Journal of child and adolescent psychopharmacology最新文献

Introduction: Accurate assessment of treatment outcomes in patients with Tourette syndrome (TS) is essential for evidence-based clinical care. This report determined the minimal clinically important difference (MCID) on the Yale Global Tic Severity Scale (YGTSS) Total Tic Score (YGTSS-TTS) and YGTSS Impairment Scale (YGTSS-I), using the Clinical Global Impression of TS Severity (CGI-TS-S) and Improvement (CGI-TS-I) as anchors, in pediatric patients with TS receiving pharmacotherapy. Materials and Methods: Analyses used data from two clinical trials of ecopipam (a randomized controlled trial and its open-label extension). Receiver operating characteristic (ROC) analysis determined the percentage reduction in YGTSS scores that distinguished patients with improvement from those with no change or worsening on the CGI-TS-S and CGI-TS-I. Spearman's correlation, empirical cumulative distribution function, and probability distribution function analyses examined relationships between YGTSS-TTS and CGI-TS-S or CGI-TS-I. Results: Overall, 133 patients (75.2% male; mean [SD] age, 12.7 [2.8]) were included; 63.2% had improvement on the CGI-TS-S, and 78.2% showed improvement on the CGI-TS-I. Percentage reduction in YGTSS scores that distinguished improvement from no change or worsening on the CGI-TS-S and CGI-TS-I ranged from 18.6%-33.3% (area under the ROC curve range, 0.71-0.81). Improvement on the YGTSS-TTS was correlated with posttreatment CGI-TS-S (r = -0.65; p < 0.001) and CGI-TS-I (r = -0.61; p < 0.001) scores. The MCID for YGTSS-TTS was achieved by 67% and 62% of patients with improvement on the CGI-TS-S and CGI-TS-I, respectively. Conclusions: This analysis is the first to determine the MCID for YGTSS in a pediatric population with TS receiving pharmacotherapy. Whether using CGI-TS-S or CGI-TS-I as the anchor, a 25% reduction in YGTSS scores was a generally appropriate minimum threshold to define clinically meaningful improvement in this population. Findings offer an objective threshold for classifying clinically meaningful improvement in children and adolescents receiving pharmacotherapy for TS in clinical practice.

Background: Aggression and irritability are common challenges in children with autism spectrum disorder (ASD), often requiring pharmacological management. Divalproex, an anticonvulsant and mood stabilizer, is used off-label for these symptoms, but its effectiveness remains unclear. This systematic review evaluates the efficacy and safety of divalproex in managing aggression and irritability in children with ASD. Methods: A systematic review was conducted following PRISMA guidelines, registered with PROSPERO (CRD420251029754). Searches were performed in PubMed, Embase, PsycINFO, and Web of Science, identifying studies involving children with ASD treated with divalproex, valproic acid, or valproate sodium. Data were extracted on study design, sample size, intervention details, outcomes, and adverse effects. Results: Ten studies met inclusion criteria, comprising three randomized controlled trials, one open-label trial, and six case reports. Intravenous (IV) divalproex demonstrated rapid reductions in aggression, suggesting potential for acute stabilization. However, oral divalproex produced inconsistent results for chronic aggression and irritability. Adverse effects included weight gain, sedation, and behavioral activation, with toxicity risks in polypharmacy settings. Discussion/Conclusion: Divalproex may offer value for acute management of aggression in children with ASD when administered intravenously. Its role in chronic management is less clear, with inconsistent outcomes and notable side effects. Clinicians should prioritize regular serum monitoring and consider alternative options for chronic use. Further research is needed to clarify its clinical role, particularly in diverse patient populations.

Objectives: The objective of this review is to review existing evidence on the management and prevention of agitation and aggression in the pediatric psychiatric inpatient setting with emphasis on general unit structure, organization, and milieu programming when discussing prevention. For management of agitation and aggression, the review focuses on de-escalation, as-needed medication, and restraint and seclusion. Methods: The existing literature search was conducted, yielding 1836 English language citations. An additional 109 studies were identified by citation search. Among them, 287 full-text studies were assessed for eligibility, and 107 studies were included for review. Studies were included if the contents of studies were shown to prevent agitation or aggression in pediatric psychiatric inpatient units, with focuses on staffing, staff training, milieu programming, and environmental changes. Studies were also included if the contents of studies discussed management of agitation and aggression with focuses on de-escalation, restraint and seclusion, and as-needed medication use. Results: We recognized multiple challenges while summarizing existing evidence in our field, including lack of definition, knowledge, and standardized measurement of agitation and aggression. Challenges further extend to heterogeneity and a constellation of small studies that are not controlled. However, existing evidence supports that management and prevention of agitation and aggression start with attention to staffing, staff training, and milieu programming. Evidence for the use of as-needed (pro re nata) medication for the management of agitation and aggression in pediatric populations is limited.

