Showing papers in "Journal of Child and Adolescent Psychopharmacology in 2022"

Psychotropic Drug Prescription in Children and Adolescents: Approved Medications in European Countries and the United States.

Abstract: Objectives: The decision to prescribe a medication and the choice of which one are often complex, particularly in the field of child and adolescent psychiatry where evidence is scarce. The aim of this review is to provide a synthesis of psychotropic drugs approved in children and adolescents for psychiatric indications in several countries. Methods: All psychopharmacological treatments used in child and adolescent psychiatry, approved by at least one regulatory agency from Switzerland, the United Kingdom, France, the European Union, or the United States, were considered. A comprehensive review of the summaries of product characteristics was performed. Results: A total of 143 psychotropic drugs were included: 47 anxiolytics/hypnotics, 45 antidepressants, 37 antipsychotics, 10 medications for attention-deficit/hyperactivity disorder (ADHD), and 4 mood stabilizers. Only a few of these drugs were approved for use in children or adolescents (38%) at least for a single psychiatric diagnosis in at least one country. The therapeutic class with the lowest rate of approved status was antidepressants (20%), followed by mood stabilizers (25%), anxiolytics/hypnotics (28%), antipsychotics (57%), and medications for ADHD (100%). Important differences in approved diagnoses, ages, and doses were observed between regulatory agencies. Tables presenting drugs for approved diagnoses based on age and regulatory agencies are presented in this article. Drugs classified by regulatory agencies, with complete data on diagnoses, ages, doses, pharmaceutical forms, and particular restrictions, are presented as Supplementary Material. Conclusion: This article provides an overview to prescribers with respect to the approved medications in children and adolescents in selected European countries and the United States.

Clozapine for Management of Childhood and Adolescent-Onset Schizophrenia: A Systematic Review and Meta-Analysis.

Abstract: Background: Schizophrenia at a young age deserves investigation because of the greater severity and burden of illness on individuals and health care than its adult onset. For this study, we included both childhood-onset schizophrenia and early-onset schizophrenia. We used the common term "childhood and adolescent-onset schizophrenia (CAOS)" for either type. This systematic review provides an overview of the clinical use, efficacy, and safety of clozapine treatment in managing CAOS. Methods: We conducted a systematic literature search in PubMed, Embase, and PsycINFO databases. We searched for randomized controlled trials (RCTs), open-label studies (OLSs), review articles, meta-analytic and observational studies. Our literature search resulted in 1242 search results. After the title, abstract, and full article review, 18 studies qualified (double-blind RCTs n = 4; OLS n = 4; observational studies n = 7; case reports n = 3). Results: Clozapine use in CAOS was generally well tolerated and not associated with any fatalities. Clozapine use in the short term (6 weeks) and long term (2-9 years) was superior in efficacy than other antipsychotics in CAOS management. Improvement in overall symptoms was maintained during long-term follow-up over the years in OLSs. Clozapine appeared to have a favorable clinical response and shorter hospital stays. Sedation and hypersalivation were commonly reported (90%), constipation was next in frequency (13%-50%). Neutropenia was seen in 6%-15% of cases and agranulocytosis (<0.1%). Although weight gain was common (up to 64%), followed by metabolic changes (8%-22%), treatment-onset diabetes was less frequent (<6%). Akathisia, tachycardia, and blood pressure changes were less commonly seen. Conclusions: Limited studies indicate that clozapine is a safe and efficacious option for CAOS management. We need large-scale and well-designed long-term RCTs for the use of clozapine in the management of CAOS.

The Impact of Pharmacotherapy of Childhood-Onset Psychiatric Disorders on the Development of Substance Use Disorders.

Abstract: Background and Objective: Child- and adolescent-onset psychopathology is known to increase the risk for developing substance use and substance use disorders (SUDs). While pharmacotherapy is effective in treating pediatric psychiatric disorders, the impact of medication on the ultimate risk to develop SUDs in these youth remains unclear. Methods: We conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) systematic review of peer-reviewed literature published on PubMed through November 2021, examining pharmacological treatments of psychiatric disorders in adolescents and young adults and their effect on substance use, misuse, and use disorder development. Results: Our search terms yielded 21 studies examining the impact of pharmacotherapy and later SUD in attention-deficit/hyperactivity disorder (ADHD), two studies on Major Depressive Disorder, and three studies on psychotic disorders. The majority of these studies reported reductions in SUD (N = 14 sides) followed by no effects (N = 10) and enhanced rates of SUD (N = 2). Studies in ADHD also reported that earlier-onset and longer-duration treatment was associated with the largest risk reduction for later SUD. Conclusions: Overall, pharmacological treatments for psychiatric disorders appear to mitigate the development of SUD, especially when treatment is initiated early and for longer durations. More studies on the development of SUD linked to the effects of psychotherapy alone and in combination with medication, medication initiation and duration, adequacy of treatment, non-ADHD disorders, and psychiatric comorbidity are necessary.

Dose Proportionality and Steady-State Pharmacokinetics of Serdexmethylphenidate/Dexmethylphenidate, a Novel Prodrug Combination to Treat Attention-Deficit/Hyperactivity Disorder

Abstract: Objective: The study was designed to determine (1) the pharmacokinetic (PK) profile of dexmethylphenidate (d-MPH) after oral administration of three dosage strengths of a new treatment containing d-MPH and a novel prodrug, serdexmethylphenidate (SDX); (2) the dose proportionality of the different SDX/d-MPH dosages; and (3) the steady-state PK profile of d-MPH and SDX after multiple dosing of SDX/d-MPH. Methods: Twenty-three healthy volunteers (aged 18–55 years) under fasted conditions received in a crossover design SDX/d-MPH 26.1/5.2 mg (Treatment A), 39.2/7.8 mg (Treatment B), and 52.3/10.4 mg (Treatment C) for a total d-MPH hydrochloride equivalent dose of 20, 30, and 40 mg, respectively. After a 96-hour washout period, all participants received four consecutive daily doses of SDX/d-MPH 52.3/10.4 mg. Blood samples were collected for measurement of plasma d-MPH and SDX and for PK analysis. Results: Administration of all three doses of SDX/d-MPH resulted in a rapid rise and slow decline in the plasma concentration of d-MPH. For Treatments A, B, and C, mean (± standard deviation) maximum concentrations (Cmax) were 7.1 ± 2.1, 9.8 ± 2.8, and 13.8 ± 3.8 ng/mL, and overall exposures (AUC0−last) were 97.2 ± 28.8, 142.5 ± 41.2, and 199.8 ± 57.2 h*ng/mL, respectively. Dose-normalized Cmax, AUC0–last, and AUC0–inf for d-MPH were similar when comparing the high and low doses versus the middle dose. Power model regression analysis revealed that Cmax and AUC0–inf proportionally increased with an increase in SDX/d-MPH dose. In the multiple-dose study, d-MPH reached steady state before the third dose, and SDX after the first dose. Conclusion: The PK profile of SDX/d-MPH is characterized by a rapid rise and a gradual decline in d-MPH concentration, with proportional Cmax and AUC0–inf across doses. The PK attributes of SDX/d-MPH may optimize symptom control from early morning to early evening, while the demonstrated dose proportionality may facilitate initial dose titration and ongoing dose adjustment.

