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Biomedical subjects

B L Handen

Publications and source records attributed to B L Handen.

At least 19 recordsLinked to original sources

Double-blind, placebo-controlled study of amantadine hydrochloride in the treatment of children with autistic disorder.

OBJECTIVE: To test the hypothesis that amantadine hydrochloride is a safe and effective treatment for behavioral disturbances--for example, hyperactivity and irritability--in children with autism. METHOD: Thirty-nine subjects (intent to treat; 5-19 years old; IQ > 35) had autism diagnosed according to DSM-IV and ICD-10 criteria using the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule-Generic. The Aberrant Behavior Checklist-Community Version (ABC-CV) and Clinical Global Impressions (CGI) scale were used as outcome variables. After a 1-week, single-blind placebo run-in, patients received a single daily dose of amantadine (2.5 mg/kg per day) or placebo for the next week, and then bid dosing (5.0 mg/kg per day) for the subsequent 3 weeks. RESULTS: When assessed on the basis of parent-rated ABC-CV ratings of irritability and hyperactivity, the mean placebo response rate was 37% versus amantadine at 47% (not significant). However, in the amantadine-treated group there were statistically significant improvements in absolute changes in clinician-rated ABC-CVs for hyperactivity (amantadine -6.4 versus placebo -2.1; p = .046) and inappropriate speech (-1.9 versus 0.4; p = .008). CGI scale ratings were higher in the amantadine group: 53% improved versus 25% (p = .076). Amantadine was well tolerated. CONCLUSIONS: Parents did not report statistically significant behavioral change with amantadine. However, clinician-rated improvements in behavioral ratings following treatment with amantadine suggest that further studies with this or other drugs acting on the glutamatergic system are warranted. The design of these and similar drug trials in children with autistic disorder must take into account the possibility of a large placebo response.

Adolescent↗

Efficacy of methylphenidate among children with autism and symptoms of attention-deficit hyperactivity disorder.

Thirteen children (ages 5.6 to 11.2 years) with autism and symptoms of attention-deficit hyperactivity disorder (ADHD) participated in a double-blind, placebo-controlled crossover study of methylphenidate (0.3 and 0.6 mg/kg per dose). Eight subjects responded positively, based upon a minimum 50% decrease on the Conners Hyperactivity Index. Ratings of stereotypy and inappropriate speech, which are often associated with autistic core features, also decreased. However, no changes were found on the Child Autism Rating Scale, a global assessment of autistic symptomotology. Significant adverse side effects occurred in some children including social withdrawal and irritability, especially at the 0.6 mg/kg dose. Results suggest that methylphenidate can be efficacious for children with autism and ADHD symptoms. However, this group of children seems to be particularly susceptible to adverse side effects.

Attention Deficit Disorder with Hyperactivity↗

Efficacy of methylphenidate among preschool children with developmental disabilities and ADHD.

OBJECTIVE: This was a double-blind, placebo-controlled, crossover design study of the safety and efficacy of methylphenidate (MPH) in 11 preschool children (aged 4.0-5.11 years) with developmental disabilities and attention-deficit hyperactivity disorder (ADHD). METHOD: MPH doses of 0.3 and 0.6 mg/kg per dose and a placebo were given. Drug response was evaluated via teacher-completed behavior checklists and clinic-based observations of activity level, attention, and compliance to adult requests. A side effects checklist was also completed by teachers and parents. RESULTS: Significant improvement on teacher ratings of hyperactivity and inattention as well as clinic-based observations of activity level and compliance were associated with MPH. Eight of 11 preschool children were medication responders (based on a minimum 40% decrease between placebo and one drug condition on either the teacher-rated Conners Hyperactivity Index or the Hyperactive-Distractible subscale of the Preschool Behavior Questionnaire). Five children exhibited significant adverse drug side effects such as severe social withdrawal, increased crying, and irritability, especially at the higher dose (0.6 mg/kg). CONCLUSIONS: Results suggest that preschool children with developmental disabilities and ADHD respond to MPH at rates similar to those of school-age children with mental retardation and ADHD. However, this population appears to be especially susceptible to adverse drug side effects.

Analysis of Variance↗

A playroom observation procedure to assess children with mental retardation and ADHD.

