Perceived Negative Effects of Tic Management Strategies in Adults With Tic Disorders.

Behavior therapy is a well-established and empirically supported treatment for tic disorders (TDs). However, concerns have been expressed about the negative effects of behavioral interventions, such as tic worsening, tic substitution, and excessive effort. This study explored perceived negative effects of tic management strategies in adults with TDs and predictors of these experiences. Participants (N = 72) completed semi-structured interviews 11 years after receiving behavior therapy or supportive therapy in a randomized clinical trial. We examined responses to interview questions about managing tics and predictors of reported negative effects. Most participants did not experience tic worsening (84%) or tic substitution (75%) from tic management strategies. The majority felt they could manage tics while participating in their environment (87%) and did not report life interference from tic management (77%). About half (45%) felt less present when managing tics. Treatment non-responders in the original trial were more likely to report negative effects of tic management strategies. No differences in reported negative consequences were found between those who received behavior therapy versus supportive therapy, suggesting that behavior therapy specifically does not lead to such adverse effects. These findings could reduce misconceptions about behavior therapy for TDs and enhance its acceptability and utilization.

Standardizing and Improving Care for Pediatric Agitation Management in the Emergency Department.

BACKGROUND AND OBJECTIVES: Pediatric mental health emergency department (ED) visits are rising in the United States, with more visits involving medication for acute agitation. Timely, standardized implementation of behavioral strategies and medications may reduce the need for physical restraint. Our objective was to standardize agitation management in a pediatric ED and reduce time in physical restraints. METHODS: A multidisciplinary team conducted a quality improvement initiative from September 2020 to August 2021, followed by a 6-month maintenance period. A barrier assessment revealed that agitation triggers were inadequately recognized, few activities were offered during long ED visits, staff lacked confidence in verbal deescalation techniques, medication choices were inconsistent, and medications were slow to take effect. Sequential interventions included development of an agitation care pathway and order set, optimization of child life and psychiatry workflows, implementation of personalized deescalation plans, and adding droperidol to the formulary. Measures include standardization of medication choice for severe agitation and time in physical restraints. RESULTS: During the intervention and maintenance periods, there were 129 ED visits with medication given for severe agitation and 10 ED visits with physical restraint use. Among ED visits with medication given for severe agitation, standardized medication choice (olanzapine or droperidol) increased from 8% to 88%. Mean minutes in physical restraints decreased from 173 to 71. CONCLUSIONS: Implementing an agitation care pathway standardized and improved care for a vulnerable and high-priority population. Future studies are needed to translate interventions to community ED settings and to evaluate optimal management strategies for pediatric acute agitation.

Study Preregistration: Measuring What Matters: Development and Dissemination of a Core Outcome Set for Pediatric Anxiety Disorders Clinical Trials.

Pediatric anxiety disorders (AD) are prevalent disorders with an impact on all aspects of a child's life and functioning.1 Although evidence supports commonly used treatments, there are notable concerns with the research to date.2 Heterogeneity in outcome selection, measurement, analysis, and reporting is a contributing factor to the hinderance of the translation of research into clinical practice.3 Recognition for outcome standardization in pediatric mental health disorders is evolving and there are several initiatives of importance, including the International Consortium for Health Outcomes Measurement (ICHOM), which has developed standardized outcome sets for use in the routine clinical mental health treatment of children and adolescents.4 Similarly, the International Alliance of Mental Health Research Funders5 advocate for use of 1 specific outcome measurement instrument (OMI) in the youth mental health research that they fund. Development of a Core Outcome Set (COS), a minimal set of outcomes that should be measured and reported in clinical trials, has been a solution in other areas of medicine to address heterogeneity in outcome selection and measurement across trials.6 The Core Outcomes and Measures in Pediatric Anxiety Clinical Trials (COMPACT) Initiative will develop a harmonized, evidence- and consensus-based COS that is meaningful to youth and families for use in future trials in pediatric AD.

Anxiety symptom trajectories from treatment to 5- to 12-year follow-up across childhood and adolescence.