Low-Dose Olanzapine in the Treatment of Adolescents with Anorexia Nervosa: An Observational Naturalistic Case-Control Study.

Abstract: Background: Although recent articles have investigated the use of low-dose olanzapine in different psychiatric conditions, only one study so far has assessed this treatment in 13 girls with anorexia nervosa (AN). Methods: Observational naturalistic case-control study aimed at reporting the use and tolerability of low-dose olanzapine in the context of a multidisciplinary hospital intervention for adolescents with AN. Three groups with AN were compared: group 1 was treated with low-dose olanzapine (≤5 mg/day), group 2 with full-dose olanzapine (>5 mg/day), and group 3 (control group) was treated without antipsychotics. Psychopathology was assessed at admission (T0) and discharge (T1) with Eating Disorders Inventory-3 Eating Disorders Risk, Body Uneasiness Test Global Severity Index (BUT-GSI), Beck's Depression Inventory-II (BDI-II), and Self-administered Psychiatric Scales for Children and Adolescents, Depression subtest (SAFA-D). Possible differences among the three groups, concerning clinical and treatment variables, were screened. Then, potential differences of T0-T1 modifications in psychopathological variables among the three treatment groups were assessed with analyses of covariance, corrected for baseline psychopathology and potential confounders, including possible concurrent antidepressants. Results: A total of 118 patients were enrolled (F = 94.1%; mean age = 15.4 ± 1.7 years), including 52 controls, 37 treated with low-dose olanzapine, and 29 with full-dose olanzapine. Low-dose olanzapine was well tolerated and used for a mean of 132.1 (±98.6) days, starting with a dosage of 3.4 (±1.2) mg/day and increasing to a maximum dose of 4.4 (±1.1) mg/day. The multidisciplinary intervention resulted in an improvement of BUT-GSI (p < 0.001), BDI-II (p < 0.001), and SAFA-D (p < 0.001) for the entire sample. Individuals treated with full-dose olanzapine experienced a significantly lower improvement in depressive measures: BDI-II (F[2,61] = 12.653, p < 0.001, η2 = 0.269) and SAFA-D (F[2,57] = 7.413, p = 0.001, η2 = 0.170), than the other groups. Discussion: This naturalistic controlled study expands the existing evidence on the use and tolerability of low-dose olanzapine in adolescents with AN. These results should be assessed in wider and prospective samples.

Psychotropic Prescriptions During the COVID-19 Pandemic Among U.S. Children and Adolescents Receiving Mental Health Services.

Abstract: Objective: Increased mental health problems among children and adolescents during the COVID-19 pandemic may have impacted psychotropic medication use. This study describes trends in monthly psychotropic medications before and early in the COVID-19 pandemic among 2- to 17-year-old children and adolescents with mental health disorders. Methods: A cross-sectional study design using the 2019-2020 IQVIA™ prescription and medical commercial claims data to estimate the proportion of children and adolescents with any psychotropic prescription in the month out of all with any mental health-related medical or prescription services in the month and the year-over-year percent change. We assessed monthly proportions of youth who filled a psychotropic prescription overall and by psychotropic class, stratified by age and gender. Results: Of the 8,896,713 children and adolescents in the sample, 24.7% received psychotropic medication during the study period. The proportion of the cohort prescribed a psychotropic medication in a given month averaged 27%-28% from January 2019 to February 2020, peaked at 36.9% in April 2020, and gradually declined to 28.7% in September 2020. The largest year-over-year percent change was in April for antipsychotic (41.9%) and antidepressant (37.9%) medication, which remained higher in September 2020 compared to September 2019, particularly among ages 6 years or older and females. Conclusion: The proportion of youth with a psychotropic prescription increased at the onset of the COVID-19 pandemic, later returning to prepandemic levels. However, antipsychotics and antidepressants remained higher than prepandemic, highlighting the need to further understand the long-lasting effects of the pandemic on children and adolescents.

Letter to the Editor: Antidepressant and Antisuicidal Effects of Esketamine in Adolescents with Major Depressive Disorder and Suicidal Ideation: A Case Series.

Abstract: Journal of Child and Adolescent PsychopharmacologyVol. 32, No. 6 Original ArticlesLetter to the Editor: Antidepressant and Antisuicidal Effects of Esketamine in Adolescents with Major Depressive Disorder and Suicidal Ideation: A Case SeriesDaniela Faria-Guimarães, Flávia Vieira, Breno Souza-Marques, Samantha S. Silva, Igor D. Bandeira, Lucca S. Souza, Raíza Alves-Pereira, Mariana Fontes, Rodrigo P. Mello, Gustavo C. Leal, Taiane A. Cardoso, Flávio Kapczinski, Acioly L.T. Lacerda, Aline S. Sampaio, and Lucas C. QuarantiniDaniela Faria-Guimarãeshttps://orcid.org/0000-0001-8076-514XLaboratório de Neuropsicofarmacologia, Serviço de Psiquiatria do Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil.Search for more papers by this author, Flávia VieiraLaboratório de Neuropsicofarmacologia, Serviço de Psiquiatria do Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil.Programa de Pós-graduação em Medicina e Saúde, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Brazil.Search for more papers by this author, Breno Souza-MarquesLaboratório de Neuropsicofarmacologia, Serviço de Psiquiatria do Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil.Programa de Pós-graduação em Medicina e Saúde, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Brazil.Search for more papers by this author, Samantha S. SilvaLaboratório de Neuropsicofarmacologia, Serviço de Psiquiatria do Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil.Programa de Pós-graduação em Medicina e Saúde, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Brazil.Search for more papers by this author, Igor D. Bandeirahttps://orcid.org/0000-0002-6714-2658Laboratório de Neuropsicofarmacologia, Serviço de Psiquiatria do Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil.Programa de Pós-graduação em Medicina e Saúde, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Brazil.Search for more papers by this author, Lucca S. SouzaLaboratório de Neuropsicofarmacologia, Serviço de Psiquiatria do Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil.Search for more papers by this author, Raíza Alves-PereiraLaboratório de Neuropsicofarmacologia, Serviço de Psiquiatria do Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil.Search for more papers by this author, Mariana FontesLaboratório de Neuropsicofarmacologia, Serviço de Psiquiatria do Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil.Search for more papers by this author, Rodrigo P. MelloLaboratório de Neuropsicofarmacologia, Serviço de Psiquiatria do Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil.Programa de Pós-graduação em Medicina e Saúde, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Brazil.Search for more papers by this author, Gustavo C. LealLaboratório de Neuropsicofarmacologia, Serviço de Psiquiatria do Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil.Programa de Pós-graduação em Medicina e Saúde, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Brazil.Search for more papers by this author, Taiane A. CardosoDepartment of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, Canada.Search for more papers by this author, Flávio KapczinskiDepartment of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, Canada.Search for more papers by this author, Acioly L.T. LacerdaLaboratório Interdisciplinar de Neurociências Clínicas, Universidade Federal de São Paulo, São Paulo, Brazil.Instituto Sinapse de Neurociências Clínicas, Campinas, Brazil.Search for more papers by this author, Aline S. SampaioLaboratório de Neuropsicofarmacologia, Serviço de Psiquiatria do Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil.Programa de Pós-graduação em Medicina e Saúde, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Brazil.Departamento de Neurociências e Saúde Mental, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Brazil.Search for more papers by this author, and Lucas C. QuarantiniAddress correspondence to: Lucas C. Quarantini, PhD, Laboratório de Neuropsicofarmacologia, Serviço de Psiquiatria do Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Serviço de Psiquiatria, 3°andar, Salvador 40110-060, Brazil E-mail Address: lcq@ufba.brLaboratório de Neuropsicofarmacologia, Serviço de Psiquiatria do Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Brazil.Programa de Pós-graduação em Medicina e Saúde, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Brazil.Departamento de Neurociências e Saúde Mental, Faculdade de Medicina da Bahia, Universidade Federal da Bahia, Salvador, Brazil.Search for more papers by this authorPublished Online:11 Aug 2022https://doi.org/10.1089/cap.2022.0013AboutSectionsView articleView Full TextSupplemental MaterialPDF/EPUBView Supplemental Data Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"Letter to the Editor: Antidepressant and Antisuicidal Effects of Esketamine in Adolescents with Major Depressive Disorder and Suicidal Ideation: A Case Series." Journal of Child and Adolescent Psychopharmacology, 32(6), pp. 366–367FiguresReferencesRelatedDetails Volume 32Issue 6Aug 2022 InformationCopyright 2022, Mary Ann Liebert, Inc., publishersTo cite this article:Daniela Faria-Guimarães, Flávia Vieira, Breno Souza-Marques, Samantha S. Silva, Igor D. Bandeira, Lucca S. Souza, Raíza Alves-Pereira, Mariana Fontes, Rodrigo P. Mello, Gustavo C. Leal, Taiane A. Cardoso, Flávio Kapczinski, Acioly L.T. Lacerda, Aline S. Sampaio, and Lucas C. Quarantini.Letter to the Editor: Antidepressant and Antisuicidal Effects of Esketamine in Adolescents with Major Depressive Disorder and Suicidal Ideation: A Case Series.Journal of Child and Adolescent Psychopharmacology.Aug 2022.366-367.http://doi.org/10.1089/cap.2022.0013Published in Volume: 32 Issue 6: August 11, 2022Online Ahead of Print:June 16, 2022PDF download

