Extension and Further Replication of the Reliability, Criterion Validity, and Treatment Sensitivity of the PANSS10 and PANSS20 for Pediatric Trials.

Introduction: The Positive and Negative Syndrome Scale (PANSS) is a widely accepted outcome measure for pediatric schizophrenia trials; however, it has notable limitations. Psychometric investigations have shown a multifactorial structure and some items have limited utility assessing symptom severity in children. To address these issues, we developed and evaluated optimized 10- and 20-item PANSS short-forms (PANSS10 and PANSS20) using patient-level clinical trial data. This study further assesses these optimized forms using independent clinical trial data. Methods: We examined patient-level data from a randomized pediatric schizophrenia trial comparing paliperidone ER to aripiprazole. Data were accessed through the Yale Open Data Access (YODA) secure platform. Analyses included confirmatory factor analyses, graded response models, ω score reliability, internal consistency, sensitivity to change, and criterion validity versus the Clinical Global Impressions of Severity (CGI-S). Bland-Altman analyses examined score calibration versus the 30-item PANSS and inclusion cut scores. Results: Participants (N = 288) were ages 12 to 17 years (M = 15.3, SD = 1.46; 66% male). Total scores for the PANSS10 and PANSS20 showed strong correlations with the 30-item PANSS (0.90 and 0.97, respectively). Average inter-item correlations were 0.10 and 0.14 and ωTotal reliabilities were 0.74 and 0.85. Both PANSS10 and PANSS20 scores showed reliability >0.80-2.3 to 4.5 SD and -3.0 to 6.0 SD about mean symptom severity, respectively. Sensitivity to treatment was also similar (partial eta squared 0.23 and 0.22), as was correlation with CGI-S at baseline (0.45 and 0.48; not significantly different). The mean item-average discrepancy with the 30-item PANSS was 0.095 for PANSS10 and 0.033 for PANSS20. Conclusions: The optimized PANSS forms continue to show impressive reliability, validity, and calibration compared with the 30-item PANSS. Researchers should consider replacing the 30-item PANSS with the PANSS10 as a clinical outcome and screening measure due to its length and psychometric performance.

Vortioxetine in children and adolescents with major depressive disorder: 6-month and 18-month open-label, flexible-dose, long-term extension studies.

Children and adolescents with severe or relapsing major depressive disorder (MDD) may require long-term antidepressant use, but safety and tolerability data on long-term treatment are limited. In a randomized, placebo-controlled trial in children and another in adolescents, vortioxetine and placebo groups showed improvement in MDD symptoms without statistically significant differences between groups. To gain insights on long-term safety and tolerability of vortioxetine in pediatric patients, participants from these two studies were enrolled in two long-term extension studies: 6 months (NCT02871297) followed by another 18 months (NCT03108625). Key safety measures included adverse events (AEs) and Columbia-Suicide Severity Rating Scale (C-SSRS); effectiveness measures included depression symptom severity, cognitive function, and overall functioning. Among the 662 patients in the 6-month extension, 61% experienced a treatment-emergent AE (TEAE), with the most common being nausea (20.8%); 2.1% had a serious AE (SAE), and 6% withdrew because of TEAEs. In the following 18-month extension (n = 94), 51% of patients experienced a TEAE, with the most common being headache (13.8%); no SAEs were reported. Based on the C-SSRS, 94% and 96% of patients reported no suicidal ideation or behavior in the 6- and 18-month studies, respectively. During the extension studies, patients continued to show improvement in depressive symptoms and cognitive and overall functioning, with > 50% of patients in remission at the end of each study, regardless of study treatment in the lead-in trial. Overall, vortioxetine remained well tolerated in pediatric patients with MDD who continued in the long-term extension studies with no observed increased risk in suicidal ideation.

Editors' Note: 2024 Annual Report Regarding JAACAP's Antiracist Journey.

