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Biomedical subjects

Robert L Findling

Publications and source records attributed to Robert L Findling.

83 records · Page 5Linked to original sources

Efficacy of Adderall and methylphenidate in attention deficit hyperactivity disorder: a drug-placebo and drug-drug response curve analysis of a naturalistic study.

Stimulant medication has, for many years, been the pharmacological treatment of choice for children and adults with attention deficit hyperactivity disorder (ADHD). Recently, several studies have documented the efficacy of a new stimulant, Adderall. Although these initial studies provide useful information for clinicians treating ADHD children, their method of data presentation has provided limited information about the clinical significance of drug effects. Thus, to address the issue of clinical significance, we completed drug-placebo response curve analyses of a blinded, placebo-controlled study of Adderall and methylphenidate (MPH). Our results show that the efficacy of Adderall and MPH to improve functioning is seen throughout the full range of improvement scores. Both drugs prevent worsening and, for a majority of patients, lead to improvements that are well into the normal range. The analyses also highlight an important subgroup of placebo responders, which suggests that future research should focus on how to predict robust placebo response in ADHD patients.

Amphetamines↗

Clinical decision-making using the General Behavior Inventory in juvenile bipolarity.

OBJECTIVE: The General Behavior Inventory (GBI) is a questionnaire that has utility in the assessment of mood disorders in adults. The purpose of this study was to examine how the GBI might optimally be used in the assessment of youths. METHOD: Children and adolescents between the ages of 5 and 17 years participated in this study. All youths were evaluated with the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS). Based on the K-SADS results, subjects were then assigned to one of four groups: a bipolar spectrum group, a depressive disorders group, a disruptive behaviors disorders group, and a no diagnosis group. Guardians completed a version of the GBI modified for parent reporting. Patients 10 years old or greater also completed the GBI as a self-report measure. RESULTS: There were 196 subjects who participated. Both parent report and youth self-report assigned patients to the appropriate diagnostic group with better than 74% accuracy. Combining information from multiple informants did not significantly improve diagnostic group assignment. CONCLUSIONS: These data suggest that the GBI may be a useful adjunct in the diagnosis of mood disorders in youths, particularly when diagnostic specificity is more important than sensitivity.

Adolescent↗

Discriminative validity of a parent version of the Young Mania Rating Scale.

OBJECTIVE: To examine the usefulness of a parent report version of the Young Mania Rating Scale (P-YMRS) in distinguishing bipolar disorder from other mental health conditions in children and adolescents. METHOD: Parents of 117 youths aged 5 to 17 years presenting to an outpatient research center completed an adapted Young Mania Rating Scale (P-YMRS). Eligible subjects underwent a diagnostic evaluation including a semistructured instrument (Schedule for Affective Disorders and Schizophrenia for School-Age Children) and also a clinical evaluation by a child and adolescent psychiatrist in more than 75% of the subjects. RESULTS: Factor analyses of the P-YMRS suggested one dimension, with a total score showing acceptable internal consistency (alpha =.75). Logistic regressions discriminated bipolar mood disorder versus unipolar disorder, versus disruptive behavior disorder, and versus any other diagnosis. Classification rates exceeded 78%, and receiver operating characteristics analyses showed good diagnostic efficiency, with areas under the curve greater than 0.82. CONCLUSIONS: The P-YMRS may be used to derive clinically meaningful information about mood disorders in youths.

Adolescent↗

Double-blind, placebo-controlled study of risperidone for the treatment of disruptive behaviors in children with subaverage intelligence.