Forty-two children (ages 6 to 12 years old) with moderate mental retardation to borderline intellectual functioning were studied in a laboratory playroom setting to determine whether children identified as ADHD (attention deficit hyperactivity disorder) or controls differed on activity and attentional measures. Children with ADHD were further divided into ADHD + conduct problems (ADHD + CD) and ADHD-only subgroups (with an ADHD-combined group comprising children of both subgroups). An interval recording system was used to code observations of independent play and a restricted academic task. Results indicated that the ADHD-combined group was significantly more vocal and engaged in a significantly greater number of toy changes than controls during independent play. Significant group differences were also noted during the restricted academic task, with the ADHD-combined and ADHD + CD groups more off-task and engaging in a greater number of toy touches than controls. Discriminant analyses found independent play measures to predict group membership in 70 percent of cases (ADHD-combined vs. controls), but in only 64 percent of cases using measures from the restricted academic task. No significant findings resulted when the ADHD subjects were further divided into two subgroups. Despite some inconsistent findings, such laboratory-based observations may be of value in the diagnosis of ADHD in children with moderate mental retardation to borderline intellectual functioning.

Attention Deficit Disorder with Hyperactivity↗

Naltrexone in young autistic children: replication study and learning measures.

OBJECTIVE: This study expanded upon previous work on naltrexone efficacy and safety in young autistic children and assessed performance on learning measures. METHOD: Eleven children with autistic disorder, aged 3.0 to 8.3 years, were studied in home, school, and outpatient laboratory, bringing to 24 the combined study sample. Naltrexone, 1.0 mg/kg, was given daily in a randomized, double-blind, crossover design. Dependent measures were parent and teacher Clinical Global Impressions (CGI) and Naltrexone Side Effects Rating Scale (SE), Conners Parent Impulsivity/Hyperactivity Factor, Teacher Hyperactivity Factor, laboratory CGI, and analysis of videotaped behavior. Learning measures were the Early Intervention Developmental Profile-Language and paired-associate learning. RESULTS: Comparisons between naltrexone and baseline, but not naltrexone and placebo, on parent and teacher ratings showed statistical significance. Three of 11 subjects improved in two or more settings. Side effects were mild. Administering naltrexone was a challenge. The combined study sample showed improvement on all parent measures and on Teacher CGI and SE-Restlessness compared with baseline and placebo. Eleven of the 24 children improved in two or more settings. Scores on learning measures did not change across conditions. CONCLUSIONS: Naltrexone was associated with modest improvement of behavior in 11 of 24 children, but learning did not improve.

Attention↗

Long-term follow-up of children with mental retardation/borderline intellectual functioning and ADHD.

Fifty-two children (ages 7 to 14 years) with moderate retardation to borderline intellectual functioning were recontacted 12 to 65 months following participation in a double-blind, placebo-controlled trial of methylphenidate (MPH). Sixty-nine percent of subjects continued to be prescribed medication for behavior control at follow-up. While 72% of the sample evidenced improvement, over two-thirds continued to be rated at or above the 98th percentile on the Hyperactivity Index of the Parent Conners. In fact, 22% of subjects had received inpatient psychiatric treatment between the time of the initial MPH trial and follow-up. Finally, subjects with high initial ratings on the Parent Conners Conduct Problems scale were more likely to be suspended from school or receive inpatient psychiatric treatment than subjects with low initial ratings. The results suggested that children with ADHD and mental retardation of borderline intellectual functioning continued to exhibit significant symptoms associated with attention deficit hyperactivity disorder (ADHD) at follow-up and that early conduct problems were predictive of continuing behavioral difficulties.

Adolescent↗

Naltrexone in young autistic children: a double-blind, placebo-controlled crossover study.

OBJECTIVE: This study evaluated the efficacy and safety of naltrexone, an opiate blocker, in the treatment of autism. METHOD: Thirteen children with autistic disorder, aged 3.4 to 8.3 years (mean 5.4), were studied in home, school, and outpatient laboratory. Naltrexone, 1.0 mg/kg, was given daily in a randomized, double-blind, placebo-controlled crossover design. Dependent measures included parent and teacher Clinical Global Impressions (CGI), Conners Rating Scales, and Naltrexone Side-Effects (SE) Rating Scale; laboratory CGI, movement actometer readings, and a 10-second interval recording system analysis of on-task, communication initiations, disruptive behavior, and self-stimulation. RESULTS: Eight of 13 subjects improved in two or more settings. Changes in parent measures (CGI, Conners Impulsivity-Hyperactivity Factor, and SE-Restlessness) and Teacher CGI achieved statistical significance. Teacher SE-Restlessness and initiation of communication in the clinic showed a trend toward improvement. Actometer readings improved in two children who were very active at baseline. Adverse side effects were behavioral, mild, and transient. Administering the bitter tablet was a challenge. CONCLUSIONS: Naltrexone offers promise as an agent for modest improvement of behavior and social communication in young children with autism. Parent and teacher measures can be useful in outpatient trials to evaluate change.

