Why do psychiatric drug research in children?
Explore the source record for details and available documents.
Adolescent↗
Biomedical subjects
Robert L Findling
Publications and source records attributed to Robert L Findling.
Toward an integration of parent and clinician report on the Young Mania Rating Scale.
BACKGROUND: The Young Mania Rating Scale (YMRS) has validity in the assessment of mania in adults. The purpose of this study was to examine how the YMRS might optimally be used in the assessment of youths. METHODS: Children and adolescents between the ages of 5 and 17 years of age 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 five groups: a bipolar I group, another bipolar spectrum group, a depressive disorders group, a disruptive behaviors disorders group, and a no diagnosis group. Guardians completed a version of the YMRS modified for parent reporting. Clinicians completed the YMRS on all participating youths. RESULTS: Both parent and clinician ratings on the YMRS assigned patients (n=117) to the appropriate diagnostic group with 71-98% accuracy. Combining information from multiple informants did not significantly improve diagnostic group assignment. LIMITATIONS: The same raters completed the clinician YMRS and the K-SADS interview involving the parent. Findings need replication in an independent sample with lower base rates of bipolar disorder, less rigorously trained and supervised raters, and using a prospective design to provide maximum generalizability of results. Current results should be interpreted as a 'best case' scenario. CONCLUSIONS: These data suggest that the YMRS may be a useful adjunct in assessing the severity of mania in youths. Tentative cutting scores are proposed to maximize efficiency, sensitivity, and specificity.
Adolescent↗
Is there progression from irritability/dyscontrol to major depressive and manic symptoms? A retrospective community survey of parents of bipolar children.
BACKGROUND: Although previous studies have discussed age-related changes in the presentation of early onset bipolar illness, the developmental progression of early symptoms remains unclear. The current study sought to trace parents' retrospective report of yearly occurrence of symptoms in a sample of children with and without a diagnosis of bipolar disorder in the community. METHODS: Parents retrospectively rated the occurrence of 37 activated and withdrawn symptoms causing dysfunction for each year of their child's life (mean age 12.6 +/- 6.9). Children were divided into three groups based on parent report of diagnosis by a community clinician: bipolar (n=78); non-bipolar diagnosis (n=38); and well (no psychiatric diagnosis) (n=82). Principal components analysis was performed to understand the relationship among the symptom variables and their potential differences among the three groups as a function of age. RESULTS: Four symptom components were derived and these began to distinguish children with bipolar disorder from the other groups at different ages. Component II (irritability/dyscontrol), which included temper tantrums, poor frustration tolerance, impulsivity, increased aggression, decreased attention span, hyperactivity and irritability, began to distinguish bipolar children from the others the earliest (i.e., from ages 1 to 6). The other components (I, III, and IV) which included symptoms more typical of adult depression (I), mania (III), and psychosis (IV), distinguished the children with a bipolar diagnosis from the others much later (between ages 7 and 12). LIMITATIONS: The data were derived from retrospective reports by parents of their children's symptoms on a yearly symptom check list instrument which has not been previously utilized. Parents' ratings were not validated by an outside rater. Moreover, the children were diagnosed in the community and a formal diagnostic interview was not given. CONCLUSIONS: By parental report, the cluster of symptoms in the irritability/dyscontrol component may characterize the earliest precursors to an illness eventually associated with more classic manic and depressive components that are diagnosed and treated as bipolar disorder in the community. These retrospective survey data suggesting a longitudinal evolution of symptom clusters in childhood bipolar-like illness identify a number of areas for prospective research and validation.
Adolescent↗
Discriminative validity of the general behavior inventory using youth report.
The present study investigated the ability of the General Behavior Inventory (GBI) to discriminate between diagnostic groups using youth self-report. One hundred and ninety-seven youths ages 10-17 years presenting at a midwestern urban outpatient clinic specializing in mood disorders completed the GBI as part of the intake process. Diagnoses were determined by a structured clinical interview (K-SADS) administered by either a child and adolescent psychiatrist or a research assistant trained to a high level of interrater reliability (kappa > .85). Games-Howell post hoc tests showed that the diagnostic groups significantly differed on the GBI's 2 subscales, Depression and Hypomanic-Biphasic. Logistic regression demonstrated that the scales discriminated between bipolar and disruptive behavior disorders, unipolar and bipolar depression, and mood and disruptive behavior disorders or no diagnosis. Receiver Operating Characteristic (ROC) curves further indicated the good diagnostic efficiency of the scales. Results indicate that the GBI's subscales might aid in making traditionally difficult differential diagnoses, such as between bipolar disorder and Attention Deficit Hyperactivity Disorder (ADHD) and between unipolar and bipolar depression.