OBJECTIVE: The current study examined trajectories of anxiety during (a) acute treatment and (b) extended follow-up to better characterize the long-term symptom trajectories of youth who received evidence-based intervention for anxiety disorders using a person-centered approach. METHOD: Participants were 319 youth (age 7-17 years at enrollment), who participated in a multicenter randomized controlled trial for the treatment of pediatric anxiety disorders, Child/Adolescent Anxiety Multimodal Study, and a 4-year naturalistic follow-up, Child/Adolescent Anxiety Multimodal Extended Long-term Study, an average of 6.5 years later. Using growth mixture modeling, the study identified distinct trajectories of anxiety across acute treatment (Weeks 0-12), posttreatment (Weeks 12-36), and the 4-year-long follow-up, and identified baseline predictors of these trajectories. RESULTS: Three nonlinear anxiety trajectories emerged: "short-term responders" who showed rapid treatment response but had higher levels of anxiety during the extended follow-up; "durable responders" who sustained treatment gains; and "delayed remitters" who did not show an initial response to treatment, but showed low levels of anxiety during the maintenance and extended follow-up periods. Worse anxiety severity and better family functioning at baseline predicted membership in the delayed remitters group. Caregiver strain differentiated short-term responders from durable responders. CONCLUSIONS: Findings suggest that initial response to treatment does not guarantee sustained treatment gains over time for some youth. Future follow-up studies that track treated youth across key developmental transitions and in the context of changing social environments are needed to inform best practices for the long-term management of anxiety.

Clinical Characteristics of Children With Tourette Syndrome With and Without Sleep Disorder.

BACKGROUND: Sleep problems are common in children with Tourette Syndrome (TS). However, research regarding their demographic and clinical profile is limited. METHODS: We examined characteristics of 114 children aged five to 17 years with a lifetime diagnosis of TS and compared children with sleep disorder (n = 32) and without sleep disorder (n = 82). Parent report from the 2014 National Survey of the Diagnosis and Treatment of ADHD and Tourette Syndrome provided demographics and clinical information, other diagnosed disorders, medication use, TS severity, and impairment. RESULTS: More children with TS with sleep disorder were from households with lower parental education (P < 0.01) and poverty (P = 0.04); had other diagnoses (P = 0.03), including obsessive-compulsive disorder (P < 0.01), oppositional defiant disorder or conduct disorder (P < 0.01), attention-deficit/hyperactivity disorder (ADHD) (P = 0.02), and autism (P = 0.03); and had ever used TS medication (P = 0.01) than children with TS without sleep disorder. More children with TS with sleep disorder had severe TS symptoms (P <0.01), tic-related impairment (P<0.01), and severe ADHD symptoms (P < 0.01) compared with children with TS without sleep disorder. CONCLUSIONS: Findings suggest greater parent-reported impact and tic-related interference in children with TS with sleep disorder compared with TS without sleep disorder. Results underscore the importance of monitoring and intervention for TS exacerbations, other diagnosed disorders, and medication use, and consideration of socioeconomic context in sleep disorder management and prevention in children with TS.

Initiation of Pharmacotherapy Following CBT in Anxious Youth: Results From the Child/Adolescent Anxiety Multimodal Study (CAMS).