Autistic Disorder↗

Classroom behavior and children with mental retardation: comparison of children with and without ADHD.

Thirty-four children (ages 6-12 years) with moderate to borderline mental retardation were studied in a laboratory classroom setting to determine whether children identified as having attention deficit hyperactivity disorder on the basis of Conners Questionnaires differed in classroom behavior. Half of the children scored 15 or greater on both the Parent and Teacher Conners; the remaining children scored 11 or less. All were participants in a Saturday Education Program serving children with mental retardation. Direct observation of the laboratory classroom documented significant differences between groups on measures of on-task behavior and fidgetiness, especially during situations where little direct teacher feedback or supervision was available. Saturday Education Program staff, while blind as to group designation, rated the two groups as differing significantly on all scales of two standardized behavior problem checklists. Checklists by parents and teachers appear to be valid measures of classroom behavior of children with moderate to borderline mental retardation.

Attention↗

Prediction of response to methylphenidate among children with ADHD and mental retardation.

OBJECTIVE: The primary purpose of this study was to predict stimulant medication response among children with attention-deficit hyperactivity disorder (ADHD) and mental retardation (MR). METHOD: Forty-seven children with ADHD and MR (IQs of 48 to 77) served as subjects; ages ranged from 6.1 to 12.5 years. Subjects participated in a double-blind, placebo-controlled study of two doses of methylphenidate (0.3 and 0.6 mg/kg per dose) and a placebo. Data were collected in each child's weekday classroom and a Saturday laboratory classroom. Stepwise multiple regression analyses were used to predict drug responses in both settings. RESULTS: Higher parent ratings of impulsivity and activity level at baseline were associated with greater gains in weekday classroom dependent measures. Similarly, higher weekday teacher measures of activity level, impulsivity, inattention, and conduct problems at baseline were related to improvement on Saturday laboratory classroom dependent measures. Finally, gender, race, and socioeconomic status (SES) were found to be important predictors, with males, Caucasian subjects, and subjects from families of higher SES more likely to evidence clinical gains on a number of variables than other subjects. CONCLUSION: These results were generally consistent with research conducted among children with ADHD but without MR. However, factors such as race and conduct problems appear to have predictive utility specific to children with MR.

Attention Deficit Disorder with Hyperactivity↗

Efficacy of methylphenidate and behavioral intervention on classroom behavior in children with ADHD and mental retardation.

Using a combination of an alternating treatment and double-blind placebo-controlled drug design, the independent and combined effects of two behavioral interventions and two doses of methylphenidate (MPH) in 3 children with Attention Deficit Hyperactivity Disorder (ADHD) and mental retardation (MR) were assessed. In this single subject design, 2 of the 3 subjects responded positively to medication as measured by increased on-task behavior. The first behavioral intervention, a token economy for on-task behavior, was ineffective for increasing either on-task behavior or work accuracy when combined with placebo. However, improvement in work accuracy was realized with implementation of a second behavioral intervention that specifically targeted accuracy independent of drug conditions. The current findings highlight both the positive effects and limitations of the two commonly used treatment modalities for ADHD. Future studies should continue to extend this area of investigative efforts to produce more data-based knowledge as to the appropriate doses of treatment, both pharmacological and behavioral, with children with both ADHD and mental retardation.

Adolescent↗

Using guided compliance versus time out to promote child compliance: a preliminary comparative analysis in an analogue context.

Children referred to child management clinics frequently exhibit noncompliance with adult requests. Using a counterbalanced ABAC design, the authors examined the relative efficacy of guided compliance versus time out as a method of promoting child adherence to adult requests. Time out effected larger increases in percentage compliance among four of five participating children.

Attention↗

Effects and noneffects of methylphenidate in children with mental retardation and ADHD.

Stimulant medication efficacy was evaluated in 14 children with attention-deficit hyperactivity disorder and IQs of 48 to 74 in a double-blind crossover study of two methylphenidate doses and placebo. Dependent measures included behavioral ratings, work output, measures of learning, attention and impulsivity, and direct observation of peer social interactions. Nine children (64%) were methylphenidate-responders, based upon the Conners Hyperactivity Index. Significant gains in on-task behavior and attentional skills were noted with methylphenidate in comparison to placebo. No improvement on measures of learning or social interactions were observed. Results extend and replicate previous research conducted by the authors.