Selective Serotonin Reuptake Inhibitors and Hydroxyzine in the Treatment of Avoidant/Restrictive Food Intake Disorder in Children and Adolescents: Rationale and Evidence

Abstract: Objective: Despite lack of evidence, various pharmacological agents are judiciously used to manage anxiety in avoidant restrictive food intake disorder (ARFID). We aimed to explore the effectiveness of selective serotonin reuptake inhibitors (SSRIs), either alone or in combination with hydroxyzine, in a well-defined cohort of children and adolescents with ARFID receiving treatment in a partial hospitalization program for eating disorders. Methods: We conducted a retrospective chart review of 53 patients with ARFID who were prescribed an SSRI (n = 39) or SSRI with hydroxyzine (n = 14). We investigated changes from admission to discharge in these two medication groups on various outcome measures assessing weight, eating behaviors, mood, anxiety, and fears about food. Results: Participants in the SSRI+hydroxyzine group were significantly older than those in the SSRI only group. The majority of participants in both groups exhibited the fear presentation of ARFID. Repeated-measures analysis of variance yielded a significant main effect for treatment for all outcome measures, indicating that patients in both groups experienced improvements in weight, eating behaviors, mood, anxiety, and fears of food. A significant main effect for medication group emerged on the Children's Depression Inventory, suggesting that the group receiving SSRI+hydroxyzine experienced greater depressive symptomatology than the SSRI-only group. We did not find any significant interactions, indicating that participants in both medication groups experienced similar improvements over the course of treatment. Conclusion: These results provide preliminary evidence that SSRIs and hydroxyzine may be helpful in the treatment of children and adolescents with ARFID. Given that hydroxyzine was prescribed to patients who experienced high pre- and/or postmeal anxiety, it possibly contributed to similar decreases in anxiety and fear of food in a more challenging subset of patients. Randomized, placebo-controlled studies for children and adolescents with ARFID are warranted to better evaluate and understand the efficacy of SSRIs and hydroxyzine in this clinical population.

Association of Lithium and Second-Generation Antipsychotics with Neurocognition in Youth with Bipolar Disorder

Abstract: Objective: Numerous studies have examined the association of antimanic medications with neurocognition in adults with bipolar disorder (BD). However, few studies have examined this topic in youth. Thus, we aimed to examine the association of lithium and second-generation antipsychotics (SGAs), the first-line antimanic medications for youth with BD, with neurocognition in a relatively large sample of youth with BD. Methods: Participants included 91 youth with BD-I, -II, or -Not Otherwise Specified, aged 13–20 years (n = 14 current lithium use, n = 51 current SGA use). We examined four tests from the Cambridge Neuropsychological Test Automated Battery: Intra/Extra Dimensional Set-Shifting Task (IED), Rapid Visual Information Processing Task (RVP), Stockings of Cambridge Test (SOC), and Affective Go/No-Go (AGN). Within-sample Z-scores were computed, and a global neurocognitive composite score and g factor derived from these tests comprised the primary outcomes. Multivariable analyses controlled for age, sex, and IQ. Results: Current lithium use was significantly associated with poorer cognitive flexibility/set-shifting (IED). After further controlling for lifetime comorbid attention-deficit/hyperactivity disorder and current depression symptoms in sensitivity analyses, the lithium finding was no longer significant. Current SGA use was significantly associated with greater affective processing bias (AGN). No significant findings survived correction for multiple comparisons. All other cognitive outcomes were not significantly associated with current lithium use, current SGA use, or total number of current medications. Conclusions: Treatment with lithium or SGAs was associated with minimal neurocognitive impairments, with small effect sizes in primary multivariable analyses. This study adds to the limited body of literature examining medication use in relation to neurocognition in youth with BD. While the current study cannot rule out associations of smaller effect size, present findings suggest that leading mood-stabilizing medications are not associated with frank neurocognitive impairments in youth with BD.

A Predictive Biomarker Model Using Quantitative Electroencephalography in Adolescent Major Depressive Disorder.

Abstract: Background: With evolving understanding of psychiatric diagnosis and treatment, demand for biomarkers for psychiatric disorders in children and adolescents has grown dramatically. This study utilized quantitative electroencephalography (qEEG) to develop a predictive model for adolescent major depressive disorder (MDD). We hypothesized that youth with MDD compared to healthy controls (HCs) could be differentiated using a singular logistic regression model that utilized qEEG data alone. Methods: qEEG data and psychometric measures were obtained in adolescents aged 14-17 years with MDD (n = 35) and age- and gender-matched HCs (n = 14). qEEG in four frequency bands (alpha, beta, theta, and delta) was collected and coherence, cross-correlation, and power data streams obtained. A two-stage analytical framework was then used to develop the final logistic regression model, which was then evaluated using a receiver-operating characteristic curve (ROC) analysis. Results: Within the initial analysis, six qEEG dyads (all coherence) had significant predictive values. Within the final biomarkers, just four predictors, including F3-C3 (R frontal) alpha coherence, P3-O1 (R parietal) theta coherence, CZ-PZ (central) beta coherence, and P8-O2 (L parietal occipital) theta power were used in the final model, which yielded an ROC area of 0.8226. Conclusions: We replicated our previous findings of qEEG differences between adolescents and HCs and successfully developed a single-value predictive model with a robust ROC area. Furthermore, the brain areas involved in behavioral disinhibition and resting state/default mode networks were again shown to be involved in the observed differences. Thus, qEEG appears to be a potential low-cost and effective intermediate biomarker for MDD in youth.