In 2020, we wrote to you about our dedication and vision for JAACAP "to be antiracist at every level."1 Over the last 4 years we have pursued initiatives "to reshape the Journal to pursue this vision."2-4 In this article, we provide an update on these goals and initiatives (Figure 1). These initiatives include both scientific journals in the JAACAP family, JAACAP and JAACAP Open. Through this work we aspire to be a leader among mental health journals in our intentional pursuit of antiracist policies and practices.

Expert consensus statement for telepsychiatry and attention-deficit hyperactivity disorder.

Changing practice patterns caused by the pandemic have created an urgent need for guidance in prescribing stimulants using telepsychiatry for attention-deficit hyperactivity disorder (ADHD). A notable spike in the prescribing of stimulants accompanied the suspension of the Ryan Haight Act, allowing the prescribing of stimulants without a face-to-face meeting. Competing forces both for and against prescribing ADHD stimulants by telepsychiatry have emerged, requiring guidelines to balance these factors. On the one hand, factors weighing in favor of increasing the availability of treatment for ADHD via telepsychiatry include enhanced access to care, reduction in the large number of untreated cases, and prevention of the known adverse outcomes of untreated ADHD. On the other hand, factors in favor of limiting telepsychiatry for ADHD include mitigating the possibility of exploiting telepsychiatry for profit or for misuse, abuse, and diversion of stimulants. This Expert Consensus Group has developed numerous specific guidelines and advocates for some flexibility in allowing telepsychiatry evaluations and treatment without an in-person evaluation to continue. These guidelines also recognize the need to give greater scrutiny to certain subpopulations, such as young adults without a prior diagnosis or treatment of ADHD who request immediate-release stimulants, which should increase the suspicion of possible medication diversion, misuse, or abuse. In such cases, nonstimulants, controlled-release stimulants, or psychosocial interventions should be prioritized. We encourage the use of outside informants to support the history, the use of rating scales, and having access to a hybrid model of both in-person and remote treatment.

Parental perceptions of body weight and appetite in infants and toddlers with cystic fibrosis.

Nutritional status has clinical relevance and is a target of guidance to parents of children with cystic fibrosis (CF). Growth is routinely monitored in CF clinics but there is no standardized way of assessing appetitive behaviors or parents' perceptions of their children's appetite. Greater understanding of these factors could improve clinical guidance regarding parent feeding behaviors. We therefore aimed to assess parent perceptions of child weight, and parent reports of child appetite using the Baby Eating Behavior Questionnaire (BEBQ), in a sample of infants and toddlers with CF, compared with a community sample. We additionally assessed relationships of parent perceptions of child weight with parent feeding behaviors in the sample with CF. Anthropometric and questionnaire data were collected for 32 infants and toddlers with CF, as well as 193 infants and toddlers drawn from RESONANCE, a community cohort study. Parents perceived children with CF to be lower in weight than their actual weight, to a greater extent than was evident in the community sample. Parents who perceived their children with CF to be underweight vs. right weight reported greater slowness in eating on the BEBQ. Parents perceived children with CF to have greater slowness in eating and lower enjoyment of food, compared to parents of children in the community sample, independent of sample differences in child weight, age, and sex. Our results demonstrate the potential utility of the BEBQ in a clinical sample and suggest it may be helpful for clinicians to assess parents' perceptions of their child's weight and appetite to promote a fuller understanding of the child's nutritional status, facilitate appropriate feeding behaviors and alleviate unnecessary concerns.

The stability and persistence of symptoms in childhood-onset ADHD.