Adolescent↗
Who are the comorbid adolescents? Agreement between psychiatric diagnosis, youth, parent, and teacher report.
The investigators examined the rates of psychiatric comorbidity for externalizing and internalizing behavior problems, using semistructured diagnostic interview and parent, teacher, and youth report on the Achenbach checklists. The study also evaluated the effects of conjunctive, compensatory, and disjunctive data combination strategies. Using the same data and identical diagnostic thresholds, between 5 and 74% of 189 youths presenting to an outpatient clinic were identified as having comorbid internalizing and externalizing problems. Parent report and semistructured interview indicated the highest comorbidity rates. Despite good cross-source agreement (rs .29-.58), there was very little agreement about which specific youths presented with comorbid internalizing and externalizing problems (kappas .14-.40). Results also indicate that single DSM-IV disorders, such as bipolar disorder, can manifest "comorbid" patterns of behavior problems on checklists.
Adolescent↗
Methodological issues and controversies in clinical trials with child and adolescent patients with bipolar disorder: report of a consensus conference.
OBJECTIVE: To achieve consensus among researchers, pharmaceutical industry representatives, federal regulatory agency staff, and family advocates on a template for clinical trials of acute mania/bipolar disorder in children and adolescents. METHOD: The American Academy of Child and Adolescent Psychiatry, in collaboration with Best Practice, convened a group of experts from the key stakeholder communities (including adult psychiatrists with expertise in bipolar disorder) and assigned them to workgroups to examine core methodological issues surrounding the design of clinical trials and, ultimately, to generate a consensus statement encompassing: (1) inclusion/exclusion criteria, (2) investigator training needs and site selection, (3) assessment and outcome measures, (4) protocol design and ethical issues unique to trials involving children/adolescents, and (5) regulatory agency perspectives on these deliberations. RESULTS: Conference participants reached agreement on 18 broad methodological questions. Key points of consensus were to assign priority to placebo-controlled studies of acute manic episodes in children and adolescents aged 10-17 years, who may or may not be hospitalized, and who may or may not suffer from common comorbid psychiatric disorders; to require that specialist diagnostic "gatekeepers" screen youths' eligibility to participate in trials; to monitor interviewer and rater competency over the course of the trial using agreed upon standards; and to develop new tools for assessment, including scales to measure aggression/rage and cognitive function, while using the best available instruments (e.g., Young Mania Rating Scale) in the interim. CONCLUSIONS: Methodologically rigorous, large-scale clinical trials of treatment of acute mania are urgently needed to provide information regarding the safety and efficacy, in youth, of diverse agents with potential mood-stabilizing properties.
Adolescent↗
Employing parent, teacher, and youth self-report checklists in identifying pediatric bipolar spectrum disorders: an examination of diagnostic accuracy and clinical utility.
The diagnosis of bipolar spectrum disorders (BPSD) is difficult to evaluate in child and adolescent populations. The current study examines whether commonly used behavior checklists- the Child Behavior Checklist, Teacher Report Form, and the Youth Self-Report form-are clinically useful in making a differential diagnosis between BPSD and other disorders. This study is the first to investigate the validity of integrating pairs of informants using these instruments to differentiate individuals with BPSD from those with disruptive behavior disorders, major depressive disorder, and any child or adolescent not meeting criteria for BPSD. Parent report best predicted diagnostic status, yet diagnostic efficiency statistics associated with these checklists were relatively poor. Results indicate that the Child Behavior Checklist has limited utility when attempting to derive clinically meaningful information about the presentation of juvenile BPSD.
Adolescent↗
Treatment recommendations for the use of antipsychotics for aggressive youth (TRAAY). Part I: a review.