Efficacy and Safety of Dextroamphetamine Transdermal System for the Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents: Results from a Pivotal Phase 2 Study

Abstract: Objectives: To assess efficacy and safety of the new Dextroamphetamine Transdermal System (d-ATS) to treat children and adolescents (aged 6–17 years) with attention-deficit/hyperactivity disorder (ADHD). Methods: In this phase 2, randomized, placebo-controlled study, 4 d-ATS patches of differing doses (5, 10, 15, and 20 mg) were evaluated. Patients began a 5-week, open-label, stepwise dose-optimization period in which they received a 5-mg d-ATS patch (applied to hip) for 9 hours. During weekly visits, patients were evaluated for possible adjustments to the next dose level based on efficacy and safety. Once at the optimal dose, that dose was maintained during a 2-week, crossover double-blind treatment period. Primary endpoint was to assess efficacy of d-ATS versus placebo as measured by Swanson, Kotkin, Agler, M-Flynn, and Pelham Scale (SKAMP) total score; key secondary endpoints included assessing onset and duration of efficacy by SKAMP total score, and additional secondary endpoints included Permanent Product Measure of Performance (PERMP) scores. Safety was assessed throughout. Results: d-ATS treatment resulted in significant improvements versus placebo in ADHD symptoms as measured by SKAMP total score, with overall least-squares mean difference (95% confidence interval) versus placebo of −5.87 (6.76, −4.97; p < 0.001) over the 12-hour assessment period. Onset of efficacy was observed at 2 hours postdose (p < 0.001), and duration of effect continued through 12 hours (patch removed at 9 hours), with significant differences between d-ATS and placebo at all time points from 2 hours onward (all p ≤ 0.003). Significant improvements versus placebo in PERMP-A and PERMP-C scores were also observed from 2 to 12 hours postdose with d-ATS treatment. d-ATS was safe and well-tolerated, with a systemic safety profile similar to that observed with oral amphetamines. Conclusions: This study demonstrates that d-ATS is an effective and well-tolerated treatment for children and adolescents with ADHD. These data indicate that d-ATS can deliver sustained levels of efficacy along with the advantages of transdermal drug delivery, making it a beneficial new treatment option. Clinical Trial Registration no.: NCT01711021.

Long-Term Effects of Lithium Use on Children and Adolescents: A Retrospective Study from Turkey.

Abstract: Background: The aim of this study was to evaluate the long-term effects of lithium treatment on white blood cell (WBC) count, serum creatinine, and thyroid-stimulating hormone (TSH) levels in children and adolescents with bipolar disorder (BD) and non-BD in a Turkish children and adolescent sample. Methods: The study is based on retrospective chart review. Children and adolescent patients with BD and non-BD prescribed lithium in a mental health and neurological disorders hospital between 2012 and 2017 were included in the study. Data were collected from the electronic medical files. Laboratory values for WBC count, serum creatinine, and TSH levels at baseline within the week before the onset of lithium, and at 1st, 3rd, 6th, and 12th month of treatment were recorded. Results: A total of 143 patients (82 females, 61 males; 100 BD, 43 non-BD) aged 9-18 were included. Non-BD diagnoses were psychotic and schizoaffective disorders, unipolar depression, attention-deficit/hyperactivity disorder, conduct disorder, severe mood dysregulation syndrome, borderline personality disorder, and autism. Mean age of the participants were 15.90 ± 1.16 years for the bipolar group and 14.88 ± 1.79 years for the nonbipolar group. Patients with BD reported more adverse effects. There was a statistically significant increase in WBC counts and TSH levels at any time point. A statistically significant elevation in serum creatinine was found at 3rd and 12th month of treatment. During the course of lithium treatment, WBC counts exceeded 13,000 in 14 (9.8%) patients, and TSH levels exceeded 5.5 mU/L in 41 patients (28.6%). Twenty-one (14.68%) patients were started on thyroxin replacement. Basal TSH levels and duration of the lithium treatment were higher in the participants with TSH levels exceeding 5.5 mU/L. Lithium maximum dose, lithium blood level, basal TSH level, and duration of treatment were higher in the participants receiving thyroxin replacement. No patients had serum creatinine levels exceeding the normal reference values. Conclusion: Our study suggests that lithium is a generally safe and tolerable agent for children and adolescents with BD and non-BD; however, close monitoring of thyroid functions particularly in patients with a higher basal TSH level and longer duration of lithium use is important.

Efficacy and Safety of Duloxetine in Children and Adolescents with Major Depressive Disorder in Japan: A Randomized Double-Blind Placebo-Controlled Clinical Trial Followed by an Open-Label Long-Term Extension Trial.

Abstract: Objective: The goal of this study was to evaluate the efficacy and safety of duloxetine in children and adolescents (9-17 years of age) with major depressive disorder (MDD) in Japan. Methods: This study consists of two clinical trials. First, a 6-week, randomized double-blind placebo-controlled clinical trial (RCT) was conducted. The primary endpoint of RCT was the change in Children's Depression Rating Scale-Revised (CDRS-R) total scores from baseline. Following RCT, an open-label long-term extension trial (OLE) was conducted to investigate the longer-term safety of duloxetine for ∼1 year. Results: In RCT, CDRS-R total score changes from baseline to 6 weeks after the start of administration (primary endpoint) were -21.03 in the duloxetine group (n = 74) and -22.42 in the placebo group (n = 74). No significant difference was observed in the primary endpoint between the groups (p = 0.5587). In addition, no significant difference was observed in secondary endpoints such as CDRS-R response rates. The proportion of patients with ≥1 treatment-emergent adverse event (TEAE) in RCT was significantly higher in the duloxetine group (78.7%) than in the placebo group (62.2%), and most were mild or moderate in severity. Changes in CDRS-R total scores during OLE, in consecutive patients from the duloxetine group in RCT (n = 63), or placebo group (n = 59) in RCT, and newly enrolled patients (n = 28), were -12.1, -11.3, and -17.8, respectively. The proportion of patients with ≥1 TEAE in OLE was 90.5%, 88.1%, and 89.3% in the respective groups, and most of them were mild or moderate in severity. Conclusions: Duloxetine did not show superiority to placebo in efficacy in children and adolescents with MDD in Japan. Overall reported TEAEs were consistent with the currently available duloxetine safety profile and no new safety finding was observed in the two clinical trials.