Attention Deficit Disorder with Hyperactivity↗

Adverse side effects of methylphenidate among mentally retarded children with ADHD.

The adverse side effects of methylphenidate were evaluated in 27 children with attention deficit hyperactivity disorder and IQs of 48 to 74 who participated in a double-blind study of two doses of methylphenidate and placebo. A checklist of 13 side effects, generated from the Physician's Desk Reference, was completed by teachers. Rates of irritability, anxiety, moodiness, and activity level decreased significantly when comparing the placebo with drug conditions. However, medication for six (22%) of the children was discontinued because of the appearance of motor tics (three children) and severe social withdrawal (two children), suggesting that mentally retarded children with attention deficit hyperactivity disorder may be at a greater risk for developing these side effects than the nonretarded population.

Anxiety↗

Efficacy of methylphenidate among mentally retarded children with attention deficit hyperactivity disorder.

Twelve children with IQ scores of 50 to 74 (educable mental retardation) who met rigorous diagnostic criteria for attention deficit hyperactivity disorder participated in a double-blind crossover study of the efficacy of two doses of methylphenidate compared with placebo. Dependent measures included behavioral ratings, classroom work output, laboratory measures of attention and learning, and direct observations of social behavior. Improvement with medication on the Conners Hyperactivity Index was observed in 75% of subjects. Significant increases in work output, on-task behavior, and attentional skills were associated with methylphenidate. However, gains in measures of attention were not associated with improvement in learning, as measured by a paired associate learning task. Additionally, no significant increases in appropriate social interactions during free play were associated with methylphenidate. The results suggest that mentally retarded children with attention deficit hyperactivity disorder respond to methylphenidate at similar rates and in similar domains to that of the nonretarded population.

Analysis of Variance↗

Methylphenidate in children with seizures and attention-deficit disorder.

This study assessed the safety and efficacy of methylphenidate in children with seizures and attention-deficit disorder. Ten children, aged 6 years 10 months to 10 years 10 months, without seizures while receiving a single antiepileptic drug, were evaluated in a double-blind medication-placebo crossover study with methylphenidate hydrochloride was administered at 0.3 mg/kg per dose and given at 8 AM and 12 PM on school days only. The use of methylphenidate was associated with statistically significant improvements on the Conners' Teacher Rating Scale and on the Finger Tapping Task and with trends toward improvement on the Matching Familiar Figures Test and Discriminant Reaction Time tests. No child had seizures during the study period nor subsequently for those who continued receiving psychostimulants. There were no significant changes of epileptiform features or back-ground activity on electroencephalograms and no alterations in antiepileptic drug levels. Methylphenidate may be a safe and effective treatment for certain children with seizures and concurrent attention-deficit disorder.

Attention Deficit Disorder with Hyperactivity↗

Delayed prompting: a review of procedural variations and results.

The delayed prompt procedure transfers stimulus control via the introduction of a time delay between the presentation of a stimulus and a prompt. This procedure has received increasingly greater attention in the literature during the past decade. The present paper reviews 26 studies that used the delayed prompt procedure in applied and laboratory settings. Subjects included developmentally disabled children and adults as well as children of normal intelligence who were taught a wide variety of tasks. Procedural variations across studies were noted in delay length and ceiling, criterion for increasing the delay, mastery criterion, and error correction. Results suggest that the delayed prompt procedure is an efficient teaching stategy, with subjects typically acquiring discriminations within a few training sessions or limited number of trials. However, not all subjects have benefited from the procedure. Additionally, little maintenance data have appeared in the literature, raising questions about long-term effectiveness. Alternative explanations for the reported success of the procedure as well as future areas of research are discussed.

Adolescent↗

Feeding induction in children who refuse to eat.

Seven chronically ill patients who refused to eat after prolonged hospitalizations were started on a feeding induction program that was based on behavior modification. Each of the children exhibited food aversions and was either dependent on central intravenous nutrition or received enteral feedings as the primary source of calories. An intervention program was initiated for six of the patients while they were hospitalized; the program was continued at home by the parents. All seven patients established consistent oral intake, and five were removed from supplemental feeding sources after implementation of the feeding induction programs.

Abnormalities, Multiple↗