OBJECTIVES: To review the evidence for the safety and efficacy of nonpharmacological and pharmacological treatments for aggression in children and adolescents. METHOD: and searches (1990-present) were conducted for double-blind, placebo-controlled studies of atypical antipsychotics for aggression and for literature on the use of other pharmacological agents and psychosocial interventions for aggression. Case reports and adult literature regarding the safety of atypical antipsychotics were used where controlled data for youth were lacking. RESULTS: Controlled data on the treatment of aggression in youth is scarce. Psychosocial interventions may be effective alone or in combination with pharmacological treatments. Psychotropic agents (e.g., stimulants, mood stabilizers, beta-blockers) have also been shown to have limited efficacy in reducing aggression. Antipsychotics, particularly the atypical antipsychotics, show substantial efficacy in the treatment of aggression in selected pediatric populations. Atypical antipsychotics are generally associated with fewer extrapyramidal symptoms than are typical antipsychotics. CONCLUSIONS: Psychosocial interventions and atypical antipsychotics are promising treatments for aggression in youth. Double-blind studies should examine the safety and efficacy of atypical antipsychotics compared to each other and to medications from other classes, the efficacy of specific medications for different subtypes of aggression, combining various psychotropic medications, optimal dosages, and long-term safety.
Adolescent↗
Treatment recommendations for the use of antipsychotics for aggressive youth (TRAAY). Part II.
OBJECTIVE: To develop treatment recommendations for the use of antipsychotic medications for children and adolescents with serious psychiatric disorders and externalizing behavior problems. METHOD: Using a combination of evidence- and consensus-based methodologies, recommendations were developed in six phases as informed by three primary sources of information: (1) current scientific evidence (published and unpublished), (2) the expressed needs for treatment-relevant information and guidance specified by clinicians in a series of focus groups, and (3) consensus of clinical and research experts derived from a formal survey and a consensus workshop. RESULTS: Fourteen treatment recommendations on the use of atypical antipsychotics for aggression in youth with comorbid psychiatric conditions were developed. Each recommendation corresponds to one of the phases of care (evaluation, treatment, stabilization, and maintenance) and includes a brief clinical rationale that draws upon the available scientific evidence and consensus expert opinion derived from survey data and a consensus workshop. CONCLUSION: Until additional research from controlled trials becomes available, these evidence- and consensus-based treatment recommendations may be a useful approach to guide the use of antipsychotics in youth with aggression.
Adolescent↗
A prospective, open-label trial of olanzapine in adolescents with schizophrenia.
BACKGROUND: Olanzapine is an atypical antipsychotic that has efficacy in adults with psychotic disorders. This preliminary study examined the effectiveness of olanzapine in adolescents with schizophrenia or its related conditions. METHOD: Adolescents aged 12-17 years (inclusive) with a diagnosis of schizophrenia, schizoaffective, or schizophreniform disorder were enrolled in this 8-week, open-label, outpatient study. The Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions Scale (CGI), and the Children's Global Assessment Scale (CGAS) were administered as outcome measures. Extrapyramidal side effects were assessed at each visit. Olanzapine was initiated at a dose of 2.5 mg/day and could be increased to a maximum total daily dose of 20 mg. RESULTS: Sixteen participants with a mean age of 13.8 (SD = 1.5) years were treated. Significant improvements were found in the PANSS, CGI severity, and CGAS scores. Reductions in both positive and negative symptoms were found. Increased appetite and sedation were the most frequently reported side effects. Two subjects required treatment for extrapyramidal side effects. CONCLUSIONS: Psychotic symptoms significantly improved during study. Overall, olanzapine was well tolerated. Future studies are needed to confirm these findings, to assess long-term treatment outcomes, and to compare the effectiveness of olanzapine with that of other antipsychotics.
Adolescent↗
How can we improve the assessment of safety in child and adolescent psychopharmacology?