OBJECTIVE: The short-term efficacy and safety of risperidone in the treatment of disruptive behaviors was examined in a well-characterized cohort of children with subaverage intelligence. METHOD: In this 6-week, multicenter, double-blind, parallel-group study of 118 children (aged 5-12 years) with severely disruptive behaviors and subaverage intelligence (IQ between 36 and 84, inclusive), the subjects received 0.02-0.06 mg/kg per day of risperidone oral solution or placebo. The a priori primary efficacy measure was the change in score from baseline to endpoint on the conduct problem subscale of the Nisonger Child Behavior Rating Form. RESULTS: The risperidone group showed significantly greater improvement than did the placebo group on the conduct problem subscale of the Nisonger Child Behavior Rating Form from week 1 through endpoint (change in score of -15.2 and -6.2, respectively). Risperidone was also associated with significantly greater improvement than placebo on all other Nisonger Child Behavior Rating Form subscales at endpoint, as well as on the Aberrant Behavior Checklist subscales for irritability, lethargy/social withdrawal, and hyperactivity; the Behavior Problems Inventory aggressive/destructive behavior subscale; a visual analogue scale of the most troublesome symptom; and the Clinical Global Impression change score. The most common adverse effects reported during risperidone treatment were headache and somnolence. The extrapyramidal symptom profile of risperidone was comparable to that of placebo. Mean weight increases of 2.2 kg. and 0.9 kg occurred in the risperidone and placebo groups, respectively. CONCLUSIONS: Risperidone was effective and well tolerated for the treatment of severely disruptive behaviors in children with subaverage IQ.

Aggression↗

A lack of self-consciousness in autism.

OBJECTIVE: This study investigated self-consciousness in autism. METHOD: An incidental memory task was conducted on 18 adults with high-functioning autism and 18 normal comparison subjects. Three kinds of orienting questions (phonological, semantic, and self-referent, i.e., "Does the word describe you?") were asked about target words (adjectives for personality traits) in order to induce different types of processing. This was followed by an unexpected recognition test. RESULTS: While semantic processing resulted in better memory than phonological processing in both groups, self-referent processing yielded better memory performance than semantic processing in the comparison group but not in the autistic group. CONCLUSIONS: The results suggest deficits in self-consciousness in individuals with autism.

Adult↗

Factor structure of the Young Mania Rating Scale for use with youths ages 5 to 17 years.

Assessed the factor structure of the Young Mania Rating Scale (YMRS). Youths presenting to a research program specializing in the pharmacological treatment of mood and disruptive behavioral disorders (N = 612) were administered a semistructured diagnostic interview. Based on the interview, youths were placed into diagnostic groups. Highly trained raters completed the YMRS for each youth. YMRS ratings were internally consistent (alpha = .91), and exploratory and confirmatory factor analyses yielded a 1-factor solution for boys and girls in both young (5 to 11 years) and older (12 to 17 years) subsamples. However, the young male group showed higher scores on several items as well as the total YMRS score. Results suggest that the YMRS total score can be meaningfully interpreted in child and adolescent samples.

Adolescent↗

The future of pharmacotherapy for paediatric anxiety.

There is a growing body of data supporting the use of pharmacological agents in the treatment of paediatric anxiety. The most compelling data exists for the use of selective serotonin re-uptake inhibitors. However, questions the safe and efficacious use of medications with anxiolytic properties still remain. Although the field has progressed in the past several years, it is evident that more research needs to be done in the future.

Adolescent↗

A double-blind, placebo-controlled study of modified-release methylphenidate in children with attention-deficit/hyperactivity disorder.

OBJECTIVE: To compare the efficacy, safety, and tolerability of once-daily administration of modified-release methylphenidate (MPH MR) with placebo in children with attention-deficit/hyperactivity disorder (ADHD). METHODS: The study was a 3-week, double-blind, 32-site, randomized clinical trial comparing MPH MR with placebo. Children were 6 to 16 years of age, had a diagnosis of ADHD, and had not failed a previous trial of stimulant treatment for ADHD. After a 1-week, single-blind, placebo-washout period, participants received a once-daily dose of MPH MR or placebo, which was started with 1 capsule (20 mg) and individually titrated up to a maximum of 3 capsules (60 mg). The primary outcome measure was specified as a reduction in ADHD symptom severity from the teacher version of the 10-item Conners' Global Index. Investigators, teachers, and parents evaluated safety. RESULTS: The study randomized 321 children: 158 to MPH MR and 163 to placebo. Children in the MPH MR group were started on a dose of 20 mg/d and reached a mean dose of 40.7 mg/d (1.28 mg/kg/d) at endpoint. Compared with placebo, MPH MR significantly reduced ADHD symptoms ratings on the teacher version of the 10-item Conners' Global Index, on the parent version of the Conners' Global Index, on the parent assessment of global efficacy, and on investigator assessment of global improvement. The most common adverse events in the MPH MR group were headache, anorexia, abdominal pain, and insomnia. Only anorexia occurred at a rate that was significantly greater than placebo. CONCLUSION: MPH MR administered once daily in the morning is effective and safe in controlling ADHD symptoms throughout the school day.