Objective: To describe youth with anxiety disorders who initiate pharmacotherapy following cognitive-behavioral therapy (CBT) in a prospective, randomized trial and to identify predictors of the decision to use pharmacotherapy.Methods: Data from CBT-treated youth (aged 7-17 years, N = 139) in the Child/Adolescent Anxiety Multimodal Study (CAMS), a multisite, randomized controlled trial that examined the efficacy of CBT, sertraline, their combination, and placebo for pediatric anxiety disorders (DSM-IV criteria), were evaluated. Initiation of pharmacotherapy following acute CBT treatment was examined over a 24-week period; the study was conducted from December 2002 through May 2007. Logistic regression models identified features associated with initiating pharmacotherapy, including symptom severity (scores on the Pediatric Anxiety Rating Scale [PARS] and the Screen for Child/Adolescent Anxiety Related Disorders [SCARED]), parent and child treatment expectations, Clinical Global Impressions-Improvement/Severity of Illness (CGI-I/S) scores, and clinical and demographic characteristics.Results: CBT non-remitters (CGI-S score > 2) who began pharmacotherapy (n = 10) and those who did not (n = 80) were similar in age (P = .445), sex (P = .324), race (P = .242), and symptom severity based on CGI-S (P = .753), PARS (P = .845), or SCARED (P = .678) scores. Mean ± SD improvement (CGI-I score) at week 12 did not differ between patients who initiated pharmacotherapy (3.00 ± 0.82) and those who did not (2.69 ± 0.89, P = .798). However, in the logistic regression, age (P = .003), race (P = .021), and parents' treatment expectation (P = .037) were significantly associated with the likelihood of initiating pharmacotherapy. Beginning pharmacotherapy in CBT non-remitters was associated with a significant improvement in CGI-S score (mean ± SD decline: -0.99 ± 0.46; 95% credible interval [CrI], -0.088 to -1.89; P = .035) from week 12 to week 36 compared to patients who did not begin pharmacotherapy.Discussion: Very few CBT non-remitters initiated pharmacotherapy, although beginning medication produced significant improvement. Younger and racial and ethnic minoritized patients as well as those with lower expectations for CBT were less likely to begin medication.Trial Registration: ClinicalTrials.gov identifier: NCT00052078.

Childhood Predictors of Long-Term Tic Severity and Tic Impairment in Tourette's Disorder.

Tics peak in late childhood and decline during adolescence. Yet, for some with Tourette's disorder, tics persist into adulthood. We evaluated childhood predictors of adult tic severity and tic impairment, and change over time. Eighty adolescents/adults were evaluated 11 years following a randomized-controlled trial of behavior therapy. An independent evaluator rated tic severity and tic impairment at baseline, posttreatment, and long-term follow-up. At baseline, parents completed demographics/medical history, and youth tic, internalizing, and externalizing symptom ratings. Youth rated premonitory urge severity and family functioning. After controlling for prior tic treatment effects, female sex and higher tic severity predicted higher tic severity in adulthood; and female sex, no stimulant medication use, higher tic severity, and poorer family functioning predicted higher tic impairment. Higher tic severity and premonitory urge severity predicted smaller reductions in tic severity, whereas higher externalizing symptoms predicted greater reduction in tic severity. Female sex predicted smaller reduction in tic impairment, and externalizing symptoms predicted greater reduction in tic impairment. Female sex and childhood tic severity are important predictors of tic severity and tic impairment in adulthood. Family functioning, premonitory urge severity, and tic severity are important modifiable targets for early or targeted intervention to improve long-term outcomes.

Urge intolerance predicts tic severity and impairment among adults with Tourette syndrome and chronic tic disorders.

Background: Individuals with Tourette Syndrome and Persistent Tic Disorders (collectively TS) often experience premonitory urges-aversive physical sensations that precede tics and are temporarily relieved by tic expression. The relationship between tics and premonitory urges plays a key role in the neurobehavioral treatment model of TS, which underlies first-line treatments such as the Comprehensive Behavioral Intervention for Tics (CBIT). Despite the efficacy of CBIT and related behavioral therapies, less than 40% of adults with TS respond to these treatments. Further examination of the relationship between premonitory urges, tic severity, and tic impairment can provide new insights into therapeutic targets to optimize behavioral treatment outcomes. This study examined whether urge intolerance-difficulty tolerating premonitory urges-predicted tic severity and tic-related impairment among adults with TS. Methods: Participants were 80 adults with TS. Assessments characterized premonitory urge, distress tolerance, tic severity, and tic impairment. We used structural equation modeling (SEM) to examine the construct of urge intolerance-comprised of premonitory urge ratings and distress tolerance ratings. We first evaluated a measurement model of urge intolerance through bifactor modeling, including tests of the incremental value of subfactors that reflect premonitory urge severity and distress tolerance within the model. We then evaluated a structural model where we predicted clinician-rated tic severity and tic impairment by the latent variable of urge intolerance established in our measurement model. Results: Analyses supported a bifactor measurement model of urge intolerance among adults with TS. Consistent with theoretical models, higher levels of urge intolerance predicted greater levels of clinician-rated tic severity and tic impairment. Conclusion: This investigation supports the construct of urge intolerance among adults with TS and distinguishes it from subcomponents of urge severity and distress tolerance. Given its predictive relationship with tic severity and tic impairment, urge intolerance represents a promising treatment target to improve therapeutic outcomes in adults with TS.