The course of childhood-onset attention deficit hyperactivity disorder (ADHD) varies across individuals; some will experience persistent symptoms while others' symptoms fluctuate or remit. We describe the longitudinal course of ADHD symptoms and associated clinical characteristics in adolescents with childhood-onset ADHD. Participants (aged 6-12 at baseline) from the Longitudinal Assessment of Manic Symptoms (LAMS) study who met DSM criteria for ADHD prior to age 12 were evaluated annually with the Kiddie Schedule for Affective Disorders and Schizophrenia for eight years. At each timepoint, participants were categorized as meeting ADHD criteria, subthreshold criteria, or not having ADHD. Stability of course was defined by whether participants experienced consistent ADHD symptoms, fluctuating symptoms, or remission. The persistence of the symptoms was defined by symptom status at the final two follow-ups (stable ADHD, stable remission, stable partial remission, unstable). Of 685 baseline participants, 431 had childhood-onset ADHD and at least two follow-ups. Half had a consistent course of ADHD, nearly 40% had a remitting course, and the remaining participants had a fluctuating course. More than half of participants met criteria for ADHD at the end of their participation; about 30% demonstrated stable full remission, 15% had unstable symptoms, and one had stable partial remission. Participants with a persistent course and stable ADHD outcome reported the highest number of symptoms and were most impaired. This work builds on earlier studies that describe fluctuating symptoms in young people with childhood-onset ADHD. Results emphasize the importance of ongoing monitoring and detailed assessment of factors likely to influence course and outcome to help young people with childhood-onset ADHD.

Randomized clinical trial of low dose suramin intravenous infusions for treatment of autism spectrum disorder.

BACKGROUND: There is a critical need for effective treatment of the core symptoms of autism spectrum disorder (ASD). The purinergic antagonist suramin may improve core symptoms through restoration of normal mitochondrial function and reduction of neuro-inflammation via its known antagonism of P2X and P2Y receptors. Nonclinical studies in fragile X knockout mice and the maternal immune activation model support these hypotheses. METHODS: We conducted a 14 week, randomized, double-blind, placebo-controlled proof -of-concept study (N = 52) to test the efficacy and safety of suramin intravenous infusions in boys aged 4-15 years with moderate to severe ASD. The study had 3 treatment arms: 10 mg/kg suramin, 20 mg/kg suramin, and placebo given at baseline, week 4, and week 8. The Aberrant Behavior Checklist of Core Symptoms (ABC-Core) (subscales 2, 3, and 5) was the primary endpoint and the Clinical Global Impressions-Improvement (CGI-I) was a secondary endpoint. RESULTS: Forty-four subjects completed the study. The 10 mg/kg suramin group showed a greater, but statistically non-significant, numeric improvement (- 12.5 ± 3.18 [mean ± SE]) vs. placebo (- 8.9 ± 2.86) in ABC-Core at Week 14. The 20 mg/kg suramin group did not show improvement over placebo. In exploratory analyses, the 10 mg/kg arm showed greater ABC Core differences from placebo in younger subjects and among those with less severe symptoms. In CGI-I, the 10 mg/kg arm showed a statistically significant improvement from baseline (2.8 ± 0.30 [mean ± SE]) compared to placebo (1.7 ± 0.27) (p = 0.016). The 20 mg/kg arm had a 2.0 ± 0.28 improvement in CGI-I, which was not statistically significant compared to placebo (p = 0.65). CONCLUSION: Suramin was generally safe and well tolerated over 14 weeks; most adverse events were mild to moderate in severity. Trial Registration Registered with the South African Health Authority, registration number DOH-27-0419-6116. CLINICALTRIALS: Gov registration ID is NCT06058962, last update posted 2023-09-28.

Editors' Note: Third Annual Report Regarding JAACAP's Antiracist Journey.

In 2020, we wrote to you of our dedication and vision for JAACAP "to be antiracist at every level."1 Over the last 3 years, we have pursued initiatives "to reshape the Journal to pursue this vision."2,3 In this article, we provide an update on these goals and initiatives (Figure 1). With the launching of our new open access journal, JAACAP Open,4 in late 2022, we now extend these initiatives to both scientific journals in the JAACAP family and aspire to be a leader among mental health journals in our intentional pursuit of antiracist policies and practices.

Psychometric Properties and Clinical Utility of CBCL and P-GBI Sleep Items in Children and Adolescents.