Risk of Obesity Among Children Prescribed Atypical Antipsychotics for Six Months or More

Abstract: Objectives: The study investigates the risk of obesity for young children prescribed an atypical antipsychotic (AAP) for 6 months or more. AAPs are associated with risk of obesity. They are used in children for a variety of psychiatric conditions and are often prescribed off-label. Long-term risk of obesity in this age group is unknown as most studies are short-term investigations and generally combine younger children with adolescents and adults. Methods: A retrospective cohort of children, 10 years old or younger, prescribed either an AAP or selective serotonin reuptake inhibitor (SSRI) for 6 months or more were followed for up to 9.5 years. The primary endpoint was the body-mass index (BMI) reaching the 95th percentile. Results: One thousand six hundred fifty-five patients met inclusion criteria. One thousand one hundred eighteen patients were prescribed an AAP and 537 were prescribed an SSRI: 1152 (74.5%) patients were male and mean (standard deviation) age was 7.9 [1.90] years at study entry. Median follow-up was 3.58 years for the AAP cohort and 3.28 years for the SSRI cohort (p = 0.02). After adjusting for baseline demographic variables, BMI, and other concomitantly prescribed medications, children prescribed AAPs for 6 months or longer were twice as likely to become obese compared with children prescribed SSRIs (adjusted hazard ratio [HR] 2.06 [95% confidence interval; CI 1.60-2.66], p < 0.0001). Further stratification by AAP revealed that the obesity risk for patients prescribed aripiprazole was 34% greater than for those prescribed risperidone (adjusted HR 1.34 [95% CI 1.01-1.78], p = 0.0033). Conclusions: The risk of obesity for young children prescribed an AAP for 6 months or more is approximately double that of children prescribed an SSRI. The risk of obesity is greater with aripiprazole than risperidone in the first year. Prescribers should consider the risk of obesity when prescribing AAPs and consider alternative treatment modalities in this vulnerable patient population.

Maternal Duplication 15q11-13 Syndrome with Autism Spectrum Disorder: Mood Stabilization by Carbamazepine

Abstract: Objectives: Maternal 15q11-13 duplication syndrome (dup15q) is one of the most frequently observed and penetrant genetic abnormalities associated with autism spectrum disorder (ASD), and commonly presents with psychiatric symptoms and seizures. Although carbamazepine has been reported as effective in managing comorbid seizures in dup15q, it has not been reported to be used as a mood stabilizer in this population. Methods: We retrospectively reviewed the charts of five consecutive patients presenting with previously diagnosed dup15q and ASD seeking treatment for psychiatric symptoms and, in four of the patients, seizures. These were the only patients with dup15q treated with carbamazepine in the Neurodevelopmental Psychopharmacology Clinic at the University of Illinois at Chicago during the review period. Results: During treatment, carbamazepine was found to be more effective than other mood stabilizers in all five patients, and in one case a better antiepileptic. Symptoms consistent with bipolar mood disorder such as hyperactivity, impulsivity, irritability, mood lability, intrusiveness, and pressured speech were improved with carbamazepine in combination with other psychotropic medications. This improvement was greater than with other mood stabilizers, including oxcarbazepine, valproate, and lamotrigine. In one case, valproate paradoxically worsened symptoms. In three cases, anxiety was improved with carbamazepine when used in conjunction with other medications targeting anxiety. Conclusions: In treating five patients with dup15q, carbamazepine more effectively stabilized mood-related symptoms than alternative treatments. Prospective randomized controlled trials are necessary to confirm this observation.

Reliability and Validity of the Bipolar Prodrome Symptom Interview and Scale-Full Prospective in Its Turkish Translation.

Abstract: Editors' Note: The Editors would like to address issues related to the acceptance of this manuscript. The original manuscript referenced the study tool as the Bipolar Prodrome Symptom Interview Scale-Prospective (BPSS-P). After the manuscript's initial acceptance, the authors requested a revision of the tool name to Bipolar Prodrome Symptom Interview Scale-Full Perspective (BPSS-FP). When this request was made, the original acceptance was rescinded, and the authors were asked to formally revise and resubmit the manuscript with an explanation for the change. This revision and subsequent review led to the final acceptance of the manuscript. The authors have assured us that the tool used in the manuscript was the BPSS-FP (version 5) as opposed to abbreviated forms of this tool that are also used in research (e.g., Bipolar Prodrome Symptom Scale-Abbreviated Screen for Patients (BPSS-AS-P).

Executive Functioning in Pediatric Anxiety and Its Relationship to Selective Serotonin Reuptake Inhibitor Treatment Response: A Double-Blind, Placebo-Controlled Trial.

Abstract: Objective: To characterize executive function in adolescents with generalized anxiety disorder (GAD) and its relationship to treatment. Methods: Using data from a double-blind, placebo-controlled trial of escitalopram in adolescents (N = 51) 12-17 years of age with GAD, we used the self-report version of the Behavior Rating Inventory of Executive Function (BRIEF-SR) to assess executive function, at baseline, and examined its relationship to treatment response as measured by the Pediatric Anxiety Rating Scale (PARS). Results: For all baseline subscores of the BRIEF-SR, T-scores were significantly elevated in adolescents with GAD compared to an age- and sex-matched normative healthy sample. In escitalopram-treated patients, baseline BRIEF-SR scores for Emotional Control (β = 0.256, 95% credibility interval [CrI]: 0.367 to 0.146, p < 0.001), Working Memory (β = 0.204, CrI: 0.2952 to 0.1134, p < 0.001), Planning/Organizing (β = -0.223, CrI: -0.1021 to -0.3436, p = 0.004), and Task Completion (β = -0.152, CrI: 0.075 to 0.228, p = 0.002) predicted the trajectory of improvement in PARS score over the 8-week trial. For youth who received placebo, only the Inhibit score was significantly, but weakly, associated with response trajectory (β = -0.081, CrI: -0.0167 to -0.1461, p = 0.015). For adolescents who had clinically significant impairment in Emotional Control, Working Memory, Planning/Organizing, and Task Completion (i.e., T-score >65), the trajectory of improvement significantly differed from patients without scores in the clinically significant range. Conclusions: Taken together, these findings point to the potential value of assessing executive function in youth with anxiety disorders as one strategy for guiding treatment selection. These data suggest that executive function may predict treatment response to psychopharmacologic treatment and point to numerous avenues for further personalizing treatment.

Monitoring of Adverse Drug Reaction-Related Parameters in Children, Youth, and Young Adults Prescribed Antipsychotic Drugs by General Practitioners

Abstract: Objective: The aim of the study was to assess monitoring of adverse drug reaction (ADR)-related parameters in children, youth, and young adults treated with second-generation antipsychotic drugs (SGAs) prescribed by general practitioners (GPs). Methods: This retrospective follow-up study included children, youth, and young adults aged 0 - 24 years, who had an initial prescription of an SGA recorded in the Clinical Practice Research Datalink between 2000 and 2017, and who were prescribed an SGA more than once for a duration of at least 6 months. It included an assessment of which ADR-related physical parameters (weight, height, body-mass index, waist circumference, pulse, blood pressure, and heart examination) and laboratory parameters (glucose, HbA1c, lipids, and prolactin) were monitored in children, youth, and young adults at least once every 6-month period, stratified by sex, age categories, and calendar years. Results: In total, 7006 patients were included and the mean duration of follow-up was 1.6 years. Monitoring frequencies of all parameters were below 25%. Blood pressure and weight were monitored in 23.6% and 23.4%, respectively, of all children, youth, and young adults during the first half year; waist circumference was monitored in 0.2%. Females were monitored more often than males, some differences between age categories were observed, and monitoring frequencies increased after 2000, but did not exceed 35% in any year. Conclusion: Monitoring frequencies of ADR-related parameters in children, youth, and young adults treated with SGAs prescribed by a GP were low. Monitoring in primary care should be improved to enable a better evaluation of the benefit-risk balance during antipsychotic drug therapy.