Editorial: Dialectical Behavior Therapy: More Is Not Always Better When Different Is Required.

The study by Berk et al.1 highlights potential trajectories of response and nonresponse to dialectical behavior therapy (DBT) as compared to individual and group supportive therapy (IGST) for teens with repeated self-harm and suicidal ideation. The authors also posit a testable function to predict responsiveness vs nonresponsiveness and provide critical guidance about when to reassess nonresponders and alter treatment. This is the fourth major article from a large federally funded, randomized controlled trial. Previous publications have highlighted superiority of DBT over IGST,2 reported the moderating factors of treatment outcomes,3 and explored the mechanism of effectiveness for DBT in the treatment of suicidal ideation and self-harm.4 These articles provide useful information given the rising rates of suicidal ideation and suicide attempts among youth5 and recent research suggesting the powerful role of social media in supporting contagion of suicidal behavior among youth.

A systematic review of the effectiveness and safety of droperidol for pediatric agitation in acute care settings.

OBJECTIVE: Agitation in children in acute care settings poses significant patient and staff safety concerns. While behavioral approaches are central to reducing agitation and oral medications are preferred, parenteral medications are used when necessary to promote safety. The goal of this systematic review was to evaluate the effectiveness and safety of an ultra-short-acting parenteral medication, droperidol, for the management of acute, severe agitation in children in acute care settings. METHODS: A systematic review of randomized controlled trials, observational studies, and case series/reports examined the effectiveness and safety of parenteral droperidol for management of acute agitation in patients ≤21 years old in acute care settings. Effectiveness outcomes included time to sedation and need for a subsequent dose of medication. Safety outcomes were adverse effects such as QTc prolongation, hypotension, respiratory depression, and dystonic reactions. RESULTS: A total of 431 unique articles were identified. Six articles met inclusion criteria: two in the prehospital setting, one in the emergency department, and three in the inpatient hospital setting. The articles included a prospective observational study, three retrospective observational studies, and two case reports. The largest study reported a median time to sedation of 14 min (interquartile range 10-20 min); other studies reported a time to sedation of 15 min or less. Across studies, 8%-22% of patients required a second dose of medication for ongoing agitation. The most frequent adverse effects were dystonic reactions and transient hypotension. One patient had QTc prolongation and another developed respiratory depression, but both had significant comorbidities that may have contributed. The risk of bias in included studies ranged from moderate to critical. CONCLUSIONS: Existing data on droperidol for management of acute agitation in children suggest that droperidol is both effective and safe for acute, severe agitation in children. Data are limited by study designs that may introduce bias.

Long-term Outcomes of Behavior Therapy for Youth With Tourette Disorder.

OBJECTIVE: To determine the long-term durability of behavior therapy for tics among youth with Tourette disorder and persistent (chronic) motor or vocal tic disorders. METHOD: Of the 126 youth who participated in a randomized controlled trial of behavior therapy 11 years prior, 80 were recruited for this longitudinal follow-up. Consenting participants were interviewed in person or remotely (Web-based video) by trained evaluators to determine the course of tics, current tic severity, and tic-related impairment. Recruitment and data collection occurred between 2014 and 2019, with an average follow-up duration of 11.2 years. RESULTS: Treatment responders to both conditions in the original trial achieved partial, but not full, tic remission. Tic severity also decreased significantly across the sample, with 40% reporting partial remission. Behavior therapy responders (n = 21) in the original trial were more likely (67%) to achieve remission at follow-up (Total Tic Score = 12.52, SD = 10.75) compared to psychoeducation/supportive therapy responders (n = 6, 0%) at follow-up (Total Tic Score = 20.67, SD = 6.92) on the Yale Global Tic Severity Scale. Tic-related impairment decreased across the sample, with no significant differences between treatment groups or responders. CONCLUSION: Despite limitations of unmeasured variables and veracity of self-report at follow-up, this study supports guidelines recommending behavior therapy as the first-line intervention for tics. Further investigation of behavior therapy as an early preventive intervention also merits attention.

