers in mental retardation or developmental disorders in children and adolescents is not definitive, the
clinician is advised to consider designing an empirical trial for each patient, utilizing pre- and postmedication
measures, when conventional treatments have been unsuccessful
Neurochemical correlates of autistic disorder: A review of the literature
Review of neurochemical investigations in autistic disorder revealed that a wide array of transmitter systems
have been studied, including serotonin, dopamine, norepinephrine, acetylcholine, oxytocin, endogenous
opioids, cortisol, glutamate, and gamma-aminobutyric acid (GABA). These studies have been complicated
by the fact that autism is a very heterogeneous disorder which often presents with comorbid behavioral
problems. In addition, many of these studies employed very small samples and inappropriate control groups,
making it difficult to draw conclusions with confidence. Overall, serotonin appears to have the most empirical
evidence for a role in autism, but this requires further investigation and replication. There is little support for
the notion that a dysfunction of norepinephrine or the endogenous opioids are related to autism. The role of
dopaminergic functioning has not been compelling thus far, though conflicting findings on central dopamine
turnover require further study. Promising new areas of study may include possible dysfunction of the
cholinergic system, oxytocin, and amino acid neurotransmitters. Implications for pharmacotherapy are
briefly discussed for each neurotransmitter system with brief research examples. Review of this work
emphasizes the need for future studies to control for subject variables, such as race, sex, pubertal status, and
distress associated with blood draws, which can affect measures of neurochemical function. In addition,
research in neurochemistry must continue to work in concert with other subspecialties to form a more
comprehensive and theory-based approach to the neurobiological correlates of autistic disorder
Methylphenidate Treatment in Children with Borderline IQ and Mental Retardation: Analysis of Three Aggregated Studies
Objective:
To determine response of low-IQ children with attention deficit hyperactivity disorder (ADHD)
symptoms to methylphenidate (MPH).
Methods:
An aggregated analysis was conducted in 90 children with low IQ who received the same dose
regimen of MPH in three independent, placebo-controlled studies. Active drug and placebo were given from
2 to 4 weeks each. Outcome measures included teacher and parent ratings on standardized behavior scales
(mean n = 84), performance on computer-controlled cognitive-motor tests (n = 62), and measures of
cardiovascular response (n = 85).
Results:
Both teachers and parents rated the children consistently as being improved on subscales assessing
attention, overactivity, and conduct problems. Some 44% of the subjects showed at least a 30% reduction
compared with placebo on teacher ratings. MPH improved accuracy on several cognitive tests, response
speed was increased on some, and seat activity declined for one of three tests; heart rate was mildly increased
(3.9 beats/minute) with MPH. Analyses of IQ and mental age as moderator variables suggested that lower
functional level (especially lower IQ) may be associated with a less favorable response to MPH.
Conclusions:
Children with low IQ and ADHD clearly respond to MPH, but their rate of beneficial response
appears to be well under that of normal-IQ children and more varied. Different attentional mechanisms may
moderate response to psychostimulants
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, ηP ^
2 =
0.43) and seat movement (p < 0.05, ηP ^
2 = 0.29) on a short-term memory task, and on a measure of static tremor
(p = 0.05, ηP ^
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, ηP ^
2 = 0.44), Conduct Problem (p = 0.02, ηP ^
2 = 0.36),
Hyperactivity (p = 0.03, ηP ^
2 = 0.32)] and on the Hyperactivity/Noncompliance subscale of the Aberrant
Behavior Checklist (p = 0.01, ηP ^
2 = 0.41). Significant increases in heart rate (p = 0.05, ηP ^
2 = 0.27) and weight (p
= 0.02, ηP ^
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
Moderators of Parent Training for Disruptive Behaviors in Young Children with Autism Spectrum Disorder