Efficacy and Safety of Blonanserin Oral Tablet in Adolescents with Schizophrenia: A 6-Week, Randomized Placebo-Controlled Study

Abstract: Objectives: To evaluate the short-term efficacy and safety of blonanserin in adolescents with schizophrenia. Methods: This 6-week multicenter, double-blind, randomized, placebo-controlled study investigated fixed-dose blonanserin (8 or 16 mg/day) in patients 12–18 years of age diagnosed with schizophrenia, as indicated by a Positive and Negative Syndrome Scale (PANSS) total score of 60–120 and a Clinical Global Impressions-Severity score of ≥3. The primary endpoint was change from baseline to week 6 in the PANSS total score, using a mixed model for repeated measures analysis. Safety was assessed by the incidence and severity of adverse events (AEs). Results: Among 151 randomized patients, 150 were included in the primary analysis population. Demographic and clinical characteristics were similar across groups at baseline. The rate of study discontinuation was 14.9%, 23.5%, and 28.3% in patients administered with placebo, blonanserin 8 mg/day, and blonanserin 16 mg/day, respectively. The least-squares mean change (95% confidence interval [CI]) from baseline to week 6 in PANSS total score was −10.6 (−16.10 to −5.10), −15.3 (−20.80 to −9.86), and −20.5 (−25.89 to −15.16) in patients administered placebo, 8 mg/day blonanserin, and 16 mg/day blonanserin, respectively. The 16-mg/day blonanserin group showed significantly greater reduction in the PANSS total score than the placebo group (least-squares mean difference [95% CI]: −9.9 [−17.61 to −2.25], p = 0.012, effect size: 0.538), although the 8-mg/day group showed no significant difference. The incidence of AEs such as akathisia, somnolence, and hyperprolactinemia was higher in the blonanserin groups than in the placebo group. AEs associated with blonanserin were generally mild and were consistent with its known profile in adults with schizophrenia. Conclusions: Blonanserin achieved a sufficient efficacy in adolescent patients, and the safety profile was similar to that in adults, which suggests that blonanserin may be a safe treatment option for adolescents with schizophrenia. Study registration number: Japic CTI-111724.

Clinicians' Adherence to Guidelines When Initiating Methylphenidate Treatment.

Abstract: Aims: Between 2008 and 2012, the number of children and adolescents in the Netherlands who received methylphenidate prescriptions increased by 35.6%. We determined guideline adherence regarding the assessment of attention-deficit/hyperactivity disorder (ADHD) and rates of off-label use in those 2 years. We also compared adherence to guidelines between mental health and pediatrics settings. Methods: We conducted a medical file audit of 506 children or adolescents who had received a first methylphenidate prescription in 2008 (n = 208) or 2012 (n = 298) across mental health (n = 333) and pediatrics outpatient clinics (n = 173) in the Netherlands and assessed adherence to seven guideline recommendations. Results: We did not find significant differences between 2008 and 2012 regarding the mean adherence to the seven recommendations (43% vs. 45%) or the percentage of off-label use (35% vs. 30%). Best adherence rates (over the years 2008 and 2012 combined) concerned the assessment of comorbidities (89%) and the involvement of teachers in the diagnostic process (75%). Least frequently adhered to were assessing ADHD severity (1%), the use of a (semi-)structured parent interview (16%), and providing psycho-education to parents (42%) or teachers (1%). Mental health settings showed better adherence than pediatrics settings (over the years 2008 and 2012 combined) concerning the use of (semi-)structured parent interviews (22% vs. 3.1%), having a separate diagnostic session directed at the child (81% vs. 63%), assessment of comorbidities (95% vs. 76%), and providing psycho-education to parents (51% vs. 24%). Conclusions: There was neither a decrease in adherence to guidelines nor an increase in off-label use between 2008 and 2012. However, there is ample room for improvement regarding guideline adherence.

Psychopharmacological Treatment Algorithms of Manic/Mixed and Depressed Episodes in Pediatric Bipolar Disorder.

Abstract: Introduction: Pediatric bipolar disorder (PBD) is a severe psychiatric illness diagnosed before the age of 18, which is associated with extreme shifts in mood characterized by manic and depressive episodes. In 2005, AACAP published algorithms to guide pharmacological treatment of manic/mixed episodes associated with PBD. At that time, lithium was the only Food and Drug Administration (FDA)-approved treatment for pediatric bipolar manic/mixed episodes. The goal of this article is to review evidence that has emerged since the AACAP algorithm in 2005. Methods: Literature searches were conducted through PubMed and limited to studies published between 2005 and 2021, using keywords that focused on randomized controlled trials (RCTs) for available psychopharmacological medications. In addition, the authors conducted in-depth searches for articles providing evidence for agents included in the 2005 AACAP algorithm. Results: Since the publication of the AACAP algorithm in 2005, multiple RCTs have been conducted in PBD, leading to FDA approval of five medications (aripiprazole, asenapine, olanzapine, quetiapine, and risperidone) for the treatment of manic/mixed episodes and two medications (lurasidone and olanzapine-fluoxetine combination) for the treatment of depressed episodes. Divalproex sodium and oxcarbazepine were studied in pediatric RCTs and failed to separate from placebo. Conclusions: We offer an update to the 2005 AACAP algorithms for the treatment of pediatric bipolar mixed/manic episodes and added an evidence-based algorithm for the treatment of depression in PBD. In addition to treatment algorithms, we review current evidence for efficacy of agents proposed in the AACAP algorithm and provide tables summarizing medication side effects and efficacy.

Practitioners' Perspective on Metabolic Monitoring of Second-Generation Antipsychotics: Existing Gaps in Knowledge, Barriers to Monitoring, and Strategies

Abstract: Introduction: Prescription of second-generation antipsychotics (SGAs) in youth is rapidly increasing globally and in Australia. Lack of timely metabolic monitoring for potential adverse effects puts youth at greater risk for lifelong adverse health impact. Metabolic monitoring is recommended as best practice to prevent and/or manage SGA-induced weight gain/metabolic syndrome. The adherence to clinical guidelines remains suboptimal. It is crucial to gauge insight to challenges and strategies from the perspective of prescribers and to recommend strategies in promoting quality use of SGAs and adherence to pharmacovigilance standards. Methods: Psychiatrists participated through semistructured interviews within the community mental health clinics in the Queensland State of Australia. The interviews focused on barriers to monitoring and strategies to enhance rate of monitoring with key focus on practical strategies for future implications in community setting. Results: Ten participants completed the interviews. Barriers were specified such as lack of adequate resources to conduct monitoring, carers' disengagement in their youth's treatments, and patients' refusal to undergo blood tests. Strategies to enhance metabolic monitoring heavily relied on organizational support, provision of training, and education opportunities. Conclusions: Clinical recommendations require mental health providers to facilitate conduction of metabolic monitoring among youth prescribed SGA/s. However, they are not provided with enough support and there are challenges that prevent such care. It is crucial to understand the challenges in managing a complex and vulnerable patient cohort. This research has thrown light on these key aspects of existing gap between best practice standards and clinical practice in youth prescribed SGAs.