OBJECTIVE: To identify approaches to improving methods for assessing tolerability and safety of psychotropic medications in children and adolescents. METHOD: Strengths and limitations of current methodology were reviewed and possible alternatives examined. RESULTS: Research on the validity of safety evaluation has been extremely limited. No evidence-based "gold standard" exists. Clinical trials remain the best design to establish causality, but sample size limitations prevent the detection of infrequent, though serious, adverse events. Other designs, such as cohort and case-control studies, and approaches, such as mining of large databases, must be considered. CONCLUSION: The current lack of methodological standardization across studies prevents generalizations and meta-analyses. Because the issues relevant to drug safety are diverse, a variety of methodological approaches and instruments are needed. It is, however, possible to adopt standard basic definitions of adverse events, degree of severity, ascertainment methods, and recording procedures, as a common "core," to which more specific assessment instruments can be added. Systematic empirical testing and validation of safety methodology is needed.
Adolescent↗
Review of safety assessment methods used in pediatric psychopharmacology.
OBJECTIVE: Elicitation is an essential and critical step in ascertaining adverse events (AEs). This report reviews elicitation methods used in published clinical trials of psychopharmacological agents in children. METHOD: Pediatric psychopharmacology reports were reviewed for safety methods in the Medline database. Studies were included if they were published 1980 or later, provided data on AEs, and described the ascertainment methodology used for determining them. RESULTS: A review of 196 pediatric psychopharmacology articles depicting safety assessments in clinical studies over the past 22 years revealed that there was no common method used for eliciting or reporting AE data. CONCLUSION: The current inconsistency in safety data ascertainment is a major limitation that likely impairs the ability to promptly and accurately identify drug-induced AEs. Research on how best to standardize safety methods should be considered a priority in pediatric psychopharmacology.
Adolescent↗
Developing methodologies for monitoring long-term safety of psychotropic medications in children: report on the NIMH conference, September 25, 2000.
OBJECTIVE: To improve the methods for long-term assessment of drug-associated side effects and advance knowledge of the safety profile of psychotropic medications in children and adolescents. METHOD: A multidisciplinary, interactive workshop was hosted by the National Institute of Mental Health (NIMH) and the Research Units on Pediatric Psychopharmacology network. Participants were experts in child and adolescent psychiatry, psychopharmacology, pharmacoepidemiology, and statistics from academia, the pharmaceutical industry, the Food and Drug Administration (FDA), and the NIMH. Evaluation of drug safety was examined from five perspectives: research design and methods, industry, regulatory requirements, bioethics, and practice settings. For each of these areas, special emphasis was placed on identifying barriers and generating solutions. RESULTS: A major obstacle is the lack of standardization of the methods used for collecting safety data. The limitations of both randomized clinical trials and passive postmarketing surveillance in assessing long-term safety were recognized. The need to consider alternative approaches, such as registries and trend analysis of population-based databases, was highlighted. Recommendations were proposed together with possible approaches to implementation. CONCLUSIONS: A concerted effort by academic researchers, industry, FDA, practitioners, and NIMH is needed to standardize methods and lay the foundations for systematic research on the long-term safety of psychotropic medications in children.
Adolescent↗
Combination lithium and divalproex sodium in pediatric bipolarity.
OBJECTIVE: Lithium carbonate (Li) or divalproex sodium (DVPX) may be effective for some juveniles with bipolar disorder. Many youths with bipolar disorder do not respond to DVPX or Li monotherapy. An open-label study was conducted to examine the effectiveness of combination DVPX and Li therapy with youths diagnosed with bipolar disorder. METHOD: Patients meeting DSM-IV criteria for bipolar I or bipolar II disorder, ages 5 to 17 years, were treated prospectively for up to 20 weeks with DVPX + Li. Assessments included the Young Mania Rating Scale (YMRS), Children's Depression Rating Scale-Revised (CDRS-R), and the Children's Global Assessment Scale (CGAS). The a priori definition of clinical remission utilized included four contiguous weekly ratings of YMRS </=12.5, CDRS-R </=40, CGAS >/=51, clinical stability, and no evidence of mood cycling. RESULTS: Ninety patients (66 males, 24 females) were treated. Significant improvement (p <.0001) in all outcome measures was observed by week 8 as well as at the end of study. The mean time in study was 11.3 weeks. Forty-seven percent (n = 42) met a priori criteria for remission. CONCLUSIONS: Symptoms of mania and depression in juvenile bipolar disorder may be safely and effectively treated acutely with DVPX + Li.
Antimanic Agents↗
An open-label pilot study of St. John's wort in juvenile depression.