OBJECTIVE: Sleep is crucial to overall health, playing a complex role in a wide range of mental health concerns in children and adults. Nevertheless, clinicians may not routinely assess sleep problems due to lack of awareness or limitations such as cost or time. Scoring sleep-related items embedded on broader scales may help clinicians get more out of tools they are already using. The current study explores evidence of reliability, validity, and clinical utility of sleep-related items embedded on two caregiver-report tools: the Child Behavior Checklist (CBCL) and Parent General Behavior Inventory (P-GBI). METHOD: Youth aged 5-18 years and their parents were recruited from both an academic medical center (N = 759) and an urban community health center (N = 618). Caregivers completed the CBCL and P-GBI as part of a more comprehensive outpatient evaluation. Exploratory factor analyses, multi-group confirmatory factor analyses, and graded response models evaluated dimensionality, reliability, and invariance across samples. Correlations and receiver operating characteristic curve analyses probed associations with diagnostic and demographic variables. RESULTS: Two subscales emerged for each itemset. Across both samples, P-GBI sleep subscales were more reliable and consistent than CBCL sleep subscales, showed greater coverage of sleepiness and insomnia constructs, were better at discriminating individuals within a wider range of sleep complaints, and showed significant correlation with mood disorder diagnoses. CONCLUSIONS: The P-GBI sleep items provide a brief, reliable measure for assessing distinct dimensions of sleep complaints and detecting mood symptoms or diagnoses related to the youth's sleep functioning, making them a useful addition to clinical practice.

Cariprazine in Pediatric Patients with Autism Spectrum Disorder: Results of a Pharmacokinetic, Safety and Tolerability Study.

Objective: Cariprazine is a dopamine D3-preferring D3/D2 and serotonin 5-HT1A receptor partial agonist approved to treat adults with schizophrenia and manic/mixed or depressive episodes associated with bipolar I disorder. This study, which is the first to evaluate cariprazine in pediatric patients with autism spectrum disorder (ASD) (including children 5-9 years of age) using an oral solution formulation, evaluated the safety, tolerability, pharmacokinetics (PK), and exploratory efficacy of cariprazine and its two major active metabolites, desmethyl cariprazine (DCAR) and didesmethyl cariprazine (DDCAR). Methods: This clinical pharmacology, open-label, multiple-dose study enrolled 25 pediatric patients from 5 to 17 years of age, who met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for ASD. All patients began treatment with cariprazine 0.5 mg once daily (QD) and underwent a titration over 7 days to maintenance doses of 1.5 or 3 mg QD for patients 13-17 years of age at Screening, 0.75 or 1.5 mg QD for patients 10-12 years of age at Screening, and 0.5 or 1.5 mg QD for patients 5-9 years of age at Screening. After 6 weeks total of dosing, there was a 6-week follow-up period. Study assessments included adverse events (AEs), safety parameters, noncompartmental PK parameters, and exploratory efficacy assessments, including the Aberrant Behavior Checklist-Irritability Subscale (ABC-I), Clinical Global Impressions (CGI-S), Caregiver Global Impressions (CgGI-S), Children's Yale-Brown Obsessive Compulsiveness Scale Modified for ASD (CYBOCS-ASD), Social Responsiveness Scale (SRS), and Vineland Adaptive Behavior Scale (VABS-III). Results: All AEs were mild or moderate in severity. Most frequent treatment-emergent adverse events (TEAEs) were increased weight, increased alanine aminotransferase, increased appetite, dizziness, agitation, and nasal congestion. Increases in weight were not considered clinically meaningful. Two subjects reported extrapyramidal symptom-related TEAEs that resolved without leading to discontinuation. Dose-normalized exposures of all analytes were modestly higher in pediatric patients from 5 to 9 years of age when compared to older patients. Consistent with previous studies, at steady state, the rank of exposure in plasma was DDCAR > cariprazine > DCAR. There was numerical improvement on all exploratory endpoints (ABC-I, CGI-S, CgGI-S, CYBOCS-ASD, SRS, and VABS-III). Conclusions: PK of cariprazine and its metabolites were characterized in pediatric patients with ASD at doses up to 3 mg QD (13-17 years) and 1.5 mg QD (5-12 years). Caripazine treatment was generally well tolerated and results from this study will inform the selection of appropriate pediatric doses for subsequent studies.