Citalopram Did Not Significantly Improve Anxiety in Children with Autism Spectrum Disorder Undergoing Treatment for Core Symptoms: Secondary Analysis of a Trial to Reduce Repetitive Behaviors.

Abstract: Objective: Anxiety disorders are among the most common co-occurring conditions in autism spectrum disorder (ASD). Despite their prevalence and impact, there are no randomized controlled trials (RCTs) aimed at evaluating the efficacy of selective serotonin reuptake inhibitors (SSRIs) for anxiolysis in this population, who may have a different biological basis for anxiety. Methods: Secondary analyses of the STAART double-blind, placebo-controlled RCT of citalopram in children with ASD examined whether citalopram reduced anxiety measured on the parent-reported Child and Adolescent Symptom Inventory-4 (CASI-4) as the primary outcome. An intention-to-treat analysis involving all 149 participants used multiple imputations for missing data and included baseline stratification factors of age group and site, among others. We prespecified as clinically significant a 33% reduction in anxiety in citalopram versus placebo, coinciding with 80% power. We tested whether communicative ability on the Vineland Communication score moderated treatment effect and explored whether initial anxiety was associated with greater adverse events, which could impact on dose titration and achieving optimal dose. Results: Both groups showed substantial reduction in anxiety. Citalopram was associated with a nonsignificant 16.5% greater reduction (observed coefficient = -0.181, bootstrap standard error = 0.126, p = 0.151, confidence interval = -0.428 to 0.066). Anxiety reports were significantly lower in children with reduced communicative ability, but communicative ability did not moderate the treatment effect (interaction p = 0.294). Initial anxiety levels were not associated with increased adverse effects (interaction ps 0.162-0.954). Conclusion: Citalopram did not statistically significantly improve anxiety in children with ASD. Clinicians should be cautious in their use of SSRIs for this indication. There remains a need for well-powered clinical trials testing the efficacy of SSRIs among autistic children with anxiety disorders.

Efficacy, Tolerability, and Acceptance of Long-Lasting Antipsychotics in Children and Adolescents: A Systematic Review.

Abstract: Objectives: While long-lasting antipsychotics (LLA) were specifically developed to address the problem of adherence in patients with chronic psychiatric disorders, their role in pediatric populations is not clear. Methods: To document the efficacy, tolerance, and acceptance of LLAs in children and adolescents, a literature search was conducted using several databases for published studies (PubMed, PsycINFO) from January 1965 to December 2020. Twenty-two studies were identified (16 case reports/series, 3 open label studies, 2 controlled studies, and 1 retrospective analysis of national database). Results: Demographic features were widely heterogeneous across studies (total N = 480, 58% male, mean age = 15.0 ± 1.8). Case reports/series presented positive therapeutic outcomes in noncompliant youths with severe mental illness. Three open-label one-arm studies supported the clinical efficacy of risperidone long-acting injection in patients previously stabilized with oral risperidone. One study showed lower clinical symptoms and higher functioning at 12 months in youths treated for an acute psychotic episode with paliperidone palmitate compared to oral risperidone. The types and rates of side effects of LLA were comparable to those observed for oral antipsychotics. Two studies suggested better metabolic and neurological tolerance of LLA compared to an oral form. Preliminary evidence supported a satisfactory level of treatment satisfaction in patients treated with LLA and their families, while concerns were raised regarding practical administration in outpatient services. However, the average quality of the evidence based on the RoB2 tool was low. Conclusions: The level of evidence was low for the efficacy of LLA in pediatric populations and very low for the tolerance and acceptance. It concerned mostly the effect of risperidone long-acting injection in adolescents with psychotic disorders. Randomized maintenance clinical trials using noninferiority analysis would be more appropriate for further research.

A Characterization of the Clinical Global Impression Scale Thresholds in the Treatment of Adolescent Depression Across Multiple Rating Scales.

Abstract: Introduction: The Clinical Global Impressions-Improvement (CGI-I) scale is widely used in clinical research to assess symptoms and functioning in the context of treatment. The correlates of the CGI-I with efficacy scales for adolescent major depressive disorder are poorly understood. This study focused on benchmarking CGI-I scores with changes in the Children's Depression Rating Scale-Revised (CDRS-R) and the Quick Inventory of Depressive Symptomatology-Adolescent (17-item) Self-Report (QIDS-A17-SR). Methods: We examined three datasets with the clinician-rated CDRS-R to ascertain equivalent percent changes in total scores and CGI-I ratings. Exploratory analyses examined corresponding percentage changes in the QIDS-A17-SR and the CGI-I ratings. The CGI-I was the reference scale for nonparametric equipercentile linking with the Equate package in R. Results: CGI-I scores of 1 mapped to ≥78%-95% change in CDRS-R scores at 4-6 weeks across three datasets. CGI-I scores of 2 mapped to 56%-94% change in CDRS-R scores at 4-6 weeks across three studies. CGI-I scores of 3 mapped to 30%-68% changes in CDRS-R scores at 4-6 weeks across three studies. CGI-I scores of 4 mapped to a range of 29%-44% at 4-6 weeks across three studies. There was no significant difference (p ≥ 0.6) between treatment groups in both the Treatment of Adolescents with Depression and Treatment of Resistant Depression in Adolescents studies, for each CGI-I score ( = 1, or = 2 or = 3, or ≥4), associated mapping of total depression severity score, or associated percent change from baseline for corresponding follow-up visits. There was no significant sex difference (p > 0.2) in CGI-I linkages to CDRS-R total or percentage changes. Conclusions: These findings establish clear relationships among CGI-I scores and the CDRS-R and the QIDS-A17-SR. These benchmarks have utility for clinical trial study design, inter-rater reliability training, and clinical implementation.

Bowel and Bladder Dysfunction Is Associated with Psychiatric Comorbidities and Functional Impairment in Pediatric Obsessive-Compulsive Disorder.

