Lithium for the Maintenance Treatment of Bipolar I Disorder: A Double-Blind, Placebo-Controlled Discontinuation Study.

Objective: This study examined the role of lithium in the maintenance treatment of pediatric patients with bipolar I disorder (BP-I).

Method: Participants aged 7 to 17 years who presented with a manic or mixed episode received 24 weeks of lithium treatment in one of two multiphase studies, the Collaborative Lithium Trials (CoLT 1 and CoLT 2). Responders were randomized to continue lithium or to be cross-titrated to placebo for up to 28 weeks.

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.

Lithium in the Acute Treatment of Bipolar I Disorder: A Double-Blind, Placebo-Controlled Study.

Background: Lithium is a benchmark treatment for bipolar disorder in adults. Definitive studies of lithium in pediatric bipolar I disorder (BP-I) are lacking.

Methods: This multicenter, randomized, double-blind, placebo-controlled study of pediatric participants (ages 7-17 years) with BP-I/manic or mixed episodes compared lithium (n = 53) versus placebo (n = 28) for up to 8 weeks.

Comorbid anxiety and social avoidance in treatment of severe childhood aggression: response to adding risperidone to stimulant and parent training; mediation of disruptive symptom response.

Objective: In the four-site Treatment of Severe Childhood Aggression (TOSCA) study, addition of risperidone to stimulant and parent training moderately improved parent-rated disruptive behavior disorder (DBD) symptoms. This secondary study explores outcomes other than DBD and attention-deficit/hyperactivity disorder (ADHD) as measured by the Child and Adolescent Symptom Inventory-4R (CASI-4R).

Methods: A total of 168 children ages 6-12 with severe aggression (physical harm), DBD, and ADHD were randomized to parent training plus stimulant plus placebo (basic treatment) or parent training plus stimulant plus risperidone (augmented treatment) for 9 weeks.

Post-acute effectiveness of lithium in pediatric bipolar I disorder.

Objective: This study examined the long-term effectiveness of lithium for the treatment of pediatric bipolar disorder within the context of combination mood stabilizer therapy for refractory mania and pharmacological treatment of comorbid psychiatric conditions.

Methods: Outpatients, ages 7-17 years, meeting American Psychiatric Association, diagnostic and statistical manual of mental disorders, 4th ed. (DSM-IV) diagnostic criteria for bipolar disorder I (BP-I) (manic or mixed) who demonstrated at least a partial response to 8 weeks of open-label treatment with lithium (phase I) were eligible to receive open-label lithium for an additional 16 weeks (phase II).

Age differences in the phenomenology of pediatric bipolar disorder.

Background: The primary purpose of this study was to explore whether age differences in the phenomenology of bipolar disorders from 4 to 17 years of age exist.

Methods: Outcome measures included questionnaires pertaining to mood symptoms, psychosocial functioning, and family history of psychiatric illness. Phenomenology was examined in two diagnostic groups: syndromal bipolar disorder (bipolar I or II) and subsyndromal bipolar disorder (bipolar disorder not otherwise specified or cyclothymia) and across six age cohorts: 4-6, 7-8, 9-10, 11-13, and 14-17 years.

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.

Dosing strategies for lithium monotherapy in children and adolescents with bipolar I disorder.

Objective: The primary goal of this exploratory study was to obtain data that could lead to evidence-based dosing strategies for lithium in children and adolescents suffering from bipolar I disorder.

Methods: Outpatients aged 7-17 years meeting Diagnostic and Statistical Manual of Mental Disorders, 4th edition, diagnostic criteria for bipolar I disorder (manic or mixed) were eligible for 8 weeks of open label treatment with lithium in one of three dosing arms. In Arm I, participants began treatment at a dose of 300 mg of lithium twice daily.

First-dose pharmacokinetics of lithium carbonate in children and adolescents.

This study examines the pharmacokinetics of oral doses of lithium carbonate immediate-release capsules after administration of 600 or 900 mg in children and adolescents with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, bipolar I disorder. Lithium plasma concentrations were followed over 48 to 72 hours in 39 subjects (20 male and 19 female subjects; ages, 7-17 years) with mixed or manic episodes enrolled at 7 clinical sites participating in the Collaborative Lithium Trials. Population pharmacokinetic modeling was performed using NONMEM, and influences of patient covariates on pharmacokinetics parameters were examined.

Double-blind maintenance safety and effectiveness findings from the Treatment of Early-Onset Schizophrenia Spectrum (TEOSS) study.

Objective: To examine the long-term safety and efficacy of three antipsychotics in early-onset schizophrenia spectrum disorders.

Method: Patients (8 to 19 years old) who had improved during an 8-week, randomized, double-blind acute trial of olanzapine, risperidone, or molindone (plus benztropine) were eligible to continue on the same medication for up to 44 additional weeks under double-blind conditions. Adjunctive medications were allowed according to defined algorithms.

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.

A pilot pharmacotherapy trial for depressed youths at high genetic risk for bipolarity.

Children and adolescents who are the offspring of a bipolar parent and who first present with major depressive disorder (MDD) are at high risk for eventually developing bipolar disorder. In this report, the authors describe a group of 9 such high-risk children and adolescents with MDD, aged 7-16 years, who were randomized to receive treatment with either paroxetine monotherapy or combination paroxetine-divalproex sodium therapy. In the long-term management of depressive symptomatology in these patients, neither treatment appeared to be particularly effective.

Double-blind comparison of first- and second-generation antipsychotics in early-onset schizophrenia and schizo-affective disorder: findings from the treatment of early-onset schizophrenia spectrum disorders (TEOSS) study.

Objective: Atypical (second-generation) antipsychotics are considered standard treatment for children and adolescents with early-onset schizophrenia and schizoaffective disorder. However, the superiority of second-generation antipsychotics over first-generation antipsychotics has not been demonstrated. This study compared the efficacy and safety of two second-generation antipsychotics (olanzapine and risperidone) with a first-generation antipsychotic (molindone) in the treatment of early-onset schizophrenia and schizoaffective disorder.

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.