OBJECTIVE: This pilot study examined the effectiveness, safety, tolerability, and pharmacodynamics of Hypericum perforatum (St. John's wort) in the treatment of youths diagnosed with major depressive disorder. METHOD: Youths 6 to 16 years of age meeting DSM-IV criteria for major depressive disorder with depressive symptoms of at least moderate severity were eligible to enroll between January 1999 and January 2001 in this 8-week, prospective, open-label, outpatient study. Outcome measures included the Children's Depression Rating Scale-Revised (CDRS-R) and the Clinical Global Impressions (CGI) scale. A priori criteria for response consisted of a CDRS-R score of </=28 and a CGI severity score </=2. Patients were initially prescribed 150 mg St. John's wort three times daily. If at the end of week 4 the patient did not meet a priori response criteria, the dose was increased to 300 mg three times daily. RESULTS: Thirty-three youths with a mean (SD) age of 10.5 (2.9) years were enrolled. After 4 weeks of St. John's wort therapy, 22 youths had their dose increased to 900 mg/day. Twenty-five of the patients met response criteria after 8 weeks of treatment. Overall, St. John's wort was well tolerated. CONCLUSION: St. John's wort may be an effective treatment for youths diagnosed with major depressive disorder. Placebo controlled trials seem indicated.
Adolescent↗
Prolactin levels during long-term risperidone treatment in children and adolescents.
BACKGROUND: This analysis was designed to investigate prolactin levels in children and adolescents on long-term risperidone treatment and explore any relationship with side effects hypothetically attributable to prolactin (SHAP). METHOD: Data from 5 clinical trials (total N = 700) were pooled for this post hoc analysis. Children and adolescents aged 5 to 15 years with subaverage intelligence quotients and conduct or other disruptive behavior disorders received risperidone treatment (0.02-0.06 mg/kg/day) for up to 55 weeks. Outcome measures analyzed included serum prolactin levels, reported adverse events, and the conduct problem subscore of the Nisonger Child Behavior Rating Form. RESULTS: Mean prolactin levels rose from 7.8 ng/mL at baseline to a peak of 29.4 ng/mL at weeks 4 to 7 of active treatment, then progressively decreased to 16.1 ng/mL at weeks 40 to 48 (N = 358) and 13.0 ng/mL at weeks 52 to 55 (N = 42). There was no relationship between pro-lactin levels and age. Females returned to a mean value within the normal range (</= 30 ng/mL) by weeks 8 to 12, and males were close to normal values (</= 18 ng/mL) by weeks 16 to 24. At least 1 SHAP was reported by 13 (2.2%) of 592 children. There was no direct correlation between prolactin elevation and SHAP. CONCLUSION: With long-term risperidone treatment in children and adolescents, serum prolactin levels tended to rise and peak within the first 1 to 2 months and then steadily decline to values within or very close to the normal range by 3 to 5 months.
Adolescent↗
Increased presence of white matter hyperintensities in adolescent patients with bipolar disorder.
Several reports have noted an increase in white matter hyperintensities (WMH) on MRI scans of adult patients with bipolar disorder. We investigated whether this increase was also evident in a group of adolescent patients with bipolar disorder. The sample consisted of 15 bipolar patients, 19 patients with schizophrenia and 16 healthy comparison subjects. All subjects were adolescents. WMH were blindly rated on T2-weighted and PD-weighted MRI scans using our own scale with documented inter-rater reliability. WMH were present in 10 of 15 bipolar patients (67%), seven of 19 patients with schizophrenia (37%) and five of 16 comparison subjects (31%). The bipolar adolescent group had a statistically significant increased presence of WMH compared both with healthy comparison subjects and the schizophrenic group. The association between WMH and bipolar disorder appears to extend to the adolescent years.
Adolescent↗
Somatic treatment for depressive illnesses in children and adolescents.
Numerous somatic interventions have been studied as potential treatments of depressive disorders in children and adolescents. These include antidepressant medications, light therapy, electro-convulsive therapy, and alternative therapies. The available evidence suggests that several somatic interventions hold promise as potentially safe and effective treatments for depressed youth; however, there is still much to be learned about these interventions. This article reviews what is known and what needs to be learned about the somatic treatment of pediatric depression.
Adolescent↗