Abstract: Objective: Neuropsychiatric disorders are common in children with bowel and bladder dysfunction (BBD), a syndrome associated with urinary frequency, urgency, holding, incontinence, and constipation. We evaluated BBD symptom severity in children and youth attending a tertiary care obsessive-compulsive disorder (OCD) clinic. Methods: Consecutive patients attending initial OCD assessments between 2016 and 2020 were invited to participate in a registry study. Diagnosis of OCD and comorbidities was established by structured clinical interview. OCD severity and impact were assessed with the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) and the Child Obsessive Compulsive Impact Scale (COIS-R; self-report), respectively. BBD symptoms were quantified with the Vancouver Symptom Score (VSS), a validated self-report measure. Results: One hundred twelve participants completed the VSS (mean age 13.5 ± 3.3, range 7-20). Based on a cutoff score of 11 corresponding to pediatric urologist-diagnosed BBD, 30.4% of participants screened positive, including more females than males (39.3% vs. 21.4%; p = 0.04). Daytime urinary incontinence was present in a greater proportion of participants with OCD forbidden thoughts (34.8% vs. 8.2%, p = 0.002), major depressive disorder (MDD; 38.5% vs. 6.8%, p = 0.001), and somatization disorder (60% vs. 9%, p = 0.001) compared with those without. A regression model including CY-BOCS, COIS-R, psychiatric comorbidities, medications, age, and gender explained 52.2% of the variance in VSS; COIS-R, tic disorder, and MDD were significant predictors. Conclusion: BBD symptoms are common and associated with high OCD-related impairment and psychiatric comorbidities. Standardized assessment may facilitate identification of BBD symptoms in this population and is critical to mitigating long-term physical and mental health impacts. Further studies are required to assess the relationship between BBD and OCD treatment outcomes.

Psychopharmacology in the Pediatric Oncology and Bone Marrow Transplant Units: Antidepressant Treatment.

Abstract: Objectives: The aim of this study was to characterize the clinical profiles, tolerability, and efficacy of two groups of antidepressants, selective serotonin reuptake inhibitors (SSRIs), and the atypical antidepressant, mirtazapine, in children and adolescents treated in a large pediatric Hematology-Oncology center. Methods: A review of computerized medical charts of 32 pediatric patients with cancer, from December 2011 to April 2020, was conducted. Efficacy and tolerability of antidepressant medications were retrospectively analyzed. The Clinical Global Impressions-Severity (CGI-S) and Clinical Global Impressions-Improvement (CGI-I) Scales were used to evaluate psychiatric symptoms severity before and following treatment, while the data on adverse events and drug-drug interactions were retrieved from the computerized medical records. Results: Thirty-two children and adolescents with cancer, 2-21 years of age (mean 14.1 ± 4.6 years), were treated with antidepressants. Fourteen patients (44%) received mirtazapine, whereas 18 patients (56%) received SSRIs: sertraline (25%), escitalopram (25%), or fluoxetine (6%). Treatment choice was dictated either by physician preference or informed by potential drug-drug interactions. The most common psychiatric diagnoses were major depressive disorders (47%), anxiety disorders (19%), and medication-induced psychiatric disorders (19%). The most common psychiatric-medical symptoms were depressed mood (94%) and anxiety (62%). CGI-S improved significantly (p < 0.05) between pretreatment and on-treatment assessments, with no statistically significant difference between SSRI and mirtazapine-treated patients. CGI-I scores at reassessment indicated improvement in most patients (84%). Adverse events of treatment were mild in all patients. Conclusions: The antidepressants used in this study, SSRIs and mirtazapine, were effective and well tolerated in children and adolescents with cancer and psychiatric comorbidities. Given the high rates of depression and anxiety in children with cancer, large-scale, multisite, prospective clinical trials of antidepressants are warranted.

Antipsychotics in the California Foster Care System: A 10-Year Analysis.

Abstract: Background: In response to concerns regarding psychotropic medication prescribing, California's foster care system implemented oversight strategies to improve prescribing and monitoring practice, particularly for antipsychotics. The impact of these policies has not been evaluated. Objectives: To examine foster youth psychotropic use data in California and their relationship to national and state policy initiatives. Methods: This study analyzed 2011-2020 data curated by the California Child Welfare Indicators Project. The platform matches Medicaid medication and laboratory claims with individual-level foster youth data to report rates of dispensed psychotropic medications, authorization status, and metabolic screening. Results: In 2011, there were 78,231 California youth in foster care, of which 10,435 (13.3%) received psychotropics and 5570 (7.1%) antipsychotics. In 2020, of 68,386 foster children, 7172 (12.2%) received psychotropics and 2068 (3.0%) antipsychotics. Proper authorizations for psychotropics were obtained for 5581 (77.8%) foster youth in 2020. Of those receiving antipsychotics, 904 (43.7%) underwent metabolic screening. The greatest declines in antipsychotic use occurred between 2013 (6.7%) and 2018 (3.1%). Overall 2011 to 2020 declines were similar for males (8.5% → 3.6%, 58% reduction, p < 0.001) and females (5.5% → 2.4%, 57% reduction, p < 0.001). Regarding age and race, greater declines occurred for children <10 years (2.33% → 0.84%, 64% reduction, p < 0.001) and Latino youth (5.4% → 2.2%, 59% reduction, p < 0.001). Conclusions: Temporal patterns in antipsychotic use suggest an impact of policies and guidelines. While 12.2% of foster youth continue to receive psychotropics, there were reductions in racial/ethnic disparities and declines in antipsychotic use. Lack of adherence to authorization and metabolic screening requirements continue to be concerning.

A Meta-Analysis of Antipsychotic-Induced Hypo- and Hyperprolactinemia in Children and Adolescents.

Abstract: Objective: Antipsychotic-related prolactin changes may expose children and adolescents to severe adverse reactions (ARs) related to pubertal development and growth. We therefore aimed to assess the effects of antipsychotics on prolactin levels and associated somatic ARs in children and adolescents. Methods: We systematically searched PubMed and CENTRAL for placebo-controlled randomized trials of antipsychotics in children and adolescents aged ≤18 years, reporting prolactin levels and related ARs. We conducted a random-effect meta-analysis and assessed risk of bias version 2 (ROB2). Results: Thirty-two randomized controlled trials with an average trial duration of 6 weeks, covering 4643 participants with an average age of 13 years and a male majority of 65.3%. Risk of bias across domains was low or unclear. The following antipsychotic compounds: aripiprazole (n = 810), asenapine (n = 506), lurasidone (n = 314), olanzapine (n = 179), paliperidone (n = 149), quetiapine (n = 381), risperidone (n = 609), and ziprasidone (n = 16) were compared with placebo (n = 1658). Compared with placebo, statistically significant higher prolactin increase occurred with risperidone (mean difference [MD] = 28.24 ng/mL), paliperidone (20.98 ng/mL), and olanzapine (11.34 ng/mL). Aripiprazole significantly decreased prolactin (MD = -4.91 ng/mL), whereas quetiapine, lurasidone, and asenapine were not associated with significantly different prolactin levels than placebo. Our results on ziprasidone are based on a single study, making it insufficient to draw strong conclusions. On average, 20.8% of patients treated with antipsychotic developed levels of prolactin that were too high (hyperprolactinemia), whereas only 1.03% of patients reported prolactin-related ARs. Data were highly limited for long-term effects. Conclusions: In children and adolescents, risperidone, paliperidone, and olanzapine are associated with significant prolactin increase, whereas aripiprazole is associated with significant decrease. Despite the significant changes in prolactin level, few ARs were reported. Study protocol on PROSPERO: CRD42018116451.