Adequacy of Children's Psychopharmacology Services: Variations by Race and Clinical Characteristics.

OBJECTIVE: An expert consensus approach was used to determine the adequacy of children's psychopharmacology and to examine whether adequacy varied by demographic or clinical characteristics. METHODS: Data were from the baseline interview of 601 children, ages 6-12 years, who had visited one of nine outpatient mental health clinics and participated in the Longitudinal Assessment of Manic Symptoms study. Children and parents were interviewed with the Kiddie Schedule for Affective Disorders and Schizophrenia and the Service Assessment for Children and Adolescents to assess the child's psychiatric symptoms and lifetime mental health services use, respectively. An expert consensus approach informed by published treatment guidelines was used to determine the adequacy of children's psychotropic medication treatment. RESULTS: Black children (compared with White children; OR=1.84, 95% CI=1.53-2.23) and those with anxiety disorders (vs. no anxiety disorder; OR=1.55, 95% CI=1.08-2.20) were more likely to receive inadequate pharmacotherapy; those whose caregivers had a bachelor's degree or more education (vs. those who had a high school education, general equivalency diploma, or less than high school education; OR=0.74, 95% CI=0.61-0.89) were less likely to receive inadequate pharmacotherapy. CONCLUSIONS: The consensus rater approach permitted use of published treatment efficacy data and patient characteristics (e.g., age, diagnoses, history of recent hospitalizations, and psychotherapy) to assess adequacy of pharmacotherapy. These results replicate findings of racial disparities reported in previous research using traditional methods to determine treatment adequacy (e.g., with a minimum number of treatment sessions) and highlight the continued need for research on racial disparities and strategies to improve access to high-quality care.

Reorienting Latent Variable Modeling for Supervised Learning.

Despite its potentials benefits, using prediction targets generated based on latent variable (LV) modeling is not a common practice in supervised learning, a dominating framework for developing prediction models. In supervised learning, it is typically assumed that the outcome to be predicted is clear and readily available, and therefore validating outcomes before predicting them is a foreign concept and an unnecessary step. The usual goal of LV modeling is inference, and therefore using it in supervised learning and in the prediction context requires a major conceptual shift. This study lays out methodological adjustments and conceptual shifts necessary for integrating LV modeling into supervised learning. It is shown that such integration is possible by combining the traditions of LV modeling, psychometrics, and supervised learning. In this interdisciplinary learning framework, generating practical outcomes using LV modeling and systematically validating them based on clinical validators are the two main strategies. In the example using the data from the Longitudinal Assessment of Manic Symptoms (LAMS) Study, a large pool of candidate outcomes is generated by flexible LV modeling. It is demonstrated that this exploratory situation can be used as an opportunity to tailor desirable prediction targets taking advantage of contemporary science and clinical insights.

Comparing self-reported quality of life in youth with bipolar versus other disorders.

OBJECTIVES: This study benchmarks quality of life (QoL) of youth with bipolar disorder (BD) against healthy youth, youth with chronic medical conditions, and youth with other psychiatric disorders. The relative impacts of depressive, (hypo)manic, mixed, and externalizing symptoms on QoL are tested for youth with BD. METHOD: In total, 657 youth completed the Schedule for Affective Disorders and Schizophrenia for Children (KSADS), the KSADS depression and mania scales, the Parent General Behavior Inventory (PGBI), and the Child Behavior Checklist (CBCL). Youth-reported QoL was determined by the Revised Children Quality of Life Questionnaire (KINDL) and was compared to healthy youth, youth with chronic medical conditions, and youth with other psychiatric disorders. RESULTS: Youth with BD reported poorer QoL overall and on most subscales compared to healthy youth, youth with chronic medical conditions, youth with behavior disorders, and youth with other non-behavior/non-mood disorders. QoL in youth with BD did not differ significantly from QoL in youth with unipolar depression. Parent-report and interview-rated depressive symptoms were associated with decreases in Total QoL and all QoL subscales except Family. Externalizing symptoms were associated with decreases in Family QoL and increases in Friend QoL, and (hypo)manic symptoms were associated with increases in Emotional Well-Being QoL. CONCLUSIONS: Depressive symptoms may drive the decline in QoL causing youth with BD to rate their QoL worse than healthy youth, youth with chronic medical conditions, and youth with behavior disorders, but not worse than youth with unipolar depression.