Combining selective serotonin reuptake inhibitors and cognitive behavioral therapy in youth with depression and anxiety.

BACKGROUND: Treatment studies of children and adolescents with internalizing disorders suggest that the combination of a selective serotonin reuptake inhibitor (SSRI) and cognitive behavioral therapy (CBT) consistently produces greater improvement than either treatment alone. We sought to determine how response to combined treatment varies across disorders (anxiety versus depression), and by specific patient characteristics. METHODS: Three large National Institutes of Health-funded trials of children and adolescents with major depression (n = 2) and anxiety disorders (n = 1) were evaluated, each comparing CBT + SSRI to SSRI only, Bayesian Hierarchical Models (BHMs) were used, for endpoint response, time course of response and predictors of response in participants who received SSRI or SSRI+CBT. RESULTS: SSRI+CBT significantly decreased symptoms by week 4 (p<0.001) across disorders. This improvement continued at week 8 and 12 (p<0.001); however, the additive benefit of CBT over SSRI monotherapy was not statistically significant until week 12 (p<0.001). The fastest response to SSRI+CBT was for patients who were younger, with milder baseline anxiety/depression symptoms and depressive disorders. The slowest response for SSRI+CBT was for boys, adolescents, minoritized children, those with severe symptoms and externalizing disorders. LIMITATIONS: Limitations included inconsistent moderators, variation in the number of observations over time and a lack of genetic or pharmacokinetic variables related to SSRI exposure across studies. CONCLUSIONS: The superiority of SSRI+CBT for youth with depression and anxiety is further supported. For purposes of rapid and greater relief, combination treatment is the superior approach across anxiety and depression and is robust to a range of participant characteristics. However, the added value of CBT (with an SSRI) occurs late in treatment. These findings represent a step towards understanding heterogeneity of treatment response and raise the possibility that interventions could be better tailored or adapted based on patient characteristics.

Academic, Interpersonal, Recreational, and Family Impairment in Children with Tourette Syndrome and Attention-Deficit/Hyperactivity Disorder.

This study describes impairment in academic, interpersonal, recreational, and family financial or occupational domains across children in three mutually exclusive diagnostic groups: ever diagnosed with Tourette syndrome (TS), attention-deficit/hyperactivity disorder (ADHD), and both disorders. In 2014, parents reported on impairment and diagnostic status of children aged 4-17 years (n = 3014). Weighted analysis and pairwise t-tests showed more children with ADHD (with or without TS) experienced impairment in overall school performance, writing, and mathematics, relative to children with TS but not ADHD. More children with TS and ADHD had problematic handwriting relative to children with ADHD but not TS. More children with TS and ADHD had problematic interpersonal relationships relative to those with ADHD but not TS. Children with TS and ADHD had higher mean impairment across domains than children with either TS or ADHD. Findings suggest assessing disorder-specific contributions to impairment could inform targeted interventions for TS and ADHD.

Repetitive Transcranial Magnetic Stimulation for Generalized Anxiety Disorder: A Systematic Literature Review and Meta-Analysis.

