A Double-Blind and Placebo-Controlled Trial of Aripiprazole in Symptomatic Youths at Genetic High Risk for Bipolar Disorder.

Objective: To determine if acute treatment with aripiprazole (APZ) would be superior to treatment with placebo in reducing dysfunctional symptoms of elevated mood and/or irritability in symptomatic children and adolescents at familial high risk for bipolar disorder (BPD) whose mood episodes occur spontaneously. These are patients we have previously referred to as suffering from "cyclotaxia."

Methods: This was single-site, randomized, double-blind, placebo-controlled outpatient clinical trial in which youths aged 5-17 years who met diagnostic criteria for either cyclothymic disorder (CYC) or BPD not otherwise specified (BP-NOS) were randomly assigned to receive either APZ or placebo.

Double-blind, randomized, placebo-controlled long-term maintenance study of aripiprazole in children with bipolar disorder.

Background: This study evaluates the long-term efficacy of aripiprazole compared to placebo in children with bipolar disorders.

Method: Outpatients aged 4 to 9 years meeting DSM-IV criteria for a bipolar disorder (I, II, not otherwise specified, cyclothymia) were eligible to receive up to 16 weeks of open-label treatment with aripiprazole (phase 1). Patients were randomized into the 72-week double-blind phase of the study once they met a priori response criteria for stabilization (phase 2).

Moderators of fluoxetine treatment response for children and adolescents with comorbid depression and substance use disorders.

Our recent 8-week, randomized, placebo-controlled trial of fluoxetine in adolescents (ages 12-17 years) with comorbid depression and substance use disorder (SUD) did not detect a significant antidepressant treatment effect. The purpose of this secondary analysis was to explore moderators of the effect of fluoxetine in this sample. Static moderators measured at baseline were depression chronicity and hopelessness severity; time-varying moderators measured at baseline and weekly during the 8-week trial period were alcohol and marijuana use severity.

An open-label study of aripiprazole in children with a bipolar disorder.

Objective: The purpose of this open-label study was to describe the effectiveness of aripiprazole (APZ) in the treatment of children with bipolar disorders suffering from manic symptomatology.

Method: Symptomatic outpatients (Young Mania Rating Scale [YMRS] score ≥15) meeting strict, unmodified, Diagnostic and Statistical Manual of Mental Disorders, 4th edition, diagnostic symptom criteria for a bipolar disorder, ages 4-9 years, were eligible. Subjects were treated prospectively with flexible doses of APZ (maximum daily dose of 15 mg/day), for up to 16 weeks or until a priori response criteria were met.

The short-term safety and efficacy of fluoxetine in depressed adolescents with alcohol and cannabis use disorders: a pilot randomized placebo-controlled trial.

Background: The objective of this study was to examine whether fluoxetine was superior to placebo in the acute amelioration of depressive symptomatology in adolescents with depressive illness and a comorbid substance use disorder.

Methods: Eligible subjects ages 12-17 years with either a current major depressive disorder (MDD) or a depressive disorder that were also suffering from a comorbid substance-related disorder were randomized to receive either fluoxetine or placebo in this single site, 8-week double-blind, placebo-controlled study. The primary outcome analysis was a random effects mixed model for repeated measurements of Children's Depression Rating Scale-Revised (CDRS-R) scores compared between treatment groups across time.

Aripiprazole in children with attention-deficit/hyperactivity disorder.

Objective: To examine the effectiveness and cognitive effects of aripiprazole (APZ) in children with a primary diagnosis of attention-deficit/hyperactivity disorder (ADHD).

Methods: Youths, ages 8-12 years, with a diagnosis of ADHD combined-type or ADHD predominately inattentive-type were enrolled into a 6-week, open-label pilot trial. Outcome measures included the ADHD Rating Scale-IV (ARS-IV), Clinical Global Impressions Scale (CGI), and Children's Global Assessment Scale (CGAS).

Evaluation and comparison of psychometric instruments for pediatric bipolar spectrum disorders in four age groups.

The primary objective of this study was to evaluate the psychometric characteristics of the Young Mania Rating Scale (YMRS), the K-SADS Mania Rating Scale (KMRS), and the Children's Depression Rating Scale-Revised (CDRS-R) across four age groups (4-7, 8-10, 11-13, and 14-17 years). The interrater reliability of K-SADS diagnoses was also examined. Participants included 1,014 youths (62.

Methylphenidate in the treatment of children and adolescents with bipolar disorder and attention-deficit/hyperactivity disorder.

Objective: To examine the short-term efficacy of methylphenidate in the treatment of youths with bipolar disorder (BD) and comorbid attention deficit/hyperactivity disorder (ADHD).

Method: A 4-week double-blind, placebo-controlled trial in youths ages 5 to 17 years was conducted. Subjects met DSM-IV criteria for bipolar disorder and ADHD, were currently receiving a stable dose of at least one thymoleptic, and while euthymic continued to have clinically significant symptoms of ADHD.

Adherence to pharmacological treatment for juvenile bipolar disorder.

Objective: The objective of this study was to describe the prevalence and correlates of adherence to divalproex sodium (DVPX) and lithium carbonate (Li) combination treatment during the initial stabilization treatment phase.

Method: Adherence to Li/DVPX combination therapy was measured by the presence or absence of minimum serum concentrations of DVPX (50 microg/mL) or Li (0.6 mmol/L).

Double-blind, placebo-controlled trial of divalproex monotherapy in the treatment of symptomatic youth at high risk for developing bipolar disorder.