Finding a Needed Diagnostic Home for Children with Impulsive Aggression.

Aggressive behavior is one of the most common reasons for referrals of youth to mental health treatment. While there are multiple publications describing different types of aggression in children, it remains challenging for clinicians to diagnose and treat aggressive youth, especially those with impulsively aggressive behaviors. The reason for this dilemma is that currently several psychiatric diagnoses include only some of the common symptoms of aggression in their criteria. However, no single diagnosis or diagnostic specifier adequately captures youth with impulsive aggression (IA). Here we review select current diagnostic categories, including behavior and mood disorders, and suggest that they do not provide an adequate description of youth with IA. We also specifically focus on the construct of IA as a distinct entity from other diagnoses and propose a set of initial, provisional diagnostic criteria based on the available evidence that describes youth with IA to use for future evaluation.

An Optimized Version of the Positive and Negative Symptoms Scale (PANSS) for Pediatric Trials.

OBJECTIVE: The accepted primary outcome measure for evaluating psychotic symptoms is decades old, long, and initially designed for adults. Surprisingly, the psychometric properties of primary outcome measures have never been reported for a pediatric sample using modern methods. The present study's aim is to use a pediatric sample to evaluate the psychometrics of the most used primary outcome measure in pediatric schizophrenia trials, the Positive and Negative Syndrome Scale (PANSS). METHOD: To evaluate the factor structure, item characteristics, and treatment sensitivity of the PANSS in a pediatric sample, secondary analyses of PANSS data at baseline and weekly throughout an 8-week randomized double-blind study of 3 antipsychotic agents (registered and previously published) were conducted. Subjects were 118 youths receiving outpatient psychiatric treatment for schizophrenia spectrum disorders (mean age = 14.26 years, SD = 2.41 years). RESULTS: A 10-item short form, keeping 2 strongest items for each factor, had r = 0.89 with the full-length scale. Each of the five 2-item subscales has alphas ranging from 0.66 to 0.84. Item Response Theory (IRT) found that the 10-item scale and 2-item subscores had high reliability across the severity range typical of those for clinical trials. Criterion validity was high, with equal sensitivity to clinical changes over time. CONCLUSION: A 10-item PANSS version eliminates weaker items in the pediatric population while preserving coverage of 5 factors and similar sensitivity to clinical changes over time. It thus may be more appropriate for subsequent pediatric trials, and for clinical use when time and efficiency are paramount.

Diagnostic accuracy of the Child and Adolescent Symptom Inventory (CASI-4R) substance use subscale in detecting substance use disorders in youth.

Identifying substance use disorders (SUDs) early and accurately improves case formulation and treatment. Previous studies have investigated validity and reliability of the Child and Adolescent Symptom Inventory (CASI) for anxiety, mood, and behavior problems. The present study's aim was to test if the embedded CASI Substance Use (SU) subscale can discriminate adolescents and young adults (AYA) with and without a SUD diagnosis accurately enough to justify clinical application within an evidence-based assessment framework. N = 479 outpatient AYA (age 14-21) and their caregivers completed K-SADS-PLW semistructured diagnostic interviews; caregivers completed the CASI and adolescents completed a parallel version, the Youth (self-report) Inventory (YI). K-SADS-PLW indicated that 33 youth met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for SUDs. Receiver Operating Characteristic (ROC) analyses found that both CASI and YI Substance Use subscale scores significantly identified K-SADS-diagnosed SUDs in AYA: Caregiver area under curve (AUC) = .91, p < .0005; YI(AUC) = .90, p < .0005. There was no significant difference in diagnostic accuracy between informants. Both subscales showed diagnostic and clinical utility in identifying AYA SUDs in outpatient mental health settings. Findings suggest that the CASI-4R subscale could be a helpful screening instrument for AYA SUDs. A case vignette illustrates the clinical application of study findings. Future research should examine rapport as a moderator of reporting accuracy, and replicate use of these measures under varying clinical scenarios. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Developing Empirical Latent Profiles of Impulsive Aggression and Mood in Youths across Three Outpatient Samples.