Objective: Rett syndrome (RTT) is a severe neurodevelopmental disorder affecting predominantly females and associated with variants in the MECP2 gene. Recent success in clinical trials have resulted in an expanded use of the Rett Syndrome Behaviour Questionnaire (RSBQ) for clinical and research purposes. Implementation of the RSBQ as a global clinical severity scale has raised concerns about its construct validity considering its content, structure, and psychometric features. To further understand RSBQ data, we analyzed RSBQ scores available in the literature with a focus on variability and influencing factors. Methods: We identified publications reporting RSBQ total and/or subscale scores and summarized relevant study information, such as type of investigation, administration method, and descriptive data. We then analyzed means and standard deviations, calculating variance-to-mean ratios (VMR), as a measure of variability, when raw score descriptive statistics were available. Where appropriate, we compared means and VMRs by Welch t-tests. Results: Of the 14 publications identified, raw total scores from 5 observational studies and 4 clinical trials (baseline) were available. Raw subscale scores from four of the five observational studies were also available. We found a wide but comparable range of mean total scores for observational studies and clinical trials. However, VMRs were significantly higher in observational studies. Subscale scores showed either high (i.e., General Mood, Breathing Problems) or low (e.g., Hand Behaviours, Body Rocking and Expressionless Face) variability. Available data demonstrated greater variability in pediatric than adult groups and less variability when using interviews or electronic RSBQ administration compared with paper forms. Total score changes over time did not affect variability. Although certain studies offered insight into the relationship between the RSBQ and other measures, overall, data were insufficient for characterizing how RSBQ variability relates to other factors. Conclusions: Our findings on score variability support the need for more comprehensive reporting of RSBQ data, cohort characterization, and methodology; and the deployment of standardized RSBQ administration methods, such as advanced data capture systems. There is potential for use of subscales as outcome measures, subject to further psychometric validation studies, including prospective investigations testing the stability of RSBQ scores and influencing factors. Further examining the relationship between RSBQ scores and other instruments will aid in its interpretation as a clinical outcome measure.

Objective: The current intense period of drug development for fragile X syndrome (FXS) and other neurodevelopmental disorders (NDDs) indications has highlighted the importance of behavioral outcome measures with strong psychometric properties and specifically content validity. The Aberrant Behavior Checklist-Community Edition (ABC-C), which has successfully been applied to autism spectrum disorder drug trials, has been revised for FXS (ABC_FX) and is widely used for both clinical and research purposes. Despite its strong psychometric validation, the ABC_FX and its parent measure have not been subjected to qualitative content validity evaluations. The present study intended to fill this gap. Methods: Using two surveys administered sequentially and developed with guidance and review from the Food and Drug Administration (FDA), we asked 10 clinicians experienced in FXS and related NDDs to determine the adequacy of the ABC_FX for assessing its behavioral constructs, its relevance to FXS, and its potential for detecting response to interventions. Various descriptive statistic parameters and ad hoc metrics were used to analyze categorical and Likert-like scale responses. Results: Experts considered that most items and all six ABC_FX subscales indeed evaluated their explicit or implicit behavioral constructs. However, item and subscale specificity were relatively low (∼25%-30%). Relevance of items of the Hyperactivity subscale was relatively high while low for many items of the Socially Unresponsive/Lethargic subscale. These items were also considered of low responsiveness potential. Irritability, Hyperactivity, Stereotypy, and Social Avoidance were the subscales with the strongest profiles, although the experts estimated that Stereotypy items may not be that responsive to treatment. A novel Anxiety construct, representing mainly recently reported observable behaviors, contributed mainly by Irritability items, emerged as a potential measure. Conclusions: The present study demonstrated the overall adequacy of the ABC_FX for its behavioral constructs, its relevance to FXS, and its potential for detecting response to treatment. It also showed that anxiety, a distinctive feature of FXS and other genetic NDDs, can also be measured by the ABC_FX. These findings can help with the implementation and interpretation of the ABC_FX, as well as with potential improvements to the measure in FXS and other NDDs.