BACKGROUND: Anxiety disorders such as generalized anxiety disorder (GAD) impact 10% of the US population, and many patients do not completely respond to first-line treatments (e.g., selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and psychotherapy). Given the dearth of evidence for non-pharmacologic, non-psychotherapeutic interventions, we performed a systematic review and meta-analysis of repetitive transcranial magnetic stimulation (rTMS) in adults with GAD. METHODS: A systematic literature review using the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines was conducted. Pre- and post-treatment anxiety scores were extracted, and a random-effects meta-analysis was conducted to determine the magnitude of improvement (standardized mean difference). Standard assessments of heterogeneity (e.g., Q-statistic, I2, and τ 2) and publication bias were performed. RESULTS: The initial search resulted in 3194 citations, of which 6 studies were included in the meta-analysis. In total, 152 patients were studied, including 97 patients who received active treatment and 55 who received sham treatment, and heterogeneity was modest (I2 13.32, Q = 5.77). In patients with GAD, rTMS produced a standardized mean difference of -1.857 (confidence interval: -2.219 to -1.494; P < .001) with a prediction interval of -2.55 to -1.16. CONCLUSIONS: The results suggest a robust effect of rTMS in GAD in the context of limited, heterogenous studies. Rigorously designed, randomized controlled trials of rTMS for GAD and related anxiety disorders are urgently needed. These studies will provide opportunities for biomarker development and integration of concurrent evidence-based psychotherapy to maximize results.

Clomipramine in Combination with Fluvoxamine: A Potent Medication Combination for Severe or Refractory Pediatric OCD.

Clomipramine (CMI) and fluvoxamine (FLV) combination therapy has been shown in adults to be a potent medication strategy for obsessive compulsive disorder (OCD). Fung et al. (2021) is the first to show similar benefit in pediatric OCD. The addition of FLV to CMI inhibits the metabolism of clomipramine to desmethylclomipramine (DCMI) and enhances the serotonergic potency of CMI by shifting the routine ratio of CMIDCMI via inhibition of the CYP450 system. The approach to CMI+FLV combination therapy outlined by Fung et al. requires close monitoring. This commentary reviews the benefits and challenges of the approach of Fung et al. (2021) and provides other strategies to take advantage of this combination. Clinicians may consider starting with CMI and adding FLV for patients with refractory OCD to offer a faster pathway to potentially more effective treatment. If a clinician prefers starting with SSRI monotherapy, choosing FLV initially allows for a simpler transition to CMI+FLV in the event that SSRI monotherapy fails.

La thérapie de combinaison de la clomipramine (CMI) et de la fluvoxamine (FLV) s'est révélée chez les adultes une stratégie médicamenteuse puissante pour le trouble obsessionnel-compulsif (TOC). Fung et coll. est le premier à montrer un bénéfice semblable dans le TOC pédiatrique. L'ajout de FLV à la CMI inhibe le métabolisme de la clomipramine pour la desméthylclomipramine (DCMI) et augmente la puissance sérotoninergique de la CMI en changeant le rapport régulier de CMI>DCMI au moyen de l'inhibition du système CYP450. L'approche de la thérapie de combinaison CMI+FLV présentée par Fung et coll. nécessite une surveillance étroite. Le présent commentaire révise les avantages et les difficultés de l'approche de Fung et coll. et offre d'autres stratégies pour profiter de cette combinaison. Les cliniciens peuvent songer à commencer avec la CMI puis à ajouter la FLV pour les patients souffrant d'un TOC réfractaire afin de leur offrir une trajectoire plus rapide vers un traitement possiblement plus efficace. Si un clinicien préfère commencer par une monothérapie d'ISRS, choisir la FLV au départ permet une transition plus simple à CMI+FLV au cas où la monothérapie d'ISRS ne fonctionne pas.

Distinguishing and Managing Acute-Onset Complex Tic-like Behaviors in Adolescence.

Consistent with international reports,1 this group of Tourette syndrome (TS) experts has noticed a recent increase in adolescents presenting with tic-like symptoms that show a markedly atypical onset and course. These sudden-onset motor movements and vocalizations are often associated with significant impairment and disability, resulting in emergency department visits and hospitalizations for some affected youths.

Editorial: Dialectical Behavior Therapy and the Function of Self-Injury.