OBJECTIVE: Aggression with impulsivity and reactivity (AIR) may distinguish a subset of youth from those with attention problems, rule-breaking behavior, or mood disorders, potentially with differential treatment response. Yet, DSM-5 and ICD-10 do not include an AIR diagnosis. Thus, we empirically grouped youths into profiles based on AIR, manic, depressive, rule-breaking, and self-harm behaviors; examined which profiles replicated across three samples; and characterized profile sets on demographic and clinical features. METHOD: After harmonizing data from three samples (n = 679, n = 392, n = 634), Latent Profile Analysis (LPA) assigned youth to profiles based on caregiver-reported measures of AIR, manic, depressive, rule-breaking, and self-harm behaviors. Profiles from each sample were grouped into sets based on profile similarity. Analyses tested differences in diagnoses, sex, and race, age, functioning, and mood severity. RESULTS: Eight-profile solutions fit best. Seven profiles replicated across samples: high AIR and self-harm, lower depressive and manic scores; high AIR, manic symptoms, and self-harm; high depression symptoms; three smaller sets with high manic and depressive symptoms and moderate AIR; and two high rates of bipolar diagnoses and family bipolar history. Two sets were high on both AIR and mood symptoms, were the most impaired, and had the highest comorbidity. CONCLUSIONS: Analyses support an empirical definition of AIR, separate from mood disorders. Profile sets distinguished by level of AIR and mood symptoms differed in demographic and diagnostic characteristics as well as functioning. Importantly, a set emerged with high AIR but low mood indicators and with high rates of ADHD and ODD, but not mood disorder.

Narrative Review: Impairing Emotional Outbursts: What They Are and What We Should Do About Them.

OBJECTIVE: Impairing emotional outbursts, defined by extreme anger or distress in response to relatively ordinary frustrations and disappointments, impact all mental health care systems, emergency departments, schools, and juvenile justice programs. However, the prevalence, outcome, and impact of outbursts are difficult to quantify because they are transdiagnostic and not explicitly defined by current diagnostic nosology. Research variably addresses outbursts under the rubrics of tantrums, anger, irritability, aggression, rage attacks, or emotional and behavioral dysregulation. Consistent methods for identifying and assessing impairing emotional outbursts across development or systems of care are lacking. METHOD: The American Academy of Child and Adolescent Psychiatry Presidential Task Force (2019-2021) conducted a narrative review addressing impairing emotional outbursts within the limitations of the existing literature and independent of diagnosis. RESULTS: Extrapolating from the existing literature, best estimates suggest that outbursts occur in 4%-10% of community children (preschoolers through adolescents). Impairing emotional outbursts may respond to successful treatment of the primary disorder, especially for some children with attention-deficit/hyperactivity disorder whose medications have been optimized. However, outbursts are generally multi-determined and often represent maladaptive or deficient coping strategies and responses. CONCLUSION: Evidence-based strategies are necessary to address factors that trigger, reinforce, or excuse the behaviors and to enhance problem-solving skills. Currently available interventions yield only modest effect sizes for treatment effect. More specific definitions and measures are needed to track and quantify outbursts and to design and assess the effectiveness of interventions. Better treatments are clearly needed.

26-Week Open-Label Extension Study Evaluating the Safety and Tolerability of Flexible Doses of Oral Ziprasidone in Children and Adolescents with Bipolar I Disorder (Most Recent Episode Manic).