Objective: To determine if divalproex sodium was superior to placebo in the treatment of symptomatic youths who suffer from a bipolar spectrum disorder and who also have a parent with a diagnosis of a bipolar illness.

Method: Youths, ages 5 to 17 years, meeting DSM-IV criteria for bipolar disorder not otherwise specified (NOS) or cyclothymia who also had at least 1 biological parent with bipolar illness were randomly assigned in a double-blind fashion to receive treatment with either dival-proex sodium or placebo for up to 5 years. Study participation ended if the subject required additional clinical intervention, if the patient developed treatment-related adverse events, or if the participant was not adherent with study procedures.

A pilot evaluation of the safety, tolerability, pharmacokinetics, and effectiveness of memantine in pediatric patients with attention-deficit/hyperactivity disorder combined type.

Background: Disturbances in N-methyl-D-aspartate (NMDA) receptor activity may play a role in attention-deficit/hyperactivity disorder (ADHD).

Objective: This study is a preliminary evaluation of the safety, pharmacokinetics, and effectiveness of the NMDA receptor antagonist memantine in pediatric ADHD.

Methods: An open-label, dose-finding, 8-week, trial in outpatients 6-12 years old with ADHD combined type.

A 26-week open-label study of quetiapine in children with conduct disorder.

Objective: The aim of this study was to describe the long-term safety and effectiveness of quetiapine in conduct disorder (CD).

Methods: This was an 18-week outpatient follow-up study of an acute trial that enrolled aggressive children ages 6-12 years with a primary diagnosis of CD. To be enrolled into this study, subjects had to have successfully completed participation in the initial 8-week, open-label, outpatient quetiapine trial.

Effectiveness, safety, and pharmacokinetics of quetiapine in aggressive children with conduct disorder.

Objective: To provide an initial description of the effectiveness and pharmacokinetics (PK) of quetiapine in aggressive children with conduct disorder (CD).

Method: This 8-week, open-label outpatient trial, enrolled patients ages 6 to 12 years with CD. Outcome measures included the Rating of Aggression Against People and/or Property Scale (RAAPPS), Nisonger Child Behavior Rating Form (NCBRF), and the Conners Parent Rating Scale (CPRS-48).

The relevance of pharmacokinetic studies in designing efficacy trials in juvenile major depression.

Introduction: Identifying evidence-based dosing strategies is a key part of new drug development in pediatric populations. Pharmacokinetic (PK) studies can provide important information regarding how best to dose medications in children and adolescents. Utilizing scientifically supported dosing strategies provides the best chance for any given drug to demonstrate both efficacy and acceptable tolerability in definitive, placebo-controlled studies.

Combination lithium and divalproex sodium in pediatric bipolar symptom re-stabilization.

Objective: It has been reported that bipolar disorder may become less responsive to previously effective treatment with each symptomatic relapse. The primary goal of this study was to assess the rate of re-stabilization after the resumption of lithium (Li) plus divalproex (DVPX) following relapse on either agent as monotherapy.

Method: This is a prospective, 8-week, open-label outpatient Li/DVPX combination therapy trial.

Early symptoms of mania and the role of parental risk.

Objectives: The objectives of this study were to: (i) describe the phenomenology of youths diagnosed with subsyndromal bipolar disorders; (ii) describe the phenomenology of youngsters who are the children of bipolar parents, who are also experiencing subsyndromal symptoms of bipolar disorder (patients with 'cyclotaxia'); and (iii) explore which symptoms may be most useful in identifying youths with cyclotaxia.

Methods: Four hundred outpatients between the ages of 5 and 17 years received a diagnostic assessment and psychometric questionnaires pertaining to mood symptomatology and psychosocial functioning. Parental diagnostic information was also obtained.

Double-blind 18-month trial of lithium versus divalproex maintenance treatment in pediatric bipolar disorder.

Objective: To determine whether divalproex sodium (DVPX) was superior to lithium carbonate (Li+) in the maintenance monotherapy treatment of youths diagnosed with bipolar disorder who had been previously stabilized on combination Li+ and DVPX (Li+/DVPX) pharmacotherapy.

Method: Youths ages 5-17 years with bipolar I or II disorder were initially treated with Li /DVPX. Patients meeting remission criteria for four consecutive weeks were then randomized in a double-blind fashion to treatment with either Li+ or DVPX for up to 76 weeks.

Somatic treatment for depressive illnesses in children and adolescents.

Numerous somatic interventions have been studied as potential treatments of depressive disorders in children and adolescents. These include antidepressant medications, light therapy, electro-convulsive therapy, and alternative therapies. The available evidence suggests that several somatic interventions hold promise as potentially safe and effective treatments for depressed youths; however, there is still much to be learned about these interventions.

Combination lithium and divalproex sodium in pediatric bipolarity.

Objective: Lithium carbonate (Li) or divalproex sodium (DVPX) may be effective for some juveniles with bipolar disorder. Many youths with bipolar disorder do not respond to DVPX or Li monotherapy. An open-label study was conducted to examine the effectiveness of combination DVPX and Li therapy with youths diagnosed with bipolar disorder.

Somatic treatment for depressive illnesses in children and adolescents.

Numerous somatic interventions have been studied as potential treatments of depressive disorders in children and adolescents. These include antidepressant medications, light therapy, electro-convulsive therapy, and alternative therapies. The available evidence suggests that several somatic interventions hold promise as potentially safe and effective treatments for depressed youth; however, there is still much to be learned about these interventions.