Adolescent↗

Use of quetiapine in children and adolescents.

The atypical antipsychotic quetiapine has been examined in children and adolescents in a randomized clinical trial, a number of open-label studies, and several chart review studies. Although only a small amount of information exists, most studies indicate that quetiapine is effective and well tolerated in various pediatric populations. Because quetiapine appears to be well tolerated in the young and associated with manifest salutary effects, it seems to be a promising agent that has potential for use in children and adolescents. This article reviews studies of quetiapine in the treatment of children and adolescents with a variety of psychiatric disorders. Despite these encouraging findings, the number of studies is small, and some have methodological limitations. Methodologically rigorous studies with substantive numbers of subjects are needed to confirm or refute these preliminary impressions.

Adolescent↗

The relevance of pharmacokinetic studies in designing efficacy trials in juvenile major depression.

INTRODUCTION: Identifying evidence-based dosing strategies is a key part of new drug development in pediatric populations. Pharmacokinetic (PK) studies can provide important information regarding how best to dose medications in children and adolescents. Utilizing scientifically supported dosing strategies provides the best chance for any given drug to demonstrate both efficacy and acceptable tolerability in definitive, placebo-controlled studies. METHODS: Results of both PK studies and randomized, placebo-controlled efficacy trials (RPCTs) in juvenile major depressive disorder (MDD) are reviewed. The degree to which the medication dosing strategies that were employed in the efficacy studies were supported by the extant PK data is considered. Medications that are reviewed include fluoxetine, sertraline, paroxetine, citalopram, escitalopram, venlafaxine, nefazodone, and mirtazapine. RESULTS: In many instances, the dosing paradigms that were used in the RPCTs differed, sometimes substantially, from the dosing strategies that would have been supported based on the results of PK studies. CONCLUSIONS: Medication dosing regimens may have contributed to the failure of several RPCTs to show drug efficacy in the treatment of pediatric MDD. In addition, the doses of medication used in these RPCTs may also have contributed to the safety and tolerability concerns that have been raised with these drugs. PK and dose-ranging studies should be performed prior to the initiation of definitive efficacy trials so that empirically supported dosing strategies can be incorporated into the design of RPCTs of antidepressants in children and adolescents suffering from MDD.

Adolescent↗

Fluoxetine 40-60 mg versus fluoxetine 20 mg in the treatment of children and adolescents with a less-than-complete response to nine-week treatment with fluoxetine 10-20 mg: a pilot study.

OBJECTIVE: The aim of this study was to compare fluoxetine dosage titration to 40-60 mg/day with fixed fluoxetine 20-mg/day treatment for an additional 10 weeks in pediatric outpatients with major depressive disorder (MDD) who had not met protocol-defined response criteria after 9-week acute fluoxetine treatment. METHODS: Patients unresponsive (less than or equal to 30% decrease in Children's Depression Rating Scale-Revised [CDRS-R] score) after 9-week fluoxetine treatment were randomly reassigned to continue at 20 mg/day or to increase to 40 mg/day. After 4 weeks, patients unresponsive to 40 mg/day could receive 60 mg/day. RESULTS: Twenty-nine (29) patients, 9-17 years of age, received fluoxetine 40-60 mg/day (n = 14) or 20 mg/day (n = 15). At the conclusion of this study phase, 10 patients (71%) on 40-60 mg/day met the response criteria, versus 5 patients (36%) on 20 mg/day (p = 0.128). Mean CDRS-R scores improved in both treatment groups (fluoxetine 40-60 mg/day, -9.4; fluoxetine 20 mg/day, -1.5; p = 0.099). Adverse events were similar in both groups. However, this study phase was statistically underpowered for detecting differences between treatment groups. CONCLUSION: More than two thirds of patients whose dosage was increased responded within 10 weeks, suggesting dose escalation may benefit some patients. Approximately one third of patients unresponsive to initial treatment with fluoxetine 20 mg responded to this fixed dosage within another 10 weeks. Fluoxetine 20-60 mg/day was well tolerated.

Adolescent↗