We conducted a 6 month, randomized trial of parent training (PT) versus a parent education program (PEP) in 180 young children (158 boys, 22 girls), ages 3-7 years, with autism spectrum disorder (ASD). PT was superior to PEP in decreasing disruptive and noncompliant behaviors. In the current study, we assess moderators of treatment response in this trial. Thirteen clinical and demographic variables were evaluated as potential moderators of three outcome variables: the Aberrant Behavior Checklist-Irritability subscale (ABC-I), Home Situations Questionnaire (HSQ), and Clinical Global Impressions-Improvement Scale (CGI-I). We used an intent-to-treat model and random effects regression. Neither IQ nor ASD severity moderated outcome on the selected outcome measures. Severity of Attention Deficit Hyperactivity Disorder (ADHD) and anxiety moderated outcomes on the ABC-I and HSQ. For instance, there was a 6.6 point difference on the ABC-I between high and low ADHD groups (p = .05) and a 5.3 point difference between high and low Anxiety groups (p = .04). Oppositional defiant disorder symptoms and household income moderated outcomes on the HSQ. None of the baseline variables moderated outcome on the CGI-I. That IQ and ASD symptom severity did not moderate outcome suggests that PT is likely to benefit a wide range of children with ASD and disruptive behavior
The treatment of severe child aggression (TOSCA) study: Design challenges
<p>Abstract</p> <p>Background</p> <p>Polypharmacy (the concurrent use of more than one psychoactive drug) and other combination interventions are increasingly common for treatment of severe psychiatric problems only partly responsive to monotherapy. This practice and research on it raise scientific, clinical, and ethical issues such as additive side effects, interactions, threshold for adding second drug, appropriate target measures, and (for studies) timing of randomization. One challenging area for treatment is severe child aggression. Commonly-used medications, often in combination, include psychostimulants, antipsychotics, mood stabilizers, and alpha-2 agonists, which vary considerably in terms of perceived safety and efficacy.</p> <p>Results</p> <p>In designing our NIMH-funded trial of polypharmacy, we focused attention on the added benefit of a second drug (risperidone) to the effect of the first (stimulant). We selected these two drugs because their associated adverse events might neutralize each other (e.g., sleep delay and appetite decrease from stimulant versus sedation and appetite increase from antipsychotic). Moreover, there was considerable evidence of efficacy for each drug individually for the management of ADHD and child aggression. The study sample comprised children (ages 6-12 years) with both diagnosed ADHD and disruptive behavior disorder (oppositional-defiant or conduct disorder) accompanied by severe physical aggression. In a staged sequence, the medication with the least problematic adverse effects (stimulant) was openly titrated in 3 weeks to optimal effect. Participants whose behavioral symptoms were not normalized received additional double-blind medication, either risperidone or placebo, by random assignment. Thus children whose behavioral symptoms were normalized with stimulant medication were not exposed to an antipsychotic. All families participated in an empirically-supported parent training program for disruptive behavior, so that the actual comparison was stimulant+parent training versus stimulant+antipsychotic+parent training.</p> <p>Conclusions</p> <p>We hope that the resolutions of the challenges presented here will be useful to other investigators and facilitate much-needed research on child psychiatric polypharmacy.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00796302">NCT00796302</a></p
Effect of Parent Training on Adaptive Behavior in Children With Autism Spectrum Disorder and Disruptive Behavior: Results of a Randomized Trial
Objective
This study examined the impact of parent training on adaptive behavior in children with autism spectrum disorder (ASD) and disruptive behavior.
Methods
This was a 24-week, 6-site, randomized trial of parent training versus parent education in 180 children with ASD (aged 3−7 years; 158 boys and 22 girls) and moderate or greater behavioral problems. Parent training included specific strategies to manage disruptive behavior over 11 to 13 sessions, 2 telephone boosters, and 2 home visits. Parent education provided useful information about autism but no behavior management strategies over 12 core sessions and 1 home visit. In a previous report, we showed that parent training was superior to parent education in reducing disruptive behavior in young children with ASD. Here, we test whether parent training is superior to parent education in improving daily living skills as measured by the parent-rated Vineland Adaptive Behavior Scales II. The long-term impact of parent training on adaptive functioning is also presented.