Objective: To describe the longer-term effectiveness, safety, and tolerability of open-label ziprasidone in children and adolescents with bipolar I disorder (BD-I). Methods: A subset of 23 participants aged 10-17 years, who were previously treated in a multi-site, 4-week randomized controlled trial received open-label ziprasidone (20-80 mg twice a day) for up to 26 weeks. Results: The most common adverse events (AEs) were fatigue (30%), somnolence (17%), and nausea (13%). Effects on weight, body mass index, and metabolic parameters (glucose, cholesterol, and triglycerides) were minimal. No participant had a Fridericia-corrected QT interval ≥ 460 msec or a change from baseline of ≥60 msec, and there were no cardiac-related AEs. Both the participants who continued ziprasidone and those who initiated ziprasidone in the open-label extension showed improvements in their symptoms of mania. Conclusions: The overall findings of the study are consistent with the accumulating knowledge on the safety profile of ziprasidone in the acute and long-term treatment of children and adolescents with BD-I, in the midst of a manic episode. ClinicalTrial.gov ID: NCT03768726.

Efficacy and Safety of Lisdexamfetamine in Preschool Children With Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: To evaluate the acute efficacy, safety, and tolerability of lisdexamfetamine dimesylate (LDX) vs placebo (PBO) in preschool-aged children with attention-deficit/hyperactivity disorder (ADHD). METHOD: This phase 3, double-blind, fixed-dose study randomly assigned children (aged 4-5 years) with ADHD to 6 weeks of LDX (5, 10, 20, 30 mg) or PBO. The prespecified primary (change from baseline at week 6 in ADHD Rating Scale IV, Preschool version, total score [ADHD-RS-IV-PS-TS]) and key secondary (Clinical Global Impression-Improvement [CGI-I] score at week 6) efficacy endpoints were assessed using linear mixed-effects models for repeated measures. Safety and tolerability assessments included treatment-emergent adverse events (TEAEs) and changes in pulse and blood pressure (BP). RESULTS: The study comprised 199 participants randomly asigned 5:5:5:5:6 to receive 5, 10, 20, 30 mg LDX or PBO, respectively. Least squares (LS) mean (95% CI) treatment difference at week 6 between pooled LDX (10, 20, 30 mg) and PBO was statistically significant for ADHD-RS-IV-PS-TS change (-5.9 [-11.01, -0.78], p = .0242; effect size [ES], -0.43). CGI-I scores improved (ie, 1-2 on CGI-I) in 41.7% for pooled LDX and 24.3% for PBO (p = .0857). The LS mean (95% CI) treatment difference between pooled LDX and PBO for CGI-I score at week 6 was -0.6 (-1.03, -0.16; p = .0074; ES, -0.52). Frequency of TEAEs was 46.6% across all 4 LDX doses vs 42.2% with PBO; the most frequent TEAEs were decreased appetite (13.7% vs 8.9%, respectively) and irritability (9.6% vs 0%). Discontinuations because of TEAEs were 5.5% for all LDX doses and 4.4% for PBO. Mean ± SD pulse/BP changes from baseline at week 6/early termination were numerically greater with LDX vs PBO (pulse beats/min: 2.7 ± 10.79 vs 1.2 ± 9.90; systolic BP, mm Hg: 1.0 ± 7.51 vs 0.3 ± 6.06; diastolic BP, mm Hg: 1.7 ± 5.90 vs 0.0 ± 6.88). CONCLUSION: In children aged 4 to 5 years with ADHD, LDX was more efficacious than PBO in reducing symptoms. The observed ES for change in ADHD-RS-IV-PS-TS appears to be smaller in magnitude than has been reported for studies of LDX conducted in older children and adolescents. LDX was generally well tolerated, and no new safety signals were identified. CLINICAL TRIAL REGISTRATION INFORMATION: Safety and Efficacy Study in Preschool Children Aged 4-5 Years With Attention-Deficit/Hyperactivity Disorder; http://www. CLINICALTRIALS: gov; NCT03260205.