The study by Asarnow et al.1 is the third major paper from a large, federally funded, randomized, controlled trial of dialectical behavior therapy (DBT) as compared to Individual and Group Supportive Therapy (IGST) for reducing self-injury in teens. The first paper established the superiority of DBT as compared to IGST.2 The second paper focused on predictors and moderators of treatment outcome.3 The goal of this, the third, publication1 is to identify the mechanism by which DBT is effective in reducing suicidal and self-injurious behavior in an at-risk group of adolescents. The value of DBT in reducing suicidal behavior is increasingly important as we face what appears to be a rise in attempt rates and suicide deaths during the COVID-19 pandemic.4.

Assessing Violence Risk in Adolescents in the Pediatric Emergency Department: Systematic Review and Clinical Guidance.

INTRODUCTION: Violence risk assessment is one of the most frequent reasons for child and adolescent psychiatry consultation with adolescents in the pediatric emergency department (ED). Here we provide a systematic review of risk factors for violence in adolescents using the risk factor categories from the MacArthur Violence Risk Assessment study. Further, we provide clinical guidance for assessing adolescent violence risk in the pediatric ED. METHODS: For this systematic review, we used the preferred reporting items for systematic reviews and meta-analyses (PRISMA) 2009 checklist. We searched PubMed and PsycINFO databases (1966-July 1, 2020) for studies that reported risk factors for violence in adolescents. RESULTS: Risk factors for adolescent violence can be organized by MacArthur risk factor categories. Personal characteristics include male gender, younger age, no religious affiliation, lower IQ, and Black, Hispanic, or multiracial race. Historical characteristics include a younger age at first offense, higher number of previous criminal offenses, criminal history in one parent, physical abuse, experiencing poor child-rearing, and low parental education level. Among contextual characteristics, high peer delinquency or violent peer-group membership, low grade point average and poor academic performance, low connectedness to school, truancy, and school failure, along with victimization, are risk factors. Also, firearm access is a risk factor for violence in children and adolescents. Clinical characteristics include substance use, depressive mood, attention deficit hyperactivity disorder, antisocial traits, callous/unemotional traits, grandiosity, and justification of violence. CONCLUSION: Using MacArthur risk factor categories as organizing principles, this systematic review recommends the Structured Assessment of Violence Risk in Youth (SAVRY) risk- assessment tool for assessing adolescent violence risk in the pediatric ED.

The Impact of Failed Antidepressant Trials on Outcomes in Children and Adolescents with Anxiety and Depression: A Systematic Review and Meta-Analysis.

Objective: To identify predictors of medication-placebo differences in double-blind placebo-controlled antidepressant trials in children and adolescents with anxiety and depression. Methods: Clinical trials in patients <18 years of age with major depressive disorder or generalized, separation or social anxiety disorders were obtained from PubMed, the Cochrane Database and clinicaltrials.gov searches from inception through 2019. Forty-nine trials (43 published and 6 unpublished) of anxiety (κ = 13) and depression (κ = 36) evaluated 19 antidepressants in 8642 child and adolescent patients; placebo and medication response rates, trial characteristics, disorder, medication class, and funding source were extracted. Antidepressant-placebo differences were examined using Bayesian hierarchical models and estimates of response were determined for trial design, disorder, and medication class variables. Using meta-regression, correlates of antidepressant-placebo difference and placebo response were examined. Results: Funding source differentiated medication-placebo differences regardless of disorder. Industry trials had larger placebo response rates (mean difference: 0.189 ± 0.066, credible interval [CrI]: 0.067 to 0.33, p = 0.0008) and smaller medication-placebo differences (-0.235 ± 0.078, CrI: -0.397 to -0.086, p = 0.005) compared with federally funded trials. However, medication response was similar for industry- and federally-funded studies (-0.046 ± 0.042, CrI: -0.130 to 0.038, p = 0.252). Conclusions: The impact of study sponsorship on trial outcome supports the assertion that industry-funded trials with high placebo response rates and small drug-placebo differences are "failed trials" and should not be described as "negative trials" or used to determine public health estimates of antidepressant efficacy in children and adolescents with anxiety and depression. Identifying the proper role and value of industry-funded trials is critical to establishing the evidence base for antidepressants in youth.