Results
At week 24, the parent training group showed a 5.7-point improvement from baseline on the Daily Living domain compared to no change in parent education (p = .004; effect size = 0.36). On the Socialization domain, there was a 5.9-point improvement in parent training versus a 3.1-point improvement in parent education (p = .11; effect size = 0.29). Gains in the Communication domain were similar across treatment groups. The gain in Daily Living was greater in children with IQ of >70. However, the interaction of treatment-by-IQ was not significant. Gains in Daily Living at week 24 were maintained upon re-evaluation at 24 weeks posttreatment.
Conclusion
These results support the model that reduction in disruptive behavior can lead to improvement in activities of daily living. By contrast, the expected trajectory for adaptive behavior in children with ASD is often flat and predictably declines in children with intellectual disability. In the parent training group, higher-functioning children achieved significant gains in daily living skills. Children with intellectual disability kept pace with time
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 ≥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
A Prospective Open Trial of Guanfacine in Children with Pervasive Developmental Disorders
Objective:
A common complaint for children with pervasive developmental disorder (PDD) is hyperactivity.
The purpose of this pilot study was to gather preliminary information on the efficacy of guanfacine in
children with PDD and hyperactivity.
Methods:
Children with PDD accompanied by hyperactivity entered the open-label trial if there was a recent
history of failed treatment with methylphenidate or the child did not improve on methylphenidate in a
multisite, placebo-controlled trial.
Results:
Children (23 boys and 2 girls) with a mean age of 9.03 (±3.14) years entered the open-label trial.
After 8 weeks of treatment, the parent-rated Hyperactivity subscale of the Aberrant Behavior Checklist
(ABC) went from a mean of 31.3 (±8.89) at baseline to 18.9 (±10.37) (effect size = 1.4; p < 0.001). The
teacher-rated Hyperactivity subscale decreased from a mean of 29.9 (±9.12) at baseline to 22.3 (±9.44)
(effect size = 0.83; p < 0.01). Twelve children (48%) were rated as Much Improved or Very Much
Improved on the Clinical Global Impressions– Improvement. Doses ranged from 1.0 to 3.0 mg/day in two
or three divided doses. Common adverse effects included irritability, sedation, sleep disturbance (insomnia
or midsleep awakening), and constipation. Irritability led to discontinuation in 3 subjects. There were no
significant changes in pulse, blood pressure, or electrocardiogram.
Conclusions:
Guanfacine may be useful for the treatment of hyperactivity in children with PDD. Placebocontrolled
studies are needed to guide clinical practice
Moderators, Mediators, and Other Predictors of Risperidone Response in Children with Autistic Disorder and Irritability
Objective/Background:
The National Institute of Mental Health (NIMH) Research Units on Pediatric Psychopharmacology
(RUPP) Autism Network found an effect size of d = 1.2 in favor of risperidone on the main outcome measure
in an 8-week double-blind, placebo-controlled trial for irritabilityin autistic disorder. This paper explores
moderators and mediators of this effect.
Method:
Intention-to-treat (ITT) analyses were conducted with suspected moderators and mediators entered
into the regression equations. MacArthur Foundation Network subgroup guidelines were followed in the
evaluation of the results.
Results:
Only baseline severity moderated treatment response: Higher severity showed greater improvement
for risperidone but not for placebo. Weight gain mediated treatment response negatively: Those who gained
more weight improved less with risperidone and more with placebo. Compliance correlated with outcome for
risperidone but not placebo. Higher dose correlated with worse outcome for placebo, but not risperidone. Of
nonspecific predictors, parent education, family income, and low baseline prolactin positively predicted
outcome; anxiety, bipolar symptoms, oppositional-defiant symptoms, stereotypy, and hyperactivity
negatively predicted outcome. Risperidone moderated the effect of change in 5'-nucleotidase, a marker of
zinc status, for which decrease was associated with improvement only with risperidone, not with placebo.
Conclusion:
The benefit–risk ratio of risperidone is better with greater symptom severity. Risperidone can be
individually titrated to optimal dosage for excellent response in the majority of children. Weight gain is not
necessary for risperidone benefit and may even detract from it. Socioeconomic advantage, low prolactin, and
absence of co-morbid problems non-specifically predict better outcome. Mineral interactions with
risperidone deserve further study
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